Pirfenidone inhibits fibrosis in foreign body reaction after glaucoma drainage device implantation.

PubMed

Jung, Kyoung In; Park, Chan Kee

2016-01-01

The aim of this study was to investigate the antiscarring effects of pirfenidone on foreign body reaction in a rabbit model of glaucoma drainage implant surgery. Adult New Zealand White rabbits had glaucoma drainage device implantation using Model FP8 Ahmed glaucoma valves. One eye was randomly assigned to receive postoperative intrableb injection of pirfenidone followed by topical treatment. The other eye underwent the same procedure but without the addition of pirfenidone. Histochemical staining and immunohistochemistry for blebs were performed. The degree of cellularity was smaller in the pirfenidone group than in the control group at 2 weeks post operation (P=0.005). A few foreign body giant cells were detected in the inner border of the capsule, and their numbers were similar in the control and pirfenidone groups (P>0.05). Using Masson's trichrome stain, the inner collagen-rich layer was found to be thinner in the pirfenidone group than the control group at 4 weeks (P=0.031) and 8 weeks (P=0.022) post operation. The percentage of proliferating cell nuclear antigen-positive cells was lower in the pirfenidone group than in the control group at 2 weeks post operation (total bleb, P=0.022; inner bleb, P=0.036). Pirfenidone treatment decreased the immunoreactivity of connective tissue growth factor at 2 weeks post operation (total bleb, P=0.029; inner bleb, P=0.018). The height and area of α-smooth muscle actin expression were lower in the pirfenidone group than the control group at 2 weeks, 4 weeks, and 8 weeks post operation (all P<0.05). Postoperative intrableb injection of pirfenidone followed by topical administration reduced fibrosis following glaucoma drainage device implantation. These findings suggest that pirfenidone may function as an antiscarring treatment in foreign body reaction after tube-shunt surgery.

Ischemic index changes in diabetic retinopathy after intravitreal dexamethasone implant using ultra-widefield fluorescein angiography: a pilot study.

PubMed

Querques, Lea; Parravano, Mariacristina; Sacconi, Riccardo; Rabiolo, Alessandro; Bandello, Francesco; Querques, Giuseppe

2017-08-01

To investigate the effect of dexamethasone intravitreal implant on peripheral ischemia in patients affected by diabetic macular edema (DME). Patients with treatment-naïve diabetic retinopathy (DR) undergoing intravitreal dexamethasone implant for DME between October 2015 and March 2017 were enrolled. Patients underwent a comprehensive ocular examination at baseline (<2 weeks before treatment) and 10 ± 2 weeks after dexamethasone implant including best-corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography, ultra-widefield (UWF) retinography and UWF fluorescein angiography (UWFA). Nine eyes of seven consecutive patients (five males; mean age 66.4 ± 6.7 years) were enrolled. Mean duration of DR was 12.3 ± 8.4 years. Mean interval between UWFA acquisitions was 12.1 ± 2.1 weeks, and the mean interval between intravitreal injection and UWFA acquisition was 11.0 ± 1.6 weeks. Mean pre- and post-injection BCVA was 0.30 ± 0.20 and 0.21 ± 0.14 logMAR (p = 0.06), respectively. Mean pre- and post-injection central macular thickness was 449.8 ± 92.5 and 356.3 ± 52.4 μm (p = 0.03), respectively. Mean pre- and post-injection ischemic index was 24.0 ± 25.0 and 9.8 ± 12.1% (p = 0.0427), respectively. Intravitreal dexamethasone implant reduces peripheral retina ischemia in patients with DR.

Switching stable patients with schizophrenia from their oral antipsychotics to aripiprazole lauroxil: a post hoc safety analysis of the initial 12-week crossover period.

PubMed

Weiden, Peter J; Du, Yangchun; Liu, Chih-Chin; Stanford, Arielle D

2018-06-26

Switching antipsychotic medications is common in patients with schizophrenia who are experiencing persistent symptoms or tolerability issues associated with their current drug regimen. This analysis assessed the safety of switching from an oral antipsychotic to the long-acting injectable antipsychotic aripiprazole lauroxil (AL). This was a post hoc analysis of outpatients with schizophrenia who were prescribed an oral antipsychotic and who enrolled in an international, open-label, long-term (52-week) safety study of AL. The analysis focused on the first 3 injections of AL 882 mg over 12 weeks, divided into the immediate 4-week crossover period between the first and second AL injections (initiation phase) and the subsequent 8 weeks (stabilization phase). Patients were grouped by preswitch oral antipsychotic medication, and safety and clinical symptoms were assessed. In total, 190 patients had switched from one of the following oral antipsychotic medications: aripiprazole, conventional antipsychotics, risperidone/paliperidone, olanzapine, or quetiapine. The 12-week completion rate was high (92.1%) and similar across the different preswitch oral antipsychotic groups. Overall, adverse event (AE) rates experienced over 12 weeks were modest; no AEs were considered serious. The most common AEs in the initiation phase were injection site pain (5.8%), insomnia (5.8%), and akathisia (3.2%). No apparent relationship was observed between preswitch medication and early-onset AEs. Mean Positive and Negative Syndrome Scale total scores remained stable during this period across preswitch antipsychotic groups. Switching from an oral antipsychotic to AL was feasible in an outpatient setting for patients with schizophrenia, and the 12-week retention rate was favorable.

The effect and complication of botulinum toxin type a injection with serial casting for the treatment of spastic equinus foot.

PubMed

Lee, Sook Joung; Sung, In Young; Jang, Dae Hyun; Yi, Jin Hwa; Lee, Jin Ho; Ryu, Ju Seok

2011-06-01

To identify the effect of serial casting combined with Botulinum toxin type A (BTX-A) injection on spastic equinus foot. Twenty-nine children with cerebral palsy who had equinus foot were recruited from the outpatient clinic of Rehabilitation Medicine. The children were divided into 2 groups, one of which received serial casting after BTX-A injection, and the other which only received BTX-A injection. Serial casting started 3 weeks after the BTX-A injection, and was changed weekly for 3 times. Spasticity of the ankle joint was evaluated using the modified Ashworth scale (MAS), and the modified Tardieu scale (MTS). Gait pattern was measured using the physician's rating scale (PRS). The degree of ankle dorsiflexion and the MAS improved significantly until 12 weeks following the BTX-A injection in the serial casting group (p<0.001), while the BTX-A injection-only group improved until 6 weeks following injection (p<0.05). The combined group showed a significantly greater increase in the degree of dorsiflexion compared to the BTX-A injection-only group at post-injection weeks 6 and 12 (p<0.05). Three children (11.5%) suffered from foot ulcers as a complication caused by the serial casting. Our study demonstrated that the effect of BTX-A injection with serial casting was superior and lasted longer than the effect of BTX-A injection only in patients with spastic equinus foot. We therefore recommend BTX-A injection with serial casting for the treatment of equinus foot. However, physicians must also consider the possible complications associated with serial casting.

COMPARED EFFICACY OF INTRA-ARTICULAR INJECTION OF METHYLPREDNISOLONE AND TRIAMCINOLONE.

PubMed

Buyuk, Abdul Fettah; Kilinc, Eray; Camurcu, Ismet Yalkin; Camur, Savas; Ucpunar, Hanifi; Kara, Adnan

2017-01-01

To compare the effect of two different corticosteroid types in bilateral and symmetrical knee osteoarthritis (OA). One hundred and twenty-six patients received injections of methylprednisolone acetate (MP) in one knee and triamcinolone hexacetonide (TH) in the contralateral knee. Patients were evaluated before injection and 2, 4, 8, 12, and 24 weeks after. Mean patient age was 68.5±9 years. Mean BMI was 26.3±2.6 kg/m 2 . At first admission, mean VAS score was 7.7±1.3 for the right side and 7.5±1.5 for the left side, and mean WOMAC score was 67.6±14.4. After bilateral intra-articular injection, VAS scores for both knees and WOMAC scores decreased significantly when initial scores were compared with 2, 4, 8, 12, and 24 weeks after injection (p<0.05). A statistically significant change was seen over time when VAS and WOMAC scores for 2, 4, 8, 12, and 24 weeks post-injection were compared to each other (p<0.05). No significant difference was seen between knee sides (p>0.05). MP and TH have similar efficacy in relieving pain and improving function. The efficacy of intra-articular corticosteroid injection peaks 2 weeks after injection and the effect continues until the 24 th week. Level of Evidence II, Comparative Prospective Study.

COMPARED EFFICACY OF INTRA-ARTICULAR INJECTION OF METHYLPREDNISOLONE AND TRIAMCINOLONE

PubMed Central

BUYUK, ABDUL FETTAH; KILINC, ERAY; CAMURCU, ISMET YALKIN; CAMUR, SAVAS; UCPUNAR, HANIFI; KARA, ADNAN

2017-01-01

ABSTRACT Objective: To compare the effect of two different corticosteroid types in bilateral and symmetrical knee osteoarthritis (OA). Methods: One hundred and twenty-six patients received injections of methylprednisolone acetate (MP) in one knee and triamcinolone hexacetonide (TH) in the contralateral knee. Patients were evaluated before injection and 2, 4, 8, 12, and 24 weeks after. Results: Mean patient age was 68.5±9 years. Mean BMI was 26.3±2.6 kg/m2. At first admission, mean VAS score was 7.7±1.3 for the right side and 7.5±1.5 for the left side, and mean WOMAC score was 67.6±14.4. After bilateral intra-articular injection, VAS scores for both knees and WOMAC scores decreased significantly when initial scores were compared with 2, 4, 8, 12, and 24 weeks after injection (p<0.05). A statistically significant change was seen over time when VAS and WOMAC scores for 2, 4, 8, 12, and 24 weeks post-injection were compared to each other (p<0.05). No significant difference was seen between knee sides (p>0.05). Conclusion: MP and TH have similar efficacy in relieving pain and improving function. The efficacy of intra-articular corticosteroid injection peaks 2 weeks after injection and the effect continues until the 24th week. Level of Evidence II, Comparative Prospective Study. PMID:29081706

Fluoroscopy-guided Sacroiliac Joint Steroid Injection for Low Back Pain in a Patient with Osteogenesis Imperfecta.

PubMed

Dawson, P U; Rose, R E; Wade, N A

2015-09-01

Osteogenesis imperfecta, also known as 'brittle bone disease', is a genetic connective tissue disease. It is characterized by bone fragility and osteopenia (low bone density). In this case, a 57-year old female presented to the University Hospital of the West Indies (UHWI), Physical Medicine and Rehabilitation Clinic with left low back pain rated 6/10 on the numeric rating scale (NRS). Clinically, the patient had sacroiliac joint mediated pain although X-rays did not show the sacroiliac joint changes. Fluoroscopy-guided left sacroiliac joint steroid injection was done. Numeric rating scale and Oswestry Disability Index (ODI) questionnaire were used to evaluate outcome. This was completed at baseline, one week follow-up and at eight weeks post fluoroscopy-guided sacroiliac joint steroid injection. Numeric rating scale improved from 6/10 before the procedure to 0/10 post procedure, and ODI questionnaire score improved from a moderate disability score of 40% to a minimal disability score of 13%. Up to eight weeks, the NRS was 0/10 and ODI remained at minimal disability of 15%. Fluoroscopy-guided sacroiliac joint injection is a known diagnostic and treatment method for sacroiliac joint mediated pain. To our knowledge, this is the first case published on the use of fluoroscopy-guided sacroiliac joint steroid injection in the treatment of sacroiliac joint mediated low back pain in a patient with osteogenesis imperfecta.

The Effect and Complication of Botulinum Toxin Type A Injection with Serial Casting for the Treatment of Spastic Equinus Foot

PubMed Central

Lee, Sook Joung; Jang, Dae Hyun; Yi, Jin Hwa; Lee, Jin Ho; Ryu, Ju Seok

2011-01-01

Objective To identify the effect of serial casting combined with Botulinum toxin type A (BTX-A) injection on spastic equinus foot. Method Twenty-nine children with cerebral palsy who had equinus foot were recruited from the outpatient clinic of Rehabilitation Medicine. The children were divided into 2 groups, one of which received serial casting after BTX-A injection, and the other which only received BTX-A injection. Serial casting started 3 weeks after the BTX-A injection, and was changed weekly for 3 times. Spasticity of the ankle joint was evaluated using the modified Ashworth scale (MAS), and the modified Tardieu scale (MTS). Gait pattern was measured using the physician's rating scale (PRS). Results The degree of ankle dorsiflexion and the MAS improved significantly until 12 weeks following the BTX-A injection in the serial casting group (p<0.001), while the BTX-A injection-only group improved until 6 weeks following injection (p<0.05). The combined group showed a significantly greater increase in the degree of dorsiflexion compared to the BTX-A injection-only group at post-injection weeks 6 and 12 (p<0.05). Three children (11.5%) suffered from foot ulcers as a complication caused by the serial casting. Conclusion Our study demonstrated that the effect of BTX-A injection with serial casting was superior and lasted longer than the effect of BTX-A injection only in patients with spastic equinus foot. We therefore recommend BTX-A injection with serial casting for the treatment of equinus foot. However, physicians must also consider the possible complications associated with serial casting. PMID:22506143

Monosodium iodoacetate-induced joint pain is associated with increased phosphorylation of mitogen activated protein kinases in the rat spinal cord.

PubMed

Lee, Younglim; Pai, Madhavi; Brederson, Jill-Desiree; Wilcox, Denise; Hsieh, Gin; Jarvis, Michael F; Bitner, Robert S

2011-05-20

Intra-articular injection of monosodium iodoacetate (MIA) in the knee joint of rats disrupts chondrocyte metabolism resulting in cartilage degeneration and subsequent nociceptive behavior that has been described as a model of osteoarthritis (OA) pain. Central sensitization through activation of mitogen activated protein kinases (MAPKs) is recognized as a pathogenic mechanism in chronic pain. In the present studies, induction of central sensitization as indicated by spinal dorsal horn MAPK activation, specifically ERK and p38 phosphorylation, was assessed in the MIA-OA model. Behaviorally, MIA-injected rats displayed reduced hind limb grip force 1, 2, and 3 weeks post-MIA treatment. In the same animals, activation of phospho ERK1/2 was gradually increased, reaching a significant level at post injection week 3. Conversely, phosphorylation of p38 MAPK was enhanced maximally at post injection week 1 and decreased, but remained elevated, thereafter. Double labeling from 3-wk MIA rats demonstrated spinal pERK1/2 expression in neurons, but not glia. In contrast, p-p38 was expressed by microglia and a subpopulation of neurons, but not astrocytes. Additionally, there was increased ipsilateral expression of microglia, but not astrocytes, in 3-wk MIA-OA rats. Consistent with increased MAPK immunoreactivity in the contralateral dorsal horn, mechanical allodynia to the contralateral hind-limb was observed 3-wk following MIA. Finally, intrathecal injection of the MEK1 inhibitor PD98059 blocked both reduced hind-limb grip force and pERK1/2 induction in MIA-OA rats. Results of these studies support the role of MAPK activation in the progression and maintenance of central sensitization in the MIA-OA experimental pain model.

Rectus abdominis overuse injury in a tennis athlete treated with traumeel.

PubMed

Natsis, Konstantinos; Lyrtzis, Christos; Papathanasiou, Efthymia; Anastasopoulos, Nikos

2012-01-01

Rectus abdominis injuries are common in tennis players at all levels of competition. Traumeel(®) injection can be used for treatment of muscle strains and hematomas. A 21-year-old female tennis athlete was injured on the non-dominant rectus abdominis during the cocking phase of the service motion. She suffered from pain and tenderness. One week later, during a serve, she experienced severe pain on the contralateral side of her abdomen. Conservative treatment was performed by the team physician with rest, ice therapy and analgesics for 20 days, but she had recurrent injuries. The ultrasonography and MRI showed hematoma of the rectus abdominis muscle. She was treated with 2 injections of Traumeel(®) on the 2(nd), 4(th), 6(th) post-traumatic day and received 1 injection on the 10(th) post-traumatic day. She also modified her serve technique. On the fourth post-treatment week the athlete had pain-free function and both the MRI appearance and the size of rectus abdominal muscle were normal. She returned to her sport activities. There is no recurrence of her injury 2 years later. Rectus abdominis hematoma must be diagnosed early. Traumeel(®) injections are effective, safe and well-tolerated for the treatment of overuse injury of the rectus abdominis following strain.

Pirfenidone inhibits fibrosis in foreign body reaction after glaucoma drainage device implantation

PubMed Central

Jung, Kyoung In; Park, Chan Kee

2016-01-01

Background The aim of this study was to investigate the antiscarring effects of pirfenidone on foreign body reaction in a rabbit model of glaucoma drainage implant surgery. Methods Adult New Zealand White rabbits had glaucoma drainage device implantation using Model FP8 Ahmed glaucoma valves. One eye was randomly assigned to receive postoperative intrableb injection of pirfenidone followed by topical treatment. The other eye underwent the same procedure but without the addition of pirfenidone. Histochemical staining and immunohistochemistry for blebs were performed. Results The degree of cellularity was smaller in the pirfenidone group than in the control group at 2 weeks post operation (P=0.005). A few foreign body giant cells were detected in the inner border of the capsule, and their numbers were similar in the control and pirfenidone groups (P>0.05). Using Masson’s trichrome stain, the inner collagen-rich layer was found to be thinner in the pirfenidone group than the control group at 4 weeks (P=0.031) and 8 weeks (P=0.022) post operation. The percentage of proliferating cell nuclear antigen-positive cells was lower in the pirfenidone group than in the control group at 2 weeks post operation (total bleb, P=0.022; inner bleb, P=0.036). Pirfenidone treatment decreased the immunoreactivity of connective tissue growth factor at 2 weeks post operation (total bleb, P=0.029; inner bleb, P=0.018). The height and area of α-smooth muscle actin expression were lower in the pirfenidone group than the control group at 2 weeks, 4 weeks, and 8 weeks post operation (all P<0.05). Conclusion Postoperative intrableb injection of pirfenidone followed by topical administration reduced fibrosis following glaucoma drainage device implantation. These findings suggest that pirfenidone may function as an antiscarring treatment in foreign body reaction after tube-shunt surgery. PMID:27143855

Fluoroscopic Caudal Epidural Injections in Managing Post Lumbar Surgery Syndrome: Two-Year Results of a Randomized, Double-Blind, Active-Control Trial

PubMed Central

Manchikanti, Laxmaiah; Singh, Vijay; Cash, Kimberly A.; Pampati, Vidyasagar; Datta, Sukdeb

2012-01-01

Study Design: A randomized, active control, double-blind trial. Objective: To evaluate the effectiveness of fluoroscopically directed caudal epidural injections with or without steroids in managing chronic low back and lower extremity pain secondary to post lumbar surgery syndrome. Summary of Background Data: There is a paucity of evidence concerning caudal epidural injections for managing chronic persistent low back pain with or without lower extremity pain caused by post lumbar surgery syndrome. Methods: This active control randomized study included 140 patients with 70 patients in each group. Group I received 0.5% lidocaine, 10 mL; Group II received 9 mL of 0.5% lidocaine mixed with 1 mL of 6 mg of nonparticulate betamethasone. The multiple outcome measures included the numeric rating scale, the Oswestry Disability Index 2.0, employment status, and opioid intake with assessments at 3, 6, 12, 18, and 24 months posttreatment. Primary outcome was defined as at least 50% improvement in pain and Oswestry Disability Index scores. Patients with a positive response to the first 2 procedures with at least 3 weeks of relief were considered to be successful. All others were considered as failures. Results: Overall in Group I, 53% and 47% of the patients and in Group II, 59% and 58% of the patients, showed significant improvement with reduction in pain scores and disability index at 12 months and 24 months. In contrast, in the successful groups, significant pain relief and improvement in function were observed in 70% and 62% of Group I at one and 2 years; in 75% and 69% of Group II at one and 2 years. The results in the successful group showed that at the end of the first year patients experienced approximately 38 weeks of relief and at the end of 2 years Group I had 62 weeks and Group II had 68 weeks of relief. Overall total relief for 2 years was 48 weeks in Group I and 54 weeks in Group II. The average procedures in the successful groups were at 4 in one year and 6 at the end of 2 years. Conclusion: Caudal epidural injections of local anesthetic with or without steroid might be effective in patients with chronic persistent low back and/or lower extremity pain in patients with post lumbar surgery syndrome. PMID:23028241

Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits.

PubMed

Chiang, En-Rung; Ma, Hsiao-Li; Wang, Jung-Pan; Liu, Chien-Lin; Chen, Tain-Hsiung; Hung, Shih-Chieh

2016-01-01

Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.

Muscle and bone follow similar temporal patterns of recovery from muscle-induced disuse due to botulinum toxin injection.

PubMed

Manske, Sarah L; Boyd, Steven K; Zernicke, Ronald F

2010-01-01

If muscle force is a primary source for triggering bone adaptation, with disuse and reloading, bone changes should follow muscle changes. We examined the timing and magnitude of changes in muscle cross-sectional area (MCSA) and bone architecture in response to muscle inactivity following botulinum toxin (BTX) injection. We hypothesized that MCSA would return to baseline levels sooner than bone properties following BTX injection. Female BALB mice (15 weeks old) were injected with 20 muL of BTX (1 U/100 g body mass, n=18) or saline (SAL, n=18) into the posterior calf musculature of one limb. The contralateral limb (CON) served as an internal control. MCSA and bone properties were assessed at baseline, 2, 4, 8, 12, and 16 weeks post-injection using in vivo micro-CT at the tibia proximal metaphysis (bone only) and diaphysis. Muscles were dissected and weighed after sacrifice. Significant GroupxLegxTime interactions indicated that the maximal decrease in MCSA (56%), proximal metaphyseal BV/TV (38%) and proximal diaphyseal Ct.Ar (7%) occurred 4 weeks after injection. There was no delay prior to bone recovery as both muscle and bone properties began to recover after this time, but MCSA and BV/TV remained 15% and 20% lower, respectively, in the BTX-injected leg than the BTX-CON leg 16 weeks post-injection. Gastrocnemius mass (primarily fast-twitch) was 14% lower in the BTX-injected leg than the SAL-injected leg, while soleus mass (primarily slow-twitch) was 15% greater in the BTX group than the SAL group. Our finding that muscle size and bone began to recover at similar times after BTX injection was unexpected. This suggested that partial weight-bearing and/or return of slow-twitch muscle activity in the BTX leg may have been sufficient to stimulate bone recovery. Alternatively, muscle function may have recovered sooner than MCSA. Our results indicated that muscle cross-sectional area, while important, may not be the primary factor associated with bone loss and recovery when muscle atrophy is induced through BTX injection. To understand the nature of the interaction between muscle and bone, future work should focus on the functional recovery of individual muscles in relation to bone. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Responses of articular and epiphyseal cartilage zones of developing avian radii to estrone treatment and a 2-G environment

NASA Technical Reports Server (NTRS)

Negulesco, J. A.; Kossler, T.

1978-01-01

Histological measurements of radii from chickens exposed to estrone and hypergravity are reported. Female chicks at two weeks post-hatch were maintained for two weeks at earth gravity or 2 G with daily injections of 0.2 or 0.4 mg estrone. Animals were sacrificed after the last injection, and the radii were processed by described histological techniques. The results suggest that proximal and distal epiphyses of developing radii show different morphological responses to estrone and hypergravity.

Comparative Efficacy of Autologous Stromal Vascular Fraction and Autologous Adipose-Derived Mesenchymal Stem Cells Combined With Hyaluronic Acid for the Treatment of Sheep Osteoarthritis.

PubMed

Lv, Xiaoteng; He, Jiyin; Zhang, Xue; Luo, Xuan; He, Na; Sun, Zhongwei; Xia, Huitang; Liu, Victor; Zhang, Li; Lin, Xiangming; Lin, Liping; Yin, Huabin; Jiang, Dong; Cao, Wei; Wang, Richard; Zhou, Guangdong; Wang, Wen

2018-01-01

The current study explored whether intra-articular (IA) injection of autologous adipose mesenchymal stem cells (ASCs) combined with hyaluronic acid (HA) achieved better therapeutic efficacy than autologous stromal vascular fraction (SVF) combined with HA to prevent osteoarthritis (OA) progression and determined how long autologous ASCs combined with HA must remain in the joint to observe efficacy. OA models were established by performing anterior cruciate ligament transection (ACLT) and medial meniscectomy (MM). Autologous SVF (1×10 7 mononuclear cells), autologous low-dose ASCs (1×10 7 ), and autologous high-dose ASCs (5×10 7 ) combined with HA, and HA alone, or saline alone were injected into the OA model animals at 12 and 15 weeks after surgery, respectively. Compared with SVF+HA treatment, low-dose ASC+HA treatment yielded better magnetic resonance imaging (MRI) scores and macroscopic results, while the cartilage thickness of the tibial plateau did not differ between low, high ASC+HA and SVF+HA treatments detected by micro-computed tomography (µCT). Immunohistochemistry revealed that high-dose ASC+HA treatment rescued hypertrophic chondrocytes expressing collagen X in the deep area of articular cartilage. Western blotting analysis indicated the high- and low-dose ASC+HA groups expressed more collagen X than did the SVF+HA group. Enzyme-linked immunosorbent assay showed treatment with both ASC+HA and SVF+HA resulted in differing anti-inflammatory and trophic effects. Moreover, superparamagnetic iron oxide particle (SPIO)-labeled autologous ASC signals were detected by MRI at 2 and 18 weeks post-injection and were found in the lateral meniscus at 2 weeks and in the marrow cavity of the femoral condyle at 18 weeks post-injection. Thus, IA injection of autologous ASC+HA may demonstrate better efficacy than autologous SVF+HA in blocking OA progression and promoting cartilage regeneration, and autologous ASCs (5×10 7 cells) combined with HA potentially survive for at least 18 weeks after IA injection.

Treatment of whiplash associated neck pain [corrected] with botulinum toxin-A: a pilot study.

PubMed

Freund, B J; Schwartz, M

2000-02-01

Up to 87% of patients with whiplash associated disorder (WAD) have some degree of muscle spasm that is contributory to both pain and dysfunction. Botulinum toxin A (BTX-A) produces prolonged muscle relaxation that is dose-dependent and can be easily targeted to affected muscles. BTX-A therapy may be an effective form of therapy offering an alternative or adjunct to conventional modalities. We investigated BTX-A as therapy in patients with WAD. This randomized, double blind, placebo controlled study compares outcome measures in 26 patients with chronic neck pain (WAD-II chronic) subsequent to a motor vehicle accident. One-half of the patients received 100 units BTX-A, diluted in 1 ml saline, while the other half received just saline (1 ml). Five trigger points received 0.2 ml each of injectant via a 30 gauge needle. Outcome measures included total subjective neck, shoulder, and head pain based on visual analog scales; objective total range of neck motion (ROM), and the Vernon-Mior subjective function index. Followup assessments were carried out at 2 and 4 weeks post-treatment. Fourteen subjects receiving BTX-A and 12 receiving saline completed the study. The treatment group showed a trend toward improvement in ROM and reduction in pain at 2 weeks post-injection. At 4 weeks post-injection the treatment group was significantly improved from preinjection levels (p < 0.01). The placebo group showed no statistically significant changes at any post-treatment time. The Vernon-Mior scale revealed a trend to improvement for both groups. BTX-A treatment of subjects with chronic WAD II neck pain resulted in a significant (p < 0.01) improvement in ROM and subjective pain compared to a placebo group, but only a trend to improvement in subjective functioning.

Delineating Fecal Contaminant Sources and Travel Times in a Karst Groundwater Basin, Inner Bluegrass Region, Kentucky

NASA Astrophysics Data System (ADS)

Ward, J. W.; Reed, T. M.; Fryar, A. E.; Brion, G. M.

2006-12-01

Because of preferential flowpaths via features such as sinkholes and conduits, karst aquifers are susceptible to non-point-source pollution from agricultural and urban drainage. With many karst aquifers being drinking- water sources, pathogens are contaminants of public health concern. Monitoring of microbial parameters (total coliforms [TC], atypical colonies [AC] and fecal coliform bacteria [FC]) transpired biweekly from December 2002 March 2004 and weekly from February October 2005 at Blue Hole Spring, which drains outlying farm lands and the town of Versailles in the Inner Bluegrass Region of Kentucky. Physicochemical parameters (discharge, temperature, specific conductance, and pH) were measured continuously during the entire period. The AC/TC ratio, which had been employed only in surface water-quality studies, was used with FC counts, precipitation and discharge data to determine sources of fecal loading to ground water as result of land-use practices. An AC/TC ratio < 10 demonstrates fresh input of fecal matter, while a larger ratio can represent a variety of occurrences, including aged fecal material input and/or lack of nutrient input into the system. AC/TC ratio data in the 2002 04 dataset behaved similarly to surface waters, with ratios > 10 during dry periods and < 10 during wet periods, while the 2005 data demonstrated a very irregular pattern. The difference in these two data sets indicated a compositional change within the groundwater basin between the two sampling periods, perhaps as a result of construction at a sewage treatment plant adjoining the spring. Solute (rhodamine WT fluorescent dye and bromide) and particle (1-μm diameter fluorescent latex microspheres) tracer tests were conducted during summer 2006 to examine contaminant mobility within the system under base-flow and storm-flow conditions. Rainfall was limited prior to the base-flow trace, totaling 0.025 cm within 2 weeks prior to the slug injection. Base-flow discharge averaged 400 m3/s and solute breakthrough began ~ 7.5 hours post injection and cleared the system after 77 hours. For the storm-flow trace, rainfall totaled 3.12 cm prior to injection, with another 9.35 cm of rainfall occurring over the two week monitoring period. Spring discharge during the storm-flow trace averaged 0.443 m3/s, with a maximum of 0.503 m3/s. Under storm-flow conditions solute breakthrough began ~ 2.33 hours post injection, with particle breakthrough beginning ~ 2.5 hours post injection. Bromide concentrations at the spring were < 0.1 ppm (the detection limit, or DL) 5.5 hours after injection, while rhodamine WT concentrations were < DL (0.1 ppb) 14 hours post injection. Microspheres were detected at the spring until 164 hours after injection. These traces demonstrate that storms in this karst basin can accelerate solute movement, and particles can remain mobile for as long as 1 week after introduction.

Aripiprazole once-monthly long-acting injectable for the treatment of schizophrenia.

PubMed

Potkin, Steven G; Preda, Adrian

2016-01-01

Patient non-adherence increases the risk for relapse and the long-term care of schizophrenia. Long-acting injectable (LAI) antipsychotics can decrease this risk by ensuring adherence. An extended formulation, aripiprazole 400 mg once-monthly (AOM 400) LAI (AOM LAI), received regulatory approval in the year 2013 for the treatment of schizophrenia. AOM LAI is the first dopamine D2 partial agonist available in a long-acting formulation for the treatment of schizophrenia. This review covers data on the efficacy and tolerability/safety of AOM LAI. AOM LAI is a lyophilized powder of aripiprazole, with an elimination half-life of 29.9 - 46.5 days, allowing for a 4-week injection interval. Antipsychotic efficacy was documented in a 12-week double-blind trial (n = 340) and in two maintenance-of-effect trials: a 38-week trial (n = 662) and a 52-week trial (n = 403). The side effect profile is similar to that of oral aripiprazole. Adverse events (≥5% and at least twice that for placebo) were typically mild or moderate and did not lead to discontinuation: increased weight, akathisia, injection site pain and sedation. The 400 mg dose is tolerated by >90% of patients. Injection does not require additional training of health personnel or post-injection observation. AOM LAI is an efficacious and well-tolerated antipsychotic treatment for schizophrenia.

Intra-articular Recombinant Human Proteoglycan 4 Mitigates Cartilage Damage Following Destabilization of the Medial Meniscus in the Yucatan Minipig

PubMed Central

Waller, Kimberly A.; Chin, Kaitlyn E.; Jay, Gregory D.; Zhang, Ling X.; Teeple, Erin; McAllister, Scott; Badger, Gary J.; Schmidt, Tannin A.; Fleming, Braden C.

2016-01-01

Background Lubricin, or proteoglycan 4 (PRG4), is a glycoprotein responsible for joint boundary lubrication. PRG4 has been previously shown to be down-regulated following traumatic joint injury such as a meniscal tear. There is preliminary evidence suggesting that intra-articular injection of PRG4 post-injury will reduce cartilage damage in rat models of surgically-induced post-traumatic osteoarthritis. Objective To determine the efficacy of intra-articular injection of full length recombinant human lubricin (rhPRG4) for reducing cartilage damage after medial meniscus destabilization (DMM) in a pre-clinical large animal model. Study Design Controlled laboratory study Methods Unilateral DMM was performed in 29 Yucutan minipigs. One week post-DMM, animals received 3 weekly intra-articular injections (3cc/injection): 1) rhPRG4 [1.3mg/ml; n=10], 2) rhPRG4+hyaluronan [1.3mg/ml rhPRG4 and 3mg/ml hyaluronan (~950 kDA); n=10], and 3) phosphate buffered saline [PBS; n=9]. Hind limbs were harvested 26 weeks post-surgery. Cartilage integrity was evaluated using macroscopic (India Ink) and microscopic (Safranin O-fast green and hematoxylin & eosin) scoring systems. Secondary outcomes evaluated using ELISA included PRG4 levels in synovial fluid, CTX-II concentrations in urine and serum, and IL-1β levels in synovial fluid and serum. Results The rhPRG4 group had significantly less macroscopic cartilage damage in the medial tibial plateau compared to the PBS group (p=.002). No difference was found between the rhPRG4+hyaluronan and PBS groups (p=.23). However, no differences in microscopic damage scores were observed between the three groups (p=.70). PRG4 production was elevated in the rhPRG4 group synovial fluid compared to the PBS group (p=.033). The rhPRG4 group presented significantly lower urinary CTX-II levels, but not serum levels, when compared to the PBS (p=.013) and rhPRG4+hyaluronan (p=.011) groups. In serum and synovial fluid, both rhPRG4 (p=.006; p=.017) and rhPRG4+hyaluronan groups (p=.009; p=.03) presented decreased IL-1β levels. Conclusion All groups exhibited significant cartilage degeneration following DMM surgery. However, animals treated with rhPRG4 had the least amount of cartilage damage and less inflammation, providing evidence that intra-articular injections of rhPRG4 may slow the progression of post-traumatic osteoarthritis. Clinical Relevance Patients with meniscal trauma are at high risk for post-traumatic osteoarthritis. This study demonstrates that an intra-articular injection regimen of rhPRG4 may attenuate cartilage damage following meniscal injury. PMID:28129516

Effects of in ovo feeding of L-arginine on the development of digestive organs, intestinal function and post-hatch performance of broiler embryos and hatchlings.

PubMed

Gao, T; Zhao, M M; Li, Y J; Zhang, L; Li, J L; Yu, L L; Gao, F; Zhou, G H

2018-02-01

This study was to investigate the effects of in ovo feeding (IOF) L-arginine (Arg) solution on the development of digestive organs, the duodenal mucosa of broiler embryos and hatchlings, and the growth performance of chicks during the first week post-hatch. A total of 720 fertilized eggs with similar weight were randomly allocated to three groups, consisting of eight replicates of 30 eggs each. Three treatments were arranged as non-injected control, diluent-injected (0.75% NaCl solution) group and Arg solution-injected group containing 1% Arg, dissolved in diluent. At 17.5 days of incubation, 0.6 ml of IOF solution was injected into amniotic fluid of each egg of injected groups. Results showed IOF of Arg solution increased (p < .05) the chick embryo weight at 19 days of incubation; the body weight gain of post-hatch broilers during 1-7 days; the weights of liver, pancreas, proventriculus and gizzard; the concentrations of duodenal ghrelin, vasoactive intestinal peptide and glucagon-like peptide 2; and the duodenum mucosal enzyme activities of alkaline phosphatase, maltase, sucrase and inducible nitric oxide synthase of 7-day-old post-hatch broilers compared with other groups. The IOF of Arg solution also increased (p < .05) the villus height (VH) and the ratio of VH to crypt depth (CD) and decreased (p < .05) the CD in duodenum of broiler embryos and post-hatch hatchlings, except for the CD at 19 days of incubation. In conclusion, IOF of 1% Arg solution into the amnion at 17.5 days of incubation could improve the development of digestive organs, the duodenal morphology, the releasing of gastrointestinal hormones and mucosal enzyme activities of broiler embryos and hatchlings and finally the growth performance of chicks during the first week post-hatch. Therefore, IOF of appropriate Arg solution could be an effective technology for regulating early nutrition supply and subsequent growth development in poultry industry. © 2017 Blackwell Verlag GmbH.

Application of in vivo micro-computed tomography in the temporal characterisation of subchondral bone architecture in a rat model of low-dose monosodium iodoacetate-induced osteoarthritis

PubMed Central

2011-01-01

Introduction Osteoarthritis (OA) is a complex, multifactorial joint disease affecting both the cartilage and the subchondral bone. Animal models of OA aid in the understanding of the pathogenesis of OA and testing suitable drugs for OA treatment. In this study we characterized the temporal changes in the tibial subchondral bone architecture in a rat model of low-dose monosodium iodoacetate (MIA)-induced OA using in vivo micro-computed tomography (CT). Methods Male Wistar rats received a single intra-articular injection of low-dose MIA (0.2 mg) in the right knee joint and sterile saline in the left knee joint. The animals were scanned in vivo by micro-CT at two, six, and ten weeks post-injection, analogous to early, intermediate, and advanced stages of OA, to assess architectural changes in the tibial subchondral bone. The articular cartilage changes in the tibiae were assessed macroscopically and histologically at ten weeks post-injection. Results Interestingly, tibiae of the MIA-injected knees showed significant bone loss at two weeks, followed by increased trabecular thickness and separation at six and ten weeks. The trabecular number was decreased at all time points compared to control tibiae. The tibial subchondral plate thickness of the MIA-injected knee was increased at two and six weeks and the plate porosity was increased at all time points compared to control. At ten weeks, histology revealed loss of proteoglycans, chondrocyte necrosis, chondrocyte clusters, cartilage fibrillation, and delamination in the MIA-injected tibiae, whereas the control tibiae showed no changes. Micro-CT images and histology showed the presence of subchondral bone sclerosis, cysts, and osteophytes. Conclusions These findings demonstrate that the low-dose MIA rat model closely mimics the pathological features of progressive human OA. The low-dose MIA rat model is therefore suitable to study the effect of therapeutic drugs on cartilage and bone in a non-trauma model of OA. In vivo micro-CT is a non-destructive imaging technique that can track structural changes in the tibial subchondral bone in this animal model, and could also be used to track changes in bone in preclinical drug intervention studies for OA treatments. PMID:22185204

[Experience in using xeomin in the treatment of arm and hand spasticity in the early rehabilitation phase of stroke].

PubMed

Kostenko, E V; Petrova, L V; Ganzhula, P A; Lisenker, L N; Otcheskaia, O V; Khozova, A A; Boĭko, A N

2012-01-01

To reduce arm and hand spasticity, 28 patients in the early rehabilitation phase of ischemic hemisphere stroke received injections of the botulinum toxin A preparation xeomin in the content of complex rehabilitation programs. The following muscles: m. biceps brachii, m. flexor digitorum profundus, m. flexor digitorum superficialis, m. flexor carpi ulnaris, m. flexor carpi radialis were injected according to standard scheme. The total dose of drug was 200U in moderate (2-3 scores on the Ashworth scale) and 300U in marked (3-4 scores on the Ashworth scale) spasticity. Efficacy and safety of treatment was assessed at baseline and 2, 4, 8, 12, 16 weeks after injections. Xeomin significantly (p<0.05) reduced muscle tonus in patients with post-stroke spasticity of different severity. Clinical effect was seen 2 weeks after injection, it reached maximum at week 4 and then slowly decreased to week 16. The improved functional activity of the paretic arm (due to patient's and caregiver's reports) remained for to 12 weeks. The treatment was most effective in the group of patients with moderate spasticity. The correlation analysis confirmed that the severity of spasticity increased with the disease duration that reduced rehabilitation efficiency. The treatment with xeomin was safe, no serious side-effects were found.

Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits.

PubMed

Labrador Velandia, Sonia; Di Lauro, Salvatore; Alonso-Alonso, Maria Luz; Tabera Bartolomé, Soraya; Srivastava, Girish Kumar; Pastor, José Carlos; Fernandez-Bueno, Ivan

2018-01-01

To evaluate the feasibility, safety, and biocompatibility of intravitreal injection of human mesenchymal stem cells (MSCs) in immunocompetent pigmented rabbits. Thirty-two pigmented rabbits (24 females, 8 males; Chinchilla-New Zealand White) were divided into 8 groups of 4 animals. Commercially prepared human MSCs were injected (0.05 ml) into the post-lens vitreous of the right eyes. Groups 1 and 4 received isotonic medium (Ringer lactate-based), groups 2, 5, 7, and 8 received a low dose of 15 × 10 6 cells/ml. Groups 3 and 6 received a high dose of 30 × 10 6 cells/ml. Clinical signs were evaluated and scored before MSCs injection and weekly for 2 or 6 weeks. Animals were sacrificed at 2 or 6 weeks after injection. Eyes, liver, spleen, and gonads were assessed by histology and by fluorescent in situ hybridization to evaluate survival and extraocular migration of MSCs. There were no relevant clinical findings between control and MSC-injected rabbit eyes at any time point. There were also no relevant histological findings between control and MSC-injected rabbits related to ocular, liver, spleen, or gonad tissues modifications. MSCs survived intravitreally for at least 2 weeks after injection. Extraocular migration of MSCs was not detected. MSCs are safe and well-tolerated when administered intravitreally at a dose of 15 × 10 6 cells/ml in pigmented rabbits. These findings enable future research to explore the intravitreal use of commercially prepared allogenic human MSCs in clinical trials of retinal diseases.

Sperm abnormalities induced by pre-pubertal exposure to cyclophosphamide are effectively mitigated by Moringa oleifera leaf extract.

PubMed

Nayak, G; Vadinkar, A; Nair, S; Kalthur, S G; D'Souza, A S; Shetty, P K; Mutalik, S; Shetty, M M; Kalthur, G; Adiga, S K

2016-03-01

Moringa oleifera L. is a medicinal plant with potential antioxidant property. This study was aimed at investigating the chemoprotective effect of Moringa oleifera leaf extract (MOE) on cyclophosphamide (CP)-induced testicular toxicity. Two-week-old male Swiss albino mice were intraperitoneally injected with phosphate-buffered saline, 50 mg kg(-1) of CP and 25 mg kg(-1) of MOE. In combination treatment, mice were injected with 25 mg kg(-1) of MOE 24 h prior to CP injection, 24 h prior and post-CP injection and 24 h post-CP injection for 5 consecutive days (10 mg kg(-1) ). Six weeks later, mice were sacrificed to assess epididymal sperm parameters. MOE alone did not have any significant effect on sperm parameters. However, acute injection of CP resulted in significant decline in motility (P < 0.001), increase in head abnormality (P < 0.01) and DNA damage (P < 0.05). Combining MOE with CP increased the sperm density, motility and reduced head defect and DNA damage, irrespective of the schedule and dosage of MOE. Administration of MOE prior to CP significantly elevated the level of superoxide dismutase and catalase with concomitant decrease in lipid peroxidation in the testicular tissue. In conclusion, MOE may have potential benefit in reducing the loss of male gonadal function following chemotherapy. © 2015 Blackwell Verlag GmbH.

Injection and adhesion palatoplasty: a preliminary study in a canine model.

PubMed

Martínez-Álvarez, Concepción; González-Meli, Beatriz; Berenguer-Froehner, Beatriz; Paradas-Lara, Irene; López-Gordillo, Yamila; Rodríguez-Bobada, Cruz; González, Pablo; Chamorro, Manuel; Arias, Pablo; Hilborn, Jöns; Casado-Gómez, Inmaculada; Martínez-Sanz, Elena

2013-08-01

Raising mucoperiosteal flaps in traditional palatoplasty impairs mid-facial growth. Hyaluronic acid-based hydrogels have been successfully tested for minimally invasive craniofacial bone generation in vivo as carriers of bone morphogenetic protein-2 (BMP-2). We aimed to develop a novel flapless technique for cleft palate repair by injecting a BMP-2 containing hydrogel. Dog pups with congenital cleft palate were either non-treated (n=4) or treated with two-flap palatoplasty (n=6) or with the proposed injection/adhesion technique (n=5). The experimental approach was to inject a hyaluronic acid-based hydrogel containing hydroxyapatite and BMP-2 subperiosteally at the cleft palate margins of pups aged six weeks. At week ten, a thin strip of the medial edge mucosa was removed and the margins were closed directly. Occlusal photographs and computed tomography (CT) scans were obtained up to week 20. Four weeks after the gel injection the cleft palate margins had reached the midline and engineered bone had enlarged the palatal bones. Removal of the medial edge mucosa and suturing allowed complete closure of the cleft. Compared to traditional palatoplasty, the injection/adhesion technique was easier, and the post-surgical recovery was faster. CT on week 20 revealed some overlapping or "bending" of palatal shelves in the two-flap repair group, which was not observed in the experimental nor control groups. A minimally invasive technique for cleft palate repair upon injectable scaffolds in a dog model of congenital cleft palate is feasible. Results suggest better growth of palatal bones. This represents an attractive clinical alternative to traditional palatoplasty for cleft palate patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Adeno-associated Virus Serotype 9 – Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction

PubMed Central

Knezevic, Tijana; Myers, Valerie D.; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K.; Gordon, Jennifer; Weiner, Kristen N.; Rabinowitz, Joseph; Ramsey, Frederick V.; Tilley, Douglas G.; Khalili, Kamel; Cheung, Joseph Y.; Feldman, Arthur M.

2016-01-01

Objectives The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. Background BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Methods Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. Results MI-BAG3 mice demonstrated a significantly (p < 0.0001) higher left ventricular ejection fraction (LVEF) 9 days after rAAV9-BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (p<0.05), increased systolic [Ca2+]i, increased [Ca2+]i transient amplitudes and increased maximal ICa amplitude. Implications The results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure. PMID:28164169

Adeno-associated Virus Serotype 9 - Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction.

PubMed

Knezevic, Tijana; Myers, Valerie D; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K; Gordon, Jennifer; Weiner, Kristen N; Rabinowitz, Joseph; Ramsey, Frederick V; Tilley, Douglas G; Khalili, Kamel; Cheung, Joseph Y; Feldman, Arthur M

2016-12-01

The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. MI-BAG3 mice demonstrated a significantly (p < 0.0001) higher left ventricular ejection fraction (LVEF) 9 days after rAAV9-BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (p<0.05), increased systolic [Ca 2+ ] i , increased [Ca 2+ ] i transient amplitudes and increased maximal I Ca amplitude. The results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

PubMed

Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

2016-02-10

Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Salubrinal improves cardiac function in rats with heart failure post myocardial infarction through reducing endoplasmic reticulum stress-associated apoptosis].

PubMed

Liu, Y; Qi, S Y; Ru, L S; Ding, C; Wang, H J; Li, A Y; Xu, B Y; Zhang, G H; Wang, D M

2016-06-24

Endoplasmic reticulum (ER) stress plays an important role in ischemia-mediated cell death. The aim of the current study is to investigate the effects of salubrinal (Sal), a selective eIF2a dephosphorylation inhibitor, on heart failure rats and related mechanisms. Heart failure was induced by coronary artery ligation (MI) in adult male Sprague-Dawley rats. To ensure comparable MI sizes post coronary artery ligation on various groups, echocardiography examination was performed before and 30 minutes after ligation in MI groups. Then rats were randomly assigned to 4 groups: Sham group (n=12), MI group (n=10), MI plus vehicle injections group (DMSO group, n=12) and MI plus Sal injection group (Sal group, n=12). Sal (1 mg/kg) or DMSO was injected via the tail vein daily for the first 3 days (starting at 30 minutes after ligation of the left coronary artery), followed by subcutaneous injections twice per week for 8 weeks. Cardiac function was assessed by echocardiography and cell apoptosis assessed by flow cytometric analysis after 8 weeks. Protein and mRNA levels of ER stress markers were evaluated by immunohistochemistry and real time RT-PCR respectively. Eight weeks later, LVEF was significantly higher, while LVESD and LVEDD values were significantly lower in Sal group compared to MI and DMSO groups (all P<0.05); LV/BW ratio was significantly higher in MI group than in Sham group ((2.30±0.40) mg/g vs.(1.78±0.31) mg/g, P<0.05), which was significantly reduced in Sal group ((1.88±0.25) mg/g), but not in DMSO group((2.25±0.36) mg/g, P<0.05 vs. MI). In addition, flow cytometric analysis showed that Sal treatment significantly reduced apoptosis but not necrosis in post MI. Immunohistochemistry and real time PCR analysis showed that the myocardial protein and mRNA expression of ER stress markers were significantly lower in Sal group than in MI group, myocardial caspase-12 expression was significantly upregulated in MI group and significantly reduced by Sal treatment. Our results suggest that reduction of ER stress and myocardial apoptosis through inhibition of eIF2α dephosphorylation may serve as the potential mechanisms for the improved cardiac function and attenuated cardiac remodeling post Sal treatment in this heart failure rat model.

Alteration of Skin Mechanical Properties in Patients Undergoing Botulinum Toxin Type A Injections of Forehead Rhytides.

PubMed

Min, Peiru; Zhang, Zheng; Grassetti, Luca; Perdanasari, Aurelia Trisliana; Torresetti, Matteo; Pu, Zheming; Zhang, Yan; Han, Sheng; Marsili, Riccardo; Zhang, Yi Xin; di Benedetto, Giovanni; Lazzeri, Davide

2016-06-01

Although application of botulinum toxin type A (BTX-A) for the treatment of forehead rhytides has become very popular, the effects of its intramuscular injections on the skin mechanical properties remain unclear. We prospectively investigated the alterations in the mechanical properties of the skin of patients who received intramuscular injections of botulinum toxin A (BTX-A) for forehead rhytides and compared two injection doses. Of the 42 enrolled patients, one randomly assigned half received intramuscular injections of two units (group I), and the other half received four units (group II) of BTX-A in each injection point. The baseline and post-treatment skin mechanical parameters, including gross elasticity (R2), net elasticity (R5), viscoelastic ratio (R6) and biological elasticity (R7), were measured using the Cutometer(®) and compared. Treatment with BTX-A resulted in significant overall alterations in the mechanical properties of skin at the injection sites of both treatment groups during the 16-week period, and no significant differences were observed between groups. Significant decreases in biological elasticity, net elasticity and viscoelasticity properties were observed at 2 weeks follow-up and began to recover at that time. All of the skin mechanical properties recovered to baseline levels by 16 weeks of follow-up in both dosage groups, which indicates that the higher dosage (4 units) did not delay relapse compared to the two-unit dosage. We concluded that intramuscular injections of BTX-A significantly regulated the gross elasticity, net elasticity, functional elasticity and viscoelastic elasticity at the injection point over a radius of 1.5 cm at 2, 4 and 8 weeks follow-up. The alteration in the skin measurements had completely diminished by the 16-week follow-up. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The effects of cross-linked thermo-responsive PNIPAAm-based hydrogel injection on retinal function.

PubMed

Turturro, Sanja B; Guthrie, Micah J; Appel, Alyssa A; Drapala, Pawel W; Brey, Eric M; Pérez-Luna, Victor H; Mieler, William F; Kang-Mieler, Jennifer J

2011-05-01

There is significant interest in biomaterials that provide sustained release of therapeutic molecules to the retina. Poly(N-isopropylacrylamide) (PNIPAAm)-based materials have received significant attention as injectable drug delivery platforms due to PNIPAAm's thermo-responsive properties at approximately 32 °C. While the drug delivery properties of PNIPAAm materials have been studied extensively, there is a need to evaluate the safety effects of hydrogel injection on retinal function. The purpose of this study was to examine the effect of poly(ethylene glycol) diacrylate (PEG-DA) crosslinked PNIPAAm hydrogel injection on retinal function. Utilizing scanning laser ophthalmoscopy (SLO), optical coherent tomography (OCT), and electroretinography (ERG), retinal function was assessed following hydrogel injection. In region near the hydrogel, there was a significant decrease in arterial and venous diameters (∼4%) and an increase in venous blood velocity (∼8%) 1 week post-injection. Retinal thickness decreased (∼6%) at 1 week and the maximum a- and b-wave amplitudes of ERG decreased (∼15%). All data returned to baseline values after week 1. These data suggest that the injection of PEG-DA crosslinked PNIPAAm hydrogel results in a small transient effect on retinal function without any long-term effects. These results further support the potential of PNIPAAm-based materials as an ocular drug delivery platform. Copyright © 2011 Elsevier Ltd. All rights reserved.

Nucleic acid immunization protects dogs against challenge with virulent canine parvovirus.

PubMed

Jiang, W; Baker, H J; Swango, L J; Schorr, J; Self, M J; Smith, B F

1998-04-01

Nucleic acid vaccines (NAVs) use expression vectors encoding one or more antigen genes to transfect host cells inducing both humoral and cellular immunity against the expressed antigen. NAV offers major advantages over conventional vaccines for the protection of humans and animals. This study shows that a plasmid DNA (pGT36VP1) encoding the full length VP1 region of canine parvovirus (CPV) induces immunity that protects dogs against challenge with virulent virus. Five dogs without anti-CPV antibodies were injected at 9 months of age with increasing doses of pGT36VP1 or saline. NAV vaccinated dogs showed an increase of serum IgG titer starting 1 week post-injection which peaked at week 2 and remained detectable for at least 14 weeks. A second dose of NAV resulted in an anamnestic response within 1 week. IgG titers peaked at week 3 and 4 after the second injection. All pGT36VP1 vaccinated dogs were protected against infection after virulent CPV challenge regardless of dose and the unvaccinated control dog was fully susceptible. This study demonstrated for the first time that a NAV can protect dogs against an infectious disease.

Autologous platelet lysates local injections for treatment of tibia non-union with breakage of the nickelclad: a case report.

PubMed

Jiang, Hong-Jiang; Tan, Xun-Xiang; Ju, Hai-Yang; Su, Jin-Ping; Yan, Wei; Song, Xiu-Gang; Qin, Li-Wu; Ju, Chang-Jun; Wang, Ling-Shuang; Zou, De-Bao

2016-01-01

Nonunions of the tibia represent challenging orthopedic problems, which require the surgeon to analyze numerous factors and choose an appropriate treatment. This article presents a case report of tibia and fibula fracture patient who failed the internal fixation surgery and successfully recovered after one course of percutaneous autologous platelet lysates injection. The patient received an internal nickelclad breakage at 9 months post-surgery but reluctant to accept a second surgery, then autologous platelet lysates (APL) injection which is a less invasive method was recommended. The injections were carried once a week for three times. Radiologic evaluation was conducted every month until recovery. To the best of our knowledge, this is the first reported case of tibia delayed union with breakage of the plate resolved with APL injection. Improved clinical evidence was observed at 4 and 6 months after injection. The patient got good bony union at 8 months post-injection. The patient didn't feel any discomfort postinjection, no complications such as infection, refracture etc. were observed. APL percutaneous injection could be a new therapeutic option for the treatment of nonunion or delayed healing fractures.

Early-life risperidone administration alters maternal-offspring interactions and juvenile play fighting.

PubMed

Gannon, Matthew A; Brown, Clifford J; Stevens, Rachel M; Griffith, Molly S; Marczinski, Cecile A; Bardgett, Mark E

2015-03-01

Risperidone is an antipsychotic drug that is approved for use in childhood psychiatric disorders such as autism. One concern regarding the use of this drug in pediatric populations is that it may interfere with social interactions that serve to nurture brain development. This study used rats to assess the impact of risperidone administration on maternal-offspring interactions and juvenile play fighting between cage mates. Mixed-sex litters received daily subcutaneous injections of vehicle or 1.0 or 3.0mg/kg of risperidone between postnatal days (PNDs) 14-42. Rats were weaned and housed three per cage on PND 21. In observations made between PNDs 14-17, risperidone significantly suppressed several aspects of maternal-offspring interactions at 1-hour post-injection. At 23 h post-injection, pups administered risperidone had lower activity scores and made fewer non-nursing contacts with their moms. In observations of play-fighting behavior made once a week between PNDs 22-42, risperidone profoundly decreased many forms of social interaction at 1h post-injection. At 23h post-injection, rats administered risperidone made more non-social contacts with their cage mates, but engaged in less social grooming. Risperidone administration to rats at ages analogous to early childhood through adolescence in humans produces a pattern of abnormal social interactions across the day that could impact how such interactions influence brain development. Copyright © 2015 Elsevier Inc. All rights reserved.

Early-Life Risperidone Administration Alters Maternal-Offspring Interactions and Juvenile Play Fighting

PubMed Central

Gannon, Matthew A.; Brown, Clifford J.; Stevens, Rachel M.; Griffith, Molly S.; Marczinski, Cecile A.; Bardgett, Mark E.

2015-01-01

Risperidone is an antipsychotic drug that is approved for use in childhood psychiatric disorders such as autism. One concern regarding the use of this drug in pediatric populations is that it may interfere with social interactions that serve to nurture brain development. This study used rats to assess the impact of risperidone administration on maternal-offspring interactions and juvenile play fighting between cage mates. Mixed-sex litters received daily subcutaneous injections of vehicle or 1.0 or 3.0 mg/kg of risperidone between postnatal days (PNDs) 14-42. Rats were weaned and housed three per cage on PND 21. In observations made between PNDs 14-17, risperidone significantly suppressed several aspects of maternal-offspring interactions at one-hour post-injection. At 23 hours post-injection, pups administered risperidone had lower activity scores and made fewer non-nursing contacts with their moms. In observations of play-fighting behavior made once a week between PNDs 22-42, risperidone profoundly decreased many forms of social interaction at one hour post-injection. At 23 hours post-injection, rats administered risperidone made more non-social contacts with their cage mates, but engaged in less social grooming. Risperidone administration to rats at ages analogous to early childhood through adolescence in humans produces a pattern of abnormal social interactions across the day that could impact how such interactions influence brain development. PMID:25600754

Urinary retention in female OAB after intravesical Botox injection: who is really at risk?

PubMed

Miotla, Pawel; Cartwright, Rufus; Skorupska, Katarzyna; Bogusiewicz, Michal; Markut-Miotla, Ewa; Futyma, Konrad; Rechberger, Tomasz

2017-06-01

Intravesical onabotulinumtoxinA (Botox) injections are effective for the treatment of idiopathic overactive bladder (OAB) symptoms. The aim of our study was to assess the predisposing factors for urinary retention in women with OAB after intravesical Botox injection. All participants were women of European descent with idiopathic OAB. OnabotulinumtoxinA (100 U) was administered in 20 intra-detrusor injections. Analysis was performed based on the results of safety assessments made during follow-up (FU) visits on weeks 2, 4 and 12, in 208 women who were treated with Botox injections for refractory OAB and who completed all FU visits. Women who required clean intermittent self-catheterisation (CISC) and those with post-void residual (PVR) greater than 200 ml were older in comparison with patients with PVR between 50 and 200 ml. Patients who required CISC were also characterised by higher parity and particularly by a higher number of vaginal deliveries. Other factors such as body mass index or comorbidities did not significantly influence PVR and the risk of CISC. Elderly and/or multiparous women are at increased risk of urinary retention after intravesical 100-U Botox injections. The risk of new onset urine retention in our study has completely disappeared 2 weeks after Botox injections. Based on our results of the way in which the PVRs have changed over time, we can conclude that OAB patients should be optimally assessed during the first 2 weeks after Botox injections.

Accelerated ischemic vascular retinopathy after intravitreally injected bevacizumab for central retinal vein occlusion in elderly patients

PubMed Central

Isola, Vincenzo; Pece, Alfredo; Massironi, Claudio; Reposi, Simone; Dimastrogiovanni, Fabio

2013-01-01

Background: Ischemic changes in the retinal circulation are an uncommon but severe adverse vascular reaction to intravitreal bevacizumab (Avastin®, Genentech, San Francisco, CA, USA/Roche, Basel, Switzerland) for central retinal vein occlusion (CRVO). In the two cases reported here, ischemic changes in the retina vasculature following intravitreal bevacizumab for CRVO were observed with the aim of describing the clinical and angiographic features of these changes. Methods: Two elderly patients with recent-onset CRVO received one off-label intravitreal injection of bevacizumab 0.05 mL/1.25 mg. Results: In Case 1, the patient’s pre-treatment visual acuity was 20/400. At 3 weeks post injection, the patient could count fingers at a distance of 1 ft (30 cm) and fluorescein angiography showed reduction in intraretinal hemorrhages and areas of retinal non-perfusion. However, at 6 weeks these were markedly increased compared with those seen in the photograph taken 3 weeks after treatment. In Case 2, the patient’s pre-treatment visual acuity was 20/200. At 1 month post injection, vision had decreased to 20/400 and fluorescein angiography showed severe macular ischemia with a remarkable capillary dropout throughout the macula. Conclusion: Ischemic retinal injury may be an uncommon but severe adverse vascular reaction to intravitreal bevacizumab for CRVO. Although progression of retinal ischemia in CRVO could be observed shortly after intravitreal bevacizumab, whether this is a drug- or procedure-related effect or part of the natural history of the condition remains uncertain. PMID:23467497

Defining the Catalytic Activity of Nanoceria in the P23H-1 Rat, a Photoreceptor Degeneration Model

PubMed Central

Wong, Lily L.; Pye, Quentin N.; Chen, Lijuan; Seal, Sudipta; McGinnis, James F.

2015-01-01

Purpose Inorganic catalytic nanoceria or cerium oxide nanoparticles (CeNPs) are bona fide antioxidants that possess regenerative radical scavenging activities in vitro. Previously, we demonstrated that CeNPs had neuroprotective and anti-angiogenic properties in rodent retinal degeneration and neovascularization models. However, the cellular mechanisms and duration of the catalytic activity of CeNPs in preventing photoreceptor cell loss are still unknown. In this study, we sought to answer these questions using the P23H-1 rat, an autosomal dominant retinitis pigmentosa (adRP) model. Methods A single dose of either saline or CeNPs was delivered intravitreally into the eyes of P23H-1 rats at 2–3 weeks of age. Retinal functions were examined at 3 to 7 weeks post injection. We quantified retinal proteins by Western blot analyses and counted the number of apoptotic (TUNEL+) profiles in the outer nuclear layer (ONL) of retinal sections. We measured free 8-isoprostanes to quantify lipid peroxidation in retinal tissues. Results We observed increased rod and cone cell functions up to three weeks post injection. Apoptotic cells were reduced by 46%, 56%, 21%, and 24% at 3, 7, 14, 21 days, respectively, after CeNPs injection compared to saline. Additionally, reduction of lipid peroxidation in the retinas of CeNPs-treated vs saline-treated animals was detected 14 days post injection. Conclusions We validated that CeNPs were effective in delaying loss of photoreceptor cell function in an adRP rat model. This represents the fourth rodent retinal disease model that shows delay in disease progression after a single application of CeNPs. We further demonstrated that CeNPs slowed the rate of photoreceptor cell death. We deduced that the catalytic activity of CeNPs in vivo in this rat model to be undiminished for at least 7 days and then declined over the next 14 days after CeNPs administration. PMID:25822196

The role of neural precursor cells and self assembling peptides in nerve regeneration

PubMed Central

2013-01-01

Objective Cranial nerve injury involves loss of central neural cells in the brain stem and surrounding support matrix, leading to severe functional impairment. Therapeutically targeting cellular replacement and enhancing structural support may promote neural regeneration. We examined the combinatorial effect of neural precursor cells (NPC) and self assembling peptide (SAP) administration on nerve regeneration. Methods Nerve injury was induced by clip compression of the rodent spinal cord. SAPs were injected immediately into the injured cord and NPCs at 2 weeks post-injury. Behavioral analysis was done weekly and rats were sacrificed at 11 weeks post injury. LFB-H&E staining was done on cord tissue to assess cavitation volume. Motor evoked potentials (MEP) were measured at week 11 to assess nerve conduction and Kaplan meier curves were created to compare survival estimates. Results NPCs and SAPs were distributed both caudal and rostral to the injury site. Behavioral analysis showed that SAP + NPC transplantation significantly improved locomotor score p <0.03) and enhanced survival (log rank test, p = 0.008) compared to control. SAP + NPC treatment also improved nerve conduction velocity (p = 0.008) but did not affect cavitation volume (p = 0.73). Conclusion Combinatorial NPC and SAP injection into injured nerve tissue may enhance neural repair and regeneration. PMID:24351041

The role of neural precursor cells and self assembling peptides in nerve regeneration.

PubMed

Zhao, Xiao; Yao, Gordon S; Liu, Yang; Wang, Jian; Satkunendrarajah, Kajana; Fehlings, Michael

2013-12-19

Cranial nerve injury involves loss of central neural cells in the brain stem and surrounding support matrix, leading to severe functional impairment. Therapeutically targeting cellular replacement and enhancing structural support may promote neural regeneration. We examined the combinatorial effect of neural precursor cells (NPC) and self assembling peptide (SAP) administration on nerve regeneration. Nerve injury was induced by clip compression of the rodent spinal cord. SAPs were injected immediately into the injured cord and NPCs at 2 weeks post-injury. Behavioral analysis was done weekly and rats were sacrificed at 11 weeks post injury. LFB-H&E staining was done on cord tissue to assess cavitation volume. Motor evoked potentials (MEP) were measured at week 11 to assess nerve conduction and Kaplan Meier curves were created to compare survival estimates. NPCs and SAPs were distributed both caudal and rostral to the injury site. Behavioral analysis showed that SAP + NPC transplantation significantly improved locomotor score p <0.03) and enhanced survival (log rank test, p = 0.008) compared to control. SAP + NPC treatment also improved nerve conduction velocity (p = 0.008) but did not affect cavitation volume (p = 0.73). Combinatorial NPC and SAP injection into injured nerve tissue may enhance neural repair and regeneration.

Mortality, Transmitter Retention, Growth, and Wound Healing in Juvenile Salmon Injected with Micro Acoustic Transmitters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liss, Stephanie A.; Brown, Richard S.; Deters, Katherine A.

A cylindrical acoustic transmitter (AT; 0.2 g) has been developed for injection into the peritoneum of fish. Laboratory studies can provide tagging guidelines to minimize the effect of implantation techniques and transmitter burden (relative weight of the transmitter to the weight of the fish) in fish before a transmitter is used in field studies. The goal of this study was to examine response variables (mortality, transmitter expulsion, growth, wound area) of juvenile Chinook Salmon (Oncorhynchus tschawytscha; 65–104 mm fork length [FL]) injected with an AT along a wide range of sizes that could lead to a guideline for minimizing taggingmore » effects. The overarching goal was to determine a minimum size threshold for fish that can be injected, while minimizing adverse transmitter effects. Juveniles (n = 700) were separated into four treatments: (1) acoustic transmitter injection (AT), (2) AT and a passive integrated transponder tag injection (AT+PIT), (3) visual implant elastomer injection (Marked control), and (4) unmarked (Unmarked control). Fish were evaluated weekly for four weeks, and again at the end of the study (60 d post-tagging). Fish injected with an AT or an AT+PIT experienced greater mortality than Marked controls. By 60 d post-tagging, transmitter expulsion was 44% for AT fish and 20% for AT+PIT fish. Fish injected with an AT or an AT+PIT grew (FL and weight gain) significantly less than Marked controls, and no minimum size thresholds were detected. Finally, initial size (FL) significantly affected wound area in AT and AT+PIT fish. A size threshold was only identified on Day 7 (85.1 mm) for AT+PIT fish, indicating that wound areas in fish < 85.1 mm were larger than wound areas of fish > 85.1 mm. This research suggests that injecting juveniles with an AT or an AT+PIT had a greater effect on smaller fish than larger fish.« less

Assessing the impact of a temporary class drug order on ethylphenidate-related infections among people who inject drugs in Lothian, Scotland: an interrupted time-series analysis.

PubMed

Yeung, Alan; Weir, Amanda; Austin, Hannah; Morrison, Kirsty; Inverarity, Donald; Sherval, Jim; Henderson, Naomi; Joshi, Shruti; Ure, Roisin; McAuley, Andrew

2017-10-01

In April 2015, the UK government enacted a temporary class drug order (TCDO) on ethylphenidate in response to reported harms associated with its use, in particular an outbreak of infections among people who inject drugs (PWID) in Lothian, Scotland. This study assesses the effect that the TCDO had on reducing the most common infections identified during the outbreak: Streptococcus pyogenes and Staphylococcus aureus. The outbreak was split into a pre-intervention period (35 weeks) and a post-intervention period (26 weeks) based around the date of the TCDO. Segmented negative binomial regression models were used to compare trends in weekly counts of infections between the pre- and post-intervention periods. PWID in the Lothian region of Scotland. Cases of S. pyogenes and S. aureus infections reported within the National Health Service, Lothian. There were 251 S. pyogenes and/or S. aureus infections recorded among 211 PWID between February 2014 and December 2015: 171 infections in the pre-intervention period and 51 in the post-intervention period. Significant trend changes in weekly S. pyogenes and/or S. aureus infections following the TCDO were found [relative risk (RR) = 0.88, 95% confidence interval (CI) = 0.82-0.94]. PWID who self-reported using novel psychoactive substances (NPS) were at higher risk of acquiring these infections (RR = 1.81, 95% CI = 1.12-2.93), particularly when comparing the risk of infection with NPS use for a specific strain, S. pyogenes emm76.0, against the risk of infection with NPS use for S. pyogenes (emm types other than emm76.0) (RR = 3.49, 95% CI = 1.32-9.21). The UK government's 2015 temporary class drug order on ethylphenidate was effective in reducing infections among people who inject drugs during an outbreak situation in Lothian, Scotland. © 2017 Crown copyright.

PAMAM Dendrimers Cross the Blood-Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice.

PubMed

Srinageshwar, Bhairavi; Peruzzaro, Sarah; Andrews, Melissa; Johnson, Kayla; Hietpas, Allison; Clark, Brittany; McGuire, Crystal; Petersen, Eric; Kippe, Jordyn; Stewart, Andrew; Lossia, Olivia; Al-Gharaibeh, Abeer; Antcliff, Aaron; Culver, Rebecca; Swanson, Douglas; Dunbar, Gary; Sharma, Ajit; Rossignol, Julien

2017-03-14

Drug delivery into the central nervous system (CNS) is challenging due to the blood-brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH₂ and G4-NH₂) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures. In vivo experiments involved transplantation of G4-90/10 into mice through (1) invasive intracranial injections into the striatum; and (2) less invasive carotid injections. The animals were sacrificed 24-h and 1-week post-transplantations and their brains were analyzed. In vivo experiments proved that the G4-90/10 can cross the BBB when injected through the carotid artery and localize within neurons and glial cells. The dendrimers were found to migrate through the corpus callosum 1-week post intracranial injection. Immunohistochemistry showed that the migrating cells are the dendrimer-infected glial cells. Overall, our results suggest that poly-amidoamine (PAMAM) dendrimers may be used as a minimally invasive means to deliver biomolecules for treating neurological diseases or disorders.

A comparison of the oral application and injection routes using the onderstepoort biological products fowl typhoid vaccine, its safety, efficacy and duration of protection in commercial laying hens.

PubMed

Purchase, C; Picard, J; McDonald, R; Bisschop, S P R

2008-03-01

This study was undertaken to establish whether the Onderstepoort Biological Products Fowl Typhoid (OBPft) vaccine registered as an injectable vaccine was effective and safe when administered orally to commercial layers. Its efficacy and duration of protection were compared with application by intramuscular injection. Commercial brown layer hens were used as they were found to be highly susceptible to Salmonella gallinarum infections. In the vaccine safety trial birds were euthanased at timed intervals spanning 4 weeks postvaccination. Necropsies were performed and samples were taken and tested. No clinical signs or mortalities could be attributed to the OBPft vaccine nor could active shedding of the vaccine strain be detected. Slight pathological changes were noted with both routes of vaccination; however, these changes were transient, returning to normal within the observation period. The injected groups showed a better serological response with the rapid serum plate agglutination (RSPA) test than the orally vaccinated groups. In the duration of protection trial, birds were challenged at 3-8-week intervals post-vaccination. All unvaccinated birds died. Protection 8 and 16 weeks after vaccination was above 60 %,by 24 weeks after challenge, the vaccine protection was below 30 %. It was found that there was no significant difference (P < 0.05) in the protection offered by either the oral or injected route of vaccination with the OBPft vaccine.

Wallula Basalt Pilot Demonstration Project: Post-injection Results and Conclusions

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGrail, Bernard Pete; Schaef, Herbert T.; Spane, Frank A.

Deep underground geologic formations are emerging as a reasonable option for long-term storage of CO 2, including large continental flood basalt formations. At the GHGT-11 and GHGT-12 conferences, progress was reported on the initial phases for Wallula Basalt Pilot demonstration test (located in Eastern Washington state), where nearly 1,000 metric tons of CO 2 were injected over a 3-week period during July/August 2013. The target CO 2 injection intervals were two permeable basalt interflow reservoir zones with a combined thickness of ~20 m that occur within a layered basalt sequence between a depth of 830-890 m below ground surface. Duringmore » the two-year post-injection period, downhole fluid samples were periodically collected during this post-injection monitoring phase, coupled with limited wireline borehole logging surveys that provided indirect evidence of on-going chemical geochemical reactions/alterations and CO 2 disposition. A final detailed post-closure field characterization program that included downhole fluid sampling, and performance of hydrologic tests and wireline geophysical surveys. Included as part of the final wireline characterization activities was the retrieval of side-wall cores from within the targeted injection zones. These cores were examined for evidence of in-situ mineral carbonization. Visual observations of the core material identified small globular nodules, translucent to yellow in color, residing within vugs and small cavities of the recovered basalt side-wall cores, which were not evident in pre-injection side-wall cores obtained from the native basalt formation. Characterization by x-ray diffraction identified these nodular precipitates as ankerite, a commonly occurring iron and calcium rich carbonate. Isotopic characterization (δ 13C, δ 18O) conducted on the ankerite nodules indicate a distinct isotopic signature that is closely aligned with that of the injected CO 2. Both the secondary mineral nodules and injected CO 2 are measurably different from the isotopic content of basalt, injection zone groundwater and for naturally occurring calcite. Final post-injection wireline geophysical logging results also indicate the presence of free-phase CO 2 at the top of the two injection interflow zones, with no vertical migration of CO 2 above the injection horizons. Furthermore, these findings are significant and demonstrate the feasibility of sequestering CO 2 in a basalt formation.« less

Wallula Basalt Pilot Demonstration Project: Post-injection Results and Conclusions

DOE PAGES

McGrail, Bernard Pete; Schaef, Herbert T.; Spane, Frank A.; ...

2017-08-18

Deep underground geologic formations are emerging as a reasonable option for long-term storage of CO 2, including large continental flood basalt formations. At the GHGT-11 and GHGT-12 conferences, progress was reported on the initial phases for Wallula Basalt Pilot demonstration test (located in Eastern Washington state), where nearly 1,000 metric tons of CO 2 were injected over a 3-week period during July/August 2013. The target CO 2 injection intervals were two permeable basalt interflow reservoir zones with a combined thickness of ~20 m that occur within a layered basalt sequence between a depth of 830-890 m below ground surface. Duringmore » the two-year post-injection period, downhole fluid samples were periodically collected during this post-injection monitoring phase, coupled with limited wireline borehole logging surveys that provided indirect evidence of on-going chemical geochemical reactions/alterations and CO 2 disposition. A final detailed post-closure field characterization program that included downhole fluid sampling, and performance of hydrologic tests and wireline geophysical surveys. Included as part of the final wireline characterization activities was the retrieval of side-wall cores from within the targeted injection zones. These cores were examined for evidence of in-situ mineral carbonization. Visual observations of the core material identified small globular nodules, translucent to yellow in color, residing within vugs and small cavities of the recovered basalt side-wall cores, which were not evident in pre-injection side-wall cores obtained from the native basalt formation. Characterization by x-ray diffraction identified these nodular precipitates as ankerite, a commonly occurring iron and calcium rich carbonate. Isotopic characterization (δ 13C, δ 18O) conducted on the ankerite nodules indicate a distinct isotopic signature that is closely aligned with that of the injected CO 2. Both the secondary mineral nodules and injected CO 2 are measurably different from the isotopic content of basalt, injection zone groundwater and for naturally occurring calcite. Final post-injection wireline geophysical logging results also indicate the presence of free-phase CO 2 at the top of the two injection interflow zones, with no vertical migration of CO 2 above the injection horizons. Furthermore, these findings are significant and demonstrate the feasibility of sequestering CO 2 in a basalt formation.« less

Intravitreal Aflibercept Injection in Eyes With Substantial Vision Loss After Laser Photocoagulation for Diabetic Macular Edema: Subanalysis of the VISTA and VIVID Randomized Clinical Trials.

PubMed

Wykoff, Charles C; Marcus, Dennis M; Midena, Edoardo; Korobelnik, Jean-François; Saroj, Namrata; Gibson, Andrea; Vitti, Robert; Berliner, Alyson J; Williams Liu, Zinaria; Zeitz, Oliver; Metzig, Carola; Schmelter, Thomas; Heier, Jeffrey S

2016-12-22

Information on the effect of anti-vascular endothelial growth factor therapy in eyes with diabetic macular edema (DME) with vision loss after macular laser photocoagulation is clinically valuable. To evaluate visual and anatomic outcomes in a subgroup of macular laser photocoagulation treatment control (hereafter laser control) eyes with substantial vision loss receiving treatment with intravitreal aflibercept injection. This investigation was a post hoc analysis of a subgroup of laser control eyes in 2 phase 3 trials-VISTA (Study of Intravitreal Aflibercept Injection in Patients With Diabetic Macular Edema) and VIVID (Intravitreal Aflibercept Injection in Vision Impairment Due to DME)-in a multicenter setting. One hundred nine laser control eyes with center-involving DME were included. Treatment with intravitreal aflibercept injection (2 mg) every 8 weeks after 5 monthly doses with sham injections on nontreatment visits starting at week 24 was initiated on meeting prespecified criteria of at least a 10-letter visual acuity loss at 2 consecutive visits or at least a 15-letter visual acuity loss from the best previous measurement at 1 visit and vision not better than at baseline. Visual and anatomic outcomes in a subgroup of laser control eyes receiving treatment with intravitreal aflibercept injection. Through week 100, a total of 63 of 154 eyes (40.9%) in VISTA and 46 of 133 eyes (34.6%) in VIVID initially randomized to laser control received treatment with intravitreal aflibercept injection. The median time from week 24 to the first intravitreal aflibercept injection treatment was 34.0 (VISTA) and 83.5 (VIVID) days. In this subgroup, the mean (SD) visual gain from baseline to week 100 was 2.2 (12.5) (VISTA) and 3.8 (10.1) (VIVID) letters. At the time of intravitreal aflibercept injection initiation, these eyes had a mean (SD) loss of 11.0 (10.1) (VISTA) and 10.0 (6.5) (VIVID) letters from baseline, and they subsequently gained a mean (SD) of 17.4 (9.7) (VISTA) and 13.6 (8.6) (VIVID) letters from the initiation of treatment with intravitreal aflibercept injection through week 100. There was a minimal mean change in central subfield thickness from baseline in these eyes at the time of intravitreal aflibercept injection initiation (an increase of 3.9 μm in VISTA and a decrease of 3.0 μm in VIVID), after which further mean (SD) reductions of 285.6 (202.6) μm (VISTA) and 313.4 (181.9) μm (VIVID) occurred through week 100. Intravitreal aflibercept injection improves visual and anatomic outcomes in eyes experiencing substantial vision loss after macular laser photocoagulation treatment for DME. clinicaltrials.gov Identifiers: NCT01363440 and NCT01331681.

Physical Therapy for an Adult with Chronic Stroke after Botulinum Toxin Injection for Spasticity: A Case Report

PubMed Central

Phadke, Chetan P.; Ismail, Farooq; Boulias, Chris

2015-01-01

ABSTRACT Purpose: In this case report, we describe the type and duration of a physical therapy and botulinum toxin type A (BoNTA) intervention directed at lower limb spasticity and the gait and balance improvement in a patient post-stroke. Treatment of focal spasticity with BoNTA intramuscular injections combined with physical therapy is recommended by rehabilitation experts. However, the optimal type and duration of physical therapy intervention to optimize any functional gains that follow chemodenervation induced by BoNTA has not been established. Method: One individual with chronic stroke who received BoNTA injections for upper and lower extremity spasticity was included. Physical therapy intervention consisted of 45- to 60-min sessions twice weekly for 12 weeks, based on the Bobath–neurodevelopmental therapy approach, and an activity-based home program. Results: After BoNTA injections and physical therapy, the patient made clinically significant improvements in balance and gait speed and became more independent with his ambulation. Conclusions: This case report demonstrates that physical therapy after BoNTA injections can result in significant functional improvements for individuals with spasticity after chronic stroke that may not be possible with BoNTA injections alone. PMID:25931655

Evaluation of Mitoquinone for Protecting Against Amikacin-Induced Ototoxicity in Guinea Pigs.

PubMed

Dirain, Carolyn O; Ng, Maria Raye Ann V; Milne-Davies, Bailey; Joseph, Jerin K; Antonelli, Patrick J

2018-01-01

Mitoquinone (MitoQ) attenuates amikacin ototoxicity in guinea pigs. MitoQ, a mitochondria-targeted derivative of the antioxidant ubiquinone, has improved bioavailability and demonstrated safety in humans. Thus, MitoQ is a promising therapeutic approach for protecting against amikacin-induced ototoxicity. Both oral and subcutaneous administrations of MitoQ were tested. Amikacin-treated guinea pigs (n = 12-18 per group) received water alone (control) or MitoQ 30 mg/l-supplemented drinking water; or injected subcutaneously with 3 to 5 mg/kg MitoQ or saline (control). Auditory brainstem responses and distortion product otoacoustic emissions were measured before MitoQ or control solution administration and after amikacin injections. Cochlear hair cell damage was assessed using scanning electron microscopy and Western blotting. With oral administration, animals that received 30 mg/l MitoQ had better hearing than controls at only 24 kHz at 3-week (p = 0.017) and 6-week (p = 0.027) post-amikacin. With subcutaneous administration, MitoQ-injected guinea pigs had better hearing than controls at only 24 kHz, 2-week post-amikacin (p = 0.013). Distortion product otoacoustic emission (DPOAE) amplitudes were decreased after amikacin injections, but were not different between treatments (p > 0.05). Electron microscopy showed minor difference in outer hair cell loss between treatments. Western blotting demonstrated limited attenuation of oxidative stress in the cochlea of MitoQ-supplemented guinea pigs. Oral or subcutaneous MitoQ provided limited protection against amikacin-induced hearing loss and cochlear damage in guinea pigs. Other strategies for attenuating aminoglycoside-induced ototoxicity should be explored.

Diversion and injection of buprenorphine-naloxone film two years post-introduction in Australia.

PubMed

Larance, Briony; Mattick, Richard; Ali, Robert; Lintzeris, Nicholas; Jenkinson, Rebecca; White, Nancy; Kihas, Ivana; Cassidy, Rosemary; Degenhardt, Louisa

2016-01-01

We report 2 years of post-marketing surveillance of the diversion and injection of buprenorphine-naloxone (BNX) film following its introduction in 2011. Interviews were conducted with people who inject drugs regularly (PWID) (2004-2013), opioid substitution therapy clients (2013, n = 492) and key experts (n = 44). Key outcomes were unsanctioned removal of supervised doses, diversion, injection and street price. Prevalence of past 6-month injection among PWID was adjusted for background availability of opioid substitution therapy medications using sales data. Among out-of-treatment PWID, the levels of regular (weekly+) BNX film injection were comparable to methadone and BNX tablets, and lower than mono-buprenorphine, adjusting for background availability. Fewer BNX film clients [3%; 95% (CI) 1-5] regularly injected their medication than mono-buprenorphine clients (25%; 95% CI 11-39), but at levels equivalent to those among methadone (3%; 95% CI 1-6) and BNX tablet clients (2%; 95% CI 0-6). Key experts perceived BNX film needed less supervised dosing time as it dissolved rapidly and was harder to remove from the mouth than sublingual tablets; however, removal of supervised doses was higher among BNX film clients (15%; 95% CI: 10-20) than methadone clients (3%; 95% CI 1-6), and not significantly different from BNX tablet (11%; 95% CI 2-21) and mono-buprenorphine clients (31%; 95% CI 16-46). Two years post-introduction, levels of BNX film diversion and injection remained comparable with those for methadone and BNX tablets, and lower than mono-buprenorphine. We found no evidence that BNX film has lower non-adherence and diversion than the tablet formulation. [Larance B, Mattick R, Ali R, Lintzeris N, Jenkinson R, White N, Kihas I, Cassidy R, Degenhardt L. Diversion and injection of buprenorphine-naloxone film two years post-introduction in Australia. Drug Alcohol Rev 2015]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Adipose Stem Cell-Based Therapeutic Targeting of Residual Androgens in African Americans with Bone-Metastatic Prostate Cancer

DTIC Science & Technology

2015-11-01

points post xenograft . We demonstrated that ADMSCs derived from African American with PC (ADMSCAA) promote LNCaP cell tumor growth in gonad-intact...Task-7: Compare the ability of ADMSCCont and ADMSCSel cells to colocalize to bone tumor xenografts in vivo. 7.1. Inject CaP cells, alone or with...construct expressing GFP (pLV-GFP). Nude mice (n=5) bearing LNCaP xenografts ( 8weeks) were injected with 2 x 105 transduced GFP-expressing ADMSCs and

Benign Post-Radiation Rectal Stricture Treated with Endoscopic Balloon Dilation and Intralesional Triamcinolone Injection

PubMed Central

Karanikas, Michael; Touzopoulos, Panagiotis; Mitrakas, Alexandros; Zezos, Petros; Zarogoulidis, Paul; Machairiotis, Nikolaos; Efremidou, Eleni; Liratzopoulos, Nikolaos; Polychronidis, Alexandros; Kouklakis, George

2012-01-01

Post-radiation stricture is a rare complication after pelvis irradiation, but must be in the mind of the clinician evaluating a lower gastrointestinal obstruction. Endoscopy has gained an important role in chronic radiation proctitis with several therapeutic options for management of intestinal strictures. The treatment of rectal strictures has been limited to surgery with high morbidity and mortality. Therefore, a less invasive therapeutic approach for benign rectal strictures, endoscopic balloon dilation with or without intralesional steroid injection, has become a common treatment modality. We present a case of benign post-radiation rectal stricture treated successfully with balloon dilation and adjuvant intralesional triamcinolone injection. A 70-year-old woman presented to the emergency room complaining for 2 weeks of diarrhea and meteorism, 11 years after radiation of the pelvis due to adenocarcinoma of the uterus. Colonoscopy revealed a stricture at the rectum and multiple endoscopic biopsies were obtained from the stricture. The stricture was treated with endoscopic balloon dilation and intralesional triamcinolone injection. The procedure appears to have a high success rate and a very low complication rate. Histologic examination of the biopsies revealed non-specific inflammatory changes of the rectal mucosa and no specific changes of the mucosa due to radiation. All biopsies were negative for malignancy. The patient is stricture-free 12 months post-treatment. PMID:23271987

Retention of Human-Induced Pluripotent Stem Cells (hiPS) With Injectable HA Hydrogels for Vocal Fold Engineering.

PubMed

Imaizumi, Mitsuyoshi; Li-Jessen, Nicole Y K; Sato, Yuka; Yang, David T; Thibeault, Susan L

2017-04-01

One prospective treatment option for vocal fold scarring is regeneration with an engineered scaffold containing induced pluripotent stem cells (iPS). In the present study, we investigated the feasibility of utilizing an injectable hyaluronic acid (HA) scaffold encapsulated with human-iPS cell (hiPS) for regeneration of vocal folds. Thirty athymic nude rats underwent unilateral vocal fold injury. Contralateral vocal folds served as uninjured controls. Hyaluronic acid hydrogel scaffold, HA hydrogel scaffold containing hiPS, and HA hydrogel scaffold containing hiPS with epidermal growth factor (EGF) were injected in both vocal folds immediately after surgery. One and 2 weeks after injection, larynges were excised for histology, immunohistochemistry, and fluorescence in situ hybridization (FISH). Presence of HA hydrogel was confirmed in vocal folds 1 and 2 weeks post injection. The FISH analysis confirmed the presence and viability of hiPS in the injected vocal folds. Histological results demonstrated that vocal folds injected with HA hydrogel scaffold containing EGF demonstrated less fibrosis than those with HA hydrogel only. Human-iPS survived in injured rat vocal folds. The HA hydrogel with hiPS and EGF ameliorated the fibrotic response. Additional work is necessary to optimize hiPS differentiation and further confirm the safety of hiPS for clinical applications.

Autologous whole blood versus corticosteroid local injection in treatment of plantar fasciitis: A randomized, controlled multicenter clinical trial.

PubMed

Karimzadeh, Afshin; Raeissadat, Seyed Ahmad; Erfani Fam, Saleh; Sedighipour, Leyla; Babaei-Ghazani, Arash

2017-03-01

Plantar fasciitis is the most common cause of heel pain. Local injection modalities are among treatment options in patients with resistant pain. The aim of the present study was to evaluate the effect of local autologous whole blood compared with corticosteroid local injection in treatment of plantar fasciitis. In this randomized controlled multicenter study, 36 patients with chronic plantar fasciitis were recruited. Patients were allocated randomly into three treatment groups: local autologous blood, local corticosteroid injection, and control groups receiving no injection. Patients were assessed with visual analog scale (VAS), pressure pain threshold (PPT), and plantar fasciitis pain/disability scale (PFPS) before treatment, as well as 4 and 12 weeks post therapy. Variables of pain and function improved significantly in both corticosteroid and autologous blood groups compared to control group. At 4 weeks following treatment, patients in corticosteroid group had significantly lower levels of pain than patients in autologous blood and control groups (higher PPT level, lower PFPS, and VAS). After 12 weeks of treatment, both corticosteroid and autologous blood groups had lower average levels of pain than control group. The corticosteroid group showed an early sharp and then more gradual improvement in pain scores, but autologous blood group had a steady gradual drop in pain. Autologous whole blood and corticosteroid local injection can both be considered as effective methods in the treatment of chronic plantar fasciitis. These treatments decrease pain and significantly improve function compared to no treatment.

Patterns of faecal nematode egg shedding after treatment of sheep with a long-acting formulation of moxidectin.

PubMed

Crilly, James Patrick; Jennings, Amy; Sargison, Neil

2015-09-15

Much of the current information on the effects of long-acting anthelmintics on nematode populations derives either from research farms or mathematical models. A survey was performed with the aim of establishing how moxidectin is currently being used on sheep farms in the south-east of Scotland. A study was undertaken on a subsection of the surveyed farms to examine the effects of long-acting moxidectin treatments in both spring and autumn on faecal nematode egg output. The survey showed that whole flock treatments of injectable 2% moxidectin were used to control sheep scab on 21% of farms. Injectable 2% moxidectin and oral moxidectin were used to control the periparturient rise in faecal nematode egg shedding by ewes on 13% and 55% of farms respectively. The effects of injectable 2% moxidectin treatment on faecal nematode egg shedding post-treatment in both the autumn and spring were investigated by faecal nematode egg counts at the time of treatment and at 2-weekly interval thereafter on eight and six farms in the autumn and spring, respectively. Faecal egg shedding recommenced at 8 weeks (autumn) and 4 weeks (spring) post-treatment. Counts increased to a peak and then declined. The mean (95% confidence interval) peak counts post-treatment were 2.8 (0.6, 5.1), 3.6 (1.7, 5.5) and 53.5 (25.1, 82.0) eggs per gram (EPG) for autumn-treated ewes, autumn-treated lambs and spring-treated ewes respectively. The spring treated sheep showed a statistically significantly earlier return to faecal egg shedding (p=0.0125, p=0.0342) compared to both other groups, statistically significantly higher peak in egg counts than the autumn treated sheep (p<0.001) and a statistically significantly longer period of positive egg counts (p=0.0148). There was no statistically significant difference in the timing of the peak FECs between autumn and spring (p=0.211). The FECs of all groups of sheep treated with an injectable long-acting formulation of moxidectin became positive earlier than would be expected from the period of persistence given on the datasheet, but post-treatment FECs were very low compared to pre-treatment counts. Copyright © 2015 Elsevier B.V. All rights reserved.

ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model.

PubMed

Miyazaki, Shingo; Diwan, Ashish D; Kato, Kenji; Cheng, Kevin; Bae, Won C; Sun, Yang; Yamada, Junichi; Muehleman, Carol; Lenz, Mary E; Inoue, Nozomu; Sah, Robert L; Kawakami, Mamoru; Masuda, Koichi

2018-04-01

To elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model. Forty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 µg) was injected into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically. In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium-binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group. GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial.

PubMed

Rabago, David; Patterson, Jeffrey J; Mundt, Marlon; Kijowski, Richard; Grettie, Jessica; Segal, Neil A; Zgierska, Aleksandra

2013-01-01

Knee osteoarthritis is a common, debilitating chronic disease. Prolotherapy is an injection therapy for chronic musculoskeletal pain. We conducted a 3-arm, blinded (injector, assessor, injection group participants), randomized controlled trial to assess the efficacy of prolotherapy for knee osteoarthritis. Ninety adults with at least 3 months of painful knee osteoarthritis were randomized to blinded injection (dextrose prolotherapy or saline) or at-home exercise. Extra- and intra-articular injections were done at 1, 5, and 9 weeks with as-needed additional treatments at weeks 13 and 17. Exercise participants received an exercise manual and in-person instruction. Outcome measures included a composite score on the Western Ontario McMaster University Osteoarthritis Index (WOMAC; 100 points); knee pain scale (KPS; individual knee), post-procedure opioid medication use, and participant satisfaction. Intention-to-treat analysis using analysis of variance was used. No baseline differences existed between groups. All groups reported improved composite WOMAC scores compared with baseline status (P <.01) at 52 weeks. Adjusted for sex, age, and body mass index, WOMAC scores for patients receiving dextrose prolotherapy improved more (P <.05) at 52 weeks than did scores for patients receiving saline and exercise (score change: 15.3 ± 3.5 vs 7.6 ± 3.4, and 8.2 ± 3.3 points, respectively) and exceeded the WOMAC-based minimal clinically important difference. Individual knee pain scores also improved more in the prolotherapy group (P = .05). Use of prescribed postprocedure opioid medication resulted in rapid diminution of injection-related pain. Satisfaction with prolotherapy was high. There were no adverse events. Prolotherapy resulted in clinically meaningful sustained improvement of pain, function, and stiffness scores for knee osteoarthritis compared with blinded saline injections and at-home exercises.

Single dose parenteral hyposensitization to poison ivy urushiol in guinea pigs.

PubMed

Walker, L A; Watson, E S; elSohly, M A

1995-08-01

Studies were carried out in guinea pigs to evaluate the potential for single dose hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by topical application of 1 mg of poison ivy urushiol to the back of the neck. In the first series of studies, three different analogs of poison ivy urushiol were studied: 1) a mixture of pentadecyl and heptadecyl catechols (PDC/HDC), the saturated side chain analog of the natural urushiol mixture; 2) a mixture of the diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac). Each of these compounds was administered as 5 mg of the free catechol i.m. each week for three weeks. A vehicle group received only corn oil injections. Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at 1 and 5 weeks post-treatment. PDC/HDC Ac induced a marked reduction in both the incidence and the severity of lesions induced by PIU at both 1 and at 5 weeks post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and were less effective than PDC/HDC Ac at 1 week post-treatment. In a second series of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac intramuscularly each week for 4 weeks, while another treatment group received a single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac was only modestly effective, with some reduction of severity of lesions at the higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the incidence and the severity of the lesions at all challenge doses were reduced. In the multiple dose group, the incidence and severity of lesions are reduced at 1 week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but were not significantly different from the single dose group. These findings indicate that the diacetate ester of PDC/HDC is an effective hyposensitizer to poison ivy urushiol, and that this hyposensitization can be reasonably accomplished in a single dose treatment regimen.

Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions--a pilot study.

PubMed

Geburek, Florian; Mundle, Kathrin; Conrad, Sabine; Hellige, Maren; Walliser, Ulrich; van Schie, Hans T M; van Weeren, René; Skutella, Thomas; Stadler, Peter M

2016-02-01

Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used to treat equine tendinopathies. Up to now, knowledge about the fate of autologous AT-MSCs after intralesional injection into equine superficial digital flexor tendons (SDFTs) is very limited. The purpose of this study was to monitor the presence of intralesionally injected autologous AT-MSCs labelled with superparamagnetic iron oxide (SPIO) nanoparticles and green fluorescent protein (GFP) over a staggered period of 3 to 9 weeks with standing magnetic resonance imaging (MRI) and histology. Four adult warmblood horses received a unilateral injection of 10 × 10(6) autologous AT-MSCs into surgically created front-limb SDFT lesions. Administered AT-MSCs expressed lentivirally transduced reporter genes for GFP and were co-labelled with SPIO particles in three horses. The presence of AT-MSCs in SDFTs was evaluated by repeated examinations with standing low-field MRI in two horses and post-mortem in all horses with Prussian blue staining, fluorescence microscopy and with immunofluorescence and immunohistochemistry using anti-GFP antibodies at 3, 5, 7 and 9 weeks after treatment. AT-MSCs labelled with SPIO particles were detectable in treated SDFTs during each MRI in T2*- and T1-weighted sequences until the end of the observation period. Post-mortem examinations revealed that all treated tendons contained high numbers of SPIO- and GFP-labelled cells. Standing low-field MRI has the potential to track SPIO-labelled AT-MSCs successfully. Histology, fluorescence microscopy, immunofluorescence and immunohistochemistry are efficient tools to detect labelled AT-MSCs after intralesional injection into surgically created equine SDFT lesions. Intralesional injection of 10 × 10(6) AT-MSCs leads to the presence of high numbers of AT-MSCs in and around surgically created tendon lesions for up to 9 weeks. Integration of injected AT-MSCs into healing tendon tissue is an essential pathway after intralesional administration. Injection techniques have to be chosen deliberately to avoid reflux of the cell substrate injected. In vivo low-field MRI may be used as a non-invasive tool to monitor homing and engraftment of AT-MSCs in horses with tendinopathy of the SDFT.

Diffusion tensor imaging as a biomarker for assessing neuronal stem cell treatments affecting areas distal to the site of spinal cord injury.

PubMed

Jirjis, Michael B; Valdez, Chris; Vedantam, Aditya; Schmit, Brian D; Kurpad, Shekar N

2017-02-01

OBJECTIVE The aims of this study were to determine if the morphological and functional changes induced by neural stem cell (NSC) grafts after transplantation into the rodent spinal cord can be detected using MR diffusion tensor imaging (DTI) and, furthermore, if the DTI-derived mean diffusivity (MD) metric could be a biomarker for cell transplantation in spinal cord injury (SCI). METHODS A spinal contusion was produced at the T-8 vertebral level in 40 Sprague Dawley rats that were separated into 4 groups, including a sham group (injury without NSC injection), NSC control group (injury with saline injection), co-injection control group (injury with Prograf), and the experimental group (injury with NSC and Prograf injection). The NSC injection was completed 1 week after injury into the site of injury and the rats in the experimental group were compared to the rats from the sham, NSC control, and co-injection groups. The DTI index, MD, was assessed in vivo at 2, 5, and 10 weeks and ex vivo at 10 weeks postinjury on a 9.4-T Bruker scanner using a spin-echo imaging sequence. DTI data of the cervical spinal cord from the sham surgery, injury with saline injection, injury with injection of Prograf only, and injury with C17.2 NSC and Prograf injection were examined to evaluate if cellular proliferation induced by intrathoracic C17.2 engraftment was detectable in a noninvasive manner. RESULTS At 5 weeks after injury, the average fractional anisotropy, longitudinal diffusion (LD) and radial diffusion (RD) coefficients, and MD of water (average of the RD and LD eigenvalues in the stem cell line-treated group) increased to an average of 1.44 × 10 -3 sec/mm 2 in the cervical segments, while the control groups averaged 0.98 × 10 -3 s/mm 2 . Post hoc Tukey's honest significant difference tests demonstrated that the transplanted stem cells had significantly higher MD values than the other groups (p = 0.032 at 5 weeks). In vivo and ex vivo findings at 10 weeks displayed similar results. This statistical difference between the stem cell line and the other groups was maintained at the 10-week postinjury in vivo and ex vivo time points. CONCLUSIONS These results indicate that the DTI-derived MD metric collected from noninvasive imaging techniques may provide useful biomarker indices for transplantation interventions that produce changes in the spinal cord structure and function. Though promising, the results demonstrated here suggest additional work is needed before implementation in a clinical setting.

Botulinum Toxin A Injections Into Pelvic Floor Muscles Under Electromyographic Guidance for Women With Refractory High-Tone Pelvic Floor Dysfunction: A 6-Month Prospective Pilot Study.

PubMed

Morrissey, Darlene; El-Khawand, Dominique; Ginzburg, Natasha; Wehbe, Salim; O'Hare, Peter; Whitmore, Kristene

2015-01-01

High-tone pelvic floor dysfunction (HTPFD) is a debilitating chronic pain disorder for many women with significant impact on their quality of life (QoL). Our objective was to determine the efficacy of electromyography-guided onabotulinumtoxinA (Botox; Allergan, Irvine, Calif) injections in treating patient's perception of pelvic pain and improving QoL measurement scores. This is a prospective pilot open-label study of women with chronic pelvic pain and HTPFD who have failed conventional therapy between January 2011 and August 2013. Botox injections (up to 300 U) were done using needle electromyography guidance, from a transperineal approach, to localize spastic pelvic floor muscles (PFMs). Data were collected at baseline, 4, 8, 12, and 24 weeks after injections. This included demographics; Visual Analog Scale (VAS) scores for pain and dyspareunia; validated questionnaires for symptoms, QoL, and sexual function; Global Response Assessment scale for pelvic pain; digital examination of PFM for tone and tenderness; and vaginal manometry. Side effects were also recorded. Out of 28 women who enrolled in the study, 21 completed the 6-month follow-up and qualified for analysis. The mean (SD) age was 35.1 (9.4) years (range, 22-50 years), and the mean (SD) body mass index was 25 (4.4). Comorbidities included interstitial cystitis/bladder pain syndrome (42.9%) and vulvodynia (66.7%). Overall, 61.9% of subjects reported improvement on Global Response Assessment at 4 weeks and 80.9% at 8, 12, and 24 weeks post injection, compared with baseline. Of the subjects who were sexually active at baseline, 58.8% (10/17), 68.8% (11/16), 80% (12/15), and 83.3% (15/18) reported less dyspareunia at 4, 8, 12, and 24 weeks, respectively. Dyspareunia Visual Analog Scale score significantly improved at weeks 12 (5.6, P = 0.011) and 24 (5.4, P = 0.004) compared with baseline (7.8). Two of the 4 patients who avoided sexual activity at baseline secondary to dyspareunia resumed and tolerated intercourse after Botox. Sexual dysfunction as measured by the Female Sexual Distress Scale significantly improved at 8 weeks (27.6, P = 0.005), 12 weeks (27.9, P = 0.006), and 24 weeks (22.6, P < 0.001) compared with baseline (34.5). The Short-Form 12 Health Survey (SF-12) showed improved QoL in the physical composite score at all post injections visits (42.9, 44, 43.1, and 45.5 vs 40 at baseline; P < 0.05), and in the mental composite score at both 12 and 24 weeks (44.3 and 47.8 vs 38.5, P = 0.012). Vaginal manometry demonstrated significant decrease in resting pressures and in maximum contraction pressures at all follow-up visits (P < 0.05). Digital assessment of PFM (on a scale from 0 to 4) showed decreased tenderness on all visits (mean of 1.9, 1.7, 1.8, 1.9; P < 0.001) compared with baseline (2.8). Reported postinjection adverse effects included worsening of the following preexisting conditions: constipation (28.6%), stress urinary incontinence (4.8%), fecal incontinence (4.8%), and new onset stress urinary incontinence (4.8%). Electromyography-guided Botox injection into PFM could be beneficial for women with refractory HTPFD who have failed conservative therapy.

PAMAM Dendrimers Cross the Blood–Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice

PubMed Central

Srinageshwar, Bhairavi; Peruzzaro, Sarah; Andrews, Melissa; Johnson, Kayla; Hietpas, Allison; Clark, Brittany; McGuire, Crystal; Petersen, Eric; Kippe, Jordyn; Stewart, Andrew; Lossia, Olivia; Al-Gharaibeh, Abeer; Antcliff, Aaron; Culver, Rebecca; Swanson, Douglas; Dunbar, Gary; Sharma, Ajit; Rossignol, Julien

2017-01-01

Drug delivery into the central nervous system (CNS) is challenging due to the blood–brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH2 and G4-NH2) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures. In vivo experiments involved transplantation of G4-90/10 into mice through (1) invasive intracranial injections into the striatum; and (2) less invasive carotid injections. The animals were sacrificed 24-h and 1-week post-transplantations and their brains were analyzed. In vivo experiments proved that the G4-90/10 can cross the BBB when injected through the carotid artery and localize within neurons and glial cells. The dendrimers were found to migrate through the corpus callosum 1-week post intracranial injection. Immunohistochemistry showed that the migrating cells are the dendrimer-infected glial cells. Overall, our results suggest that poly-amidoamine (PAMAM) dendrimers may be used as a minimally invasive means to deliver biomolecules for treating neurological diseases or disorders PMID:28335421

Effects of an intravitreal injection of interleukin-35-expressing plasmid on pro-inflammatory and anti-inflammatory cytokines.

PubMed

Hou, Chao; Wu, Qianni; Ouyang, Chen; Huang, Ting

2016-09-01

In order to explore the potential effects of interleukin (IL)-35 on IL-10, transforming growth factor-β (TGF-β), interferon-γ (INF)-γ, IL-12 and IL-17, a pcDNA3.1‑IL-35 plasmid was injected into the vitreous cavity of BALB/c mice. Enzyme-linked immunosorbent assay, western blot analysis and quantitative PCR analysis were performed to confirm the successful expression of IL-35. Slit-lamp biomicroscopy, hematoxylin and eosin staining and immunofluorescence were employed to detect the status of eyes, and western blot analysis was performed to examine the expression of corneal graft rejection-related cytokines. There were no abnormalities in the eyes pre-mydriasis or post-mydriasis and no injuries to the cornea or retina following the injection of IL-35-expressing plasmid. An immunofluorescence assay detected the positive expression of IL-35 in corneal epithelial cells from IL-35‑injected mice and negative staining in the control group. Further study revealed that IL-35 enhanced the expression of IL-10 and TGF-β which reached their highest levels at 1 and 2 weeks after injection, respectively (p<0.01). Moreover, the expression of INF-γ and IL-12 was decreased significantly at 2 weeks after the injection of IL-35-expressing plasmid (p<0.05), and the expression of IL-17 was suppressed notably at 4 weeks after the injection (p<0.05). The intravitreal injection of IL-35-expressing plasmid in mice downregulates the expression of pro-inflammatory cytokines and upregulates the expression of anti-inflammatory cytokines. Thus, IL-35 may further be assessed as a potential target for the treatment of corneal graft rejection.

Allogeneic Cardiospheres Delivered via Percutaneous Transendocardial Injection Increase Viable Myocardium, Decrease Scar Size, and Attenuate Cardiac Dilatation in Porcine Ischemic Cardiomyopathy

PubMed Central

Tseliou, Eleni; Cheng, Ke; Luthringer, Daniel J.; Ho, Chak-Sum; Takayama, Kentaro; Minamino, Naoto; Dawkins, James F.; Chowdhury, Supurna; Duong, Doan Trang; Seinfeld, Jeffrey; Middleton, Ryan C.; Dharmakumar, Rohan; Li, Debiao; Marbán, Linda; Makkar, Raj R.; Marbán, Eduardo

2014-01-01

Background Epicardial injection of heart-derived cell products is safe and effective post-myocardial infarction (MI), but clinically-translatable transendocardial injection has never been evaluated. We sought to assess the feasibility, safety and efficacy of percutaneous transendocardial injection of heart-derived cells in porcine chronic ischemic cardiomyopathy. Methods and Results We studied a total of 89 minipigs; 63 completed the specified protocols. After NOGA-guided transendocardial injection, we quantified engraftment of escalating doses of allogeneic cardiospheres or cardiosphere-derived cells in minipigs (n = 22) post-MI. Next, a dose-ranging, blinded, randomized, placebo-controlled (“dose optimization”) study of transendocardial injection of the better-engrafting product was performed in infarcted minipigs (n = 16). Finally, the superior product and dose (150 million cardiospheres) were tested in a blinded, randomized, placebo-controlled (“pivotal”) study (n = 22). Contrast-enhanced cardiac MRI revealed that all cardiosphere doses preserved systolic function and attenuated remodeling. The maximum feasible dose (150 million cells) was most effective in reducing scar size, increasing viable myocardium and improving ejection fraction. In the pivotal study, eight weeks post-injection, histopathology demonstrated no excess inflammation, and no myocyte hypertrophy, in treated minipigs versus controls. No alloreactive donor-specific antibodies developed over time. MRI showed reduced scar size, increased viable mass, and attenuation of cardiac dilatation with no effect on ejection fraction in the treated group compared to placebo. Conclusions Dose-optimized injection of allogeneic cardiospheres is safe, decreases scar size, increases viable myocardium, and attenuates cardiac dilatation in porcine chronic ischemic cardiomyopathy. The decreases in scar size, mirrored by increases in viable myocardium, are consistent with therapeutic regeneration. PMID:25460005

Sustained neuroprotection from a single intravitreal injection of PGJ₂ in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy.

PubMed

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M; Bernstein, Steven L

2014-10-08

Prostaglandin J₂ (PGJ₂) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ₂ in a nonhuman primate model of NAION (pNAION). We assessed PGJ₂ toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ₂ or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ₂ or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. PGJ₂ caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ₂ used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ₂; however, the amplitudes returned to normal in all animals within 1 week. In all eyes, a single IVT dose of PGJ₂ administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). In nonhuman primates, PGJ₂ administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ₂ is neuroprotective when administered up to 5 hours after induction of pNAION. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Transplantation of bone marrow stem cells as well as mobilization by granulocyte-colony stimulating factor promotes recovery after spinal cord injury in rats.

PubMed

Urdzíková, Lucia; Jendelová, Pavla; Glogarová, Katerina; Burian, Martin; Hájek, Milan; Syková, Eva

2006-09-01

Emerging clinical studies of treating brain and spinal cord injury (SCI) with autologous adult stem cells led us to compare the effect of an intravenous injection of mesenchymal stem cells (MSCs), an injection of a freshly prepared mononuclear fraction of bone marrow cells (BMCs) or bone marrow cell mobilization induced by granulocyte colony stimulating factor (G-CSF) in rats with a balloon- induced spinal cord compression lesion. MSCs were isolated from rat bone marrow by their adherence to plastic, labeled with iron-oxide nanoparticles and expanded in vitro. Seven days after injury, rats received an intravenous injection of MSCs or BMCs or a subcutaneous injection of GCSF (from day 7 to 11 post-injury). Functional status was assessed weekly for 5 weeks after SCI, using the Basso-Beattie-Bresnehan (BBB) locomotor rating score and the plantar test. Animals with SCI treated with MSCs, BMCs, or G-CSF had higher BBB scores and better recovery of hind limb sensitivity than controls injected with saline. Morphometric measurements showed an increase in the spared white matter. MR images of the spinal cords were taken ex vivo 5 weeks after SCI using a Bruker 4.7-T spectrometer. The lesions populated by grafted MSCs appeared as dark hypointense areas. Histology confirmed a large number of iron-containing and PKH 26-positive cells in the lesion site. We conclude that treatment with three different bone marrow cell populations had a positive effect on behavioral outcome and histopathological assessment after SCI, which was most pronounced after MSC injection.

An ex vivo gene therapy approach in X-linked retinoschisis.

PubMed

Bashar, Abu E; Metcalfe, Andrew L; Viringipurampeer, Ishaq A; Yanai, Anat; Gregory-Evans, Cheryl Y; Gregory-Evans, Kevin

2016-01-01

X-linked retinoschisis (XLRS) is juvenile-onset macular degeneration caused by haploinsufficiency of the extracellular cell adhesion protein retinoschisin (RS1). RS1 mutations can lead to either a non-functional protein or the absence of protein secretion, and it has been established that extracellular deficiency of RS1 is the underlying cause of the phenotype. Therefore, we hypothesized that an ex vivo gene therapy strategy could be used to deliver sufficient extracellular RS1 to reverse the phenotype seen in XLRS. Here, we used adipose-derived, syngeneic mesenchymal stem cells (MSCs) that were genetically modified to secrete human RS1 and then delivered these cells by intravitreal injection to the retina of the Rs1h knockout mouse model of XLRS. MSCs were electroporated with two transgene expression systems (cytomegalovirus (CMV)-controlled constitutive and doxycycline-induced Tet-On controlled inducible), both driving expression of human RS1 cDNA. The stably transfected cells, using either constitutive mesenchymal stem cell (MSC) or inducible MSC cassettes, were assayed for their RS1 secretion profile. For single injection studies, 100,000 genetically modified MSCs were injected into the vitreous cavity of the Rs1h knockout mouse eye at P21, and data were recorded at 2, 4, and 8 weeks post-injection. The control groups received either unmodified MSCs or vehicle injection. For the multiple injection studies, the mice received intravitreal MSC injections at P21, P60, and P90 with data collection at P120. For the single- and multiple-injection studies, the outcomes were measured with electroretinography, optokinetic tracking responses (OKT), histology, and immunohistochemistry. Two lines of genetically modified MSCs were established and found to secrete RS1 at a rate of 8 ng/million cells/day. Following intravitreal injection, RS1-expressing MSCs were found mainly in the inner retinal layers. Two weeks after a single injection of MSCs, the area of the schisis cavities was reduced by 65% with constitutive MSCs and by 83% with inducible MSCs, demonstrating improved inner nuclear layer architecture. This benefit was maintained up to 8 weeks post-injection and corresponded to a significant improvement in the electroretinogram (ERG) b-/a-wave ratio at 8 weeks (2.6 inducible MSCs; 1.4 untreated eyes, p<0.05). At 4 months after multiple injections, the schisis cavity areas were reduced by 78% for inducible MSCs and constitutive MSCs, more photoreceptor nuclei were present (700/µm constitutive MSC; 750/µm inducible MSC; 383/µm untreated), and the ERG b-wave was significantly improved (threefold higher with constitutive MSCs and twofold higher with inducible MSCs) compared to the untreated control group. These results establish that extracellular delivery of RS1 rescues the structural and functional deficits in the Rs1h knockout mouse model and that this ex vivo gene therapy approach can inhibit progression of disease. This proof-of-principle work suggests that other inherited retinal degenerations caused by a deficiency of extracellular matrix proteins could be targeted by this strategy.

Pyloric sphincter characteristics using EndoFLIP® in gastroparesis.

PubMed

Saadi, M; Yu, D; Malik, Z; Parkman, H P; Schey, R

2018-04-27

Pyloric sphincter abnormalities may be detected in gastroparesis. Botulinum toxin A (BoNT/A) injection into the pylorus has been used to treat gastroparesis with varying results. The aim of the present article was to assess whether pyloric sphincter characteristics using the endoscopic functional lumen imaging probe (EndoFLIP ® ) with impedance planimetry in patients with gastroparesis correlated with symptoms, gastric emptying, and therapeutic response to pyloric sphincter BoNT/A injection. EndoFLIP ® study was performed on patients undergoing gastroparesis treatment with BoNT/A. The gastroparesis cardinal symptom index (GCSI) was applied prior to treatment and at post-treatment weeks 2, 4, 8, and 12. Forty-four patients were enrolled (30 with idiopathic gastroparesis, 14 with diabetic gastroparesis). Smaller pyloric diameter, cross-sectional area (CSA), and distensibility correlated with worse vomiting and retching severity at baseline. Greater gastric retention tended to correlate with decreased CSA and pyloric distensibility. BoNT/A treatment resulted in a significant decrease in the GCSI score at 2 and 4 weeks after treatment, but not at post-treatment weeks 8 or 12. Nausea, early satiety, postprandial fullness, and upper abdominal pain improved up to 12 weeks, whereas loss of appetite, stomach fullness, and stomach visibly larger improved only up to 4 weeks. Retching and vomiting failed to improve. Greater pyloric compliance at baseline correlated with greater improvement in early satiety and náusea at 8 weeks and greater pyloric distensibility correlated with improvement in upper abdominal pain. EndoFLIP ® characteristics of the pylorus provided important pathophysiologic information in patients with gastroparesis, in relation to symptoms, gastric emptying, and predicting the response to treatment directed at the pylorus. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Changes in mipomersen dosing regimen provide similar exposure with improved tolerability in randomized placebo-controlled study of healthy volunteers.

PubMed

Flaim, Joann D; Grundy, John S; Baker, Brenda F; McGowan, Mary P; Kastelein, John J P

2014-03-13

Mipomersen, an apolipoprotein B synthesis inhibitor, demonstrated significant reductions in low-density lipoprotein (LDL) cholesterol, non-high density lipoprotein cholesterol, and apolipoprotein B in 4 phase 3 studies at the FDA-approved subcutaneous dose of 200 mg once weekly. A short-term phase 1 study in healthy volunteers was conducted to evaluate the relative bioavailability, safety, and tolerability of mipomersen in 2 test dose regimens in reference to the 200 mg weekly dose regimen. Eighty-four adults were randomized to 1 of 3 cohorts (30 mg once daily, 70 mg 3 times weekly, or 200 mg once weekly) and then mipomersen or placebo (3:1 ratio) for 3 weeks of treatment. Comparable mipomersen post-distribution phase plasma concentrations were observed across the 3 dose regimens suggesting similar tissue exposure. Injection site reactions were reported, but did not lead to treatment discontinuation. The median incidence of these responses per injection was decreased by lowering the dose. Signals from a diverse panel of systemic inflammation markers were essentially indistinguishable between dose regimens and placebo treatment. The one exception was a modest transient post-dose elevation of C-reactive protein (CRP) in the mipomersen 200 mg weekly group. This elevation was not associated with an increase in other proinflammatory markers. This study demonstrated a similar drug exposure and overall safety profile between the 3 dosing regimens. Exploratory assessment of a diverse panel of biomarkers found no indication of a systemic inflammatory response to mipomersen treatment. These results support assessment of alternative dose regimens in longer-term studies. http://www.clinicaltrials.gov. Unique identifier: NCT01061814.

Effects of in ovo feeding of l-arginine on breast muscle growth and protein deposition in post-hatch broilers.

PubMed

Yu, L L; Gao, T; Zhao, M M; Lv, P A; Zhang, L; Li, J L; Jiang, Y; Gao, F; Zhou, G H

2018-02-26

In ovo feeding (IOF) of l-arginine (Arg) can affect growth performance of broilers, but the response of IOF of Arg on breast muscle growth is unclear, and the mechanism involved in protein deposition remains unknown. Hense, this experiment was conducted to evaluate the effects of IOF of Arg on breast muscle growth and protein-deposited signalling in post-hatch broilers. A total of 720 fertile eggs were collected from 34-week-old Arbor Acres breeder hens and distributed to three treatments: (1) non-injected control group; (2) 7.5 g/l (w/v) NaCl diluent-injected control group; (3) 0.6 mg Arg/egg solution-injected group. At 17.5 days of incubation, fertile eggs were injected 0.6 ml solutions into the amnion of the injected groups. Upon hatching, 80 male chicks were randomly assigned to eight replicates of 10 birds each and fed ad libitum for 21 days. The results indicated that IOF of Arg increased relative breast muscle weight compared with those of control groups at hatch, 3-, 7- and 21-day post-hatch (P<0.05). In the Arg-injected group, the plasma total protein and albumen concentrations were higher at 7- and 21-day post-hatch than those of control groups (P<0.05). The alanine aminotransferase activity in Arg group was higher at hatch than that of control groups (P<0.05). The levels of triiodothyronine at four time points and thyroxine hormones at hatch, 7- and 21-day post-hatch in Arg group were higher than those of control groups (P<0.05). In addition, IOF of Arg increased the amino acid concentrations of breast muscle at hatch, 7- and 21-day post-hatch (P<0.05). In ovo feeding of Arg also enhanced mammalian target of rapamycin, ribosomal protein S6 kinase-1 and eIF4E-bindingprotein-1 messenger RNA expression levels at hatch compared with those of control groups (P<0.05). It was concluded that IOF of Arg treatment improved breast muscle growth, which might be associated with the enhancement of protein deposition.

Extended Duration of Transgene Expression from Pegylated POD Nanoparticles Enables Attenuation of Photoreceptor Degeneration

PubMed Central

Binder, Christina; Cashman, Siobhan M.; Kumar-Singh, Rajendra

2013-01-01

Retinitis pigmentosa (RP) is the most genetically heterogeneous disorder known to cause blindness, involving over 50 different genes. Previously, we have described nanoparticles (NPs) 150 nm in size, comprised of a 3.5 kD peptide (POD) complexed to PEG and DNA (PEGPOD DNA). These NPs expressing GDNF enabled rescue of photoreceptor degeneration in mice up to 11 days post injection. In the current study we examine use of scaffold/ matrix attachment regions (S/MARs), CpG depletion and titration of DNA content of PEGPOD DNA NPs to extend the duration of transgene expression. S/MARs and CpGs did not significantly influence the duration of transgene expression, but did influence its stability. These parameters enabled us to extend transgene expression from 48 hours to 10 weeks. At 77 days post injection, we observed a 76% rescue of the thickness of the retinal outer nuclear layer (ONL) and at 37 days post injection we observed 53% and 55% rescue of the A and B wave ERG amplitudes respectively and 60% rescue of the ONL. Our studies suggest that PEGPOD DNA NPs have potential as gene delivery vectors for the retina. PMID:24278479

Integrated Bio-behavioral Approach to Improve Adherence to Pre-exposure Prophylaxis and Reduce HIV Risk in People Who Use Drugs: A Pilot Feasibility Study.

PubMed

Shrestha, Roman; Altice, Frederick L; Karki, Pramila; Copenhaver, Michael M

2018-03-26

This study reports the feasibility, acceptability, and preliminary efficacy of the bio-behavioral community-friendly health recovery program-an integrated, HIV prevention intervention to improve pre-exposure prophylaxis (PrEP) adherence and HIV-risk reduction behaviors among high-risk people who use drugs. We used a within-subjects, pretest-posttest follow-up design to recruit participants, who were HIV-uninfected, methadone-maintained and reported HIV-risk behaviors and had initiated PrEP (n = 40; males: 55%). Participants were assessed at baseline (T 0 ), immediately post-intervention (4 weeks: T 4 ) and 4 weeks post-intervention (T 8 ). Immediately after completing the four weekly intervention groups, participants underwent a post-intervention assessment including in-depth qualitative interviews. Feasibility was high, assessed by participant willingness to enroll (90.1%) and retention (95%). Results showed that participants were highly satisfied and perceived the intervention as valuable and acceptable [mean: 81.3 (range 0-100)]. Significant enhancements in self-reported PrEP adherence [F(2,74) = 7.500, p = 0.001] and PrEP-related knowledge [F(2,74) = 3.828, p = 0.026] were observed. Drug-related (e.g., injection of drugs, sharing of injection equipment) and sex-related (e.g., number of sexual partners, condomless sex) risk behaviors were reduced, while information, motivation, and behavioral skills (IMB) constructs increased. The results support feasibility and high acceptability and support further examination of the efficacy of this combination bio-behavioral intervention in a prospective clinical trial.

Trials for development of once-a-month injectable, hormonal male contraceptive using dienogest plus testosterone undecanoate: dose standardization, efficacy and reversibility studies in rats.

PubMed

Misro, Man M; Chaki, Shankar P; Kaushik, Mahesh C; Nandan, Deoki

2009-06-01

The study was conducted to test the potential of using dienogest (DNG) plus testosterone undecanoate (TU) in rats for development of a once-a-month injectable male hormonal contraceptive. Dose selection studies were initiated with administration of DNG in three different doses of 20, 30 and 40 mg/kg body weight (bw) per week plus TU 25 mg/kg bw once in every 6 weeks. Status of spermatogenesis and sperm count in epididymis was evaluated. The frequency of DNG intervention was later extended to every 2- and 4-week intervals. Mating studies, toxicity and reversibility of spermatogenesis following stoppage of treatment were carried out with DNG 40 mg/kg bw at 4-week intervals. Complete arrest of spermatogenesis was observed after 60 days of treatment at all doses of DNG (20, 30 and 40 mg/kg bw per week)+TU. However, weights of testis and accessory sex organs (epididymis, prostate and seminal vesicle) declined significantly 60 days post treatment compared to vehicle-treated controls. Epididymis in the treated animals was completely devoid of sperm. When the frequency of DNG injection (20 mg/kg bw) was extended to once every 15 days, a few immotile and decapitated sperm were observed in the epididymis. With TU treatment unchanged, animals receiving DNG (40 mg/kg bw) once either every 2- or 4-week intervals demonstrated good and uniform arrest of spermatogenesis. DNG 40 mg/kg per 4 weeks+TU also demonstrated a significant rise in germ cell apoptosis in the seminiferous epithelium. There was no significant increase in the serum high-density lipoprotein and low-density lipoprotein levels at the end of 120 days of treatment. Following withdrawal of treatment after 60 or 120 days, qualitative restoration of spermatogenesis was rapid in the former compared to the latter. Dienogest plus TU has the potential for development as a monthly injectable showing reversible hormonal male contraception with good efficacy.

A new in vivo animal model to create intervertebral disc degeneration characterized by MRI, radiography, CT/discogram, biochemistry, and histology.

PubMed

Zhou, HaoWei; Hou, ShuXun; Shang, WeiLin; Wu, WenWen; Cheng, Yao; Mei, Fang; Peng, BaoGan

2007-04-15

A new in vivo sheep model was developed that produced disc degeneration through the injection of 5-bromodeoxyuridine (BrdU) into the intervertebral disc. This process was studied using magnetic resonance imaging (MRI), radiography, CT/discogram, histology, and biochemistry. To develop a sheep model of intervertebral disc degeneration that more faithfully mimics the pathologic hallmarks of human intervertebral disc degeneration. Recent studies have shown age-related alterations in proteoglycan structure and organization in human intervertebral discs. An animal model that involves the use of age-related changes in disc cells can be beneficial over other more invasive degenerative models that involves directly damaging the matrix of disc tissue. Twelve sheep were injected with BrdU or vehicle (phosphate-buffered saline) into the central region of separate lumbar discs. Intact discs were used as controls. At the 2-, 6-, 10-, and 14-week time points, discs underwent MRI, radiography, histology, and biochemical analyses. A CT/discogram study was performed at the 14-week time point. MRI demonstrated a progressive loss of T2-weighted signal intensity at BrdU-injected discs over the 14-week study period. Radiograph findings included osteophyte and disc space narrowing formed by 10 weeks post-BrdU treatment. CT discography demonstrated internal disc disruption in several BrdU-treated discs at the 14-week time point. Histology showed a progressive loss of the normal architecture and cell density of discs from the 2-week time point to the 14-week time point. A progressive loss of cell proliferation capacity, water content, and proteoglycans was also documented. BrdU injection into the central region of sheep discs resulted in degeneration of intervertebral discs. This progressive, degenerative process was confirmed using MRI, histology, and by observing changes in biochemistry. Degeneration occurred in a manner that was similar to that observed in human disc degeneration.

Comparative study between biofeedback retraining and botulinum neurotoxin in the treatment of anismus patients.

PubMed

Farid, Mohamed; El Monem, Hisham Abd; Omar, Waleed; El Nakeeb, Ayman; Fikry, Amir; Youssef, Tamer; Yousef, Mohamed; Ghazy, Hosam; Fouda, Elyamani; El Metwally, Teto; Khafagy, Wael; Ahmed, Sabry; El Awady, Salih; Morshed, Mosaad; El Lithy, Ramadan

2009-01-01

Anismus is a significant cause of chronic constipation. This study came to revive the results of BFB training and BTX-A injection in the treatment of anismus patients. Forty-eight patients with anismus (33 women; mean age 39.6 +/- 15.9) were included in this study. All patients fulfilled Rome II criteria for functional constipation. All patients underwent anorectal manometry, balloon expulsion test, defecography, and electromyography (EMG) activity of the EAS. All patients had non-relaxing puborectalis muscle. The patients were randomized into two groups. Group I patients received biofeedback therapy, two times per week for about 1 month. Group II patients were injected with BTX-A. Follow-up was conducted weekly in the first month then monthly for about 1 year. In the BFB training group, three patients quit before the end of sessions with no improvement; initial improvement was recorded in 12 patients (50%) while long-term success was recorded in six patients (25%). In the BTX-A group, clinical improvement was recorded in 17 patients (70.83%), but the improvement persisted only in eight patients (33.3%). There is a significant difference between BTX-A group and BFB group regarding the initial success, but this significant difference disappeared at the end of follow-up. Manometric relaxation was achieved significantly post-BFB and post-BTX-A injection with no significant difference between the two groups. Biofeedback training has a limited therapeutic effect on patients suffering from anismus. BTX-A injection seems to be successful for temporary treatment of anismus.

Antisense Morpholino Oligonucleotides Reduce Neurofilament Synthesis and Inhibit Axon Regeneration in Lamprey Reticulospinal Neurons.

PubMed

Zhang, Guixin; Jin, Li-qing; Hu, Jianli; Rodemer, William; Selzer, Michael E

2015-01-01

The sea lamprey has been used as a model for the study of axonal regeneration after spinal cord injury. Previous studies have suggested that, unlike developing axons in mammal, the tips of regenerating axons in lamprey spinal cord are simple in shape, packed with neurofilaments (NFs), and contain very little F-actin. Thus it has been proposed that regeneration of axons in the central nervous system of mature vertebrates is not based on the canonical actin-dependent pulling mechanism of growth cones, but involves an internal protrusive force, perhaps generated by the transport or assembly of NFs in the distal axon. In order to assess this hypothesis, expression of NFs was manipulated by antisense morpholino oligonucleotides (MO). A standard, company-supplied MO was used as control. Axon retraction and regeneration were assessed at 2, 4 and 9 weeks after MOs were applied to a spinal cord transection (TX) site. Antisense MO inhibited NF180 expression compared to control MO. The effect of inhibiting NF expression on axon retraction and regeneration was studied by measuring the distance of axon tips from the TX site at 2 and 4 weeks post-TX, and counting the number of reticulospinal neurons (RNs) retrogradely labeled by fluorescently-tagged dextran injected caudal to the injury at 9 weeks post-TX. There was no statistically significant effect of MO on axon retraction at 2 weeks post-TX. However, at both 4 and 9 weeks post-TX, inhibition of NF expression inhibited axon regeneration.

High-fat diet exacerbates pain-like behaviors and periarticular bone loss in mice with CFA-induced knee arthritis.

PubMed

Loredo-Pérez, Aleyda A; Montalvo-Blanco, Carlos E; Hernández-González, Luis I; Anaya-Reyes, Maricruz; Fernández Del Valle-Laisequilla, Cecilia; Reyes-García, Juan G; Acosta-González, Rosa I; Martínez-Martínez, Arisai; Villarreal-Salcido, Jaira C; Vargas-Muñoz, Virginia M; Muñoz-Islas, Enriqueta; Ramírez-Rosas, Martha B; Jiménez-Andrade, Juan M

2016-05-01

Our aim was to quantify nociceptive spontaneous behaviors, knee edema, proinflammatory cytokines, bone density, and microarchitecture in high-fat diet (HFD)-fed mice with unilateral knee arthritis. ICR male mice were fed either standard diet (SD) or HFD starting at 3 weeks old. At 17 weeks, HFD and SD mice received intra-articular injections either with Complete Freund's Adjuvant (CFA) or saline into the right knee joint every 7 days for 4 weeks. Spontaneous pain-like behaviors and knee edema were assessed for 26 days. At day 26 post-first CFA injection, serum levels of IL-1β, IL-6, and RANKL were measured by ELISA, and microcomputed tomography analysis of knee joints was performed. HFD-fed mice injected with CFA showed greater spontaneous pain-like behaviors of the affected extremity as well as a decrease in the weight-bearing index compared to SD-fed mice injected with CFA. Knee edema was not significantly different between diets. HFD significantly exacerbated arthritis-induced bone loss at the distal femoral metaphysis but had no effect on femoral diaphyseal cortical bone. HFD did not modify serum levels of proinflammatory cytokines. HFD exacerbates pain-like behaviors and significantly increases the magnitude of periarticular trabecular bone loss in a murine model of unilateral arthritis. © 2016 The Obesity Society.

Ultrasound-guided injection of triamcinolone and bupivacaine in the management of De Quervain's disease.

PubMed

Jeyapalan, Kanagaratnam; Choudhary, Surabhi

2009-11-01

The aim of this study was to describe the technique and usefulness of ultrasound-guided intrasynovial injection of triamcinolone and bupivacaine in treatment of de Quervain's disease. A total of 17 patients with symptomatic De Quervain's disease were included in this study. The procedure involved confirmation of diagnosis with ultrasound followed by guided injection of a mixture of 20 mg of triamcinolone (40 mg/ml) and 1 ml of 0.5% bupivacaine. Ultrasound guidance with a high resolution 15-Mhz footprint probe was used for injection into the first dorsal extensor compartment tendon sheath (E1). The response to ultrasound-guided injection was ascertained at the post procedure outpatient clinic appointment according to the follow-up clinic notes. There were 14 female and 3 male patients aged 29 to 74 years. Mean duration of symptoms was 8.9 months. One patient had an atypical septum in the first extensor compartment and the extensor pollicis brevis alone was involved. The mean post-injection follow-up was at 6.75 weeks. One patient was lost to follow-up. Fifteen out of 16 patients had significant symptomatic relief (93.75%). There were no immediate or delayed complications. Recurrence of symptoms was seen in 3 (20%) patients. Ultrasound-guided injection of triamcinolone and bupivacaine is safe and useful in controlling symptoms of De Quervain's disease. Correct needle placement with ultrasound guidance avoids intratendinous injection as well as local complications like fat atrophy and depigmentation.

Outcomes of intradetrusor onabotulinum toxin A injection in patients with Parkinson's disease.

PubMed

Vurture, Gregory; Peyronnet, Benoit; Feigin, Andrew; Biagioni, Milton C; Gilbert, Rebecca; Rosenblum, Nirit; Frucht, Steven; Di Rocco, Alessandro; Nitti, Victor W; Brucker, Benjamin M

2018-05-16

To assess the safety and efficacy of intradetrusor onabotulinum toxin A injections for the treatment of overactive bladder (OAB) in patients with Parkinson's disease (PD). All PD patients who underwent intradetrusor injections of onabotulinum toxin A (BoNT-A) for storage symptoms between 2010 and 2017 were included in a retrospective study. A 100 U dose of BoNT-A (Botox®, Allergan Irvine, CA) was used for the first injection in all patients. The primary endpoint was clinical success defined as any subjective improvement in OAB symptoms self-assessed by the patients 4 weeks after the injections. Out of 24 patients analyzed, 19 reported improvement of their OAB symptoms 4 weeks after the first injection (79.2%) with complete resolution of urgency urinary incontinence in seven patients (29.1%; P < 0.001). The average post-void residual (PVR) increased significantly after the first injection from 17.6 to 125.3 mL (P < 0.001). Three of the patients had to start clean intermittent catheterization (CIC) after the first injection (12.5%). Out of 49 injections in total, only five caused incomplete bladder emptying requiring the use of CIC (10.2%). Higher pre-injection PVR was significantly associated with both a lower chance of symptomatic improvement (P = 0.04) and a higher risk of incomplete bladder emptying with institution of CIC (P = 0.047). Intradetrusor injections of BoNT-A 100 U appeared as a safe and effective option in PD patients with OAB symptoms and a low PVR before the injection. Higher preoperative PVR was the strongest predictor of both treatment failure and postoperative urinary retention requiring CIC. © 2018 Wiley Periodicals, Inc.

Successful management of metastatic transmissible venereal tumour to skin of mammary region.

PubMed

Varughese, E E; Singla, V K; Ratnakaran, U; Gandotra, V K

2012-12-01

A Dalmatian female presented with a history of vaginal bleeding and was diagnosed as having transmissible venereal tumour (TVT) after cytological examination of the vaginal growth revealed typical TVT cells. A cytology of the aspirate from multiple nodules in the skin near the abdominal and inguinal pair of mammary glands revealed similar cells suggestive of metastasis to skin of mammary region. Chemotherapy was initiated with weekly injections of vincristine sulphate (0.025 mg/kg BW, IV, SID) and haematological examination was performed pre- and post-treatment to assess the prognosis of the patient and side effects of the drug. The major side effects observed during the course of the treatment were high body temperature, mild neutropaenia and significant decrease in packed cell volume, haemoglobin, total leucocyte and erythrocyte count. Four weekly injections of vincristine were administered, and 4 weeks from initiation of treatment, the tumour and nodules were gone, suggesting complete recovery. © 2012 Blackwell Verlag GmbH.

The effect of botulinum toxin A (Botox) injections used to treat limb spasticity on speech patterns in children with dysarthria and cerebral palsy: A report of two cases.

PubMed

Workinger, Marilyn Seif; Kent, Raymond D; Meilahn, Jill R

2017-05-19

Botulinum toxin A (Btx-A) injections are used to treat limb spasticity in children with cerebral palsy (CP) resulting in improved gross and fine motor control. This treatment has also been reported to have additional functional effects, but the effect of treatment on speech has not been reported. This report presents results of longitudinal speech evaluation of two children with CP given injections of Btx-A for treatment of limb spasticity. Speech evaluations were accomplished at baseline (date of injections) and 4- and 10-weeks post-injections. Improvements in production of consonants, loudness control, and syllables produced per breath were found. Parental survey also suggested improvements in subjects' speech production and willingness to speak outside the testing situation. Future larger studies are warranted to assess the nature of the changes observed related to Btx-A.

Novel strategy for prevention of esophageal stricture after endoscopic surgery.

PubMed

Mizutani, Taro; Tadauchi, Akimitsu; Arinobe, Manabu; Narita, Yuji; Kato, Ryuji; Niwa, Yasumasa; Ohmiya, Naoki; Itoh, Akihiro; Hirooka, Yoshiki; Honda, Hiroyuki; Ueda, Minoru; Goto, Hidemi

2010-01-01

Recently, novel endoscopic surgery, including endoscopic submucosal dissection (ESD), was developed to resect a large superficial gastrointestinal cancer. However, circumferential endoscopic surgery in the esophagus can lead to esophageal stricture that affects the patient's quality of life. This major complication is caused by scar formation, and develops during the two weeks after endoscopic surgery. We hypothesized that local administration of a controlled release anti-scarring agent can prevent esophageal stricture after endoscopic surgery. The aims of this study were to develop an endoscopically injectable anti-scarring drug delivery system, and to verify the efficacy of our strategy to prevent esophageal stricture. We focused on 5-Fluorouracil (5-FU) as an anti-scarring agent, which has already been shown to be effective not only for treatment of cancers, but also for treatment of hypertrophic skin scars. 5-FU was encapsulated by liposome, and then mixed with injectable 2% atelocollagen (5FLC: 5FU-liposome-collagen) to achieve sustained release. An in vitro 5-FU releasing test from 5FLC was performed using high-performance liquid chromatography (HPLC). Inhibition of cell proliferation was investigated using normal human dermal fibroblast cells (NHDF) with 5FLC. In addition, a canine esophageal mucosal resection was carried out, and 5FLC was endoscopically injected into the ulcer immediately after the operation, and compared with a similar specimen injected with saline as a control. 5-FU was gradually released from 5FLC for more than 2 weeks in vitro. The solution of 5-FU released from 5FLC inhibited NHDF proliferation more effectively than 5-FU alone. In the canine model, no findings of stricture were observed in the 5FLC-treated dog at 4 weeks after the operation and no vomiting occurred. In contrast, marked esophageal strictures were observed with repeated vomiting in the control group. Submucosal fibrosis was markedly reduced histologically in the 5FLC-treated dog compared with the control. 5FLC showed sustained release of 5-FU and decreased cell proliferation in vitro. The clinically relevant canine model demonstrated that local endoscopic injection of 5FLC can prevent post-operative esophageal stricture. These results suggest that our strategy may be useful for preventing post-operative esophageal stricture.

Prevention of hypoglycemia-induced neuronal death by minocycline

PubMed Central

2012-01-01

Diabetic patients who attempt strict management of blood glucose levels frequently experience hypoglycemia. Severe and prolonged hypoglycemia causes neuronal death and cognitive impairment. There is no effective tool for prevention of these unwanted clinical sequelae. Minocycline, a second-generation tetracycline derivative, has been recognized as an anti-inflammatory and neuroprotective agent in several animal models such as stroke and traumatic brain injury. In the present study, we tested whether minocycline also has protective effects on hypoglycemia-induced neuronal death and cognitive impairment. To test our hypothesis we used an animal model of insulin-induced acute hypoglycemia. Minocycline was injected intraperitoneally at 6 hours after hypoglycemia/glucose reperfusion and injected once per day for the following 1 week. Histological evaluation for neuronal death and microglial activation was performed from 1 day to 1 week after hypoglycemia. Cognitive evaluation was conducted 6 weeks after hypoglycemia. Microglial activation began to be evident in the hippocampal area at 1 day after hypoglycemia and persisted for 1 week. Minocycline injection significantly reduced hypoglycemia-induced microglial activation and myeloperoxidase (MPO) immunoreactivity. Neuronal death was significantly reduced by minocycline treatment when evaluated at 1 week after hypoglycemia. Hypoglycemia-induced cognitive impairment is also significantly prevented by the same minocycline regimen when subjects were evaluated at 6 weeks after hypoglycemia. Therefore, these results suggest that delayed treatment (6 hours post-insult) with minocycline protects against microglial activation, neuronal death and cognitive impairment caused by severe hypoglycemia. The present study suggests that minocycline has therapeutic potential to prevent hypoglycemia-induced brain injury in diabetic patients. PMID:22998689

Human eccrine sweat gland cells reconstitute polarized spheroids when subcutaneously implanted with Matrigel in nude mice.

PubMed

Li, Haihong; Zhang, Mingjun; Chen, Liyun; Li, Xuexue; Zhang, Bingna

2016-10-01

Increasing evidence indicates that maintenance of cell polarity plays a pivotal role in the regulation of glandular homeostasis and function. We examine the markers for polarity at different time points to investigate the formation of cell polarity during 3D reconstitution of eccrine sweat glands. Mixtures of eccrine sweat gland cells and Matrigel were injected subcutaneously into the inguinal regions of nude mice. At 2, 3, 4, 5 and 6 weeks post-implantation, Matrigel plugs were removed and immunostained for basal collagen IV, lateral β-catenin, lateroapical ZO-1 and apical F-actin. The results showed that the cell polarity of the spheroids appeared in sequence. Formation of basal polarity was prior to lateral, apical and lateroapical polarity. Collagen IV was detected basally at 2 weeks, β-catenin laterally and ZO-1 lateroapically at 3 weeks, and F-actin apically at 4 weeks post-implantation. At week 5 and week 6, the localization and the positive percentage of collagen IV, β-catenin, ZO-1 or F-actin in spheroids was similar to that in native eccrine sweat glands. We conclude that the reconstituted 3D eccrine sweat glands are functional or potentially functional.

Identification of the active components in Bone Marrow Soup: a mitigator against irradiation-injury to salivary glands.

PubMed

Fang, Dongdong; Hu, Shen; Liu, Younan; Quan, Vu-Hung; Seuntjens, Jan; Tran, Simon D

2015-11-03

In separate studies, an extract of soluble intracellular contents from whole bone marrow cells, named "Bone Marrow (BM) Soup", was reported to either improve cardiac or salivary functions post-myocardial infarction or irradiation (IR), respectively. However, the active components in BM Soup are unknown. To demonstrate that proteins were the active ingredients, we devised a method using proteinase K followed by heating to deactivate proteins and for safe injections into mice. BM Soup and "deactivated BM Soup" were injected into mice that had their salivary glands injured with 15Gy IR. Control mice received either injections of saline or were not IR. Results at week 8 post-IR showed the 'deactivated BM Soup' was no better than injections of saline, while injections of native BM Soup restored saliva flow, protected salivary cells and blood vessels from IR-damage. Protein arrays detected several angiogenesis-related factors (CD26, FGF, HGF, MMP-8, MMP-9, OPN, PF4, SDF-1) and cytokines (IL-1ra, IL-16) in BM Soup. In conclusion, the native proteins (but not the nucleic acids, lipids or carbohydrates) were the therapeutic ingredients in BM Soup for functional salivary restoration following IR. This molecular therapy approach has clinical potential because it is theoretically less tumorigenic and immunogenic than cell therapies.

Comparison between Steroid Injection and Stretching Exercise on the Scalene of Patients with Upper Extremity Paresthesia: Randomized Cross-Over Study.

PubMed

Kim, Yong Wook; Yoon, Seo Yeon; Park, Yongbum; Chang, Won Hyuk; Lee, Sang Chul

2016-03-01

To compare the therapeutic effects on upper extremity paresthesia of intra-muscular steroid injections into the scalene muscle with those of stretching exercise only. Twenty patients with upper extremity paresthesia who met the criteria were recruited to participate in this single-blind, crossover study. Fourteen of 20 patients were female. The average age was 45.0 ± 10.5 years and duration of symptom was 12.2 ± 8.7 months. Each participant completed one injection and daily exercise program for 2 weeks. After randomization, half of all patients received ultrasound-guided injection of scalene muscles before exercise, while the other was invested for the other patients. After two weeks, there was a significant decrease of the visual analog scale score of treatment effect compared with baseline in both groups (6.90 to 2.85 after injection and 5.65 to 4.05 after stretching exercise, p<0.01). However, injection resulted in greater improvements than stretching exercise (p<0.01). The number of patients with successful treatment, defined as >50% reduction in post-treatment visual analog scale, was 18 of 20 (90.0%) after injection, compared to 5 of 20 (25.0%) after stretching exercise. There were no cases of unintended brachial plexus block after injection. Ultrasound-guided steroid injection or stretching exercise of scalene muscles led to reduced upper extremity paresthesia in patients who present with localized tenderness in the scalene muscle without electrodiagnostic test abnormalities, although injection treatment resulted in more improvements. The results suggest that symptoms relief might result from injection into the muscle alone not related to blockade of the brachial plexus.

Comparison between Steroid Injection and Stretching Exercise on the Scalene of Patients with Upper Extremity Paresthesia: Randomized Cross-Over Study

PubMed Central

Kim, Yong Wook; Yoon, Seo Yeon; Park, Yongbum; Chang, Won Hyuk

2016-01-01

Purpose To compare the therapeutic effects on upper extremity paresthesia of intra-muscular steroid injections into the scalene muscle with those of stretching exercise only. Materials and Methods Twenty patients with upper extremity paresthesia who met the criteria were recruited to participate in this single-blind, crossover study. Fourteen of 20 patients were female. The average age was 45.0±10.5 years and duration of symptom was 12.2±8.7 months. Each participant completed one injection and daily exercise program for 2 weeks. After randomization, half of all patients received ultrasound-guided injection of scalene muscles before exercise, while the other was invested for the other patients. Results After two weeks, there was a significant decrease of the visual analog scale score of treatment effect compared with baseline in both groups (6.90 to 2.85 after injection and 5.65 to 4.05 after stretching exercise, p<0.01). However, injection resulted in greater improvements than stretching exercise (p<0.01). The number of patients with successful treatment, defined as >50% reduction in post-treatment visual analog scale, was 18 of 20 (90.0%) after injection, compared to 5 of 20 (25.0%) after stretching exercise. There were no cases of unintended brachial plexus block after injection. Conclusion Ultrasound-guided steroid injection or stretching exercise of scalene muscles led to reduced upper extremity paresthesia in patients who present with localized tenderness in the scalene muscle without electrodiagnostic test abnormalities, although injection treatment resulted in more improvements. The results suggest that symptoms relief might result from injection into the muscle alone not related to blockade of the brachial plexus. PMID:26847305

Aripiprazole Lauroxil Long-Acting Injectable: The Latest Addition to Second-Generation Long-Acting Agents.

PubMed

Aggarwal, Arpit; Gopalakrishna, Ganesh; Lauriello, John

2016-01-01

Antipsychotics have long been the mainstay for the treatment of schizophrenia and other psychotic disorders. Long-acting injectables (LAI) of antipsychotics-provided once every two weeks to once every three months-promise to reduce the incidence of nonadherence. ARISTADA(™) (aripiprazole lauroxil; ALLAI) extended-release injectable suspension was approved by the U.S. Food and Drug Administration in October 2015 for the treatment of schizophrenia, and is the newest entrant in the LAI market. ALLAI is available as a single-use, pre-filled syringe, can be started in three different dosages, and also has the option of every six-week dosing. Treatment with oral aripiprazole is recommended for the first twenty-one days after the first ALLAI injection, which is a potential disadvantage. Adverse effects include sensitivity to extrapyramidal symptoms, especially akathisia, which is well documented in other aripiprazole preparations. There is no available data comparing ALLAI to other antipsychotics, and more head-to-head trials comparing different LAI formulations are needed. Based on the available data, ALLAI is an effective and safe option for treatment of schizophrenia. Further studies and post-marketing data will provide better understanding of this formulation.

Effects of Nursing Students' Practices Using Smartphone Videos on Fundamental Nursing Skills, Self-Efficacy, and Learning Satisfaction in South Korea

ERIC Educational Resources Information Center

Jeong, HyeSun

2017-01-01

This is a quasi-experimental study with a non-equivalent group pre-test and post-test designed to investigate the effects of learning with smartphone video recordings in fundamental nursing practice. General "intramuscular injection" practice for sophomore nursing students was given to the experimental and control groups for two weeks.…

Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model.

PubMed

Iijima, H; Ito, A; Nagai, M; Tajino, J; Yamaguchi, S; Kiyan, W; Nakahata, A; Zhang, J; Wang, T; Aoyama, T; Nishitani, K; Kuroki, H

2017-06-01

To evaluate the dose-response relationship of exercise loading in the cartilage-subchondral bone (SB) unit in surgically-induced post-traumatic osteoarthritis (PTOA) of the knee. Destabilized medial meniscus (DMM) surgery was performed on the right knee of 12-week-old male Wistar rats, and sham surgery was performed on the contralateral knee. Four weeks after the surgery, the animals were subjected to moderate (12 m/min) or intense (21 m/min) treadmill exercises for 30 min/day, 5 days/week for 4 weeks. PTOA development in articular cartilage and SB was examined using histological and immunohistochemical analyses, micro-computed tomography (micro-CT) analysis, and biomechanical testing at 8 weeks after surgery. Gremlin-1 was injected to determine the role of bone morphogenetic protein (BMP) signaling on PTOA development following moderate exercise. Moderate exercise increased BMP-2, BMP-4, BMP-6, BMP receptor 2, pSmad-5, and inhibitor of DNA binding protein-1 expression in the superficial zone chondrocytes and suppressed cartilage degeneration, osteophyte growth, SB damage, and osteoclast-mediated SB resorption. However, intense exercise had little effect on BMP expression and even caused progression of these osteoarthritis (OA) changes. Gremlin-1 injection following moderate exercise caused progression of the PTOA development down to the level of the non-exercise DMM-operated knee. Exercise regulated cartilage-SB PTOA development in DMM-operated knees in a dose-dependent manner. Our findings shed light on the important role of BMP expression in superficial zone chondrocytes in attenuation of PTOA development following physiological exercise loading. Further studies to support a mechanism by which BMPs would be beneficial in preventing PTOA progression are warranted. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Canine Lipomas Treated with Steroid Injections: Clinical Findings

PubMed Central

Lamagna, Barbara; Greco, Adelaide; Guardascione, Anna; Navas, Luigi; Ragozzino, Manuela; Paciello, Orlando; Brunetti, Arturo; Meomartino, Leonardo

2012-01-01

Lipomas are common benign tumours of fat cells. In most cases, surgical excision is curative and simple to perform; however, such a procedure requires general anaesthesia and may be associated with delayed wound healing, seroma formation and nerve injury in deep and intramuscular tumours. The objective of this study was to evaluate treatment of subcutaneous, subfascial or intermuscular lipomas using intralesional steroid injections in dogs. Fifteen dogs presenting with lipomas were selected for treatment with ultrasound-guided intralesional injection of triamcinolone acetonide at a dose of 40 mg/mL. Nine subcutaneous and subfascial tumours showed a complete regression. The other lipomas decreased in diameter, achieving, in some cases, remission of discomfort and regression of lameness. Steroid injection was a relatively safe and effective treatment for lipomas in dogs; only six dogs experienced polyuria/polydipsia for about 2 weeks post-treatment. PMID:23226250

Effect of post injections on mixture preparation and unburned hydrocarbon emissions in a heavy-duty diesel engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Connor, Jacqueline; Musculus, Mark P. B.; Pickett, Lyle M.

This work explores the mechanisms by which a post injection can reduce unburned hydrocarbon (UHC) emissions in heavy-duty diesel engines operating at low-temperature combustion conditions. Post injections, small, close-coupled injections of fuel after the main injection, have been shown to reduce UHC in the authors’ previous work. In this work, we analyze optical data from laser-induced fluorescence of both CH 2O and OH and use chemical reactor modeling to better understand the mechanism by which post injections reduce UHC emissions. The results indicate that post-injection efficacy, or the extent to which a post injection reduces UHC emissions, is a strongmore » function of the cylinder pressure variation during the post injection. However, the data and analysis indicate that the pressure and temperature rise from the post injection combustion cannot solely explain the UHC reduction measured by both engine-out and optical diagnostics. In conclusion, the fluid-mechanic, thermal, and chemical interaction of the post injection with the main-injection mixture is a key part of UHC reduction; the starting action of the post jet and the subsequent entrainment of surrounding gases are likely both important processes in reducing UHC with a post injection.« less

Effect of post injections on mixture preparation and unburned hydrocarbon emissions in a heavy-duty diesel engine

DOE PAGES

O'Connor, Jacqueline; Musculus, Mark P. B.; Pickett, Lyle M.

2016-05-30

This work explores the mechanisms by which a post injection can reduce unburned hydrocarbon (UHC) emissions in heavy-duty diesel engines operating at low-temperature combustion conditions. Post injections, small, close-coupled injections of fuel after the main injection, have been shown to reduce UHC in the authors’ previous work. In this work, we analyze optical data from laser-induced fluorescence of both CH 2O and OH and use chemical reactor modeling to better understand the mechanism by which post injections reduce UHC emissions. The results indicate that post-injection efficacy, or the extent to which a post injection reduces UHC emissions, is a strongmore » function of the cylinder pressure variation during the post injection. However, the data and analysis indicate that the pressure and temperature rise from the post injection combustion cannot solely explain the UHC reduction measured by both engine-out and optical diagnostics. In conclusion, the fluid-mechanic, thermal, and chemical interaction of the post injection with the main-injection mixture is a key part of UHC reduction; the starting action of the post jet and the subsequent entrainment of surrounding gases are likely both important processes in reducing UHC with a post injection.« less

Sustained Neuroprotection From a Single Intravitreal Injection of PGJ2 in a Nonhuman Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

PubMed Central

Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M.; Bernstein, Steven L.

2014-01-01

Purpose. Prostaglandin J2 (PGJ2) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ2 in a nonhuman primate model of NAION (pNAION). Methods. We assessed PGJ2 toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ2 or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ2 or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. Results. Toxicity: PGJ2 caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ2 used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ2; however, the amplitudes returned to normal in all animals within 1 week. Efficacy: In all eyes, a single IVT dose of PGJ2 administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). Conclusions. In nonhuman primates, PGJ2 administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ2 is neuroprotective when administered up to 5 hours after induction of pNAION. PMID:25298416

Continuous subcutaneous administration of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine in the treatment of post-herpetic neuralgia.

PubMed

Eide, K; Stubhaug, A; Oye, I; Breivik, H

1995-05-01

The effect of continuous subcutaneous (s.c.) infusion of ketamine on nerve injury pain was examined in patients with post-herpetic neuralgia. Five patients that reported pain relief after acute intravenous injection of ketamine were included in this open prospective study. Ketamine was administered continuously in increasing doses using a portable infusion pump (CADD-PLUS, Pharmacia), and the treatment period for each infusion rate (0.05, 0.075, 0.10, or 0.15 mg/kg/h) was 7 days and nights. Relief of continuous pain, as evaluated daily by visual analogue scales, was observed at the infusion rate of 0.05 mg/kg/h, but was most marked during infusion of 0.15 mg/kg/h. All the patients reported that ketamine reduced the severity of continuous pain as well as reduced the severity and number of attacks of spontaneous pain. Changes in evoked pain (allodynia and wind-up-like pain) were recorded before change of infusion rate. Allodynia was maximally reduced 59-100% after 1 week infusion of 0.05 mg/kg/h, and wind-up-like pain was maximally reduced 60-100% after 1 week infusion of 0.15 mg/kg/h. Itching and painful indurations at the injection site was the most bothersome side-effect and for this reason 1 patient discontinued treatment after 2 weeks. Other common side-effects were nausea, fatigue and dizziness. The present results show that continuous, spontaneous and evoked pain in patients with post-herpetic neuralgia is reduced by continuous s.c. infusion of ketamine, but is associated with intolerable side effects.

Post-weaning social isolation of female rats, anxiety-related behavior, and serotonergic systems

PubMed Central

Lukkes, Jodi L.; Engelman, Glenn H.; Zelin, Naomi S.; Hale, Matthew W.; Lowry, Christopher A.

2012-01-01

Our previous studies have shown that post-weaning social isolation of male rats leads to sensitization of serotonergic systems and increases in anxiety-like behavior in adulthood. Although studies in humans suggest that females have an increased sensitivity to stress and risk for the development of neuropsychiatric illnesses, most studies involving laboratory rats have focused on males while females have been insufficiently studied. The objective of this study was to investigate the effects of post-weaning social isolation on subsequent responses of an anxiety-related dorsal raphe nucleus (DR)-basolateral amygdala system to pharmacological challenge with the anxiogenic drug, N-methyl-beta-carboline-3-carboxamide (FG-7142; a partial inverse agonist at the benzodiazepine allosteric site on the γ-aminobutyric acid (GABA)A receptor). Juvenile female rats were reared in isolation or in groups of three for a 3-week period from weaning to mid-adolescence, after which all rats were group-reared for an additional 2 weeks. We then used dual immunohistochemical staining for c-Fos and tryptophan hydroxylase in the DR or single immunohistochemical staining for c-Fos in the basolateral amygdala. Isolation-reared rats, but not group-reared rats, injected with FG-7142 had increased c-Fos expression within the basolateral amygdala and in serotonergic neurons in the dorsal, ventrolateral, caudal and interfascicular parts of the DR relative to appropriate vehicle-injected control groups. These data suggest that post-weaning social isolation of female rats sensitizes a DR-basolateral amygdala system to stress-related stimuli, which may lead to an increased sensitivity to stress- and anxiety-related responses in adulthood. PMID:22297173

GCaMP expression in retinal ganglion cells characterized using a low-cost fundus imaging system

NASA Astrophysics Data System (ADS)

Chang, Yao-Chuan; Walston, Steven T.; Chow, Robert H.; Weiland, James D.

2017-10-01

Objective. Virus-transduced, intracellular-calcium indicators are effective reporters of neural activity, offering the advantage of cell-specific labeling. Due to the existence of an optimal time window for the expression of calcium indicators, a suitable tool for tracking GECI expression in vivo following transduction is highly desirable. Approach. We developed a noninvasive imaging approach based on a custom-modified, low-cost fundus viewing system that allowed us to monitor and characterize in vivo bright-field and fluorescence images of the mouse retina. AAV2-CAG-GCaMP6f was injected into a mouse eye. The fundus imaging system was used to measure fluorescence at several time points post injection. At defined time points, we prepared wholemount retina mounted on a transparent multielectrode array and used calcium imaging to evaluate the responsiveness of retinal ganglion cells (RGCs) to external electrical stimulation. Main results. The noninvasive fundus imaging system clearly resolves individual (RGCs and axons. RGC fluorescence intensity and the number of observable fluorescent cells show a similar rising trend from week 1 to week 3 after viral injection, indicating a consistent increase of GCaMP6f expression. Analysis of the in vivo fluorescence intensity trend and in vitro neurophysiological responsiveness shows that the slope of intensity versus days post injection can be used to estimate the optimal time for calcium imaging of RGCs in response to external electrical stimulation. Significance. The proposed fundus imaging system enables high-resolution digital fundus imaging in the mouse eye, based on off-the-shelf components. The long-term tracking experiment with in vitro calcium imaging validation demonstrates the system can serve as a powerful tool monitoring the level of genetically-encoded calcium indicator expression, further determining the optimal time window for following experiment.

Neurotrophin gene therapy for sustained neural preservation after deafness.

PubMed

Atkinson, Patrick J; Wise, Andrew K; Flynn, Brianna O; Nayagam, Bryony A; Hume, Clifford R; O'Leary, Stephen J; Shepherd, Robert K; Richardson, Rachael T

2012-01-01

The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the residual spiral ganglion neurons. These neurons, however, undergo progressive degeneration after hearing loss, marked initially by peripheral fibre retraction and ultimately culminating in cell death. This research aims to use gene therapy techniques to both hold and reverse this degeneration by providing a sustained and localised source of neurotrophins to the deafened cochlea. Adenoviral vectors containing green fluorescent protein, with or without neurotrophin-3 and brain derived neurotrophic factor, were injected into the lower basal turn of scala media of guinea pigs ototoxically deafened one week prior to intervention. This single injection resulted in localised and sustained gene expression, principally in the supporting cells within the organ of Corti. Guinea pigs treated with adenoviral neurotrophin-gene therapy had greater neuronal survival compared to contralateral non-treated cochleae when examined at 7 and 11 weeks post injection. Moreover; there was evidence of directed peripheral fibre regrowth towards cells expressing neurotrophin genes after both treatment periods. These data suggest that neurotrophin-gene therapy can provide sustained protection of spiral ganglion neurons and peripheral fibres after hearing loss.

Continuing medical education-driven skills acquisition and impact on improved patient outcomes in family practice setting.

PubMed

Bellamy, N; Goldstein, L D; Tekanoff, R A

2000-01-01

An abundance of educational theory, design, and delivery of continuing medical education (CME) learning interventions, including their impact on learners, are described in the health and social sciences literature. However, establishing a direct correlation between the acquisition of new skills by learners and patient outcomes as a result of a planned CME learning intervention has been difficult to demonstrate. The learning intervention described here tested the impact of an injection skills-acquisition program for family physicians treating osteoarthritis of the knee by measuring patient outcomes using the pain and function subscales of the Western Ontario and McMaster (WOMAC) 3.0 osteoarthritis index, a standardized and fully validated patient-centered outcome measurement. It was hypothesized that patients of family physicians who participated in this skills-acquisition CME program would benefit from treatment administered by their physician during the time between injection skills acquisition to 6 weeks post-injection. Inclusion of a validated health status measure administered pre- and post-injection in addition to more traditional faculty and participant program evaluations was deemed necessary to test this hypothesis. Rheumatology, orthopedic surgery, and family medicine specialists from across Canada were invited to contribute to the planning, curriculum elaboration, and delivery of the viscosupplement injector preceptorship (VIP) program. Thirty-nine orthopedic and rheumatology specialists agreed to serve as expert faculty and participated in training 474 Canadian family and general practitioners over 8 months. The learning intervention involved a review of pertinent literature by a local preceptor and a summary of recommendations of the planning committee, followed by demonstration of injector skills and then supervised practice with patients, who received hylan G-F 20 (Synvisc, Ridgefield, NJ) usually in the offices of the family physicians. The pain and function subscales of the WOMAC 3.0 questionnaire were self-administered to each patient in their physician's office, prior to receiving their joint injection and again at or near 6-weeks post-injection. Data were analyzed in the Department of Epidemiology and Biostatistics at The University of Western Ontario, London, ON. Clinically important statistically significant improvements in pain and physical function were noted in patients who received viscosupplementation treatment from family physicians who had recently acquired the necessary injection skills. Approximately three-quarters of the patients experienced a reduction in pain and an improvement in physical function of at least 20%. These results suggest a positive relationship between acquisition of a new skill by learners and improved patient outcomes as a result of this planned CME learning intervention.

Daily penicillin serum concentrations following injection of 1.2 mega-units of ”all-purpose” penicillin

PubMed Central

Tinkler, A. E.; Hedges, A. J.; Shannon, R.

1965-01-01

In view of evidence suggesting that 1.2 mega-units of ”all-purpose” penicillin (300 000 IU potassium penicillin G, 300 000 IU procaine penicillin G and 600 000 IU benzathine penicillin) did not maintain treponemicidal serum concentrations during the week following injection—which if true, might necessitate a reappraisal of prophylactic and treatment schedules in wide use against syphilis—daily assays were performed to determine the penicillinaemia levels in ambulant adult males for one week following intramuscular injection with this dosage of two ”all-purpose” products (168 assays in all, 24 each day). Statistical evaluation of the results showed that the mean daily serum concentrations were, in fact, treponemicidal during the whole week after injection. The means of groups of 24 assays fell within narrow daily ranges on each of the seven post-injection days, suggesting that the long-acting component (benzathine penicillin) gives reliable and predictable daily levels in a high proportion of cases. This is in contrast to those penicillins which rely for their long-acting property on the oily gel in which they are suspended. On the other hand, the extremes of penicillinaemia for any individual in a large group were shown to cover a very wide range, demonstrating that a particular patient's failure to respond to standard treatment or prophylaxis can be due to factors quite unrelated to the quality or specificity of the product or to the sensitivity of the organism causing disease. PMID:5294592

Acute versus chronic phase mechanisms in a rat model of CRPS.

PubMed

Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Kingery, Wade S; Clark, John David

2016-01-19

Tibia fracture followed by cast immobilization in rats evokes nociceptive, vascular, epidermal, and bone changes resembling complex regional pain syndrome (CRPS). In most cases, CRPS has three stages. Over time, this acute picture, allodynia, warmth, and edema observed at 4 weeks, gives way to a cold, dystrophic but still painful limb. In the acute phase (at 4 weeks post fracture), cutaneous immunological and NK1-receptor signaling mechanisms underlying CRPS have been discovered; however, the mechanisms responsible for the chronic phase are still unknown. The purpose of this study is to understand the mechanisms responsible for the chronic phases of CRPS (at 16 weeks post fracture) at both the peripheral and central levels. We used rat tibial fracture/cast immobilization model of CRPS to study molecular, vascular, and nociceptive changes at 4 and 16 weeks post fracture. Immunoassays and Western blotting were carried out to monitor changes in inflammatory response and NK1-receptor signaling in the skin and spinal cord. Skin temperature and thickness were measured to elucidate vascular changes, whereas von Frey testing and unweighting were carried out to study nociceptive changes. All data were analyzed by one-way analysis of variance (ANOVA) followed by Neuman-Keuls multiple comparison test to compare among all cohorts. In the acute phase (at 4 weeks post fracture), hindpaw allodynia, unweighting, warmth, edema, and/or epidermal thickening were observed among 90 % fracture rats, though by 16 weeks (chronic phase), only the nociceptive changes persisted. The expression of the neuropeptide signaling molecule substance P (SP), NK1 receptor, inflammatory mediators TNFα, IL-1β, and IL-6 and nerve growth factor (NGF) were elevated at 4 weeks in sciatic nerve and/or skin, returning to normal levels by 16 weeks post fracture. The systemic administration of a peripherally restricted IL-1 receptor antagonist (anakinra) or of anti-NGF inhibited nociceptive behaviors at 4 weeks but not 16 weeks. However, spinal levels of NK1 receptor, TNFα, IL-1β, and NGF were elevated at 4 and 16 weeks, and intrathecal injection of an NK1-receptor antagonist (LY303870), anakinra, or anti-NGF each reduced nociceptive behaviors at both 4 and 16 weeks. These results demonstrate that tibia fracture and immobilization cause peripheral changes in neuropeptide signaling and inflammatory mediator production acutely, but central spinal changes may be more important for the persistent nociceptive changes in this CRPS model.

Community reentry challenges after release from prison among people who inject drugs in St. Petersburg, Russia.

PubMed

Cepeda, Javier A; Vetrova, Marina V; Lyubimova, Alexandra I; Levina, Olga S; Heimer, Robert; Niccolai, Linda M

2015-01-01

Little is known about the context of the post-release risk environment among formerly incarcerated people who inject drugs (PWID) in Russia. The purpose of this paper is to explore these challenges as they relate to reentry, relapse to injection opioid use, and overdose. The authors conducted 25 in-depth semi-structured interviews among PWID living in St Petersburg, Russia who had been incarcerated within the past two years. Participants were recruited from street outreach (n=20) and a drug treatment center (n=5). Emergent themes related to the post-release environment included financial instability, negative interactions with police, return to a drug using community, and reuniting with drug using peers. Many respondents relapsed to opioid use immediately after release. Those whose relapse occurred weeks or months after their release expressed more motivation to resist. Alcohol or stimulant use often preceded the opioid relapse episode. Among those who overdosed, alcohol use was often reported prior to overdosing on opioids. Future post-release interventions in Russia should effectively link PWID to social, medical, and harm reduction services. Particular attention should be focussed on helping former inmates find employment and overdose prevention training prior to leaving prison that should also cover the heightened risk of concomitant alcohol use. In addition to describing a syndemic involving the intersection of incarceration, injection drug use, poverty, and alcohol abuse, the findings can inform future interventions to address these interrelated public health challenges within the Russian setting.

Intraarticular triamcinolone hexacetonide injection in children with chronic arthritis: a survey of clinical practice.

PubMed

Yang, M H; Lee, W I; Chen, L C; Lin, S J; Huang, J L

1999-01-01

To assess the efficacy of the intraarticular steroid(IAS) injection in the management of arthritis and the possible related complications in children with chronic arthritis. We evaluated 11 children of chronic arthritis (4 girls and 7 boys), age of onset ranged from 2-13.6 years, who had persistent arthritis treated with IAS from November 1994 to June 1997. The results of injections showed that the beneficial effect was noted within one day to 2 weeks without significant adverse reactions, remission exceeding 6 months was seen in 10 of 11 patients (in 14 of 18 joints). According to subgroups of chronic arthritis, the remission rate of IAS injection in children with pauciarticular arthritis reached 100%. A significant fall in C-reactive protein (CRP) between pre- and post-IAS injection (p = 0.03), but there were no differences in hemoglobin (Hb), white blood cells (WBCs), thrombocytes (Plts), erythrocyte sedimentation rate (ESR) and osteocalcin level. No injection-related complications were found. In conclusion, the IAS injection was an effective and safe treatment in children with chronic arthritis with no obvious complications especially in pauciarticular arthritis.

Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant

PubMed Central

Yang, Xu; Ricciardi, Benjamin F.; Dvorzhinskiy, Aleksey; Brial, Caroline; Lane, Zachary; Bhimani, Samrath; Burket, Jayme C.; Hu, Bin; Sarkisian, Alexander M.; Ross, F. Patrick; van der Meulen, Marjolein C.H.; Bostrom, Mathias P.G.

2015-01-01

Background: Long-term fixation of uncemented joint implants requires early mechanical stability and implant osseointegration. To date, osseointegration has been unreliable and remains a major challenge in cementless total knee arthroplasty. We developed a murine model in which an intra-articular proximal tibial titanium implant with a roughened stem can be loaded through the knee joint. Using this model, we tested the hypothesis that intermittent injection of parathyroid hormone (iPTH) would increase proximal tibial cancellous osseointegration. Methods: Ten-week-old female C57BL/6 mice received a subcutaneous injection of PTH (40 μg/kg/day) or a vehicle (n = 45 per treatment group) five days per week for six weeks, at which time the baseline group was killed (n = 6 per treatment group) and an implant was inserted into the proximal part of the tibiae of the remaining mice. Injections were continued until the animals were killed at one week (n = 7 per treatment group), two weeks (n = 14 per treatment group), or four weeks (n = 17 per treatment group) after implantation. Outcomes included peri-implant bone morphology as analyzed with micro-computed tomography (microCT), osseointegration percentage and bone area fraction as shown with backscattered electron microscopy, cellular composition as demonstrated by immunohistochemical analysis, and pullout strength as measured with mechanical testing. Results: Preimplantation iPTH increased the epiphyseal bone volume fraction by 31.6%. When the data at post-implantation weeks 1, 2, and 4 were averaged for the iPTH-treated mice, the bone volume fraction was 74.5% higher in the peri-implant region and 168% higher distal to the implant compared with the bone volume fractions in the same regions in the vehicle-treated mice. Additionally, the trabecular number was 84.8% greater in the peri-implant region and 74.3% greater distal to the implant. Metaphyseal osseointegration and bone area fraction were 28.1% and 70.1% higher, respectively, in the iPTH-treated mice than in the vehicle-treated mice, and the maximum implant pullout strength was 30.9% greater. iPTH also increased osteoblast and osteoclast density by 65.2% and 47.0%, respectively, relative to the values in the vehicle group, when the data at post-implantation weeks 1 and 2 were averaged. Conclusions: iPTH increased osseointegration, cancellous mass, and the strength of the bone-implant interface. Clinical Relevance: Our murine model is an excellent platform on which to study biological enhancement of cancellous osseointegration. PMID:26135074

Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant.

PubMed

Yang, Xu; Ricciardi, Benjamin F; Dvorzhinskiy, Aleksey; Brial, Caroline; Lane, Zachary; Bhimani, Samrath; Burket, Jayme C; Hu, Bin; Sarkisian, Alexander M; Ross, F Patrick; van der Meulen, Marjolein C H; Bostrom, Mathias P G

2015-07-01

Long-term fixation of uncemented joint implants requires early mechanical stability and implant osseointegration. To date, osseointegration has been unreliable and remains a major challenge in cementless total knee arthroplasty. We developed a murine model in which an intra-articular proximal tibial titanium implant with a roughened stem can be loaded through the knee joint. Using this model, we tested the hypothesis that intermittent injection of parathyroid hormone (iPTH) would increase proximal tibial cancellous osseointegration. Ten-week-old female C57BL/6 mice received a subcutaneous injection of PTH (40 μg/kg/day) or a vehicle (n = 45 per treatment group) five days per week for six weeks, at which time the baseline group was killed (n = 6 per treatment group) and an implant was inserted into the proximal part of the tibiae of the remaining mice. Injections were continued until the animals were killed at one week (n = 7 per treatment group), two weeks (n = 14 per treatment group), or four weeks (n = 17 per treatment group) after implantation. Outcomes included peri-implant bone morphology as analyzed with micro-computed tomography (microCT), osseointegration percentage and bone area fraction as shown with backscattered electron microscopy, cellular composition as demonstrated by immunohistochemical analysis, and pullout strength as measured with mechanical testing. Preimplantation iPTH increased the epiphyseal bone volume fraction by 31.6%. When the data at post-implantation weeks 1, 2, and 4 were averaged for the iPTH-treated mice, the bone volume fraction was 74.5% higher in the peri-implant region and 168% higher distal to the implant compared with the bone volume fractions in the same regions in the vehicle-treated mice. Additionally, the trabecular number was 84.8% greater in the peri-implant region and 74.3% greater distal to the implant. Metaphyseal osseointegration and bone area fraction were 28.1% and 70.1% higher, respectively, in the iPTH-treated mice than in the vehicle-treated mice, and the maximum implant pullout strength was 30.9% greater. iPTH also increased osteoblast and osteoclast density by 65.2% and 47.0%, respectively, relative to the values in the vehicle group, when the data at post-implantation weeks 1 and 2 were averaged. iPTH increased osseointegration, cancellous mass, and the strength of the bone-implant interface. Our murine model is an excellent platform on which to study biological enhancement of cancellous osseointegration. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

WE-EF-BRA-10: Prophylactic Cranial Irradiation Reduces the Incidence of Brain Metastasis in a Mouse Model of Metastatic Breast Cancerr

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, D; Debeb, B; Larson, R

Purpose: Prophylactic cranial irradiation (PCI) is a clinical technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with acute lymphoblastic leukemia and small-cell lung cancer. We examined whether PCI could benefit breast cancer patients at high risk of developing brain metastases. Methods: We utilized our mouse model in which 500k green fluorescent protein (GFP)-labeled breast cancer cells injected into the tail vein of SCID/Beige mice resulted in brain metastases in approximately two-thirds of untreated mice. To test the efficacy of PCI, one set of mice was irradiated five days after cell injection withmore » a single fraction of 4-Gy (two 2-Gy opposing fields) whole-brain irradiation on the XRAD 225Cx small-animal irradiator. Four controls were included: a non-irradiated group, a group irradiated two days prior to cell injection, and two groups irradiated 3 or 6 weeks after cell injection. Mice were sacrificed four and eight weeks post-injection and were evaluated for the presence of brain metastases on a fluorescent stereomicroscope. Results: The incidence of brain metastasis in the non-irradiated group was 77% and 90% at four and eight weeks, respectively. The PCI group had a significantly lower incidence, 20% and 30%, whereas the other three control groups had incidence rates similar to the non-treated control (70% to 100%). Further, the number of metastases and the metastatic burden were also significantly lower in the PCI group compared to all other groups. Conclusion: The timing of irradiation to treat subclinical disease is critical, as a small dose of whole-brain irradiation given five days after cell injection abrogated tumor burden by greater than 90%, but had no effect when administered twenty-one days after cell injection. PCI is likely to benefit breast cancer patients at high risk of developing brain metastases and should be strongly considered in the clinic.« less

Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial.

PubMed

Wang, Yuanyuan; Shimmin, Andrew; Ghosh, Peter; Marks, Paul; Linklater, James; Connell, David; Hall, Stephen; Skerrett, Donna; Itescu, Silviu; Cicuttini, Flavia M

2017-08-02

Few clinical trials have investigated the safety and efficacy of mesenchymal stem cells for the management of post-traumatic osteoarthritis. The objectives of this pilot study were to determine the safety and tolerability and to explore the efficacy of a single intra-articular injection of allogeneic human mesenchymal precursor cells (MPCs) to improve clinical symptoms and retard joint structural deterioration over 24 months in patients following anterior cruciate ligament (ACL) reconstruction. In this phase Ib/IIa, double-blind, active comparator clinical study, 17 patients aged 18-40 years with unilateral ACL reconstruction were randomized (2:1) to receive either a single intra-articular injection of 75 million allogeneic MPCs suspended in hyaluronan (HA) (MPC + HA group) (n = 11) or HA alone (n = 6). Patients were monitored for adverse events. Immunogenicity was evaluated by anti-HLA panel reactive antibodies (PRA) against class I and II HLAs determined by flow cytometry. Pain, function, and quality of life were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and SF-36v2 scores. Joint space width was measured from radiographs, and tibial cartilage volume and bone area assessed from magnetic resonance imaging (MRI). Moderate arthralgia and swelling within 24 h following injection that subsided were observed in 4 out of 11 in the MPC + HA group and 0 out of 6 HA controls. No cell-related serious adverse effects were observed. Increases in class I PRA >10% were observed at week 4 in the MPC + HA group that decreased to baseline levels by week 104. Compared with the HA group, MPC + HA-treated patients showed greater improvements in KOOS pain, symptom, activities of daily living, and SF-36 bodily pain scores (p < 0.05). The MPC + HA group had reduced medial and lateral tibiofemoral joint space narrowing (p < 0.05), less tibial bone expansion (0.5% vs 4.0% over 26 weeks, p = 0.02), and a trend towards reduced tibial cartilage volume loss (0.7% vs -4.0% over 26 weeks, p = 0.10) than the HA controls. Intra-articular administration of a single allogeneic MPC injection following ACL reconstruction was safe, well tolerated, and may improve symptoms and structural outcomes. These findings suggest that MPCs warrant further investigations as they may modulate some of the pathological processes responsible for the development of post-traumatic osteoarthritis following ACL reconstruction. ClinicalTrials.gov ( NCT01088191 ) registration date: March 11, 2010.

A Quantitative and Standardized Method for the Evaluation of Choroidal Neovascularization Using MICRON III Fluorescein Angiograms in Rats

PubMed Central

Wigg, Jonathan P.; Zhang, Hong; Yang, Dong

2015-01-01

Introduction In-vivo imaging of choroidal neovascularization (CNV) has been increasingly recognized as a valuable tool in the investigation of age-related macular degeneration (AMD) in both clinical and basic research applications. Arguably the most widely utilised model replicating AMD is laser generated CNV by rupture of Bruch’s membrane in rodents. Heretofore CNV evaluation via in-vivo imaging techniques has been hamstrung by a lack of appropriate rodent fundus camera and a non-standardised analysis method. The aim of this study was to establish a simple, quantifiable method of fluorescein fundus angiogram (FFA) image analysis for CNV lesions. Methods Laser was applied to 32 Brown Norway Rats; FFA images were taken using a rodent specific fundus camera (Micron III, Phoenix Laboratories) over 3 weeks and compared to conventional ex-vivo CNV assessment. FFA images acquired with fluorescein administered by intraperitoneal injection and intravenous injection were compared and shown to greatly influence lesion properties. Utilising commonly used software packages, FFA images were assessed for CNV and chorioretinal burns lesion area by manually outlining the maximum border of each lesion and normalising against the optic nerve head. Net fluorescence above background and derived value of area corrected lesion intensity were calculated. Results CNV lesions of rats treated with anti-VEGF antibody were significantly smaller in normalised lesion area (p<0.001) and fluorescent intensity (p<0.001) than the PBS treated control two weeks post laser. The calculated area corrected lesion intensity was significantly smaller (p<0.001) in anti-VEGF treated animals at 2 and 3 weeks post laser. The results obtained using FFA correlated with, and were confirmed by conventional lesion area measurements from isolectin stained choroidal flatmounts, where lesions of anti-VEGF treated rats were significantly smaller at 2 weeks (p = 0.049) and 3 weeks (p<0.001) post laser. Conclusion The presented method of in-vivo FFA quantification of CNV, including acquisition variable corrections, using the Micron III system and common use software establishes a reliable method for detecting and quantifying CNV enabling longitudinal studies and represents an important alternative to conventional CNV quantification methods. PMID:26024231

Identification of the active components in Bone Marrow Soup: a mitigator against irradiation-injury to salivary glands

PubMed Central

Fang, Dongdong; Hu, Shen; Liu, Younan; Quan, Vu-Hung; Seuntjens, Jan; Tran, Simon D.

2015-01-01

In separate studies, an extract of soluble intracellular contents from whole bone marrow cells, named “Bone Marrow (BM) Soup”, was reported to either improve cardiac or salivary functions post-myocardial infarction or irradiation (IR), respectively. However, the active components in BM Soup are unknown. To demonstrate that proteins were the active ingredients, we devised a method using proteinase K followed by heating to deactivate proteins and for safe injections into mice. BM Soup and “deactivated BM Soup” were injected into mice that had their salivary glands injured with 15Gy IR. Control mice received either injections of saline or were not IR. Results at week 8 post-IR showed the ‘deactivated BM Soup’ was no better than injections of saline, while injections of native BM Soup restored saliva flow, protected salivary cells and blood vessels from IR-damage. Protein arrays detected several angiogenesis-related factors (CD26, FGF, HGF, MMP-8, MMP-9, OPN, PF4, SDF-1) and cytokines (IL-1ra, IL-16) in BM Soup. In conclusion, the native proteins (but not the nucleic acids, lipids or carbohydrates) were the therapeutic ingredients in BM Soup for functional salivary restoration following IR. This molecular therapy approach has clinical potential because it is theoretically less tumorigenic and immunogenic than cell therapies. PMID:26526154

Injection of the rheumatoid knee: does intra-articular methotrexate or rifampicin add to the benefits of triamcinolone hexacetonide?

PubMed

Blyth, T; Stirling, A; Coote, J; Land, D; Hunter, J A

1998-07-01

Does the addition of 600 mg rifampicin or 50 mg methotrexate improve pain relief after injection of the rheumatoid knee with 20 mg triamcinolone hexacetonide (TH)? Eighty-two patients on stable therapy were allocated at random to receive intra-articular TH alone, TH and methotrexate (TH+M) or TH and rifampicin (TH+R). Pain was recorded by a weekly chart and analysed using the area under the curve (AUC), periods of total pain relief and duration of effect. Examinations and microwave thermography were performed by an independent meteorologist at baseline, 3 and 6 months. Using the AUC, pain was significantly better in the TH+R group compared with TH alone (P=0.039, Mann Whitney U). The median duration of improved pain scores was 13.5 weeks with TH alone, 10 with TH+M and 19 with TH+R. Examination and microwave thermography revealed improvements compared with baseline, but there were no significant differences between the groups. Eleven of 28 patients treated with TH + R developed a flare of post-injection pain. Whilst the addition of rifampicin improved pain relief, the occurrence of pain after injection remains a problem. Measures to minimize this are needed when TH+R is used.

Treatment of intra-oral injection phobia: a randomized delayed intervention controlled trial among Norwegian 10- to 16-year-olds.

PubMed

Berge, Karin G; Agdal, Maren Lillehaug; Vika, Margrethe; Skeie, Marit Slåttelid

2017-05-01

To evaluate the effect of five sessions of cognitive behavioural therapy (CBT) for 10- to 16-year-olds with intra-oral injection phobia. This was a randomized delayed intervention controlled trial in 67 patients, fulfilling the DSM-5 criteria for specific phobia. All patients received the same CBT performed by dentists specially trained in CBT. The patients were randomly assigned to either an immediate treatment group (ITG) (34 patients) or a waitlist-control group (WCG) (33 patients). The WCG was put on a waitlist for 5 weeks. After treatment, all patients were combined for post-treatment analyses. Assessments including the psychometric self-report scales Intra-oral injection fear scale (IOIF-s), Children's Fear Survey Schedule-Dental Subscale (CFSS-DS), Injection Phobia Scale for children (IS-c) and Mutilation Questionnaire for children (MQ-c) and a behavioural avoidance test (BAT) followed by a questionnaire on cognitions during the BAT, occurred pre-, post-treatment/waitlist and at a 1-year follow-up. CBT had a significant effect compared to no treatment (WCG). After treatment, the scores on the psychometric self-report scales were significantly reduced and higher levels in the BAT were achieved. The results were maintained at 1-year follow-up. Of the 67 patients, 70.1% received intra-oral injections during CBT treatment, whereas 69.4% of those completing the CBT, in need for further dental treatment, managed to receive the necessary intra-oral injections at their regular dentist. The 10- to 16-year-olds diagnosed with intra-oral injection phobia benefitted positively on CBT performed by specially trained dentists.

40 CFR 146.93 - Post-injection site care and site closure.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) The pressure differential between pre-injection and predicted post-injection pressures in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Post-injection site care and site... Applicable to Class VI Wells § 146.93 Post-injection site care and site closure. (a) The owner or operator of...

40 CFR 146.93 - Post-injection site care and site closure.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) The pressure differential between pre-injection and predicted post-injection pressures in the... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Post-injection site care and site... Applicable to Class VI Wells § 146.93 Post-injection site care and site closure. (a) The owner or operator of...

40 CFR 146.93 - Post-injection site care and site closure.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) The pressure differential between pre-injection and predicted post-injection pressures in the... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Post-injection site care and site... Applicable to Class VI Wells § 146.93 Post-injection site care and site closure. (a) The owner or operator of...

Treatment of cervical pregnancy with ultrasound-guided local methotrexate injection.

PubMed

Yamaguchi, M; Honda, R; Erdenebaatar, C; Monsur, M; Honda, T; Sakaguchi, I; Okamura, Y; Ohba, T; Katabuchi, H

2017-12-01

Cervical pregnancy (CP) is a rare type of ectopic pregnancy. While methotrexate (MTX) is generally the first-line method of choice for clinically stable women, there is still no consensus on the most appropriate treatment for this abnormal pregnancy. The aim of this study was to investigate the efficacy of a single local MTX injection under transvaginal ultrasound guidance for the initial treatment of CP and to assess post-treatment fertility. We reviewed retrospectively 15 patients with CP treated with local MTX injection under transvaginal ultrasound guidance. In all patients, the serum human chorionic gonadotropin (hCG) levels were monitored and the gestational sac was evaluated using ultrasonography after treatment. Magnetic resonance imaging (MRI) was performed as necessary. We evaluated the patients' clinical characteristics and clinical course after treatment, the efficacy of the treatment and the post-treatment fertility in patients desiring subsequent pregnancy. The median estimated gestational age at the time of MTX injection was 6 + 2 (range, 5 + 2 to 11 + 0) weeks. All 15 patients were treated successfully, without the need for blood transfusion or surgical procedures; however, three patients required an additional local MTX injection due to a poor decline in serum hCG level following the initial injection, while one patient required uterine artery embolization due to persistent vaginal bleeding and an enlarging gestational sac with blood vessels visible on contrast-enhanced MRI. The mean time following initial MTX injection for hCG normalization was 43.8 (95% CI, 33.3-54.3) days and for resumption of menses was 68.4 (95% CI, 51.9-84.9) days. Seven of the 10 women desiring subsequent pregnancy following treatment had uneventful pregnancy, one became pregnant but miscarried spontaneously at 8 weeks of gestation, one was treated by laparoscopic surgery after diagnosis of a tubal pregnancy and one did not conceive. A single, ultrasound-guided, local MTX injection is apparently effective for the treatment of CP without the need for concomitant procedures or surgical intervention. Furthermore, this conservative technique both preserves fertility and allows for the possibility of subsequent uneventful pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

N-Acetylcysteine Restores Sevoflurane Postconditioning Cardioprotection against Myocardial Ischemia-Reperfusion Injury in Diabetic Rats.

PubMed

Lin, Jiefu; Wang, Tingting; Li, Yalan; Wang, Mengxia; Li, Haobo; Irwin, Michael G; Xia, Zhengyuan

2016-01-01

The effect of sevoflurane postconditioning (sevo-postC) cardioprotection is compromised in diabetes which is associated with increased oxidative stress. We hypothesized that antioxidant N-Acetylcysteine may enhance or restore sevo-postC cardioprotection in diabetes. Control or streptozotocin-induced Type 1 diabetic rats were either untreated or treated with N-Acetylcysteine for four weeks starting at five weeks after streptozotocin injection and were subjected to myocardial ischemia-reperfusion injury (IRI), in the absence or presence of sevo-postC. Diabetes showed reduction of cardiac STAT3 activation (p-STAT3) and adiponectin with concomitantly increase of FoxO1 and CD36, which associated with reduced sevo-postC cardioprotection. N-Acetylcysteine and sevo-postC synergistically reduced the infarct size in diabetic groups. N-Acetylcysteine remarkably increased cardiac p-STAT3 which was further enhanced by sevo-postC. N-Acetylcysteine but not sevo-postC decreased myocardial FoxO1 while sevo-postC but not N-Acetylcysteine significantly increased myocardiac adiponectin in diabetic rats. It is concluded that late stage diabetic rats displayed reduction of cardiac p-STAT3, adiponectin deficiency, and increase of FoxO1 and CD36 expression, which may be responsible for the loss of myocardial responsiveness to sevo-postC cardioprotection. N-Acetylcysteine restored Sevo-postC cardioprotection in diabetes possibly through enhancing cardiac p-STAT3 and adiponectin and reducing Fox1 and CD36.

Advantages of Pure Platelet-Rich Plasma Compared with Leukocyte- and Platelet-Rich Plasma in Treating Rabbit Knee Osteoarthritis

PubMed Central

Yin, Wen-Jing; Xu, Hai-Tao; Sheng, Jia-Gen; An, Zhi-Quan; Guo, Shang-Chun; Xie, Xue-Tao; Zhang, Chang-Qing

2016-01-01

Background Concentrated leukocytes in leukocyte- and platelet-rich plasma (L-PRP) may deliver increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage. However, to date no relevant studies have substantiated that in vivo. Material/Methods Autologous L-PRP and pure platelet-rich plasma (P-PRP) were prepared, measured for componential composition, and injected intra-articularly after 4, 5, and 6 weeks post-anterior cruciate ligament transection. Caffeic acid phenethyl ester (CAPE) was injected intraperitoneally to inhibit NF-κB activation. All rabbits were sacrificed after 8 weeks postoperative. Enzyme-linked immunosorbent assays were performed to determine interleukin 1β (IL-1β) and prostaglandin E2 (PGE2) concentrations in the synovial fluid, Indian ink staining was performed for gross morphological assessment, and hematoxylin and eosin staining and toluidine blue staining were performed for histological assessment. Results Compared with L-PRP, P-PRP injections achieved better outcomes regarding the prevention of cartilage destruction, preservation of cartilaginous matrix, and reduction of IL-1β and PGE2 concentrations. CAPE injections reversed the increased IL-1β and PGE2 concentrations in the synovial fluid after L-PRP injections and improved the outcome of L-PRP injections to a level similar to P-PRP injections, while they had no influence on the therapeutic efficacy of P-PRP injections. Conclusions Concentrated leukocytes in L-PRP may release increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage, and finally, result in a inferior efficacy of L-PRP to P-PRP for the treatment of osteoarthritis. PMID:27086145

Advantages of Pure Platelet-Rich Plasma Compared with Leukocyte- and Platelet-Rich Plasma in Treating Rabbit Knee Osteoarthritis.

PubMed

Yin, Wen-Jing; Xu, Hai-Tao; Sheng, Jia-Gen; An, Zhi-Quan; Guo, Shang-Chun; Xie, Xue-Tao; Zhang, Chang-Qing

2016-04-17

BACKGROUND Concentrated leukocytes in leukocyte- and platelet-rich plasma (L-PRP) may deliver increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage. However, to date no relevant studies have substantiated that in vivo. MATERIAL AND METHODS Autologous L-PRP and pure platelet-rich plasma (P-PRP) were prepared, measured for componential composition, and injected intra-articularly after 4, 5, and 6 weeks post-anterior cruciate ligament transection. Caffeic acid phenethyl ester (CAPE) was injected intraperitoneally to inhibit NF-κB activation. All rabbits were sacrificed after 8 weeks postoperative. Enzyme-linked immunosorbent assays were performed to determine interleukin 1β (IL-1β) and prostaglandin E2 (PGE2) concentrations in the synovial fluid, Indian ink staining was performed for gross morphological assessment, and hematoxylin and eosin staining and toluidine blue staining were performed for histological assessment. RESULTS Compared with L-PRP, P-PRP injections achieved better outcomes regarding the prevention of cartilage destruction, preservation of cartilaginous matrix, and reduction of IL-1β and PGE2 concentrations. CAPE injections reversed the increased IL-1β and PGE2 concentrations in the synovial fluid after L-PRP injections and improved the outcome of L-PRP injections to a level similar to P-PRP injections, while they had no influence on the therapeutic efficacy of P-PRP injections. CONCLUSIONS Concentrated leukocytes in L-PRP may release increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage, and finally, result in a inferior efficacy of L-PRP to P-PRP for the treatment of osteoarthritis.

Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes

NASA Astrophysics Data System (ADS)

Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

2015-08-01

Objective. Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach. Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg-1. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main results. Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance. Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

Testing a West Nile virus vaccine in sandhill cranes (Grus canadensis)

USGS Publications Warehouse

Olsen, Glenn H.; Miller, K.; Docherty, D.; Sileo, L.; Chavez-Ramirez, Felipe

2005-01-01

Eight sandhill cranes (Grus canadensis) were vaccinated with a commercial equine West Nile virus vaccine (Fort Dodge Animal Health, Fort Dodge, Iowa, USA) at the USGS Patuxent Wildlife Research Center, Laurel, Maryland, USA. Three doses of the vaccine were given, the first dose (day 0) was followed by a second 21 days later and the third dose 7 days after the second day 28 after the first dose). All doses were 0.50 ml. In addition, 5 sandhill cranes were given injections of similar amounts of sterile water on the same schedule. Blood for complete blood counts, serum chemistries, and serological testing was collected at weekly intervals. Ten weeks after the first injection of the vaccine and 6 weeks after the last of the 3 injections of the vaccine, the cranes were shipped to the USGS National Wildlife Heath Center, Madison, Wisconsin, USA. After a two-week adjustment period, 11 of these cranes were injected intramuscularly with one mosquito dose of West Nile virus. Two of the vaccinated cranes were not challenged and acted as uninfected controls. One week post challenge the only abnormal findings were slight weight loss (average 6% loss since the time of challenge with West Nile virus) and elevated white blood cell counts (heterophilic leukocytosis). There were no deaths and no clinically ill cranes (unvaccinated or vaccinated cranes) among the 11 challenged birds. All cranes were euthanized 6 weeks post challenge, and necropsies were performed. Pre-challenge titers showed no titer response to the vaccinations. However, when challenged, vaccinated cranes developed titers more quickly (within 7-10 days), and were viremic and shed virus via the cloaca for a shorter period of time than the unvaccinated cranes (2-7 days for vaccinated cranes versus 2-10 days for unvaccinated cranes). No remarkable lesions were noted in any of the cranes during the necropsy examinations. Histopathological findings are available for only four of the cranes at this time. Three of those had mild to moderate encephalitis, myelitis, and myocarditis. Initial histopathological findings also indicated a difference in the lesions found in the brains of the vaccinated versus unvaccinated cranes. The fourth crane was a vaccinated unchallenged control that had none of the lesions described. We concluded, based on the findings of no adverse reactions and the higher titers and reduced viremia seen in the cranes, that, indeed, the vaccine is safe for use in cranes and can be effective in reducing the severity of a natural infection. We would recommend this vaccine for use in adult cranes. A companion study is looking at the safety and efficacy of the vaccine for crane chicks as young as 7-10 days of age and that will be reported at a later date.

Biphasic and bilateral changes in striatal VGLUT1 and 2 protein expression in hemi-Parkinson rats.

PubMed

Massie, Ann; Schallier, Anneleen; Vermoesen, Katia; Arckens, Lutgarde; Michotte, Yvette

2010-09-01

Parkinson's disease is characterized by disturbed glutamatergic neurotransmission in the striatum. Important mediators of extracellular glutamate levels are the vesicular glutamate transporters VGLUT1 and VGLUT2 in respectively corticostriatal and thalamostriatal afferents, next to the high-affinity Na(+)/K(+)-dependent glutamate transporters and the cystine/glutamate antiporter. In the present study, we compared bilateral striatal VGLUT1 and VGLUT2 protein expression as well as VGLUT1 and VGLUT2 transcript levels in the neocortex and parafascicular nucleus of hemi-Parkinson rats at different time intervals post unilateral 6-OHDA injection into the medial forebrain bundle versus controls. Three weeks post-injection we detected increased striatal VGLUT1 expression together with decreased VGLUT2 expression. On the other hand, after twelve weeks, the expression of VGLUT1 was decreased in hemi-Parkinson rats whereas the striatal expression of VGLUT2 was comparable to control rats. No effect could be seen on VGLUT transcript levels in the respective projection areas at any time. In conclusion, we observed a biphasic and bilateral change in the protein expression levels of both VGLUTs in the striatum of hemi-Parkinson rats indicative for a different and time-dependent change in glutamatergic neurotransmission from the two types of striatal afferents. Copyright 2010 Elsevier Ltd. All rights reserved.

Evaluation of intra-articular injection of autologous platelet lysate (PL) in horses with osteoarthritis of the distal interphalangeal joint.

PubMed

Tyrnenopoulou, Panagiota; Diakakis, Nikolaos; Karayannopoulou, Maria; Savvas, Ioannis; Koliakos, Georgios

2016-06-01

Regenerative medicine has become one of the most promising therapies of equine osteoarthritis. Platelet lysate (PL) is rich in bioactive proteins and growth factors that play a crucial role in tissue healing. To evaluate the efficacy of intra-articularly injected autologous PL in equine athletes with naturally occurring osteoarthritis. Fifteen warmblood geldings aged 8-19 years with osteoarthritis of the distal interphalangeal joint were included in this study. They were randomly divided into two groups; 10 horses received intra-articular injections of PL and 5 of normal saline (controls). Before treatment, platelet-derived growth factor (PDGF) levels in basal plasma and prepared PL were estimated. Each joint was injected twice within a three-week period. Lameness was evaluated using the American Association of Equine Practitioners grading system, before treatment and 10 days after each intra-articular injection. Horses were examined fortnightly for one year. Radiographic examination was performed six months post-treatment. The generalized estimating equation test was used for statistical analysis. Acceptable levels of PDGF were detected in PLs (mean ± SD: 258.0 ± 52.3 pg/ml). The majority of horses (9/10) responded positively to PL treatment presenting lower lameness grades (p < 0.0005) compared to controls 10 days after the second injection, and returned to normal athletic activity. Radiographs revealed no changes in osteoarthritis lesions six months after treatment. One year post-injections, however, all horses relapsed to their initial degree of lameness. Intra-articularly injected autologous PL is an efficient method for temporarily managing osteoarthritis of the distal interphalangeal joint in athletic horses.

Effects of adjuvants for human use in systemic lupus erythematosus (SLE)-prone (New Zealand black/New Zealand white) F1 mice.

PubMed

Favoino, E; Favia, E I; Digiglio, L; Racanelli, V; Shoenfeld, Y; Perosa, F

2014-01-01

The safety of four different adjuvants was assessed in lupus-prone New Zealand black/New Zealand white (BW)F1 mice. Four groups of mice were injected intraperitoneally with incomplete Freund's adjuvant (IFA), complete Freund's adjuvant (CFA), squalene (SQU) or aluminium hydroxide (ALU). An additional group received plain phosphate-buffered saline (PBS) (UNT group). Mice were primed at week 9 and boosted every other week up to week 15. Proteinuria became detectable at weeks 17 (IFA group), 24 (CFA group), 28 (SQU and ALU groups) and 32 (UNT group). Different mean values were obtained among the groups from weeks 17 to 21 [week 17: one-way analysis of variance (anova) P = 0·016; weeks 18 and 19: P = 0·048; weeks 20 and 21: P = 0·013] being higher in the IFA group than the others [Tukey's honestly significant difference (HSD) post-test P < 0·05]. No differences in anti-DNA antibody levels were observed among groups. Anti-RNP/Sm antibody developed at week 19 in only one CFA-treated mouse. Mean mouse weight at week 18 was lower in the ALU group than the IFA (Tukey's HSD post-test P = 0·04), CFA (P = 0·01) and SQU (P < 0·0001) groups, while the mean weight in the SQU group was higher than in the IFA (P = 0·009), CFA (P = 0·013) and UNT (P = 0·005) groups. The ALU group weight decreased by almost half between weeks 29 and 31, indicating some toxic effect of ALU in the late post-immunization period. Thus, SQU was the least toxic adjuvant as it did not (i) accelerate proteinuria onset compared to IFA; (ii) induce toxicity compared to ALU or (iii) elicit anti-RNP/Sm autoantibody, as occurred in the CFA group. © 2013 British Society for Immunology.

Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34).

PubMed

Ren, Yongxin; Liu, Bo; Feng, Yuxu; Shu, Lei; Cao, Xiaojian; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

2011-01-01

Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH. Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/-)) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/-) mice compared to vehicle-treated wild-type and Pth(-/-) mice. Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.

Patient compliance with extended low molecular weight heparin injections following hip and knee arthroplasty.

PubMed

Deakin, Dan E; Mishreki, Andrew; Aslam, Nadim; Docker, Charles

2010-01-01

The use of extended duration thromboprophylaxis following hip and knee arthroplasty is becoming widespread. The aim of our study was to determine patient compliance with extended duration thromboprophylaxis using low molecular weight (LMWH) injections following hip and knee arthroplasty. 42 consecutive patients undergoing hip and knee arthroplasty were prospectively contacted during their fifth post operative week. A fully anonymised questionnaire was completed by each patient. All patients responded. One was excluded having been prescribed warfarin for pre existing atrial fibrillation. Twenty nine (71%) patients were discharged with the intention of self administering LMWH injections. Eight (20%) and four (9%) patients were discharged with the intention of administration by a relative or district nurse respectively. No patient required the person administering the injections to be changed after discharge from hospital. 90% (n=37) of patients reported not missing any doses. 10% (n=2) of patients missed one dose and 10% (n=2) missed two doses. Patient compliance with extended duration thromboprophylaxis using LMWH injections is extremely high. Oral thromboprophylaxis may be useful in the minority of patients requiring daily visits by a nurse to administer injections.

Intramyocardial injection of autologous cardiospheres or cardiosphere-derived cells preserves function and minimizes adverse ventricular remodeling in pigs with heart failure post-myocardial infarction.

PubMed

Lee, Shuo-Tsan; White, Anthony J; Matsushita, Satoshi; Malliaras, Konstantinos; Steenbergen, Charles; Zhang, Yiqiang; Li, Tao-Sheng; Terrovitis, John; Yee, Kristine; Simsir, Sinan; Makkar, Raj; Marbán, Eduardo

2011-01-25

The purpose of this study was to test the safety and efficacy of direct injection of cardiosphere-derived cells (CDCs) and their 3-dimensional precursors, cardiospheres, for cellular cardiomyoplasty in a mini-pig model of heart failure after myocardial infarction. Intracoronary administration of CDCs has been demonstrated to reduce infarct size and improve hemodynamic indexes in the mini-pig model, but intramyocardial injection of CDCs or cardiospheres has not been assessed in large animals. Autologous cardiospheres or CDCs grown from endomyocardial biopsies were injected through thoracotomy 4 weeks after anteroseptal myocardial infarction. Engraftment optimization with luciferase-labeled CDCs guided the choice of cell dose (0.5 million cells/site) and target tissue (20 peri-infarct sites). Pigs were randomly allocated to placebo (n = 11), cardiospheres (n = 8), or CDCs (n = 10). Functional data were acquired before injection and again 8 weeks later, after which organs were harvested for histopathology. Beyond the immediate perioperative period, all animals survived to protocol completion. Ejection fraction was equivalent at baseline, but at 8 weeks was higher than placebo in both of the cell-treated groups (placebo vs. CDC, p = 0.01; placebo vs. cardiospheres, p = 0.01). Echocardiographic and hemodynamic indexes of efficacy improved disproportionately with cardiospheres; likewise, adverse remodeling was more attenuated with cardiospheres than with CDCs. Provocative electrophysiologic testing showed no differences among groups, and no tumors were found. Dosage-optimized direct injection of cardiospheres or CDCs is safe and effective in preserving ventricular function in porcine ischemic cardiomyopathy. Although CDCs and cardiospheres have equivalent effects on left ventricular ejection fraction, cardiospheres are superior in improving hemodynamics and regional function, and in attenuating ventricular remodeling. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

GRIN: "GRoup versus INdividual physiotherapy following lower limb intra-muscular Botulinum Toxin-A injections for ambulant children with cerebral palsy: an assessor-masked randomised comparison trial": study protocol.

PubMed

Thomas, Rachel E; Johnston, Leanne M; Boyd, Roslyn N; Sakzewski, Leanne; Kentish, Megan J

2014-02-07

Cerebral palsy is the most common cause of physical disability in childhood. Spasticity is a significant contributor to the secondary impairments impacting functional performance and participation. The most common lower limb spasticity management is focal intramuscular injections of Botulinum Toxin-Type A accompanied by individually-delivered (one on one) physiotherapy rehabilitation. With increasing emphasis on improving goal-directed functional activity and participation within a family-centred framework, it is timely to explore whether physiotherapy provided in a group could achieve comparable outcomes, encouraging providers to offer flexible models of physiotherapy delivery. This study aims to compare individual to group-based physiotherapy following intramuscular Botulinum Toxin-A injections to the lower limbs for ambulant children with cerebral palsy aged four to fourteen years. An assessor-masked, block randomised comparison trial will be conducted with random allocation to either group-based or individual physiotherapy. A sample size of 30 (15 in each study arm) will be recruited. Both groups will receive six hours of direct therapy following Botulinum Toxin-A injections in either an individual or group format with additional home programme activities (three exercises to be performed three times a week). Study groups will be compared at baseline (T1), then at 10 weeks (T2, efficacy) and 26 weeks (T3, retention) post Botulinum Toxin-A injections. Primary outcomes will be caregiver/s perception of and satisfaction with their child's occupational performance goals (Canadian Occupational Performance Measure) and quality of gait (Edinburgh Visual Gait Score) with a range of secondary outcomes across domains of the International Classification of Disability, Functioning and Health. This paper outlines the study protocol including theoretical basis, study hypotheses and outcome measures for this assessor-masked, randomised comparison trial comparing group versus individual models of physiotherapy following intramuscular injections of Botulinum Toxin-A to the lower limbs for ambulant children with cerebral palsy. ACTRN12611000454976.

Community reentry challenges after release from prison among people who inject drugs in St. Petersburg, Russia

PubMed Central

Cepeda, Javier A.; Vetrova, Marina V.; Lyubimova, Alexandra I.; Levina, Olga S.; Heimer, Robert; Niccolai, Linda M.

2016-01-01

Purpose Little is known about the context of the post-release risk environment among formerly incarcerated people who inject drugs (PWID) in Russia. The purpose of this paper is to explore these challenges as they relate to reentry, relapse to injection opioid use, and overdose. Design/methodology/approach The authors conducted 25 in-depth semi-structured interviews among PWID living in St Petersburg, Russia who had been incarcerated within the past two years. Participants were recruited from street outreach (n = 20) and a drug treatment center (n = 5). Findings Emergent themes related to the post-release environment included financial instability, negative interactions with police, return to a drug using community, and reuniting with drug using peers. Many respondents relapsed to opioid use immediately after release. Those whose relapse occurred weeks or months after their release expressed more motivation to resist. Alcohol or stimulant use often preceded the opioid relapse episode. Among those who overdosed, alcohol use was often reported prior to overdosing on opioids. Practical implications Future post-release interventions in Russia should effectively link PWID to social, medical, and harm reduction services. Particular attention should be focussed on helping former inmates find employment and overdose prevention training prior to leaving prison that should also cover the heightened risk of concomitant alcohol use. Originality/value In addition to describing a syndemic involving the intersection of incarceration, injection drug use, poverty, and alcohol abuse, the findings can inform future interventions to address these interrelated public health challenges within the Russian setting. PMID:26277925

Utility of circulating serum miRNAs as biomarkers of early cartilage degeneration in animal models of post-traumatic osteoarthritis and inflammatory arthritis.

PubMed

Kung, L H W; Zaki, S; Ravi, V; Rowley, L; Smith, M M; Bell, K M; Bateman, J F; Little, C B

2017-03-01

The purpose of this study was to determine if serum microRNA (miRNA) signatures were biomarkers of early cartilage degeneration in preclinical mouse models of post-traumatic osteoarthritis (OA) and inflammatory arthritis. Cartilage degeneration was induced in 10-12 week old male C57BL6 mice by destabilization of the medial meniscus (DMM) or intra-articular injection of methylated-bovine-serum-albumin (AIA), with sham-operated or saline-injected control animals (n = 6/treatment/time). Total serum RNA and knee joints were isolated at 1, 4 and 16 weeks post-induction. Cartilage degeneration was scored histologically. Serum miRNA expression profiling was performed using Agilent microarrays and validated by qPCR. DMM-operated and AIA mice had characteristic cartilage degeneration (proteoglycan loss, chondrocyte hypertrophy, structural damage), that increased significantly with time compared with controls, and with distinct temporal differences between arthritis models. However, expression profiling revealed no statistically significant dysregulation of serum miRNAs between AIA vs saline-injected or DMM vs sham-operated control mice at the critical early disease stages. The inability to detect DMM or AIA serum miRNA signatures compared with controls was not due to the insensitivity of the expression profiling approach since significant changes were observed in miRNA expression between the arthritis models and between time points. While distinct patterns of progressive cartilage degradation were induced in the arthritis models, we were unable to identify any serum miRNAs that were significantly dysregulated in early stages of disease compared with controls. This suggests circulating serum miRNAs may not be useful as cartilage biomarkers in distinguishing the early or progressive stages of arthritis cartilage degeneration. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Cyclooxygenase system contributes to the maintenance of post convulsive period of epileptic phenomena in the genetically epileptic El mice.

PubMed

Okada, Kazumasa; Yamashita, Uki; Tsuji, Sadatoshi

2006-09-01

Recent studies have shown that cytokines and cyclooxygenase (COX)-2 are up-regulated in the brain of human epilepsy patients and animal models of epilepsy. We investigated the effect of inflammatory responses induced by intramuscular injection of turpentine on the epileptic phenomenon in genetically epileptic El mice. As parameters of epileptic seizure, seizure threshold (number of toss-ups to induce convulsion), duration of actual convulsion and duration of post actual convulsive period (period from the offset of convulsion to full recovery) were evaluated. The post actual convulsive period was prolonged without any change of seizure threshold or duration of actual convulsion 24 h after turpentine injection. Although pretreatment with indomethacin for one week did not change the seizure parameters, indomethacin suppressed the prolongation of the post actual convulsive period induced by turpentine. The mRNA expression of IL-1beta, IL-6 and COX-2 in the cerebral cortex was detected by RT-PCR. There was no difference in the mRNA expression in the cerebral cortex before and 24 h after seizure. The mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex were up-regulated 24 h after turpentine injection. On the other hand, the up-regulated mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex after turpentine treatment were not suppressed by indomethacin. These results suggest that prostaglandins induced with COX-2 in the cerebral cortex seem to play an important role in the maintenance of the post convulsive period, but not in induction and maintenance of the actual convulsive state.

Evaluation of traditional plant extracts for innate immune mechanisms and disease resistance against fish bacterial Aeromonas hydrophila and Pseudomonas sp.

NASA Astrophysics Data System (ADS)

Hardi, E. H.; Saptiani, G.; Kusuma, I. W.; Suwinarti, W.; Nugroho, R. A.

2018-03-01

The purposes of this study were to evaluate effect of ethanol herbal extracts of Boesenbergia pandurata, Solanum ferox and Zingimber zerumbet on Tilapia (Oreochromis nilaticus) innate immune mechanisms and disease resistance against Aeromonas hydrophila and Pseudomonas sp. Fish were intramuscularly injected with 0.1 mL/fish (1010 CFU mL-1) of each bacterium on the day 6th of post treatment using extract by several methods (injection, oral administration and immersion). The doses of extract were 600 ppm of B. pandurata, 900 ppm S. ferox and 200 ppm of Z. zerumbet. The percentage mortality, Relative Percent Survival (RPS) and innate immune response were assessed on weeks 1, 2, 3 and 4. All the methods were effective to enhance the immune parameters after 2 weeks application and the RPS of treatment reached more than 90 %. The results showed that the injection method of extracts was the most effective method to control A. hydrophila and Pseudomonas sp. The result indicated that all the doses of extracts could be significantly influence the immune response and protect the health status of tilapia against A. hydrophila and Pseudomonas sp. infections.

Optical coherence tomography and computer-aided diagnosis of a murine model of chronic kidney disease

NASA Astrophysics Data System (ADS)

Wang, Bohan; Wang, Hsing-Wen; Guo, Hengchang; Anderson, Erik; Tang, Qinggong; Wu, Tongtong; Falola, Reuben; Smith, Tikina; Andrews, Peter M.; Chen, Yu

2017-12-01

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function over time. Histopathological analysis of the condition of glomeruli and the proximal convolutional tubules over time can provide valuable insights into the progression of CKD. Optical coherence tomography (OCT) is a technology that can analyze the microscopic structures of a kidney in a nondestructive manner. Recently, we have shown that OCT can provide real-time imaging of kidney microstructures in vivo without administering exogenous contrast agents. A murine model of CKD induced by intravenous Adriamycin (ADR) injection is evaluated by OCT. OCT images of the rat kidneys have been captured every week up to eight weeks. Tubular diameter and hypertrophic tubule population of the kidneys at multiple time points after ADR injection have been evaluated through a fully automated computer-vision system. Results revealed that mean tubular diameter and hypertrophic tubule population increase with time in post-ADR injection period. The results suggest that OCT images of the kidney contain abundant information about kidney histopathology. Fully automated computer-aided diagnosis based on OCT has the potential for clinical evaluation of CKD conditions.

Open-label study evaluating outpatient urethral sphincter injections of onabotulinumtoxinA to treat women with urinary retention due to a primary disorder of sphincter relaxation (Fowler's syndrome).

PubMed

Panicker, Jalesh N; Seth, Jai H; Khan, Shahid; Gonzales, Gwen; Haslam, Collette; Kessler, Thomas M; Fowler, Clare J

2016-05-01

To assess the efficacy (defined as improvements in maximum urinary flow rate [Qmax ] of ≥50%, post-void residual urine volume [PVR] and scores on the International Prostate Symptom Score [IPSS] questionnaire) and safety of urethral sphincter injections of onabotulinumtoxinA in women with a primary disorder of urethral sphincter relaxation, characterised by an elevated urethral pressure profile (UPP) and specific findings at urethral sphincter electromyography (EMG), i.e. Fowler's syndrome. In this open-label pilot Institutional Review Board-approved study, 10 women with a primary disorder of urethral sphincter relaxation (elevated UPP, sphincter volume, and abnormal EMG) presenting with obstructed voiding (five) or in complete urinary retention (five) were recruited from a single tertiary referral centre. Baseline symptoms were assessed using the IPSS, and Qmax and PVR were measured. After 2% lidocaine injection, 100 U of onabotulinumtoxinA was injected into the striated urethral sphincter, divided on either side, under EMG guidance. Patients were reviewed at 1, 4 and 10 weeks after injection, and assessed using the IPSS, Qmax and PVR measurements. The UPP was repeated at week 4. The mean (range) patient age was 40 (25-65) years, and the mean symptom scores on the IPSS improved from 25.6 to 14.1, and the mean 'bother' score reduced from 6.1 to 3.5 at week 10. As compared with a baseline mean Qmax of 8.12 mL/s in the women who could void, the Qmax improved to 15.8 mL/s at week 10. Four of the five women in complete retention could void spontaneously, with a mean Qmax of 14.3 mL/s at week 10. The mean PVR decreased from 260 to 89 mL and the mean static UPP improved from 113 cmH2 O at baseline to 90 cmH2 O. No serious side-effects were reported. Three women with a history of recurrent urinary tract infections developed a urinary tract infection. There were no reports of stress urinary incontinence. Seven of the 10 women opted to return for repeat injections. This pilot study shows an improvement in patient-reported lower urinary tract symptoms, and the objective parameters of Qmax , PVR and UPP, at 10 weeks after urethral sphincter injections of onabotulinumtoxinA. No serious side-effects were reported. This treatment could represent a safe outpatient treatment for young women in retention due to a primary disorder of urethral sphincter relaxation. However, a larger study is required to confirm the findings of this pilot study. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Bone marrow mesenchymal stem cells do not enhance intra-synovial tendon healing despite engraftment and homing to niches within the synovium.

PubMed

Khan, Mohammad R; Dudhia, Jayesh; David, Frederic H; De Godoy, Roberta; Mehra, Vedika; Hughes, Gillian; Dakin, Stephanie G; Carr, Andrew J; Goodship, Allen E; Smith, Roger K W

2018-06-19

Intra-synovial tendon injuries display poor healing, which often results in reduced functionality and pain. A lack of effective therapeutic options has led to experimental approaches to augment natural tendon repair with autologous mesenchymal stem cells (MSCs) although the effects of the intra-synovial environment on the distribution, engraftment and functionality of implanted MSCs is not known. This study utilised a novel sheep model which, although in an anatomically different location, more accurately mimics the mechanical and synovial environment of the human rotator cuff, to determine the effects of intra-synovial implantation of MSCs. A lesion was made in the lateral border of the lateral branch of the ovine deep digital flexor tendon within the digital sheath and 2 weeks later 5 million autologous bone marrow MSCs were injected under ultrasound guidance into the digital sheath. Tendons were recovered post mortem at 1 day, and 1-2, 4, 12 and 24 weeks after MSC injection. For the 1-day and 1-2-week groups, MSCs labelled with fluorescent-conjugated magnetic iron-oxide nanoparticles (MIONs) were tracked with MRI, histology and flow cytometry. The 4, 12 and 24-week groups were implanted with non-labelled cells and compared with saline-injected controls for healing. The MSCs displayed no reduced viability in vitro to an uptake of 20.0 ± 4.6 pg MIONs per cell, which was detectable by MRI at minimal density of ~ 3 × 10 4 cells. Treated limbs indicated cellular distribution throughout the tendon synovial sheath but restricted to the synovial tissues, with no MSCs detected in the tendon or surgical lesion. The lesion was associated with negligible morbidity with minimal inflammation post surgery. Evaluation of both treated and control lesions showed no evidence of healing of the lesion at 4, 12 and 24 weeks on gross and histological examination. Unlike other laboratory animal models of tendon injury, this novel model mimics the failed tendon healing seen clinically intra-synovially. Importantly, however, implanted stem cells exhibited homing to synovium niches where they survived for at least 14 days. This phenomenon could be utilised in the development of novel physical or biological approaches to enhance localisation of cells in augmenting intra-synovial tendon repair.

Nandrolone decanoate increases satellite cell numbers in the chicken pectoralis muscle.

PubMed

Allouh, Mohammed Z; Rosser, Benjamin W C

2010-02-01

The anabolic androgenic steroid nandrolone decanoate has minimal androgenic effects and, thus, is widely used to induce muscle hypertrophy in both patients and athletes. Although increases in satellite cell numbers and satellite cells giving rise to new myonuclei are associated with hypertrophy in many experimental models, the relationship between nandrolone and satellite cells is poorly understood. Here we test the hypothesis that nandrolone administration is associated with an increase in satellite cell numbers in muscle. Nandrolone was injected at weekly intervals for four weeks into the right pectoralis muscle of female white leghorn chickens aged 63 days post hatch. Age/size/sex matched control birds received saline injections. The contralateral pectoralis was excised for study from each control and nandrolone treated bird. An antibody against Pax7 and immunocytochemical techniques were used to identify satellite cells. Nandrolone significantly increased mean pectoralis mass by approximately 22%, and mean fiber diameter by about 24%. All satellite cell indices that were quantified increased significantly in chicken pectoralis with administration of nandrolone. Nandrolone injected birds had on average higher satellite cell frequencies (#SC nuclei/all nuclei within basal lamina), number of satellite cells per millimeter of fiber, and satellite cell concentrations (closer together). Myonuclei were further apart (less concentrated) in nandrolone injected muscle. However, an overall increase in myonuclear numbers was revealed by a significantly greater mean number of myonuclei per millimeter of fiber in nandrolone injected muscle. Our results suggest that satellite cells may be key cellular vectors for nandrolone induced muscle fiber hypertrophy.

Long term effects of lipopolysaccharide on satellite glial cells in mouse dorsal root ganglia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blum, E.; Procacci, P.; Conte, V.

Lipopolysaccharide (LPS) has been used extensively to study neuroinflammation, but usually its effects were examined acutely (24 h<). We have shown previously that a single intraperitoneal LPS injection activated satellite glial cells (SGCs) in mouse dorsal root ganglia (DRG) and altered several functional parameters in these cells for at least one week. Here we asked whether the LPS effects would persist for 1 month. We injected mice with a single LPS dose and tested pain behavior, assessed SGCs activation in DRG using glial fibrillary acidic protein (GFAP) immunostaining, and injected a fluorescent dye intracellularly to study intercellular coupling. Electron microscopymore » was used to quantitate changes in gap junctions. We found that at 30 days post-LPS the threshold to mechanical stimulation was lower than in controls. GFAP expression, as well as the magnitude of dye coupling among SGCs were greater than in controls. Electron microscopy analysis supported these results, showing a greater number of gap junctions and an abnormal growth of SGC processes. These changes were significant, but less prominent than at 7 days post-LPS. We conclude that a single LPS injection exerts long-term behavioral and cellular changes. The results are consistent with the idea that SGC activation contributes to hyperalgesia. - Highlights: • A single lipopolysaccharides injection activated glia in mouse dorsal root ganglia for 30 days. • This was accompanied by increased communications by gap junctions among glia and by hyperalgesia. • Glial activation and coupling may contribute to chronic pain.« less

Intramuscular glucocorticoid injection versus placebo injection in hip osteoarthritis: a 12-week blinded randomised controlled trial.

PubMed

Dorleijn, Desirée M J; Luijsterburg, Pim A J; Reijman, Max; Kloppenburg, Margreet; Verhaar, Jan A N; Bindels, Patrick J E; Bos, Pieter Koen; Bierma-Zeinstra, Sita M A

2018-06-01

Guidelines recommend intra-articular glucocorticoid injection in patients with painful hip osteoarthritis. However, intra-articular hip injection is an invasive procedure. The efficacy of systemic glucocorticoid treatment for pain reduction in hip osteoarthritis is unknown. This randomised, double-blind, trial assessed effectiveness in hip pain reduction of an intramuscular glucocorticoid injection compared with a placebo injection in patients with hip osteoarthritis. Patients with painful hip osteoarthritis were randomised to either 40 mg triamcinolone acetate or placebo with an intramuscular injection into the gluteus muscle. The primary outcomes were severity of hip pain at rest, during walking (0-10) and WOMAC pain at 2-week postinjection. We used linear mixed models for repeated measurements at 2, 4, 6 and 12 weeks for the intention-to-treat data analysis. Of the 107 patients randomised, 106 could be analysed (52 in the glucocorticoid group, 54 in the placebo group). At 2-week follow-up, compared with placebo injection, the intramuscular glucocorticoid injection showed a significant and clinically relevant difference in hip pain reduction at rest (difference -1.3, 95% CI -2.3 to -0.3). This effect persisted for the entire 12-week follow-up. For hip pain during walking, the effect was present at 4-week, 6-week and 12-week follow-ups, and for WOMAC pain the effect was present at 6-week and 12-week follow-up. An intramuscular glucocorticoid injection showed effectiveness in patients with hip osteoarthritis on one of the three primary outcomes at 2-week postinjection. All primary outcomes showed effectiveness from 4 to 6 weeks, up to a 12-week follow-up. NTR2966. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice

PubMed Central

Danilov, Camelia A.; Steward, Oswald

2015-01-01

Previous studies indicate that conditional genetic deletion of phosphatase and tensin homolog (PTEN) in neonatal mice enhances the ability of axons to regenerate following spinal cord injury (SCI) in adults. Here, we assessed whether deleting PTEN in adult neurons post-SCI is also effective, and whether enhanced regenerative growth is accompanied by enhanced recovery of voluntary motor function. PTENloxP/loxP mice received moderate contusion injuries at cervical level 5 (C5). One group received unilateral injections of adeno-associated virus expressing CRE (AAV-CRE) into the sensorimotor cortex; controls received a vector expressing green fluorescent protein (AAV-GFP) or injuries only (no vector injections). Forelimb function was tested for 14 weeks post-SCI using a grip strength meter (GSM) and a hanging task. The corticospinal tract (CST) was traced by injecting mini-ruby BDA into the sensorimotor cortex. Forelimb gripping ability was severely impaired immediately post-SCI but recovered slowly over time. The extent of recovery was significantly greater in PTEN-deleted mice in comparison to either the AAV-GFP group or the injury only group. BDA tract tracing revealed significantly higher numbers of BDA-labeled axons in caudal segments in the PTEN-deleted group compared to control groups. In addition, in the PTEN-deleted group, there were exuberant collaterals extending from the main tract rostral to the lesion, into and around the scar tissue at the injury site. These results indicate that PTEN deletion in adult mice shortly post-SCI can enhance regenerative growth of CST axons and forelimb motor function recovery. PMID:25704959

CANDIDA ENDOPHTHALMITIS FROM THE REACTIVATION OF A DORMANT LENTICULAR FUNGAL ABSCESS IN A PREMATURE INFANT.

PubMed

Yanoga, Fatoumata; Garcia-Gonzalez, Jose M; Greenwald, Mark; Shapiro, Michael J; Blair, Michael P

2017-01-01

To report a case of fungal endophthalmitis from reactivation of a dormant lenticular fungal abscess in a severely premature infant. Single retrospective case report. A female born at 23 and 6/7 weeks and weighing 620 g was diagnosed at age 29 weeks post menstrual age with persistent tunica vasculosa lentis, lenticular opacity, and aggressive posterior retinopathy of prematurity, and received bilateral intravitreal injection of bevacizumab. At the time of injection she was receiving systemic antibiotics for sepsis and fungemia. The retinopathy of prematurity regressed, as did the tunica vasculosa lentis, but a small plaque remained on the lens. At 5.5 months of age, patient presented with hypopyon and elevated intraocular pressure. Culture of intraocular fluid demonstrated Candida albicans. Candida lenticular abscess is a rare complication of systemic fungemia in premature infants. Bevacizumab-induced regression of tunica vasculosa lentis may have decreased the ability of systemically administered antifungal medications to reach the colonized lens.

Effects of Particle Size and Porosity on In Vivo Remodeling of Settable Allograft Bone/Polymer Composites

PubMed Central

Prieto, Edna M.; Talley, Anne D.; Gould, Nicholas R.; Zienkiewicz, Katarzyna J.; Drapeau, Susan J.; Kalpakci, Kerem N.

2014-01-01

Established clinical approaches to treat bone voids include the implantation of autograft or allograft bone, ceramics, and other bone void fillers (BVFs). Composites prepared from lysine-derived polyurethanes and allograft bone can be injected as a reactive liquid and set to yield BVFs with mechanical strength comparable to trabecular bone. In this study, we investigated the effects of porosity, allograft particle size, and matrix mineralization on remodeling of injectable and settable allograft/polymer composites in a rabbit femoral condyle plug defect model. Both low viscosity (LV) and high viscosity (HV) grafts incorporating small (<105 μm) particles only partially healed at 12 weeks, and the addition of 10% demineralized bone matrix did not enhance healing. In contrast, composite grafts with large (105 – 500 μm) allograft particles healed at 12 weeks post-implantation, as evidenced by radial μCT and histomorphometric analysis. This study highlights particle size and surface connectivity as influential parameters regulating the remodeling of composite bone scaffolds. PMID:25581686

Induction of monooxygenation in rainbow trout by polybrominated biphenyls: a comparative study.

PubMed Central

Elcombe, C R; Lech, J J

1978-01-01

Two commercial polychlorinated biphenyl mixtures (Aroclor 1254 and Aroclor 1242) and one polybrominated biphenyl mixture (FireMaster BP-6) were examined for their abilities to induce hepatic microsomal monooxygenation in rainbow trout (Salmo gairdneri). Pretreatment of rainbow trout with Aroclors 1254 and 1242 (150 mg/kg IP) resulted in an approximate 10-fold induction of arylhydrocarbon (benzo[a]pyrene) hydroxylation, ethoxycoumarin-O-deethylation and ethoxyresorufin-O-deethylation within 7 days after injection. These enzyme activities remained elevated above control values for at least 2-3 weeks. Administration of FireMaster BP-6 (150 mg/kg IP) also resulted in an induction of several monooxygenase activities. Arylhydrocarbon (benzo[a]pyrene) hydroxylation, ethoxycoumarin-O-deethylation and ethoxyresorufin-O-deethylation were increased by 6-, 3,- and 25-fold, respectively. Only the latter two activities remained elevated two weeks post-injection. Ethylmorphine-N-demethylation was unaffected by the polyhalogenated biphenyls. Significant increases in P-450 hemoprotein were not observed after pretreatment with any of the polyhalogenated biphenyls studied. PMID:209992

Molecular biology of Group A Streptococcus and its implications in vaccine strategies.

PubMed

Brahmadathan, N K

2017-01-01

Infections due to Streptococcus pyogenes and their complications are a problem of major concern in many countries, including India. Primary prophylaxis with benzathine penicillin is the key to control and prevent sequelae such as acute rheumatic fever and rheumatic heart disease (RF/RHD) or post-streptococcal glomerulonephritis (PSGN). Non-compliance to prophylaxis due to fear of injection and anaphylaxis is major issues in RF/RHD control in India and leads to continued high prevalence of infection and post-streptococcal sequelae. Differing reports on the efficacy of two weekly, three weekly or monthly injections raise questions on the actual dosages to be administered. Availability of more effective antibiotics with better dosages has replaced the use of penicillin; hence, companies are reluctant to manufacture penicillin preparations in India. It is in this context that a concept of a Group A streptococci vaccine is looked at and whether or not a globally designed vaccine will be useful in the Indian context. Modern molecular techniques and genomic analysis of S. pyogenes have identified many molecules as vaccine candidates among which the M-protein has attracted the most attention. High diversity of M (emm) types in endemic regions raises questions about the efficacy of such a vaccine. A recent 30-valent M-protein-based vaccine that elicits antibodies to homologous as well as non-vaccine M types looks promising. This review will discuss the genomics of S. pyogenes, the various candidate vaccine molecules and highlight their efficacy in the Indian context where control of post-streptococcal sequelae remains a challenge.

Schistosoma mansoni: radiation dose and morphologic integrity of schistosomules as factors for an effective cryopreserved live vaccine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, F.A.; Stirewalt, M.; Leef, J.L.

1984-01-01

The effectiveness of a cryopreserved, irradiated schistosomule vaccine against an homologous Schistosoma mansoni cercarial challenge was tested in C57B1/6 mice. Highly significant levels of protection developed consistently when mice were immunized with the vaccine irradiated at 10-20 Krad, i.e., doses below that considered optimal for irradiated cercariae (50 Krad). Cryopreserved schistosomules irradiated at 10 or 20 Krad induced greater levels of protection than did schistosomules irradiated at 2, 5, 30, or 50 Krad. Protective immunity developed as early as 3 weeks post-immunization. When immunizing inocula were injected at various times post-thaw, or when schistosomule subpopulations of normal-appearing, damaged or deadmore » organisms were injected, those populations which had appeared to sustain the least degree of damage were those most capable of stimulating protective immunity. These findings highlight the hazards of extrapolating conditions considered standard for an irradiated cercarial vaccine to one in which cryopreservation, for storage of the schistosomules, is an added stress.« less

Safety and efficacy of bi-annual intra-articular LBSA0103 injections in patients with knee osteoarthritis.

PubMed

Lee, Jin Kyu; Choi, Chong-Hyuk; Oh, Kwang-Jun; Kyung, Hee-Soo; Yoo, Ju-Hyung; Ha, Chul-Won; Bin, Seong-Il; Kang, Seung-Baik; Kim, Myung Ku; Lee, Ju-Hong; Lee, Myung Chul

2017-11-01

The objective of this study is to assess the safety and efficacy of repeated intra-articular injection of high molecular weight hyaluronic acid (LBSA0103) at a 26-week interval, in patients with osteoarthritis of the knee. The study was an open-label, single arm, multicentre prospective trial conducted in patients with symptomatic knee osteoarthritis. The intervention consisted of two intra-articular injections of LBSA0103, with the second injection performed 26 weeks after the first injection. The primary outcome was the incidence of adverse drug reactions related to each injection. Assessment of efficacy of repeated injections in terms of maintenance of pain relief was a secondary objective of this study. Of the 185 patients screened, 174 patients received the first injection and 153 patients received both injections of LBSA0103. Nine adverse drug reactions occurred in seven patients (4.02%) after the first injection, while only one adverse drug reaction occurred (0.65%) after the second injection. As a secondary outcome measure, the improvements in the efficacy parameters including total WOMAC score and weight-bearing pain were all significant at both week 13 and 39 compared to the baseline value (P < 0.001), and improvements after the second injection were consistent with those after the initial injection of LBSA0103 (between week 26 and week 39, P < 0.001). Repeated intra-articular injection of LBSA0103 at a 26-week interval is safe without increased risk of adverse drug reactions. Additionally, LBSA0103 is effective in reduction of osteoarthritis knee pain and in maintenance of pain reduction for a 39-week period when a second injection is administered.

Increased Tumor Oxygenation and Drug Uptake During Anti-Angiogenic Weekly Low Dose Cyclophosphamide Enhances the Anti-Tumor Effect of Weekly Tirapazamine

PubMed Central

Doloff, J.C.; Khan, N.; Ma, J.; Demidenko, E.; Swartz, H.M.; Jounaidi, Y.

2010-01-01

Metronomic cyclophosphamide treatment is associated with anti-angiogenic activity and is anticipated to generate exploitable hypoxia using hypoxia-activated prodrugs. Weekly administration of tirapazamine (TPZ; 5 mg/kg body weight i.p.) failed to inhibit the growth of 9L gliosarcoma tumors grown s.c. in scid mice. However, the anti-tumor effect of weekly cyclophosphamide (CPA) treatment (140 mg/kg BW i.p.) was substantially enhanced by weekly TPZ administration. An extended tumor free period and increased frequency of tumor eradication without overt toxicity were observed when TPZ was given 3, 4 or 5 days after each weekly CPA treatment. Following the 2nd CPA injection, Electron Paramagnetic Resonance (EPR) Oximetry indicated significant increases in tumor pO2, starting at 48 hr, which further increased after the 3rd CPA injection. pO2 levels were, however, stable in growing untreated tumors. A strong negative correlation (−0.81) between tumor pO2 and tumor volume during 21 days of weekly CPA chemotherapy was observed, indicating increasing tumor pO2 with decreasing tumor volume. Furthermore, CPA treatment resulted in increased tumor uptake of activated CPA. CPA induced increases in VEGF RNA, which reached a maximum on day 1, and in PLGF RNA which was sustained throughout the treatment, while anti-angiogenic host thrombospondin-1 increased dramatically through day 7 post-CPA treatment. Weekly cyclophosphamide treatment was anticipated to generate exploitable hypoxia. However, our findings suggest that weekly CPA treatment induces a functional improvement of tumor vasculature, which is characterized by increased tumor oxygenation and drug uptake in tumors, thus counter-intuitively, benefiting intratumoral activation of TPZ and perhaps other bioreductive drugs. PMID:19754361

Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis

PubMed Central

2014-01-01

Introduction Post-traumatic arthritis (PTA) is a progressive, degenerative response to joint injury, such as articular fracture. The pro-inflammatory cytokines, interleukin 1(IL-1) and tumor necrosis factor alpha (TNF-α), are acutely elevated following joint injury and remain elevated for prolonged periods post-injury. To investigate the role of local and systemic inflammation in the development of post-traumatic arthritis, we targeted both the initial acute local inflammatory response and a prolonged 4 week systemic inflammatory response by inhibiting IL-1 or TNF-α following articular fracture in the mouse knee. Methods Anti-cytokine agents, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor II (sTNFRII), were administered either locally via an acute intra-articular injection or systemically for a prolonged 4 week period following articular fracture of the knee in C57BL/6 mice. The severity of arthritis was then assessed at 8 weeks post-injury in joint tissues via histology and micro computed tomography, and systemic and local biomarkers were assessed in serum and synovial fluid. Results Intra-articular inhibition of IL-1 significantly reduced cartilage degeneration, synovial inflammation, and did not alter bone morphology following articular fracture. However, systemic inhibition of IL-1, and local or systemic inhibition of TNF provided no benefit or conversely led to increased arthritic changes in the joint tissues. Conclusion These results show that intra-articular IL-1, rather than TNF-α, plays a critical role in the acute inflammatory phase of joint injury and can be inhibited locally to reduce post-traumatic arthritis following a closed articular fracture. Targeted local inhibition of IL-1 following joint injury may represent a novel treatment option for PTA. PMID:24964765

EFFICACY of P188 ON LAPINE MENISCUS PRESERVATION FOLLOWING BLUNT TRAUMA

PubMed Central

Coatney, Garrett A.; Abraham, Adam C.; Fischenich, Kristine M.; Button, Keith D.; Haut, Roger C.; Haut Donahue, Tammy L.

2015-01-01

Traumatic injury to the knee leads to the development of posttraumatic osteoarthritis. The objective of this study was to characterize the effects of a single intra-articular injection of a non-ionic surfactant, Poloxamer 188 (P188), in preservation of meniscal tissue following trauma through maintenance of meniscal glycosaminoglycan (GAG) content and mechanical properties. Flemish Giant rabbits were subjected to a closed knee joint, traumatic compressive impact with the joint constrained to prevent anterior tibial translation. The contralateral limb served as an un-impacted control. Six animals (treated) received an injection of P188 in phosphate buffered saline (PBS) post trauma, and another six animals (sham) received a single injection of PBS to the impacted limb. Histological analyses for GAG was determined 6 weeks post trauma, and functional outcomes were assessed using stress relaxation micro-indentation. The impacted limbs of the sham group demonstrated a significant decrease in meniscal GAG coverage compared to non-impacted limbs (p < 0.05). GAG coverage of the impacted P188 treated limbs was not significantly different than contralateral non-impacted limbs in all regions except the medial anterior (p < 0.05). No significant changes were documented in mechanics for either the sham or treated groups compared to their respective control limbs. This suggests that a single intra-articular injection of P188 shows promise in prevention of trauma induced GAG loss. PMID:25846264

Ultrasound imaging-guided intracardiac injection to develop a mouse model of breast cancer brain metastases followed by longitudinal MRI.

PubMed

Zhou, Heling; Zhao, Dawen

2014-03-06

Breast cancer brain metastasis, occurring in 30% of breast cancer patients at stage IV, is associated with high mortality. The median survival is only 6 months. It is critical to have suitable animal models to mimic the hemodynamic spread of the metastatic cells in the clinical scenario. Here, we are introducing the use of small animal ultrasound imaging to guide an accurate injection of brain tropical breast cancer cells into the left ventricle of athymic nude mice. Longitudinal MRI is used to assessing intracranial initiation and growth of brain metastases. Ultrasound-guided intracardiac injection ensures not only an accurate injection and hereby a higher successful rate but also significantly decreased mortality rate, as compared to our previous manual procedure. In vivo high resolution MRI allows the visualization of hyperintense multifocal lesions, as small as 310 µm in diameter on T2-weighted images at 3 weeks post injection. Follow-up MRI reveals intracranial tumor growth and increased number of metastases that distribute throughout the whole brain.

40 CFR 146.93 - Post-injection site care and site closure.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Post-injection site care and site... Applicable to Class VI Wells § 146.93 Post-injection site care and site closure. (a) The owner or operator of a Class VI well must prepare, maintain, and comply with a plan for post-injection site care and site...

Injectable Microsphere Gel Progressively Improves Global Ventricular Function, Regional Contractile Strain, and Mitral Regurgitation after Myocardial Infarction

PubMed Central

McGarvey, Jeremy R; Kondo, Norihiro; Witschey, Walter RT; Takebe, Manabu; Aoki, Chikashi; Burdick, Jason A.; Spinale, Francis G; Gorman, Joseph H; Pilla, James J; Gorman, Robert C

2014-01-01

Background There is continued need for therapies which reverse or abate the remodeling process following myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model. Methods Twenty five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into four groups: one week treatment, one week control, four week treatment, and four week control. Following infarction, animals received either twenty 150μl calcium hydroxyapatite gel or saline injections within the infarct. At their respective timepoints, echocardiograms, cardiac MRI, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content. Results Global and regional LV function were depressed in all infarcted subjects at one week compared to healthy controls. By four weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared to infarcted controls (EF 48.5±1.9% vs. 38.0±1.7%, p<0.01). Similarly, regional borderzone radial contractile strain (16.3±1.5% vs. 11.2±1.5%, p=0.04), MR grade (0.4±0.2 vs. 1.2±0.2, p=0.04), and infarct thickness (7.8±0.5mm vs. 4.5±0.2mm, p<0.01) were improved at this timepoint in the treatment group compared to infarct controls. Conclusions Calcium hydroxyapatite injection following MI progressively improves global LV function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is viable alternative in the current management of heart failure. PMID:25524397

Negligible Colon Cancer Risk from Food-Borne Acrylamide Exposure in Male F344 Rats and Nude (nu/nu) Mice-Bearing Human Colon Tumor Xenografts

PubMed Central

Raju, Jayadev; Roberts, Jennifer; Sondagar, Chandni; Kapal, Kamla; Aziz, Syed A.; Caldwell, Don; Mehta, Rekha

2013-01-01

Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet) reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control) or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM) or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu) mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control) or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a “complete carcinogen”, but acts as a “co-carcinogen” by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters. PMID:24040114

Protective and Anti-Pathology Effects of Sm Fructose-1,6-Bisphosphate Aldolase-Based DNA Vaccine against Schistosoma mansoni by Changing Route of Injection

PubMed Central

Saber, Mohamed; Hammam, Olft; Karim, Amr; Medhat, Amina; Khela, Mamdouh; El-Dabaa, Ehab

2013-01-01

This study aimed to evaluate the efficacy of fructose-1,6-bis phosphate aldolase (SMALDO) DNA vaccination against Schistosoma mansoni infection using different routes of injection. The SMALDO has been cloned into the eukaryotic expression vector pcDNA3.1/V5-His TOPO-TA and was used in injecting Swiss albino mice intramuscularly (IM), subcutaneously (SC), or intraperitoneally (IP) (50 µg/mouse). Mice vaccinated with non-recombinant pcDNA3.1 served as controls. Each group was immunized 4 times at weeks 0, 2, 4, and 6. Two weeks after the last booster dose, all mice groups were infected with 80 S. mansoni cercariae via tail immersion. At week 8 post-infection, animals were sacrificed for assessment of parasitological and histopathological parameters. High anti-SMALDO IgG antibody titers were detected in sera of all vaccinated groups (P<0.01) compared to the control group. Both the IP and SC vaccination routes resulted in a significant reduction in worm burden (46.2% and 28.9%, respectively, P<0.01). This was accompanied by a significant reduction in hepatic and intestinal egg counts (41.7% and 40.2%, respectively, P<0.01) in the IP group only. The number of dead eggs was significantly increased in both IP and IM groups (P<0.01). IP vaccination recorded the highest significant reduction in granuloma number and diameter (54.7% and 29.2%, respectively, P<0.01) and significant increase in dead miracidia (P<0.01). In conclusion, changing the injection route of SMALDO DNA vaccination significantly influenced the efficacy of vaccination. SMALDO DNA vaccination via IP route could be a promising protective and anti-pathology vaccine candidate against S. mansoni infection. PMID:23710082

A time-dependent degeneration manner of condyle in rat CFA-induced inflamed TMJ.

PubMed

Xu, Liqin; Guo, Huilin; Li, Cheng; Xu, Jie; Fang, Wei; Long, Xing

2016-01-01

Temporomandibular joint (TMJ) inflammation is a potential risk factor of osteoarthritis (OA) but the detailed degenerative changes in the inflamed TMJ remain unclear. In this study, we evaluated the changes of condylar cartilage and subchondral bone in rat inflamed TMJ induced by Freund's complete adjuvant (CFA). Articular cavity was injected with CFA and the TMJ samples were collected 1, 2, 3, and 4-week post-injection. Hematoxylin & Eosin (H&E) staining, toluidine blue (TB) staining, Safranin O (S.O) staining, Masson trichrome staining and micro-CT were used to assess TMJ degeneration during inflammation. Osteoclast and osteoblast activities were analyzed by tartrate-resistant acid phosphatase (TRAP) staining and osteocalcin (OCN) immunohistochemistry staining respectively. The expression of receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) in condylar cartilage and subchondral bone was also evaluated through immunohistochemistry and RANKL/OPG ratio was evaluated. Reduced cartilage thickness, decreased number of chondrocytes, and down-regulated proteoglycan expression were observed in the condylar cartilage in the inflamed TMJ. Enhanced osteoclast activity, and expanded bone marrow cavity were reached the peak in the 2-week after CFA-injection. Meanwhile the RANKL/OPG ratio in the cartilage and subchondral bone also increased in the 2-week CFA-injection. Immature, unmineralized new bones with irregular trabecular bone structure, atypical condylar shape, up-regulated OCN expression, and decreased bone mineral density (BMD) were found in the inflamed TMJ. The time-dependent degeneration manner of TMJ cartilage and subchondral bone was found in CFA-induced arthritis rat model. The degeneration in the TMJ with inflammation might be a risk factor and should be concerned.

Protective and anti-pathology effects of Sm fructose-1,6-bisphosphate aldolase-based DNA vaccine against schistosoma mansoni by changing route of injection.

PubMed

Saber, Mohamed; Diab, Tarek; Hammam, Olft; Karim, Amr; Medhat, Amina; Khela, Mamdouh; El-Dabaa, Ehab

2013-04-01

This study aimed to evaluate the efficacy of fructose-1,6-bis phosphate aldolase (SMALDO) DNA vaccination against Schistosoma mansoni infection using different routes of injection. The SMALDO has been cloned into the eukaryotic expression vector pcDNA3.1/V5-His TOPO-TA and was used in injecting Swiss albino mice intramuscularly (IM), subcutaneously (SC), or intraperitoneally (IP) (50 µg/mouse). Mice vaccinated with non-recombinant pcDNA3.1 served as controls. Each group was immunized 4 times at weeks 0, 2, 4, and 6. Two weeks after the last booster dose, all mice groups were infected with 80 S. mansoni cercariae via tail immersion. At week 8 post-infection, animals were sacrificed for assessment of parasitological and histopathological parameters. High anti-SMALDO IgG antibody titers were detected in sera of all vaccinated groups (P<0.01) compared to the control group. Both the IP and SC vaccination routes resulted in a significant reduction in worm burden (46.2% and 28.9%, respectively, P<0.01). This was accompanied by a significant reduction in hepatic and intestinal egg counts (41.7% and 40.2%, respectively, P<0.01) in the IP group only. The number of dead eggs was significantly increased in both IP and IM groups (P<0.01). IP vaccination recorded the highest significant reduction in granuloma number and diameter (54.7% and 29.2%, respectively, P<0.01) and significant increase in dead miracidia (P<0.01). In conclusion, changing the injection route of SMALDO DNA vaccination significantly influenced the efficacy of vaccination. SMALDO DNA vaccination via IP route could be a promising protective and anti-pathology vaccine candidate against S. mansoni infection.

Disruption of Long-Term Alcohol-Related Memory Reconsolidation: Role of β-Adrenoceptors and NMDA Receptors

PubMed Central

Wouda, Jelte A.; Diergaarde, Leontien; Riga, Danai; van Mourik, Yvar; Schoffelmeer, Anton N. M.; De Vries, Taco J.

2010-01-01

Disrupting reconsolidation of drug-related memories may be effective in reducing the incidence of relapse. In the current study we examine whether alcohol-related memories are prone to disruption by the β-adrenergic receptor antagonist propranolol (10 mg/kg) and the NMDA receptor antagonist MK801 (0.1 mg/kg) following their reactivation. In operant chambers, male Wistar rats were trained to self-administer a 12% alcohol solution. After 3 weeks of abstinence, the animals were placed in the self-administration cages and were re-exposed to the alcohol-associated cues for a 20-min retrieval period, immediately followed by a systemic injection of either propranolol, MK801 or saline. Rats were tested for cue-induced alcohol seeking on the following day. Retrieval session, injection and test were repeated on two further occasions at weekly intervals. Both propranolol and MK801 administration upon reactivation did not reduce alcohol seeking after the first reactivation test. However, a significant reduction of alcohol seeking was observed over three post-training tests in propranolol treated animals, and MK801 treated animals showed a strong tendency toward reduced alcohol seeking (p = 0.06). Our data indicate that reconsolidation of alcohol-related memories can be disrupted after a long post-training interval and that particularly β-adrenergic receptors may represent novel targets for pharmacotherapy of alcoholism, in combination with cue-exposure therapies. PMID:21152256

Effects of in vivo injection of anti-chicken CD25 monoclonal antibody on regulatory T cell depletion and CD4+CD25- T cell properties in chickens.

PubMed

Shanmugasundaram, Revathi; Selvaraj, Ramesh K

2012-03-01

Regulatory T cells (Tregs) are defined as CD4(+)CD25(+) cells in chickens. This study examined the effects of an anti-chicken CD25 monoclonal antibody injection (0.5 mg/bird) on in vivo depletion of Tregs and the properties of CD4(+)CD25(-) cells in Treg-depleted birds. The CD4(+)CD25(+) cell percentage in the blood was lower at 8 d post injection than at 0 d. Anti-CD25-mediated CD4(+)CD25(+) cell depletion in blood was maximum at 12 d post injection. The anti-CD25 antibody injection depleted CD4(+)CD25(+) cells in the spleen and cecal tonsils, but not in the thymus, at 12 d post antibody injection. CD4(+)CD25(-) cells from the spleen and cecal tonsils of birds injected with the anti-chicken CD25 antibody had higher proliferation and higher IL-2 and IFNγ mRNA amounts than the controls at 12 d post injection. At 20 d post injection, CD4(+)CD25(+) cell percentages in the blood, spleen and thymus were comparable to that of the 0 d post injection. It could be concluded that anti-chicken CD25 injection temporarily depleted Treg population and increased and IL-2 and IFNγ mRNA amounts in CD4(+)CD25(-) cells at 12d post injection. Copyright © 2011 Elsevier Ltd. All rights reserved.

Beneficial effects of activated macrophages on sulfur mustard-induced cutaneous burns, an in vivo experience.

PubMed

Dachir, Shlomit; Cohen, Maayan; Sahar, Rita; Graham, John; Eisenkraft, Arik; Horwitz, Vered; Kadar, Tamar

2014-12-01

Macrophages are known to have key functions in almost every stage of wound healing and there is evidence for their beneficial effects in treating decubital ulcers and deep sternal wound infections in human. This study aimed to investigate the efficacy of a treatment with activated macrophages on ameliorating acute and long-term sulfur mustard (SM) induced skin injuries in the hairless guinea pig (HGP) model. HGP were exposed to SM vapor and treated with either a single or multiple intra-dermal injections of human activated macrophages in suspension (hAMS) into the wound bed. Clinical and histological evaluations were conducted up to 4 weeks post-exposure. A single treatment with hAMS early after exposure (15 min and 6 h) resulted in a reduction in the number of damaged cells and vesications in the epidermis at 24 h. A substantial increase in cellular infiltration, mostly polymorphonuclears, was taking place in the hAMS-treated animals starting as early as 1 h after exposure. This flow of inflammatory cells continued, in the treated group, for at least 4 weeks, long after the injected macrophages were not detected. Repeated injections of hAMS (15 min, 48 h and 7 d post-exposure) decreased significantly the area of the wounds and improved the integrity of the barrier function as expressed by measuring trans-epidermal water loss up to 10 d. Our results indicate that the role of macrophages in wound healing is complex; their efficacy may depend on the timing of administration. Further investigation is required to determine whether they are required during the early phase of wound development and/or during the late phase of scar formation and remodeling.

Combining glial cell line-derived neurotrophic factor gene delivery (AdGDNF) with L-arginine decreases contusion size but not behavioral deficits after traumatic brain injury.

PubMed

Degeorge, M L; Marlowe, D; Werner, E; Soderstrom, K E; Stock, M; Mueller, A; Bohn, M C; Kozlowski, D A

2011-07-27

Our laboratory has previously demonstrated that viral administration of glial cell line-derived neurotrophic factor (AdGDNF), one week prior to a controlled cortical impact (CCI) over the forelimb sensorimotor cortex of the rat (FL-SMC) is neuroprotective, but does not significantly enhance recovery of sensorimotor function. One possible explanation for this discrepancy is that although protected, neurons may not have been functional due to enduring metabolic deficiencies. Additionally, metabolic events following TBI may interfere with expression of therapeutic proteins administered to the injured brain via gene therapy. The current study focused on enhancing the metabolic function of the brain by increasing cerebral blood flow (CBF) with l-arginine in conjunction with administration of AdGDNF immediately following CCI. An adenoviral vector harboring human GDNF was injected unilaterally into FL-SMC of the rat immediately following a unilateral CCI over the FL-SMC. Within 30min of the CCI and AdGDNF injections, some animals were injected with l-arginine (i.v.). Tests of forelimb function and asymmetry were administered for 4weeks post-injury. Animals were sacrificed and contusion size and GDNF protein expression measured. This study demonstrated that rats treated with AdGDNF and l-arginine post-CCI had a significantly smaller contusion than injured rats who did not receive any treatment, or injured rats treated with either AdGDNF or l-arginine alone. Nevertheless, no amelioration of behavioral deficits was seen. These findings suggest that AdGDNF alone following a CCI was not therapeutic and although combining it with l-arginine decreased contusion size, it did not enhance behavioral recovery. Copyright © 2011 Elsevier B.V. All rights reserved.

Infection experiments with novel Piscine orthoreovirus from rainbow trout (Oncorhynchus mykiss) in salmonids

PubMed Central

Taksdal, Torunn; Olsen, Anne Berit; Wessel, Øystein; Mikkelsen, Susie Sommer; Alencar, Anna Luiza Farias; Olesen, Niels Jørgen

2017-01-01

A new disease in farmed rainbow trout (Onchorhyncus mykiss) was described in Norway in 2013. The disease mainly affected the heart and resembled heart and skeletal muscle inflammation (HSMI) in Atlantic salmon (Salmo salar L.). HSMI is associated with Piscine orthoreovirus (PRV), and a search for a similar virus in the diseased rainbow trout led to detection of a sequence with 85% similarity to PRV. This finding called for a targeted effort to assess the risk the new PRV-variant pose on farmed rainbow trout and Atlantic salmon by studying infection and disease pathogenesis, aiming to provide more diagnostic knowledge. Based on the genetic relationship to PRV, the novel virus is referred to as PRV-Oncorhynchus mykiss (PRV-Om) in contrast to PRV-Salmo salar (PRV-Ss). In experimental trials, intraperitoneally injected PRV-Om was shown to replicate in blood in both salmonid species, but more effectively in rainbow trout. In rainbow trout, the virus levels peaked in blood and heart of cohabitants 6 weeks post challenge, along with increased expression of antiviral genes (Mx and viperin) in the spleen, with 80–100% of the cohabitants infected. Heart inflammation was diagnosed in all cohabitants examined 8 weeks post challenge. In contrast, less than 50% of the Atlantic salmon cohabitants were infected between 8 and 16 weeks post challenge and the antiviral response in these fish was very low. From 12 weeks post challenge and onwards, mild focal myocarditis was demonstrated in a few virus-positive salmon. In conclusion, PRV-Om infects both salmonid species, but faster transmission, more notable antiviral response and more prominent heart pathology were observed in rainbow trout. PMID:28678799

Morphine hyposensitivity in streptozotocin-diabetic rats: Reversal by dietary l-arginine treatment.

PubMed

Lotfipour, Shahrdad; Smith, Maree T

2018-01-01

Painful diabetic neuropathy (PDN) is a long-term complication of diabetes. Defining symptoms include mechanical allodynia (pain due to light pressure or touch) and morphine hyposensitivity. In our previous work using the streptozotocin (STZ)-diabetic rat model of PDN, morphine hyposensitivity developed in a temporal manner with efficacy abolished at 3 months post-STZ and maintained for 6 months post-STZ. As this time course mimicked that for the temporal development of hyposensitivity to the pain-relieving effects of the furoxan nitric oxide (NO) donor, PRG150 (3-methylfuroxan-4-carbaldehyde) in STZ-diabetic rats, we hypothesized that progressive depletion of endogenous NO bioactivity may underpin the temporal loss of morphine sensitivity in STZ-diabetic rats. Furthermore, we hypothesized that replenishment of NO bioactivity may restore morphine sensitivity in these animals. Diabetes was induced in male Dark Agouti rats by intravenous injection of STZ (85 mg/kg). Diabetes was confirmed on day 7 if blood glucose concentrations were ≥15 mmol/L. Mechanical allodynia was fully developed in the bilateral hindpaws by 3 weeks of STZ-diabetes in rats and this was maintained for the study duration. Morphine hyposensitivity developed in a temporal manner with efficacy abolished by 3 months post-STZ. Administration of dietary l-arginine (NO precursor) at 1 g/d to STZ-diabetic rats according to a 15-week prevention protocol initiated at 9 weeks post-STZ prevented abolition of morphine efficacy. When given as an 8-week intervention protocol in rats where morphine efficacy was abolished, dietary l-arginine at 1 g/d progressively rescued morphine efficacy and potency. Our findings implicate NO depletion in the development of morphine hyposensitivity in STZ-diabetic rats. © 2017 John Wiley & Sons Australia, Ltd.

Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.

PubMed

Robinson, Jennifer G; Farnier, Michel; Krempf, Michel; Bergeron, Jean; Luc, Gérald; Averna, Maurizio; Stroes, Erik S; Langslet, Gisle; Raal, Frederick J; El Shahawy, Mahfouz; Koren, Michael J; Lepor, Norman E; Lorenzato, Christelle; Pordy, Robert; Chaudhari, Umesh; Kastelein, John J P

2015-04-16

Alirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and efficacy. We conducted a randomized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy. Patients were randomly assigned in a 2:1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24. At week 24, the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points (P<0.001); the treatment effect remained consistent over a period of 78 weeks. The alirocumab group, as compared with the placebo group, had higher rates of injection-site reactions (5.9% vs. 4.2%), myalgia (5.4% vs. 2.9%), neurocognitive events (1.2% vs. 0.5%), and ophthalmologic events (2.9% vs. 1.9%). In a post hoc analysis, the rate of major adverse cardiovascular events (death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) was lower with alirocumab than with placebo (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31 to 0.90; nominal P=0.02). Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels. In a post hoc analysis, there was evidence of a reduction in the rate of cardiovascular events with alirocumab. (Funded by Sanofi and Regeneron Pharmaceuticals; ODYSSEY LONG TERM ClinicalTrials.gov number, NCT01507831.).

Histologic Evaluation of Micronized AlloDerm After Injection Laryngoplasty in a Rabbit Model.

PubMed

Oldenburg, Michael S; Janus, Jeff; Voss, Steve; San Marina, Serban; Chen, Tiffany; Garcia, Joaquin; Ekbom, Dale

2017-05-01

Micronized AlloDerm is a commonly used injectable material for injection laryngoplasty; however, the histologic response to laryngeal implantation and resorption rate over time have not been elucidated. This study aimed to evaluate the in vivo response of micronized AlloDerm over time after laryngeal implantation using a rabbit model. Animal model. The left recurrent laryngeal nerve was sectioned in five New Zealand White rabbits to create a vocal cord paralysis. Two weeks later, injection laryngoplasty was performed with 100 μL of micronized AlloDerm. Animals were sacrificed 4 (two rabbits) and 12 (three rabbits) weeks after injection. Histologic sections were stained and evaluated by a single pathologist. Volume estimates were made by assuming the implant took an ellipsoid shape using dimensions calculated from histologic slides. In all cases, histological analysis revealed a lymphocytic inflammatory response infiltrating the peripheral margins of injection. After 4 weeks, the volume of injected material remaining in two rabbits was 404 and 278 mm 3 (average 341 mm 3 ). After 12 weeks, the volume of injected material remaining in three rabbits was 0, 61, and 124 mm 3 (average 62 mm 3 ), an 82% difference in volume of material between animals sacrificed at 4 weeks versus 12 weeks. Injection laryngoplasty using micronized AlloDerm induces a lymphocytic inflammatory response after injection in a rabbit model. Though a significant amount of material remains after 4 weeks, by 12 weeks the majority has been reabsorbed. NA Laryngoscope, 127:E166-E169, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Carboplatin loaded polymethylmethacrylate nano-particles in an adjunctive role in retinoblastoma: An animal trial

PubMed Central

Shome, Debraj; Kalita, Dhrubajyoti; Jain, Viral; Sarin, Rajiv; Maru, Girish B.; Bellare, Jayesh R.

2014-01-01

Purpose: The purpose of the study is to compare the intra-vitreal concentrations of carboplatin, post peri-ocular injections of commercially available carboplatin (CAC) and a novel carboplatin loaded polymethylmethacrylate nanoparticulate carboplatin (NPC), in either eye, as a model system for treatment of advanced intra-ocular retinoblastoma (RB). Design: Experimental, comparative, animal study. Materials and Methods: Polymethylmethacrylate nanoparticles were prepared by free radical emulsion polymerization of methyl methacrylate in aqueous solution of carboplatin in the presence of surfactant sodium dodecyl sulfate and thermal initiator ammonium persulfate. 21 Sprague-Dawley rats, aged between 6 weeks and 3 months were enrolled. The right eye of each rat was injected peri-ocularly with CAC formulation (1 ml of 10 mg/ml) and the left eye with NPC (1 ml of 10 mg/ml), post-anesthesia, by an ophthalmologist trained in ocular oncology. Three rats each were euthanized on days 1, 3, 5, 7, 14, 28 and 42, post-injection and both eyes were carefully enucleated. Intra-vitreal concentrations of CAC and NPC were determined with Inductively Coupled Plasma Atomic Emission Spectroscopy. Analysis of data was done with paired t-test. Results: The intra-vitreal concentration of carboplatin with NPC was ~3-4 times higher than with CAC in all animals, on all the days (P < 0.05). Conclusion: A higher trans-scleral permeability gradient is obtained with the novel nanoparticles than with the commercial drug, leading to sustained higher levels of carboplatin in the vitreous. Peri-ocular injection of NPC could thus have an adjuvant efficacy in the treatment for advanced clinical RB, specifically those with vitreous seeds. PMID:24881606

Cytidine 5'-diphosphocholine (CDP-choline) adversely effects on pilocarpine seizure-induced hippocampal neuronal death.

PubMed

Kim, Jin Hee; Lee, Dong Won; Choi, Bo Young; Sohn, Min; Lee, Song Hee; Choi, Hui Chul; Song, Hong Ki; Suh, Sang Won

2015-01-21

Citicoline (CDP-choline; cytidine 5'-diphosphocholine) is an important intermediate in the biosynthesis of cell membrane phospholipids. Citicoline serves as a choline donor in the biosynthetic pathways of acetylcholine and neuronal membrane phospholipids, mainly phosphatidylcholine. The ability of citicoline to reverse neuronal injury has been tested in animal models of cerebral ischemia and clinical trials have been performed in stroke patients. However, no studies have examined the effect of citicoline on seizure-induced neuronal death. To clarify the potential therapeutic effects of citicoline on seizure-induced neuronal death, we used an animal model of pilocarpine-induced epilepsy. Temporal lobe epilepsy (TLE) was induced by intraperitoneal injection of pilocarpine (25mg/kg) in adult male rats. Citicoline (100 or 300 mg/kg) was injected into the intraperitoneal space two hours after seizure onset and a second injection was performed 24h after the seizure. Citicoline was injected once per day for one week after pilocarpine- or kainate-induced seizure. Neuronal injury and microglial activation were evaluated at 1 week post-seizure. Surprisingly, rather than offering protection, citicoline treatment actually enhanced seizure-induced neuronal death and microglial activation in the hippocampus compared to vehicle treated controls. Citicoline administration after seizure-induction increased immunoglobulin leakage via BBB disruption in the hippocampus compared with the vehicle-only group. To clarify if this adverse effect of citicoline is generalizable across alternative seizure models, we induced seizure by kainate injection (10mg/kg, i.p.) and then injected citicoline as in pilocarpine-induced seizure. We found that citicoline did not modulate kainate seizure-induced neuronal death, BBB disruption or microglial activation. These results suggest that citicoline may not have neuroprotective effects after seizure and that clinical application of citicoline after seizure needs careful consideration. Copyright © 2014 Elsevier B.V. All rights reserved.

Oral or parenteral administration of curcumin does not prevent the growth of high-risk t(4;11) acute lymphoblastic leukemia cells engrafted into a NOD/SCID mouse model

PubMed Central

ZUNINO, SUSAN J.; STORMS, DAVID H.; NEWMAN, JOHN W.; PEDERSEN, THERESA L.; KEEN, CARL L.; DUCORE, JONATHAN M.

2013-01-01

In this study, the efficacy of orally and parenter-ally administered curcumin was evaluated in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice (NOD.CB17-Prkdcscid/J mice) engrafted with the human t(4;11) acute lymphoblastic leukemia line, SEM. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, the chemotherapeutic potential was examined by injecting mice intraperitoneally with curcumin (5 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO) or DMSO alone (control) every other day, or vincristine (0.5 mg/kg body weight) 3 times per week for 4 weeks (n=16 per group). The intraperitoneal administration of curcumin did not inhibit the growth of the leukemia cells. To determine the efficacy of oral curcumin, mice were fed a control diet or a diet containing 0.5% w/w curcumin 3 weeks prior to the injection of the leukemia cells and throughout the experimental period (n=16 per group). To determine whether dietary curcumin can enhance the efficacy of a conventional chemotherapeutic agent, vincristine was injected intraperitoneally into leukemic mice fed the different diets. Dietary curcumin did not delay the engraftment or growth of leukemia cells, or sensitize the cells to vincristine. Liquid chromatography-tandem mass spectrometry analyses of mouse sera showed that curcumin rapidly metabolized to glucuronidated and sulfated forms within 1 h post-injection and these were the major curcumin metabolites found in the sera of the mice fed the curcumin diet. In contrast to the findings in previous in vitro models, the current data indicate that orally or parenterally administered curcumin is not a potent preventive agent against high-risk t(4;11) acute lymphoblastic leukemia. PMID:23232667

Ultrasound-guided plasma rich in growth factors injections and scaffolds hasten motor nerve functional recovery in an ovine model of nerve crush injury.

PubMed

Sánchez, Mikel; Anitua, E; Delgado, D; Prado, R; Sánchez, P; Fiz, N; Guadilla, J; Azofra, J; Pompei, O; Orive, G; Ortega, M; Yoshioka, T; Padilla, S

2017-05-01

In the present study we evaluated the motor recovery process of peripheral nerve injury (PNI), based on electrophysiological and histomorphometric criteria, after treatment with plasma rich in growth factors (PRGF) injections and scaffolds in an ovine model. Three groups of sheep underwent a nerve crush lesion: the first group (n = 3) was left to recover spontaneously (SR); the second group was administered saline injections (SI; n = 5) and a third group (n = 6) received PRGF injections and scaffolds immediately after the crush injury. At post-intervention week 8, 70% of sheep in the PRGF group were CMAP-positive, with no electrophysiological response in the rest of the groups. Histomorphometric analysis 12 weeks after the surgical intervention revealed that the average axonal density of the SR (1184 ± 864 axons/µm 2 ) and SI (3109 ± 2450 axons/µm 2 ) groups was significantly inferior to the control (8427 ± 2433 axons/µm 2 ) and also inferior to the PRGF group (5276 ± 4148 axons/µm 2 ), showing no significant differences between the control and PRGF groups. The axonal size of the SR and SI groups was significantly smaller compared with the control group (18 ± 4 µm 2 ), whereas the axonal size of the PRGF group (6 ± 5 µm 2 ) did not show statistical differences from the control. Morphometry of the target muscles indicated that the PRGF group had the lowest percentage volume reduction 12 weeks after the crush injury. The PRGF group had larger muscle fibre areas than the SI and SR groups, although the differences did not reach statistical significance. Overall, these data suggest that the PRGF injections and scaffolds hastened functional axon recovery and dampened atrophy of the target muscles in an ovine model. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Comparison Between Botulinum Toxin A Injection and Lacrimal Punctal Plugs for the Control of Post-LASIK Dry Eye Manifestations: A Prospective Study.

PubMed

Fouda, Sameh M; Mattout, Hala K

2017-06-01

Laser in situ keratomelieusis (LASIK) is one of the commonest refractive procedures performed nowadays. The dry eye problem is nearly universal in all patients after LASIK and it can be so annoying that the post-operative patient satisfaction is sometimes precluded. Conventional treatment includes the use of artificial tears. Alternative methods such as punctal plugs and botulinum toxin injection can be used for the management of post-LASIK dry eye. The aim of this study is to compare botulinum toxin injection in the orbicularis muscle to lacrimal punctal plugs for the control of post-LASIK dry eye manifestations. This is a prospective study that included 60 patients who had LASIK eye surgery for correction of refractive errors. Patients were randomly assigned to one of three methods of dry eye management; the first method was conventional medical treatment with preservative-free tear substitutes only (group A: 20 patients = 40 eyes); the second method was intraoperative injection of botulinum toxin A (BTA) in the orbicularis muscle below the lower punctum of both eyes (group B: 20 patients = 40 eyes) and the third method was intraoperative insertion of temporary extended duration silicone punctal plugs in the lower punctum of both eyes (group C: 20 patients = 40 eyes). In the first follow-up visit after 2 weeks, the two test groups (B, C) showed a statistically significant increase in both tear film break up time (TBUT) and Schirmer test score with a decrease in the OSDI score and daily frequency of lubricants used in comparison to the control group A. These differences were maintained in the next follow-up visit but they became statistically insignificant at the 3rd and 6th post-operative months. Complications were encountered more in the punctal plug patients (60%) than in BTA patients (25%) and this difference was statistically significant. The use of BTA injection to control dry eye symptoms by inducing temporary punctal ectropion is an effective method to improve patient satisfaction after LASIK eye surgery. It has higher level of patient satisfaction and fewer complications in comparison to punctal plugs or topical standard dry eye treatment.

A randomised study of ilio-inguinal nerve blocks following inguinal hernia repair: a stopped randomised controlled trial.

PubMed

Walker, Stuart; Orlikowski, Chris

2008-02-01

Local anaesthetic use for post-operative pain control is widely used following open inguinal hernia repair but this is not without risk. The aim of this study was to compare ilio-inguinal nerve block and wound irrigation in patients undergoing open inguinal hernia repair under general anaesthetic in a randomised, double blind, placebo controlled trial. Adult patients admitted for unilateral primary open mesh repair of an inguinal hernia were recruited. The patients received a standard general anaesthetic. Prior to skin incision, an ilio-inguinal injection was performed by the anaesthetist with either ropivicaine or normal saline. Prior to closure of the wound, the wound was irrigated with either ropivicaine or normal saline. Post-operatively, all patients received fentynal patient controlled analgesia and regular oral analgesia. Pain scores and visual analogue scores were recorded until discharge. Patients were then contacted by telephone at 24h, 48h, 2weeks and 4weeks post-operatively and asked a standard series of questions, mainly related to post-operative pain. After 12 patients had been recruited the trial was stopped as 5 of the 8 patients who received an ilio-inguinal nerve block suffered a neurological complication. Ilio-inguinal nerve block with ropivicaine should be avoided.

Single Shot Epidural Injection for Cervical and Lumbosaccral Radiculopathies: A Preliminary Study

PubMed Central

Nawani, Digambar Prasad; Asthana, Veena

2010-01-01

Background Epidural steroid injection is an established treatment modality for intervertebral disc prolapse leading to radiculopathy. In cases where two levels of radiculopathy are present, two separate injections are warranted. Herein, we present our experience of management of such cases with a single epidural injection of local anaesthetic, tramadol and methylprednisolone, and table tilt for management of both radiculopathies. Methods 50 patients of either sex aged between 35-65 years presenting with features of cervical and lumbar radiculopathic pain were included and were subjected to single lumbar epidural injection of local anaesthetic, tramadol and methylprednisolone, in the lateral position. The table was then tilted in the trendelberg position with a tilt of 25 degrees, and patients were maintained for 10 minutes before being turned supine. All patients were administered 3 such injections with an interval of 2 weeks between subsequent injections, and pain relief was assessed with a visual analogue scale. Immediate complications after the block were assessed. Results Immediate and post procedural complications observed were nausea and vomiting (20%), painful injection site (4%), hypotension (10%) and high block (4%). Pain relief was assessed after the three injections by three grades: 37 (74%) had complete resolution of symptoms; 18% had partial relief and 8% did not benefit from the procedure. Conclusions This technique may be used as an alternative technique for pain relief in patients with unilateral cervical and lumbar radiculopathies. PMID:21217889

A New Technique for the Treatment of Lumbar Facet Joint Syndrome Using Intra-articular Injection with Autologous Platelet Rich Plasma.

PubMed

Wu, Jiuping; Du, Zhenwu; Lv, Yang; Zhang, Jun; Xiong, Wei; Wang, Ruiqiang; Liu, Rui; Zhang, Guizhen; Liu, Qinyi

2016-01-01

Lumbar facet joint syndrome is currently suggested to be a main source of axial low back pain, and a large portion of axial low back pain is caused by disorders in lumbar facet joints. Intra-articular injection is one of the most common treatment methods in the early clinical application. Therefore, we attempt to seek a new injectable material, autologous platelet rich plasma (PRP), to treat lumbar facet syndrome, as well as to assess its therapeutic effectiveness and safety. A prospective clinic evaluation. The outpatient clinic of a single academic medical center. Total 19 patients with lumbar facet joint syndrome (8 men, 11 women; mean ages: 52.53 ± 6.79 years, range: 38 - 62 years) were enrolled to receive lumbar facet joint injection with autologous PRP under x-ray fluoroscopic control. Patients were followed up immediately, at one week, one month, 2 months, and 3 months following treatment, and the elements of this analysis included low back pain visual analogue scale (VAS) at rest and during flexion, Roland-Morris Disability Questionnaire (RMQ), Oswestry Disability Index (ODI), and modified MacNab criteria for the pain relief. All the 19 patients completed the intra-articular injections with autologous PRP successfully. At one week after treatment, low back pain reduced significantly compared with prior to treatment both at rest and during flexion. The outcomes were assessed as "good" or "excellent" for 9 patients (47.37%) immediately after treatment, 14 patients (73.68%) at one week, 15 patients (78.95%) at one month, 15 patients (78.95%) at 2 months, and 15 patients (78.95%) at 3 months. Statistically significant differences were observed based on RMQ and a more than 10% improvement in lumbar functional capacity was observed based on ODI between pre-treatment and post-treatment. In addition, there were no severe relevant complications during the whole process of injection and follow-up period. A control group and the curative effect observations with longer follow-up may lead to a more convincing result for our study. In the short-term period of 3 months, the new technique of lumbar facet joint injection with autologous PRP is effective and safe for patients with lumbar facet joint syndrome. Key words: Low back pain, lumbar facet joint syndrome, autologous platelet rich plasma, intra-articular injection.

Long-acting injectable antipsychotics update: lengthening the dosing interval and expanding the diagnostic indications.

PubMed

Citrome, Leslie

2017-10-01

Long-acting injectable (LAI) antipsychotics are a useful but underutilized option in the management of schizophrenia. Areas covered: This is a narrative review of newer LAI antipsychotics approved by the US Food and Drug Administration and is an update to a previously published review from 2013. Emphasized are new indications and new dosing intervals. Expert commentary: Ensuring that persons receiving oral antipsychotics are aware that LAI antipsychotics are available is important. The use of LAI antipsychotics can decrease the risk of relapse in both first-episode and chronic schizophrenia. Available treatments differ in terms of specific indications, approved injection sites, needle gauge, injection volume, injection interval, requirements for oral supplementation, availability of pre-filled syringes, storage needs, and post-injection observation period, as well as potential drug-drug interactions and commonly encountered adverse reactions. Approved indications have expanded beyond schizophrenia to also include bipolar maintenance (risperidone microspheres and aripiprazole monohydrate) and schizoaffective disorder (paliperidone palmitate monthly). Intervals between injections can be longer than one month (six-week or two-month aripiprazole lauroxil, and three-month paliperidone palmitate). After a review of the evidence-base, guidance is offered on the appropriate selection among the LAI formulations of both first and second-generation antipsychotics.

Serum Penicillin G Levels Are Lower Than Expected in Adults within Two Weeks of Administration of 1.2 Million Units

PubMed Central

Hansen, Christian J.; Russell, Kevin L.; Blumer, Jeffrey L.

2011-01-01

When introduced in the 1950s, benzathine penicillin G (BPG) was shown to be effective in eradicating group A beta-hemolytic streptococcus (GAS) for at least 3 weeks after administration. Several studies since the 1990s suggest that at 3–4 weeks serum penicillin G levels are less than adequate (below MIC90 of 0.016 µg/ml). We studied these levels for 4 weeks after the recommended dose of BPG in military recruits, for whom it is used as prophylaxis against GAS. The 329 subjects (mean age 20 years) each received 1.2 million units BPG IM and gave sera 1 day post injection and twice more at staggered time points over 4 weeks. Serum penicillin G levels were measured by liquid chromatography/tandem mass spectometry. The half-life of serum penicillin G was 4.1 days. By day 11, mean levels were <0.02 µg/ml, and by day 15<0.01 µg/ml. Levels in more than 50% of the subjects were below 0.02 µg/ml on day 9, and <.01 µg/ml on day 16. There was no demonstrable effect of subject body-surface area nor of the four different lots of BPG used. These data indicate that in healthy young adults serum penicillin G levels become less than protective <2½ weeks after injection of 1.2 million units of BPG. The findings require serious consideration in future medical and public health recommendations for treatment and prophylaxis of GAS upper respiratory tract infections. PMID:21991307

Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice.

PubMed

Danilov, Camelia A; Steward, Oswald

2015-04-01

Previous studies indicate that conditional genetic deletion of phosphatase and tensin homolog (PTEN) in neonatal mice enhances the ability of axons to regenerate following spinal cord injury (SCI) in adults. Here, we assessed whether deleting PTEN in adult neurons post-SCI is also effective, and whether enhanced regenerative growth is accompanied by enhanced recovery of voluntary motor function. PTEN(loxP/loxP) mice received moderate contusion injuries at cervical level 5 (C5). One group received unilateral injections of adeno-associated virus expressing CRE (AAV-CRE) into the sensorimotor cortex; controls received a vector expressing green fluorescent protein (AAV-GFP) or injuries only (no vector injections). Forelimb function was tested for 14weeks post-SCI using a grip strength meter (GSM) and a hanging task. The corticospinal tract (CST) was traced by injecting mini-ruby BDA into the sensorimotor cortex. Forelimb gripping ability was severely impaired immediately post-SCI but recovered slowly over time. The extent of recovery was significantly greater in PTEN-deleted mice in comparison to either the AAV-GFP group or the injury only group. BDA tract tracing revealed significantly higher numbers of BDA-labeled axons in caudal segments in the PTEN-deleted group compared to control groups. In addition, in the PTEN-deleted group, there were exuberant collaterals extending from the main tract rostral to the lesion and into and around the scar tissue at the injury site. These results indicate that PTEN deletion in adult mice shortly post-SCI can enhance regenerative growth of CST axons and forelimb motor function recovery. Copyright © 2015 Elsevier Inc. All rights reserved.

Effectiveness of polydeoxyribonucleotide injection versus normal saline injection for treatment of chronic plantar fasciitis: a prospective randomised clinical trial.

PubMed

Kim, Jae Kwang; Chung, Jae Yoon

2015-07-01

Polydeoxyribonucleotide (PDRN) has been used for the treatment of chronic tendinosis. This prospective randomised study was conducted to evaluate the efficacy and complications of PDRN injection for treatment of plantar fasciitis. Forty patients with a clinical diagnosis of plantar fasciitis were randomly allocated to PDRN injection (PDRN group, n = 20) or normal saline injection (placebo group, n = 20). Injections were performed weekly for three weeks. Clinical evaluations were done at baseline and four and 12 weeks after treatment began using the visual analogue scale (VAS) for foot pain and Manchester-Oxford Foot Questionnaire (MOXFQ). We also monitored the complications in both groups at one, two, four and 12 weeks after initial treatment. The PDRN group achieved a significant improvement in VAS and MOXFQ scores at four weeks after treatment, and this improvement continued until 12 weeks after treatment. On the other hand, the placebo group did not achieve a significant improvement in the VAS or MOXFQ scores at four or 12 weeks. The initial VAS and MOXFQ scores of the PDRN group were not significantly different from those of the placebo group. At four weeks after treatment, the VAS and MOXFQ scores of the PDRN group were better than those of the placebo group, but the difference was not statistically significant. At 12 weeks after treatment, the VAS and MOXFQ scores of the PDRN group were significantly better than those of the placebo group. We noticed no injection-related complications, such as itching, urticaria, redness or infection signs around the injection site in either group. PDRN injection is an effective and safe treatment option and may be considered for plantar fasciitis.

Organochlorine contaminants in double-crested cormorants from Green Bay, Wisconsin: II. Effects of an extract derived from cormorant eggs on the chicken embryo

USGS Publications Warehouse

Powell, D.C.; Aulerich, R.J.; Meadows, J.C.; Tillitt, D.E.; Stromborg, K.L.; Kubiak, T.J.; Giesy, J.P.; Bursian, S.J.

1997-01-01

White Leghorn chicken (Gallus domesticus) eggs were injected prior to incubation with one of four concentrations (0.001, 0.01, 0.1, and 1.0 egg-equivalent) of an extract derived from 1,000 double-crested cormorant (Phalacrocorax auritus) eggs collected at Spider Island adjacent to Green Bay in Lake Michigan. One egg-equivalent corresponded to the concentration of contaminants present in an average cormorant egg. This was approximately 322 pg toxic equivalents (TEQs)/g, ww egg with polychlorinatedbiphenyl congener 126 (3,3′,4,4′,5-pentachlorobiphenyl) accounting for over 70% of the TEQs. Injection of 1.0 egg-equivalent resulted in 77% mortality at hatch. The incidence of developmental abnormalities (structural defects or edema) was not affected by injection of the extract. Body weight gain of chicks was reduced in the 1.0 egg-equivalent dose group in the first, second, and third week's post-hatch. Relative brain weights were greater and relative bursa weights were less in the 1.0 egg-equivalent dose group than in the vehicle control at three weeks of age. There were no significant differences in the relative weights of the heart, liver, spleen, testes, or comb among treated and control birds.

Traumatic Brain Injury in Adult Rats Causes Progressive Nigrostriatal Dopaminergic Cell Loss and Enhanced Vulnerability to the Pesticide Paraquat

PubMed Central

Hutson, Che Brown; Lazo, Carlos R.; Mortazavi, Farzad; Giza, Christopher C.; Hovda, David

2011-01-01

Abstract Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic neurons and the accumulation of alpha-synuclein. Both traumatic brain injury (TBI) and pesticides are risk factors for PD, but whether TBI causes nigrostriatal dopaminergic cell loss in experimental models and whether it acts synergistically with pesticides is unknown. We have examined the acute and long-term effects of TBI and exposure to low doses of the pesticide paraquat, separately and in combination, on nigrostriatal dopaminergic neurons in adult male rats. In an acute study, rats received moderate TBI by lateral fluid percussion (LFP) injury, were injected with saline or paraquat (10 mg/kg IP) 3 and 6 days after LFP, were sacrificed 5 days later, and their brains processed for immunohistochemistry. TBI alone increased microglial activation in the substantia nigra, and caused a 15% loss of dopaminergic neurons ipsilaterally. Paraquat increased the TBI effect, causing a 30% bilateral loss of dopaminergic neurons, reduced striatal tyrosine hydroxylase (TH) immunoreactivity more than TBI alone, and induced alpha-synuclein accumulation in the substantia nigra pars compacta. In a long-term study, rats received moderate LFP, were injected with saline or paraquat at 21 and 22 weeks post-injury, and were sacrificed 4 weeks later. At 26 weeks post injury, TBI alone induced a 30% bilateral loss of dopaminergic neurons that was not exacerbated by paraquat. These data suggest that TBI is sufficient to induce a progressive degeneration of nigrostriatal dopaminergic neurons. Furthermore, TBI and pesticide exposure, when occurring within a defined time frame, could combine to increase the PD risk. PMID:21644813

Abscopal effect of boron neutron capture therapy (BNCT): proof of principle in an experimental model of colon cancer.

PubMed

Trivillin, Verónica A; Pozzi, Emiliano C C; Colombo, Lucas L; Thorp, Silvia I; Garabalino, Marcela A; Monti Hughes, Andrea; González, Sara J; Farías, Rubén O; Curotto, Paula; Santa Cruz, Gustavo A; Carando, Daniel G; Schwint, Amanda E

2017-11-01

The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 10 6 DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 × 10 6 DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm 3 . In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm 3 . The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect.

Ultrasound-guided intrasphincteric botulinum toxin injection relieves obstructive defecation due to Hirschsprung's disease and internal anal sphincter achalasia.

PubMed

Church, Joseph T; Gadepalli, Samir K; Talishinsky, Toghrul; Teitelbaum, Daniel H; Jarboe, Marcus D

2017-01-01

Chronic obstructive defecation can occur in patients with Hirschsprung Disease (HD) and internal anal sphincter (IAS) achalasia. Injection of Botulinum Toxin (BoTox) into the IAS can temporarily relieve obstructive defecation, but can be challenging when performed by tactile sense alone. We compared results of BoTox injections with and without ultrasound (US) guidance. We retrospectively reviewed BoTox injections into the IAS for obstructive defecation over 5years. Analyzed outcomes included short-term improvement, defined as resolution of enterocolitis, new ability to spontaneously defecate, and/or normalization of bowel movement frequency 2weeks post-operatively, as well as requirement of more definitive surgical therapy (myotomy/myomectomy, colectomy, colostomy, cecostomy/appendicostomy, and/or sacral nerve stimulator implantation). Outcomes were compared using t-test and Fisher's Exact test, with significance defined as p<0.05. Twelve patients who underwent BoTox injection were included, including 5 patients who underwent injections both with and without ultrasound. Ten underwent an ultrasound-guided injection (13 injection procedures), 5 of whom had HD. Seven underwent an injection without ultrasound guidance (17 injection procedures), 5 of whom had HD. Procedures performed with US resulted in greater short-term improvement (76% versus 65% without ultrasound) and less requirement of a definitive procedure for obstructive defecation (p<0.05). US-guided BoTox injection is safe and effective for obstructive defecation, and may decrease the need for a definitive operation. III. Copyright © 2017 Elsevier Inc. All rights reserved.

Percutaneous trans-hepatic gelfoam-cyanoacrylate glue embolization for ruptured post-traumatic hepatic artery pseudo-aneurysm in a limited-resource scenario.

PubMed

Kumar, Manoj; Goel, Prabudh; Rawat, J D; Kumari, Shweta; Shankhwar, S N; Kureel, S N

2013-05-01

We present our experience with an indigenously designed percutaneous trans-hepatic ultrasound-guided Gelfoam sponge cum cyanoacrylate glue-based embolization technique for the treatment of a ruptured post-traumatic aneurysm of a branch of the right hepatic artery (RHA) as a 'life-saving emergent' procedure in a patient unfit for surgery or endovascular intervention and in a 'limited-resource' scenario (non-availability of Digital Subtraction Angiography Suite). An 8-year-old boy sustained crush-injury to the right lobe of the liver in a road-traffic accident and presented in shock. After resuscitation, a laparotomy and repair of the right lobe of liver were undertaken. Bleeding restarted 1 week after the surgery; the patient bled from drain site and went into shock. Exploration was not advisable in view of poor general condition, and sepsis, deranged coagulation and parental reluctance in view of guarded prognosis. Multi-detector Computed Tomography Angiography was performed after resuscitation which revealed active bleed from a ruptured pseudo-aneurysm of a branch of RHA. The bleeding artery was identified with duplex sonography and was embolized by the percutaneous trans-hepatic route proximal to the site of pseudo-aneurysm and rupture by a two-step process. Initially, a thin paste/'slurry' made of powdered gelfoam dissolved in sterile saline was injected into the bleeding vessel. Subsequently, the area was sealed by injecting 1.0 ml of N-butyl-2-cyanoacrylate glue. Hemostasis was confirmed by Color and Power Doppler Ultrasonography both post-procedure and after 48 h. With supportive management, the patient showed a rapid recovery and was discharged after 2 weeks. He continues to be well at 3-month follow-up. The technique was effective in controlling hemostasis and life-saving in our set-up.

The use of virtual reality computer simulation in learning Port-A cath injection.

PubMed

Tsai, Sing-Ling; Chai, Sin-Kuo; Hsieh, Li-Feng; Lin, Shirling; Taur, Fang-Meei; Sung, Wen-Hsu; Doong, Ji-Liang

2008-03-01

Cost-benefit management trends in Taiwan healthcare settings have led nurses to perform more invasive skills, such as Port-A cath administration of medications. Accordingly, nurses must be well-prepared prior to teaching by the mentor and supervision method. The purpose of the current study was to develop a computer-assisted protocol using virtual reality (VR) in performing Port-A cath as a training program for novice nurses. A pre-tested and post-tested control group experimental design was used in this study. Seventy-seven novice nurses were invited from one large medical center hospital in North Taiwan. Thirty-seven and forty nurses were randomly assigned to experimental and control groups. First, we designed a 40 minute port-A cath injection VR simulation. Then, the experimental group practiced this simulation two times over 3 weeks. The control group attended the traditional class. The post-test 1 was right after completion of the simulation practice. The post-test 2 was after the second simulation practice in 3 weeks. The results showed that most novice nurses lacked Port-A cath experience both in the classroom and during the period of their practice training. The knowledge score regarding the Port-A cath technique was significantly higher in the nurses that participated in the simulation training than in the control group. The novice nurses were most satisfied with the reduction in their fear of performing the Port-A cath technique and their enhanced clinical skills. VR simulation significantly reduced error rates and increased correct equipment selection, showing that nurses who participated in the simulation may be better prepared for inserting Port-A cath.

AAV-mediated netrin-1 overexpression increases peri-infarct blood vessel density and improves motor function recovery after experimental stroke.

PubMed

Sun, Hui; Le, Thang; Chang, Tiffany T J; Habib, Aisha; Wu, Steven; Shen, Fanxia; Young, William L; Su, Hua; Liu, Jialing

2011-10-01

Apart from its role in axon guidance, netrin-1 is also known to be pro-angiogenic. The aim of this study is to determine whether adeno-associated viral (AAV) mediated overexpression of netrin-1 improves post-stroke neurovascular structure and recovery of function. AAV-Netrin-1 or AAV-LacZ of 1×10(10) genome copies each was injected medial and posterior to ischemic lesion at one hour following reperfusion using the distal middle cerebral artery occlusion (MCAO) method. Quantitative RT-PCR revealed that the expression of netrin-1 transgene began as early as one day and increased dramatically about 3 weeks following vector injection. Western blot analysis and confocal microscopy suggested that both the endogenous and transduced netrin-1 were expressed in the neurons of the peri-infarct cortex after MCAO. AAV-mediated netrin-1 overexpression significantly increased vascular density in the peri-infarct cortex and promoted the migration of immature neurons into the peri-infarct white matter, but it did not significantly reduce infarct size. Netrin-1 overexpression also enhanced post-stroke locomotor activity, improved exploratory behavior, and reduced ischemia-induced motor asymmetry in forelimb usage. However, it had little effect on post-stroke spatial learning and memory. Our results suggest that AAV mediated netrin-1 overexpression improves peri-infarct vascular density and post stroke motor function. Published by Elsevier Inc.

Rapamycin attenuates bladder hypertrophy during long-term outlet obstruction in vivo: tissue, matrix and mechanistic insights.

PubMed

Schröder, Annette; Kirwan, Tyler P; Jiang, Jia-Xin; Aitken, Karen J; Bägli, Darius J

2013-06-01

Previous molecular studies showed that the mTOR inhibitor rapamycin prevents bladder smooth muscle hypertrophy in vitro. We investigated the effect of rapamycin treatment in vivo on bladder smooth muscle hypertrophy in a rat model of partial bladder outlet obstruction. A total of 48 female Sprague-Dawley® rats underwent partial bladder outlet obstruction and received daily subcutaneous injections of rapamycin (1 mg/kg) or vehicle commencing 2 weeks postoperatively. A total of 36 rats underwent sham surgery and received rapamycin or vehicle. Rats were sacrificed 3, 6 and 12 weeks after surgery. Before sacrifice, voiding was observed in a metabolic cage for 24 hours. Bladder-to-body weight in gm bladder weight per kg body weight and post-void residual urine were assessed. We evaluated Col1a1, Col3a1, Eln and Mmp7 mRNA expression and histology. Two-factor ANOVA and the post hoc t test were applied. Bladder outlet obstruction caused a significant increase in bladder weight in all obstructed groups. Three weeks postoperatively (1 week of treatment) there was no difference in the bladder-to-body weight ratio in the obstructed group. However, at 6 and 12 weeks (4 and 10 weeks of treatment, respectively) the bladder-to-body weight ratio of rats with obstruction plus rapamycin was significantly lower than that of rats with obstruction plus vehicle. Post-void residual urine volume after 6 and 12 weeks of obstruction was lower in obstructed rats with rapamycin compared to that in obstructed rats with vehicle. Rapamycin decreased the obstruction induced expression of Col1a1, Col3a1, Eln and Mmp7. Rapamycin prevents mechanically induced hypertrophy in cardiovascular smooth muscle. In vivo mTOR inhibition may attenuate obstruction induced detrusor hypertrophy and help preserve bladder function. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A subgroup-specific evaluation of the efficacy of intraarticular triamcinolone hexacetonide in juvenile chronic arthritis.

PubMed

Breit, W; Frosch, M; Meyer, U; Heinecke, A; Ganser, G

2000-11-01

To determine the subgroup-specific differences of intraarticular triamcinolone hexacetonide (TH) in the treatment of joint inflammation in patients with juvenile chronic arthritis (JCA). A retrospective review of 194 children of all subgroups of JCA, treated by a single or repeated TH injection between 1989 to 1994. Efficacy and duration of benefit were evaluated after a mean duration of 3, 15, 30, and 64 weeks. In all, 1439 TH injections were given to 194 patients; 368 of these were reinjections. The median duration of improvement of all injections was 74 weeks. Responses were significantly different among subgroups (p = 0.0001): there were 121 weeks of efficacy in early-onset pauciarticular JCA type I (223 injections), 47 weeks in late-onset pauciarticular JCA type II (190 injections), 105 weeks in rheumatoid factor negative polyarticular JCA (445 injections), 63 weeks in rheumatoid factor positive polyarticular JCA (127 injections), and 36 weeks in systemic JCA (413 injections). Forty-one injections were done in other rheumatic diseases. In relation to this result there were also differences with regard to joint groups, antinuclear antibody (ANA) and HLA-B27 status, and sex. Side effects were rare: infections of skin or joints were not noted; skin and lipoatrophy were seen after 15 injections, necrosis of the hip in one case, luxation of 2 shoulders of one patient, and periarticular calcification in 3 patients. Intraarticular TH is an effective therapy for inflammatory joint disease in all subgroups of JCA. The risk of major complications is low. The median duration of improvement depends on the subgroup of the disease.

Comparison of corticosteroid, autologous blood or sclerosant injections for chronic tennis elbow.

PubMed

Branson, R; Naidu, K; du Toit, C; Rotstein, A H; Kiss, R; McMillan, D; Fooks, L; Coombes, B K; Vicenzino, B

2017-06-01

To compare three different ultrasound-guided injections for chronic tennis elbow. Assessor-blinded, randomized controlled comparative trial. 44 patients with clinically diagnosed tennis elbow, confirmed by Doppler ultrasound, received under ultrasound guidance, a single corticosteroid injection (n=14), or two injections (separated by 4 weeks) of either autologous blood (n=14) or polidocanol (n=16). Clinical and ultrasound examination was performed at baseline, 4, 12 and 26 weeks. Complete recovery or much improvement was greater for corticosteroid injection than autologous blood and polidocanol at 4 weeks (p<0.001, number needed to treat 1 (95% CI 1-2)). In contrast, at 26 weeks corticosteroid was significantly worse than polidocanol (p=0.004, number needed to harm 2 (1-6)). Recurrence after corticosteroid injection was significantly higher than autologous blood or polidocanol (p=0.007, number needed to harm 2 (1-4)). Corticosteroid injection produced greater reduction in tendon thickness and vascularity than autologous blood at 4 weeks only. Compared to autologous blood, polidocanol reduced tendon thickness at 4 and 12 weeks and reduced echogenicity and hyperaemia after 12 or 26 weeks respectively. Injections of corticosteroid cannot be recommended over polidocanol or autologous blood, because despite beneficial short-term effect there were inferior long-term effects. Whether polidocanol or autologous blood injections are effective is unknown, especially as their global effect profiles are not unlike previously reported for wait-and-see. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

GRIN: “GRoup versus INdividual physiotherapy following lower limb intra-muscular Botulinum Toxin-A injections for ambulant children with cerebral palsy: an assessor-masked randomised comparison trial”: study protocol

PubMed Central

2014-01-01

Background Cerebral palsy is the most common cause of physical disability in childhood. Spasticity is a significant contributor to the secondary impairments impacting functional performance and participation. The most common lower limb spasticity management is focal intramuscular injections of Botulinum Toxin-Type A accompanied by individually-delivered (one on one) physiotherapy rehabilitation. With increasing emphasis on improving goal-directed functional activity and participation within a family-centred framework, it is timely to explore whether physiotherapy provided in a group could achieve comparable outcomes, encouraging providers to offer flexible models of physiotherapy delivery. This study aims to compare individual to group-based physiotherapy following intramuscular Botulinum Toxin-A injections to the lower limbs for ambulant children with cerebral palsy aged four to fourteen years. Methods/Design An assessor-masked, block randomised comparison trial will be conducted with random allocation to either group-based or individual physiotherapy. A sample size of 30 (15 in each study arm) will be recruited. Both groups will receive six hours of direct therapy following Botulinum Toxin-A injections in either an individual or group format with additional home programme activities (three exercises to be performed three times a week). Study groups will be compared at baseline (T1), then at 10 weeks (T2, efficacy) and 26 weeks (T3, retention) post Botulinum Toxin-A injections. Primary outcomes will be caregiver/s perception of and satisfaction with their child’s occupational performance goals (Canadian Occupational Performance Measure) and quality of gait (Edinburgh Visual Gait Score) with a range of secondary outcomes across domains of the International Classification of Disability, Functioning and Health. Discussion This paper outlines the study protocol including theoretical basis, study hypotheses and outcome measures for this assessor-masked, randomised comparison trial comparing group versus individual models of physiotherapy following intramuscular injections of Botulinum Toxin-A to the lower limbs for ambulant children with cerebral palsy. Trial registration ACTRN12611000454976 PMID:24502231

Tenascin-C Prevents Articular Cartilage Degeneration in Murine Osteoarthritis Models.

PubMed

Matsui, Yuriyo; Hasegawa, Masahiro; Iino, Takahiro; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Sudo, Akihiro

2018-01-01

Objective The objective of this study was to determine whether intra-articular injections of tenascin-C (TNC) could prevent cartilage damage in murine models of osteoarthritis (OA). Design Fluorescently labeled TNC was injected into knee joints and its distribution was examined at 1 day, 4 days, 1 week, 2 weeks, and 4 weeks postinjection. To investigate the effects of TNC on cartilage degeneration after surgery to knee joints, articular spaces were filled with 100 μg/mL (group I), 10 μg/mL (group II) of TNC solution, or control (group III). TNC solution of 10 μg/mL was additionally injected twice after 3 weeks (group IV) or weekly after 1 week, 2 weeks, and 3 weeks (group V). Joint tissues were histologically assessed using the Mankin score and the modified Chambers system at 2 to 8 weeks after surgery. Results Exogenous TNC was maintained in the cartilage and synovium for 1 week after administration. Histological scores in groups I and II were better than scores in group III at 4 and 6 weeks, but progressive cartilage damage was seen in all groups 8 weeks postoperatively. Sequential TNC injections (groups IV and V) showed significantly better Mankin score than single injection (group II) at 8 weeks. Conclusion TNC administered exogenously remained in the cartilage of knee joints for 1 week, and could decelerate articular cartilage degeneration in murine models of OA. We also showed that sequential administration of TNC was more effective than a single injection. TNC could be an important molecule for prevention of articular cartilage damage.

Evaluation of group versus individual physiotherapy following lower limb intra-muscular Botulinum Toxin-Type A injections for ambulant children with cerebral palsy: A single-blind randomized comparison trial.

PubMed

Thomas, Rachel E; Johnston, Leanne M; Sakzewski, Leanne; Kentish, Megan J; Boyd, Roslyn N

2016-01-01

This study aimed to evaluate efficacy of group (GRP) versus individual (IND) physiotherapy rehabilitation following lower limb intramuscular injections of Botulinum Toxin-Type A (BoNT-A) for ambulant children with cerebral palsy (CP). Following lower limb BoNT-A injections, 34 children were randomly allocated to GRP (n=17; mean age 7y8m SD 2.0; 13 males; Gross Motor Function Classification System (GMFCS) I=5, II=8, III=4) or IND physiotherapy (n=17; mean age 8y7m SD 2.0; 11 males; GMFCS I=9, II=5, III=3). Primary outcomes were the Canadian Occupational Performance Measure (COPM) and Edinburgh Visual Gait Score (EVGS) assessed at baseline, 10 and 26 weeks post intervention. There were no baseline differences between groups. GRP intervention had greater, but not clinically meaningful, improvement in COPM satisfaction (estimated mean difference EMD 1.7, 95% CI 0.4-3.1; p<0.01) at 26 weeks. Both groups demonstrated clinically significant improvements in COPM performance and satisfaction, but minimal change in quality of gait (EVGS). Six hours of direct physiotherapy (either GRP or IND) with an additional indirect dose (median 16 episodes) of individualized home programme activities following lower limb BoNT-A injections, however, was inadequate to drive clinically meaningful changes in lower limb motor outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Yttrium-90 DOTA peptide chimeric L6 toxicity and therapeutic potential in nude mice with human breast tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeNardo, S.J.; Zhong, G.R.; Miers, L.A.

1994-05-01

Chimeric L6 MoAb (ChL6) as I-131 ChL6 has shown therapeutic promise for radioimmunotherapy in breast cancer patients. In order to enhance this therapeutic potential, we have developed an yttrium-90 (Y-90) ChL6 radiopharmaceutical by conjugating Y-90 DOTA peptide to ChL6 using DOTA-Gly-3L(p-isothiocyanato)-Phe-NH2. This DOTA peptide forms neutral complexes with trivalent metals allowing excess chelating agents and divalent metal complexes to be removed by ion exchange chromatography prior to conjugation, thus yielding a high Y-90/DOTA ratio on the final immune conjugate. Groups of 9-10 nude mice bearing subcutaneous 40-200 mg HBT 3477 xenographs were given 150,250,350,400,450 or 500 {mu}Ci of Y-90 DOTAmore » peptide ChL6 (specific activity 1.1-3.5 {mu}Ci/{mu}g). Live cell immunoreactivity was 73-80% and 100% Y-90 moved with ChL6 on SEC3000 HPLC and TLC. Peripheral blood counts, weight, tumor size, blood and body clearance of Y-90 were monitored for 10 weeks. Whole body autoradiography was performed at 1,3 and 5 days post injection at the 250 and 450 {mu}Ci dose levels. No mouse that received less than 450 {mu}Ci of Y-90 died. The LD50/30 was 479 {mu}Ci. The nadirs of RBC, WBC and platelets were 10-20 days post 479 {mu}Ci. The nadirs of RBC, WBC and platelets were 10-20 days post injection. The depth of the nadir was dose dependent but occured in all groups. In the lowest dose group having substantial tumor response (350{mu}Ci) mean tumor volume decreased by >50% and 5 of 19 tumors completely regressed over the 10 week follow-up. This is the greatest LD50/30 for Y-90 immunoconjugate reported in nude mice to date. These results confirm the significance of the biodistribution and autoradiographic studies demonstrating tumor uptake of 18 {plus_minus} 8% ID/gm with 3/1 tumor to liver and 8/1 tumor to bone ratios 1, 3, and 5 days post injection.« less

Intravenously Delivered Mesenchymal Stem Cells: Systemic Anti-Inflammatory Effects Improve Left Ventricular Dysfunction in Acute Myocardial Infarction and Ischemic Cardiomyopathy.

PubMed

Luger, Dror; Lipinski, Michael J; Westman, Peter C; Glover, David K; Dimastromatteo, Julien; Frias, Juan C; Albelda, M Teresa; Sikora, Sergey; Kharazi, Alex; Vertelov, Grigory; Waksman, Ron; Epstein, Stephen E

2017-05-12

Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm. To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post-acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities. Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O 2 , were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×10 6 ) were injected 24 hours post-myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×10 6 MSCs or saline intravenously 24 hours post-myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre-acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post-myocardial infarction were randomized to tail-vein injection of 2×10 6 MSCs, with injection repeated at week 3 (n=16) versus PBS control (n=16). MSCs significantly increased LV ejection fraction and decreased LV end-systolic volume. Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities. © 2017 American Heart Association, Inc.

Enriched environment protects the nigrostriatal dopaminergic system and induces astroglial reaction in the 6-OHDA rat model of Parkinson's disease.

PubMed

Anastasía, Agustín; Torre, Luciana; de Erausquin, Gabriel A; Mascó, Daniel H

2009-05-01

Enriched environment (EE) is neuroprotective in several animal models of neurodegeneration. It stimulates the expression of trophic factors and modifies the astrocyte cell population which has been said to exert neuroprotective effects. We have investigated the effects of EE on 6-hydroxydopamine (6-OHDA)-induced neuronal death after unilateral administration to the medial forebrain bundle, which reaches 85-95% of dopaminergic neurons in the substantia nigra after 3 weeks. Continuous exposure to EE 3 weeks before and after 6-OHDA injection prevents neuronal death (assessed by tyrosine hydroxylase staining), protects the nigrostriatal pathway (assessed by Fluorogold retrograde labeling) and reduces motor impairment. Four days after 6-OHDA injection, EE was associated with a marked increase in glial fibrillary acidic protein staining and prevented neuronal death (assessed by Fluoro Jade-B) but not partial loss of tyrosine hydroxylase staining in the anterior substantia nigra. These results robustly demonstrate that EE preserves the entire nigrostriatal system against 6-OHDA-induced toxicity, and suggests that an early post-lesion astrocytic reaction may participate in the neuroprotective mechanism.

The amelioration of cardiac dysfunction after myocardial infarction by the injection of keratin biomaterials derived from human hair.

PubMed

Shen, Deliang; Wang, Xiaofang; Zhang, Li; Zhao, Xiaoyan; Li, Jingyi; Cheng, Ke; Zhang, Jinying

2011-12-01

Cardiac dysfunction following acute myocardial infarction is a major cause of advanced cardiomyopathy. Conventional pharmacological therapies rely on prompt reperfusion and prevention of repetitive maladaptive pathways. Keratin biomaterials can be manufactured in an autologous fashion and are effective in various models of tissue regeneration. However, its potential application in cardiac regeneration has not been tested. Keratin biomaterials were derived from human hair and its structure morphology, carryover of beneficial factors, biocompatibility with cardiomyocytes, and in vivo degradation profile were characterized. After delivery into infarcted rat hearts, the keratin scaffolds were efficiently infiltrated by cardiomyocytes and endothelial cells. Injection of keratin biomaterials promotes angiogenesis but does not exacerbate inflammation in the post-MI hearts. Compared to control-injected animals, keratin biomaterials-injected animals exhibited preservation of cardiac function and attenuation of adverse ventricular remodeling over the 8 week following time course. Tissue western blot analysis revealed up-regulation of beneficial factors (BMP4, NGF, TGF-beta) in the keratin-injected hearts. The salient functional benefits, the simplicity of manufacturing and the potentially autologous nature of this biomaterial provide impetus for further translation to the clinic. Copyright © 2011 Elsevier Ltd. All rights reserved.

Treatment for hepatitis C virus infection among people who inject drugs attending opioid substitution treatment and community health clinics: the ETHOS Study.

PubMed

Grebely, Jason; Alavi, Maryam; Micallef, Michelle; Dunlop, Adrian J; Balcomb, Anne C; Phung, Nghi; Weltman, Martin D; Day, Carolyn A; Treloar, Carla; Bath, Nicky; Haber, Paul S; Dore, Gregory J

2016-02-01

To estimate adherence and response to therapy for chronic hepatitis C virus (HCV) infection among people with a history of injecting drug use. A secondary aim was to identify predictors of HCV treatment response. Prospective cohort recruited between 2009 and 2012. Participants were treated with peg-interferon alfa-2a/ribavirin for 24 (genotypes 2/3, G2/3) or 48 weeks (genotype 1, G1). Six opioid substitution treatment (OST) clinics, two community health centres and one Aboriginal community-controlled health organization providing drug treatment services in New South Wales, Australia. Among 415 people with a history of injecting drug use and chronic HCV assessed by a nurse, 101 were assessed for treatment outcomes (21% female). Study outcomes were treatment adherence and sustained virological response (SVR, undetectable HCV RNA >24 weeks post-treatment). Among 101 treated, 37% (n = 37) had recently injected drugs (past 6 months) and 62% (n = 63) were receiving OST. Adherence ≥ 80% was 86% (n = 87). SVR was 74% (75 of 101), with no difference observed by sex (males: 76%, females: 67%, P = 0.662). In adjusted analysis, age < 35 (versus ≥ 45 years) [adjusted odds ratio (aOR) = 5.06, 95% confidence interval (CI) = 1.47, 17.40] and on-treatment adherence ≥ 80% independently predicted SVR (aOR = 19.41, 95% CI = 3.61, 104.26]. Recent injecting drug use at baseline was not associated with SVR. People with a history of injecting drug use and chronic hepatitis C virus attending opioid substitution treatment and community health clinics can achieve adherence and responses to interferon-based therapy similar to other populations, despite injecting drugs at baseline. Younger age and adherence are predictive of improved response to hepatitis C virus therapy. © 2015 Society for the Study of Addiction.

Alternating Bi-Weekly Intravitreal Ranibizumab and Bevacizumab for Refractory Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment.

PubMed

Witkin, Andre J; Rayess, Nadim; Garg, Sunir J; Maguire, Joseph I; Storey, Philip; Kaiser, Richard S; Hsu, Jason; Vander, James F; Ho, Allen C

2017-01-01

To describe visual and anatomical outcomes following bi-weekly intravitreal ranibizumab/bevacizumab injections in eyes with refractory neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED). Retrospective, consecutive, interventional case series. Eighteen patients diagnosed with neovascular AMD that were refractory to anti-VEGF therapy and received alternating biweekly ranibizumab/bevacizumab injections were included. Patients with neovascular AMD and PED that were refractory to at least 11 monthly ranibizumab or bevacizumab injections were included in this study at a large, single retina practice. Following inclusion, patients received four bi-weekly alternating ranibizumab/bevacizumab intravitreal injections. After completing a course of four bi-weekly injections, patients were treated with variable regimens of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. The primary outcomes of the study included change in visual acuity (VA) and central foveal thickness (CFT) at eight weeks follow-up. Study eyes had previously received a mean of 22 intravitreal anti-VEGF injections. At enrollment, mean VA was 20/95 and mean CFT was 455 µm. After four bi-weekly anti-VEGF injections, mean VA improved to 20/65 (p < 0.001), and mean CFT decreased to 387 µm (p = 0.029). In patients with PED, there was a mean 27.9% reduction in height (p = 0.046) at eight weeks' follow-up. Four injections of bi-weekly alternating ranibizumab/bevacizumab improved visual acuity and reduced macular thickness in a number of patients with refractory neovascular AMD and PED.

Predictors of visual outcomes in patients with neovascular age-related macular degeneration treated with anti-vascular endothelial growth factor therapy: post hoc analysis of the VIEW studies.

PubMed

Lanzetta, Paolo; Cruess, Alan F; Cohen, Salomon Y; Slakter, Jason S; Katz, Todd; Sowade, Olaf; Zeitz, Oliver; Ahlers, Christiane; Mitchell, Paul

2018-04-16

Identify predictors for response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular (wet) age-related macular degeneration (nAMD). Retrospective, post hoc analysis of VIEW 1/2. Patients were randomized 1:1:1:1 to 0.5 mg intravitreal aflibercept (IVT-AFL) injection every 4 weeks (0.5q4); 2 mg IVT-AFL every 4 weeks (2q4); 2 mg IVT-AFL every 8 weeks (2q8) after an initial three injections at weeks 0, 4 and 8 or 0.5 mg intravitreal ranibizumab every 4 weeks (0.5q4). 1815 patients [IVT-AFL 2q4 (n = 613); IVT-AFL 2q8 (n = 607); ranibizumab 0.5q4 (n = 595)] were included. Baseline demographics/characteristics were evenly balanced. Younger age (49-69 years), lower visual acuity (VA) [10.0-≤45.0 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] and smaller choroidal neovascularization (CNV) size [0.0-≤3.1 disc areas (DA)] at baseline were associated with the most vision gain (≥15 letters) over 52 weeks (all nominal p < 0.0001).Younger age, higher baseline VA (>64.0-≤83.0 letters) and smaller CNV size were associated with a VA ≥20/40 at week 52. Predominantly classic CNV at baseline (nominal p = 0.0007), older age (≥90 years), lower baseline VA (10.0-≤ 45.0 ETDRS letters) and larger CNV size (>10.1-≤32.6 DA) were all associated with a VA ≤20/200 at week 52 (all nominal p < 0.0001). Along with treatment (nominal p < 0.0001), lower VA (p = 0.0166) and smaller central retinal thickness (both nominal p = 0.0190) were predictors for dry retina development. Younger age, lower VA and smaller CNV size at baseline were all associated with greater vision gains over 52 weeks while younger age, higher VA and smaller CNV size at treatment start were more likely to achieve best-corrected VA 20/40 or better after a year's treatment, suggesting the benefit of early anti-VEGF treatment. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Experimental evidence supports the abscess theory of development of radicular cysts.

PubMed

Nair, P N R; Sundqvist, Göran; Sjögren, Ulf

2008-08-01

The objective of this study was to experimentally induce inflammatory cysts in an animal model so as to test the hypothesis that radicular cysts develop via the "abscess pathway." Twenty-eight perforated custom-made Teflon cages were surgically implanted into defined locations in the back of 7 Sprague Dawley rats. A week after the implantation of the cages, a known quantity of freshly grown, close allogeneic oral keratinocytes in phosphate buffer solution (PBS) was injected into each cage. One cage per animal was treated as the control that received only epithelial cells. The remaining 3 cages of each animal were trials. Seven days post epithelial cell inoculation; a suspension of 0.2 mL of Fusobacterium nucleatum (10(8) bacteria per mL) was injected into each of the 3 trial cages. Two, 12, and 24 weeks after the inoculation of the bacteria, the cages were taken out, and the tissue contents were fixed and processed by correlative light and transmission electron microscopy. Sixteen of the 21 trial cages could be processed and yielded results. Inoculations of epithelial cells followed 1 week later by F. nucleatum into tissue cages resulted in the development inflammatory cysts in 2 of the 16 cages. The 2 cages contained a total of 4 cystic sites. None of the control cages showed the presence of any cyst-like pathology. Inflammatory cysts were induced by initiating acute inflammatory foci (abscess/necrotic area) by bacterial injection that got enclosed by a proliferating epithelium. This finding provides strong experimental evidence in support of the "abscess theory" of development of radicular cysts.

One session treatment for pediatric blood-injection-injury phobia: A controlled multiple baseline trial.

PubMed

Oar, Ella L; Farrell, Lara J; Waters, Allison M; Conlon, Elizabeth G; Ollendick, Thomas H

2015-10-01

The present study evaluated the effectiveness of a modified One Session Treatment (OST), which included an e-therapy homework maintenance program over 4 weeks for Blood-Injection-Injury (BII) phobia in children and adolescents. Using a single case, non-concurrent multiple-baseline design, 24 children and adolescents (8-18 years; 7 males, 17 females) with a primary diagnosis of BII phobia were randomly assigned to a one, two or three week baseline prior to receiving OST. Primary outcome measures included diagnostic severity, diagnostic status, and child and parent fear ratings. Secondary outcome measures included avoidance during behavioural avoidance tasks (BAT), global functioning and self and parent reported anxiety, fear and depression. Efficacy was assessed at post-treatment, 1-month, and 3-month follow-up. BII symptoms and diagnostic severity remained relatively stable during the baseline periods and then significantly improved following implementation of the intervention. Treatment response was supported by changes across multiple measures, including child, parent and independent clinician ratings. At post-treatment 8 of the 24 (33.33%) children were BII diagnosis free. Treatment gains improved at follow-ups with 14 (58.33%) children diagnosis free at 1-month follow-up and 15 (62.5%) diagnosis free at 3-month follow-up. Preliminary findings support the effectiveness of a modified OST approach for BII phobic youth with treatment outcomes improving over follow-up intervals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Viral vectors encoding endomorphins and serine histogranin attenuate neuropathic pain symptoms after spinal cord injury in rats.

PubMed

Nasirinezhad, Farinaz; Gajavelli, Shyam; Priddy, Blake; Jergova, Stanislava; Zadina, James; Sagen, Jacqueline

2015-01-07

The treatment of spinal cord injury (SCI)-induced neuropathic pain presents a challenging healthcare problem. The lack of available robust pharmacological treatments underscores the need for novel therapeutic methods and approaches. Due to the complex character of neuropathic pain following SCI, therapies targeting multiple mechanisms may be a better choice for obtaining sufficient long-term pain relief. Previous studies in our lab showed analgesic effects using combinations of an NMDA antagonist peptide [Ser1]histogranin (SHG), and the mu-opioid peptides endomorphins (EMs), in several pain models. As an alternative to drug therapy, this study evaluated the analgesic potential of these peptides when delivered via gene therapy. Lentiviruses encoding SHG and EM-1 and EM-2 were intraspinally injected, either singly or in combination, into rats with clip compression SCI 2 weeks following injury. Treated animals showed significant reduction in mechanical and thermal hypersensitivity, compared to control groups injected with GFP vector only. The antinociceptive effects of individually injected components were modest, but the combination of EMs and SHG produced robust and sustained antinociception. The onset of the analgesic effects was observed between 1-5 weeks post-injection and sustained without decrement for at least 7 weeks. No adverse effects on locomotor function were observed. The involvement of SHG and EMs in the observed antinociception was confirmed by pharmacologic inhibition using intrathecal injection of either the opioid antagonist naloxone or an anti-SHG antibody. Immunohistochemical analysis showed the presence of SHG and EMs in the spinal cord of treated animals, and immunodot-blot analysis of CSF confirmed the presence of these peptides in injected animals. In a separate group of rats, delayed injection of viral vectors was performed in order to mimic a more likely clinical scenario. Comparable and sustained antinociceptive effects were observed in these animals using the SHG-EMs combination vectors compared to the group with early intervention. Findings from this study support the potential for direct gene therapy to provide a robust and sustained alleviation of chronic neuropathic pain following SCI. The combination strategy utilizing potent mu-opioid peptides with a naturally-derived NMDA antagonist may produce additive or synergistic analgesic effects without the tolerance development for long-term management of persistent pain.

Short-term efficacy of sacroiliac joint corticosteroid injection based on arthrographic contrast patterns.

PubMed

Scholten, Paul M; Patel, Shounuck I; Christos, Paul J; Singh, Jaspal R

2015-04-01

To determine the relationship between sacroiliac joint (SIJ) contrast dispersal patterns during SIJ corticosteroid injection and pain relief at 2 and 8 weeks after the procedure. The association between the number of positive provocative SIJ physical examination maneuvers (minimum of one in all patients undergoing SIJ injection) and the patient's response to the intervention was also assessed. Retrospective chart review. Academic outpatient musculoskeletal practice. Fifty-four subjects who underwent therapeutic SIJ corticosteroid injection were screened for inclusion; 49 subjects were included in the final analysis. A retrospective review of electronic medical records identified patients who underwent SIJ corticosteroid injection. Fluoroscopic contrast flow patterns were categorized as type I (intra-articular injection with cephalad extension within the SIJ) or type II (intra-articular injection with poor cephalad extension). Self-reported numeric pain rating scale (NPRS) values at the time of injection and 2 and 8 weeks after the procedure were recorded. The number of positive provocative SIJ physical examination maneuvers at the time of the initial evaluation was also recorded. The primary outcome measure was the effect of contrast patterns (type I or type II) on change in NPRS values at 2 weeks and 8 weeks after the injection. The secondary outcome measure was the association between the number of positive provocative SIJ physical examination maneuvers and decrease in the level of pain after the procedure. At 2 weeks after the procedure, type I subjects demonstrated a significantly lower mean NPRS value compared with type II subjects (2.8 ± 1.4 versus 3.8 ± 1.6, respectively, P = .02). No statistically significant difference was observed at 8 weeks after the procedure. NPRS values were significantly reduced both at 2 weeks and 8 weeks, compared with baseline, in both subjects identified as having type I flow and those with type II flow (P < .0001 for all within-group comparisons). Fluoroscopically guided corticosteroid injections into the SIJ joint are effective in decreasing NPRS values in patients with SIJ-mediated pain. Delivery of corticosteroid to the superior portion of the SIJ leads to a greater reduction in pain at 2 weeks, but not at 8 weeks. Patients with at least one positive provocative maneuver should benefit from an intra-articular corticosteroid injection. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Reorganization of laryngeal motoneurons after crush injury in the recurrent laryngeal nerve of the rat

PubMed Central

Hernández-Morato, Ignacio; Valderrama-Canales, Francisco J; Berdugo, Gabriel; Arias, Gonzalo; McHanwell, Stephen; Sañudo, José; Vázquez, Teresa; Pascual-Font, Arán

2013-01-01

Motoneurons innervating laryngeal muscles are located in the nucleus ambiguus (Amb), but there is no general agreement on the somatotopic representation and even less is known on how an injury in the recurrent laryngeal nerve (RLN) affects this pattern. This study analyzes the normal somatotopy of those motoneurons and describes its changes over time after a crush injury to the RLN. In the control group (control group 1, n = 9 rats), the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were injected with cholera toxin-B. In the experimental groups the left RLN of each animal was crushed with a fine tip forceps and, after several survival periods (1, 2, 4, 8, 12 weeks; minimum six rats per time), the PCA and TA muscles were injected as described above. After each surgery, the motility of the vocal folds was evaluated. Additional control experiments were performed; the second control experiment (control group 2, n = 6 rats) was performed labeling the TA and PCA immediately prior to the section of the superior laryngeal nerve (SLN), in order to eliminate the possibility of accidental labeling of the cricothyroid (CT) muscle by spread from the injection site. The third control group (control group 3, n = 5 rats) was included to determine if there is some sprouting from the SLN into the territories of the RLN after a crush of this last nerve. One week after the crush injury of the RLN, the PCA and TA muscles were injected immediately before the section of the SLN. The results show that a single population of neurons represents each muscle with the PCA in the most rostral position followed caudalwards by the TA. One week post-RLN injury, both the somatotopy and the number of labeled motoneurons changed, where the labeled neurons were distributed randomly; in addition, an area of topographical overlap of the two populations was observed and vocal fold mobility was lost. In the rest of the survival periods, the overlapping area is larger, but the movement of the vocal folds tends to recover. After 12 weeks of survival, the disorganization within the Amb is the largest, but the number of motoneurons is similar to control, and all animals recovered the movement of the left vocal fold. Our additional controls indicate that no tracer spread to the CT muscle occurred, and that many of the labeled motoneurons from the PCA after 1 week post-RLN injury correspond to motoneurons whose axons travel in the SLN. Therefore, it seems that after RLN injury there is a collateral sprouting and collateral innervation. Although the somatotopic organization of the Amb is lost after a crush injury of the RLN and does not recover in the times studied here, the movement of the vocal folds as well as the number of neurons that supply the TA and the PCA muscles recovered within 8 weeks, indicating that the central nervous system of the rat has a great capacity of plasticity. PMID:23444899

THE REAL ESTATE OF MYOBLAST CARDIAC TRANSPLANTATION – NEGATIVE REMODELING IS ASSOCIATED WITH LOCATION

PubMed Central

McCue, Jonathan D.; Swingen, Cory; Feldberg, Tanya; Caron, Gabe; Kolb, Adam; Denucci, Christopher; Prabhu, Somnath; Motilall, Randy; Breviu, Brian; Taylor, Doris A.

2009-01-01

Background Skeletal myoblast (SKMB) transplantation has been proposed as a therapy for ischemic cardiomyopathy due to its possible role in myogenesis. The relative safety and efficacy based on location within scar is not known. We hypothesized that SKMB transplanted into peripheral scar (compared to central scar) would more effectively attenuate negative left ventricular (LV) remodeling but at the risk of arrhythmia. Methods 34 New Zealand White rabbits underwent mid-left anterior descending artery (LAD) ligation to produce a transmural LV infarction. One month after LAD ligation SKMBs were injected either in the scar center (n=13) or scar periphery (n=10) and compared to saline injection (n=11). Holter monitoring and MRI was performed pre-injection; Holter monitoring was continued until two weeks post injection, with follow-up MRI at one month. Results Centrally-treated animals demonstrated increased LV end systolic volume, end diastolic volume and mass that correlated with injected cell number. There was a trend toward attenuation of negative LV remodeling in peripherally-treated animals compared to vehicle. Significant late ectopy was seen in several centrally-injected animals with no late ectopy seen in peripherally-injected animals. Conclusions We noted untoward effects with respect to negative LV remodeling following central injection, suggesting that transplanted cell location with respect to scar may be a key factor in the safety and efficacy of SKMB cardiac transplantation. Administration of SKMBs into peripheral scar appears safe with a trend toward improved function in comparison to sham injection. PMID:18187097

Intradetrusor Injections of Onabotulinum Toxin-A in Children With Urinary Incontinence due to Neurogenic Detrusor Overactivity Refractory to Antimuscarinic Treatment.

PubMed

Tarcan, Tufan; Akbal, Cem; Sekerci, Cağri A; Top, Tuncay; Simşek, Ferruh

2014-04-01

This was a prospective single-arm study to assess the efficacy and safety of intradetrusor injections of onabotulinum toxin-A in children with urinary incontinence associated with neurogenic detrusor overactivity due to myelomeningocele. All patients had failed the first-line treatment of a combination of oral antimuscarinics and intermittent catheterization. The study group consisted of 31 children with myelomeningocele with a mean age of 7.95 years (range, 5-3 years) who were followed up for a mean of 29 weeks. The amount of onabotulinum toxin A injected was 10 U/kg with a maximal dose of 300 U. There were 20 to 30 injection sites with rigid cystoscopic guidance under general anesthesia. Thirty of 31 patients reported dryness between intermittent catheterization intervals. The mean reduction in maximum detrusor pressure and the mean increase in maximum cystometric capacity from baseline were 53% and 51.5%, respectively, 6 weeks after injection. We found a 324% increase in mean bladder compliance and a 57% increase in mean intermittent catheterization volumes. The mean duration of efficacy was 28 weeks with a single injection and 36 weeks for repeated injections (minimum, 16 weeks; maximum, 52 weeks). The mean time interval between repeated onabotulinum toxin-A injections was 7 months (maximum, 13 months). Intradetrusor injections of onabotulinum toxin-A were well tolerated. Onabotulinum toxin-A injections into the bladder wall provide a significant symptomatic and urodynamic improvement in children with neurogenic detrusor overactivity due to myelomeningocele who are on intermittent catheterization. The treatment seems to be safe and very well tolerated.

Improvement of upper trunk posture during walking in hemiplegic patients after injections of botulinum toxin into the arm.

PubMed

Hefter, Harald; Rosenthal, Dietmar

2017-03-01

It has been hypothesized that altered trunk movements during gait in post-stroke patients or children with cerebral palsy are compensatory to lower limb impairment. Improvement of trunk movements and posture after injections of botulinum toxin into the affected arm would be at variance with this hypothesis and hint towards a multifactorial trunk control deficit. Clinical gait analysis was performed in 11 consecutively recruited hemiplegic patients immediately before and 4weeks after a botulinum toxin type A-injection into the affected arm. Kinematic data were collected using an 8 camera optical motion-capturing system and reflective skin-markers were attached according to a standard plug-in-gait model. Deviation of the trunk in lateral and forward direction and the trajectory of the C7-marker in a sacrum-fixed horizontal plane were analyzed in addition to classical gait parameters. The Wilson-signed-rank test was used for pre/post-botulinum toxin comparisons. After botulinum toxin injections a significant improvement of forearm flexion scores from 2.57 to 2.0 (p<0.014), and a reduced lateral deviation of the upper trunk from 3.5degrees to 2.5degrees (p<0.014) were observed. Free-walkers tended to walk faster (p<0.046, 1-sided), with reduced pre-swing duration of both legs and an increased step length of the non-affected leg. The C7-marker trajectory was shifted towards the midline. Injections of botulinum toxin into the affected arm of hemiplegic patients improve abnormal trunk lateral flexion. This shift of the center of mass of the upper body towards the midline improves various gait parameters including gait speed. Copyright © 2017. Published by Elsevier Ltd.

Cryopreserved human amniotic membrane injection for plantar fasciitis: a randomized, controlled, double-blind pilot study.

PubMed

Hanselman, Andrew E; Tidwell, John E; Santrock, Robert D

2015-02-01

Treatment options for plantar fasciitis have resulted in varied patient outcomes. The aim of this study was to compare a novel treatment, cryopreserved human amniotic membrane (c-hAM), to a traditional treatment, corticosteroid. Our hypothesis was that c-hAM would be safe and comparable to corticosteroids for plantar fasciitis in regard to patient outcomes. A randomized, controlled, double-blind, single-center pilot study was completed. Patients were randomized into one of 2 treatment groups: c-hAM or corticosteroid. Patients received an injection at their initial baseline visit with an option for a second injection at their first 6-week follow-up. Total follow-up was obtained for 12 weeks after the most recent injection. The primary outcome measurement was the Foot Health Status Questionnaire (FHSQ). The secondary outcome measurements were the Visual Analog Scale (VAS) and verbally reported percentage improvement. Data were analyzed between groups for the 2 different cohorts (1 injection versus 2 injections). Twenty-three patients had complete follow-up. Fourteen were randomized to receive corticosteroid and 9 were randomized to receive c-hAM. Three patients in each group received second injections. With the numbers available, the majority of outcome measurements showed no statistical difference between groups. The corticosteroid did, however, have greater FHSQ shoe fit improvement (P = .0244) at 6 weeks, FHSQ general health improvement (P = .0132) at 6 weeks, and verbally reported improvement (P = .041) at 12 weeks in the one-injection cohort. Cryopreserved hAM had greater FHSQ foot pain improvement (P = .0113) at 18 weeks in the 2-injection cohort. Cryopreserved hAM injection may be safe and comparable to corticosteroid injection for treatment of plantar fasciitis. This is a pilot study and requires further investigation. Level I, prospective randomized trial. © The Author(s) 2014.

Spontaneous spinal epidural haematoma: a rare cause of quadriplegia in the post-partum period.

PubMed

Bose, S; Ali, Z; Rath, G P; Prabhakar, H

2007-12-01

Spontaneous spinal epidural haematoma (SSEH) is a rare cause of neurological deficit in the pregnant and post-partum patients. However, SSEH with associated myelitis presenting as quadriplegia and respiratory paralysis in the post-partum period has never been reported. We report the development of acute onset quadriplegia progressing to respiratory arrest in a 24-yr-old woman 2 weeks after normal vaginal delivery. There was no history suggestive of any coagulopathy (inherited or acquired), eclampsia, pre-existing neurological deficit, or iatrogenic manipulations such as spinal/epidural injections. Magnetic resonance imaging revealed a posterior epidural haematoma extending from C4-C7 and areas of signal changes in spinal cord from cervicomedullary junction to D5 level (suggestive of demyelination). We highlight this rare cause of quadriplegia; focusing on the altered dynamics of the epidural vasculature in the peripartum period leading to SSEH.

Fibrosarcomas at presumed sites of injection in dogs: characteristics and comparison with non-vaccination site fibrosarcomas and feline post-vaccinal fibrosarcomas.

PubMed

Vascellari, M; Melchiotti, E; Bozza, M A; Mutinelli, F

2003-08-01

Fifteen fibrosarcomas, surgically excised from presumed sites of injection in dogs, and 10 canine fibrosarcomas excised from sites not used for injection were histologically and immunohistochemically compared with 20 feline post-vaccinal fibrosarcomas. Canine fibrosarcomas from presumed injection sites were of grade I (3), of grade II (4) and grade III (8). Two fibrosarcomas from non-injection sites were of grade I, four of grade II and four of grade III. Feline samples were classified as grade I (2), grade II (4) and grade III (14). All fibrosarcomas from presumed injection sites of both species showed lymphocytic inflammatory infiltration located at the tumour periphery, while two canine fibrosarcomas from non-injection sites showed perivascular inflammatory infiltration within the neoplasm. All samples were immunohistochemically examined for vimentin, smooth muscle actin, muscle specific actin and desmin expression. All tumours were positive for vimentin. Ten canine fibrosarcomas from presumed injection sites and all feline samples contained cells consistent with a myofibroblastic immunophenotype. Aluminium deposits were detected in eight canine fibrosarcomas from presumed injection sites and 11 feline post-vaccinal fibrosarcomas by the aurintricarboxylic acid method. The present study identifies distinct similarities between canine fibrosarcomas from presumed injection sites and feline post-vaccinal fibrosarcomas, suggesting the possibility of the development of post-injection sarcomas not only in cats, but also in dogs.

Harm reduction measures and injecting inside prison versus mandatory drugs testing: results of a cross sectional anonymous questionnaire survey. The European Commission Network on HIV Infection and Hepatitis in Prison.

PubMed Central

Bird, A. G.; Gore, S. M.; Hutchinson, S. J.; Lewis, S. C.; Cameron, S.; Burns, S.

1997-01-01

OBJECTIVES: (a) To determine both the frequency of injecting inside prison and use of sterilising tablets to clean needles in the previous four weeks; (b) to assess the efficiency of random mandatory drugs testing at detecting prisoners who inject heroin inside prison; (c) to determine the percentage of prisoners who had been offered vaccination against hepatitis B. DESIGN: Cross sectional willing anonymous salivary HIV surveillance linked to a self completion risk factor questionnaire. SETTING: Lowmoss prison, Glasgow, and Aberdeen prison on 11 and 30 October 1996. SUBJECTS: 293 (94%) of all 312 inmates at Lowmoss and 146 (93%) of all 157 at Aberdeen, resulting in 286 and 143 valid questionnaires. MAIN OUTCOME MEASURES: Frequency of injecting inside prison in the previous four weeks by injector inmates who had been in prison for at least four weeks. RESULTS: 116 (41%) Lowmoss and 53 (37%) Aberdeen prisoners had a history of injecting drug use but only 4% of inmates (17/395; 95% confidence interval 2% to 6%) had ever been offered vaccination against hepatitis B. 42 Lowmoss prisoners (estimated 207 injections and 258 uses of sterilising tablets) and 31 Aberdeen prisoners (229 injections, 221 uses) had injected inside prison in the previous four weeks. The prisons together held 112 injector inmates who had been in prison for more than four weeks, of whom 57 (51%; 42% to 60%) had injected in prison in the past four weeks; their estimated mean number of injections was 6.0 (SD 5.7). Prisoners injecting heroin six times in four weeks will test positive in random mandatory drugs testing on at most 18 days out of 28. CONCLUSIONS: Sterilising tablets and hepatitis B vaccination should be offered to all prisoners. Random mandatory drugs testing seriously underestimates injector inmates' harm reduction needs. PMID:9233321

Age-related macular degeneration: using morphological predictors to modify current treatment protocols.

PubMed

Ashraf, Mohammed; Souka, Ahmed; Adelman, Ron A

2018-03-01

To assess predictors of treatment response in neovascular age-related macular degeneration (AMD) in an attempt to develop a patient-centric treatment algorithm. We conducted a systematic search using PubMed, EMBASE and Web of Science for prognostic indicators/predictive factors with the key words: 'age related macular degeneration', 'neovascular AMD', 'choroidal neovascular membrane (CNV)', 'anti-vascular endothelial growth factor (anti-VEGF)', 'aflibercept', 'ranibizumab', 'bevacizumab', 'randomized clinical trials', 'post-hoc', 'prognostic', 'predictive', 'response' 'injection frequency, 'treat and extend (TAE), 'pro re nata (PRN)', 'bi-monthly' and 'quarterly'. We only included studies that had an adequate period of follow-up (>1 year), a single predefined treatment regimen with a predetermined re-injection criteria, an adequate number of patients, specific morphological [optical coherence tomography (OCT)] criteria that predicted final visual outcomes and injection frequency and did not include switching from one drug to the other. We were able to identify seven prospective studies and 16 retrospective studies meeting our inclusion criteria. There are several morphological and demographic prognostic indicators that can predict response to therapy in wet AMD. Smaller CNV size, subretinal fluid (SRF), retinal angiomatous proliferation (RAP) and response to therapy at 12 weeks (visual, angiographic or OCT) can all predict good visual outcomes in patients receiving anti-VEGF therapy. Patients with larger CNV, older age, pigment epithelial detachment (PED), intraretinal cysts (IRC) and vitreomacular adhesion (VMA) achieved less visual gains. Patients having VMA/VMT required more intensive treatment with increased treatment frequency. Patients with both posterior vitreous detachment (PVD) and SRF require infrequent injections. Patients with PED are prone to recurrences of fluid activity with a reduction in visual acuity (VA). A regimen that involves less intensive therapy and extended follow-up intervals (4 weekly) can be suggested for patients who show adequate visual response and have both SRF and PVD at baseline. In addition, patients with poor prognostic indicators such as IRC, VMA, large CNV size, older age and poor response at 12 weeks should be extended very cautiously with the possibility of fixed monthly/bimonthly (every 2 months) treatments if they fail to achieve dryness. Patients with PED at baseline should receive monthly/bimonthly injections of anti-VEGF therapy or can be extended very cautiously (two weekly intervals) using a TAE protocol. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Treating Self-Injection Phobia in Patients Prescribed Injectable Medications: A Case Example Illustrating a Six-Session Treatment Model

ERIC Educational Resources Information Center

Cox, Darcy; Mohr, David C.; Epstein, Lucy

2004-01-01

This article provides a case description of a patient with multiple sclerosis prescribed interferon beta-1a (IFN[beta]-1a), a weekly intramuscular injection, who met "DSM-IV" criteria for specific phobia, blood/injection type. This patient successfully completed a 6-week manualized cognitive-behavioral treatment for self-injection anxiety. Issues…

Cortical and subcortical connections of V1 and V2 in early postnatal macaque monkeys.

PubMed

Baldwin, Mary K L; Kaskan, Peter M; Zhang, Bin; Chino, Yuzo M; Kaas, Jon H

2012-02-15

Connections of primary (V1) and secondary (V2) visual areas were revealed in macaque monkeys ranging in age from 2 to 16 weeks by injecting small amounts of cholera toxin subunit B (CTB). Cortex was flattened and cut parallel to the surface to reveal injection sites, patterns of labeled cells, and patterns of cytochrome oxidase (CO) staining. Projections from the lateral geniculate nucleus and pulvinar to V1 were present at 4 weeks of age, as were pulvinar projections to thin and thick CO stripes in V2. Injections into V1 in 4- and 8-week-old monkeys labeled neurons in V2, V3, middle temporal area (MT), and dorsolateral area (DL)/V4. Within V1 and V2, labeled neurons were densely distributed around the injection sites, but formed patches at distances away from injection sites. Injections into V2 labeled neurons in V1, V3, DL/V4, and MT of monkeys 2-, 4-, and 8-weeks of age. Injections in thin stripes of V2 preferentially labeled neurons in other V2 thin stripes and neurons in the CO blob regions of V1. A likely thick stripe injection in V2 at 4 weeks of age labeled neurons around blobs. Most labeled neurons in V1 were in superficial cortical layers after V2 injections, and in deep layers of other areas. Although these features of adult V1 and V2 connectivity were in place as early as 2 postnatal weeks, labeled cells in V1 and V2 became more restricted to preferred CO compartments after 2 weeks of age. Copyright © 2011 Wiley-Liss, Inc.

Grafting of neural stem and progenitor cells to the hippocampus of young, irradiated mice causes gliosis and disrupts the granule cell layer

PubMed Central

Sato, Y; Shinjyo, N; Sato, M; Osato, K; Zhu, C; Pekna, M; Kuhn, H G; Blomgren, K

2013-01-01

Ionizing radiation persistently reduces the pool of neural stem and progenitor cells (NSPCs) in the dentate gyrus (DG) of the hippocampus, which may explain some of the learning deficits observed in patients treated with radiotherapy, particularly pediatric patients. A single dose of 8 Gy irradiation (IR) was administered to the brains of postnatal day 14 (P14) C57BL/6 mice and 1.0 × 105 bromodeoxyuridine-labeled, syngeneic NSPCs were injected into the hippocampus 1 day, 1 week or 6 weeks after IR. Cell survival and phenotype were evaluated 5 weeks after grafting. When grafted 1 day post-IR, survival and neuronal differentiation of the transplanted NSPCs were lower in irradiated brains, whereas the survival and cell fate of grafted cells were not significantly different between irradiated and control brains when transplantation was performed 1 or 6 weeks after IR. A young recipient brain favored neuronal development of grafted cells, whereas the older recipient brains displayed an increasing number of cells developing into astrocytes or unidentified cells. Injection of NSPCs, but not vehicle, induced astrogliosis and reduced thickness of the dorsal blade of the GCL after 5 months. In summary, we demonstrate that age and interval between IR and grafting can affect survival and differentiation of grafted NSPCs. The observed long-term gliosis and degeneration warrant caution in the context of NSPC grafting for therapeutical purposes. PMID:23598403

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu Shunying; Chen Yundai; Li Libing

Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrastmore » echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 +- 9.01 vs. 41.94 +- 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 +- 1303 vs. 1667 +- 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 +- 1084 vs. 1566 +- 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.« less

Effect of the non-steroidal anti-inflammatory drug, carprofen, on weaned sheep following non-surgical mulesing by intradermal injection of cetrimide.

PubMed

Colditz, I G; Lloyd, J B; Paull, D R; Lee, C; Giraudo, A; Pizzato, C; Fisher, A D

2009-01-01

To assess in weaned lambs the palliative effects of the non-steroidal anti-inflammatory drug, carprofen, following intradermal injection of cetrimide to induce non-surgical mulesing. We allocated 40 weaned lambs (20-22 weeks old) to four groups of 10 animals: (1) control, 2) conventional surgical mules, (3) intradermal treatment and (4) intradermal treatment + carprofen. Non-surgical mulesing was induced by intradermal injection of 4% (w/w) cetrimide + 3% (w/w) polyvinylpyrrolidone in water. In group 4, carprofen (4 mg/kg, SC) was administered 1 h before intradermal treatment. Five weaners, including an animal from each treatment, were run in each pen. Neutrophil to lymphocyte ratio, cortisol, beta-endorphin and haptoglobin levels and rectal temperature were monitored at least daily for the first 7 days after treatment, then weekly until day 28. Body weight was measured weekly and behaviour was measured every 15 min for 12 h on the day of treatment, then on days 1, 2, 4, 6, 12, 21 and 28 following treatment. The intradermal treatment resulted in high fever and elevated blood cortisol by 12 h. Rectal temperatures were significantly elevated until 5 days after treatment, cortisol was elevated until 3 days after treatment, haptoglobin for at least 7 days after treatment and the neutrophil to lymphocyte ratio until 4 days after treatment. Average daily gain was depressed in the week following treatment. Abnormal behaviours (hunched standing, stiff walking, pawing, lateral lying and lying intention) were increased on the day of treatment and for 6 days post treatment. Carprofen reduced the time spent in abnormal behaviours by approximately two-thirds but did not ameliorate the physiological responses to the intradermal treatment. In weaner sheep, carprofen ameliorated the behavioural responses, but was unable to provide relief from the intense and sustained physiological responses to non-surgical mulesing by intradermal injection of cetrimide. Systemic side-effects may be unavoidable with formulations based on quaternary ammonium compounds that are designed to reduce the risk of fly strike in sheep by remodelling breech tissue through induction of tissue necrosis.

Intermittent calorie restriction enhances epithelial-mesenchymal transition through the alteration of energy metabolism in a mouse tumor model

PubMed Central

Kusuoka, Osamu; Fujiwara-Tani, Rina; Nakashima, Chie; Fujii, Kiyomu; Ohmori, Hitoshi; Mori, Takuya; Kishi, Shingo; Miyagawa, Yoshihiro; Goto, Kei; Kawahara, Isao; Kuniyasu, Hiroki

2018-01-01

The effect of intermittent calorie restriction (ICR) on cancer is controversial. In this study, we examined the effects of ICR and food content in syngeneic BALB/c mice injected with CT26 mouse colon cancer cells. Mice were subjected to 24-h fasting once a week for 4 weeks, and then provided with a control, high-calorie, or trans fatty acid-rich diet. While ICR resulted in increases in tumor weights, metastasis and in the number of cancer stem cells (CSCs) in the tumors or blood of mice fed the control and high-fat diets, it had no effect on body weight after 4 weeks. In particular, we detected increases in the numbers of CSCs in the tumor or blood on the day after starvation, when food overconsumption was detected. Conversely, continuous calorie restriction had no effect on tumor weight, metastasis, or the number of CSCs in tumors or blood. In the post-starvation period, energy metabolism in the tumor was altered from oxidative phosphorylation to glycolysis/lactate fermentation, with the acquisition of the epithelial-mesenchymal transition (EMT) phenotype. Hyperglycemia at the post-starvation period induced the expression of insulin-like growth factor-1, hypoxia-induced factor-1α and Nanog, as well as the phosphorylation of Stat3. Taken together, these findings suggest that ICR induces an increase in the number of CSCs and enhances EMT by promoting the Warburg/Crabtree effect following post-fasting food overconsumption. PMID:29345287

A phase II trial of vaccination with autologous, tumor-derived heat-shock protein peptide complexes Gp96, in combination with GM-CSF and interferon-alpha in metastatic melanoma patients.

PubMed

Pilla, Lorenzo; Patuzzo, Roberto; Rivoltini, Licia; Maio, Michele; Pennacchioli, Elisabetta; Lamaj, Elda; Maurichi, Andrea; Massarut, Samuele; Marchianò, Alfonso; Santantonio, Cristina; Tosi, Diego; Arienti, Flavio; Cova, Agata; Sovena, Gloria; Piris, Adriano; Nonaka, Daisuke; Bersani, Ilaria; Di Florio, Annabella; Luigi, Mariani; Srivastava, Pramod K; Hoos, Axel; Santinami, Mario; Parmiani, Giorgio

2006-08-01

The aim of this study was to determine the immunogenicity and antitumor activity of autologous, tumor-derived heat shock protein gp96-peptide complex vaccine (HSPPC-96; Oncophage given with GM-CSF and IFN-alpha in pre-treated metastatic (AJCC stage IV) melanoma patients. Patients underwent surgical resection of metastatic lesions for HSPPC-96 production. HSPPC-96 was administered subcutaneously (s.c.) in four weekly intervals (first cycle). Patients with more available vaccine and absence of progressive disease received four additional injections in 2-week intervals (second cycle) or more. GM-CSF was given s.c. at the same site at days -1, 0 and +1, while IFN-alpha (3 MU) was administered s.c. at a different site at days +4 and +6. Antigen-specific anti-melanoma T and NK lymphocyte response was assessed by enzyme-linked immunospot assay on peripheral blood mononuclear cells obtained before and after vaccination. Thirty-eight patients were enrolled, 20 received at least four injections (one cycle) of HSPPC-96 and were considered assessable. Toxicity was mild and most treatment-related adverse events were local erythema and induration at the injection site. Patients receiving at least four injections of HSPPC-96 were considered evaluable for clinical response: of the 18 patients with measurable disease post surgery, 11 showed stable disease (SD). The ELISPOT assay revealed an increased class I HLA-restricted T and NK cell-mediated post-vaccination response in 5 out of 17 and 12 out of the 18 patients tested, respectively. Four of the five class I HLA-restricted T cell responses fall in the group of SD patients. Vaccination with autologous HSPPC-96 together with GM-CSF and IFN-alpha is feasible and accompanied by mild local and systemic toxicity. Both tumor-specific T cell-mediated and NK cell responses were generated in a proportion of patients. Clinical activity was limited to SD. However, both immunological and clinical responses were not improved as compared with those recorded in a previous study investigating HSPPC-96 monotherapy.

Fluoroscopically Guided Sacroiliac Joint Injections: Comparison of the Effects of Intraarticular and Periarticular Injections on Immediate and Short-Term Pain Relief.

PubMed

Nacey, Nicholas C; Patrie, James T; Fox, Michael G

2016-11-01

The purpose of this study was to determine whether intraarticular sacroiliac joint injections provide greater immediate and short-term pain relief than periarticular sacroiliac joint injections do. The records of all fluoroscopically guided sacroiliac joint injections performed over a 4-year period were identified. Patients who received an injection of 0.5 mL of bupivacaine and 0.5 mL (20 mg) of triamcinolone and who had preinjection, immediate, and 1-week postinjection pain scores (0-10 numeric scale) were included. Images from the procedures were retrospectively reviewed by two musculoskeletal radiologists to determine intraarticular or periarticular administration of the injection with discrepancies resolved by consensus. One hundred thirteen injections in 99 patients (65 women, 34 men; mean age, 59.4 years) met the inclusion criteria. There were 55 intraarticular and 58 periarticular injections. The mean preinjection, immediate, and 1-week postinjection pain scores for the intraarticular injections were 6.0, 1.6, and 4.1 and for the periarticular injections were 6.1, 2.0, and 4.2. The mean immediate and 1-week postinjection pain reduction were statistically significant in both groups (p < 0.001). After adjustment for age, sex, preinjection pain score, time of year, and indication for injection, no significant difference in the preinjection to immediately postinjection change in pain between intraarticular and periarticular injections (mean change, 0.37; p = 0.319) or in the preinjection to 1-week postinjection change in pain (mean change, 0.06; p = 0.888) was noted. The mean fluoroscopy times were 42.4 seconds for intraarticular injections and 60.5 seconds for periarticular injections (p = 0.32). Although both intraarticular and periarticular sacroiliac joint injections provide statistically significant immediate and 1-week postinjection pain relief, no significant difference in the degree of pain relief achieved with intraarticular and periarticular injections was noted.

Prevention of polydimethylsiloxane microsphere migration using a mussel-inspired polydopamine coating for potential application in injection therapy.

PubMed

Chung, Eun-Jae; Jun, Dae-Ryong; Kim, Dong-Wook; Han, Mi-Jung; Kwon, Tack-Kyun; Choi, Sung-Wook; Kwon, Seong Keun

2017-01-01

The use of injectable bulking agents is a feasible alternative procedure for conventional surgical therapy. In this study, poly(dimethylsiloxane) (PDMS) microspheres coated with polydopamine (PDA) were developed as a potential injection agent to prevent migration in vocal fold. Uniform PDMS microspheres are fabricated using a simple fluidic device and then coated with PDA. Cell attachment test reveals that the PDA-coated PDMS (PDA-PDMS) substrate favors cell adhesion and attachment. The injected PDA-PDMS microspheres persist without migration on reconstructed axial CT images, whereas, pristine PDMS locally migrates over a period of 12 weeks. The gross appearance of the implants retrieved at 4, 8, 12 and 34 weeks indicates that the PDA-PDMS group maintained their original position without significant migration until 34 weeks after injection. By contrast, there is diffuse local migration of the pristine PDMS group from 4 weeks after injection. The PDA-coated PDMS microspheres can potentially be used as easily injectable, non-absorbable filler without migration.

Prevention of polydimethylsiloxane microsphere migration using a mussel-inspired polydopamine coating for potential application in injection therapy

PubMed Central

Kim, Dong-Wook; Han, Mi-Jung; Kwon, Tack-Kyun; Choi, Sung-Wook

2017-01-01

The use of injectable bulking agents is a feasible alternative procedure for conventional surgical therapy. In this study, poly(dimethylsiloxane) (PDMS) microspheres coated with polydopamine (PDA) were developed as a potential injection agent to prevent migration in vocal fold. Uniform PDMS microspheres are fabricated using a simple fluidic device and then coated with PDA. Cell attachment test reveals that the PDA-coated PDMS (PDA-PDMS) substrate favors cell adhesion and attachment. The injected PDA-PDMS microspheres persist without migration on reconstructed axial CT images, whereas, pristine PDMS locally migrates over a period of 12 weeks. The gross appearance of the implants retrieved at 4, 8, 12 and 34 weeks indicates that the PDA-PDMS group maintained their original position without significant migration until 34 weeks after injection. By contrast, there is diffuse local migration of the pristine PDMS group from 4 weeks after injection. The PDA-coated PDMS microspheres can potentially be used as easily injectable, non-absorbable filler without migration. PMID:29095854

Efficacy of mesotherapy in facial rejuvenation: a histological and immunohistochemical evaluation

PubMed Central

El-Domyati, Moetaz; El-Ammawi, Tarek S.; Moawad, Osama; El-Fakahany, Hasan; Medhat, Walid; Mahoney, Mỹ G.; Uitto, Jouni

2012-01-01

Background Mesotherapy, commonly known as “biorejuvenation” or “biorevitalization”, is a technique used to rejuvenate the skin by means of a transdermal injection of a multivitamin solution and natural plant extracts that are thought to improve the signs of skin aging. Objectives This prospective study aimed to evaluate the clinical effect of mesotherapy applied to periorbital wrinkles and to quantitatively evaluate histological changes in the skin occurring in response to the same treatment. Methods Six volunteers with Fitzpatrick skin types III or IV and Glogau class I–III wrinkles were subjected to a three-month course of mesotherapy injections in the periocular area (six sessions administered at two-week intervals). Standard photographs and skin biopsies were obtained from the treatment area at baseline, at the end of treatment, and at three months post-treatment. Quantitative evaluation of collagen types I, III, and VII, newly synthesized collagen, total elastin, and tropoelastin was performed using a computerized morphometric analysis. Results The clinical evaluation of volunteers at baseline, end of treatment, and three months post-treatment revealed no significant differences. Histological and immunostaining analysis of collagen types I, III, and VII, newly synthesized collagen, total elastin, and tropoelastin showed no statistically significant changes (P > 0.05) after mesotherapy injection. Conclusions The present study indicates that mesotherapy for skin rejuvenation does not result in statistically significant histological changes or clinical improvement. PMID:22788806

Early Retinal and Choroidal Coat Thickness Changes After Intravitreal Dexamethasone Implant Injection for Diabetic Macular Edema.

PubMed

Horozoğlu, Fatih; Sever, Özkan

2018-06-05

Intravitreal steroid injection is one of the treatment choices in diabetic macular edema (DME). Dexamethasone (Dx) implant is the most novel form of intravitreal steroid therapy. Macular thickness improvement is well known effect of Dx implant however; subfoveal choroidal coat thickness (SFCT) changes need to be investigated. To evaluate the early central macular thickness (CMT) and SFCT alterations after single dose dexamethasone implant injection in DME. Retrospective cross-sectional study. We identified 29 patients with DME (29 eyes) who underwent optical coherence tomography (OCT) and fundus fluoroscein angiography (FFA). All patients received a single dose intravitreal Dx implant and were followed for CMT and SFCT alterations for the post-injection first hour, first day, first week, first month and third month. The preoperative mean CMT and SFCT measurements were 592.3±122.3 (412-879) μm and 264.8±53.7 (165-397) μm, respectively. CMT measurements significantly decreased from the first hour (p<0.050) and kept decreasing till 3 month (p<0.001); while SFCT decrement was just significant at the first day (p<0.05). When we compared the decrease in SFCT and CMT, 1 hour was similar, however not significant, 1.5% SFCT and 5% CMT decrease was, respectively (p>0.050). CMT decrease rate was significantly higher than SFCT at 1 day, 1 week, 1 month and 3 month (p<0.001). Intravitreal Dx implant has got a meaningful effect on CMT in patients with DME while SFCT decreases significantly at first hour and first day.

The effectiveness of fluoroscopic cervical interlaminar epidural injections in managing chronic cervical disc herniation and radiculitis: preliminary results of a randomized, double-blind, controlled trial.

PubMed

Manchikanti, Laxmaiah; Cash, Kimberly A; Pampati, Vidyasagar; Wargo, Bradley W; Malla, Yogesh

2010-01-01

Chronic neck pain is a common problem in the adult population with a typical 12-month prevalence of 30% to 50%. Cervical disc herniation and radiculitis is one of the common conditions described responsible for chronic neck and upper extremity pain. Cervical epidural injections for managing chronic neck pain with disc herniation are one of the commonly performed non-surgical interventions in the United States. However, the literature supporting cervical interlaminar epidural steroids in managing chronic neck pain is scant. A randomized, double-blind, controlled trial. A private interventional pain management practice and specialty referral center in the United States. To evaluate the effectiveness of cervical interlaminar epidural injections of local anesthetic with or without steroids in providing effective and long-lasting relief in the management of chronic neck pain and upper extremity pain in patients with disc herniation and radiculitis, and to evaluate the differences between local anesthetic with or without steroids. Patients were randomly assigned to one of 2 groups: Group I patients received cervical interlaminar epidural injections of local anesthetic (lidocaine 0.5%, 5 mL); Group II patients received cervical interlaminar epidural injections with 0.5% lidocaine, 4 mL, mixed with 1 mL of non-particulate betamethasone. Multiple outcome measures were utilized. They included the Numeric Rating Scale (NRS), the Neck Disability Index (NDI), employment status, and opioid intake. Assessments were done at baseline and 3, 6, and 12 months post-treatment. Significant pain relief was defined as 50% or more; significant improvement in disability score was defined as a reduction of 50% or more. Significant pain relief (> or = 50%) was demonstrated in 77% of patients in both groups. Functional status improvement was demonstrated by a reduction (> or = 50%) in the NDI scores in 74% of Group I and 71% of Group II at 12 months. The overall average procedures per year were 3.7 +/- 1.1 in Group I and 4.0 +/- 0.91 in Group II; the average total relief per year was 39.45 +/- 11.59 weeks in Group I and 41.06 +/- 11.56 weeks in Group II over the 52 week study period in the patients defined as successful. The initial therapy was considered to be successful if a patient obtained consistent relief with 2 initial injections lasting at least 4 weeks. All others were considered failures. The study results are limited by the lack of a placebo group and a preliminary report of 70 patients, 35 in each group. Cervical interlaminar epidural injections with local anesthetic with or without steroids might be effective in 77% of patients with chronic function-limiting neck pain and upper extremity pain secondary to cervical disc herniation and radiculitis.

Turnover of bone marrow-derived cells in the irradiated mouse cornea

PubMed Central

Chinnery, Holly R; Humphries, Timothy; Clare, Adam; Dixon, Ariane E; Howes, Kristen; Moran, Caitlin B; Scott, Danielle; Zakrzewski, Marianna; Pearlman, Eric; McMenamin, Paul G

2008-01-01

In light of an increasing awareness of the presence of bone marrow (BM)-derived macrophages in the normal cornea and their uncertain role in corneal diseases, it is important that the turnover rate of these resident immune cells be established. The baseline density and distribution of macrophages in the corneal stroma was investigated in Cx3cr1gfp transgenic mice in which all monocyte-derived cells express enhanced green fluorescent protein (eGFP). To quantify turnover, BM-derived cells from transgenic eGFP mice were transplanted into whole-body irradiated wild-type recipients. Additionally, wild-type BM-derived cells were injected into irradiated Cx3cr1+/gfp recipients, creating reverse chimeras. At 2, 4 and 8 weeks post-reconstitution, the number of eGFP+ cells in each corneal whole mount was calculated using epifluorescence microscopy, immunofluorescence staining and confocal microscopy. The total density of myeloid-derived cells in the normal Cx3cr1+/gfp cornea was 366 cells/mm2. In BM chimeras 2 weeks post-reconstitution, 24% of the myeloid-derived cells had been replenished and were predominantly located in the anterior stroma. By 8 weeks post-reconstitution 75% of the myeloid-derived cells had been replaced and these cells were distributed uniformly throughout the stroma. All donor eGFP+ cells expressed low to moderate levels of CD45 and CD11b, with approximately 25% coexpressing major histocompatibility complex class II, a phenotype characteristic of previous descriptions of corneal stromal macrophages. In conclusion, 75% of the myeloid-derived cells in the mouse corneal stroma are replenished after 8 weeks. These data provide a strong basis for functional investigations of the role of resident stromal macrophages versus non-haematopoietic cells using BM chimeric mice in models of corneal inflammation. PMID:18540963

Blood Glucose Levels Following Intra-Articular Steroid Injections in Patients with Diabetes: A Systematic Review.

PubMed

Choudhry, M N; Malik, R A; Charalambous, Charalambos Panayiotou

2016-03-22

Parenterally administered steroids have been shown to affect the metabolism of glucose and to cause abnormal blood glucose levels in diabetic patients. These abnormal blood glucose levels in diabetic patients raise concerns that intra-articular steroid injections also may affect blood glucose levels. We performed a systematic review of studies examining the effect of intra-articular steroid injections on blood glucose levels in patients with diabetes mellitus. A literature search of the PubMed, EMBASE, AMED, and CINAHL databases using all relevant keywords and phrases revealed 532 manuscripts. After the application of inclusion criteria, seven studies with a total of seventy-two patients were analyzed. All studies showed a rise in blood glucose levels following intra-articular steroid injection. Four of the seven studies showed a substantial increase in blood glucose. Peak values reached as high as 500 mg/dL. The peak increase in blood glucose did not occur immediately following intra-articular steroid injection, and in some cases it took several days to occur. In many patients, post-injection hyperglycemia occurred within twenty-four to seventy-two hours. Intra-articular steroid injections may cause hyperglycemia in patients with diabetes mellitus, and patients should be warned of this complication. Diabetic patients should be advised to regularly monitor their blood glucose levels for up to a week after injection and should seek medical advice if safe thresholds are breached. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Changing use of surgical antibiotic prophylaxis in Thika Hospital, Kenya: a quality improvement intervention with an interrupted time series design.

PubMed

Aiken, Alexander M; Wanyoro, Anthony K; Mwangi, Jonah; Juma, Francis; Mugoya, Isaac K; Scott, J Anthony G

2013-01-01

In low-income countries, Surgical Site Infection (SSI) is a common form of hospital-acquired infection. Antibiotic prophylaxis is an effective method of preventing these infections, if given immediately before the start of surgery. Although several studies in Africa have compared pre-operative versus post-operative prophylaxis, there are no studies describing the implementation of policies to improve prescribing of surgical antibiotic prophylaxis in African hospitals. We conducted SSI surveillance at a typical Government hospital in Kenya over a 16 month period between August 2010 and December 2011, using standard definitions of SSI and the extent of contamination of surgical wounds. As an intervention, we developed a hospital policy that advised pre-operative antibiotic prophylaxis and discouraged extended post-operative antibiotics use. We measured process, outcome and balancing effects of this intervention in using an interrupted time series design. From a starting point of near-exclusive post-operative antibiotic use, after policy introduction in February 2011 there was rapid adoption of the use of pre-operative antibiotic prophylaxis (60% of operations at 1 week; 98% at 6 weeks) and a substantial decrease in the use of post-operative antibiotics (40% of operations at 1 week; 10% at 6 weeks) in Clean and Clean-Contaminated surgery. There was no immediate step-change in risk of SSI, but overall, there appeared to be a moderate reduction in the risk of superficial SSI across all levels of wound contamination. There were marked reductions in the costs associated with antibiotic use, the number of intravenous injections performed and nursing time spent administering these. Implementation of a locally developed policy regarding surgical antibiotic prophylaxis is an achievable quality improvement target for hospitals in low-income countries, and can lead to substantial benefits for individual patients and the institution.

Changing Use of Surgical Antibiotic Prophylaxis in Thika Hospital, Kenya: A Quality Improvement Intervention with an Interrupted Time Series Design

PubMed Central

Aiken, Alexander M.; Wanyoro, Anthony K.; Mwangi, Jonah; Juma, Francis; Mugoya, Isaac K.; Scott, J. Anthony G

2013-01-01

Introduction In low-income countries, Surgical Site Infection (SSI) is a common form of hospital-acquired infection. Antibiotic prophylaxis is an effective method of preventing these infections, if given immediately before the start of surgery. Although several studies in Africa have compared pre-operative versus post-operative prophylaxis, there are no studies describing the implementation of policies to improve prescribing of surgical antibiotic prophylaxis in African hospitals. Methods We conducted SSI surveillance at a typical Government hospital in Kenya over a 16 month period between August 2010 and December 2011, using standard definitions of SSI and the extent of contamination of surgical wounds. As an intervention, we developed a hospital policy that advised pre-operative antibiotic prophylaxis and discouraged extended post-operative antibiotics use. We measured process, outcome and balancing effects of this intervention in using an interrupted time series design. Results From a starting point of near-exclusive post-operative antibiotic use, after policy introduction in February 2011 there was rapid adoption of the use of pre-operative antibiotic prophylaxis (60% of operations at 1 week; 98% at 6 weeks) and a substantial decrease in the use of post-operative antibiotics (40% of operations at 1 week; 10% at 6 weeks) in Clean and Clean-Contaminated surgery. There was no immediate step-change in risk of SSI, but overall, there appeared to be a moderate reduction in the risk of superficial SSI across all levels of wound contamination. There were marked reductions in the costs associated with antibiotic use, the number of intravenous injections performed and nursing time spent administering these. Conclusion Implementation of a locally developed policy regarding surgical antibiotic prophylaxis is an achievable quality improvement target for hospitals in low-income countries, and can lead to substantial benefits for individual patients and the institution. PMID:24244390

Single-use autoinjector for once-weekly intramuscular injection of IFNβ-1a.

PubMed

Limmroth, Volker; Gerbershagen, Kathrin

2014-12-01

IFNβ products and glatiramer acetate are established treatment first-line options in long-term disease-modifying therapy of multiple sclerosis (MS). These self-injectable medications are used once weekly to once daily. Injection-related issues are common patient-cited reasons for nonadherence. Autoinjectors have been shown to support long-term adherence to injectable medications. The ability to self-inject in MS patients has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patient independence. The recently introduced easy-to-use prefilled once-weekly pen is a safe and effective device for intramuscular (IM) IFNβ-1a application and provides a convenient method for self-injection. We reviewed the available published evidence on the characteristics of this device. The once-weekly pen facilitates self-injection and was preferred over prefilled syringes by patients in a prospective open-label, multicenter Phase IIIb trial in MS patients who had been using IM IFNβ-1a in prefilled syringes. The simple and safe handling, shielded short needle, single-use disposable design and virtually painless injection by the device may contribute to adherence, quality of life and independence in patients using IM IFNβ-1a.

Costs for collagenase injections compared with fasciectomy in the treatment of Dupuytren's contracture: a retrospective cohort study

PubMed Central

Atroshi, Isam; Strandberg, Emelie; Lauritzson, Anna; Ahlgren, Eva; Waldén, Markus

2014-01-01

Objectives To compare collagenase injections and surgery (fasciectomy) for Dupuytren's contracture (DC) regarding actual total direct treatment costs and short-term outcomes. Design Retrospective cohort study. Setting Orthopaedic department of a regional hospital in Sweden. Participants Patients aged 65 years or older with previously untreated DC of 30° or greater in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints of the small, ring or middle finger. The collagenase group comprised 16 consecutive patients treated during the first 6 months following the introduction of collagenase as treatment for DC at the study centre. The controls were 16 patients randomly selected among those operated on with fasciectomy at the same centre during the preceding 3 years. Interventions Treatment with collagenase was given during two standard outpatient clinic visits (injection of 0.9 mg, distributed at multiple sites in a palpable cord, and next-day finger extension under local anaesthesia) followed by night-time splinting. Fasciectomy was carried out in the operating room (day surgery) under general or regional anaesthesia using standard technique, followed by therapy and splinting. Primary and secondary outcome measures Actual total direct costs (salaries of all medical personnel involved in care, medications, materials and other relevant costs), and total MCP and PIP extension deficit (degrees) measured by hand therapists at 6–12 weeks after the treatment. Results Collagenase injection required fewer hospital outpatient visits to a therapist and nurse than fasciectomy. Total treatment cost for collagenase injection was US$1418.04 and for fasciectomy US$2102.56. The post-treatment median (IQR) total extension deficit was 10 (0–30) for the collagenase group and 10 (0–34) for the fasciectomy group. Conclusions Treatment of DC with one collagenase injection costs 33% less than fasciectomy with equivalent efficacy at 6 weeks regarding reduction in contracture. PMID:24435894

Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial.

PubMed

Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Ahangar, Azadeh Gharooee; Abadi, Porya Hassan; Mojgani, Parviz; Ahangar, Omid Gharooi

2017-01-01

Knee osteoarthritis is the most common joint disease. We aimed to compare the efficacy and safety of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA) on pain and function of patients with knee osteoarthritis. In this single-blinded randomized clinical trial, patients with symptomatic osteoarthritis of knee were assigned to receive 2 intra-articular injections of our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary outcome was the mean change from baseline until 2 and 6 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance for repeated-measures statistical test. A total of 69 patients entered final analysis. The mean age of patients was 58.2 ± 7.41 years and 81.2% were women. In particular, total WOMAC index decreased from 42.9 ± 13.51 to 26.8 ± 13.45 and 24.4 ± 16.54 at 2 and 6 months in the newly developed PRGF group (within subjects P  = .001), and from 38.8 ± 12.62 to 27.8 ± 11.01 and 27.4 ± 11.38 at 2 and 6 months in the HA group (within subjects P  = .001), respectively (between subjects P  = .631). There was no significant difference between PRGF and HA groups in patients' satisfaction and minor complications of injection, whereas patients in HA group reported significantly lower injection-induced pain. In 6 months follow up, our newly developed PRGF and HA, both are effective options to decrease pain and improvement of function in patients with symptomatic mild to moderate knee osteoarthritis.

Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur.

PubMed

Hao, Yongqiang; Ma, Yongcheng; Wang, Xuepeng; Jin, Fangchun; Ge, Shengfang

2012-04-01

Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-four-month-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction. Copyright © 2011 Orthopaedic Research Society.

New fat-derived products for treating skin-induced lesions of scleroderma in nude mice.

PubMed

Serratrice, Nicolas; Bruzzese, Laurie; Magalon, Jérémy; Véran, Julie; Giraudo, Laurent; Aboudou, Houssein; Ould-Ali, Djaffar; Nguyen, Pierre Sébastien; Bausset, Olivier; Daumas, Aurélie; Casanova, Dominique; Granel, Brigitte; Andrac-Meyer, Lucile; Sabatier, Florence; Magalon, Guy

2014-12-17

Scleroderma is characterized by cutaneous manifestations that mainly affect the hands, arms and face. As of today, there is no treatment for fibrotic skin lesions of scleroderma. Previously we generated and validated a model of scleroderma-like skin sclerosis in nude mice, appropriate to inject human derived products. We showed that the subcutaneous injection of micro-fat (MF), purified and injected using small caliber cannulas, have anti-fibrotic and pro-angiogenic effects and appears more suitable for the treatment of skin lesions of scleroderma compared to the gold standard (Coleman's technique or macro-fat). Here we compared the long-term efficacy of micro-fat "enriched" with other therapeutic products including the stromal vascular fraction (SVF) of fat and platelet-rich plasma (PRP) from blood in our murine model of scleroderma. We used 72 nude mice in this study. We formed six experimental groups: Macro-fat, MF, SVF, PRP, MF + SVF, MF + PRP. This project has three phases: i) Induction of skin sclerosis by daily subcutaneous injections of bleomycin (BLM) for 4 weeks in nude mice; ii) Purification and injection of the different cell therapy products; iii) Histological analyses done 8 weeks post-injections. MF + SVF and MF + PRP significantly reversed dermal and epidermal sclerosis (P <0.01). Macro-fat, SVF, PRP only corrected the dermal sclerosis (P <0.05). Epidermal sclerosis was reduced in treatments containing MF (P <0.01). MF was more stable. Products containing the SVF were associated with a significant increase of the local vascularization (P <0.01). All tested substances were effective in treating skin-induced lesions of scleroderma with different levels of fibrosis and vascular improvement; MF derived products are more stable and SVF demonstrated better pro-angiogenic effects. The observed efficacy of this combination of products in the animal model provides a rationale for potential clinical applications to treat human disease.

The effect of subacromial injections of autologous conditioned plasma versus cortisone for the treatment of symptomatic partial rotator cuff tears.

PubMed

von Wehren, Lutz; Blanke, Fabian; Todorov, Atanas; Heisterbach, Patricia; Sailer, Jannis; Majewski, Martin

2016-12-01

Rotator cuff tears are one of the most common causes of shoulder malfunction and pain, which lead to a significant reduction in the quality of life. This present study investigated the effects of subacromial platelet-rich plasma injections [i.e. autologous conditioned plasma (ACP) injections] as compared to standard subacromial cortisone injection therapy in 50 patients with partial rotator cuff tears. Before injection, and 6 weeks, 12 weeks and 6 months thereafter, the patients were assessed by the Constant-Murley score (CMS), the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), the simple shoulder test (SST) and a pain visual analogue scale (VAS). An MRI was also performed before and 6 months after injection. Both patient groups had statistically significant better shoulder score outcomes over time. ASES, SST and CMS outcomes after 12 versus 6 weeks were better in the ACP group as compared to the cortisone group. VAS, ASES and CMS outcomes after 12 weeks versus baseline in the ACP group were better as compared to the cortisone group. There was a statistically significant difference between ACP group and cortisone group 12 weeks after injection regarding VAS, ASES, SST and CMS in favour of the ACP group. The MRI showed an improvement in grade of tendinopathy in both groups, however, without statistically significant differences between the two groups. Compared with cortisone injections, ACP injections show earlier benefit as compared to cortisone injections although a statistically significant difference after 6 months could not be found. Therefore, subacromial ACP injections are a good alternative to subacromial cortisone injections, especially in patients with contraindication to cortisone. Therapeutic study, Level III.

Long lasting immunity in chickens induced by a single shot of influenza vaccine prepared from inactivated non-pathogenic H5N1 virus particles against challenge with a highly pathogenic avian influenza virus.

PubMed

Sasaki, Takashi; Kokumai, Norihide; Ohgitani, Toshiaki; Sakamoto, Ryuichi; Takikawa, Noriyasu; Lin, Zhifeng; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Kida, Hiroshi

2009-08-20

An influenza vaccine was prepared from inactivated whole particles of the non-pathogenic strain A/duck/Hokkaido/Vac-1/04 (H5N1) virus using an oil adjuvant containing anhydromannitol-octadecenoate-ether (AMOE). The vaccine was injected intramuscularly into five 4-week-old chickens, and 138 weeks after vaccination, they were challenged intranasally with 100 times 50% chicken lethal dose of the highly pathogenic avian influenza (HPAI) virus A/chicken/Yamaguchi/7/04 (H5N1). All 5 chickens survived without exhibiting clinical signs of influenza, although 2 days post-challenge, 3 vaccinated chickens shed limited titres of viruses in laryngopharyngeal swabs.

Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury.

PubMed

Lee, Yee-Shuan; Funk, Lucy H; Lee, Jae K; Bunge, Mary Bartlett

2018-04-01

Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury (SCI) and is currently in clinical trials. In our continuing efforts to improve Schwann cell transplantation strategies, we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion. Since macrophages are major inflammatory contributors to the acute spinal cord injury, and are the major phagocytic cells, we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI. To test this hypothesis, rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not. In rat subjected to macrophage depletion, liposomes filled with clodronate were intraperitoneally injected at 1, 3, 6, 11, and 18 days post injury. Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline. Schwann cells were transplanted 1 week post injury in all rats. Biotinylated dextran amine (BDA) was injected at thoracic level 5 to evalute axon regeneration. The Basso, Beattie, and Bresnahan locomotor test, Gridwalk test, and sensory test using von Frey filaments were performed to assess functional recovery. Immunohistochemistry was used to detect glial fibrillary acidic protein, neurofilament, and green fluorescent protein (GFP), and also to visulize BDA-labelled axons. The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides. The numbers of BDA-positive axons were also quantified. At 8 weeks after Schwann cell transplantation, there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone. These changes were not associated, however, with improved Schwann cell survival, axon growth, or locomotor recovery. Although combining Schwann cell transplantation with macrophage depletion does improve histopathology of the injury site, the effect on axon growth and behavioral recovery appears no better than what can be achieved with Schwann cell transplants alone.

NELL-1 Injection Maintains Long-Bone Quantity and Quality in an Ovariectomy-Induced Osteoporotic Senile Rat Model

PubMed Central

Kwak, Jinny; Zara, Janette N.; Chiang, Michael; Ngo, Richard; Shen, Jia; James, Aaron W.; Le, Khoi M.; Moon, Crystal; Zhang, Xinli; Gou, Zhongru; Ting, Kang

2013-01-01

Over 10 million Americans have osteoporosis, and is the predominant cause of fractures in the elderly. Treatment of fractures in the setting of osteoporosis is complicated by a suboptimal bone regenerative response due to a decline in the number of osteoblasts, their function, and survival. Consequently, an osteogenic therapeutic to prevent and treat fractures in patients with osteoporosis is needed. Nel-like molecule-1 (NELL-1), a novel osteoinductive growth factor, has been shown to promote bone regeneration. In this study, we aim to demonstrate the capacity of recombinant NELL-1 to prevent ovariectomy (OVX)-induced osteoporosis in a senile rat model. Ten-month-old female Sprague-Dawley rats underwent either sham surgery or OVX. Subsequently, 50 μL of 600 μg/mL NELL-1 lyophilized onto a 0–50-μm tricalcium phosphate (TCP) carrier was injected into the femoral bone marrow cavity while phosphate-buffered saline (PBS) control was injected into the contralateral femur. Our microcomputed tomography results showed that OVX+PBS/TCP control femurs showed a continuous decrease in the bone volume (BV) and bone mineral density (BMD) from 2 to 8 weeks post-OVX. In contrast, OVX+NELL-1/TCP femurs showed resistance to OVX-induced bone resorption showing BV and BMD levels similar to that of SHAM femurs at 8 weeks post-OVX. Histology showed increased endosteal-woven bone, as well as decreased adipocytes in the bone marrow of NELL-1-treated femurs compared to control. NELL-1-treated femurs also showed increased immunostaining for bone differentiation markers osteopontin and osteocalcin. These findings were validated in vitro, in which addition of NELL-1 in OVX bone marrow stem cells resulted in increased osteogenic differentiation. Thus, NELL-1 effectively enhances in situ osteogenesis in the bone marrow, making it potentially useful in the prevention and treatment of osteoporotic fractures. PMID:23083222

Cellular selectivity of AAV serotypes for gene delivery in neurons and astrocytes by neonatal intracerebroventricular injection

PubMed Central

Hammond, Sean L.; Leek, Ashley N.; Richman, Evan H.

2017-01-01

The non-pathogenic parvovirus, adeno-associated virus (AAV), is an efficient vector for transgene expression in vivo and shows promise for treatment of brain disorders in clinical trials. Currently, there are more than 100 AAV serotypes identified that differ in the binding capacity of capsid proteins to specific cell surface receptors that can transduce different cell types and brain regions in the CNS. In the current study, multiple AAV serotypes expressing a GFP reporter (AAV1, AAV2/1, AAVDJ, AAV8, AAVDJ8, AAV9, AAVDJ9) were screened for their infectivity in both primary murine astrocyte and neuronal cell cultures. AAV2/1, AAVDJ8 and AAV9 were selected for further investigation of their tropism throughout different brain regions and cell types. Each AAV was administered to P0-neonatal mice via intracerebroventricular injections (ICV). Brains were then systematically analyzed for GFP expression at 3 or 6 weeks post-infection in various regions, including the olfactory bulb, striatum, cortex, hippocampus, substantia nigra (SN) and cerebellum. Cell counting data revealed that AAV2/1 infections were more prevalent in the cortical layers but penetrated to the midbrain less than AAVDJ8 and AAV9. Additionally, there were differences in the persistence of viral transgene expression amongst the three serotypes examined in vivo at 3 and 6 weeks post-infection. Because AAV-mediated transgene expression is of interest in neurodegenerative diseases such as Parkinson’s Disease, we examined the SN with microscopy techniques, such as CLARITY tissue transmutation, to identify AAV serotypes that resulted in optimal transgene expression in either astrocytes or dopaminergic neurons. AAVDJ8 displayed more tropism in astrocytes compared to AAV9 in the SN region. We conclude that ICV injection results in lasting expression of virally encoded transgene when using AAV vectors and that specific AAV serotypes are required to selectively deliver transgenes of interest to different brain regions in both astrocytes and neurons. PMID:29244806

Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury

PubMed Central

Lee, Yee-Shuan; Funk, Lucy H.; Lee, Jae K.; Bunge, Mary Bartlett

2018-01-01

Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury (SCI) and is currently in clinical trials. In our continuing efforts to improve Schwann cell transplantation strategies, we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion. Since macrophages are major inflammatory contributors to the acute spinal cord injury, and are the major phagocytic cells, we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI. To test this hypothesis, rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not. In rat subjected to macrophage depletion, liposomes filled with clodronate were intraperitoneally injected at 1, 3, 6, 11, and 18 days post injury. Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline. Schwann cells were transplanted 1 week post injury in all rats. Biotinylated dextran amine (BDA) was injected at thoracic level 5 to evalute axon regeneration. The Basso, Beattie, and Bresnahan locomotor test, Gridwalk test, and sensory test using von Frey filaments were performed to assess functional recovery. Immunohistochemistry was used to detect glial fibrillary acidic protein, neurofilament, and green fluorescent protein (GFP), and also to visulize BDA-labelled axons. The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides. The numbers of BDA-positive axons were also quantified. At 8 weeks after Schwann cell transplantation, there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone. These changes were not associated, however, with improved Schwann cell survival, axon growth, or locomotor recovery. Although combining Schwann cell transplantation with macrophage depletion does improve histopathology of the injury site, the effect on axon growth and behavioral recovery appears no better than what can be achieved with Schwann cell transplants alone. PMID:29722321

Comparative effects of in ovo versus subcutaneous administration of the Marek's disease vaccine and pre-placement holding time on the post-hatch performance of Ross 708 broilers1,2,3.

PubMed

Peebles, E D; Barbosa, T M; Cummings, T S; Dickson, J; Womack, S K; Gerard, P D

2017-05-01

Effects of 2 types of methods of administration (moa; in ovo or s.c.) of the Marek's disease (MD) vaccine and 4 and 18 h pre-placement holding times (pht) on the performance of male broilers through 48 d of age were investigated. Ross 708 broiler hatching eggs (3,900) were either in ovo-vaccinated at 18 d of incubation or chicks from eggs that were not in ovo-injected were vaccinated s.c. at hatch, and chicks from each moa group were held for one of the 2 pht. In ovo injections (50 μL) were delivered by a commercial multi-egg injector and s.c. injections (0.2 mL) were delivered by an automatic pneumatic s.c. injector. Sixteen birds were assigned to each of 15 replicate floor pens belonging to each of the 4 moa and pht combination groups. Mortality and BW gain were determined at weekly intervals, and feed consumption and conversion were determined in the zero to 14, 14 to 28, 28 to 42, and 42 to 48 d age intervals. No interactive effects between moa and pht were observed for any variable, and mortality was not significantly affected by moa or pht. The 14 to 28 d feed consumption and 14 to 21 d BW gain of s.c.-vaccinated birds were lower than that of in ovo-vaccinated birds, and the increase in pht from 4 to 18 h decreased feed consumption through 28 d post hatch and BW gain through 35 d post hatch. Overall, the performances of male Ross 708 broilers through 48 d of age in response to in ovo and s.c. injections of the MD vaccine were comparable, and delays in hatchling placement should be less that 18 h in duration. Furthermore, despite the decrease in BW gain through 35 d associated with the reduction in feed consumption through 28 d in response to the 14 h increase in pht, in ovo injection did not exacerbate the effect of the increase in pht. © 2016 Poultry Science Association Inc.

Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis.

PubMed

Lin, Yu-Ching; Wu, Wei-Ting; Hsu, Yu-Chun; Han, Der-Sheng; Chang, Ke-Vin

2018-02-01

To explore the effectiveness of botulinum toxin compared with non-surgical treatments in patients with lateral epicondylitis. Data sources including PubMed, Scopus, Embase and Airity Library from the earliest record to February 2017 were searched. Study design, patients' characteristics, dosage/brand of botulinum toxin, injection techniques, and measurements of pain and hand grip strength were retrieved. The standardized mean differences (SMDs) in pain relief and grip strength reduction were calculated at the following time points: 2-4, 8-12, and 16 weeks or more after injection. Six randomized controlled trials (321 participants) comparing botulinum toxin with placebo or corticosteroid injections were included. Compared with placebo, botulinum toxin injection significantly reduced pain at all three time points (SMD, -0.729, 95% confidence interval [CI], -1.286 to -0.171; SMD, -0.446, 95% CI, -0.740 to -0.152; SMD, -0.543, 95% CI, -0.978 to -0.107, respectively). Botulinum toxin was less effective than corticosteroid at 2-4 weeks (SMD, 1.153; 95% CI, 0.568-1.737) and both treatments appeared similar in efficacy after 8 weeks. Different injection sites and dosage/brand did not affect effectiveness. Botulinum toxin decreased grip strength 2-4 weeks after injection, and high equivalent dose could extend its paralytic effects to 8-12 weeks. When treating lateral epicondylitis, botulinum toxin was superior to placebo and could last for 16 weeks. Corticosteroid and botulinum toxin injections were largely equivalent, except the corticosteroid injections were better at pain relief in the early stages and were associated with less weakness in grip in the first 12 weeks.

Chronic post-operative iris prosthesis endophthalmitis in a patient with traumatic aniridia: a case report.

PubMed

Firl, Kevin C; Montezuma, Sandra R

2016-11-09

Post-operative endophthalmitis is a serious complication of intraocular surgery which may present acutely or chronically. Chronic post-operative endophthalmitis is characterized by decreased visual acuity, mild pain, and low-grade uveitis several weeks or months after intraocular surgery which may be responsive to corticosteroids, but recur upon tapering. Low virulence organisms such as Propionibacterium acnes are the most common culprit organisms, and treatment most often consists of both intravitreal antibiotic injections and surgery. Aniridia is a condition defined by total or partial loss of the iris and leads to decreased visual quality marked by glare and photophobia. Treatment of complex or severe cases of traumatic aniridia in which surgical repair is difficult may consist of implantation of iris prostheses, devices designed to reduce symptoms of aniridia. Though chronic, post-operative endophthalmitis has been associated with most intraocular surgeries including intraocular lens implantation after cataract removal, it has never been described in a patient with an iris prosthesis. In this case report, we describe the case of a 49 year old, male construction worker with traumatic aniridia who experienced chronic, recurrent low-grade intraocular inflammation and irritation for months after implantation of the Ophtec 311 prosthetic iris. Symptoms and signs of inflammation improved temporarily with sub-Tenon's capsule triamcinolone injections. Ultimately after more than 2 post-operative years, the iris prosthesis was explanted, and intravitreal cultures showed P. acnes growth after 5 days. Intravitreal antibiotics treated the infection successfully. To our knowledge, this is the first reported case of chronic, post-operative endophthalmitis in a patient with an iris prosthesis. Chronic, post-operative endophthalmitis may be a difficult to identify in the context of traumatic aniridia and iris prosthesis implantation due to other potential etiologies of chronic intraocular inflammation such as implant-induced chafing. Clinicians should suspect chronic, post-operative endophthalmitis in any case of recurrent, low-grade intraocular inflammation.

The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vuong, Te, E-mail: tvuong@jgh.mcgill.ca; Waschke, Kevin; Niazi, Tamim

Purpose: Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). Methods and Materials: Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receivemore » the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. Results: At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). Conclusions: This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.« less

Efficacy of a DNA vaccine carrying Eimeria maxima Gam56 antigen gene against coccidiosis in chickens.

PubMed

Xu, Jinjun; Zhang, Yan; Tao, Jianping

2013-04-01

To control coccidiosis without using prophylactic medications, a DNA vaccine targeting the gametophyte antigen Gam56 from Eimeria maxima in chickens was constructed, and the immunogenicity and protective effects were evaluated. The ORF of Gam56 gene was cloned into an eukaryotic expression vector pcDNA3.1(zeo)+. Expression of Gam56 protein in COS-7 cells transfected with recombinant plasmid pcDNA-Gam56 was confirmed by indirect immunofluorescence assay. The DNA vaccine was injected intramuscularly to yellow feathered broilers of 1-week old at 3 dosages (25, 50, and 100 µg/chick). Injection was repeated once 1 week later. One week after the second injection, birds were challenged orally with 5×10(4) sporulated oocysts of E. maxima, then weighed and killed at day 8 post challenge. Blood samples were collected and examined for specific peripheral blood lymphocyte proliferation activity and serum antibody levels. Compared with control groups, the administration of pcDNA-Gam56 vaccine markedly increased the lymphocyte proliferation activity (P<0.05) at day 7 and 14 after the first immunization. The level of lymphocyte proliferation started to decrease on day 21 after the first immunization. A similar trend was seen in specific antibody levels. Among the 3 pcDNA-Gam56 immunized groups, the median dosage group displayed the highest lymphocyte proliferation and antibody levels (P<0.05). The median dosage group had the greatest relative body weight gain (89.7%), and the greatest oocyst shedding reduction (53.7%). These results indicate that median dosage of DNA vaccine had good immunogenicity and immune protection effects, and may be used in field applications for coccidiosis control.

Efficacy of a DNA Vaccine Carrying Eimeria maxima Gam56 Antigen Gene against Coccidiosis in Chickens

PubMed Central

Xu, Jinjun; Zhang, Yan

2013-01-01

To control coccidiosis without using prophylactic medications, a DNA vaccine targeting the gametophyte antigen Gam56 from Eimeria maxima in chickens was constructed, and the immunogenicity and protective effects were evaluated. The ORF of Gam56 gene was cloned into an eukaryotic expression vector pcDNA3.1(zeo)+. Expression of Gam56 protein in COS-7 cells transfected with recombinant plasmid pcDNA-Gam56 was confirmed by indirect immunofluorescence assay. The DNA vaccine was injected intramuscularly to yellow feathered broilers of 1-week old at 3 dosages (25, 50, and 100 µg/chick). Injection was repeated once 1 week later. One week after the second injection, birds were challenged orally with 5×104 sporulated oocysts of E. maxima, then weighed and killed at day 8 post challenge. Blood samples were collected and examined for specific peripheral blood lymphocyte proliferation activity and serum antibody levels. Compared with control groups, the administration of pcDNA-Gam56 vaccine markedly increased the lymphocyte proliferation activity (P<0.05) at day 7 and 14 after the first immunization. The level of lymphocyte proliferation started to decrease on day 21 after the first immunization. A similar trend was seen in specific antibody levels. Among the 3 pcDNA-Gam56 immunized groups, the median dosage group displayed the highest lymphocyte proliferation and antibody levels (P<0.05). The median dosage group had the greatest relative body weight gain (89.7%), and the greatest oocyst shedding reduction (53.7%). These results indicate that median dosage of DNA vaccine had good immunogenicity and immune protection effects, and may be used in field applications for coccidiosis control. PMID:23710081

Detection of BrdU-label Retaining Cells in the Lacrimal Gland: Implications for Tissue Repair

PubMed Central

You, Samantha; Tariq, Ayesha; Kublin, Claire L.; Zoukhri, Driss

2011-01-01

The purpose of the present study was to determine if the lacrimal gland contains 5-bromo-2’-deoxyuridine (BrdU)-label retaining cells and if they are involved in tissue repair. Animals were pulsed daily with BrdU injections for 7 consecutive days. After a chase period of 2, 4, or 12 weeks, the animals were sacrificed and the lacrimal glands were removed and processed for BrdU immunostaining. In another series of experiments, the lacrimal glands of 12-week chased animals were either left untreated or were injected with interleukin 1 (IL-1) to induce injury. Two and half day post-injection, the lacrimal glands were removed and processed for BrdU immunostaining. After 2 and 4 week of chase period, a substantial number of lacrimal gland cells were BrdU+ (11.98 ± 1.84 and 7.95 ± 1.83 BrdU+ cells/mm2, respectively). After 12 weeks of chase, there was a 97% decline in the number of BrdU+ cells (0.38 ± 0.06 BrdU+ cells/mm2), suggesting that these BrdU-label retaining cells may represent slow-cycling adult stem/progenitor cells. In support of this hypothesis, the number of BrdU labeled cells increased over 7-fold during repair of the lacrimal gland (control: 0.41 ± 0.09 BrdU+ cells/mm2, injured: 2.91 ± 0.62 BrdU+ cells/mm2). Furthermore, during repair, among BrdU+ cells 58.2 ± 3.6 % were acinar cells, 26.4 ± 4.1% were myoepithelial cells, 0.4 ± 0.4% were ductal cells, and 15.0 ± 3.0% were stromal cells. We conclude that the murine lacrimal gland contains BrdU-label retaining cells that are mobilized following injury to generate acinar, myoepithelial and ductal cells. PMID:22101331

Systemic Gene Delivery Transduces the Enteric Nervous System of Guinea Pigs and Cynomolgus Macaques

PubMed Central

Gombash, Sara E; Cowley, Christopher J; Fitzgerald, Julie A; Lepak, Christina A; Neides, Mitchell G; Hook, Kathryn; Todd, Levi J; Wang, Guo-Du; Mueller, Christian; Kaspar, Brian K; Bielefeld, Eric C; Fischer, Andrew J; Wood, Jackie D; Foust, Kevin D

2017-01-01

Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or PBS. Piglets were euthanized three weeks post-injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9 treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders. PMID:28771235

Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.

PubMed

Gombash, S E; Cowley, C J; Fitzgerald, J A; Lepak, C A; Neides, M G; Hook, K; Todd, L J; Wang, G-D; Mueller, C; Kaspar, B K; Bielefeld, E C; Fischer, A J; Wood, J D; Foust, K D

2017-10-01

Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or phosphate-buffered saline. Piglets were euthanized three weeks post injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP-positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9-treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders.

Influence of the cardiac glycoside digoxin on cardiac troponin I, acid-base and electrolyte balance, and haematobiochemical profiles in healthy donkeys (Equus asinus).

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd

2014-03-12

The effect of digoxin administration on the serum concentration of the cardiac troponin I (cTnI) has not been reported to date in equidae. This study was therefore designed to evaluate the effect of digoxin on cardiac cell damage in donkeys (Equus asinus) as assessed by cTnI, acid-base and electrolyte balance and haematobiochemical profiles. Ten clinically healthy donkeys were given an IV infusion of digoxin at a dose of 14 μg/kg. Blood samples were collected from the donkeys up through 72 h post-injection. Three of the donkeys exhibited increased heart and respiratory rates post-injection. In the other seven animals, the heart and respiratory rates were lower 4 h post-injection. The serum digoxin concentration increased significantly at many time points after injection. The serum concentration of cTnI did not differ significantly between pre- and post-injection. An increase in blood pH was noted at 3 h after digoxin injection. There were also increases in PO2 and in oxygen saturation. Decreases in PCO2 at 2 to 48 h post-injection as well as a decrease in blood lactate at 4 h post-injection were observed. The serum concentration of glucose remained significantly elevated at all-time points after digoxin injection. It is concluded that administration of digoxin to healthy donkeys (14 μg/kg) did not result in elevations of serum cTnI concentration, signs of digoxin intoxication, ECG abnormalities and did not increase serum concentrations of blood urea nitrogen and creatinine.

[Immunization against varicella and zoster].

PubMed

Floret, Daniel

2007-06-01

Two vaccines against varicella-zoster virus are available in France. These live attenuated vaccines are derived from the Oka strain used in Japan since 1974. They are indicated for healthy subjects from 12 months of age, at a dose of one injection until 12 years of age, and two injections 4-8 weeks apart for older children and adults. Seroconversion occurs in 95% of cases and the antibodies persist beyond 5 years. Clinical efficacy is about 85% against all forms of varicella and nearly 100% against severe forms. Post-exposure vaccination within 3 days may also prevent the disease. A universal immunization program against varicella was implemented in the USA in 1995. Now, with vaccine coverage at about 80%, the incidence of the disease has been reduced by 85%, with the largest decrease in 1- to 4-year-olds. Tolerability is generally good, with only mild reactions at the injection site and moderate fever The length of protection is not yet known. A two-dose schedule seems advisable to avoid breakthrough varicella, which occurs in 4% of vaccinees each year. Insufficient coverage is expected to lead to later disease onset, with more severe cases in adolescents and adults. Universal immunization could also increase the incidence of zoster. These problems indeed seem to be emerging in the United States. France has adopted restrictive guidelines on VZV vaccination, but they are expected to be revised when the combined MMR-V vaccine becomes available. Zoster vaccine, prepared with the same strain but at a higher concentration, has moderate efficacy on zoster and on post-zoster neuralgia in patients over 70. This vaccine is not yet recommended in France, because the length of protection is not known and there is a potential risk of delaying the occurrence of zoster and, thus, of increasing the risk of post zoster neuralgia.

Comparative study between surgical and non-surgical treatment of anismus in patients with symptoms of obstructed defecation: a prospective randomized study.

PubMed

Faried, Mohamed; El Nakeeb, Ayman; Youssef, Mohamed; Omar, Waleed; El Monem, Hisham Abd

2010-08-01

This study came to compare the results of biofeedback retraining biofeedback (BFB), botulinum toxin botulinum type A (BTX-A) injection and partial division of puborectalis (PDPR) in the treatment of anismus patients. Consecutive patients treated for anismus fulfilled Rome II criteria for functional constipation at our institution were evaluated for inclusion. Participants were randomly allocated to receive BFB, BTX-A injection, and PDPR. All patients underwent anorectal manometry, balloon expulsion test, defecography, and electromyography activity of the anal sphincter. Follow up was conducted weekly in the first month then monthly for about 1 year. Study variables included clinical improvement, patient satisfaction, and objective improvement. Sixty patients with anismus were randomized and completed the study. The groups differed significantly regarding clinical improvement at 1 month (50% for BFB, 75%BTX-A injection, and 95% for PDPR, P = 0.006) and differences persisted at 1 year (30% for BFB, 35%BTX-A injection, and 70% for PDPR, P = 0.02). Constipation score of the patients significantly improved postPDPR and BTX-A injection. Manometric relaxation was achieved significantly in the three groups. Biofeedback retraining has a limited therapeutic effect, BTX-A injection seems to be successful for temporary treatment but PDPR is found to be an effective with lower morbidity in contrast to its higher success rate in treating anismus.

The point-touch technique for botulinum toxin injection in adductor spasmodic dysphonia: quality of life assessment.

PubMed

Morzaria, S; Damrose, E J

2011-07-01

Botulinum toxin injection under electromyographic guidance is the 'gold standard' for adductor spasmodic dysphonia treatment. The point-touch technique, an alternative injection method which relies on anatomical landmarks, is cheaper, quicker and more accessible, but has not yet gained widespread acceptance due to concerns about patient satisfaction. To assess swallowing and voice-related quality of life following point-touch botulinum toxin injection in adductor spasmodic dysphonia patients. Stanford University Voice and Swallowing Center. Prospective case series (evidence level four). Consecutive adductor spasmodic dysphonia patients with a stable botulinum toxin dose-response relationship were recruited prospectively. The Eating Assessment Tool and Voice-Related Quality of Life questionnaires were completed pre-treatment and at 10 and 30 per cent completion of the injection cycle, respectively. Thirty-seven patients completed follow up. The mean total botulinum toxin dose was 0.88 units. Pre-treatment Voice-Related Quality of Life questionnaire results reflected the burden of disease. Post-treatment Eating Assessment Tool and Voice-Related Quality of Life questionnaire results were collected at 2.53 and 7.84 weeks, respectively; the former showed an increase in dysphagia, albeit statistically insignificant, while the latter showed significantly improved scores (both domain and total). The point-touch technique is a viable alternative for botulinum toxin injection in the treatment of adductor spasmodic dysphonia.

The effect of intra-articular hyaluronate and tramadol injection on patients with adhesive capsulitis of the shoulder.

PubMed

Kim, Kyung-Hee; Suh, Jung-Woo; Oh, Ki Young

2017-08-03

Local administration of opioids causes effective analgesia without adverse effects related to the central nervous system. After the beneficial demonstration of peripheral opioid receptors in joint synovia, intra-articular opioid injections were used for pain treatment. Clinical studies have reported the safety and efficacy of hyaluronate injection in the shoulder joint of patients with osteoarthritis, periarthritis, rotator cuff tears, and adhesive capsulitis. To estimate the efficacy of intra-articular hyaluronate and tramadol injection for adhesive capsulitis of the shoulder compared with that of intra-articular hyaluronate injection alone. Thirty patients with adhesive capsulitis of the shoulder were randomized to the hyaluronate group (n= 16) or the tramadol group (n= 14). Hyaluronate group members were administered five weekly intra-articular hyaluronate injections; tramadol group members were administered three weekly intra-articular hyaluronate and tramadol injections and then two weekly intra-articular injections of hyaluronate. Visual Analog Scale (VAS), passive range of motion (PROM) of the shoulder joint, and Shoulder Pain and Disability Index (SPADI) scores were assessed at baseline and weeks 1, 2, 3, 4, and 6 after the initial injection. A significant improvement was observed in VAS, PROM, and SPADI scores between time points in both groups. In comparison in both groups at weeks 1 and 2 after the initial injection the VAS scores of the tramadol group were significantly lower than those of the hyaluronate group. Intra-articular hyaluronate with tramadol showed more rapid and strong analgesic effects than intra-articular hyaluronate alone and did not induce any adverse effects.

Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

PubMed Central

Bertoglio, Daniele; Amhaoul, Halima; Van Eetveldt, Annemie; Houbrechts, Ruben; Van De Vijver, Sebastiaan; Ali, Idrish; Dedeurwaerdere, Stefanie

2017-01-01

The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE). Wistar Han (Charles River, France) and Sprague-Dawley (Harlan, The Netherlands) rats were subjected to KASE using the Hellier kainic acid (KA) and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG) in a subgroup of animals, while animals were sacrificed 1 week (subacute phase) and 12 weeks (chronic phase) post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei), microglial activation (OX-42 and translocator protein), and neurodegeneration (Fluorojade C) were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001) in SD/H (median 8.3 days) animals compared to WH/CR (median 15.4 days). During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01). However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure burden itself. The divergences in disease progression and seizure outcome, in addition to the histopathological dissimilarities, further substantiate the existence of strain differences for the KASE rat model of TLE. PMID:29163349

Corticosteroid injection in early treatment of lateral epicondylitis.

PubMed

Newcomer, K L; Laskowski, E R; Idank, D M; McLean, T J; Egan, K S

2001-10-01

To analyze whether a corticosteroid injection in combination with rehabilitation early in the course of lateral epicondylitis (LE) alters the outcome up to 6 months after injection compared with a control injection and rehabilitation. Randomized, controlled, double-blind study. Sports medicine center in a tertiary care center. Subjects with a diagnosis of LE whose symptoms had been present less than 4 weeks were included. Subjects were recruited by word of mouth and through advertising. The 39 subjects who were recruited were 18 to 65 years old. 19 subjects were randomized to receive rehabilitation and a sham injection, and 20 were randomized to receive rehabilitation and a corticosteroid injection. At 4 and 8 weeks, they were reevaluated and their treatment programs were modified, if indicated. Outcome measurements were performed at baseline, 4 weeks, 8 weeks, and 6 months, and included a functional pain questionnaire and a visual analogue pain scale. Painless grip strength on the affected side and maximal grip strength bilaterally were measured at baseline, 4 weeks, and 8 weeks. There were no significant differences in outcome between the two groups with the exception of an improvement in the visual analogue pain scale in the corticosteroid group from 8 weeks to 6 months. Outcome measurements in both groups improved significantly over time; more than 80% of subjects reported improvements from baseline to 6 months for all scales. A corticosteroid injection does not provide a clinically significant improvement in the outcome of LE, and rehabilitation should be the first line of treatment in patients with a short duration of symptoms.

Predictors of response to intra-articular steroid injections in patients with osteoarthritis of the knee joint.

PubMed

Fatimah, Nibah; Salim, Babur; Raja, Ejaz-Ul-Haq; Nasim, Amjad

2016-10-01

This study aimed to determine the factors associated with response to intra-articular steroid injection (IASI) in patients with knee joint osteoarthritis. One hundred seventy-four female patients, age ranging from 30 to 80 years, diagnosed to have osteoarthritis of the knee joint, were given IASI. Response to IASI was assessed by using WOMAC and VAS at 2 weeks, 4 weeks and 3 months. At 3 months, the subjects were categorized as responders, partial responders and non-responders to treatment by IASI. Various factors were narrowed down to see their effect on response, namely age, BMI, smoking habits, comorbidities, presence of clinical effusion, radiographic score, local knee tenderness, range of movement and socioeconomic status. One hundred twenty-four patients completed the study. 16.1 % showed 50 % or more improvement in WOMAC score at 3 months post IASI therapy, whereas 38.7 % of OA patients had more than 50 % improvement in VAS score. Out of all factors, range of movement, local knee tenderness and radiographic score of the affected joint are the three parameters which can predict the improvement in WOMAC score after 3 months of IASI therapy (P = 0.013, P = 0.045 and P = 0.000, respectively). Age of the patient can predict improvement in VAS at 3 months post IASI (P = 0.027). We conclude that age, range of movement, local knee tenderness and radiographic score of the affected joint can predict response to IASI after 3 months of IASI therapy.

Fibrin-Targeted Magnetic Resonance Imaging Allows In Vivo Quantification of Thrombus Fibrin Content and Identifies Thrombi Amenable for Thrombolysis

PubMed Central

Jenkins, Julia; Modarai, Bijan; Wiethoff, Andrea J.; Phinikaridou, Alkystis; Grover, Steven P.; Patel, Ashish S.; Schaeffter, Tobias; Smith, Alberto; Botnar, Rene M.

2014-01-01

Objective Deep venous thrombosis is a major health problem. Thrombolytic therapies are effective in recanalizing the veins and preventing post-thrombotic complications, but there is no consensus on selection criteria. The aim of this study was to investigate a fibrin-specific MRI contrast agent (EP-2104R) for the accurate quantification of thrombus’ fibrin content in vivo and for the identification of thrombus suitable for thrombolysis. Approach and Results Venous thrombosis was induced in the inferior vena cava of 8- to 10-week-old male BALB/C mice and MRI performed 2, 4, 7, 10, 14, and 21 days later. Eighteen mice were scanned at each time point pre and 2 hours post injection of EP-2104R (8.0 μmol/kg) with 12 mice at each time point used to correlate fibrin contrast uptake with thrombus’ histological stage and fibrin content. Six mice at each time point were immediately subjected to intravascular thrombolytic therapy (10 mg/kg of tissue-type plasminogen activator). Mice were imaged to assess response to lytic therapy 24 hours after thrombolytic treatment. Two mice at each time point were scanned post injection of 0.2 mmol/kg of Gd-DTPA (gadolinium with diethylenetriaminepentacetate, Magnevist, Schering AG, Berlin, Germany) for control purpose. Contrast uptake was correlated positively with the fibrin content of the thrombus measured by Western blotting (R2=0.889; P<0.001). Thrombus relaxation rate (R1) post contrast and the change in visualized thrombus size on late gadolinium enhancement inversion recovery MRI pre–EP-2104R and post–EP-2104R injection were the best predictors for successful thrombolysis (area under the curve, 0.989 [95% confidence interval, 0.97–1.00] and 0.994 [95% confidence interval, 0.98–1.00] respectively). Conclusions MRI with a fibrin-specific contrast agent accurately estimates thrombus fibrin content in vivo and identifies thrombi that are amenable for thrombolysis. PMID:24723557

A review of aripiprazole long-acting injection.

PubMed

Chue, Pierre; Chue, James

2016-01-01

To review the published literature on aripiprazole once monthly, a second generation antipsychotic (SGA) recently developed as a long-acting injection (LAI), in the form of a suspension of lyophilized aripiprazole reconstituted with an aqueous diluent, for intramuscular administration. An electronic database search was conducted using the key words; relevant articles were then hand searched and websites (FDA, EMA, Otsuka, Lundbeck, NIH) reviewed. Efficacy has been demonstrated in preventing relapse in a 52 week study versus placebo, and non-inferiority to oral aripiprazole in a 38 week study, as well as in the treatment of hospitalized adult patients with acutely relapsed schizophrenia. Aripiprazole LAI appears cost-effective versus other SGA-LAIs, with improved health-related quality of life and functioning in a head-to-head study with paliperidone LAI. A 6 month (pre and post), mirror-image switch study demonstrated a reduction in hospitalization and associated costs compared with previous antipsychotic treatment. Safety and tolerability are comparable to oral aripiprazole with no new safety signals. Experience with oral aripiprazole and the current availability of the long-acting formulation suggest a potential benefit in a variety of clinical scenarios and therefore consideration as a treatment option in the treatment of schizophrenia.

Inhibitory effect of natural coumarin compounds, esculetin and esculin, on oxidative DNA damage and formation of aberrant crypt foci and tumors induced by 1,2-dimethylhydrazine in rat colons.

PubMed

Kaneko, Takao; Tahara, Shoichi; Takabayashi, Fumiyo

2007-11-01

The effects of esculetin (6,7-dihydroxycoumarin) and its 6-glycoside, esculin, on 8-oxo-2'-deoxyguanosine (8-oxodG) formation and carcinogenesis induced by a chemical carcinogen, 1,2-dimethylhydrazine (DMH), were examined in the colons of male Fischer 344 rats. Animals were given water containing esculetin or esculin for 7 d before subcutaneous injection of DMH (20 mg/kg body wt), killed 24 h after DMH treatment, and the levels of thiobarbituric acid reactive substances (TBARS) and 8-oxodG in the colons were determined. Both esculetin and esculin suppressed significantly the DMH-induced increases in 8-oxodG and TBARS in rat colon mucosa. We further investigated the modifying effect of esculin intake on the development of DMH-induced colonic aberrant crypt foci (ACF). Animals were given DMH once a week for 4 weeks to induce ACF. They then received water containing esculin ad libitum for 5 weeks (initiation phase) or 11 weeks after DMH treatment (post-initiation phase). Animals in the positive control group received tap water throughout the experiment. At the end of the experiment (16 weeks), the ingestion of esculin during the initiation phase significantly reduced the incidence of gross tumors, the number of ACF per rat and the mean number of AC per focus, while the esculin treatment during the post-initiation phase significantly decreased only the number of ACF per rat. These results suggest that esculin intake has an inhibitory effect on DMH-induced oxidative DNA damage and carcinogenesis in rat colons.

Repeated low-dose exposures to sarin, soman, or VX affect acoustic startle in guinea pigs.

PubMed

Smith, C D; Lee, R B; Moran, A V; Sipos, M L

2016-01-01

Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post-exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period. Published by Elsevier Inc.

[Necessity of applying pharmacovigilance in post-marketing safety monitoring of traditional Chinese medicine injections].

PubMed

Wang, Hai-Nan; Chen, Wen; Fu, Zheng; Du, Wen-min; He, Jia

2008-03-01

Traditional Chinese medicine (TCM) injection has become one of the hotspots in the new TCM research and development. The serious adverse drug reactions happened in clinical have arosed attention widely in the whole society. It's very urgent to monitor the post-marketing safety of TCM injections. This paper elucidated the pharmacovigilance's necessity in the post-marketing safety monitoring of TCM injections, basing on the reason of safety problem of TCM injections and the future developing trend of adverse drug reaction monitoring. Also, this paper introduced the rapid signal detection method of spontaneous reporting system database by data mining technology.

Does size difference in allogeneic cancellous bone granules loaded with differentiated autologous cultured osteoblasts affect osteogenic potential?

PubMed

Lee, Sang-Uk; Chung, Yang-Guk; Kim, Seok-Jung; Oh, Il-Hoan; Kim, Yong-Sik; Ju, Sung-Hun

2014-02-01

We study the efficacy of bone regeneration by using two differently sized allogeneic cancellous bone granules loaded with autologous cultured osteoblasts in a rabbit model. Critical-sized bone defects of the radial shaft were made in 40 New Zealand White rabbits. Small allogeneic bone granules (150-300 μm in diameter) loaded with cultured differentiated autologous osteoblasts were implanted into one forearm (SBG group) and large bone granules (500-710 μm) loaded with osteoblasts were implanted into the forearm of the other side (LBG group). Radiographic evaluations were performed at 3, 6, 9 and 12 weeks and histology and micro-CT image analysis were carried out at 6 and 12 weeks post-implantation. On radiographic evaluation, the LBG group showed a higher bone quantity index at 3 and 6 weeks post-implantation (P < 0.05) but statistical significance was lost at 9 and 12 weeks. The progression of biological processes of the SBG group was faster than that of the LBG group. On micro-CT image analysis, the LBG group revealed a higher total bone volume and surface area than the SBG group at 6 weeks (P < 0.05) but the difference decreased at 12 weeks and was without statistical significance. Histological evaluation also revealed faster progression of new bone formation and maturation in the SBG group. Thus, the two differently sized allogeneic bone granules loaded with co-cultured autologous osteoblasts show no differences in the amount of bone regeneration, although the SBG group exhibits faster progression of bone regeneration and remodeling. This method might therefore provide benefits, such as a short healing time and easy application in an injectable form, in a clinical setting.

Parametric investigation of secondary injection in post-chamber on combustion performance for hybrid rocket motor

NASA Astrophysics Data System (ADS)

Cai, Guobiao; Cao, Binbin; Zhu, Hao; Tian, Hui; Ma, Xuan

2017-11-01

The objective of this effort is to study the combustion performance of a hybrid rocket motor with the help of 3D steady-state numerical simulation, which applies 90% hydrogen peroxide as the oxidizer and hydroxyl-terminated polybutadiene as the fuel. A method of secondary oxidizer injection in post-chamber is introduced to investigate the flow field characteristics and combustion efficiency. The secondary injection medium is the mixed gas coming from liquid hydrogen peroxide catalytic decomposition. The secondary injectors are uniformly set along the circumferential direction of the post-chamber. The simulation results obtained by above model are verified by experimental data. Three influencing parameters are considered: secondary injection diameter, secondary injection angle and secondary injection numbers. Simulation results reveals that this design could improve the combustion efficiency with respect to the same motor without secondary injection. Besides, the secondary injection almost has no effect on the regression rate and fuel sueface temperature distribution. It is also presented that the oxidizer is injected by 8 secondary injectors with a diameter of 7-8 mm in the direction of 120°in post-chamber is identified as the optimized secondary injection pattern, through which combustion efficiency, specific impulse efficiency as well as utilization of propellants are all improved obviously.

Topical steroid and non-steroidal anti-inflammatory drugs inhibit inflammatory cytokine expression on the ocular surface in the botulinum toxin B-induced murine dry eye model.

PubMed

Zhu, Lei; Zhang, Cheng; Chuck, Roy S

2012-01-01

To evaluate the effect of the topical steroid, fluorometholone, and the non-steroidal anti-inflammatory drugs (NSAIDs), nepafenac and ketorolac, on inflammatory cytokine expression of the ocular surface in the botulium toxin B-induced murine dry eye model. Topical artificial tears (0.5% carboxymethylcellulose sodium), 0.1% fluorometholone, 0.1% nepafenac, and 0.4% ketorolac were applied 3 times per day in a dry eye mouse model 1 week after intralacrimal botulium toxin B (BTX-B) or saline (sham) injection. Tear production and corneal fluorescein staining were evaluated in all groups before injection at baseline and at 3 time points up to 4 weeks after injection. The pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were evaluated by immunohistochemistry. BTX-B-injected mice showed significantly decreased aqueous tear production and increased corneal fluorescein staining at the 1 and 2 week time points compared with normal control and saline-injected mice. In the BTX-B-injected mice, immunofluorescent staining for TNF-α and IL-1β in corneal and conjunctival epithelial cells increased significantly at the 2 and 4 week time points compared to that of normal and saline-injected mice, and returned to normal levels at the 4 week time point. Topical fluorometholone significantly improved corneal surface staining in the BTX-B-injected mice after 1 week of treatment, and increased the tear production within 2 weeks, but without statistical significant difference. Topical fluorometholone significantly decreased the staining of TNF-α and IL-1β in corneal and conjunctival epithelia after 1-week treatment. Topical artificial tears, 0.1% nepafenac, and 0.4% ketorolac did not show obvious effects on tear production, corneal surface staining, and levels of IL-1β and TNF-α expression in normal, and BTX-B-injected dry eye mice. Topical fluorometholone caused suppression of inflammatory cytokine expression on the ocular surface in the Botulium toxin B-induced murine dry eye model, while topical NSAIDs demonstrated no clearly beneficial effects.

Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study.

PubMed

Korobelnik, Jean-François; Holz, Frank G; Roider, Johann; Ogura, Yuichiro; Simader, Christian; Schmidt-Erfurth, Ursula; Lorenz, Katrin; Honda, Miki; Vitti, Robert; Berliner, Alyson J; Hiemeyer, Florian; Stemper, Brigitte; Zeitz, Oliver; Sandbrink, Rupert

2014-01-01

To evaluate the efficacy and safety of intravitreal aflibercept injections for treatment of macular edema secondary to central retinal vein occlusion (CRVO). A randomized, multicenter, double-masked phase 3 study. A total of 177 treatment-naive patients with macular edema secondary to CRVO were randomized in a 3:2 ratio. Patients received either 2-mg intravitreal aflibercept or sham injections every 4 weeks for 20 weeks. From week 24 to 48, the aflibercept group received aflibercept as needed (pro re nata [PRN]), and the sham group continued receiving sham injections. The primary efficacy end point was the proportion of patients who gained 15 letters or more in best-corrected visual acuity (BCVA) at week 24. This study reports week 52 results including the proportion of patients who gained 15 letters or more in BCVA and the mean change from baseline BCVA and central retinal thickness. Efficacy end points at week 52 were all exploratory. At week 52, the mean percentage of patients gaining 15 letters or more was 60.2% in the aflibercept group and 32.4% in the sham group (P = 0.0004). Aflibercept patients, compared with sham patients, had a significantly higher mean improvement in BCVA (+16.9 letters vs. +3.8 letters, respectively) and reduction in central retinal thickness (-423.5 μm vs. -219.3 μm, respectively) at week 52 (P < 0.0001 for both). Aflibercept patients received a mean of 2.5 injections (standard deviation, 1.7 injections) during PRN dosing. The most common ocular adverse events in the aflibercept group were related to the injection procedure or the underlying disease, and included macular edema (33.7%), increased intraocular pressure (17.3%), and eye pain (14.4%). Treatment with intravitreal aflibercept provided significant functional and anatomic benefits after 52 weeks as compared with sham. The improvements achieved after 6 monthly doses at week 24 largely were maintained until week 52 with as-needed dosing. Intravitreal aflibercept generally was well tolerated. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Immunotherapeutic effects of chitin in comparison with chitosan against Leishmania major infection.

PubMed

Hoseini, Mostafa Haji Molla; Moradi, Maryam; Alimohammadian, Mohammad Hossein; Shahgoli, Vahid Khaze; Darabi, Hayedeh; Rostami, Ali

2016-04-01

Chitin and chitosan microparticles (MPs) are important immune system stimulators. The aim of this study was to evaluate the protective effects of these compounds in comparison with each other against Leishmania infection in BALB/c mice infected with Leishmania major (L. major). Female BALB/c mice were injected subcutaneously with 2×10(5) promastigotes. Chitin and/or chitosan MPs (<40 μm) were subcutaneously injected in the BALB/c mice with two-day intervals until two weeks. Mice in all groups were sacrificed at 12 weeks post-infection. Enumeration of viable parasites was performed using limiting dilution assay. Furthermore, the animals (5 mice/group) were sacrificed two weeks post-infection. The lymph node cells were isolated and the effects of the chitinous MPs on the proliferation and production of cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) were determined. The mean sizes of lesions were significantly smaller in chitin (0.6±0.12 mm) and chitosan treated groups (1.2±0.8 mm) than in the control group (6.2±1.7 mm) (P<0.05). The parasite load in the lymph nodes of the treated mice was significantly lower than that in the lymph nodes of controls (1.31×10(6) vs 8.24×10(7) parasite/lymph node [P=0.032] and 7.49×10(6) vs 8.24×10(7) parasite/lymph node [P=0.05] for chitin and chitosan MPs treatment, respectively). We found that chitinous MPs induced cell proliferation and that chitin but not chitosan increased TNF-α and IL-10 production. Chitin appears that it has more effect than chitosan against leishmaniasis. The current study revealed that chitinous MPs had significant activity against L. major and could be considered as new therapeutic modality in leishmaniasis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

PubMed Central

Yoshizumi, Tomo; Zhu, Yang; Jiang, Hongbin; D’Amore, Antonio; Sakaguchi, Hirokazu; Tchao, Jason; Tobita, Kimimasa; Wagner, William R.

2016-01-01

Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes. PMID:26774561

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction.

PubMed

Yoshizumi, Tomo; Zhu, Yang; Jiang, Hongbin; D'Amore, Antonio; Sakaguchi, Hirokazu; Tchao, Jason; Tobita, Kimimasa; Wagner, William R

2016-03-01

Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Effect of Finasteride and Dutasteride on the Growth of WPE1-NA22 Prostate Cancer Xenografts in Nude Mice

PubMed Central

Opoku-Acheampong, Alexander B.; Nelsen, Michelle K.; Unis, Dave; Lindshield, Brian L.

2012-01-01

Background 5α-reductase 1 (5αR1) and 5α-reductase 2 (5αR2) convert testosterone into the more potent androgen dihydrotestosterone. 5αR2 is the main isoenzyme in normal prostate tissue; however, most prostate tumors have increased 5αR1 and decreased 5αR2 expression. Previously, finasteride (5αR2 inhibitor) treatment begun 3 weeks post-tumor implantation had no effect on Dunning R3327-H rat prostate tumor growth. We believe the tumor compensated for finasteride treatment by increasing tumor 5αR1 expression or activity. We hypothesize that finasteride treatment would not significantly alter tumor growth even if begun before tumor implantation, whereas dutasteride (5αR1 and 5αR2 inhibitor) treatment would decrease tumor growth regardless of whether treatment was initiated before or after tumor implantation. Methodology/Principal Findings Sixty 8-week-old male nude mice were randomized to Control, Pre- and Post-Finasteride, and Pre- and Post-Dutasteride (83.3 mg drug/kg diet) diet groups. Pre- and post-groups began their treatment diets 1–2 weeks prior to or 3 weeks after subcutaneous injection of 1×105 WPE1-NA22 human prostate cancer cells, respectively. Tumors were allowed to grow for 22 weeks; tumor areas, body weights, and food intakes were measured weekly. At study's conclusion, prostate and seminal vesicle weights were significantly decreased in all treatment groups versus the control; dutasteride intake significantly decreased seminal vesicle weights compared to finasteride intake. No differences were measured in final tumor areas or tumor weights between groups, likely due to poor tumor growth. In follow-up studies, proliferation of WPE1-NA22 prostate cancer cells and parent line RWPE-1 prostate epithelial cells were unaltered by treatment with testosterone, dihydrotestosterone, or mibolerone, suggesting that these cell lines are not androgen-sensitive. Conclusion The lack of response of WPE1-NA22 prostate cancer cells to androgen treatment may explain the inadequate tumor growth observed. Additional studies are needed to determine whether finasteride and dutasteride are effective in decreasing prostate cancer development/growth. PMID:22242155

Effectiveness of initial extracorporeal shock wave therapy on the newly diagnosed lateral or medial epicondylitis.

PubMed

Lee, Sang Seok; Kang, Sangkuk; Park, Noh Kyoung; Lee, Chan Woo; Song, Ho Sup; Sohn, Min Kyun; Cho, Kang Hee; Kim, Jung Hwan

2012-10-01

To evaluate the effectiveness of initial extracorporeal shock wave therapy (ESWT) for patients newly diagnosed with lateral or medial epicondylitis, compared to local steroid injection. An analysis was conducted of twenty-two patients who were newly confirmed as lateral or medial epicondylitis through medical history and physical examination. The ESWT group (n=12) was treated once a week for 3 weeks using low energy (0.06-0.12 mJ/mm(2), 2,000 shocks), while the local steroid injection group (n=10) was treated once with triamcinolone 10 mg mixed with 1% lidocaine solution. Nirschl score and 100 point score were assessed before and after the treatments of 1st, 2nd, 4th and 8th week. And Roles and Maudsley score was assessed one and eight weeks after the treatments. Both groups showed significant improvement in Nirschl score and 100 point score during the entire period. The local steroid injection group improved more in Nirschl score at the first week and in 100 point score at the first 2 weeks, compared to those of the ESWT group. But the proportion of excellent and good grades of Roles and Maudsley score in the ESWT group increased more than that of local steroid injection group by the final 8th week. The ESWT group improved as much as the local steroid injection group as treatment for medial and lateral epicondylitis. Therefore, ESWT can be a useful treatment option in patients for whom local steroid injection is difficult.

Effect of Intra-articular Hyaluronic Acid Injection on Hemiplegic Shoulder Pain After Stroke.

PubMed

Jang, Myung Hun; Lee, Chang-Hyung; Shin, Yong-Il; Kim, Soo-Yeon; Huh, Sung Chul

2016-10-01

To evaluate the efficacy of intra-articular hyaluronic acid (IAHA) injection for hemiplegic shoulder pain (HSP) after stroke. Thirty-one patients with HSP and limited range of motion (ROM) without spasticity of upper extremity were recruited. All subjects were randomly allocated to group A (n=15) for three weekly IAHA injection or group B (n=16) for a single intra-articular steroid (IAS) injection. All injections were administered by an expert physician until the 8th week using a posterior ultrasonography-guided approach. Shoulder joint pain was measured using the Wong-Baker Scale (WBS), while passive ROM was measured in the supine position by an expert physician. There were no significant intergroup differences in WBS or ROM at the 8th week. Improvements in forward flexion and external rotation were observed from the 4th week in the IAHA group and the 8th week in the IAS group. Subjects experienced a statistically significant improvement in pain from the 1st week in the IAS and from the 8th week in IAHA group, respectively. IAHA seems to have a less potent ability to reduce movement pain compared to steroid in the early period. However, there was no statistically significant intergroup difference in WBS and ROM improvements at the 8th week. IAHA might be a good alternative to steroid for managing HSP when the use of steroid is limited.

An adenosine kinase inhibitor attenuates tactile allodynia in a rat model of diabetic neuropathic pain.

PubMed

Lynch, J J; Jarvis, M F; Kowaluk, E A

1999-01-08

The present study was conducted to characterize the development of tactile allodynia in the streptozotocin-induced rat model of diabetes, and to evaluate the antinociceptive effects of systemically administered morphine and the adenosine kinase inhibitor, 5'-deoxy-5-iodotubercidin (5'd-5IT) in this model. Rats were injected with 75 mg/kg streptozotocin (i.p.), and blood glucose levels were determined 3-4 weeks later. Diabetic (blood glucose levels > or = 250 mg/dl) and vehicle-injected rats were examined weekly for the development of tactile allodynia by measuring the threshold for hind paw withdrawal using von Frey hairs. Withdrawal thresholds were reduced to 6.8+/-0.6 g (mean+/-S.E.M.) in approximately one-third of streptozotocin-treated rats 7 weeks after streptozotocin treatment as compared to control thresholds (13.2+/-0.1 g), and this allodynia persisted for at least an additional 7 weeks. In additional experiments, morphine sulfate (5-21 micromol/kg, i.p.) produced dose-dependent antinociceptive effects on tactile allodynia for up to 2 h post-dosing. The adenosine kinase inhibitor, 5'd-5IT (2.5 and 5 micromol/kg, i.p.) also dose-dependently attenuated tactile allodynia. Pretreatment with the opioid receptor antagonist, naloxone (27 micromol/kg, i.p.) or the non-selective adenosine receptor antagonist, theophylline (111 micromol/kg, i.p.) significantly diminished the anti-allodynic effects of morphine and 5'd-5IT, respectively. The present study demonstrates that the potent and selective adenosine kinase inhibitor, 5'd-5IT, is equally effective as morphine in blocking tactile allodynia in this model.

Effect of ice on pain after corticosteroid injection in the hand and wrist: a randomized controlled trial.

PubMed

An, T W; Boone, S L; Boyer, M I; Gelberman, R H; Osei, D A; Calfee, R P

2016-11-01

This prospective, randomized controlled study was designed to determine if applying ice to the site of corticosteroid injections in the hand and wrist reduces post-injection pain. Patients receiving corticosteroid injections in the hand or wrist at a tertiary institution were enrolled. Subjects were randomized to apply ice to the injection site and take scheduled over-the-counter analgesics ( n = 36) or take scheduled over-the-counter analgesics alone ( n = 32). There were no significant differences in the mean pain score between the two groups at any time-point (pre-injection or 1-5 days post-injection). In regression modelling, the application of ice did not predict pain after injection. Visual analogue pain scores increased at least 2 points (0-10 scale) after injection in 17 out of 36 patients in the ice group versus ten out of 32 control patients. We conclude that the application of ice in addition to over-the-counter analgesics does not reduce post-injection pain after corticosteroid injection in the hand or wrist. I Therapeutic Study.

Heavy-Duty Low-Temperature and Diesel Combustion & Heavy-Duty Combustion Modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musculus, Mark P.

Regulatory drivers and market demands for lower pollutant emissions, lower carbon dioxide emissions, and lower fuel consumption motivate the development of clean and fuel-efficient engine operating strategies. Most current production engines use a combination of both in-cylinder and exhaust emissions-control strategies to achieve these goals. The emissions and efficiency performance of in-cylinder strategies depend strongly on flow and mixing processes associated with fuel injection. Various diesel engine manufacturers have adopted close-coupled post-injection combustion strategies to both reduce pollutant emissions and to increase engine efficiency for heavy-duty applications, as well as for light- and medium-duty applications. Close-coupled post-injections are typically shortmore » injections that follow a larger main injection in the same cycle after a short dwell, such that the energy conversion efficiency of the post-injection is typical of diesel combustion. Of the various post-injection schedules that have been reported in the literature, effects on exhaust soot vary by roughly an order of magnitude in either direction of increasing or decreasing emissions relative to single injections (O’Connor et al., 2015). While several hypotheses have been offered in the literature to help explain these observations, no clear consensus has been established. For new engines to take full advantage of the benefits that post-injections can offer, the in-cylinder mechanisms that affect emissions and efficiency must be identified and described to provide guidance for engine design.« less

Influence of the cardiac glycoside digoxin on cardiac troponin I, acid–base and electrolyte balance, and haematobiochemical profiles in healthy donkeys (Equus asinus)

PubMed Central

2014-01-01

Background The effect of digoxin administration on the serum concentration of the cardiac troponin I (cTnI) has not been reported to date in equidae. This study was therefore designed to evaluate the effect of digoxin on cardiac cell damage in donkeys (Equus asinus) as assessed by cTnI, acid–base and electrolyte balance and haematobiochemical profiles. Ten clinically healthy donkeys were given an IV infusion of digoxin at a dose of 14 μg/kg. Blood samples were collected from the donkeys up through 72 h post-injection. Results Three of the donkeys exhibited increased heart and respiratory rates post-injection. In the other seven animals, the heart and respiratory rates were lower 4 h post-injection. The serum digoxin concentration increased significantly at many time points after injection. The serum concentration of cTnI did not differ significantly between pre- and post-injection. An increase in blood pH was noted at 3 h after digoxin injection. There were also increases in PO2 and in oxygen saturation. Decreases in PCO2 at 2 to 48 h post-injection as well as a decrease in blood lactate at 4 h post-injection were observed. The serum concentration of glucose remained significantly elevated at all-time points after digoxin injection. Conclusions It is concluded that administration of digoxin to healthy donkeys (14 μg/kg) did not result in elevations of serum cTnI concentration, signs of digoxin intoxication, ECG abnormalities and did not increase serum concentrations of blood urea nitrogen and creatinine. PMID:24621180

Platelet-rich plasma for chronic lateral epicondylitis: is one injection sufficient?

PubMed

Glanzmann, Michael C; Audigé, Laurent

2015-12-01

Chronic lateral epicondylitis is generally treated using nonsurgical methods including physiotherapy and infiltrations of cortisone or platelet-rich plasma (PRP). The latter is known for its simple application as well as associated low risk of adverse events, which lend to its widespread use in treating various musculoskeletal conditions. There is limited evidence on the effectiveness of PRP injections to optimally treat chronic lateral epicondylitis. This study explored the effectiveness of single or repeated injections for patients with symptoms that spanned 6 months or more and were unresponsive to alternate conservative measures. Patients with chronic lateral epicondylitis received PRP injections in 4-week intervals that were complemented with standardized physical therapy. Patient-reported outcomes based on the patient-rated elbow evaluation (PREE), quick disabilities of the arm, shoulder and hand (qDASH), and EuroQol (five dimensions) 3-level version (EQ5D3L) questionnaires were documented at each visit including 6 months after the first injection. These outcomes were compared between patients receiving 1 vs. 2 or 3 PRP injections. Sixty-two patients received one (n = 36) or more (n = 26) PRP injections. The mean baseline to 6-month follow-up scores of the PREE and qDASH questionnaires improved significantly from 54.0 to 23.0 and 50.3 to 20.7, respectively. The mean baseline EQ5D3L-visual analogue scale score improved from 62.5 to 82.9 by 6 months post-injection. These outcomes did not significantly differ between the patients who received varying numbers of injections. Patients with chronic lateral epicondylitis reported significant pain relief and gain in function as well as quality of life 6 months after localized PRP treatment. A single PRP injection may be sufficient.

The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model

PubMed Central

Yamaguchi, Shoki; Aoyama, Tomoki; Ito, Akira; Nagai, Momoko; Iijima, Hirotaka; Tajino, Junichi; Zhang, Xiangkai; Kiyan, Wataru; Kuroki, Hiroshi

2016-01-01

The repair of articular cartilage is challenging owing to the restriction in the ability of articular cartilage to repair itself. Therefore, cell supplementation therapy is possible cartilage repair method. However, few studies have verified the efficacy and safety of cell supplementation therapy. The current study assessed the effect of exercise on early the phase of cartilage repair following cell supplementation utilizing mesenchymal stromal cell (MSC) intra-articular injection. An osteochondral defect was created on the femoral grooves bilaterally of Wistar rats. Mesenchymal stromal cells that were obtained from male Wistar rats were cultured in monolayer. After 4 weeks, MSCs were injected into the right knee joint and the rats were randomized into an exercise or no-exercise intervention group. The femurs were divided as follows: C group (no exercise without MSC injection); E group (exercise without MSC injection); M group (no exercise with MSC injection); and ME group (exercise with MSC injection). At 2, 4, and 8 weeks after the injection, the femurs were sectioned and histologically graded using the Wakitani cartilage repair scoring system. At 2 weeks after the injection, the total histological scores of the M and ME groups improved significantly compared with those of the C group. Four weeks after the injection, the scores of both the M and ME groups improved significantly. Additionally, the scores in the ME group showed a significant improvement compared to those in the M group. The improvement in the scores of the E, M, and ME groups at 8 weeks were not significantly different. The findings indicate that exercise may enhance cartilage repair after an MSC intra-articular injection. This study highlights the importance of exercise following cell transplantation therapy. PMID:26968036

The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model.

PubMed

Yamaguchi, Shoki; Aoyama, Tomoki; Ito, Akira; Nagai, Momoko; Iijima, Hirotaka; Tajino, Junichi; Zhang, Xiangkai; Kiyan, Wataru; Kuroki, Hiroshi

2016-01-01

The repair of articular cartilage is challenging owing to the restriction in the ability of articular cartilage to repair itself. Therefore, cell supplementation therapy is possible cartilage repair method. However, few studies have verified the efficacy and safety of cell supplementation therapy. The current study assessed the effect of exercise on early the phase of cartilage repair following cell supplementation utilizing mesenchymal stromal cell (MSC) intra-articular injection. An osteochondral defect was created on the femoral grooves bilaterally of Wistar rats. Mesenchymal stromal cells that were obtained from male Wistar rats were cultured in monolayer. After 4 weeks, MSCs were injected into the right knee joint and the rats were randomized into an exercise or no-exercise intervention group. The femurs were divided as follows: C group (no exercise without MSC injection); E group (exercise without MSC injection); M group (no exercise with MSC injection); and ME group (exercise with MSC injection). At 2, 4, and 8 weeks after the injection, the femurs were sectioned and histologically graded using the Wakitani cartilage repair scoring system. At 2 weeks after the injection, the total histological scores of the M and ME groups improved significantly compared with those of the C group. Four weeks after the injection, the scores of both the M and ME groups improved significantly. Additionally, the scores in the ME group showed a significant improvement compared to those in the M group. The improvement in the scores of the E, M, and ME groups at 8 weeks were not significantly different. The findings indicate that exercise may enhance cartilage repair after an MSC intra-articular injection. This study highlights the importance of exercise following cell transplantation therapy.

The Efficacy of Cyclic Injection of Bone Morphogenetic Protein-2 in Large-Scale Calvarial Bone Defects.

PubMed

Choi, Jin Mi; Jeong, Woo Shik; Park, Eun Jung; Choi, Jong Woo

2017-03-01

Bone morphogenetic protein-2 (BMP-2) appears to be one of the most potent growth factors thus far studied. However, recent publications on the clinical application of BMP-2 revealed that its correct control is the paramount issue in clinical practice. For improving BMP-2 delivery, the cyclic administration might be an alternative. Accordingly, the authors cyclically injected BMP-2 in a cyclic injection model of large cranial defects to maintain the proper dosage during the bone healing process. A 10-mm diameter calvarial bone defect was produced using a round drill in 8-week-old Sprague-Dawley rats. Silk-hydroxyapatite scaffolds soaked in the appropriate concentration of BMP-2 were implanted into the defect. The animals were split into 4 single-injection groups and 3 multiple-injection groups; the latter groups received weekly subcutaneous injections of BMP-2 solution (1, 5, and 10 μg/mL) for 4 weeks, whereas the former groups received a single injection of BMP-2 at these concentrations. Each rat underwent computed tomography at 8 weeks. In terms of total volumes of the new bone, the 5 μg/mL multiple-injection BMP-2 group had significantly greater increases in bone volume than the single-injection groups. In terms of bone thickness, the multiple-injection groups had better outcomes than the single-injection groups. Thus, the cyclic injection protocol restored the original thickness without overgrowth. Cyclic injection of BMP-2 permits more accurate dosage control than single injection and improves thickness and dense bone regeneration. Therefore, it may represent a promising approach for future clinical trials. Further investigation using a greater number of animals is required.

Effects of one-time and two-time intra-articular injection of hyaluronic acid sodium salt after joint surgery in dogs

PubMed Central

Boonsri, Burin; Sripratak, Thatdanai; Markmee, Patsanan

2013-01-01

Thirty-one dogs with patellar luxation (grades 2 and 3) were categorized into three groups. Group 1 (G.1; n = 12) had sodium hyaluronate (SHA) intra-articularly injected into the stifle joint that received surgery. Group 2 (G.2; n = 10) received SHA twice: first after surgery and then 1 week later. Group 3 (G.3; n = 9) served as a control, without injection. Blood was collected before injection and then once a week for 4 weeks after injection for evaluation of chondroitin sulfate (CS-WF6) and hyaluronan (HA). The results revealed significantly (p < 0.05) improved clinical scores by the end of week 4 in G.1 and G.2 relative to G.3; however, there was no significant difference between G.1 and G.2. There was a significant decrease (p < 0.05) in serum CS-WF6 levels beginning at week 2 in G.1 and G.2. At weeks 3 and 4, serum HA in G.1 and G.2 differed from that in G.3 (p < 0.05). No significant difference (p > 0.05) was observed in serum biomarkers between G.1 and G.2. In conclusion, intra-articular injection with SHA after joint surgery may improve homeostasis of the joint, retarding the process of OA. PMID:23814475

Intraarticular injection autologous platelet-rich plasma and bone marrow concentrate in a goat osteoarthritis model.

PubMed

Wang, Zhen; Zhai, Chenjun; Fei, Hao; Hu, Junzheng; Cui, Weiding; Wang, Zhen; Li, Zeng; Fan, Weimin

2018-02-21

To evaluate the effects of intraarticular injections of autologous platelet-rich plasma (PRP) or bone marrow concentrate (BMC) on osteoarthritis (OA), 24 adult goats were equally divided into control (Ctrl), saline (NS), PRP, and BMC groups, and OA was induced by surgery in NS, PRP, and BMC groups. Autologous PRP and BMC were obtained from whole blood and bone marrow aspirates, respectively. The data revealed, platelets were increased in BMC by 1.8-fold, monocytes by 5.6-fold, TGF-β1 by 7.7-fold, and IGF-1 by 3.6-fold (p < 0.05), and platelets were increased in PRP by 2.9-fold, and TGF-β1 by 3.3-fold (p < 0.05). From the sixth week post-operation, saline, PRP, and BMC were administered by intraarticular injection once every 4 weeks, three consecutive times. After the animals were sacrificed, inflammatory cytokines in the synovial fluid was measured, and bone and cartilage degeneration progression was observed by macroscopy, histology, and immunohistochemistry. Compared with the NS group, the level of inflammatory cytokines was reduced in the PRP and BMC groups (p < 0.05). Histologically, delayed cartilage degeneration and higher levels of extracellular matrix (ECM) were observed in both PRP and BMC treated groups (p < 0.05). Furthermore, the BMC group showed greater cartilage protection and less ECM loss than the PRP group (p < 0.05). In summary, this study showed that intraarticular injection of autologous PRP and BMC has therapeutic efficacy in a goat osteoarthritis model, with the greater benefit in terms of cartilage protection being observed in the BMC-treated group than PRP. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Platelet-rich plasma injection in the treatment of frozen shoulder: A randomized controlled trial with 6-month follow-up
.

PubMed

Lin, Junhong

2018-06-22

Platelet-rich plasma (PRP) has been utilized in the treatment of chronic injuries. The current study aimed to evaluate the efficiency of PRP in the treatment of frozen shoulder compared to procaine. 60 patients with frozen shoulder were randomly divided into two groups. The PRP group was injected with 2 mL prepared PRP, while in the control group procaine was used. The stretching and formal strengthening exercises were carried out in both groups during the 6-month follow-up. Visual analog scale (VAS) score was used to assess the subjective pain intensity of the patients. The general shoulder assessment instruments (University of California at Los Angeles (UCLA) shoulder scale) was applied to measure the shoulder function of the patients. The evaluation was performed before treatment and 1 week, 1 month, 3 months, and 6 months after the first injection. The efficiency of PRP was superior to and longer than procaine. VAS scores were both declined in PRP and control group after 1 week, 1 month, and 3 months of first injection. By contrast, it was elevated was elevated in the control group while continued to decline in PRP group. The UCLA scores were almost linearly improved in the PRP group, while the UCLA scores decreased to a lower level at the final follow-up visit compared to that post 3 months in the control group. PRP and procaine were effective in treating frozen shoulder. PRP was more effective and had a more prolonged efficiency than the procaine control. Nevertheless, the definite conclusion should come from further large-scale clinical trials.
.

Hypertonic saline-epinephrine local injection therapy for post-endoscopic sphincterotomy bleeding: removal of blood clots using pure ethanol local injection.

PubMed

Sakai, Yuji; Tsuyuguchi, Toshio; Sugiyama, Harutoshi; Nishikawa, Takao; Kurosawa, Jo; Saito, Masayoshi; Tawada, Katsunobu; Mikata, Rintaro; Tada, Motohisa; Ishihara, Takeshi; Yokosuka, Osamu

2013-08-01

Bleeding following endoscopic sphincterotomy (EST) is a rare but unavoidable complication of the procedure. We routinely perform local injection of hypertonic saline-epinephrine (HSE) for the treatment of post-EST bleeding. Any blood clot is removed only by irrigation with water after local injection of pure ethanol into the blood clot to cause crusting. We evaluated the usefulness of this treatment method. Subjects were 8 patients (1.2%) with post-EST bleeding requiring hemostatic intervention among 682 patients undergoing EST. After determination of the bleeding point, local injection of HSE was performed. When an adherent blood clot was present, pure ethanol was injected into the blood clot and then irrigation with water was performed to remove the blood clot. Endoscopic hemostasis was successfully achieved in all the 8 patients (100%). In 4 patients (50%), the adherent blood clots were successfully removed only with pure ethanol local injection into the blood clot followed by irrigation with water. No complications of the hemostatic procedure occurred in any patients. This study indicated that hemostasis with HSE local injection can be safe and useful for the treatment of post-EST bleeding, and also that blood clot removal with pure ethanol local injection can be useful.

Cardiovascular progenitor-derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure.

PubMed

Kervadec, Anaïs; Bellamy, Valérie; El Harane, Nadia; Arakélian, Lousineh; Vanneaux, Valérie; Cacciapuoti, Isabelle; Nemetalla, Hany; Périer, Marie-Cécile; Toeg, Hadi D; Richart, Adèle; Lemitre, Mathilde; Yin, Min; Loyer, Xavier; Larghero, Jérôme; Hagège, Albert; Ruel, Marc; Boulanger, Chantal M; Silvestre, Jean-Sébastien; Menasché, Philippe; Renault, Nisa K E

2016-06-01

Cell-based therapies are being explored as a therapeutic option for patients with chronic heart failure following myocardial infarction. Extracellular vesicles (EV), including exosomes and microparticles, secreted by transplanted cells may orchestrate their paracrine therapeutic effects. We assessed whether post-infarction administration of EV released by human embryonic stem cell-derived cardiovascular progenitors (hESC-Pg) can provide equivalent benefits to administered hESC-Pg and whether hESC-Pg and EV treatments activate similar endogenous pathways. Mice underwent surgical occlusion of their left coronary arteries. After 2-3 weeks, 95 mice included in the study were treated with hESC-Pg, EV, or Minimal Essential Medium Alpha Medium (alpha-MEM; vehicle control) delivered by percutaneous injections under echocardiographic guidance into the peri-infarct myocardium. functional and histologic end-points were blindly assessed 6 weeks later, and hearts were processed for gene profiling. Genes differentially expressed between control hearts and hESC-Pg-treated and EV-treated hearts were clustered into functionally relevant pathways. At 6 weeks after hESC-Pg administration, treated mice had significantly reduced left ventricular end-systolic (-4.20 ± 0.96 µl or -7.5%, p = 0.0007) and end-diastolic (-4.48 ± 1.47 µl or -4.4%, p = 0.009) volumes compared with baseline values despite the absence of any transplanted hESC-Pg or human embryonic stem cell-derived cardiomyocytes in the treated mouse hearts. Equal benefits were seen with the injection of hESC-Pg-derived EV, whereas animals injected with alpha-MEM (vehicle control) did not improve significantly. Histologic examination suggested a slight reduction in infarct size in hESC-Pg-treated animals and EV-treated animals compared with alpha-MEM-treated control animals. In the hESC-Pg-treated and EV-treated groups, heart gene profiling identified 927 genes that were similarly upregulated compared with the control group. Among the 49 enriched pathways associated with these up-regulated genes that could be related to cardiac function or regeneration, 78% were predicted to improve cardiac function through increased cell survival and/or proliferation or DNA repair as well as pathways related to decreased fibrosis and heart failure. In this post-infarct heart failure model, either hESC-Pg or their secreted EV enhance recovery of cardiac function and similarly affect cardiac gene expression patterns that could be related to this recovery. Although the mechanisms by which EV improve cardiac function remain to be determined, these results support the idea that a paracrine mechanism is sufficient to effect functional recovery in cell-based therapies for post-infarction-related chronic heart failure. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Preventive effects of fermented brown rice and rice bran against N-nitrosobis (2-oxopropyl) amine-induced pancreatic tumorigenesis in male hamsters.

PubMed

Kuno, Toshiya; Takahashi, Satoru; Tomita, Hiroyuki; Hisamatsu, Kenji; Hara, Akira; Hirata, Akihiro; Kobayashi, Hiroshi; Mori, Hideki

2015-12-01

Fermented brown rice by Aspergillus oryzae (FBRA) is known to have the potential to prevent chemical carcinogenesis of the colon, liver, esophagus, urinary bladder, stomach and lungs in rodents. The present study examined the possible chemopreventive effects of FBRA on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic tumorigenesis in hamsters. Five-week-old male Syrian golden hamsters were divided into seven groups. Groups 1-5 were subcutaneously injected with BOP (10 mg/kg body weight) four times during week 6 to induce pancreatic tumors, while groups 6 and 7 were injected with saline. Groups 2 and 3 were fed diets containing 5 and 10% FBRA, respectively, during the initiation phase. By contrast, groups 4 and 5 were fed diets containing 5 and 10% FBRA, respectively, during the post-initiation phase. Group 6 received a diet containing 10% FBRA throughout the experiment, and group 7 was kept on the basal diet alone and served as the untreated control. At the termination of the study (week 22), oral intake of 10% FBRA (group 5) during the post-initiation phase was identified to have significantly reduced the multiplicity (number of lesions/animal) of ductal adenocarcinoma [pancreatic intraepithelial neoplasia 3 (PanIN3); carcinoma in situ and invasive carcinoma] in comparison with group 1 control hamsters (0.24±0.44 vs. 0.71±0.72; P<0.05). Treatment with 10% FBRA in the post-initiation phase inhibited the progression of normal/precancerous lesions (PanIN1, mild hyperplastic lesions; and PanIN2, papillary hyperplasia) to ductal adenocarcinomas. Furthermore, dietary exposure to 10% FBRA during the initiation (group 3) and post-initiation phases (group 5) significantly reduced the multiplicity of PanIN2 (group 3, 0.55±0.69; group 5, 0.45±0.69; versus group 1, 1.26±1.24; P<0.05 and P<0.01, respectively). A significant reduction of Ki-67 positivity of PanIN2 in group 5 was also confirmed (group 5, 0.05±0.03; group 1, 0.22±0.12; P<0.01). Using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, augmentation of apoptosis by FBRA exposure in the non-lesional ductal epithelium and proliferative lesions was not evident. These findings indicate that FBRA exhibits inhibitory effects on BOP-induced pancreatic tumorigenesis in hamsters due to the reduced proliferation rate of tumor cells. Thus, FBRA may be a promising chemopreventive agent in human pancreatic cancer.

A recombinant lentiviral PDGF-driven mouse model of proneural glioblastoma.

PubMed

Rahme, Gilbert J; Luikart, Bryan W; Cheng, Chao; Israel, Mark A

2018-02-19

Mouse models of glioblastoma (GBM), the most aggressive primary brain tumor, are critical for understanding GBM pathology and can contribute to the preclinical evaluation of therapeutic agents. Platelet-derived growth factor (PDGF) signaling has been implicated in the development and pathogenesis of GBM, specifically the proneural subtype. Although multiple mouse models of PDGF-driven glioma have been described, they require transgenic mice engineered to activate PDGF signaling and/or impair tumor suppressor genes and typically represent lower-grade glioma. We designed recombinant lentiviruses expressing both PDGFB and a short hairpin RNA targeting Cdkn2a to induce gliomagenesis following stereotactic injection into the dentate gyrus of adult immunocompetent mice. We engineered these viruses to coexpress CreERT2 with PDGFB, allowing for deletion of floxed genes specifically in transduced cells, and designed another version of this recombinant lentivirus in which enhanced green fluorescent protein was coexpressed with PDGFB and CreERT2 to visualize transduced cells. The dentate gyrus of injected mice showed hypercellularity one week post-injection and subsequently developed bona fide tumors with the pathologic hallmarks of GBM leading to a median survival of 77 days post-injection. Transcriptomic analysis of these tumors revealed a proneural gene expression signature. Informed by the genetic alterations observed in human GBM, we engineered a novel mouse model of proneural GBM. While reflecting many of the advantages of transgenic mice, this model allows for the facile in vivo testing of gene function in tumor cells and makes possible the rapid production of large numbers of immunocompetent tumor-bearing mice for preclinical testing of therapeutics. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Neck surface electromyography as a measure of vocal hyperfunction before and after injection laryngoplasty

PubMed Central

Stepp, Cara E.; Heaton, James T.; Jetté, Marie E.; Burns, James A.; Hillman, Robert E.

2012-01-01

Objectives The goal of this preliminary study was to determine if neck surface electromyography (sEMG) is sensitive to possible changes in vocal hyperfunction associated with injection laryngoplasty, particularly with respect to alterations in the degree of vocal hyperfunction. Methods Thirteen individuals undergoing office-based injection laryngoplasty for glottal phonatory insufficiency were prospectively studied using a battery of acoustic, aerodynamic, endoscopic, and anterior neck surface electromyographic (sEMG) assessments before the procedure and approximately one week after. Results Anterior neck sEMG was not significantly reduced (p < 0.05) post-procedure; however, perceptual ratings of strain and false vocal fold (FVF) compression were both significantly reduced, reflecting a decrease in vocal hyperfunction. Conclusions The results do not support the use of anterior neck sEMG measures to assess vocal hyperfunction, and place into question the use of some other measures (estimates of anterior-posterior (AP) supraglottal compression, quantitative measures of AP and FVF supraglottal compression, and acoustic vowel rise times) that have been considered reflective of vocal hyperfunction. PMID:21033026

Safety and Efficacy of Intra-articular Injection of Platelet-Rich Plasma in Patients With Ankle Osteoarthritis.

PubMed

Fukawa, Taisuke; Yamaguchi, Satoshi; Akatsu, Yorikazu; Yamamoto, Yohei; Akagi, Ryuichiro; Sasho, Takahisa

2017-06-01

An intra-articular injection of platelet-rich plasma (PRP) may be an effective treatment for osteoarthritis (OA). However, its efficacy in ankle OA has not been investigated yet. The purpose of this study was to assess the safety and efficacy of an intra-articular injection of PRP in patients with ankle OA during a 24-week period. Twenty ankles of 20 patients with varus-type ankle OA who received intra-articular injections of PRP were evaluated. PRP was extracted from whole blood by using the double-spin technique. Three injections of 2-mL PRP were administered to the ankle at an interval of 2 weeks under ultrasonographic guidance. Adverse events and efficacy were assessed at 4, 12, and 24 weeks after the last injection. Clinical outcomes were assessed by using the visual analog scale (VAS) for pain, the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale, and the Self-Administered Foot Evaluation Questionnaire (SAFE-Q). No serious adverse effects were observed during the follow-up period. The VAS and JSSF scale scores significantly decreased from baseline to 4, 12, and 24 weeks after treatment ( P < .001). The mean score in the pain-related subscale of the SAFE-Q significantly improved from baseline to 12 weeks after treatment ( P = .04). Overall, the amount of pain reduction was maximal at 12 weeks after the last injection, and the effect was reduced at 24 weeks. The patients with late-stage OA had worse scores in all outcomes than those with early-stage OA. Intra-articular injections of PRP resulted in no serious adverse effects and significantly reduced pain in the patients with ankle OA. PRP treatment can be safe and effective and may be an option in the treatment of ankle OA. Level IV, case series.

Post-Injection Induced Seismicity in EGS: Triggering Mechanisms and Mitigation.

NASA Astrophysics Data System (ADS)

De Simone, S.; Carrera, J.; Vilarrasa, V.

2017-12-01

Induced microseismicity is a controversial issue related to Enhanced Geothermal Systems (EGS) and in general with fluid injection into deep geological formations. The occurring of felt earthquakes after stopping injection especially generates concern, because the correlation between injection and seismic activity is unclear. The aim of this work is to advance in the understanding of the processes that may induce or trigger co- and post-injection seismicity. To this end we investigate the thermo-hydro-mechanical coupling by means of numerical simulations of hydraulic stimulation of deep geothermal systems. We find that preferential flow through conductive fractures or fault zones provokes pressure and temperature perturbations that result in not only heterogeneous variation of the stress field, but also highly anisotropic variations of the local stress tensor. Anisotropic variations tend to stabilize some fractures, but destabilize others. Moreover, activation of shear slip causes a significant variation of the stress field that enlarges the range of critical fracture orientations. We find that post-injection seismicity may occur on non-critically oriented faults that were originally stable. During injection, such faults become destabilized by thermal and shear slip stress changes, but remain static by the superposition of the stabilizing effect of pressure forces. However, these fractures become unstable and fail when the pressure forcing dissipates shortly after injection stops abruptly, which suggests that a slow reduction in injection rate may mitigate post-injection seismicity.

Efficacy and safety of collagenase clostridium histolyticum for Dupuytren disease nodules: a randomized controlled trial.

PubMed

Costas, Bronier; Coleman, Stephen; Kaufman, Greg; James, Robert; Cohen, Brian; Gaston, R Glenn

2017-08-30

To determine the safety and efficacy of collagenase clostridium histolyticum (CCH) injection for the treatment of palmar Dupuytren disease nodules. In this 8-week, double-blind trial, palpable palmar nodules on one hand of adults with Dupuytren disease were selected for treatment. Patients were randomly assigned using an interactive web response system to receive a dose of 0.25 mg, 0.40 mg, or 0.60 mg (1:1:1 ratio) and then allocated to active treatment (CCH) or placebo (4:1 ratio). All patients and investigators were blinded to treatment. One injection was made in the selected nodule on Day 1. Caliper measurements of nodule length and width were performed at screening and at Weeks 4 and 8. Investigator-reported nodular consistency and hardness were evaluated at baseline and Weeks 1, 4, and 8. Investigator-rated patient improvement (1 [very much improved] to 7 [very much worse]) and patient satisfaction were assessed at study end. In the efficacy population (n = 74), percentage changes in area were significantly greater with CCH 0.40 mg (-80.1%, P = 0.0002) and CCH 0.60 mg (-78.2%, P = 0.0003), but not CCH 0.25 mg (-58.3%, P = 0.079), versus placebo (-42.2%) at post-treatment Week 8. Mean change in nodular consistency and hardness were significantly improved with CCH versus placebo at Weeks 4 and 8 (P ≤ 0.0139 for all). At Week 8, investigator global assessment of improvement was significantly greater with CCH 0.40 mg and 0.60 mg (P ≤ 0.0014) but not statistically significant with CCH 0.25 mg versus placebo (P = 0.13). Most patients were "very satisfied" or "quite satisfied" with CCH 0.40 mg and 0.60 mg. Contusion/bruising (50.0% to 59.1%) was the most common adverse event with CCH treatment. In patients with Dupuytren disease, a single CCH injection significantly improved palmar nodule size and hardness. The safety of CCH was similar to that observed previously in patients with Dupuytren contracture. ClinicalTrials.gov identifier: NCT02193828 . Date of trial registration: July 2, 2014 to December 5, 2014.

Preliminary results of a randomized, equivalence trial of fluoroscopic caudal epidural injections in managing chronic low back pain: Part 2--Disc herniation and radiculitis.

PubMed

Manchikanti, Laxmaiah; Singh, Vijay; Cash, Kimberly A; Pampati, Vidyasagar; Damron, Kim S; Boswell, Mark V

2008-01-01

The pathophysiology of lumbar radicular pain is a subject of ongoing research. The prevalence of sciatica or radiculitis ranges from 1.2% to 43%. Epidural injections are one of the most commonly performed interventions in the United States in managing chronic low back and lower extremity pain secondary to disc herniation and radiculitis. There is a paucity of evidence with contemporary methodology used in performing epidural injections under fluoroscopy and based on pain relief and functional status improvement. A randomized, double-blind, equivalence trial. An interventional pain management practice, a specialty referral center, a private practice setting in the United States. To evaluate the effectiveness of caudal epidural injections with or without steroids in managing chronic low back and lower extremity pain secondary to disc herniation or radiculitis in providing effective and long-lasting pain relief and evaluate the differences between local anesthetic with or without steroids. Patients were assigned to one of 2 groups; Group I patients received caudal epidural injections with an injection of local anesthetic (lidocaine 0.5%), whereas, Group II patients received caudal epidural injections with 0.5% lidocaine 9 mL mixed with 1 mL of steroid. Randomization was performed by computer-generated random allocations sequence by simple randomization. Multiple outcome measures were utilized which included the Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake with assessment at 3 months, 6 months, and 12 months post-treatment. Significant pain relief was defined as 50% or more, whereas significant improvement in disability score was defined as a reduction of 40% or more. The percentage of patients with significant pain relief of 50% or greater at 12 months was 79% in Group I and 81% in Group II. Reduction of Oswestry scores of at least 40% was seen in 83% of the patients in Group I and 91% in Group II. The overall average procedures per year were 3.9 +/- 1.26 in Group I and 3.6 +/- 1.08 in Group II with an average total relief per year of 35.2 +/- 17.18 weeks in Group I and 35.9 +/- 15.34 weeks in Group II over a period of 52 weeks. The results of this study are limited by lack of a placebo group and a preliminary report of 42 patients in each group. Caudal epidural injections with or without steroids may be effective in patients with disc herniation or radiculitis with between 79% to 91% of patients showing significant pain relief and improvement in functional status.

Trastuzumab Injection

MedlinePlus

... with other medications to treat certain types of stomach cancer that have spread to other parts of the ... weeks. When trastuzumab injection is used to treat stomach cancer, it is usually given once every 3 weeks. ...

The Effect of Albumin and Platelet-Poor Plasma Supplemented Botulinum A Toxin on Bioavaliability: An Experimental Rabbit Model.

PubMed

Sibar, Serhat; Findikcioglu, Kemal; Zinnuroglu, Murat; Cenetoglu, Seyhan

2017-04-01

Today, botulinum toxin is commonly used for cosmetic purposes throughout the world. Despite various agents reducing the efficiency of toxin are well defined, the studies related to increasing the bioavailability are limited. The purpose of our study is to assess the effect of the preparation of toxin by diluting with platelet-poor plasma (PPP) and/or albumin instead of standard dilution (saline) on bioavailability in cosmetic-purpose botulinum toxin applications.In the study, 24 New Zealand rabbits were used. Right anterior auricular muscle was preferred for toxin injections. Subjects were divided in 4 groups and in every group; botulinum A toxin (BTxA) that was prepared by different dilution methods was injected. 2.5 U saline-diluted BTxA was injected to the subjects in group 1, 2.5 U ready-to-use rabbit albumin-diluted BTxA was injected to group 2 and 2.5 U autologous PPP-diluted BTxA was injected to group 3 and pure saline was injected to group 4.Before the injection (0th week) and in the second, sixth, and 12th weeks after the injection, visual and electroneuromyographic evaluations of the ears of the subjects were performed.In the second week, median amplitude levels in group 2 were significantly found lower than other groups.In the sixth week, median amplitude levels in group 1 were significantly found lower than other groups.In 12th week, no significant difference was found among all the groups in terms of median amplitude levels.Visual findings were also correlated with electroneuromyographic findings.It was observed that the dilution of BTxA with albumin had caused a stronger paralysis when compared to dilution with saline or PPP at the beginning (second week); however, in the following weeks (sixth week), it was seen that dilution with saline had maintained paralysis better when compared with other dilution methods.In cosmetic BTxA applications, dilution of the toxin with albumin or PPP instead of standard dilution has no positive effect on bioavailability and such modifications regarding this kind of dilution are found unsuitable. Further studies are needed to directly relate the results with clinical applications.

Treatment of hyperfunctioning thyroid nodules by percutaneous ethanol injection.

PubMed

Larijani, Bagher; Pajouhi, Mohammad; Ghanaati, Hossein; Bastanhagh, Mohammad-Hassan; Abbasvandi, Fereshteh; Firooznia, Kazem; Shirzad, Mahmood; Amini, Mohammad-Reza; Sarai, Maryam; Abbasvandi, Nasreen; Baradar-Jalili, Reza

2002-12-06

BACKGROUND: Autonomous thyroid nodules can be treated by a variety of methods. We assessed the efficacy of percutaneous ethanol injection in treating autonomous thyroid nodules. METHODS: 35 patients diagnosed by technetium-99 scanning with hyperfunctioning nodules and suppressed sensitive TSH (sTSH) were given sterile ethanol injections under ultrasound guidance. 29 patients had clinical and biochemical hyperthyroidism. The other 6 had sub-clinical hyperthyroidism with suppressed sTSH levels (<0.24 &mgr;IU/ml) and normal thyroid hormone levels. Ethanol injections were performed once every 1-4 weeks. Ethanol injections were stopped when serum T3, T4 and sTSH levels had returned to normal, or else injections could no longer be performed because significant side effects. Patients were followed up at 3, 6 and, in 15 patients, 24 months after the last injection. RESULTS: Average pre-treatment nodule volume [18.2 PlusMinus; 12.7 ml] decreased to 5.7 PlusMinus; 4.6 ml at 6 months follow-up [P < 0.001]. All patients had normal thyroid hormone levels at 3 and 6 months follow-up [P < 0.001 relative to baseline]. sTSH levels increased from 0.09 PlusMinus; 0.02 &mgr;IU/ml to 0.65 PlusMinus; 0.8 &mgr;IU/ml at the end of therapy [P < 0.05]. Only 3 patients had persistent sTSH suppression at 6 months post-therapy. T4 and sTSH did not change significantly between 6 months and 2 years [P > 0.05]. Ethanol injections were well tolerated by the patients, with only 2 cases of transient dysphonia. CONCLUSION: Our findings indicate that ethanol injection is an alternative to surgery or radioactive iodine in the treatment of autonomous thyroid nodules.

Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times.

PubMed

Fauser, Sascha; Muether, Philipp S

2016-11-01

To determine clinical correlations to intraocular vascular endothelial growth factor A (VEGF-A) suppression times (VSTs) on the treatment of neovascular age-related macular degeneration (nAMD) with ranibizumab (Lucentis) or aflibercept (Eylea). Seven of 89 treatment-naïve nAMD eyes showed persistent choroidal neovascular membrane (CNV) activity throughout a spectral domain optical coherence tomography (SD-OCT)-driven pro re nata (PRN) regimen of intravitreal ranibizumab injections over 28±4 months. The treatment was switched to PRN aflibercept injections and patients were followed for another 15±2 months. A total of 160 aqueous humour specimens were collected before the intravitreal injections, and their VEGF-A concentrations were assayed by Luminex multiplex bead analysis (Luminex, Austin, Texas, USA). Intraocular VEGF-A concentrations were correlated to CNV activity shown by SD-OCT. The mean duration of suppression of VEGF-A concentrations in aqueous humour below the lower limit of quantification of our assay was 34±5 (26-69) days for ranibizumab and 67±14 (49-89) days for aflibercept (p<0.001). The percentual reduction of central retinal volume (CRV) 6 weeks after injection was higher for aflibercept compared with ranibizumab (p=0.009). The time point of clinical re-activity occurred about 50% earlier than the respective VST for each ranibizumab and aflibercept. The VST under aflibercept treatment exceeded that under ranibizumab treatment by a factor of 2. This difference correlated with differential clinical CRV reduction 6 weeks after the respective injection. For both medications, clinical activity was found at a time point as early as 50% of the individual VST. NCT01213667, post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A randomized, double-blind, controlled study of ultrasound-guided corticosteroid injection into the joint of patients with inflammatory arthritis.

PubMed

Cunnington, Joanna; Marshall, Nicola; Hide, Geoff; Bracewell, Claire; Isaacs, John; Platt, Philip; Kane, David

2010-07-01

Most corticosteroid injections into the joint are guided by the clinical examination (CE), but up to 70% are inaccurately placed, which may contribute to an inadequate response. The aim of this study was to investigate whether ultrasound (US) guidance improves the accuracy and clinical outcome of joint injections as compared with CE guidance in patients with inflammatory arthritis. A total of 184 patients with inflammatory arthritis and an inflamed joint (shoulder, elbow, wrist, knee, or ankle) were randomized to receive either US-guided or CE-guided corticosteroid injections. Visual analog scales (VAS) for assessment of function, pain, and stiffness of the target joint, a modified Health Assessment Questionnaire, and the EuroQol 5-domain questionnaire were obtained at baseline and at 2 weeks and 6 weeks postinjection. The erythrocyte sedimentation rate and C-reactive protein level were measured at baseline and 2 weeks. Contrast injected with the steroid was used to assess the accuracy of the joint injection. One-third of CE-guided injections were inaccurate. US-guided injections performed by a trainee rheumatologist were more accurate than the CE-guided injections performed by more senior rheumatologists (83% versus 66%; P = 0.010). There was no significant difference in clinical outcome between the group receiving US-guided injections and the group receiving CE-guided injections. Accurate injections led to greater improvement in joint function, as determined by VAS scores, at 6 weeks, as compared with inaccurate injections (30.6 mm versus 21.2 mm; P = 0.030). Clinicians who used US guidance reliably assessed the accuracy of joint injection (P < 0.001), whereas those who used CE guidance did not (P = 0.29). US guidance significantly improves the accuracy of joint injection, allowing a trainee to rapidly achieve higher accuracy than more experienced rheumatologists. US guidance did not improve the short-term outcome of joint injection.

Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251.

PubMed

Andrews, Chasity D; Bernard, Leslie St; Poon, Amanda Yee; Mohri, Hiroshi; Gettie, Natanya; Spreen, William R; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Hong, Zhi; Ho, David D; Markowitz, Martin

2017-02-20

We evaluated the effectiveness of cabotegravir (CAB; GSK1265744 or GSK744) long acting as preexposure prophylaxis (PrEP) against intravenous simian immunodeficiency virus (SIV) challenge in a model that mimics blood transfusions based on the per-act probability of infection. CAB long acting is an integrase strand transfer inhibitor formulated as a 200 mg/ml injectable nanoparticle suspension that is an effective PrEP agent against rectal and vaginal simian/human immunodeficiency virus transmission in macaques. Three groups of rhesus macaques (n = 8 per group) were injected intramuscularly with CAB long acting and challenged intravenously with 17 animal infectious dose 50% SIVmac251 on week 2. Group 1 was injected with 50 mg/kg on week 0 and 4 to evaluate the protective efficacy of the CAB long-acting dose used in macaque studies mimicking sexual transmission. Group 2 was injected with 50 mg/kg on week 0 to evaluate the necessity of the second injection of CAB long acting for protection against intravenous challenge. Group 3 was injected with 25 mg/kg on week 0 and 50 mg/kg on week 4 to correlate CAB plasma concentrations at the time of challenge with protection. Five additional macaques remained untreated as controls. CAB long acting was highly protective with 21 of the 24 CAB long-acting-treated macaques remaining aviremic, resulting in 88% protection. The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection. These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs.

Polymer Injection Therapy to Reverse Remodel the Papillary Muscles: Efficacy in Reducing Mitral Regurgitation in a Chronic Ischemic Model

PubMed Central

Solis, Jorge; Levine, Robert A.; Johnson, Benjamin; Guerrero, J. Luis; Handschumacher, Mark D.; Suzanne, Suzanne; Lam, Kaitlyn; Berlin, Jason; Braithwaite, Gavin J.C.; Muratoglu, Orhun K.; Vlahakes, Gus J.; Hung, Judy

2010-01-01

Ischemic mitral regurgitation (IMR) results from displacement of the papillary muscles due to ischemic ventricular distortion. Recurrent IMR is frequent after annuloplasty, particularly when left ventricular remodeling continues to progress. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced left ventricular remodeling. Methods Nine sheep underwent ligation of circumflex branches to produce chronic ischemic MR over eight weeks. Once MR developed, PVA was injected into the myocardium underlying the infarcted PM. 2D and 3D echocardiograms and hemodynamic data were obtained pre infarct (baseline), pre PVA (Chronic MR) and post PVA. Results One animal died early, one did not develop MR, and the remaining 7 developed moderate MR. PVA injection significantly decreased the MR from moderate to trace. This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (32.6 ± 4.4 to 27.6 ± 4.2 mm, P<0.05), tenting volume (2.1±0.3 to 1.6 ± 0.3 mm2 P<0.05) and leaflet closure area (9.3 ± 0.8 to 8.2 ± 0.7 mm2, P<0.04). PVA was not associated with significant decreases in LVEF (42 ± 3 % vs 40 ± 2 %, p=ns) or end-systolic elastance. Measures of left ventricular diastolic function, tau (99 ± 55 ms to 87 ± 36;) and left ventricular stiffness coefficient (0.04 ± 0.03 to 0.05 ± 0.03) did not increase post PVA. Conclusions PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving ischemic mitral regurgitation by correcting papillary muscle position, thus relieving tethering that causes ischemic mitral regurgitation. PMID:20736444

Polymer injection therapy to reverse remodel the papillary muscles: efficacy in reducing mitral regurgitation in a chronic ischemic model.

PubMed

Solis, Jorge; Levine, Robert A; Johnson, Benjamin; Guerrero, J Luis; Handschumacher, Mark D; Sullivan, Suzanne; Lam, Kaitlyn; Berlin, Jason; Braithwaite, Gavin J C; Muratoglu, Orhun K; Vlahakes, Gus J; Hung, Judy

2010-10-01

Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P=0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P=0.01), and leaflet closure area (8.8±1.3 cm(2)to 7.6±1.3 cm(2), P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P=NS), end-systolic elastance, τ (82±36 ms to 72±26, P=NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.

Examination of toxicity and collagen linearity after the administration of the protein cross-linker genipin in equine tendon and dermis: a pilot study.

PubMed

Bellefeuille, M; Peters, D F; Nolin, M; Slusarewicz, P; Telgenhoff, D

2017-05-01

Collagen cross-linking is an attractive therapeutic route aimed at supplementing natural collagen stabilisation. In this study the toxicity of the cross-linker genipin (GP) was examined in avascular (tendon) and vascular (dermis) tissue. High doses of GP were injected intratendinously into three yearling horses and evaluated at various time points up to 30 days. A second group of three yearlings were injected into the dermis and evaluated at various time points up to 1 year. Metrics used included lameness, circumferential swelling, ultrasound evaluation, microscopic morphology, collagen production and systemic effect on blood parameters. The tendon injection sites exhibited mild lameness and swelling with no apparent systemic toxicity or stabilisation defects. Treated tendons exhibited increased linear collagen microscopically. Dermal injections showed similar results, with mild swelling at the injection site. Microscopic morphology resulted in a decrease in dermal collagen at 30 days post-injection. Dermis injected at the high dose of 355 mmol/L examined 1 year post-treatment appeared similar to the untreated biopsies; however, there was an increase in mature collagen. GP injection appeared to be well tolerated, with transient lameness and mild circumferential swelling when injected into the tendon and local tissue swelling when injected into the dermis. No systemic hypersensitivities or toxicities were observed. Microscopically, GP resulted in increased linear collagen in tendons at 30 days post-injection and overall increased collagen in dermal tissue when evaluated 1 year post-injection. © 2017 Australian Veterinary Association.

Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

PubMed Central

Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

2016-01-01

Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials. PMID:27184924

Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

NASA Astrophysics Data System (ADS)

Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

2016-05-01

Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.

Uptake of wheel-filtration among clients of a supervised injecting facility: Can structured education work?

PubMed

Steele, Maureen; Silins, Edmund; Flaherty, Ian; Hiley, Sarah; van Breda, Nick; Jauncey, Marianne

2018-01-01

Wheel-filtration of pharmaceutical opioid tablets is a recognised harm reduction strategy, but uptake of the practice among people who inject drugs is low. The study aimed to: (i) examine perceptions of filtration practices; (ii) provide structured education on wheel-filtration; and (iii) assess uptake of the practice. Frequent opioid tablet injectors (n = 30) attending a supervised injecting facility in Sydney, Australia, received hands-on instruction on wheel-filtration based on recommended practice. Pre-education, post-education and follow-up questionnaires were administered. Wheel-filtration was generally regarded as better than cotton-filtration (the typical method) in terms of perceived effects on health, ease of use and overall drug effect. Sixty-eight percent of those who said they would try wheel-filtration after the education had actually done so. Of those who usually used cotton-filtration, over half (60%) had used wheel-filtration two weeks later. Uptake of safer preparation methods for pharmaceutical opioid tablets increases after structured education in wheel-filtration. Findings suggest that SIFs are an effective site for this kind of education. Supervised injecting facility workers are uniquely positioned to provide harm reduction education at the time of injection. [Steele M, Silins E, Flaherty I, Hiley S, van Breda N, Jauncey M. Uptake of wheel-filtration among clients of a supervised injecting facility: Can structured education work? Drug Alcohol Rev 2018;37:116-120]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Risk of urinary tract infection after detrusor botulinum toxin A injections for refractory neurogenic detrusor overactivity in patients with no antibiotic treatment.

PubMed

Mouttalib, Sofia; Khan, Shahid; Castel-Lacanal, Evelyne; Guillotreau, Julien; De Boissezon, Xavier; Malavaud, Bernard; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

2010-12-01

To determine if antibiotic prophylaxis is required for intradetrusor botulinum toxin A (BoNT-A) injections. This was a prospective non-randomized study. Inclusion criteria were adult patients with neurogenic detrusor overactivity who failed anticholinergic-based first-line treatment and had sterile urine culture 7 days before injections, a negative dipstick test on the day of the injections, and were performing clean intermittent self-catheterization. Injections were performed using a rigid cystoscope, under local anaesthetic. Patients received BoNT-A as either Botox® (Allergan Inc., Irvine, CA, USA) 300 U in 30 sites or Dysport® (Ipsen Ltd, Ipsen, Paris, France) 750 U in 20 sites. Urine culture was done 6 days and 6 weeks after the injections. If urinary tract infection (UTI) was suspected, a physician performed a complete physical examination. The primary outcome criterion was the occurrence of UTI during the first week after injections. In all, 42 patients (22 women, 20 men) with a mean (sd) age 45.3 (16.4) years were included. A symptomatic UTI occurred during the first week after the injections in three patients (7.1%). The urinary colonization rate was 31% and 26% at 6 days and 6 weeks after injection, respectively. The most common bacterium was Escherichia coli (62.5%). There were no differences between 20 and 30 injection sites or between the sexes. The rate of UTI after intradetrusor injections of BoNT-A was 7.1%. The most frequent bacterium involved was Escherichia coli. These results indicate that antibiotic prophylaxis for intradetrusor BoNT-A injections seems necessary. © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

Anti-Nociceptive Effects of Elcatonin Injection for Postmenopausal Women with Back Pain: A Randomized Controlled Trial

PubMed Central

Ikegami, Shota; Kamimura, Mikio; Uchiyama, Shigeharu; Nakagawa, Hiroyuki; Hashidate, Hiroyuki; Takahara, Kenji; Takahashi, Jun; Kato, Hiroyuki

2010-01-01

Background: Eel calcitonin (elcatonin) injection is widely used for elderly patients suffering from somatic pain in Japan. However, there have been few reports on the analgesic effects of elcatonin injection. The purpose of this study was to examine the analgesic effects of elcatonin injection in postmenopausal women with lower back pain. Methods: This study was designed as a double-blind, randomized, placebo-controlled study. Thirty-six women aged ≥50 years with acute lower back pain participated in this study. They were randomly divided into two treatment groups according to whether they received a placebo or a weekly trigger point injection of elcatonin (20 units). They were observed for 5 weeks and the extent of pain at motion and at rest according to the visual analog scale (VAS) was evaluated. The mean VAS scores for the elcatonin group were then compared with those of the placebo group. Results: There were no statistically significant differences in the mean VAS scores for pain at rest between the two groups during the 5-week treatment course. However, the mean VAS scores for motion pain in the elcatonin group were significantly lower than those in the placebo group at the third, fifth and sixth weeks. Conclusions: Elcatonin injection (20 units) significantly relieved motion pain in the lower back in postmenopausal women after three weeks of treatment. This analgesic effect continued for the subsequent 3 weeks. PMID:20448810

Consequences of Developmental Exposure to Concentrated Ambient Ultrafine Particle Air Pollution Combined with the Adult Paraquat and Maneb Model of the Parkinson’s Disease Phenotype in Male Mice

PubMed Central

Allen, Joshua L; Liu, Xiufang; Weston, Douglas; Conrad, Katherine; Oberdörster, Günter; Cory-Slechta, Deborah A

2014-01-01

Current evidence suggests suceptibility of both the substantia nigra and striatum to exposure to components of air pollution. Further, air pollution has been associated with increased risk of PD diagnsosis in humans or PD-like pathology in animals. This study examined whether exposure of mice to concentrated ambient ultrafine particles (CAPS; <100 nm diameter) during the first two weeks of life would alter susceptibility to induction of the Parkinson’s disease phenyotype (PDP) in a pesticide-based paraquat and maneb (PQ+MB) model during adulthood utilizing i.p. injections of 10 mg/kg PQ and 30 mg/kg MB 2× per week for 6 weeks. Evidence of CAPS-induced enhancement of the PQ+MB PDP was limited primarily to delayed recovery of locomotor activity 24 post injection of PQ+MB that could be related to alterations in striatal GABA inhibitory function. Absence of more extensive interactions might also reflect the finding that CAPS and PQ+MB appeared to differentially target the nigrostriatal dopamine and amino acid systems, with CAPS impacting striatum and PQ+MB impacting dopamine-glutamate function in midbrain; both CAPS and PQ+MB elevated glutamate levels in these specific regions, consistent with potential excitotoxicity. These findings demonstrate the ability of postnatal CAPS to produce locomotor dysfunction and dopaminergic and glutamateric changes, independent of PQ+MB, in brain regions involved in the PDP. PMID:24486957

The influence of manganese treatment on the distribution of metal elements in rats and the protection by sodium para-amino salicylic acid.

PubMed

Yuan, Zong-Xiang; Chen, Hai-Bin; Li, Shao-Jun; Huang, Xiao-Wei; Mo, Yu-Huan; Luo, Yi-Ni; He, Sheng-Nan; Deng, Xiang-Fa; Lu, Guo-Dong; Jiang, Yue-Ming

2016-07-01

Manganese (Mn) overexposure induced neurological damages, which could be potentially protected by sodium para-aminosalicylic acid (PAS-Na). In this study, we systematically detected the changes of divalent metal elements in most of the organs and analyzed the distribution of the metals in Mn-exposed rats and the protection by PAS-Na. Sprague Dawley (SD) rats received intraperitoneal injections of 15mg/kg MnCl2·4H2O (5d/week for 3 weeks), followed by subcutaneous (back) injections of PAS-Na (100 and 200mg/kg, everyday for 5 weeks). The concentrations of Mn and other metal elements [Iron (Fe), Copper (Cu), Zinc (Zn), Magnesium (Mg), Calcium (Ca)] in major organs (liver, spleen, kidney, thighbone and iliac bone, cerebral cortex, hippocampus and testes) and blood by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). The results showed that Mn overexposure significantly increased Mn in most organs, Fe and Zn in liver, Fe and Mg in blood; however decreased Fe, Cu, Zn, Mg and Ca in cortex, Cu and Zn in kidney, Cu and Mg in iliac bone, and Zn in blood. In contrast, PAS-Na treatment restored most changes particularly in cortex. In conclusion, excessive Mn exposure disturbed the balance of other metal elements but PAS-Na post-treatments could restore these alterations. Copyright © 2016 Elsevier GmbH. All rights reserved.

Effect of nicotinic acid on the sleep time and tolerance induced by ethanol in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basilio, C.; Toro, A.; Yojay, L.

The intraperitoneal (i.p.) administration (50 mg/kg) of nicotinic acid (NA), markedly decreased the sleep time of rats pretreated (10 min before), post-treated (10 min after) or simultaneously treated with ethanol (4 g/Kg i.p.). A similar effect was observed on the sleep time induced by pentobarbital (37 mg/Kg i.p.). Blood alcohol levels (BAL) were the same or slightly higher in the animals pretreated with NA than in the control animals pre-injected with saline. Nicotinamide and NAD had no effect. A total of three doses of ethanol, each one administered weekly or biweekly, induced tolerance, which persisted for approximately six weeks. Aftermore » this period, a hypersensitivity to ethanol appeared to develop. This phenomenon was not observed when NA was pre-injected 10 min before each dose of ethanol. The sleep time of the latter animals did not change neither during the treatment period nor after six weeks without any treatment. BAL were slightly higher in NA treated than in control animals. The authors concluded that the effect of NA on the sleep time and tolerance induced by ethanol is not due to an increased rate of its metabolism and/or elimination but to a long-lasting effect that decreases the sensitivity of the nervous cells to ethanol. The mechanisms involved in the shortening of the sleep time as well as those responsible for the loss of the capacity to develop tolerance are under current investigation.« less

Comparison of Clinical Efficacy Between Interlaminar and Transforaminal Epidural Injection in Patients With Axial Pain due to Cervical Disc Herniation.

PubMed

Lee, Jung Hwan; Lee, Sang-Ho

2016-01-01

Transforaminal (TF) approach is preferred by physician to interlaminar (IL) approach because it can deliver injectates directly around nerve root and dorsal root ganglion, which is regarded as main pain sources. Axial neck pain is originated from sinuvertebral nerve located in ventral epidural spaces, which has been described to be related to central or paramedian disc herniation. It is very questionable that TF injection is also more effective than IL injection in the patients with axial neck or interscapular pain. This study was to evaluate clinical efficacy of cervical epidural injection in patients with axial pain due to cervical disc herniation and to compare the clinical outcomes between TF and IL approaches. Fifty-six and 52 patients who underwent IL and TF epidural injections, respectively, for axial neck/interscapular pain due to central or paramedian cervical disc herniation were included. Numeric Rating Scale (NRS) and Neck Disability Index (NDI) were compared between both groups at 2 and 8 weeks after treatment. Successful pain relief was defined if a 50% or more reduction of NRS score was achieved in comparison with pretreatment one. Successful functional improvement was defined if at least a 40% reduction of NDI was obtained. Overall, 79 (73.1%) and 57 (52.8%) among 108 patients showed successful pain relief at 2 and 8 weeks, respectively. Seventy-six (70.4%) and 52 (48.1%) had successful functional improvement at 2 and 8 weeks, respectively. The IL and TF groups showed no significant difference in proportion of successful results of NRS 2 weeks (73.2% vs 67.3%) and 8 weeks (48.2% vs 48.1%). Also, no significant difference was obtained in proportion of successful NDI between 2 groups at 2 weeks (75.0% vs 71.2%) and 8 weeks (53.6% vs 51.9%). Cervical epidural injection showed favorable results in 2 weeks and moderate results in 8 weeks in patients with axial pain due to cervical disc herniation. IL and TF showed no significant difference in clinical efficacy. Considering TF was relevant to more serious side effects, IL was more recommendable in these patients.

Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study.

PubMed

Bashaireh, Khaldoon; Naser, Ziad; Hawadya, Khaled Al; Sorour, Sorour; Al-Khateeb, Rami Nabeel

2015-01-01

The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period. The study was a post-marketing Phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1-4) in the tibio-femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection. An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated. The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3.36, the stiffness score was 0.42, and the physical performance score was 11.5. All side effects were local and transient, and included pain, swelling, and redness of the knee. Most side effects were treated. Hyaluronan should be encouraged as an alternative or adjunct treatment to oral analgesics to reduce their required doses, and delay potential future surgical intervention.

Safety study of intravitreal and suprachoroidal Laponite clay in rabbit eyes.

PubMed

Prieto, Esther; Vispe, Eugenio; De Martino, Alba; Idoipe, Miriam; Rodrigo, María J; Garcia-Martin, Elena; Fraile, José M; Polo-Llorens, Vicente; Mayoral, José A

2018-03-01

To study the safety and biocompatibility of Laponite clay (LAP) within an intravitreal and suprachoroidal administration in rabbit eyes. Thirty-two New Zealand albino rabbits were divided into two experimental groups to test intravitreal (IVT group) and suprachoroidal (SCS group) administration of a 100-μl and 50-μl Laponite suspension respectively. Following injection, the eyes were monitored by ocular tonometry, slit-lamp eye examination and indirect ophthalmoscopy, at 24 h, 1, 4, 12, and 14 weeks post administration. Histological examination was also performed to determine whether any ocular pathological change had occurred. Throughout the study, LAP presence in vitreous was estimated by complexometric titration with ethylenediaminetetraacetic acid (EDTA), taking advantage of the Laponite high content of magnesium ions. Neither significant differences in the intraocular pressure, nor relevant ocular complications were found in the two experimental groups after LAP administration. The histology of the retina remained unchanged. LAP presence in vitreous could be indirectly confirmed by complexometric titration until 14 weeks post administration in eyes of IVT group. Laponite could be considered as a vehicle for potential clinical use in ocular drug administration, due to its proven ocular biocompatibility and its transparency in gel state.

[Pregnancy and childbirth in a patient with a spinal cord lesion].

PubMed

Vanderbeke, I; Boll, D; Verguts, J K

2008-05-17

A 37-year-old woman with a spinal cord lesion at the level of TvIII due to a car-accident, became pregnant. She had posttraumatic syringomyely at Cv-TvIII, for which she underwent syringo-arachnoidal drainage. At approximately six weeks of amenorrhoea she presented at the emergency room with vaginal bleeding. She was treated with dalteparine 5000 IU once daily given by intramuscular injection until 6 weeks post partum. Weekly urine checks were advised. At 36 6/7 weeks of pregnancy, the patient was admitted to hospital for daily cardiotocography and 4-hourly contraction monitoring. After spontaneous rupture of the membranes she went into labour and had a vaginal delivery of a son weighing 3320 g. His Apgar score was 6 after 1 min and 9 after 5 min; arterial pH was 7.31. For three months after giving birth she received specialist care at home as well as help and counselling from a rehabilitation centre. In pregnant women with a spinal cord lesion, special attention should be paid to urinary tract infections, pressure areas, anaemia and thrombo-embolic symptoms. During partus, cardiotocographic monitoring should be carried out, also in patients with TvI-Tx lesions regularly from 36 weeks. In pregnant women with lesions from TvI, medical attendants should be aware of the possibility of autonomous dysreflection. Epidural anaesthesia should be administered and episiotomy or rupture avoided. Post partum, the bladder should always be completely emptied and pressure areas and signs ofthrombo-embolic complications monitored. A urological bladder function consultation should be requested, and, ifepisiotomy or rupture does occur, extra care should be taken to avoid infection. The ergonomic situation at home should be evaluated to ensure that any ergonomic changes necessary for the care of the patient and her newborn, take place in time.

Protective effects of systemic treatment with methylprednisolone in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION).

PubMed

Huang, Tzu-Lun; Huang, Shun-Ping; Chang, Chung-Hsing; Lin, Kung-Hung; Chang, Shu-Wen; Tsai, Rong-Kung

2015-02-01

This study investigated the protective effects of the administration of steroids on optic nerves (ON) and retinal ganglion cells (RGCs) in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION). We induced rAION using rose bengal and argon laser irradiation in a photodynamic procedure on the optic discs of rats. The treated groups received methylprednisolone (MP) via peritoneal injection for 2 weeks. The control group received intraperitoneal injections of phosphate-buffered saline (PBS) post-rAION. At the 4th week post-infarct, MP treatments significantly rescued the RGCs (mm(2)) in the central retinas (1920 ± 210, p < 0.001) and mid-peripheral retinas (950 ± 240, respectively, p = 0.018) compared with those of the PBS-treated rats (central: 900 ± 210 and mid-peripheral: 440 ± 180). Functional assessment with flash visual-evoked potentials demonstrated that P1 latency (ms) was shortened in the MP group compared to the PBS group (108 ± 14 and 147 ± 9, respectively, p < 0.001). In addition, the P1 amplitude (uV) was enhanced in the MP group compared to the PBS group (55 ± 12 and 41 ± 13, respectively, p < 0.05). TUNEL assays showed a decrease in the number of apoptotic cells in the RGC layers of MP-treated retinas compared to the PBS-treated group (p < 0.05). ED1 positive cells (/HPF) were significantly decreased in the ONs of the MP group compared to the PBS group (p < 0.001). In conclusion, systemic administration of MP had neuroprotective effects on RGC survival and ON function in the rAION animal model. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lipopolysaccharide-mediated inflammatory priming potentiates painful post-traumatic trigeminal neuropathy.

PubMed

Boucher, Yves; Moreau, Nathan; Mauborgne, Annie; Dieb, Wisam

2018-06-18

We explored the molecular and behavioral effects of a perineural Lipopolysaccharide (LPS)-mediated inflammatory priming on the development and maintenance of painful post-traumatic trigeminal neuropathy (PPTTN) following infra-orbital nerve chronic constriction injury (CCI-IoN) in rats. Rats were pretreated with repetitive perineural injections in the vicinity of the IoN of either LPS or vehicle (Vhcl) before being submitted to CCI-IoN. Orofacial pain-like behaviors (response to Von Frey Filament testing and spontaneous isolated face grooming) were measured during the period of LPS injections (three weeks) and following CCI-IoN surgery (two weeks). Local LPS administration induced an early pain-like behavior (i.e. an increase in spontaneous pain [SP] or mechanical static allodynia [MSA]) in both conditions, and following CCI-IoN, MSA and SP developed earlier and more severely in LPS-pretreated rats than in the control group. Ipsilateral increases of key neuropathic pain mRNA markers in the IoN parenchyma, trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) were observed in CCI-IoN injured animals as compared to controls. Although no significant molecular differences could be observed within the IoN parenchyma between LPS and Vhcl-pretreated animals, a significant increase of key inflammatory cytokine Interleukin 1 beta (IL - 1β) could be found in the TG of LPS-pretreated CCI-injured animals versus controls. Finally, a higher increase of inducible nitric oxide synthase (iNOS) in ipsilateral Sp5C of LPS-pretreated animals was observed as compared to Sp5C of Vhcl-pretreated animals. These results suggest a key role of inflammatory priming in the development and maintenance of PPTTN implicating IL-1β/iNOS-dependent central sensitization mechanisms. Copyright © 2018. Published by Elsevier Inc.

Continuous prophylaxis with recombinant factor IX Fc fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption.

PubMed

Iorio, Alfonso; Krishnan, Sangeeta; Myrén, Karl-Johan; Lethagen, Stefan; McCormick, Nora; Yermakov, Sander; Karner, Paul

2017-04-01

Continuous prophylaxis for patients with hemophilia B requires frequent injections that are burdensome and that may lead to suboptimal adherence and outcomes. Hence, therapies requiring less-frequent injections are needed. In the absence of head-to-head comparisons, this study compared the first extended-half-life-recombinant factor IX (rFIX) product-recombinant factor IX Fc fusion protein (rFIXFc)-with conventional rFIX products based on annualized bleed rates (ABRs) and factor consumption reported in studies of continuous prophylaxis. This study compared ABRs and weekly factor consumption rates in clinical studies of continuous prophylaxis treatment with rFIXFc and conventional rFIX products (identified by systematic literature review) in previously-treated adolescents and adults with moderate-to-severe hemophilia B. Meta-analysis was used to pool ABRs reported for conventional rFIX products for comparison. Comparisons of weekly factor consumption were based on the mean, reported or estimated from the mean dose per injection. Five conventional rFIX studies (injections 1 to >3 times/week) met the criteria for comparison with once-weekly rFIXFc reported by the B-LONG study. The pooled mean ABR for conventional rFIX was slightly higher than but comparable to rFIXFc (difference=0.71; p = 0.210). Weekly factor consumption was significantly lower with rFIXFc than in conventional rFIX studies (difference in means = 42.8-74.5 IU/kg/week [93-161%], p < 0.001). Comparisons of clinical study results suggest weekly injections with rFIXFc result in similar bleeding rates and significantly lower weekly factor consumption compared with more-frequently-injected conventional rFIX products. The real-world effectiveness of rFIXFc may be higher based on results from a model of the impact of simulated differences in adherence.

Cervical epidural injections in chronic discogenic neck pain without disc herniation or radiculitis: preliminary results of a randomized, double-blind, controlled trial.

PubMed

Manchikanti, Laxmaiah; Cash, Kimberly A; Pampati, Vidyasagar; Wargo, Bradley W; Malla, Yogesh

2010-01-01

Chronic neck pain is a common problem in the adult population with a typical 12-month prevalence of 30% to 50%. However, there is a lack of consensus regarding the causes and treatments of chronic neck pain. Despite limited evidence, cervical epidural injections are one of the commonly performed non-surgical interventions in the management of chronic neck pain. A randomized, double-blind, active control trial. An interventional pain management practice, a specialty referral center, a private practice setting in the United States. To evaluate the effectiveness of cervical interlaminar epidural injections with local anesthetic with or without steroids in the management of chronic neck pain with or without upper extremity pain in patients without disc herniation or radiculitis or facet joint pain. Patients without disc herniation or radiculitis and negative for facet joint pain by means of controlled diagnostic medial branch blocks were randomly assigned to one of 2 groups: injection of local anesthetic only or local anesthetic mixed with non-particulate betamethasone. Seventy patients were included in this analysis. Randomization was performed by computer-generated random allocation sequence by simple randomization. Multiple outcome measures were utilized including the Numeric Rating Scale (NRS), the Neck Disability Index (NDI), employment status, and opioid intake with assessment at 3, 6, and 12 months post-treatment. Significant pain relief or functional status was defined as a 50% or more reduction. Significant pain relief (> or = 50%) was demonstrated in 80% of patients in both groups and functional status improvement (> or = 50%) in 69% of Group I and 80% of Group II. The overall average procedures per year were 3.9 +/- 1.01 in Group I and 3.9 +/- 0.8 in Group II with an average total relief per year of 40.3 +/- 14.1 weeks in Group I and 42.1 +/- 9.9 weeks in Group II over a period of 52 weeks in the successful group. The results of this study are limited by the lack of a placebo group and a preliminary report of 70 patients, with 35 patients in each group. Cervical interlaminar epidural injections with local anesthetic with or without steroids may be effective in patients with chronic function-limiting discogenic.

OnabotulinumtoxinA Improves Pain in Patients With Post-Stroke Spasticity: Findings From a Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Wissel, Jörg; Ganapathy, Vaidyanathan; Ward, Anthony B; Borg, Jörgen; Ertzgaard, Per; Herrmann, Christoph; Haggstrom, Anders; Sakel, Mohamed; Ma, Julia; Dimitrova, Rozalina; Fulford-Smith, Antony; Gillard, Patrick

2016-07-01

Patients with post-stroke spasticity (PSS) commonly experience pain in affected limbs, which may impact quality of life. To assess onabotulinumtoxinA for pain in patients with PSS from the BOTOX(®) Economic Spasticity Trial, a multicenter, randomized, double-blind, placebo-controlled trial. Patients with PSS (N = 273) were randomized to 22- to 34-week double-blind treatment with onabotulinumtoxinA + standard care (SC) or placebo injection + SC and were eligible to receive open-label onabotulinumtoxinA up to 52 weeks. Assessments included change from baseline on the 11-point pain numeric rating scale, proportion of patients with baseline pain ≥4 achieving ≥30% and ≥50% improvement in pain, and pain interference with work at Week 12, end of double-blind treatment, and Week 52. At baseline, most patients (74.3%) experienced pain and 47.4% had pain ≥4 (pain subgroup). Mean pain reduction from baseline at Week 12 was significantly greater with onabotulinumtoxinA + SC (-0.77, 95% CI -1.14 to -0.40) than placebo + SC (-0.13, 95% CI -0.51 to 0.24; P < 0.05). Higher proportions of patients in the pain subgroup achieved ≥30% and ≥50% reductions in pain at Week 12 with onabotulinumtoxinA + SC (53.7% and 37.0%, respectively) compared with placebo (28.8% and 18.6%, respectively; P < 0.05). Reductions in pain were sustained through Week 52. Compared with placebo + SC, onabotulinumtoxinA consistently reduced pain interference with work. This is the first randomized, placebo-controlled trial demonstrating statistically significant and clinically meaningful reductions in pain and pain interference with work with onabotulinumtoxinA in patients with PSS. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Successful single treatment with ziv-aflibercept for existing corneal neovascularization following ocular chemical insult in the rabbit model.

PubMed

Gore, Ariel; Horwitz, Vered; Cohen, Maayan; Gutman, Hila; Cohen, Liat; Gez, Rellie; Kadar, Tamar; Dachir, Shlomit

2018-06-01

To evaluate the efficacy of ziv-aflibercept as a treatment for established corneal neovascularization (NV) and to compare its efficacy to that of bevacizumab following ocular chemical insult of sulfur mustard (SM) in the rabbit model. Chemical SM burn was induced in the right eye of NZW rabbits by vapor exposure. Ziv-aflibercept (2 mg) was applied once to neovascularized eyes by subconjunctival injection while subconjunctival bevacizumab (5 mg) was administered twice a week, for 3 weeks. Non-treated exposed eyes served as a control. A clinical follow-up employed by slit-lamp microscope, was performed up to 12 weeks following exposure and digital photographs of the cornea were taken for measurement of blood vessels length using the image analysis software. Eyes were taken for histological evaluation 2, 4 and 8 weeks following treatment for general morphology and for visualization of NV, using H&E and Masson Trichrome stainings, while conjunctival goblet cell density was determined by PAS staining. Corneal NV developed, starting as early as two weeks after exposure. A single subconjunctival treatment of ziv-aflibercept at 4 weeks post exposure, significantly reduced the extent of existing NV already one week following injection, an effect which lasted for at least 8 weeks following treatment, while NV in the non-treated exposed eyes continued to advance. The extensive reduction in corneal NV in the ziv-aflibercept treated group was confirmed by histological evaluation. Bevacizumab multiple treatment showed a benefit in NV reduction, but to a lesser extent compared to the ziv-aflibercept treatment. Finally, ziv-aflibercept increased the density of conjunctival goblet cells as compared to the exposed non-treated group. Subconjunctival ziv-aflibercept single treatment presented a highly efficient long-term therapeutic benefit in reducing existing corneal NV, following ocular sulfur mustard exposure. These findings show the robust anti-angiogenic efficacy of ziv-aflibercept and demonstrate the advantage of this treatment over the other anti-angiogenic therapies in ameliorating corneal NV and protecting the ocular surface. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stable Rat Model of Mechanical Allodynia in Diabetic Peripheral Neuropathy: The Role of Nerve Compression.

PubMed

Liao, Chenlong; Yang, Min; Liu, Pengfei; Zhong, Wenxiang; Zhang, Wenchuan

2018-05-01

 Preclinical studies involving animal models are essential for understanding the underlying mechanisms of diabetic neuropathic pain.  Rats were divided into four groups: two controls and two experimental. Diabetes mellitus was induced by streptozotocin (STZ) injection in two experimental groups. The first group involved one sham operation. The second group involved one latex tube encircling the sciatic nerve. The vehicle-injection rats were used as two corresponding control groups: sham operation and encircled nerves. By the third week, STZ-injected rats with encircled nerves were further divided into three subgroups: one involving continuing observation and the other two involving decompression (removal of the latex tube) at different time points (third week and fifth week). Weight and blood glucose were monitored, and behavioral analysis, including paw withdrawal threshold (PWT) and latency, was performed every week during the experimental period (7 weeks).  Hyperglycemia was induced in all STZ-injected rats. A significant increase in weight was observed in the control groups when compared with the experimental groups. By the third week, more STZ-injected rats with encircled nerves developed mechanical allodynia than those without ( P  < 0.05), while no significant difference was noted ( P  > 0.05) on the incidence of thermal hyperalgesia. Mechanical allodynia, but not thermal hyperalgesia, could be ameliorated by the removal of the latex tube at an early stage (third week).  With the combined use of a latex tube and STZ injection, a stable rat model of painful diabetic peripheral neuropathy (DPN) manifesting both thermal hyperalgesia and mechanical allodynia has been established. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial

PubMed Central

Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Ahangar, Azadeh Gharooee; Abadi, Porya Hassan; Mojgani, Parviz; Ahangar, Omid Gharooi

2017-01-01

Background and objectives: Knee osteoarthritis is the most common joint disease. We aimed to compare the efficacy and safety of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA) on pain and function of patients with knee osteoarthritis. Methods: In this single-blinded randomized clinical trial, patients with symptomatic osteoarthritis of knee were assigned to receive 2 intra-articular injections of our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary outcome was the mean change from baseline until 2 and 6 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance for repeated-measures statistical test. Results: A total of 69 patients entered final analysis. The mean age of patients was 58.2 ± 7.41 years and 81.2% were women. In particular, total WOMAC index decreased from 42.9 ± 13.51 to 26.8 ± 13.45 and 24.4 ± 16.54 at 2 and 6 months in the newly developed PRGF group (within subjects P = .001), and from 38.8 ± 12.62 to 27.8 ± 11.01 and 27.4 ± 11.38 at 2 and 6 months in the HA group (within subjects P = .001), respectively (between subjects P = .631). There was no significant difference between PRGF and HA groups in patients’ satisfaction and minor complications of injection, whereas patients in HA group reported significantly lower injection-induced pain. Conclusions: In 6 months follow up, our newly developed PRGF and HA, both are effective options to decrease pain and improvement of function in patients with symptomatic mild to moderate knee osteoarthritis. PMID:29051707

TrkB signalling pathway mediates the protective effects of exercise in the diabetic rat retina.

PubMed

Allen, Rachael S; Hanif, Adam M; Gogniat, Marissa A; Prall, Brian C; Haider, Raza; Aung, Moe H; Prunty, Megan C; Mees, Lukas M; Coulter, Monica M; Motz, Cara T; Boatright, Jeffrey H; Pardue, Machelle T

2018-05-01

Diabetic retinopathy is a leading cause of vision loss. Treatment options for early retinopathy are sparse. Exercise protects dying photoreceptors in models of retinal degeneration, thereby preserving vision. We tested the protective effects of exercise on retinal and cognitive deficits in a type 1 diabetes model and determined whether the TrkB pathway mediates this effect. Hyperglycaemia was induced in Long Evans rats via streptozotocin injection (STZ; 100 mg/kg). Following confirmed hyperglycaemia, both control and diabetic rats underwent treadmill exercise for 30 min, 5 days/week at 0 m/min (inactive groups) or 15 m/min (active groups) for 8 weeks. A TrkB receptor antagonist (ANA-12), or vehicle, was injected 2.5 h before exercise training. We measured spatial frequency and contrast sensitivity using optokinetic tracking biweekly post-STZ; retinal function using electroretinography at 4 and 8 weeks; and cognitive function and exploratory behaviour using Y-maze at 8 weeks. Retinal neurotrophin-4 was measured using ELISA. Compared with non-diabetic controls, diabetic rats showed significantly reduced spatial frequency and contrast sensitivity, delayed electroretinogram oscillatory potential and flicker implicit times and reduced cognitive function and exploratory behaviour. Exercise interventions significantly delayed the appearance of all deficits, except for exploratory behaviour. Treatment with ANA-12 significantly reduced this protection, suggesting a TrkB-mediated mechanism. Despite this, no changes in retinal neurotrohin-4 were observed with diabetes or exercise. Exercise protected against early visual and cognitive dysfunction in diabetic rats, suggesting that exercise interventions started after hyperglycaemia diagnosis may be a beneficial treatment. The translational potential is high, given that exercise treatment is non-invasive, patient controlled and inexpensive. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Vitamin C and vitamin E supplementation alleviates oxidative stress induced by dexamethasone and improves fertility of breeder roosters.

PubMed

Min, Yuna; Sun, Tongtong; Niu, Zhuye; Liu, Fuzhu

2016-08-01

This study was conducted to determine the effect of supplemental dietary vitamin C (VC) and vitamin E (VE) on improving semen quality and antioxidative status in breeder roosters challenged with dexamethasone (DEX). 120 45-week-old Lveyang black-boned breeder roosters were divided into 5 experimental treatments, including negative group, positive group, and three trial groups, which were fed basal diet supplemented with 300mg/kg VC, 200mg/kg VE, or 300mg/kg VC and 200mg/kg VE (VC+VE). At 49 weeks of age, the positive control and trial groups were subcutaneously injected 3 times every other day with DEX 4 mg/kg body weight, the negative control group was sham injected with saline. At 50 weeks of age, average daily feed intake of birds challenged with DEX significantly increased (P<0.05), however, serum testosterone significantly decreased (P<0.05). Dietary supplementation of VC+VE enhanced serum testosterone and sperm motility remarkably (P<0.05). There were no differences in sperm viability between the DEX-treated groups. During the post-stress recovery period (52 weeks of age), dietary supplementation of VE and VC+VE significantly increased the body weight of birds under oxidative stress (P<0.01). VC, VE, and VC+VE groups had greater sperm viability than control group (P<0.01). Additionally, there was a decrease in the semen plasma malondialdehyde content (P<0.05) of the VC and VC+VE groups, and in the testicular malondialdehyde content (P<0.01) of the VE and VC+VE groups. In summary, VC, VE, especially their combination alleviate the oxidative stress induced by DEX and are favorable for the fertility of breeder roosters. Copyright © 2016. Published by Elsevier B.V.

Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study.

PubMed

Brown, David M; Heier, Jeffrey S; Clark, W Lloyd; Boyer, David S; Vitti, Robert; Berliner, Alyson J; Zeitz, Oliver; Sandbrink, Rupert; Zhu, Xiaoping; Haller, Julia A

2013-03-01

To evaluate intravitreal aflibercept injections (IAI; also called VEGF Trap-Eye) for patients with macular edema secondary to central retinal vein occlusion (CRVO). Randomized controlled trial. This multicenter study randomized 189 patients (1 eye/patient) with macular edema secondary to CRVO to receive 6 monthly injections of either 2 mg intravitreal aflibercept (IAI 2Q4) (n = 115) or sham (n = 74). From week 24 to week 52, all patients received 2 mg intravitreal aflibercept as needed (IAI 2Q4 + PRN and sham + IAI PRN) according to retreatment criteria. The primary endpoint was the proportion of patients who gained ≥15 ETDRS letters from baseline at week 24. Additional endpoints included visual, anatomic, and quality-of-life NEI VFQ-25 outcomes at weeks 24 and 52. At week 24, 56.1% of IAI 2Q4 patients gained ≥15 letters from baseline compared with 12.3% of sham patients (P < .001). At week 52, 55.3% of IAI 2Q4 + PRN patients gained ≥15 letters compared with 30.1% of sham + IAI PRN patients (P < .001). At week 52, IAI 2Q4 + PRN patients gained a mean of 16.2 letters of vision vs 3.8 letters for sham + IAI PRN (P < .001). The most common adverse events for both groups were conjunctival hemorrhage, eye pain, reduced visual acuity, and increased intraocular pressure. Monthly injections of 2 mg intravitreal aflibercept for patients with macular edema secondary to CRVO resulted in a statistically significant improvement in visual acuity at week 24, which was largely maintained through week 52 with intravitreal aflibercept PRN dosing. Intravitreal aflibercept injection was generally well tolerated. Copyright © 2013 Elsevier Inc. All rights reserved.

Increased long-term immunity to Bacillus anthracis protective antigen in mice immunized with a CIA06B-adjuvanted anthrax vaccine.

PubMed

Wui, Seo Ri; Han, Ji Eun; Kim, Yeon Hee; Rhie, Gi-eun; Lee, Na Gyong

2013-04-01

Anthrax is an acute infectious disease caused by Bacillus anthracis. We previously reported that the adjuvant CIA06B, which consists of TLR4 agonist CIA05 and aluminum hydroxide (alum), enhanced the immune response to anthrax protective antigen (PA) in mice. This study was carried out to determine whether CIA06B can enhance long-term immune responses to PA in mice. BALB/c mice were immunized intramuscularly three times at 2-week intervals with recombinant PA alone or PA combined with alum or CIA06B. At 8 and 24 weeks post-immunization, the immunological responses including serum anti-PA IgG antibody titer, toxin-neutralizing antibody titer, splenic cytokine secretion and the frequency of PA-specific memory B cells were assessed. Compared with mice injected with PA alone or PA plus alum, mice injected with PA plus CIA06B had higher titers of serum anti-PA IgG antibodies, and higher frequencies of PA-specific memory B cells and interferon-γ secreting cells. Furthermore, anti-PA antibodies induced by CIA06B were more effective in neutralizing anthrax toxin. These results demonstrated that CIA06B is capable of providing long-term immunity when used as an adjuvant in a PA-based anthrax vaccine.

A Two-Phase Pilot Study to Evaluate the Safety and Tolerability of an In Situ Polymerizing Collagen.

PubMed

Inglefield, Christopher; Rone-McCrate, Rebecca; Brooks, Robert; Zhu, Jiaxun; Grant, Sheila; DeVore, Dale P

2017-09-01

Demand for collagen-based fillers has declined primarily because of limited long-term clinical benefit and the introduction of hyaluronic acid compositions. In situ polymerizing collagen is a noncrosslinked solution of porcine collagen containing a collagenase shield that undergoes fibrillogenesis on injected into tissues forming a natural matrix. Conduct a prospective, single-center, dual-phase open-label study in 8 subjects to evaluate the safety, tolerability, and efficacy of the porcine collagen composition. In Phase I, potential hypersensitivity of the collagen composition was evaluated after skin testing in the back (men) or forearms of subjects (women). In Phase II, subjects showing no signs of hypersensitivity received collagen injections into the nasolabial area followed by evaluation at 1, 4, 8, and 12 weeks using the Global Aesthetic Improvement Scale. None of the subjects had signs of hypersensitivity and all continued in Phase II. The treating physician(s) reported no post-treatment adverse events. Improvement of the nasolabial fold was observed by the physicians and confirmed by assessment of high-resolution photographs and Global Aesthetic Improvement Scale scores over the 12-week treatment were maintained. In this pilot clinical study in situ polymerizing collagen was shown to be safe and effective throughout the 3-month study period.

Effects of Multiple Intra-articular Injections of 0.5% Bupivacaine on Normal and Osteoarthritic Joints in Rats.

PubMed

Iwasaki, Koji; Sudo, Hideki; Kasahara, Yasuhiko; Yamada, Katsuhisa; Ohnishi, Takashi; Tsujimoto, Takeru; Iwasaki, Norimasa

2016-10-01

To determine the in vivo effects of multiple local anesthetic injections of 0.5% bupivacaine on normal and osteoarthritic articular cartilage. Rats with normal knee joints received an intra-articular injection of 0.9% saline solution or 0.5% bupivacaine in their right knees joint once a week for 5 consecutive weeks, starting 4 weeks after the beginning of the experiment. Rats were humanely killed at 8, 16, and 24 weeks. In a parallel experiment, rats underwent anterior cruciate ligament transection to induce osteoarthritic changes. These rats were subjected to the same protocol as those with normal knee joints, starting 4 weeks after the procedure. Static weight-bearing tests were performed on both hind limbs to evaluate changes in weight-bearing ability throughout the experiments. Rats were humanely killed at 8 and 16 weeks. Cell viability was assessed with confocal microscopy, using samples from the distal femur. Histologic assessment of osteoarthritis was performed using samples from the tibial plateau based on the Osteoarthritis Research Society International (OARSI) cartilage histopathology assessment system (i.e., OARSI score). Static weight-bearing tests showed no significant changes after intra-articular injection of saline solution or bupivacaine, and bupivacaine injection did not increase weight bearing compared with saline solution injection, regardless of whether there were osteoarthritic changes. There were also no significant differences in cell viability, cell density, or OARSI scores between the saline solution and bupivacaine groups at each time point, regardless of whether osteoarthritic changes were induced. This study suggested that single or intermittent intra-articular bupivacaine injections might not have deleterious effects on either osteoarthritic or normal joints. There is no strong evidence that intra-articular bupivacaine injection induces degenerative changes in articular cartilage. Therefore, these results may apply to normal and osteoarthritic joints. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Effects of maternal dexamethasone treatment on pancreatic β cell function in the pregnant mare and post natal foal.

PubMed

Valenzuela, O A; Jellyman, J K; Allen, V L; Holdstock, N B; Fowden, A L

2017-01-01

Synthetic glucocorticoids are used to treat inflammatory conditions in horses. In other pregnant animals, glucocorticoids are given to stimulate fetal maturation with long-term metabolic consequences for the offspring if given preterm. However, their metabolic effects during equine pregnancy remain unknown. Thus, this study investigated the metabolic effects of dexamethasone administration on pregnant pony mares and their foals after birth. Experimental study. A total of 3 doses of dexamethasone (200 μg/kg bwt i.m.) were given to 6 pony mares at 48 h intervals beginning at ≈270 days of pregnancy. Control saline injections were given to 5 mares using the same protocol. After fasting overnight, pancreatic β cell responses to exogenous glucose were measured in the mares before, during and after treatment. After birth, pancreatic β cell responses to exogenous glucose and arginine were measured in the foals at 2 and 12 weeks. In mares during treatment, dexamethasone but not saline increased basal insulin concentrations and prolonged the insulin response to exogenous glucose. Basal insulin and glucose concentrations still differed significantly between the 2 groups 72 h post treatment. Dexamethasone treatment significantly reduced placental area but had little effect on foal biometry at birth or subsequently. Foal β cell function at 2 weeks was unaffected by maternal treatment. However, by 12 weeks, pancreatic β cell sensitivity to arginine, but not glucose, was less in foals delivered by dexamethasone- than saline-treated mares. Dexamethasone administration induced changes in maternal insulin-glucose dynamics, indicative of insulin resistance and had subtle longer term effects on post natal β cell function of the foals. The programming effects of dexamethasone in horses may be mediated partially by altered maternal metabolism and placental growth. © 2016 EVJ Ltd.

Combined Microwave Ablation and Cementoplasty in Patients with Painful Bone Metastases at High Risk of Fracture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pusceddu, Claudio, E-mail: clapusceddu@gmail.com; Sotgia, Barbara, E-mail: barbara.sotgia@gmail.com; Fele, Rosa Maria, E-mail: rosellafele@tiscali.it

2016-01-15

PurposeTo retrospectively evaluate the effectiveness of computed tomography-guided percutaneous microwave ablation (MWA) and cementoplasty in patients with painful bone metastases at high risk of fracture.Materials and MethodsThirty-five patients with 37 metastatic bone lesions underwent computed tomography-guided MWA combined with cementoplasty (polymethylmethacrylate injection). Vertebrae, femur, and acetabulum were the intervention sites and the primary end point was pain relief. Pain severity was estimated by visual analog scale (VAS) before treatment; 1 week post-treatment; and 1, 6, and 12 months post-treatment. Functional outcome was assessed by improved patient walking ability. Radiological evaluation was performed at baseline and 3 and 12 months post-procedure.ResultsIn all patients, painmore » reduction occurred from the first week after treatment. The mean reduction in the VAS score was 84, 90, 90 % at week 1, month 1, and month 6, respectively. Improved walking ability occurred in 100 and 98 % of cases at the 1- and 6-month functional outcome evaluations, respectively. At the 1-year evaluation, 25 patients were alive, and 10 patients (28 %) had died because of widespread disease. The mean reduction in the VAS score and improvement in surviving patients’ walking ability were 90 and 100 %, respectively. No patients showed evidence of local tumor recurrence or progression and pathological fracture in the treated sites.ConclusionOur results suggest that MWA combined with osteoplasty is safe and effective when treating painful bone metastases at high risk of fracture. The number of surviving patients at the 1-year evaluation confirms the need for an effective and long-lasting treatment.« less

Steroid Injection Versus Physiotherapy for Patients With Adhesive Capsulitis of the Shoulder

PubMed Central

Sun, Yaying; Lu, Shuai; Zhang, Peng; Wang, Zhaohui; Chen, Jiwu

2016-01-01

Abstract To compare the effect of steroid injection and physiotherapy for patients with adhesive capsulitis of the shoulder (ACS). An electronic search was performed on Pubmed, Embase, and Cochrane library, and reference lists were also reviewed for randomized controlled trials (RCTs) comparing steroid injection and physiotherapy for patients with ACS. The quality of included studies were assessed using PEDro scale. Standardized mean differences (SMDs) and 95% confidence interval (CI) were used for comparisons. The primary outcome was functional improvement. Nine RCTs including 453 patients were identified. From 6–7 weeks to 24–26 weeks postintervention, no superiority was noted in favor of either steroid injection or physiotherapy for functional improvement (SMD 0.28; 95% CI −0.01–0.58; P = 0.06) or pain relief (SMD −0.10; 95% CI −0.70–0.50; P = 0.75). Steroid injection provided more improvement in passive external rotation at 24 to 26 weeks (3 studies, SMD 0.42; 95% CI 0.11–0.72; P = 0.007) but not at 6 to 7 weeks (4 studies, SMD 0.63; 95% CI 0.36–0.89; P = 0.32) or 12 to 16 weeks (3 studies, SMD −0.07; 95% CI −0.79–0.65; P = 0.85). Steroid injection was as safe as physiotherapy for patients with ACS (risk ratio 0.94; 95% CI 0.67–1.31). Both steroid injection and physiotherapy are equally effective for patients with ACS. One steroid injection might be the 1st choice for ACS. Results should be interpreted with caution due to the heterogeneity among the studies. PMID:27196452

Administration of vitamin D3 by injection or drinking water alters serum 25-hydroxycholecalciferol concentrations of nursery pigs

PubMed Central

Ma, Jingyun; Lim, Jina; Monegue, H. James; Stuart, Robert L.

2018-01-01

Objective Two experiments were conducted to evaluate vitamin D3 administration to nursery pigs by injection or in drinking water on serum 25-hydroxycholecalciferol (25-OHD3) concentrations. Methods At weaning, 51 pigs (27 and 24 pigs in experiments 1 and 2, respectively) were allotted to vitamin D3 treatments. Treatments in experiment 1 were: i) control (CON), no vitamin administration beyond that in the diet, ii) intramuscular (IM) injection of 40,000 IU of vitamin D3 at weaning, and iii) water administration, 5,493 IU of vitamin D3/L drinking water for 14 d postweaning. Treatments in experiment 2 were: i) control (CON), no vitamin administration, and ii) water administration, 92 IU of d-α-tocopherol and 5,493 IU of vitamin D3/L drinking water for 28 d postweaning. The lightest 2 pigs within each pen were IM injected with an additional 1,000 IU of d-α-tocopherol, 100,000 IU of retinyl palmitate, and 100,000 IU of vitamin D3. Results In both experiments, serum 25-OHD3 was changed after vitamin D3 administration (p<0.05). In experiment 1, injection and water groups had greater values than CON group through d 35 and 21 post-administration, respectively (p<0.05). In experiment 2, serum values peaked at d 3 post-administration in the injection groups regardless of water treatments (p<0.05) whereas CON and water-only groups had peaks at d 14 and 28 post-administration, respectively (p<0.05). Even though the injection groups had greater serum 25-OHD3 concentrations than the non-injection groups through d 7 post-administration regardless of water treatments (p<0.05), the water-only group had greater values than the injection-only group from d 21 post-administration onward (p<0.05). Conclusion Serum 25-OHD3 concentrations in pigs increased either by vitamin D3 injection or drinking water administration. Although a single vitamin D3 injection enhanced serum 25-OHD3 concentrations greater than water administration in the initial period post-administration, a continuous supply of vitamin D3 via drinking water could maintain higher serum values than the single injection. PMID:28823124

Biodistribution and Immunogenicity of Allogeneic Mesenchymal Stem Cells in a Rat Model of Intraarticular Chondrocyte Xenotransplantation.

PubMed

Marquina, Maribel; Collado, Javier A; Pérez-Cruz, Magdiel; Fernández-Pernas, Pablo; Fafián-Labora, Juan; Blanco, Francisco J; Máñez, Rafael; Arufe, María C; Costa, Cristina

2017-01-01

Xenogeneic chondrocytes and allogeneic mesenchymal stem cells (MSC) are considered a potential source of cells for articular cartilage repair. We here assessed the immune response triggered by xenogeneic chondrocytes when injected intraarticularly, as well as the immunoregulatory effect of allogeneic bone marrow-derived MSC after systemic administration. To this end, a discordant xenotransplantation model was established by injecting three million porcine articular chondrocytes (PAC) into the femorotibial joint of Lewis rats and monitoring the immune response. First, the fate of MSC injected using various routes was monitored in an in vivo imaging system. The biodistribution revealed a dependency on the injection route with MSC injected intravenously (i.v.) succumbing early after 24 h and MSC injected intraperitoneally (i.p.) lasting locally for at least 5 days. Importantly, no migration of MSC to the joint was detected in rats previously injected with PAC. MSC were then administered either i.v. 1 week before PAC injection or i.p. 3 weeks after to assess their immunomodulatory function on humoral and adaptive immune parameters. Anti-PAC IgM and IgG responses were detected in all PAC-injected rats with a peak at week 2 postinjection and reactivity remaining above baseline levels by week 18. IgG2a and IgG2b were the predominant and long-lasting IgG subtypes. By contrast, no anti-MSC antibody response was detected in the cohort injected with MSC only, but infusion of MSC before PAC injection temporarily augmented the anti-PAC antibody response. Consistent with a cellular immune response to PAC in PAC-injected rats, cytokine/chemokine profiling in serum by antibody array revealed a distinct pattern relative to controls characterized by elevation of multiple markers at week 2, as well as increases in proliferation in draining lymph nodes. Notably, systemic administration of allogeneic MSC under the described conditions did not diminish the immune response. IL-2 measurements in cocultures of rat peripheral blood lymphocytes with PAC indicated that PAC injection induced some T-cell hyporesponsiveness that was not enhanced in the cohorts additionally receiving MSC. Thus, PAC injected intraarticularly in Lewis rats induced a cellular and humoral immune response that was not counteracted by the systemic administration of allogeneic MSC under the described conditions.

Biodistribution and Immunogenicity of Allogeneic Mesenchymal Stem Cells in a Rat Model of Intraarticular Chondrocyte Xenotransplantation

PubMed Central

Marquina, Maribel; Collado, Javier A.; Pérez-Cruz, Magdiel; Fernández-Pernas, Pablo; Fafián-Labora, Juan; Blanco, Francisco J.; Máñez, Rafael; Arufe, María C.; Costa, Cristina

2017-01-01

Xenogeneic chondrocytes and allogeneic mesenchymal stem cells (MSC) are considered a potential source of cells for articular cartilage repair. We here assessed the immune response triggered by xenogeneic chondrocytes when injected intraarticularly, as well as the immunoregulatory effect of allogeneic bone marrow-derived MSC after systemic administration. To this end, a discordant xenotransplantation model was established by injecting three million porcine articular chondrocytes (PAC) into the femorotibial joint of Lewis rats and monitoring the immune response. First, the fate of MSC injected using various routes was monitored in an in vivo imaging system. The biodistribution revealed a dependency on the injection route with MSC injected intravenously (i.v.) succumbing early after 24 h and MSC injected intraperitoneally (i.p.) lasting locally for at least 5 days. Importantly, no migration of MSC to the joint was detected in rats previously injected with PAC. MSC were then administered either i.v. 1 week before PAC injection or i.p. 3 weeks after to assess their immunomodulatory function on humoral and adaptive immune parameters. Anti-PAC IgM and IgG responses were detected in all PAC-injected rats with a peak at week 2 postinjection and reactivity remaining above baseline levels by week 18. IgG2a and IgG2b were the predominant and long-lasting IgG subtypes. By contrast, no anti-MSC antibody response was detected in the cohort injected with MSC only, but infusion of MSC before PAC injection temporarily augmented the anti-PAC antibody response. Consistent with a cellular immune response to PAC in PAC-injected rats, cytokine/chemokine profiling in serum by antibody array revealed a distinct pattern relative to controls characterized by elevation of multiple markers at week 2, as well as increases in proliferation in draining lymph nodes. Notably, systemic administration of allogeneic MSC under the described conditions did not diminish the immune response. IL-2 measurements in cocultures of rat peripheral blood lymphocytes with PAC indicated that PAC injection induced some T-cell hyporesponsiveness that was not enhanced in the cohorts additionally receiving MSC. Thus, PAC injected intraarticularly in Lewis rats induced a cellular and humoral immune response that was not counteracted by the systemic administration of allogeneic MSC under the described conditions. PMID:29163532

[Strategy of constructing post-market integral evaluation system of traditional Chinese medicine injection].

PubMed

Zhang, Xiao-Yu; Wang, Yan-Ping; Lin, Li-Kai; Shang, Hong-Cai; Wang, Yong-Yan

2017-08-01

As an important representative of modern Chinese medicine, traditional Chinese medicine (TCM) injzection has become an indispensable part of the Chinese medicine industry. However, its development is now restricted by the bottleneck of insufficient core competitiveness, low-level research and production, even injection quality and the safe use are not guaranteed. Thus, it is urgent to reevaluate post-marketing TCM injection generally and to make secondary development. Under current circumstances, taking major brands which have good clinical and market foundation, as well as research value, as the main subject of cultivation and evaluation is an important approach to innovative development of TCM injection industry. Unlike oral proprietary Chinese medicine, the cultivatation of major brands of TCM injection needs higher technical support, quality standards and more timely feedback. Therefore, a post-market integral evaluation system adaptive to TCM injection is required. This article discussed some key points on the construction of a post-market integral evaluation system of TCM injection in three levels： optimizing evaluation methods, building synergistic innovation platforms which combine the medical research institutions and pharmaceutical enterprises, and finally constructing the integral evaluation system. A "five to one" structure has been proposed to enhance TCM injection effectiveness, safety and adaptability on the whole, which are from the following aspects： mechanism research, clinical evidence validation, literature information mining, sustainable development of resources and industrialization operation. Copyright© by the Chinese Pharmaceutical Association.

Chemopreventive evaluation of a Schiff base derived copper (II) complex against azoxymethane-induced colorectal cancer in rats.

PubMed

Hajrezaie, Maryam; Hassandarvish, Pouya; Moghadamtousi, Soheil Zorofchian; Gwaram, Nura Suleiman; Golbabapour, Shahram; Najihussien, Abdrabuh; Almagrami, Amel Abdullah; Zahedifard, Maryam; Rouhollahi, Elham; Karimian, Hamed; Fani, Somaye; Kamalidehghan, Behnam; Majid, Nazia Abdul; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

2014-01-01

Based on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF). This study involved five groups of male rats. The negative control group was injected with normal saline once a week for 2 weeks and fed 10% Tween 20 for 10 weeks, the cancer control group was subcutaneously injected with 15 mg/kg azoxymethane once per week for two consecutive weeks, the positive control group was injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and 35 mg/kg 5-fluorouracil (injected intra-peritoneally) for 4 weeks, and the experimental groups were first injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and then fed 2.5 or 5 mg/kg of the Schiff base compound once a day for 10 weeks. Application of the Schiff base compound suppressed total colonic ACF formation by up to 72% to 74% (P<0.05) when compared with the cancer control group. Analysis of colorectal specimens revealed that treatments with the Schiff base compound decreased the mean crypt scores in azoxymethane-treated rats. Significant elevations of superoxide dismutase, glutathione peroxidase and catalase activities and a reduction in the level of malondialdehyde were also observed. Histologically, all treatment groups exhibited significant decreases in dysplasia compared to the cancer control group (P<0.05). Immunohistochemical staining demonstrated down-regulation of the PCNA protein. Comparative western blot analysis revealed that COX-2 and Bcl2 were up-regulated and Bax was down-regulated compared with the AOM control group. The current study demonstrated that the Cu(BrHAP)2 compound has promising chemoprotective activities that are evidenced by significant decreases in the numbers of ACFs in azoxymethane-induced colon cancer.

Chemopreventive Evaluation of a Schiff Base Derived Copper (II) Complex against Azoxymethane-Induced Colorectal Cancer in Rats

PubMed Central

Hajrezaie, Maryam; Hassandarvish, Pouya; Moghadamtousi, Soheil Zorofchian; Gwaram, Nura Suleiman; Golbabapour, Shahram; NajiHussien, Abdrabuh; Almagrami, Amel Abdullah; Zahedifard, Maryam; Rouhollahi, Elham; Karimian, Hamed; Fani, Somaye; Kamalidehghan, Behnam; Majid, Nazia Abdul; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

2014-01-01

Background Based on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF). Methodology This study involved five groups of male rats. The negative control group was injected with normal saline once a week for 2 weeks and fed 10% Tween 20 for 10 weeks, the cancer control group was subcutaneously injected with 15 mg/kg azoxymethane once per week for two consecutive weeks, the positive control group was injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and 35 mg/kg 5-fluorouracil (injected intra-peritoneally) for 4 weeks, and the experimental groups were first injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and then fed 2.5 or 5 mg/kg of the Schiff base compound once a day for 10 weeks. Application of the Schiff base compound suppressed total colonic ACF formation by up to 72% to 74% (P<0.05) when compared with the cancer control group. Analysis of colorectal specimens revealed that treatments with the Schiff base compound decreased the mean crypt scores in azoxymethane-treated rats. Significant elevations of superoxide dismutase, glutathione peroxidase and catalase activities and a reduction in the level of malondialdehyde were also observed. Histologically, all treatment groups exhibited significant decreases in dysplasia compared to the cancer control group (P<0.05). Immunohistochemical staining demonstrated down-regulation of the PCNA protein. Comparative western blot analysis revealed that COX-2 and Bcl2 were up-regulated and Bax was down-regulated compared with the AOM control group. Conclusion The current study demonstrated that the Cu(BrHAP)2 compound has promising chemoprotective activities that are evidenced by significant decreases in the numbers of ACFs in azoxymethane-induced colon cancer. PMID:24618844

Satisfaction with Subcutaneous Golimumab and its Auto-Injector among Rheumatoid Arthritis Patients with Inadequate Response to Adalimumab or Etanercept.

PubMed

Dehoratius, Raphael J; Brent, Lawrence H; Curtis, Jeffrey R; Ellis, Lorie A; Tang, Kezhen L

2018-06-01

Patient perceptions of treatment success, including satisfaction/preference, may complement clinical efficacy assessments. Our objective was to evaluate satisfaction with subcutaneous golimumab and its auto-injector in patients with rheumatoid arthritis (RA) and an inadequate adalimumab/etanercept response. In the multicenter, assessor-blinded GO-SAVE study, 433 patients with active RA (28-joint Disease Activity Score incorporating erythrocyte sedimentation rate [DAS28-ESR] ≥ 3.6 and six or more swollen and six or more tender joints) despite methotrexate and past adalimumab/etanercept treatment received open-label subcutaneous golimumab 50 mg every 4 weeks (q4w) through week 12. Week 16 responders (DAS28-ESR improvement from baseline > 1.2 and score ≤ 3.2) continued therapy through week 52; nonresponders were randomized (1:2) to double-blind subcutaneous golimumab 50 mg q4w or intravenous golimumab 2 mg/kg [weeks 16, 20, every 8 weeks (q8w)]. Patients rated satisfaction with their injection experience on a 5-point scale (1 = very dissatisfied; 5 = very satisfied) at screening, week 8 (all enrolled patients), and week 44 (for patients continuing open-label subcutaneous golimumab 50 mg q4w). Discomfort, pain, stinging, burning, and redness related to injection were assessed (none, mild, moderate, severe). Similar proportions of patients (N = 433) had most recently received adalimumab (50.3%) or etanercept (49.7%) prior to golimumab. Overall satisfaction (somewhat/very) with the golimumab injection experience was reported by 84.4% of patients at week 8 versus 63.4% of patients who were satisfied with prior adalimumab/etanercept. Patients receiving open-label subcutaneous golimumab through week 44 (N = 75) reported much less discomfort (60.9%), redness (60.9%), pain (59.4%), stinging (67.2%), and burning (65.6%) with the golimumab injection than with their previous tumor necrosis factor antagonist medication injection. Most patients with RA receiving golimumab following adalimumab/etanercept inadequate response were satisfied with their overall golimumab experience, including its auto-injector versus their previous injection device. CLINICAL TRIALS.GOV: NCT01004432; EudraCT 2009-010582-23.

Clinical evaluation of pazopanib eye drops versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration.

PubMed

Csaky, Karl G; Dugel, Pravin U; Pierce, Amy J; Fries, Michael A; Kelly, Deborah S; Danis, Ronald P; Wurzelmann, John I; Xu, Chun-Fang; Hossain, Mohammad; Trivedi, Trupti

2015-03-01

To evaluate pazopanib eye drops in subjects with active subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Multicountry, randomized, parallel-group, double-masked, active and placebo-controlled, dose-ranging study of eye drops. A total of 510 subjects (93% white; 58% female; mean age, 75.3 years) whose AMD was previously managed by anti-vascular endothelial growth factor intravitreal injections. Treatments administered for 52 weeks included placebo eye drops instilled 4 times daily (n=73); pazopanib 5 mg/ml instilled 3 (n=72) or 4 times daily (n=74); pazopanib 10 mg/ml instilled 2 (n=73), 3 (n=73), or 4 times daily (n=72); or ranibizumab injection administered once every 4 weeks (n=73). In addition, for all eye drop treatment groups, open-label ranibizumab was administered as needed. The main outcome measures were best-corrected visual acuity (BCVA) and injection frequency assessed at week 52. Safety was assessed every 4 weeks and pazopanib plasma concentrations were determined at weeks 4 and 24. At week 52, pazopanib, with allowance for as-needed ranibizumab injections, was noninferior to monthly ranibizumab as well as to as-needed ranibizumab administered with placebo eye drops in maintaining BCVA (estimated BCVA gains of 0.3-1.8 vs. 1.4 vs. 0.2 letters, respectively). Pazopanib treatment did not reduce as-needed ranibizumab injections by ≥50% (prespecified efficacy criterion). At week 52, there were no clinically meaningful changes from baseline in retinal thickness or morphology, CNV size, or lesion characteristics on optical coherence tomography or fluorescein angiography. Complement factor H genotype had no effect on the responses to pazopanib and/or ranibizumab (BCVA, injection rate, or optical coherence tomography/fluorescein angiography changes). Steady-state concentrations of pazopanib in plasma seemed to be reached by week 4. The most common ocular adverse events related to pazopanib and ranibizumab were application site pain (3%) and injection site hemorrhage (1%), respectively. No treatment-related serious adverse events were reported. Pazopanib was well tolerated. Daily pazopanib eye drops in neovascular AMD subjects did not result in therapeutic benefit beyond that obtained with ranibizumab alone. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Effects of Pre and Post-Rigor Marinade Injection on Some Quality Parameters of Longissimus Dorsi Muscles

PubMed Central

Fadıloğlu, Eylem Ezgi; Serdaroğlu, Meltem

2018-01-01

Abstract This study was conducted to evaluate the effects of pre and post-rigor marinade injections on some quality parameters of Longissimus dorsi (LD) muscles. Three marinade formulations were prepared with 2% NaCl, 2% NaCl+0.5 M lactic acid and 2% NaCl+0.5 M sodium lactate. In this study marinade uptake, pH, free water, cooking loss, drip loss and color properties were analyzed. Injection time had significant effect on marinade uptake levels of samples. Regardless of marinate formulation, marinade uptake of pre-rigor samples injected with marinade solutions were higher than post rigor samples. Injection of sodium lactate increased pH values of samples whereas lactic acid injection decreased pH. Marinade treatment and storage period had significant effect on cooking loss. At each evaluation period interaction between marinade treatment and injection time showed different effect on free water content. Storage period and marinade application had significant effect on drip loss values. Drip loss in all samples increased during the storage. During all storage days, lowest CIE L* value was found in pre-rigor samples injected with sodium lactate. Lactic acid injection caused color fade in pre-rigor and post-rigor samples. Interaction between marinade treatment and storage period was found statistically significant (p<0.05). At day 0 and 3, the lowest CIE b* values obtained pre-rigor samples injected with sodium lactate and there were no differences were found in other samples. At day 6, no significant differences were found in CIE b* values of all samples. PMID:29805282

Effects of Pre and Post-Rigor Marinade Injection on Some Quality Parameters of Longissimus Dorsi Muscles.

PubMed

Fadıloğlu, Eylem Ezgi; Serdaroğlu, Meltem

2018-04-01

This study was conducted to evaluate the effects of pre and post-rigor marinade injections on some quality parameters of Longissimus dorsi (LD) muscles. Three marinade formulations were prepared with 2% NaCl, 2% NaCl+0.5 M lactic acid and 2% NaCl+0.5 M sodium lactate. In this study marinade uptake, pH, free water, cooking loss, drip loss and color properties were analyzed. Injection time had significant effect on marinade uptake levels of samples. Regardless of marinate formulation, marinade uptake of pre-rigor samples injected with marinade solutions were higher than post rigor samples. Injection of sodium lactate increased pH values of samples whereas lactic acid injection decreased pH. Marinade treatment and storage period had significant effect on cooking loss. At each evaluation period interaction between marinade treatment and injection time showed different effect on free water content. Storage period and marinade application had significant effect on drip loss values. Drip loss in all samples increased during the storage. During all storage days, lowest CIE L* value was found in pre-rigor samples injected with sodium lactate. Lactic acid injection caused color fade in pre-rigor and post-rigor samples. Interaction between marinade treatment and storage period was found statistically significant ( p <0.05). At day 0 and 3, the lowest CIE b* values obtained pre-rigor samples injected with sodium lactate and there were no differences were found in other samples. At day 6, no significant differences were found in CIE b* values of all samples.

Lineage Analysis in Pulmonary Arterial Hypertension

DTIC Science & Technology

2012-06-01

undergo pneunomectomy followed one week later by intravenous injection of monocrotaline pyrrole . The fate of GFP-expressing cells of endothelial lineage...pneumonectomy followed one week later by jugular vein injection of monocrotaline pyrrole in dimethyl formamide. Expression of smooth muscle alpha actin in...cells. We induced experimental pulmonary hypertension in SM22 Cre x mT/mG mice, by injecting monocrotaline pyrrole into the pulmonary circulation of

77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

... for Injection, administered as two doses 4 weeks apart to intact male pigs for the reduction of boar... pigs and barrows. Do not use in intact male pigs intended for breeding because of the disruption of.... Pigs should be slaughtered no earlier than 3 weeks and no later than 10 weeks after the second dose...

Ultrasound-guided retro-calcaneal bursa corticosteroid injection for refractory Achilles tendinitis in patients with seronegative spondyloarthropathy: efficacy and follow-up study.

PubMed

Srivastava, Puja; Aggarwal, Amita

2016-06-01

Ultrasound (US)-guided corticosteroid injection has been shown to be safe and effective for varied causes of plantar fasciitis; however, its use for Achilles tendinitis is controversial. We studied the efficacy and changes in US findings at Achilles enthesitis after corticosteroid injection in patients with spondyloarthropathy (SpA). Patients with SpA with symptomatic Achilles enthesitis, refractory to 6 weeks of full-dose NSAIDs, were offered US-guided local corticosteroid injection. Injected entheses were examined by US (both B mode and power Doppler) at baseline and 6 weeks after injection. Standard OMERACT definitions were used to define enthesitis. Achilles tendon thickness >5.29 mm, 2 cm proximal to insertion in long axis, was considered thickened. Twenty-seven symptomatic Achilles tendons (in 18 patients) were injected with 20 mg methylprednisolone under US guidance baseline, and 6-week follow-up US features were compared. All patients reported improvement in pain (VAS) in the affected tendon after injection (p < 0.0001). Simultaneously, improvement in local inflammatory changes were noted, in the form of significant reduction in tendon thickness (p < 0.0001), vascularity (p < 0.0001), peritendinous oedema (p = 0.001), bursitis and bursal vascularity (p < 0.001 and < 0.0001, respectively). There was no change in bone erosions and enthesophyte. None of the patients had tendon rupture or other injection-related complications at 6 weeks of follow-up. US-guided local corticosteroid injection is an effective and safe modality for refractory Achilles enthesitis in patients with SpA and leads to reversion of acute changes at entheseal site.

Repeated aripiprazole administration attenuates cocaine seeking in a rat model of relapse.

PubMed

Feltenstein, Matthew W; Do, Phong H; See, Ronald E

2009-12-01

Aripiprazole (Abilify) is an atypical antipsychotic drug characterized by partial agonist activity at dopamine (DA) D(2)/D(3) receptors and a low side-effect profile. While we previously demonstrated that acute aripiprazole blocked the reinstatement of cocaine seeking in an animal model of relapse, clinical treatment of relapse prevention necessitates testing the effects of aripiprazole following prolonged abstinence, as well as after repeated administration during withdrawal from cocaine. We assessed the effects of repeated aripiprazole treatment on cocaine seeking after abstinence and during conditioned cue-induced and cocaine-primed reinstatement in rats. Rats self-administered intravenous cocaine paired with a light + tone stimulus for 10-14 days, followed by 2 weeks of abstinence. Following post-abstinence relapse testing, lever responding was allowed to extinguish, with subsequent reinstatement testing occurring either in the presence of the conditioned stimulus, or after a cocaine-priming injection (10 mg/kg, intraperitoneal (IP)). Following 3 or 7 days of pretreatment, rats received an injection of aripiprazole (0.25, 0.5, and 1.0 mg/kg, IP) or vehicle prior to post-abstinence relapse and reinstatement testing. Vehicle-pretreated animals showed robust cocaine seeking during relapse and reinstatement testing, an effect that was significantly attenuated by aripiprazole pretreatment, although no lasting effects were found in the absence of acute injection. These findings support the possibility that repeated aripiprazole may be an effective therapeutic agent for the prevention of relapse in abstinent cocaine users. Based on its antipsychotic profile, aripiprazole may be particularly useful for individuals diagnosed with comorbid psychoses, such as schizophrenia or bipolar disorder.

Blocking of beta-2 adrenergic receptors hastens recovery from hypoglycemia-associated social withdrawal.

PubMed

Park, Min Jung; Guest, Christopher B; Barnes, Meredith B; Martin, Jonathan; Ahmad, Uzma; York, Jason M; Freund, Gregory G

2008-11-01

Hypoglycemia is associated with a variety of adverse behaviors including fatigue, confusion and social withdrawal. While these clinical symptoms are well characterized, the mechanism of their cause is not understood. Here we investigated how insulin-induced hypoglycemia causes social withdrawal. Male 8-12-week-old C57BL/6J mice were injected intraperitoneally (IP) with or without and/or insulin, norepinephrine (NE) and epinephrine (Epi), terbutaline and butoxamine with subsequent measurement of blood glucose, social withdrawal and plasma catecholamines. Insulin generated (0.75h post-injection) significant hypoglycemia with blood glucose nadirs of 64+/-4 and 48+/-5mg/dl for 0.8 and 1.2units/kg of insulin, respectively. Insulin (0.8 or 1.2units/kg) caused near total social withdrawal at 0.75h with full recovery not occurring until 4h (0.8units/kg) or 8h (1.2units/kg) post-insulin injection. Insulin also caused a marked elevation in plasma catecholamines. Basal 12h fasting NE and Epi were 287+/-38 and 350+/-47pg/ml, respectively. Insulin at 0.8units/kg increased plasma NE and Epi to 994+/-73 and 1842+/-473pg/ml, respectively. Administration of exogenous NE or Epi caused social withdrawal similar in magnitude to insulin. Importantly, administration of the beta-2 adrenergic receptor agonist terbutaline also caused social withdrawal while administration of the beta-2 adrenergic receptor antagonist butoxamine blocked NE-induced social withdrawal. Finally, butoxamine blocked insulin-induced social withdrawal. These data demonstrate that hypoglycemia-associated social withdrawal is dependent on catecholamines via a beta-2 receptor-mediated pathway.

The development of analgesic, pro- and anti-convulsant opiate effects in the rat.

PubMed

Van Praag, H; Falcon, M; Guendelman, D; Frenk, H

1993-01-01

Evidence indicates that the neonate is capable, if not perceiving nociception, then at least reacting to nociceptive stimuli. These responses can be inhibited by opiates such as morphine. The analgesic potency of morphine in rat pups increases with maturation, due to (a) the proliferation of opiate receptors and (b), the maturation of supraspinal descending inhibition which becomes functional at 3 weeks post-natally. Tolerance to repeated injections of morphine in pups is less pronounced than in adults since it is masked by several processes, it has been demonstrated to occur within the first two weeks of life. Toxic effects of morphine in the neonate, as can be demonstrated both in behavior and EEG, differ from those in adults. Thus, convulsions induced by morphine which have been reported to occur in adults, were absent in pups. Excitatory effects of morphine in behavior develop in 3 different stages. During the first week morphine caused behavioral activation which is not mediated by specific opiate receptors. In the second week morphine produces EEG spikes in a dose-dependent fashion, but at this age these spikes were not reversible by opiate antagonists. Opiate specific EEG spikes and other opiate specific excitatory effects start to predominate during the third week of life.

Mesenchymal Stem Cells in the Bone Marrow Provide a Supportive Niche for Early Disseminated Breast Tumor Initiating Cells

DTIC Science & Technology

2013-06-01

transplanted into the mammary fat pad of NUDE mice to establish tumorigenicity in vivo. At 3 months post- injection , micrometastases to the lung, liver...E-cadherin, nuclear β catenin and fibronectin but were negative for ERα and vimentin. The injection of bone marrow isolated from mice previously... injected with tumorspheres into the mammary fat pad, resulted in large tumor formation in the mammary fat pad 2 months post- injection . The tumors

Effectiveness of benzocaine in reducing deep cavity restoration and post-extraction stress in dental patients.

PubMed

Al-Samadani, Khalid H; Gazal, Giath

2015-11-01

To investigate the effectiveness of topical anesthetic, 20% benzocaine in relieving pain and stress in patients following deep cavity restoration and extraction of teeth under local anesthesia (LA). A prospective clinical trial was conducted from October 2014 until April 2015 at Taibah University, Al Madinah Al Munawarah, Kingdom of Saudi Arabia. Forty-five patients were included in the 20% benzocaine group, and 46 in the normal saline group. Evaluation of the dental stress was made pre-operatively and immediately post-operative treatment using the visual analogue scale (VAS). Furthermore, discomfort of the injections were recorded by the patients after each treatment on standard 100 mm VAS, tagged at the endpoints with "no pain" (0 mm) and "unbearable pain" (100 mm). There were statistically significant differences between the mean stress scores for patients in the benzocaine and normal saline groups post-operatively (p=0.002). There were significant differences between the mean pain scores for patients in the post buccal injection (p=0.001), post palatal injection (p=0.01), and the post inferior alveolar nerve block groups (p=0.02). Buccal, palatal, and inferior alveolar nerve block injections were more painful for patients in the normal saline group than the benzocaine group. This investigation has demonstrated that post-operative stress associated with deep cavity restoration and dental extractions under LA can be reduced by the application of topical anesthetic (20% benzocaine) at the operative site for intra-oral injections.

Effectiveness of benzocaine in reducing deep cavity restoration and post-extraction stress in dental patients

PubMed Central

Al-Samadani, Khalid H.; Gazal, Giath

2015-01-01

Objectives: To investigate the effectiveness of topical anesthetic, 20% benzocaine in relieving pain and stress in patients following deep cavity restoration and extraction of teeth under local anesthesia (LA). Methods: A prospective clinical trial was conducted from October 2014 until April 2015 at Taibah University, Al Madinah Al Munawarah, Kingdom of Saudi Arabia. Forty-five patients were included in the 20% benzocaine group, and 46 in the normal saline group. Evaluation of the dental stress was made pre-operatively and immediately post-operative treatment using the visual analogue scale (VAS). Furthermore, discomfort of the injections were recorded by the patients after each treatment on standard 100 mm VAS, tagged at the endpoints with “no pain” (0 mm) and “unbearable pain” (100 mm). Results: There were statistically significant differences between the mean stress scores for patients in the benzocaine and normal saline groups post-operatively (p=0.002). There were significant differences between the mean pain scores for patients in the post buccal injection (p=0.001), post palatal injection (p=0.01), and the post inferior alveolar nerve block groups (p=0.02). Buccal, palatal, and inferior alveolar nerve block injections were more painful for patients in the normal saline group than the benzocaine group. Conclusion: This investigation has demonstrated that post-operative stress associated with deep cavity restoration and dental extractions under LA can be reduced by the application of topical anesthetic (20% benzocaine) at the operative site for intra-oral injections. PMID:26593169

Ultrasound-guided subacromial injections of sodium hyaluronate for the management of rotator cuff tendinopathy: a prospective comparative study with rehabilitation therapy.

PubMed

Merolla, G; Bianchi, P; Porcellini, G

2013-06-01

Rotator cuff (RC) tendinopathy is a common cause of pain and shoulder dysfunction. The literature evidence suggests that a combination of overuse and extrinsic compression may induce chronic RC tendinopathy. Aim of the current study was to compare the results of subacromial sodium hyaluronate injections with rehabilitation therapy. We enrolled 48 patients (M/F: 26/22; mean age: 50 years; shoulder right/left: 29/19) with persistent shoulder pain for at least 4 months. Exclusion criteria were as follows: RC tear, calcifying tendinitis, glenohumeral instability, osteoarthritis, rheumatic diseases, physical therapy and/or injection in the previous 4 months, shoulder surgery, anesthetic nerve block, trauma, and severe medical diseases. The included subjects received either two ultrasound-guided subacromial hyaluronic acid (HA) injections (25 patients, HA group) at baseline and 14 days, or underwent rehabilitation therapy (23 patients, Physio group) including active shoulder mobilization, soft tissue stretching and humeral head positioner and propeller muscles strengthening for 30 days (3 sessions every week). Clinical assessment of shoulder function was performed with visual analog scale score for pain (0-100), Oxford Shoulder Score (OSS), and Constant-Murley Score (CS). Overall, patients were examined at baseline, week 2, week 4, week 12, and week 24. Statistical significance was set at 5 % (p < 0.05). Reduction in overall pain in the HA group was statistically significant at week 2 (p < 0.05) week 4 (p < 0.05), week 12 comparing to baseline. Similarly, pain subscores (at night and with activity) were significantly lower at week 2 (p < 0.05), week 4 (p < 0.05), and week 12 (p < 0.05), respectively. In the Physio group, pain decreased significantly at week 2 (p < 0.05) but not maintained at week 4 (p > 0.05), week 12 (p > 0.05), and week 24 (p > 0.05). CS and OSS in the HA group increased significantly at week 2 (p < 0.05), week 4 (p < 0.05), and week 12 (p < 0.05). A non-statistically significant increase in clinical scores was found at week 24 (p > 0.05). A significant improvement of CS and OSS we found in the Physio group at week 2 (p < 0.05), but not at weeks 4, 12, and 24 (p > 0.05). Subacromial HA injections could be an effective and safe alternative treatment for patients suffering from RC tendinopathy. We believe that the results of this study are encouraging but not lasting and we might suppose that a series of three to four subacromial sodium hyaluronate injections could provide good mid- and long-term clinical benefits.

Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel.

PubMed

Fukui, Takaaki; Kitamura, Nobuto; Kurokawa, Takayuki; Yokota, Masashi; Kondo, Eiji; Gong, Jian Ping; Yasuda, Kazunori

2014-04-01

Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.

Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study.

PubMed

Lee, Hyunah; Park, Jae Berm; Lee, Sanghoon; Baek, Soyoung; Kim, HyunSoo; Kim, Sung Joo

2013-04-11

Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. MSCs were derived from negative HLA cross-match donors. Donor bone marrow was harvested 5 weeks prior to KT. At the time of transplantation, 1 x 106 cell/kg of donor MSC was directly injected into the bone marrow of the recipient's right iliac bone. Patients' clinical outcomes, presence of mixed chimerism by short tandem repeat polymerase chain reaction, analysis of plasma FoxP3 mRNA and cytokine level, and mixed lymphocyte reaction (MLR) were performed. Seven patients enrolled in this study and received donor MSC injections simultaneously with LDKT. The median age of recipients was 36 years (32 ~ 48). The number of HLA mismatches was 3 or less in 5 and more than 3 in 2. No local complications or adverse events such as hypersensitivity occurred during or after the injection of donor MSC. There was no graft failure, but the biopsy-proven acute rejections were observed in 3 recipients during the follow-up period controlled well with steroid pulse therapy (SPT). The last serum creatinine was a median of 1.23 mg/dL (0.83 ~ 2.07). Mixed chimerism was not detected in the peripheral blood of the recipients at 1 and 8 week of post-transplantation. Donor-specific lymphocyte or T cell proliferation and Treg priming responses were observed in some patients. Plasma level of IL-10, a known mediator of MSC-induced immune suppression, increased in the patients with Treg induction. Donor MSC injection into the iliac bone at the time of KT was feasible and safe. A possible correlation was observed between the induction of inhibitory immune responses and the clinical outcome in the MSC-kidney transplanted patients. Further research will be performed to evaluate the efficacy of MSC injection for the induction of mixed chimerism and subsequent immune tolerance in KT.

Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study

PubMed Central

Bashaireh, Khaldoon; Naser, Ziad; Hawadya, Khaled Al; Sorour, Sorour; Al-Khateeb, Rami Nabeel

2015-01-01

Purpose The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period. Materials and methods The study was a post-marketing Phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1–4) in the tibio–femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection. Main outcome measure(s) An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated. Main results The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3.36, the stiffness score was 0.42, and the physical performance score was 11.5. All side effects were local and transient, and included pain, swelling, and redness of the knee. Most side effects were treated. Conclusion Hyaluronan should be encouraged as an alternative or adjunct treatment to oral analgesics to reduce their required doses, and delay potential future surgical intervention. PMID:25897212

Efficacy and safety of single injection of cross-linked sodium hyaluronate vs. three injections of high molecular weight sodium hyaluronate for osteoarthritis of the knee: a double-blind, randomized, multi-center, non-inferiority study.

PubMed

Ha, Chul-Won; Park, Yong-Beom; Choi, Chong-Hyuk; Kyung, Hee-Soo; Lee, Ju-Hong; Yoo, Jae Doo; Yoo, Ju-Hyung; Choi, Choong-Hyeok; Kim, Chang-Wan; Kim, Hee-Chun; Oh, Kwang-Jun; Bin, Seong-Il; Lee, Myung Chul

2017-05-26

This randomized, double-blind, multi-center, non-inferiority trial was conducted to assess the efficacy and safety of a cross-linked hyaluronate (XLHA, single injection form) compared with a linear high molecular hyaluronate (HMWHA, thrice injection form) in patients with symptomatic knee osteoarthritis. Two hundred eighty seven patients with osteoarthritis (Kellgren-Lawrence grade I to III) were randomized to each group. Three weekly injections were given in both groups but two times of saline injections preceded XLHA injection to maintain double-blindness. Primary endpoint was the change of weight-bearing pain (WBP) at 12 weeks after the last injection. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis index; patient's and investigator's global assessment; pain at rest, at night, or in motion; OMERACT-OARSI responder rate; proportion of patients achieving at least 20 mm or 40% decrease in WBP; and rate of rescue medicine use and its total consumption. Mean changes of WBP at 12 weeks after the last injection were -33.3 mm with XLHA and -29.2 mm with HMWHA, proving non-inferiority of XLHA to HMWHA as the lower bound of 95% CI (-1.9 mm, 10.1 mm) was well above the predefined margin (-10 mm). There were no significant between-group differences in all secondary endpoints. Injection site pain was the most common adverse event and no remarkable safety issue was identified. This study demonstrated that a single injection of XLHA was non-inferior to three weekly injections of HMWHA in terms of WBP reduction, and supports XLHA as an effective and safe treatment for knee osteoarthritis. ClinicalTrials.gov ( NCT01510535 ). This trial was registered on January 6, 2012.

Platelet-rich plasma versus steroid injection for subacromial impingement syndrome.

PubMed

Say, F; Gurler, D; Bulbul, M

2016-04-01

To compare the 6-week and 6-month outcome in 60 patients who received a single-dose injection of platelet-rich plasma (PRP) or steroid for subacromial impingement syndrome (SIS). 22 men and 38 women (mean age, 49.7 years) opted to receive a single-dose injection of PRP (n=30) or steroid (n=30) for SIS that had not responded to conservative treatment for >3 months. The PRP or a mixture of 1 ml 40 mg methylprednisolone and 8 ml prilocaine was administered via a dorsolateral approach through the interval just beneath the dorsal acromial edge. Both groups were instructed to perform standard rotator cuff stretching and strengthening exercises for 6 weeks. The use of non-steroid anti-inflammatory drugs was prohibited. Patients were evaluated before and 6 weeks and 6 months after treatment using the Constant score, visual analogue scale (VAS) for pain, and range of motion (ROM) of the shoulder. No local or systemic complication occurred. Improvement in the Constant score and VAS for pain at week 6 and month 6 was significantly better following steroid than PRP injection. The difference in the Constant score was greater than the mean clinically important difference of 10.4. Nonetheless, the 2 groups were comparable for improvement in ROM of the shoulder. Steroid injection was more effective than PRP injection for treatment of SIS in terms of the Constant score and VAS for pain at 6 weeks and 6 months.

A randomised controlled trial of intra-articular corticosteroid injection of the carpometacarpal joint of the thumb in osteoarthritis

PubMed Central

Meenagh, G; Patton, J; Kynes, C; Wright, G

2004-01-01

Objective: To investigate the efficacy of corticosteroid injections into the carpometacarpal joint of the thumb (CMCJ) in patients with osteoarthritis. Design: A double blind, randomised controlled trial using 40 hospital referred patients with CMCJ osteoarthritis who received intra-articular injections of 5 mg triamcinolone hexacetonide (0.25 ml) or sterile 0.9% saline (0.25 ml). Injections were given under imaging control. Main outcome measures: The primary outcome was improvement in a pain visual analogue score (VAS) of 20% at 24 weeks. In addition patients were assessed at 4, 12, and 24 weeks for joint stiffness, joint tenderness, and physician and patient global assessments. Hand radiographs were evaluated for the degree of CMC joint space narrowing and marginal osteophytes according to the OARSI atlas. Results: Baseline clinical variables were not significantly different between the two treatment groups. There was no improvement in the VAS of pain at 24 weeks. At each assessment point there was no significant difference between the steroid and placebo groups in median values for joint stiffness, joint tenderness, or patient and physician global assessments. Non-parametric analysis of each group individually revealed statistically significant improvements in patient and physician global assessments at weeks 4, 12, and 24 in the placebo group and at weeks 4 and 12 in the steroid group. Conclusions: No clinical benefit was gained from intra-articular steroid injection to the CMCJ in moderate to severe osteoarthritis compared with placebo injection. PMID:15361383

Effectiveness of Platelet-rich Plasma Injection for Rotator Cuff Tendinopathy: A Prospective Open-label Study.

PubMed

Scarpone, Michael; Rabago, David; Snell, Edward; Demeo, Patrick; Ruppert, Kristine; Pritchard, Perry; Arbogast, Gennie; Wilson, John J; Balzano, John F

2013-03-01

Assess platelet rich plasma (PRP) injection for rotator cuff tendinopathy (RCT). Prospective open label study with 1-year follow-up. Participants recruited from an outpatient sports medicine clinic had clinically and magnetic resonance image (MRI)-demonstrated RCT refractory to physical therapy and corticosteroid injection. They received one ultrasound-guided injection of 3.0 mL of 1% xylocaine followed by 3.5 mL of PRP at the lesion and surrounding tendon. 0-10 visual analog scale (VAS; baseline, 8, 12, and 52 weeks). functional shoulder tests assessing rotator cuff strength and endurance (at baseline and 8 and 12 weeks), MRI severity (1-5 points [at baseline and 4 and 8 weeks]), and patient satisfaction (52 weeks). Eighteen participants with 19 assessed shoulders reported VAS pain score improvement from 7.5 ± 0.3 points to 0.5 ± 0.3 points by week 12 and 0.4 ± 0.2 (P = .0001) points at week 52. Functional outcomes significantly improved; the largest effect was seen in the external rotation test: 33.5 ± 5.7 seconds to 62.6 ± 7.2 seconds at week 12 (P = .0001). MRI appearance improved by 1 to 3 points in 16 of 18 assessed shoulders. Seventeen participants were "completely satisfied" (12) or "satisfied" (5). One participant was "unsatisfied." A single ultrasound-guided, intralesional injection of PRP resulted in safe, significant, sustained improvement of pain, function, and MRI outcomes in participants with refractory RCT. Randomized multidisciplinary effectiveness trials that add ultrasound and validated clinical outcome measures are needed to further assess PRP for RCT.

Exercise therapy after ultrasound-guided corticosteroid injections in patients with subacromial pain syndrome: a randomized controlled trial.

PubMed

Ellegaard, Karen; Christensen, Robin; Rosager, Sara; Bartholdy, Cecilie; Torp-Pedersen, Søren; Bandholm, Thomas; Danneskiold-Samsøe, Bente; Bliddal, Henning; Henriksen, Marius

2016-06-04

Subacromial pain syndrome (SAPS) accounts for around 50 % of all cases of shoulder pain. The most commonly used treatments are glucocorticosteroid (steroid) injections and exercise therapy; however, despite treatment SAPS patients often experience relapse of their symptoms. Therefore the clinical effect of combining steroid and exercise therapy is highly relevant to clarify. The aim of this randomized controlled trial was to investigate if exercise therapy added to steroid injection in patients with SAPS will improve the effect of the injection therapy on shoulder pain. In this two-arm randomized trial running over 26 weeks, patients with unilateral shoulder pain (> 4 weeks) and thickened subacromial bursa (> 2 mm on US) were included. At baseline all participants received two steroid injections into the painful shoulder with an interval of one week. Subsequently they were randomized (1:1) to either 10 weeks exercise of the involved shoulder (intervention group) or exercise of the uninvolved shoulder (control group). The patients were re-examined after the exercise program (at week 13) and again at week 26. The primary outcome assessed after 26 weeks was change in shoulder pain analyzed using the intention-to-treat principle (non-responder imputation). Ninety-nine SAPS patients (58 female) participated (49 intervention/50 control). At both follow up visits (week 13 and 26) no statistically significant between-group differences in pain changes on a visual analog scale (mm) were seen (13 weeks: pain at rest 1.7 (95 % CI -3.6 to 7.0; P = 0.53); pain in activity 2.2 (95 % CI -6.5 to 10.9; P = 0.61), 26 weeks: rest 5.6 (95 % CI -0.9 to 12.1; P = 0.09); activity 2.2 (95 % CI -6.8 to 11.2; P = 0.62). The reduction in pain was most evident in the control group at all four pain measurements. The only difference between groups was seen by US examination at week 13, where fewer participants with impingement were observed in the intervention group compared with the controls (9 vs. 19 participants; P = 0.03). Exercise therapy in the painful shoulder in SAPS patients did not improve the effectiveness of steroid injections for shoulder pain in patients with unilateral SAPS and enlarged subacromial bursa on US examination. ClinicalTrials.gov ( NCT01506804 ). Registration date 5 May 2011.

Insulin response to a spontaneously ingested standard meal during the development of obesity in GTG-injected mice.

PubMed

Blair, S C; Caterson, I D; Cooney, G J

1996-04-01

(1) To determine glucose and insulin levels in response to ingestion of a standard meal during the development of gold-thioglucose (GTG)-induced obesity. (2) To examine whether the pancreatic beta-cells of GTG-injected mice possess sufficient insulin secretory capacity to compensate for the increasing tissue insulin resistance that occurs with the development of this obesity. The insulin secretory response to a standard meal of chow was examined in chronically catheterised conscious mice 2, 5 and 10 weeks after induction of obesity by a single injection of GTG. At 2 weeks after administration of GTG both the basal insulinaemia and the incremental area under the curve (iAUC) of insulin release after a chow meal were increased compared with age-matched lean control mice (2 week control: 1004 +/- 316 min/microU/ml; 2 week GTG: 1968 +/- 300 min/microU/ml; P < 0.05). By 5 weeks, the GTG-injected mice were approximately 42% heavier than their lean controls and showed a marked glucose intolerance. This was accompanied by hyperinsulinaemia in both the basal state and also in response to ingestion of the chow meal as indicated by the increase in the iAUC of insulin (5 week control: 1113 +/- 331 min/microU/ml; 5 week GTG: 2682 +/- 295 min/microU/ml; P < 0.05). At 10 weeks after GTG administration body weight was further increased, as was the degree of glucose intolerance. Plasma insulin levels, in both the basal state and in response to the ingestion of chow, were also further elevated by 10 weeks following GTG injection (10 week control: 1234 +/- 311 min/microU/ml; 10 week GTG: 6640 +/- 1198 min/microU/ml; P < 0.05). It is apparent that the secretion of insulin in response to a standard chow meal increases progressively with the development of obesity. This finding, in conjunction with an earlier study showing that the insulin secretory response to intravenously administered glucose becomes impaired in the latter stages of the development of obesity in GTG-injected mice [Blair SC, Caterson ID, Cooney GJ. Diabetes 1993; 42: 1153-1158], suggests that the ability of beta-cells of GTG-obese animals to produce and secrete insulin is not impaired but that the beta-cells may become insensitive to glucose within the circulation.

The Effects of Tissue-Nonspecific Alkaline Phosphatase Gene Therapy on Craniosynostosis and Craniofacial Morphology in the FGFR2C342Y/+ Mouse Model of Crouzon Craniosynostosis

PubMed Central

Wang, E; Nam, HK; Liu, J; Hatch, NE

2015-01-01

Objectives Craniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue-nonspecific alkaline phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs. Material & Methods Neonatal Crouzon (FGFRC342Y/+) and wild type (FGFR+/+) mice were injected with lentivirus to deliver a recombinant form of TNAP. Mice were sacrificed at four weeks post-natal. Serum was collected to test for alkaline phosphatase (AP), phosphorus, and calcium levels. Craniofacial bone fusion and morphology was assessed by micro-computed tomography. Results Injection with the TNAP lentivirus significantly increased serum AP levels (increased serum AP levels are indicative of efficient transduction and production of the recombinant protein), but results were variable and dependent upon viral lot and the litter of mice injected. Morphologic analysis revealed craniofacial form differences for inferior surface (p=.023) and cranial height (p=.014) regions between TNAP lentivirus injected and vehicle-injected Crouzon mice. With each unit increase in AP level, the odds of lambdoid suture fusion decreased by 84.2% and these results came close to statistical significance (p=.068). Conclusion These results suggest that TNAP deficiency may mediate FGFR2-associated craniosynostosis. Future studies should incorporate injection of recombinant TNAP protein, to avoid potential side effects and variable efficacy of lentiviral gene delivery. PMID:25865549

Autologous tenocyte implantation into shoulder tendon pathology in an elite swimmer.

PubMed

Schwab, Laura M; Blanch, Peter; Young, Mark

2018-01-01

The use of novel bioengineer treatment techniques such as Autologous Tenocyte Implantation (ATI) have shown promising improvements in both pain ratings and functional outcomes in elbow, gluteal and shoulder tendon pathology. This case will review the injury timeline of ATI intervention in an elite male swimmer with subscapularis tendon pathology and investigate whether ATI has a concomitant healing effect associated with improved functional outcomes. A palmaris longus tendon biopsy was performed and cells were expanded by in-vitro culture. Autologous tenocytes were injected into the subscapularis site identified. Three blinded radiologists reported on pre and post shoulder MRIs using the same 3T MRI protocol. A validated rating scale for severity of tendinopathy (0-3) and degree of tear (0-3) was used and hand-held Dynamometry (HHD) strength was recorded. Independent blinded radiology review demonstrated a significant reduction in tear size and improved tendon morphology. IR strength on HHD returned to baseline strength levels post ATI (231-253N) 6 weeks post intervention. The athlete returned to full training (volume and intensity) pain free and international level competition at 4 months post ATI. An athlete who had previously undergone unsuccessful conservative management demonstrated significant improvement in function and in tendon morphology post intervention. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fructose-fed streptozotocin-injected rat: an alternative model for type 2 diabetes.

PubMed

Wilson, Rachel D; Islam, Md Shahidul

2012-01-01

The main objective of the study was to develop an alternative non-genetic rat model for type 2 diabetes (T2D). Six-week-old male Sprague-Dawley rats (190.56 ± 23.60 g) were randomly divided into six groups, namely: Normal Control (NC), Diabetic Control (DBC), Fructose-10 (FR10), Fructose-20 (FR20), Fructose-30 (FR30) and Fructose-40 (FR40) and were fed a normal rat pellet diet ad libitum for 2 weeks. During this period, the two control groups received normal drinking water whilst the fructose groups received 10, 20, 30 and 40% fructose in drinking water ad libitum, respectively. After two weeks of dietary manipulation, all groups except the NC group received a single injection (i.p.) of streptozotocin (STZ) (40 mg/kg b.w.) dissolved in citrate buffer (pH 4.4). The NC group received only a vehicle buffer injection (i.p.). One week after the STZ injection, animals with non-fasting blood glucose levels > 300 mg/dl were considered as diabetic. Three weeks after the STZ injection, the animals in FR20, FR30 and FR40 groups were eliminated from the study due to the severity of diabetes and the FR10 group was selected for the remainder of the 11 weeks experimental period. The significantly (p < 0.05) higher fluid intake, blood glucose, serum lipids, liver glycogen, liver function enzymes and insulin resistance (HOMA-IR) and significantly (p < 0.05) lower body weight, oral glucose tolerance, number of pancreatic β-cells and pancreatic β-cell functions (HOMA-β) of FR10 group demonstrate that the 10% fructose-fed followed by 40 mg/kg of BWSTZ injected rat can be a new and alternative model for T2D.

Botulinum Toxin in Parkinson Disease Tremor: A Randomized, Double-Blind, Placebo-Controlled Study With a Customized Injection Approach.

PubMed

Mittal, Shivam Om; Machado, Duarte; Richardson, Diana; Dubey, Divyanshu; Jabbari, Bahman

2017-09-01

In essential tremor and Parkinson disease (PD) tremor, administration of onabotulinumtoxinA via a fixed injection approach improves the tremor, but many patients (30%-70%) develop moderate to severe hand weakness, limiting the use of onabotulinumtoxinA in clinical practice. To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for the treatment of tremor in PD. In this double-blind, placebo-controlled, crossover trial, 30 patients each received 7 to 12 (mean, 9) IncoA injections into hand and forearm muscles using a customized approach. The study was performed from June 1, 2012, through June 30, 2015, and participants were followed for 24 weeks. Treatment efficacy was evaluated by the tremor subsets of the Unified Parkinson's Disease Rating Scale and the Patient Global Impression of Change 4 and 8 weeks after each of the 2 sets of treatments. Hand strength was assessed using an ergometer. There was a statistically significant improvement in clinical rating scores of rest tremor and tremor severity 4 and 8 weeks after the IncoA injection and of action/postural tremor at 8 weeks. There was a significant improvement in patient perception of improvement at 4 and 8 weeks in the IncoA group. There was no statistically significant difference in grip strength at 4 weeks between the 2 groups. Injection of IncoA via a customized approach improved PD tremor on a clinical scale and patient perception, with a low occurrence of significant hand weakness. clinicaltrials.gov Identifier: NCT02419313. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Efficacy and Safety of Intravesical OnabotulinumtoxinA Injection in Patients with Detrusor Hyperactivity and Impaired Contractility

PubMed Central

Wang, Chung-Cheng; Lee, Cheng-Ling; Kuo, Hann-Chorng

2016-01-01

We investigated the efficacy and safety of intravesical onabotulinumtoxinA injection in patients with detrusor hyperactivity and impaired contractility (DHIC). Twenty-one patients with urodynamically proven DHIC and 21 age-matched patients with overactive bladder (OAB) with urodynamic detrusor overactivity were treated with intravesical injections of 100 U of onabotulinumtoxinA. The overactive bladder symptom score, urgency severity score, patient perception of bladder condition, global response assessment, voiding diary, and procedure-related adverse events (AE) at baseline, two weeks, one, three, and six months after treatment were assessed. The results showed that the subjective symptom scores improved significantly in both groups, and the scores did not differ between the groups. The decrease in urgency episodes and urgency urinary incontinence were noted in OAB patients but not in DHIC patients. Although the incidence of AEs was comparable between the groups, the therapeutic efficacy lasted for a mean of 4.9 ± 4.8 months in DHIC patients and 7.2 ± 3.3 months in OAB patients (p = 0.03). We concluded that the efficacy of intravesical onabotulinumtoxinA injection for DHIC patients was limited and short-term. Nevertheless, AEs did not increase in DHIC. Intravesical onabotulinumtoxinA might not be a good indication in patients with DHIC and high post-voiding residual urine. Physicians should inform patients of the potential benefits and risks of onabotulinumtoxinA injection for treatment of DHIC. PMID:26999209

Direct comparison of administration routes for AAV8-mediated ocular gene therapy.

PubMed

Igarashi, Tsutomu; Miyake, Koichi; Asakawa, Nagisa; Miyake, Noriko; Shimada, Takashi; Takahashi, Hiroshi

2013-05-01

We recently demonstrated that direct subretinal (SR) injection of adeno-associated virus (AAV) type 8 (AAV8) into photoreceptor cells and retinal pigment epithelium (RPE) is a highly efficient model of gene delivery. The current study compared transduction efficiency and expression patterns associated with various routes of vector administration. The efficacy of intravitreal (VT), SR and subconjunctival (SC) injections for delivery of AAV8-derived vectors, i.e. those expressing luciferase (Luc) and enhanced green fluorescent protein (GFP) - AAV8/Luc and AAV8/GFP, respectively - were compared in an animal (mouse) model (n = 8 mice/group). Transduction efficiency and expression patterns were examined at post-injection weeks 1 and 2, and months 1, 3, 6 and 12 via in vivo imaging. One year after AAV injection, AAV8/Luc-treated mice exhibited stable and sustained high expression of vector in the VT and SR groups, but not in the SC group (VT:SR:SC = 3,218:2,923:115; 1 × 10(5 )photons/s). Histological analysis showed that GFP expression was observed in the inner retina of VT group mice, and in photoreceptor cells and RPE of SR group mice, whereas no GFP expression was noted in the SC group. Electroretinography (ERG) revealed adverse effects following SR delivery. Results suggest that both SR and VT injections of AAV8 vectors are useful routes for administering ocular gene therapy, and stress the importance of selecting an appropriate administration route, i.e. one that targets specific cells, for treating ocular disorders.

Paracrine Effects of Bone Marrow Soup Restore Organ Function, Regeneration, and Repair in Salivary Glands Damaged by Irradiation

PubMed Central

Tran, Simon D.; Liu, Younan; Xia, Dengsheng; Maria, Ola M.; Khalili, Saeed; Wang, Renee Wan-Jou; Quan, Vu-Hung; Hu, Shen; Seuntjens, Jan

2013-01-01

Background There are reports that bone marrow cell (BM) transplants repaired irradiated salivary glands (SGs) and re-established saliva secretion. However, the mechanisms of action behind these reports have not been elucidated. Methods To test if a paracrine mechanism was the main effect behind this reported improvement in salivary organ function, whole BM cells were lysed and its soluble intracellular contents (termed as “BM Soup”) injected into mice with irradiation-injured SGs. The hypothesis was that BM Soup would protect salivary cells, increase tissue neovascularization, function, and regeneration. Two minor aims were also tested a) comparing two routes of delivering BM Soup, intravenous (I.V.) versus intra-glandular injections, and b) comparing the age of the BM Soup’s donors. The treatment-comparison group consisted of irradiated mice receiving injections of living whole BM cells. Control mice received irradiation and injections of saline or sham-irradiation. All mice were followed for 8 weeks post-irradiation. Results BM Soup restored salivary flow rates to normal levels, protected salivary acinar, ductal, myoepithelial, and progenitor cells, increased cell proliferation and blood vessels, and up-regulated expression of tissue remodeling/repair/regenerative genes (MMP2, CyclinD1, BMP7, EGF, NGF). BM Soup was as an efficient therapeutic agent as injections of live BM cells. Both intra-glandular or I.V. injections of BM Soup, and from both young and older mouse donors were as effective in repairing irradiated SGs. The intra-glandular route reduced injection frequency/dosage by four-fold. Conclusion BM Soup, which contains only the cell by-products, can be advantageously used to repair irradiation-damaged SGs rather than transplanting whole live BM cells which carry the risk of differentiating into unwanted/tumorigenic cell types in SGs. PMID:23637870

Paracrine effects of bone marrow soup restore organ function, regeneration, and repair in salivary glands damaged by irradiation.

PubMed

Tran, Simon D; Liu, Younan; Xia, Dengsheng; Maria, Ola M; Khalili, Saeed; Wang, Renee Wan-Jou; Quan, Vu-Hung; Hu, Shen; Seuntjens, Jan

2013-01-01

There are reports that bone marrow cell (BM) transplants repaired irradiated salivary glands (SGs) and re-established saliva secretion. However, the mechanisms of action behind these reports have not been elucidated. To test if a paracrine mechanism was the main effect behind this reported improvement in salivary organ function, whole BM cells were lysed and its soluble intracellular contents (termed as "BM Soup") injected into mice with irradiation-injured SGs. The hypothesis was that BM Soup would protect salivary cells, increase tissue neovascularization, function, and regeneration. Two minor aims were also tested a) comparing two routes of delivering BM Soup, intravenous (I.V.) versus intra-glandular injections, and b) comparing the age of the BM Soup's donors. The treatment-comparison group consisted of irradiated mice receiving injections of living whole BM cells. Control mice received irradiation and injections of saline or sham-irradiation. All mice were followed for 8 weeks post-irradiation. BM Soup restored salivary flow rates to normal levels, protected salivary acinar, ductal, myoepithelial, and progenitor cells, increased cell proliferation and blood vessels, and up-regulated expression of tissue remodeling/repair/regenerative genes (MMP2, CyclinD1, BMP7, EGF, NGF). BM Soup was as an efficient therapeutic agent as injections of live BM cells. Both intra-glandular or I.V. injections of BM Soup, and from both young and older mouse donors were as effective in repairing irradiated SGs. The intra-glandular route reduced injection frequency/dosage by four-fold. BM Soup, which contains only the cell by-products, can be advantageously used to repair irradiation-damaged SGs rather than transplanting whole live BM cells which carry the risk of differentiating into unwanted/tumorigenic cell types in SGs.

Cocaine self-administration under variable-dose schedules in squirrel monkeys.

PubMed

Panlilio, Leigh V; Thorndike, Eric B; Schindler, Charles W

2006-06-01

Squirrel monkeys self-administered cocaine under a variable-dose schedule, with the dose varied from injection to injection. As in earlier studies with rats, post-injection pauses varied as a monotonic function of dose, allowing a cocaine dose-effect curve to be obtained during each session. These curves were shifted by pretreatment with dopamine antagonists, demonstrating that this procedure may provide an efficient means of evaluating treatments that affect drug self-administration. However, drug intake eventually became "dysregulated" after extensive training (100-300 sessions), with relatively short pauses following all doses. Dose-sensitivity was restored by adding a 60-s timeout period after each injection, suggesting that dysregulation occurred because the monkeys developed a tendency to self-administer another injection before the previous injection had been adequately distributed. Finally, when the response requirement under the variable-dose schedule was increased from 1 to 10, both the post-injection pause and the rate of responding following the pause ("run rates") were found to vary with dose. The dose-dependency of run rates suggests that post-injection pauses reflect not only motivational factors, such as satiety, but also the direct effects of cocaine on leverpressing.

In vivo diffusion characteristics following perineural injection of the deep branch of the lateral plantar nerve with mepivacaine or iohexol in horses.

PubMed

Contino, E K; King, M R; Valdés-Martínez, A; McIlwraith, C W

2015-03-01

Hindlimb proximal suspensory desmopathy is a common injury of sport horses but diagnosis can be difficult because diagnostic analgesia of the region lacks specificity. Perineural analgesia of the deep branch of the lateral plantar nerve (DBLPN) has been proposed as a more specific method of isolating pain of the proximal aspect of the suspensory ligament but the technique has not been evaluated in vivo. To determine the extent of diffusion of contrast medium and mepivacaine following DBLPN analgesia using a single-needle injection technique and to determine if there is inadvertent involvement of the tarsal sheath and/or tarsometatarsal (TMT) joint using this technique. In vivo experimental study. Perineural injection of the DBLPN was performed in 16 limbs with 3 ml of either mepivacaine hydrochloride or positive contrast medium. Contrast medium-injected limbs were radiographed 5, 15, and 30 min post injection and diffusion characteristics were described. In mepivacaine-injected limbs, synovial fluid from the TMT joint was obtained 10 and 20 min post injection and mepivacaine concentrations were analysed. At 5, 15 and 30 min post injection, the contrast medium extended, on average, 19.6, 20.6 and 21.0 mm proximal and 38.0, 43.5 and 51.9 mm distal to the injection site, respectively. Three of 8 (37.5%) limbs had evidence of contrast medium in the tarsal sheath. Two of 8 (25%) limbs had mepivacaine concentrations within the TMT joint sufficient to produce analgesia (>300 mg/l) at 10 min post injection. Contrast medium diffused further in a distal direction than in a proximal direction. Analgesia of the DBLPN can result in inadvertent involvement of the tarsal sheath and/or TMT joint. © 2014 EVJ Ltd.

Prolonged intra-myocardial growth hormone administration ameliorates post-infarction electrophysiologic remodeling in rats.

PubMed

Kontonika, Marianthi; Barka, Eleonora; Roumpi, Maria; La Rocca, Vassilios; Lekkas, Panagiotis; Daskalopoulos, Evangelos P; Vilaeti, Agapi D; Baltogiannis, Giannis G; Vlahos, Antonios P; Agathopoulos, Simeon; Kolettis, Theofilos M

2017-02-01

Experimental studies indicate improved ventricular function after treatment with growth hormone (GH) post-myocardial infarction, but its effect on arrhythmogenesis is unknown. Here, we assessed the medium-term electrophysiologic remodeling after intra-myocardial GH administration in (n = 33) rats. GH was released from an alginate scaffold, injected around the ischemic myocardium after coronary ligation. Two weeks thereafter, ventricular tachyarrhythmias were induced by programmed electrical stimulation. Monophasic action potentials were recorded from the infarct border, coupled with evaluation of electrical conduction and repolarization from a multi-electrode array. The arrhythmia score was lower in GH-treated rats than in alginate-treated rats or controls. The shape and the duration of the action potential at the infarct border were preserved, and repolarization-dispersion was attenuated after GH; moreover, voltage rise was higher and activation delay was shorter. GH normalized also right ventricular parameters. Intra-myocardial GH preserved electrical conduction and repolarization-dispersion at the infarct border and decreased the incidence of induced tachyarrhythmias in rats post-ligation. The long-term antiarrhythmic potential of GH merits further study.

Short curcumin treatment modulates oxidative stress, arginase activity, aberrant crypt foci, and TGF-β1 and HES-1 transcripts in 1,2-dimethylhydrazine-colon carcinogenesis in mice.

PubMed

Bounaama, Abdelkader; Djerdjouri, Bahia; Laroche-Clary, Audrey; Le Morvan, Valérie; Robert, Jacques

2012-12-16

This study investigated the effect of short curcumin treatment, a natural antioxidant on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in mice. The incidence of aberrant crypt foci (ACF) was 100%, with 54 ± 6 per colon, 10 weeks after the first DMH injection and reached 67 ± 12 per colon after 12 weeks. A high level of undifferentiated goblet cells and a weak apoptotic activity were shown in dysplastic ACF. The morphological alterations of colonic mucosa were associated to severe oxidative stress ratio with 43% increase in malondialdehyde vs. 36% decrease in GSH. DMH also increased inducible nitric synthase (iNOS) mRNA transcripts (250%), nitrites level (240%) and arginase activity (296%), leading to nitrosative stress and cell proliferation. Curcumin treatment, starting at week 10 post-DMH injection for 14 days, reduced the number of ACF (40%), iNOS expression (25%) and arginase activity (73%), and improved redox status by approximately 46%, compared to DMH-treated mice. Moreover, curcumin induced apoptosis of dysplastic ACF cells without restoring goblet cells differentiation. Interestingly, curcumin induced a parallel increase in TGF-β1 and HES-1 transcripts (42% and 26%, respectively). In conclusion, the protective effect of curcumin was driven by the reduction of arginase activity and nitrosative stress. The up regulation of TGF-β1 and HES-1 expression by curcumin suggests for the first time, a potential interplay between these signalling pathways in the chemoprotective mechanism of curcumin. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The effect of changing condition of walking speed on the knee angle of rats with osteoarthritis.

PubMed

Nam, Chan-Woo; Kim, Kyoung; Na, Sang-Su

2017-08-01

[Purpose] The purpose of this study was to investigate the positive effect of exercise on knee osteoarthritis in rats with osteoarthritis induced by applying effective walking speed when changing speed conditions during walking. [Subjects and Methods] The rats used in this study were male Sprague-Dawley rats weighing 300 g and 7 weeks old, and 20 rats were used. The Osteoarthritis (OA) rats model was induced by MIA (monoiodoacetate). The rats was randomly divided into experimental group (MIA injection group) and control group (normal cell line injection group). Treadmill exercise was provided two groups for 2 weeks, 4 days per week. The knee joint angle of the stance was divided into pre-test and post-test, and each group was subjected to paired sample test. Independent sample t-test was conducted to examine the difference between experimental group and control group. [Results] There were statistically significant changes in the control and experimental groups. The knee angle was changed from 99.70 ± 2.40 to 85.60 ± 2.67 in the control group. The knee angle was changed from 100.96 ± 1.36 to 87.71 ± 1.57 in the experimental group. [Conclusion] In conclusion, the angle of the knee gradually decreases. It is considered a characteristic of progressive osteoarthritis. The change of knee angle was less in the experimental group than in the control group. This means that the stiffness of the joints during the walking exercise was less progressed in the experimental group than in the control group.

The effect of changing condition of walking speed on the knee angle of rats with osteoarthritis

PubMed Central

Nam, Chan-Woo; Kim, Kyoung; Na, Sang-Su

2017-01-01

[Purpose] The purpose of this study was to investigate the positive effect of exercise on knee osteoarthritis in rats with osteoarthritis induced by applying effective walking speed when changing speed conditions during walking. [Subjects and Methods] The rats used in this study were male Sprague-Dawley rats weighing 300 g and 7 weeks old, and 20 rats were used. The Osteoarthritis (OA) rats model was induced by MIA (monoiodoacetate). The rats was randomly divided into experimental group (MIA injection group) and control group (normal cell line injection group). Treadmill exercise was provided two groups for 2 weeks, 4 days per week. The knee joint angle of the stance was divided into pre-test and post-test, and each group was subjected to paired sample test. Independent sample t-test was conducted to examine the difference between experimental group and control group. [Results] There were statistically significant changes in the control and experimental groups. The knee angle was changed from 99.70 ± 2.40 to 85.60 ± 2.67 in the control group. The knee angle was changed from 100.96 ± 1.36 to 87.71 ± 1.57 in the experimental group. [Conclusion] In conclusion, the angle of the knee gradually decreases. It is considered a characteristic of progressive osteoarthritis. The change of knee angle was less in the experimental group than in the control group. This means that the stiffness of the joints during the walking exercise was less progressed in the experimental group than in the control group. PMID:28878468

Cholera toxin, a potent inducer of epidermal hyperplasia but with no tumor promoting activity in mouse skin carcinogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuroki, T.; Chida, K.; Munakata, K.

1986-05-29

Intracutaneous injection of cholera toxin into mice induced epidermal hyperplasia to a greater extent than 12-O-tetra-decanoylphorbol-13-acetate. It also induced adenylate cyclase and through weakly, ornithine decarboxylase of the epidermis. Cholera toxin, however, showed no tumor promoting activity in mouse skin carcinogenesis. In the single stage promotion, cholera toxin (50 ng) was injected once a week for 10 weeks into the skin of SENCAR mice initiated with 25 ..mu..g 7,12-dimethyl-benz(a)anthracene, but no tumors developed. In the two-stage promotion test, cholera toxin (10-100 ng) was injected for one or two weeks into the initiated skin and then mezerein (4 ..mu..g) was appliedmore » twice a week for 18 weeks, but the toxin did not increase incidence or numbers of papillomas.« less

Scatter Photocoagulation Does Not Reduce Macular Edema or Treatment Burden in Patients with Retinal Vein Occlusion: The RELATE Trial.

PubMed

Campochiaro, Peter A; Hafiz, Gulnar; Mir, Tahreem A; Scott, Adrienne W; Solomon, Sharon; Zimmer-Galler, Ingrid; Sodhi, Akrit; Duh, Elia; Ying, Howard; Wenick, Adam; Shah, Syed Mahmood; Do, Diana V; Nguyen, Quan D; Kherani, Saleema; Sophie, Raafay

2015-07-01

To determine whether scatter and grid laser photocoagulation (laser) adds benefit to ranibizumab injections in patients with macular edema from retinal vein occlusion (RVO) and to compare 0.5-mg with 2.0-mg ranibizumab. Randomized, double-masked, controlled clinical trial. Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO). Subjects were randomized to 0.5 mg or 2.0 mg ranibizumab every 4 weeks for 24 weeks and re-randomized to pro re nata ranibizumab plus laser or ranibizumab alone. Mean change from baseline best-corrected visual acuity (BCVA) at week 24 for BCVA at weeks 48, 96, and 144 for second randomization. Mean improvement from baseline BCVA at week 24 was 15.5 and 15.8 letters in the 0.5-mg and 2.0-mg CRVO groups, and 12.1 and 14.6 letters in the 0.5-mg and 2.0-mg BRVO groups. For CRVO, but not BRVO, there was significantly greater reduction from baseline mean central subfield thickness (CST) in the 2.0-mg versus 0.5-mg group (396.1 vs. 253.5 μm; P = 0.03). For the second randomization in CRVO patients, there was no significant difference from week 24 BCVA in the ranibizumab plus laser versus the ranibizumab only groups at week 48 (-3.3 vs. 0.0 letters), week 96 (+0.69 vs. -1.6 letters), or week 144 (+0.4 vs. -6.7 letters), and a significant increase from week 24 mean CST at week 48 (+94.7 vs. +15.2 μm; P = 0.05) but not weeks 96 or 144. For BRVO, there was a significant reduction from week 24 mean BCVA in ranibizumab plus laser versus ranibizumab at week 48 (-7.5 vs. +2.8; P < 0.01) and week 96 (-2.0 vs. +4.8; P < 0.03), but not week 144, and there were no differences in mean CST change from week 24 at weeks 48, 96, or 144. Laser failed to increase edema resolution or to reduce the ranibizumab injections between weeks 24 and 144. In patients with macular edema resulting from RVO, there was no short-term clinically significant benefit from monthly injections of 2.0-mg versus 0.5-mg ranibizumab injections and no long-term benefit in BCVA, resolution of edema, or number of ranibizumab injections obtained by addition of laser treatment to ranibizumab. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A soft, transparent, freely accessible cranial window for chronic imaging and electrophysiology

PubMed Central

Heo, Chaejeong; Park, Hyejin; Kim, Yong-Tae; Baeg, Eunha; Kim, Yong Ho; Kim, Seong-Gi; Suh, Minah

2016-01-01

Chronic in vivo imaging and electrophysiology are important for better understanding of neural functions and circuits. We introduce the new cranial window using soft, penetrable, elastic, and transparent, silicone-based polydimethylsiloxane (PDMS) as a substitute for the skull and dura in both rats and mice. The PDMS can be readily tailored to any size and shape to cover large brain area. Clear and healthy cortical vasculatures were observed up to 15 weeks post-implantation. Real-time hemodynamic responses were successfully monitored during sensory stimulation. Furthermore, the PDMS window allowed for easy insertion of microelectrodes and micropipettes into the cortical tissue for electrophysiological recording and chemical injection at any location without causing any fluid leakage. Longitudinal two-photon microscopic imaging of Cx3Cr1+/− GFP transgenic mice was comparable with imaging via a conventional glass-type cranial window, even immediately following direct intracortical injection. This cranial window will facilitate direct probing and mapping for long-term brain studies. PMID:27283875

Radioprotective effect of Ganoderma lucidum (Leyss. ex. Fr. ) Karst after X-ray irradiation in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsu, H.Y.; Lian, S.L.; Lin, C.C.

1990-01-01

Six to seven week old male mice of ICR strain were exposed to 500 or 650 cGy of X-ray during experiments to determine if Ganoderma lucidum could be a factor in modification of radiation damage. Continuous intraperitoneal injection of the extract from Ganoderma lucidum before or after irradiation of 500 and 650 cGy of X-ray was found to improve the 30-day survival fractions of ICR mice, but wasn't significant by statistical analysis. The administration also enhanced the recoveries of the body weights and increased the recovery of hemograms of irradiated mice from radiation damage by injecting before or after radiationmore » exposure, especially for the treatment of 500 cGy irradiation. The 10-day CFUs was significantly higher for Ganoderma lucidum treated groups than for untreated groups. However, the differences of radioprotective effect between the X-ray irradiated groups with Ganoderma lucidum pretreated and post-treated were not significant (p greater than 0.05).« less

Therapeutic synergism in the treatment of post-stroke arm paresis utilizing botulinum toxin, robotic therapy, and constraint-induced movement therapy.

PubMed

Takebayashi, Takashi; Amano, Satoru; Hanada, Keisuke; Umeji, Atsushi; Takahashi, Kayoko; Koyama, Tetsuo; Domen, Kazuhisa

2014-11-01

Botulinum toxin type A (BtxA) injection, constraint-induced movement therapy (CIMT), and robotic therapy (RT) each represent promising approaches to enhance arm motor recovery after stroke. To provide more effective treatment for a 50-year-old man with severe left spastic hemiparesis, we attempted to facilitate CIMT with adaptive approaches to extend the wrist and fingers using RT for 10 consecutive weeks after BtxA injection. This combined treatment resulted in substantial improvements in arm function and the amount of arm use in activities of daily living, and may be effective for stroke patients with severe arm paresis. However, we were unable to sufficiently prove the efficacy of combined treatment based only on a single case. To fully elucidate the efficacy of the combined approach for patients with severe hemiparesis after stroke, future studies of a larger number of patients are needed. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Hyperglycemia and hepatic tumors in ICR mice neonatally injected with streptozotocin.

PubMed

Ariza, Lorena; Zaguirre, Mireia; García, Marta; Blasco, Ester; Rabanal, Rosa Maria; Bosch, Assumpició; Otaegui, Pedro José

2014-07-01

Repeated, low-dose administration of streptozotocin (STZ) is widely used to induce insulin-dependent diabetes mellitus in mice. The authors adapted this method using neonatal mice and determined the long-term effects of STZ injection in the mice. After receiving intraperitoneal injections of STZ at postnatal day 3 (P3), P4 and P8, male and female mice were hyperglycemic by week 4. A clear sex difference was found, with blood glucose levels in STZ-treated males remaining higher than those in STZ-treated females until week 23. Whereas STZ-treated males remained hyperglycemic until week 23, STZ-treated females did not have significantly higher glucose levels than control mice after week 18. Additionally, STZ-treated mice had neoplastic lesions in their livers by week 4, with a progression in the severity of these lesions until week 24. The results confirm that, in addition to pancreatic beta cell toxicity, STZ has an oncogenic effect on the liver when administered to neonates.

A pooled analysis of injection site-related adverse events in patients with schizophrenia treated with olanzapine long-acting injection.

PubMed

Atkins, Susan; Detke, Holland C; McDonnell, David P; Case, Michael G; Wang, Shufang

2014-01-14

Depot antipsychotic injections are an important tool for the management of patients with schizophrenia who have difficulty with adherence to oral medication. However, pain and discomfort at the injection site can be a potential impediment to the use of these long-acting formulations. We report here the results of a pooled analysis of injection site-related adverse events (AEs) collected during treatment with the olanzapine long-acting injection (olanzapine LAI). Unsolicited injection site-related AEs were pooled from 7 olanzapine LAI clinical trials conducted in patients between March 2001 and December 2010. All patients had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) or Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of schizophrenia or schizoaffective disorder and were between the ages of 18 and 75. Doses ranged from 45 to 405 mg olanzapine LAI, and injection intervals were 2, 3, or 4 weeks. Events were evaluated for severity, timing, possible risk factors, and outcome. A criterion of p < .05 for statistical significance was used for all tests. A total of 1752 patients received at least 1 olanzapine LAI injection. Of these, 92 patients (5.3%) reported at least 1 injection site-related AE, with "pain" being the most common type (2.9%). Most events were mild (81.4%) and the median duration was 3 days. Four patients (0.2%) discontinued due to injection site-related AEs. Dose volume and body mass index did not appear to affect the probability of injection site-related AEs. However, patients who experienced a post-injection delirium/sedation syndrome event (n = 37) were more likely to have or have had an injection site-related AE at some time during the study. Incidence of injection site-related AEs appeared to decrease over time. In 94.2% of the injection site-related AEs, no specific treatment or concomitant medication was reported; in 9 cases, patients received pharmacologic treatment for reaction, mass, abscess, rash, or pain. Injection site-related AEs with olanzapine LAI were generally mild. The incidence and nature of these injection site-related AEs were generally similar to those occurring during treatment with other injectable antipsychotics. ClinicalTrials.gov ID; URL: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.

Initiation into prescription opioid injection and associated trends in heroin use among people who use illicit drugs.

PubMed

Lake, Stephanie; Milloy, M-J; Dong, Huiru; Hayashi, Kanna; Wood, Evan; Kerr, Thomas; DeBeck, Kora

2016-12-01

Prescription opioid (PO) injection among people who use illicit drugs (PWUD) is an ongoing concern, yet little is known about drug use trajectories associated with initiating PO injection, including potential associations with heroin use. This study aimed to identify predictors of PO injection initiation among PWUD, and examine trends in heroin use before and after initiating PO injection. Data were merged from three cohorts of PWUD recruited between September 2005 and November 2015. Predictors of PO injection initiation were identified using extended Cox regression models. Trends in heroin use pre- and post-initiation were examined with McNemar's test and compared to matched controls with linear growth curve models. Among 1580 participants, 247 initiated PO injection yielding an incidence density of 3.9 (95% Confidence Interval [CI]: 3.4-4.4) per 100 person-years. In a multivariable analysis, independent predictors of PO injection initiation included heroin injection (Adjusted Hazard Ratio [AHR]=4.39, 95% CI: 3.24-5.95) and non-injection PO use (AHR=1.99, 95% CI: 1.25-3.17). In a sub-analysis, compared to matched controls, PO injection corresponded with elevated heroin use post-initiation (p≤0.05). In this study, heroin use and non-injection PO use strongly predicted PO injection initiation. Those who initiated PO injecting had elevated heroin use patterns post-initiation compared to controls. These findings suggest that transitioning to PO injection does not appear to be a substitute for heroin use among PWUD. These findings highlight the importance of addressing PO injection in harm reduction and treatment settings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Overcoming nursing barriers to intensive care unit early mobilisation: A quality improvement project.

PubMed

Hunter, Oluwatobi O; George, Elisabeth L; Ren, Dianxu; Morgan, Douglas; Rosenzweig, Margaret; Klinefelter Tuite, Patricia

2017-06-01

To increase adherence with intensive care unit mobility by developing and implementing a mobility training program that addresses nursing barriers to early mobilisation. An intensive care unit mobility training program was developed, implemented and evaluated with a pre-test, immediate post-test and eight-week post-test. Patient mobility was tracked before and after training. A ten bed cardiac intensive care unit. The training program's efficacy was measured by comparing pre-test, immediate post-test and 8-week post-test scores. Patient mobilisation rates before and after training were compared. Protocol compliance was measured in the post training group. Nursing knowledge increased from pre-test to immediate post-test (p<0.0001) and pre-test to 8-week post-test (p<0.0001). Mean test scores decreased by seven points from immediate post-test (80±12) to 8-week post-test (73±14). Fear significantly decreased from pre-test to immediate post-test (p=0.03), but not from pre-test to 8-week post-test (p=0.06) or immediate post-test to 8-week post-test (p=0.46). Post training patient mobility rates increased although not significantly (p=0.07). Post training protocol compliance was 78%. The project successfully increased adherence with intensive care unit mobility and indicates that a training program could improve adoption of early mobility. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy and Safety of Single Botulinum Toxin Type A (Botox®) Injection for Relief of Upper Trapezius Myofascial Trigger Point: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Kwanchuay, Photsawee; Petchnumsin, Thavatchai; Yiemsiri, Pichet; Pasuk, Nakkamol; Srikanok, Wannarat; Hathaiareerug, Chanasak

2015-12-01

Botulinum toxin injection has been applied for pain relief in various chronic pain syndromes. Recently, systematic review studies reported inconclusive effects of Botulinum toxin in myofascial pain management. The present study aimed to demonstrate the efficacy and safety of Botulinum toxin type A (BTxA) (Botox®) injection for pain reduction in myofascial trigger point (MTrP) of the upper trapezius muscle. Thirty-three patients with 48 MTrP on the upper trapezius muscles over three months with moderate to severe pain intensity diagnosed at physical medicine and rehabilitation outpatient department were recruited between December 2011 and March 2012. Eligible patients were blinded and randomly injected with single 0.2 ml (20 IU) of BTxA for 24 MTrP and 0.2 ml of 0.9% NaCl solution for 24 MTrP at the most tender trigger point on the upper trapezius muscle. All patients were advised for stretching exercise and ergonomic adaptation throughout the study. At 3- and 6-week after injections, visual analogue scale (VAS), the pressure pain threshold (PPT), and reported adverse effects were measured. Both BTxA and control groups demonstrated statistically significant differences in VAS reduction and increased PPT after 3 weeks and 6 weeks compared with before treatment. There were no statistically significant differences in VAS reduction from baseline between the two groups at 3- and 6-week after treatment. A statistically significant difference in improvement of PPT from baseline and 6-week after BTxA injection compared with 0.9% NaCl group was shown (1.0 ± 0.9 and 0.5 ± 0.7, p = 0.036). There was mild degree side-effects that spontaneous resolved within one week in both groups without significant difference in percentage. No severe adverse effects were reported during the study. The efficacy in VAS reduction of a single 20 IU of Botulinum toxin type A (Botox®) injection was not different from 0.9% NaCl for myofascial trigger point at the upper trapezius muscle. However Botulinum toxin type A (Botox®) showed statistically significant more increased in pressure pain threshold at 6-week after injection without severe adverse effects.

Post-discharge compliance to venous thromboembolism prophylaxis in high-risk orthopaedic surgery: results from the ETHOS registry.

PubMed

Bergqvist, David; Arcelus, Juan I; Felicissimo, Paulo

2012-02-01

Venous thromboembolism (VTE) risk persists for several weeks following high-risk orthopaedic surgery (HROS). The ETHOS registry evaluated post-operative VTE prophylaxis prescribed, and actual VTE prophylaxis received, compared with the 2004 American College of Chest Physicians (ACCP) guidelines in HROS patients. We performed a subanalysis of ETHOS to assess patient compliance with ACCP-adherent prophylaxis after discharge and the factors predicting poor compliance. Consecutive patients undergoing hip fracture surgery, total hip arthroplasty, or knee arthroplasty were enrolled at discharge from 161 centres in 17 European countries if they had received adequate in-hospital VTE prophylaxis. Data on prescribed and actual prophylaxis received were obtained from hospital charts and patient post-discharge diaries. Good compliance was defined as percentage treatment intake ≥80% with no more than two consecutive days without treatment. A total of 3,484 patients (79.4%) received ACCP-adherent anticoagulant prescription at discharge and 2,999 (86.0%) had an evaluable patient diary. In total, 87.7% of evaluable patients were compliant with prescribed treatment after discharge. The most common reason for non-compliance (33.4%) was "drug was not bought". Injection of treatment was not a barrier to good compliance. Main factors affecting compliance related to purchase of and access to treatment, patient education, the person responsible for administering injections, country, and type of hospital ward at discharge. Within our study population, patient compliance with ACCP-adherent thromboprophylaxis prescribed at discharge was good. Improvements in patient education and prescribing practices at discharge may be important in further raising compliance levels in high-risk orthopaedic surgery patients.

Association between post-dinner dietary intakes and nocturnal hypoglycemic risk in adult patients with type 1 diabetes.

PubMed

Desjardins, Katherine; Brazeau, Anne-Sophie; Strychar, Irene; Leroux, Catherine; Gingras, Véronique; Rabasa-Lhoret, Rémi

2014-12-01

To describe (i) current bedtime nutritional practices and (ii) the association between post-dinner dietary intake and the occurrence of non-severe nocturnal hypoglycemia (NH) in real-life conditions among adult patients with type 1 diabetes using insulin analogs. One hundred adults (median [interquartile range]: age 46.4 [36.0-55.8] years, HbA1c 7.9 [7.3-8.6] % (63 [56-70] mmol/mol)) using multiple daily injections (n=67) or insulin pump (n=33) wore a blinded continuous glucose monitoring system and completed a food diary for 72-h. NH occurred on 28% of 282 nights analyzed. (i) Patients reported post-dinner dietary intakes on 63% of the evenings. They injected rapid-acting insulin boluses on 64 occasions (23% of 282 evenings). These insulin boluses were mostly injected with (n=37) dietary intakes. (ii) Post-dinner dietary intake was not associated with NH occurrence in univariate analyses. In multivariate analyses, the injection of rapid-acting insulin modulated the association between post-dinner dietary intake and NH: with insulin, post-dinner carbohydrate intake was positively associated with NH (odds ratio (OR): 1.16 [95% confidence interval, CI: 1.04-1.29] per 5g increase, p=0.008); without insulin, post-dinner protein intake was inversely associated with NH occurrence (OR [95% CI]: 0.88 [0.78-1.00] per 2g increase, p=0.048). NH remains frequent in adults with type 1 diabetes. There is a complex relationship between post-dinner dietary intake and NH occurrence, including the significant role of nutrient content and rapid-acting insulin injection that requires further investigation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The effect of intra-articular glucocorticosteroids and exercise on symptoms and bone marrow lesions in knee osteoarthritis: a secondary analysis of results from a randomized controlled trial.

PubMed

Nielsen, F K; Boesen, M; Jurik, A G; Bliddal, H; Nybing, J D; Ellegaard, K; Bartholdy, C; Bandak, E; Henriksen, M

2018-03-02

To evaluate if the relative volume of bone marrow lesions (BMLs) changed in patients with knee osteoarthritis (OA) during a therapeutic study. This study is a sub-study to a larger clinical trial which compared the clinical effects of intra-articular corticosteroid injection in knee OA to placebo injection, both given prior to exercise therapy. Clinical assessment using the Knee injury and Osteoarthritis Outcome Score (KOOS) and magnetic resonance imaging (MRI) examinations with BML assessments were performed at baseline and follow-up after 14 weeks and 26 weeks, respectively. The BML volume was determined using a computer assisted method focusing on participants with valid baseline and follow-up MRI examinations. Any changes in BML and KOOS were analyzed and investigated for associations. Fifty participants received steroid and placebo injection, respectively, of which 41 and 45 had complete MRI examinations at week 14, and 36 and 33 at week 26, respectively. All participants received 12 weeks of exercise. A significant change in relative BML volume was observed between the corticosteroid group and the placebo group after 14 weeks [-1.1% vs 2.7%; between-group difference, 3.8% (95% CI 0.5-7.0)] but not after 26 weeks [0.8% vs 1.6%; between-group difference, 0.8% (95% CI -2.8 to 4.4)]. No significant association was found between changes in relative BML volume and KOOS. Despite the statistically significant difference in BML volume at 14 weeks after corticosteroid injection and 12 weeks exercise therapy compared to placebo injection and exercise, there is very little evidence on a relationship between corticosteroids and BML volume. EudraCT number: 2012-002607-18. Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Ultrasonography and clinical outcome comparison of extracorporeal shock wave therapy and corticosteroid injections for chronic plantar fasciitis: A randomized controlled trial

PubMed Central

Lai, Ta-Wei; Ma, Hsiao-Li; Lee, Meng-Shiunn; Chen, Po-Ming; Ku, Ming-Chou

2018-01-01

Objectives: Extracorporeal shockwave therapy (ESWT) and corticosteroid injection (CSI) are treatment options for plantar fasciitis. Their clinical outcome comparison remains a debate. Also, the thickness changes of the plantar fascia on objective evaluation under the medium energy ESWT and CSI therapy are elusive. Methods: A total of 97 patients with chronic plantar fasciitis were enrolled in the randomized prospective trial. Forty-seven patients received extracorporeal shock wave therapy (ESWT), and fifty patients received corticosteroid injection (CSI). The thickness of the plantar fascia was evaluated respectively before ESWT and CSI, and at the 4th and 12th week after ESWT and CSI by ultrasonography. Pain level and clinical outcomes were recorded using visual analogue scale (VAS) and 100-points scoring systems. Correlation analysis was performed between the thickness change and clinical outcome. Results: Under ultrasonography, we observed more increase of plantar fascia thickness of ESWT group than CSI group at 4th week (p=0.048). VAS of plantar fasciitis patients receiving ESWT was lower than those who received corticosteroid injection (0.001 and p<0.001, at 4th and 12th week). On the assessment of 100-points scoring systems, the pain level of patients with ESWT was lower than those with CSI at the 12th week (p<0.001). On the other hand, the increase of plantar fascia thickness at 4th week was positively correlated with the decrease of VAS score at 12th week follow-up (R=0.302, P=0.039). Conclusions: At 4th week after treatment, the thickness of plantar fascia increased. Then it decreased gradually, but not to the baseline at 12th week. On the pain level outcome at 12th week, extracorporeal shockwave therapy (ESWT) was more efficient than corticosteroid injection (CSI) on chronic plantar fasciitis. The more change of plantar fascia after ESWT, the more efficient on clinical outcome. PMID:29504578

Ultrasonography and clinical outcome comparison of extracorporeal shock wave therapy and corticosteroid injections for chronic plantar fasciitis: A randomized controlled trial.

PubMed

Lai, Ta-Wei; Ma, Hsiao-Li; Lee, Meng-Shiunn; Chen, Po-Ming; Ku, Ming-Chou

2018-03-01

Extracorporeal shockwave therapy (ESWT) and corticosteroid injection (CSI) are treatment options for plantar fasciitis. Their clinical outcome comparison remains a debate. Also, the thickness changes of the plantar fascia on objective evaluation under the medium energy ESWT and CSI therapy are elusive. A total of 97 patients with chronic plantar fasciitis were enrolled in the randomized prospective trial. Forty-seven patients received extracorporeal shock wave therapy (ESWT), and fifty patients received corticosteroid injection (CSI). The thickness of the plantar fascia was evaluated respectively before ESWT and CSI, and at the 4 th and 12 th week after ESWT and CSI by ultrasonography. Pain level and clinical outcomes were recorded using visual analogue scale (VAS) and 100-points scoring systems. Correlation analysis was performed between the thickness change and clinical outcome. Under ultrasonography, we observed more increase of plantar fascia thickness of ESWT group than CSI group at 4 th week (p=0.048). VAS of plantar fasciitis patients receiving ESWT was lower than those who received corticosteroid injection (0.001 and p⟨0.001, at 4 th and 12 th week). On the assessment of 100-points scoring systems, the pain level of patients with ESWT was lower than those with CSI at the 12 th week (p⟨0.001). On the other hand, the increase of plantar fascia thickness at 4 th week was positively correlated with the decrease of VAS score at 12 th week follow-up (R=0.302, P=0.039). At 4 th week after treatment, the thickness of plantar fascia increased. Then it decreased gradually, but not to the baseline at 12 th week. On the pain level outcome at 12 th week, extracorporeal shockwave therapy (ESWT) was more efficient than corticosteroid injection (CSI) on chronic plantar fasciitis. The more change of plantar fascia after ESWT, the more efficient on clinical outcome.

Fear of repeated injections in children younger than 4 years receiving subcutaneous allergy immunotherapy.

PubMed

de Vos, Gabriele; Shankar, Viswanathan; Nazari, Ramin; Kooragayalu, Shravan; Smith, Mitchell; Wiznia, Andrew; Rosenstreich, David

2012-12-01

Allergy immunotherapy during early childhood may have potential benefits for the prevention of asthma and allergy morbidity. However, subcutaneous immunotherapy has not yet been prospectively researched in children younger than 4 years, primarily because of safety concerns, including the fear and psychological distress young children may experience with repeated needle injections. To quantify fear in atopic children younger than 4 years with a history of wheezing who are receiving subcutaneous immunotherapy. Fear of injection was graded during a total of 788 immunotherapy injection visits in 18 children (age, 37 months; SD, 9 months) receiving subcutaneous allergy immunotherapy. The parent and the injection nurse assigned fear scores on a scale of 0 to 10 after each injection visit. At the time of analysis, children had a median of 49 injection visits (range, 12-88) during a median study period of 81.5 weeks (range, 15-165 weeks). Fifteen children (83%) lost their fear of injections during the study. A fear score of 0 was achieved after a mean of 8.4 visits (SD, 7.4). The more injection visits were missed, the more likely children were to retain fear of injections (hazard ratio, 0.13; 95% confidence interval, 0.02-1.02; P=.05). Age, adverse events, number of injections at each visit, and change of injection personnel were not associated with increased fear. Our analysis suggests that most children receiving weekly subcutaneous immunotherapy lose their fear of injections during the treatment course. Children with increased intervals between visits may be at higher risk of experiencing fear of injections. clinicaltrial.gov identifier NCT01028560. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A Randomized Trial Among Compression Plus Nonsteroidal Antiinflammatory Drugs, Aspiration, and Aspiration With Steroid Injection for Nonseptic Olecranon Bursitis.

PubMed

Kim, Joon Yub; Chung, Seok Won; Kim, Joo Hak; Jung, Jae Hong; Sung, Gwang Young; Oh, Kyung-Soo; Lee, Jong Soo

2016-03-01

Olecranon bursitis might be a minor problem in the outpatient clinic but relatively be common to occur. However, there are few well-designed studies comparing approaches to treatment. (1) Which treatment (compression bandaging with nonsteroidal antiinflammatory drugs [NSAIDs], aspiration, or aspiration with steroid injections) is associated with the highest likelihood of resolution of nonseptic olecranon bursitis? (2) Which treatment is associated with earliest resolution of symptoms? (3) What factors are associated with treatment failure by 4 weeks? We enrolled 133 patients from two centers; after applying prespecified exclusions (septic bursitis or concomitant inflammatory arthritis, intraarticular elbow pathology, recent aspiration or steroid injection done elsewhere, and refusal to participate), 90 patients were randomly allocated to receive compression bandaging with NSAIDs (C), aspiration (A), or aspiration with steroid injection (AS) groups (30 patients in each). The groups were similar at baseline in terms of age and gender. Seven patients (four from Group A and three from Group AS) were lost to followup. All patients were followed up weekly for 4 weeks, and the same treatment procedure was repeated if the bursitis recurred with any substantial fluid collection. At 4 weeks, the state of resolution and pain visual analog scale (VAS) were evaluated. Failed resolution was defined as presence of persistent olecranon bursal fluid collection at Week 4 after the initiation of the treatment; on the contrary, if bursal fluid collection was clinically reduced or completely disappeared by the end of Week 4, the treatment was considered successful. We compared the proportion of resolution by Week 4 and the median times to resolution among the treatment groups. In addition, we evaluated whether the resolution affected pain VAS and what factors were associated with the resolution. There were no differences in the proportion of patients whose bursitis resolved by Week 4 among the three treatment groups (Group C: 25 of 30 [83%], relative risk of resolution failure: 0.68 [95% confidence interval {CI}, 0.27-1.72], p = 0.580; Group A: 17 of 26 [65%], relative risk of resolution failure: 2.19 [95% CI, 0.98-4.87], p = 0.083; Group AS: 23 of 27 [85%], relative risk of resolution failure: 0.59 [95% CI, 0.22-1.63], p = 0.398) (p = 0.073). Steroid injection after aspiration (Group AS) was associated with the earliest resolution (2.3 weeks [range, 1-4 weeks]) when compared with aspiration alone (Group A; 3.1 weeks [range, 2-4 weeks]) and compression bandaging with NSAIDs (Group C; 3.2 weeks [range, 2-4 weeks]), p = 0.015). Longer duration of symptoms before treatment was the only factor associated with treatment failure by 4 weeks (failed resolution: 6 weeks [range, 2-9 weeks]; successful resolution: 4 weeks [range, 0.4-6 weeks]; p = 0.008). With the numbers available, there were no differences in efficacy when compression bandaging with NSAIDs, aspiration, and aspiration with steroid injection were compared. However, we were powered only to detect a 30% difference, meaning that if there were a smaller difference in efficacy among the groups, we might not have detected it in a study of this size. Our data can be used as pilot data to power future prospective (and likely multicenter) trials. Because olecranon bursitis can recur, and because treatments like aspiration and aspiration with steroid injection can cause complications, unless future trials demonstrate clear efficacy advantages of aspiration and/or injection both at short and longer terms, we suggest that compression bandaging and a short course of NSAIDs may offer the most appropriate balance of safety and efficacy. Level II, therapeutic study.

Mitigation of radiation-induced lung injury with EUK-207 and genistein: effects in adolescent rats.

PubMed

Mahmood, J; Jelveh, S; Zaidi, A; Doctrow, S R; Hill, R P

2013-02-01

Exposure of civilian populations to radiation due to accident, war or terrorist act is an increasing concern. The lung is one of the more radiosensitive organs that may be affected in people receiving partial-body irradiation and radiation injury in lung is thought to be associated with the development of a prolonged inflammatory response. Here we examined how effectively damage to the lung can be mitigated by administration of drugs initiated at different times after radiation exposure and examined response in adolescent animals for comparison with the young adult animals that we had studied previously. We studied the mitigation efficacy of the isoflavone genistein (50 mg/kg) and the salen-Mn superoxide dismutase-catalase mimetic EUK-207 (8 mg/kg), both of which have been reported to scavenge reactive oxygen species and reduce activity of the NFkB pathway. The drugs were given by subcutaneous injection to 6- to 7-week-old Fisher rats daily starting either immediately or 2 weeks after irradiation with 12 Gy to the whole thorax. The treatment was stopped at 28 weeks post irradiation and the animals were assessed for levels of inflammatory cytokines, activated macrophages, oxidative damage and fibrosis at 48 weeks post irradiation. We demonstrated that both genistein and EUK-207 delayed and suppressed the increased breathing rate associated with pneumonitis. These agents also reduced levels of oxidative damage (50-100%), levels of TGF-β1 expression (75-100%), activated macrophages (20-60%) and fibrosis (60-80%). The adolescent rats developed pneumonitis earlier following irradiation of the lung than did the adult rats leading to greater severe morbidity requiring euthanasia (∼37% in adolescents vs. ∼10% in young adults) but the extent of the mitigation of the damage was similar or slightly greater.

Inhalation reproductive toxicology studies: Sperm morphology study of n-hexane in B6C3F1 mice: Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mast, T.J.; Hackett, P.L.; Decker, J.R.

The straight-chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent routinely used in industrial environments. Although myelinated nerve tissue is the primary target organ of hexane, the testes have also been identified as being sensitive to hexacarbon exposure. The objective of this study was to evaluate the epididymal sperm morphology of male B6D3F1 mice 5 weeks after exposure to 0, 200, 1000, or 5000 ppM n-hexane, 20 h/day for 5 consecutive days. Two concurrent positive control groups of animals were injected intraperitoneally with either 200 or 250 mg/kg ethyl methanesulfonate, a known mutagen, once each day for 5 consecutive days. Themore » mice were weighed just prior to the first day of exposure and at weekly intervals until sacrifice. During the fifth post-exposure week the animals were killed and examined for gross lesions of the reproductive tract and suspensions of the epididymal sperm were prepared for morphological evaluations. The appearance and behavior of the mice were unremarkable throughout the experiment and there were no deaths. No evidence of lesions in any organ was noted at sacrifice. Mean body weights of male mice exposed to n-hexane were not significantly different from those for the 0-ppM animals at any time during the study. Analyses of the sperm morphology data obtained 5 weeks post-exposure (the only time point examined) indicated that exposure of male mice to relatively high concentrations of n-hexane vapor for 5 days produced no significant effects on the morphology of sperm relative to that of the 0-ppM control group. 24 refs., 2 figs., 7 tabs.« less

Post-Mortem Magnetic Resonance Imaging Appearances of Feticide in Perinatal Deaths.

PubMed

Shelmerdine, Susan C; Hickson, Melissa; Sebire, Neil J; Arthurs, Owen J

2018-06-06

The aim of this study was to characterise the imaging features seen in fetuses having undergone feticide by intracardiac potassium chloride injection compared to those of non-terminated fetuses at post-mortem magnetic resonance imaging (PMMRI). A case-control study was performed comparing PMMRI findings between two groups of patients - those having undergone feticide were matched to a control group of miscarried/stillborn fetuses. The groups were matched according to gestational age, weight, and time since death. Two independent readers reviewed the PMMRI for thoracic, abdominal, and musculoskeletal imaging features. The Fishers exact test was conducted for differences between the patient groups. Twenty-six cases of feticide (mean gestation 25 weeks [20-36]) and 75 non-terminated fetuses (mean gestation 26.7 weeks [19-36]) were compared. There was a higher proportion of feticide cases demonstrating pneumothorax (23.1 vs. 1.3%, p = 0.001), haemothorax (42.3 vs. 4%, p = 0.001), pneumopericardium (30.8 vs. 5.3%, p = 0.002), and haemopericardium (34.6 vs. 0%, p = 0.0001). Intracardiac gas and intra-abdominal findings were higher in the feticide group, but the differences were not statistically significant. Characteristic PMMRI features of feticide can help improve reporter confidence in differentiating iatrogenic from physiological/pathological processes. © 2018 S. Karger AG, Basel.

Effect of manual therapy versus proprioceptive neuromuscular facilitation in dynamic balance, mobility and flexibility in field hockey players. A randomized controlled trial.

PubMed

Espí-López, Gemma V; López-Martínez, Susana; Inglés, Marta; Serra-Añó, Pilar; Aguilar-Rodríguez, Marta

2018-04-22

To compare the effectiveness of a specific Manual Therapy (MT) protocol applied to field hockey players (FHP), versus a Proprioceptive Neuromuscular Facilitation (PNF) protocol, in the improvement of dynamic balance, active range of movement and lumbar flexibility one-week and four-weeks after the treatment. Randomized controlled trial. Participants were assigned to 2 groups: MT and PNF. 30 min' sessions were performed once a week for three weeks. Three evaluations were performed: basal, one-week and four-weeks post-treatment. University of Valencia (Spain). 22 in MT group and 20 in PNF group. Dynamic Balance, measured with Star Excursion Balance Test; Active Range of Motion (ROM), using a manual goniometer and Lumbar Flexibility, assessed with Fingertip-to-floor test. Both groups significantly improved in lateral and medial dynamic balance one-week post-treatment (p < 0.05); but the improvement in the MT group lasted until the fourth-week after treatment in both reaches (lateral and medial) (p < 0.05). MT group also obtained significant improvements in dorsal flexion of the ankle in the fourth-week post-treatment (p < 0.05) and in lumbar flexibility one-week post-treatment (p < 0.05). MT and PNF improve dynamic balance one-week post-treatment; however, the improvement obtained through MT is maintained four-weeks later. Only MT improves dorsal flexion of the ankle four-weeks post-treatment and lumbar flexibility one-week post-treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Injectable polypeptide hydrogels via methionine modification for neural stem cell delivery.

PubMed

Wollenberg, A L; O'Shea, T M; Kim, J H; Czechanski, A; Reinholdt, L G; Sofroniew, M V; Deming, T J

2018-04-05

Injectable hydrogels with tunable physiochemical and biological properties are potential tools for improving neural stem/progenitor cell (NSPC) transplantation to treat central nervous system (CNS) injury and disease. Here, we developed injectable diblock copolypeptide hydrogels (DCH) for NSPC transplantation that contain hydrophilic segments of modified l-methionine (Met). Multiple Met-based DCH were fabricated by post-polymerization modification of Met to various functional derivatives, and incorporation of different amino acid comonomers into hydrophilic segments. Met-based DCH assembled into self-healing hydrogels with concentration and composition dependent mechanical properties. Mechanical properties of non-ionic Met-sulfoxide formulations (DCH MO ) were stable across diverse aqueous media while cationic formulations showed salt ion dependent stiffness reduction. Murine NSPC survival in DCH MO was equivalent to that of standard culture conditions, and sulfoxide functionality imparted cell non-fouling character. Within serum rich environments in vitro, DCH MO was superior at preserving NSPC stemness and multipotency compared to cell adhesive materials. NSPC in DCH MO injected into uninjured forebrain remained local and, after 4 weeks, exhibited an immature astroglial phenotype that integrated with host neural tissue and acted as cellular substrates that supported growth of host-derived axons. These findings demonstrate that Met-based DCH are suitable vehicles for further study of NSPC transplantation in CNS injury and disease models. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effects of pressure on arthritic knees in a rat model of CFA-induced arthritis.

PubMed

Koo, Sung Tae; Lee, Chang-Hyung; Choi, Hyeunseok; Shin, Yong Il; Ha, Ki Tae; Ye, Hanna; Shim, Hyun Bo

2013-01-01

Pain is influenced by weather changes under certain circumstances, and inflammatory pain in animal models is ameliorated by pressure, but the underlying mechanism of atmospheric pressure has not been clearly elucidated. To examine the effect of pressure on pain in an arthritic animal model. Controlled animal study. Laboratory animal study. Following an injection of complete Freund's adjuvant (CFA) into one side of a knee joint, 32 rats were assigned randomly to 2 groups and either placed under 1 or 2.5 atmospheres absolute (ATA) in a hyperbaric chamber for 5 hours. The pain levels were assessed daily for up to 2 weeks post-injection to determine the changes in weight bearing (WB) of the affected limbs. In addition, the levels of gelatinase, MMP-2, and MMP-9 expression in the synovial fluids of the knees were analyzed. After arthritis induction, the rats in the 1 ATA group showed reduced WB of the affected limbs (< 10% of normal limbs). This reduction in WB peaked at 2 days after the injection and then decreased spontaneously. Nevertheless, the pain behavior lasted for more than 2 weeks. In the 2.5 ATA group, the WB was significantly better during the experiment.  The MMP-9/MMP-2 ratio increased at 7 and 14 days after the CFA injection in the 1 ATA group. However, repetitive exposure to 2.5 ATA significantly reduced this ratio in the 2.5 ATA group. Although a sufficient number of samples were used to support the hypothesis that high atmospheric pressure improves a painful condition in this study, an additional larger-scale study will be needed to confirm these findings. Exposure to elevated pressures appears to relieve arthritic pain for extended periods by reducing the inflammatory process and should be considered as a possible alternative pain-reducing therapy.

Adding triamcinolone improves viscosupplementation: a randomized clinical trial.

PubMed

de Campos, Gustavo Constantino; Rezende, Marcia U; Pailo, Alexandre F; Frucchi, Renato; Camargo, Olavo Pires

2013-02-01

Intraarticular injections, mainly using long-lasting corticosteroid suspensions, have long been used to treat knee osteoarthritis. Viscosupplementation is a relatively new approach with injection of a variety of agents. When comparing viscosupplementation with intraarticular injections of corticosteroids from baseline to the fourth week, steroids have been more effective for pain relief. By the fourth week they provide similar relief, but beyond that viscosupplementation appears to provide greater pain reduction. The delayed onset of symptomatic improvement combined with reports of reactive synovitis may discourage physicians and patients. We therefore addressed three questions: Does the addition of triamcinolone to viscosupplementation (1) improve first-week pain and function compared with viscosupplementation alone, (2) diminish adverse effects of viscosupplementation alone, and (3) alter 6-month pain and function of viscosupplementation alone? We prospectively enrolled 104 patients with knee osteoarthritis and randomized them to receive either a single intraarticular injection (6 mL) of hylan GF-20 (Group viscosupplementation [Group VS]), or a single intraarticular injection of hylan GF-20 (6 mL) and 1 mL (20 mg) of triamcinolone hexacetonide (Group VS + T). VAS, WOMAC™, and Lequesne questionnaires were completed at baseline and at Weeks 1, 4, 12, and 24. At Week 1 the WOMAC and VAS scores were lower in Group VS + T, compared with Group VS. There was no difference regarding the adverse effects. At Weeks 4, 12, and 24 there were no differences in the groups. The addition of triamcinolone hexacetonide improves first-week symptom and functional scores of viscosupplementation, but not beyond. It does not seem to increase the likelihood of adverse effects. Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Early initiation of post-sternotomy cardiac rehabilitation exercise training (SCAR): study protocol for a randomised controlled trial and economic evaluation

PubMed Central

Lobley, Grace; Worrall, Sandra; Powell, Richard; Kimani, Peter K; Banerjee, Prithwish; Barker, Thomas

2018-01-01

Introduction Current guidelines recommend abstinence from supervised cardiac rehabilitation (CR) exercise training for 6 weeks post-sternotomy. This practice is not based on empirical evidence, thus imposing potentially unnecessary activity restrictions. Delayed participation in CR exercise training promotes muscle atrophy, reduces cardiovascular fitness and prolongs recovery. Limited data suggest no detrimental effect of beginning CR exercise training as early as 2 weeks post-surgery, but randomised controlled trials are yet to confirm this. The purpose of this trial is to compare CR exercise training commenced early (2 weeks post-surgery) with current usual care (6 weeks post-surgery) with a view to informing future CR guidelines for patients recovering from sternotomy. Methods and analysis In this assessor-blind randomised controlled trial, 140 cardiac surgery patients, recovering from sternotomy, will be assigned to 8 weeks of twice-weekly supervised CR exercise training commencing at either 2 weeks (early CR) or 6 weeks (usual care CR) post-surgery. Usual care exercise training will adhere to current UK recommendations. Participants in the early CR group will undertake a highly individualised 2–3 week programme of functional mobility, strength and cardiovascular exercise before progressing to a usual care CR programme. Outcomes will be assessed at baseline (inpatient), pre-CR (2 or 6 weeks post-surgery), post-CR (10 or 14 weeks post-surgery) and 12 months. The primary outcome will be change in 6 min walk distance. Secondary outcomes will include measures of functional fitness, quality of life and cost-effectiveness. Ethics and dissemination Recruitment commenced on July 2017 and will complete by December 2019. Results will be disseminated via national governing bodies, scientific meetings and peer-reviewed journals. Trial registration number NCT03223558; Pre-results. PMID:29574443

An open-label, multicenter study to evaluate the safe and effective use of the single-use autoinjector with an Avonex® prefilled syringe in multiple sclerosis subjects

PubMed Central

2011-01-01

Background The ability to self-inject in patients with multiple sclerosis (MS) has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patients' independence. However, injection anxiety, needle phobia and disease-related disability are major barriers to a patient's ability to self-administer treatment. Use of an autoinjector may improve patients' ability to self-inject. This study evaluated the safe and effective use of Avonex Pen™ (prefilled pen), a single use autoinjector, for intramuscular delivery of interferon beta-1a (IM IFNβ-1a, Avonex) in MS patients. Methods This was a Phase IIIb, open-label, single-country, multicenter trial in MS patients currently using IM IFNβ-1a prefilled syringes. Patients received weekly 30 mcg IM IFNβ-1a treatment over 4 weeks. On Day 1, patients self-administered IM IFNβ-1a using a prefilled syringe at the clinic. On Day 8, patients received training on the prefilled pen and self-administered IM IFNβ-1a using the device. On Day 15, patients self-administered IM IFNβ-1a at home using the prefilled pen. A final injection occurred at the clinic on Day 22 when patients self-administered IM IFNβ-1a using the prefilled pen while clinic staff observed and completed a detailed questionnaire documenting patients' ability to self-inject with the device. Serum neopterin levels were evaluated pre and post-injection on Days 1 and 8. Adverse events were monitored throughout. Results Seventy-one (96%) patients completed the study. The overall success rate in safely and effectively using the prefilled pen was 89%. No device malfunctions occurred. One unsuccessful administration occurred at Day 22 due to patient error; no patient injury resulted. Patients gave the prefilled pen high ratings (8.7-9.3) on a 10-point scale for ease of use (0 = extremely difficult, 10 = extremely easy). Ninety-four percent of patients preferred the prefilled pen over the prefilled syringe. Induction of serum neopterin levels, serving as a biomarker for type 1 interferon action, was similar to that of the prefilled syringe. The prefilled pen demonstrated a safety profile comparable to the prefilled syringe. Conclusions The prefilled pen is a safe and effective device for administration of IM IFNβ-1a and represents an alternative method for self-injection for MS patients using this therapy. Trial registration This study is registered at clinicaltrials.gov, identifier: NCT00828204 PMID:21999176

Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology.

PubMed

Saw, Khay-Yong; Anz, Adam; Merican, Shahrin; Tay, Yong-Guan; Ragavanaidu, Kunaseegaran; Jee, Caroline S Y; McGuire, David A

2011-04-01

The purpose of this study was to evaluate the quality of articular cartilage regeneration after arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous peripheral blood progenitor cells (PBPCs) in combination with hyaluronic acid (HA). Five patients underwent second-look arthroscopy with chondral core biopsy. These 5 patients are part of a larger pilot study in which 180 patients with International Cartilage Repair Society grade III and IV lesions of the knee joint underwent arthroscopic subchondral drilling followed by postoperative intra-articular injections. Continuous passive motion was used on the operated knee 2 hours per day for 4 weeks. Partial weight bearing was observed for the first 6 to 8 weeks. Autologous PBPCs were harvested 1 week after surgery. One week after surgery, 8 mL of the harvested PBPCs in combination with 2 mL of HA was injected intra-articularly into the operated knee. The remaining PBPCs were divided into vials and cryopreserved. A total of 5 weekly intra-articular injections were given. Second-look arthroscopy confirmed articular cartilage regeneration, and histologic sections showed features of hyaline cartilage. Apart from the minimal discomfort of PBPC harvesting and localized pain associated with the intra-articular injections, there were no other notable adverse reactions. Articular hyaline cartilage regeneration is possible with arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous PBPCs in combination with HA. Level IV, therapeutic case series. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects.

PubMed

Spreen, William; Ford, Susan L; Chen, Shuguang; Wilfret, David; Margolis, David; Gould, Elizabeth; Piscitelli, Stephen

2014-12-15

GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from <8% to 28% of corresponding plasma concentrations. These data suggest 744 LA injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

Efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for stage 4 retinopathy of prematurity.

PubMed

Cheng, Hui-Chen; Lee, Shui-Mei; Hsieh, Yi-Ting; Lin, Po-Kang

2015-04-01

To investigate the efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity. Retrospective case series study. The medical records of patients receiving intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity from January 2007 to May 2012 in Taipei Veterans General Hospital were reviewed. A total of 13 eyes of 7 patients (3 boys and 4 girls) with Stage 4 retinopathy of prematurity were included. The mean gestational age and birth weight were 27.6 ± 2.6 weeks (range, 24.5-30.5 weeks) and 893.1 ± 293.2 g (range, 550-1422 g), respectively. The mean age at the time of injection was 38.2 ± 1.9 weeks (range, 36.0-41.5 weeks) postmenstrual age, and the mean follow-up period was 37.8 ± 19.5 months (range, 11.0-67.5 months). The active neovascularization regressed rapidly, and the anatomical outcomes were favorable in all patients. One eye developed recurrent retinal hemorrhage with localized retinal detachment 21 weeks after initial treatment, which resolved after a second injection. There were no ocular or systemic complications in these patients. Intravitreal injection of anti-vascular endothelial growth factor agents may be effective as monotherapy or as supplement to failed laser treatment for patients with Stage 4 retinopathy of prematurity without additional surgical intervention. Further randomized controlled trials are necessary to compare the clinical efficacy and safety with other conventional interventions.

Cannabidiol-Δ9-tetrahydrocannabinol interactions on acute pain and locomotor activity.

PubMed

Britch, Stevie C; Wiley, Jenny L; Yu, Zhihao; Clowers, Brian H; Craft, Rebecca M

2017-06-01

Previous studies suggest that cannabidiol (CBD) may potentiate or antagonize Δ 9 -tetrahydrocannabinol's (THC) effects. The current study examined sex differences in CBD modulation of THC-induced antinociception, hypolocomotion, and metabolism. In Experiment 1, CBD (0, 10 or 30mg/kg) was administered 15min before THC (0, 1.8, 3.2, 5.6 or 10mg/kg), and rats were tested for antinociception and locomotion 15-360min post-THC injection. In Experiments 2 and 3, CBD (30mg/kg) was administered 13h or 15min before THC (1.8mg/kg); rats were tested for antinociception and locomotion 30-480min post-THC injection (Experiment 2), or serum samples were taken 30-360min post-THC injection to examine CBD modulation of THC metabolism (Experiment 3). In Experiment 1, CBD alone produced no antinociceptive effects, while enhancing THC-induced paw pressure but not tail withdrawal antinociception 4-6h post-THC injection. CBD alone increased locomotor activity at 6h post-injection, but enhanced THC-induced hypolocomotion 4-6h post-THC injection, at lower THC doses. There were no sex differences in CBD-THC interactions. In Experiments 2 and 3, CBD did not significantly enhance THC's effects when CBD was administered 13h or 15min before THC; however, CBD inhibited THC metabolism, and this effect was greater in females than males. These results suggest that CBD may enhance THC's antinociceptive and hypolocomotive effects, primarily prolonging THC's duration of action; however, these effects were small and inconsistent across experiments. CBD inhibition of THC metabolism as well other mechanisms likely contribute to CBD-THC interactions on behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

Cannabidiol-Δ9-tetrahydrocannabinol interactions on acute pain and locomotor activity

PubMed Central

Britch, Stevie C.; Wiley, Jenny L.; Yu, Zhihao; Clowers, Brian H.; Craft, Rebecca M.

2017-01-01

Background Previous studies suggest that cannabidiol (CBD) may potentiate or antagonize Δ9-tetrahydrocannabinol’s (THC) effects. The current study examined sex differences in CBD-THC interactions on antinociception, locomotion, and THC metabolism. Methods In Experiment 1, CBD (0, 10 or 30 mg/kg) was administered 15 min before THC (0, 1.8, 3.2, 5.6 or10 mg/kg), and rats were tested for antinociception and locomotion 15–360 min post-THC injection. In Experiments 2 and 3, CBD (30 mg/kg) was administered 13 hr or 15 min before THC (1.8 mg/kg); rats were tested for antinociception and locomotion 30–480 min post-THC injection (Experiment 2), or serum samples were taken 30–360 min post-THC injection to examine CBD modulation of THC metabolism (Experiment 3). Results In Experiment 1, CBD alone produced no antinociceptive effects, while enhancing THC-induced paw pressure but not tail withdrawal antinociception 4–6 hr post-THC injection. CBD alone increased locomotor activity at 6 hr post-injection, but enhanced THC-induced hypolocomotion 4–6 hr post-THC injection, at lower THC doses. There were no sex differences in CBD-THC interactions. In Experiments 2 and 3, CBD did not significantly enhance THC’s effects when CBD was administered 13 hr or 15 min before THC; however, CBD inhibited THC metabolism, and this effect was greater in females than males. Conclusions These results suggest that CBD may enhance THC’s antinociceptive and hypolocomotive effects, primarily prolonging THC’s duration of action; however, these effects were small and inconsistent across experiments. CBD inhibition of THC metabolism as well other mechanisms likely contribute to CBD-THC interactions on behavior. PMID:28445853

[Case-control study on local injection of autoallergic platelet rich plasma or whole blood for the treatment of tennis elbow].

PubMed

Zhao, Li-Lai; Tong, Pei-Jian; Xiao, Lu-Wei; Zhu, Qiu-Liang; Xu, Bin; Yan, Mao-Hua

2014-11-01

To compare therapeutic effects of local injection with autoallergic platelet rich plasma (PRP) or autoallergic whole blood (AWB) for the treatment of chronic tennis elbow. From January 2011 to January 2014, 40 patients with chronic tennis elbow were divided into 2 groups, 20 cases in each group: PRP group and AWB group. There were 20 patients in PRP group treated with local injection of autoallergic platelet rich plasma, including 5 males and 15 females, with an average age of (47.50 ± 9.86) years old; and the average course of disease was (4.67 ± 3.27) months. Among the 20 patients in AWB group treated with local injection of autoallergic whole blood, 3 patients were male and 17 patients were female, with an average age of (46.50 ± 9.96) years old;and the average course of disease was (4.53 ± 2.27) months. The elbow joint was fixed with elastic stockings after injection. All the patients were guided to do strengthening and extension exercises during the follow-up period. Visual analog scale (VAS), Mayo scores for elbow and pressure pain threshold (PPT) were used to evaluate clinical effects after injection immediately and 4,8 weeks after treatment. Results:All the patients were followed up,there were no infections and swelling occurred. The VAS, Mayo and PPT scores of patients in PRP group were improved from pre-therapy 7.22 ± 1.32, 56.71 ± 10.90 and 17.47 ± 4.62 to 2.73 ± 1.00, 91.59 ± 6.95 and 21.35 ± 4.80 respectively 8 weeks after treatment. The VAS, Mayo and PPT scores of patients in AWB group were improved from pre-therapy 7.16 ±1.27, 54.72 ± 8.36 and 17.06 ± 4.83 to 3.81 ± 1.36, 82.06 ± 7.89 and 20.12 ± 4.97 respectively 8 weeks after treatment. All the pain and functional variables including VAS, PPT, and Mayo scores were improved significantly in both groups 4 weeks after injection. On the 4th week after injection, there was no statistically significant difference in PPT between two groups; while the VAS and Mayo score of AWB group were lower than those of PRP group. On the 8th week after injection, the VAS of AWB group was higher than that of PRP group; but the Mayo and PPT scores of AWB group were lower than those of PRP group. PRP and AWB injections are both effective to treat chronic lateral epicondylitis. Compared with AWB injection, PRP injection may be more effective in releasing pain and improving function for a longer time.

Dopamine, Noradrenaline and Serotonin Receptor Densities in the Striatum of Hemiparkinsonian Rats following Botulinum Neurotoxin-A Injection.

PubMed

Mann, T; Zilles, K; Dikow, H; Hellfritsch, A; Cremer, M; Piel, M; Rösch, F; Hawlitschka, A; Schmitt, O; Wree, A

2018-03-15

Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D 1 , D 2 /D 3 , α 1 , α 2 , and 5HT 2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography. We found a moderate increase in D 1 receptor density 3 weeks post lesion that decreased during longer survival times, a significant increase of D 2 /D 3 receptor density, and 50% reduction in 5HT 2A receptor density. α 1 receptor density remained unaltered in hemi-PD and α 2 receptors demonstrated a slight right-left difference increasing with post lesion survival. In a second step, the possible role of receptors on the known reduction of apomorphine-induced rotations in hemi-PD rats by intrastriatally injected Botulinum neurotoxin-A (BoNT-A) was analyzed by measuring the receptor densities after BoNT-A injection. The application of this neurotoxin reduced D 2 /D 3 receptor density, whereas the other receptors mainly remained unaltered. Our results provide novel data for an understanding of the postlesional plasticity of dopaminergic, noradrenergic and serotonergic receptors in the hemi-PD rat model. The results further suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing the interhemispheric imbalance in D 2 /D 3 receptor density. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of intravenous endotoxin on blood cell profiles of broilers housed in cages and floor litter environments.

PubMed

Wang, W; Wideman, R F; Chapman, M E; Bersi, T K; Erf, G F

2003-12-01

Commercial broilers are constantly exposed to airborne microorganisms and endotoxin (lipopolysaccharide, LPS). It has been shown that microbial contamination of the air was higher in broiler houses using floor litter than in broiler houses using netting-type floors. The current study evaluated the effect of housing conditions on blood leukocyte profiles and tested the hypothesis that, when compared to broilers reared in clean stainless steel cages (Cage group), broilers raised on floor litter (Floor group) should experience a higher environmental challenge and have a desensitized immune system that may exhibit better tolerance/resistance to subsequent intravenous LPS challenge. Hematological parameters were evaluated prior to and following i.v. administration of 1 mg/kg BW Salmonella typhimurium LPS (dissolved at 1 mg/0.25 mL in PBS) or i.v. injection of 0.25 mL/kg BW PBS alone. The results showed that prior to LPS/PBS injection, broilers in the cage group had higher heterophil and monocyte concentrations, a higher B cell percentage within the lymphocyte population, and a higher heterophil to lymphocyte (H:L) ratio in the blood. The i.v. LPS injection resulted in 25% mortality in the cage group and 42% mortality in the floor group within 8 h post-injection. LPS reduced the concentrations of total white blood cells (WBC) and all differential WBC except eosinophils and increased thrombocyte concentrations within 1 h post-injection in both groups. All of these values returned to their respective pre-injection levels within 48 h post-injection in the surviving birds. The two groups exhibited similar overall hematological changes after LPS injection except that the cage group showed a higher H:L ratio at 8 h post-injection and a lower B-cell percentage within the lymphocyte population at 48 h post-injection when compared with the floor group. We concluded that the immune systems of broilers reared on floor litter were desensitized and exhibited less pronounced leukocyte responses to i.v. LPS when compared with those of broilers reared in clean stainless steel cages. However, such desensitization of the immune system did not help broilers survive subsequent i.v. LPS challenge.

Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer’s disease or corticobasal degeneration brains

PubMed Central

Boluda, Susana; Iba, Michiyo; Zhang, Bin; Raible, Kevin M.; Lee, Virginia M-Y.; Trojanowski, John Q.

2015-01-01

Filamentous tau pathologies are hallmark lesions of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and corticobasal degeneration (CBD) which show cell type-specific and topographically distinct tau inclusions. Growing evidence supports templated transmission of tauopathies through functionally interconnected neuroanatomical pathways suggesting that different self-propagating strains of pathological tau could account for the diverse manifestations of neurodegenerative tauopathies. Here, we describe the rapid and distinct cell type-specific spread of pathological tau following intracerebral injections of CBD or AD brain extracts enriched in pathological tau (designated CBD-Tau and AD-Tau, respectively) in young human mutant P301S tau transgenic (Tg) mice (line PS19) ~6–9 months before they show onset of mutant tau transgene-induced tau pathology. At 1 month post-injection of CBD-Tau, tau inclusions developed predominantly in oligodendrocytes of the fimbria and white matter near the injection sites with infrequent intraneuronal tau aggregates. In contrast, injections of AD-Tau in young PS19 mice induced tau pathology predominantly in neuronal perikarya with little or no oligodendrocyte involvement 1 month post-injection. With longer post-injection survival intervals of up to 6 months, CBD-Tau- and AD-Tau-induced tau pathology spread to different brain regions distant from the injection sites while maintaining the cell type-specific pattern noted above. Finally, CA3 neuron loss was detected 3 months post-injection of AD-Tau but not CBD-Tau. Thus, AD-Tau and CBD-Tau represent specific pathological tau strains that spread differentially and may underlie distinct clinical and pathological features of these two tauopathies. Hence, these strains could become targets to develop disease-modifying therapies for CBD and AD. PMID:25534024

AAV1/2-induced overexpression of A53T-α-synuclein in the substantia nigra results in degeneration of the nigrostriatal system with Lewy-like pathology and motor impairment: a new mouse model for Parkinson's disease.

PubMed

Ip, Chi Wang; Klaus, Laura-Christin; Karikari, Akua A; Visanji, Naomi P; Brotchie, Jonathan M; Lang, Anthony E; Volkmann, Jens; Koprich, James B

2017-02-01

α-Synuclein is a protein implicated in the etiopathogenesis of Parkinson's disease (PD). AAV1/2-driven overexpression of human mutated A53T-α-synuclein in rat and monkey substantia nigra (SN) induces degeneration of nigral dopaminergic neurons and decreases striatal dopamine and tyrosine hydroxylase (TH). Given certain advantages of the mouse, especially it being amendable to genetic manipulation, translating the AAV1/2-A53T α-synuclein model to mice would be of significant value. AAV1/2-A53T α-synuclein or AAV1/2 empty vector (EV) at a concentration of 5.16 x 10 12 gp/ml were unilaterally injected into the right SN of male adult C57BL/6 mice. Post-mortem examinations included immunohistochemistry to analyze nigral α-synuclein, Ser129 phosphorylated α-synuclein and TH expression, striatal dopamine transporter (DAT) levels by autoradiography and dopamine levels by high performance liquid chromatography. At 10 weeks, in AAV1/2-A53T α-synuclein mice there was a 33% reduction in TH+ dopaminergic nigral neurons (P < 0.001), 29% deficit in striatal DAT binding (P < 0.05), 38% and 33% reductions in dopamine (P < 0.001) and DOPAC (P < 0.01) levels and a 60% increase in dopamine turnover (homovanilic acid/dopamine ratio; P < 0.001). Immunofluorescence showed that the AAV1/2-A53T α-synuclein injected mice had widespread nigral and striatal expression of vector-delivered A53T-α-synuclein. Concurrent staining with human PD SN samples using gold standard histological methodology for Lewy pathology detection by proteinase K digestion and application of specific antibody raised against human Lewy body α-synuclein (LB509) and Ser129 phosphorylated α-synuclein (81A) revealed insoluble α-synuclein aggregates in AAV1/2-A53T α-synuclein mice resembling Lewy-like neurites and bodies. In the cylinder test, we observed significant paw use asymmetry in the AAV1/2-A53T α-synuclein group when compared to EV controls at 5 and 9 weeks post injection (P < 0.001; P < 0.05). These data show that unilateral injection of AAV1/2-A53T α-synuclein into the mouse SN leads to persistent motor deficits, neurodegeneration of the nigrostriatal dopaminergic system and development of Lewy-like pathology, thereby reflecting clinical and pathological hallmarks of human PD.

Leptin ameliorates ischemic necrosis of the femoral head in rats with obesity induced by a high-fat diet.

PubMed

Zhou, Lu; Jang, Kyu Yun; Moon, Young Jae; Wagle, Sajeev; Kim, Kyoung Min; Lee, Kwang Bok; Park, Byung-Hyun; Kim, Jung Ryul

2015-03-23

Obesity is a risk factor for ischemic necrosis of the femoral head (INFH). The purpose of this study was to determine if leptin treatment of INFH stimulates new bone formation to preserve femoral head shape in rats with diet-induced obesity. Rats were fed a high-fat diet (HFD) or normal chow diet (NCD) for 16 weeks to induce progressive development of obesity. Avascular necrosis of the femoral head (AVN) was surgically induced. Adenovirus-mediated introduction of the leptin gene was by intravenous injection 2 days before surgery-induced AVN. At 6 weeks post-surgery, radiologic and histomorphometric assessments were performed. Leptin signaling in tissues was examined by Western blot. Osteogenic markers were analyzed by real-time RT-PCR. Radiographs showed better preservation of femoral head architecture in the HFD-AVN-Leptin group than the HFD-AVN and HFD-AVN-LacZ groups. Histology and immunohistochemistry revealed the HFD-AVN-Leptin group had significantly increased osteoblastic proliferation and vascularity in infarcted femoral heads compared with the HFD-AVN and HFD-AVN-LacZ groups. Intravenous injection of leptin enhanced serum VEGF levels and activated HIF-1α pathways. Runx 2 and its target genes were significantly upregulated in the HFD-AVN-Leptin group. These results indicate that leptin resistance is important in INFH pathogenesis. Leptin therapy could be a new strategy for INFH.

Leptin ameliorates ischemic necrosis of the femoral head in rats with obesity induced by a high-fat diet

PubMed Central

Zhou, Lu; Jang, Kyu Yun; Moon, Young Jae; Wagle, Sajeev; Kim, Kyoung Min; Lee, Kwang Bok; Park, Byung-Hyun; Kim, Jung Ryul

2015-01-01

Obesity is a risk factor for ischemic necrosis of the femoral head (INFH). The purpose of this study was to determine if leptin treatment of INFH stimulates new bone formation to preserve femoral head shape in rats with diet-induced obesity. Rats were fed a high-fat diet (HFD) or normal chow diet (NCD) for 16 weeks to induce progressive development of obesity. Avascular necrosis of the femoral head (AVN) was surgically induced. Adenovirus-mediated introduction of the leptin gene was by intravenous injection 2 days before surgery-induced AVN. At 6 weeks post-surgery, radiologic and histomorphometric assessments were performed. Leptin signaling in tissues was examined by Western blot. Osteogenic markers were analyzed by real-time RT-PCR. Radiographs showed better preservation of femoral head architecture in the HFD-AVN-Leptin group than the HFD-AVN and HFD-AVN-LacZ groups. Histology and immunohistochemistry revealed the HFD-AVN-Leptin group had significantly increased osteoblastic proliferation and vascularity in infarcted femoral heads compared with the HFD-AVN and HFD-AVN-LacZ groups. Intravenous injection of leptin enhanced serum VEGF levels and activated HIF-1α pathways. Runx 2 and its target genes were significantly upregulated in the HFD-AVN-Leptin group. These results indicate that leptin resistance is important in INFH pathogenesis. Leptin therapy could be a new strategy for INFH. PMID:25797953

Monitoring of tumor growth and metastasis potential in MDA-MB-435s/ tk-luc human breast cancer xenografts

NASA Astrophysics Data System (ADS)

Chang, Ya-Fang; Lin, Yi-Yu; Wang, Hsin-Ell; Liu, Ren-Shen; Pang, Fei; Hwang, Jeng-Jong

2007-02-01

Molecular imaging of reporter gene expression provides a rapid, sensitive and non-invasive monitoring of tumor behaviors. In this study, we reported the establishment of a novel animal model for longitudinal examination of tumor growth kinetics and metastatic spreading in vivo. The highly metastatic human breast carcinoma MDA-MB-435s cell line was engineered to stably express herpes simplex virus type 1 thymidine kinase (HSV-1- tk) and luciferase ( luc). Both 131I-FIAU and D-luciferin were used as reporter probes. For orthotopic tumor formation, MDA-MB-435s/ tk-luc cells were implanted into the first nipple of 6-week-old female NOD/SCID mice. For metastatic study, cells were injected via the lateral tail vein. Mice-bearing MDA-MB-435s/ tk-luc tumors were scanned for tumor growth and metastatsis using Xenogen IVIS50 system. Gamma scintigraphy and whole-body autoradiography were also applied to confirm the tumor localization. The results of bioluminescence imaging as well as histopathological finding showed that tumors could be detected in femur, spine, ovary, lungs, kidney, adrenal gland, lymph nodes and muscle at 16 weeks post i.v. injection, and correlated photons could be quantified. This MDA-MB-435s/ tk-luc human breast carcinoma-bearing mouse model combined with multimodalities of molecular imaging may facilitate studies on the molecular mechanisms of cancer invasion and metastasis.

Anti-fibrotic Role of miR-214 in Thioacetamide-induced Liver Cirrhosis in Rats.

PubMed

Izawa, Takeshi; Horiuchi, Takashi; Atarashi, Machi; Kuwamura, Mitsuru; Yamate, Jyoji

2015-08-01

An increasing number of studies have focused on the role of microRNAs in liver fibrosis/cirrhosis. miR-214 has recently attracted more attention as a fibrosis-related factor; however, the molecular mechanisms in hepatic fibrogenesis remain largely unknown. Here, we investigate the pathological role of miR-214 during progression of liver cirrhosis in rats. Rats were injected intraperitoneally with thioacetamide at a dose of 100 mg/kg body weight, twice a week. The liver was collected at post first injection weeks 5, 10, 15, and 20. Hepatic expression of miR-214 was analyzed by real-time polymerase chain reaction, in situ hybridization, and laser microdissection. The effects of miR-214 overexpression were investigated by in vitro transfection using fibroblastic MT-9 cells. miR-214 was highly upregulated in the fibrotic area in parallel with the cirrhosis progression. miR-214 overexpression in MT-9 cells under transforming growth factor-β1 stimulation resulted in decreased cell number and increased expression of cleaved caspase 3 and decreased expression of α-smooth muscle actin, suggesting that miR-214 induces apoptosis and inhibits myofibroblast differentiation in fibroblastic cells under stimulation of fibrogenic factors. These data indicate an anti-fibrotic role of miR-214 in chemically induced liver fibrosis/cirrhosis. © 2015 by The Author(s).

High performance liquid chromatography determination of dexamethasone in plasma to evaluate its systemic absorption following intra-space pterygomandibular injection of twin-mix (mixture of 2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone): randomized control trial.

PubMed

Bhargava, Darpan; Deshpande, Ashwini; Thomas, Shaji; Sharma, Yogesh; Khare, Piush; Sahu, Sanjeev Kumar; Dubey, Suyash; Pandey, Ankit; Sreekumar, K

2016-09-01

To determine systemic absorption of dexamethasone by detection of plasma concentration using high performance liquid chromatography following its administration along with local anesthetic agent as a mixture via pterygomandibular space. A prospective randomized double-blind clinical study was undertaken to analyze the plasma concentration of dexamethasone after intra-space pterygomandibular injection along with local anesthesia. The study was performed as per split mouth model where the mandibular quadrant allocation was done on a random basis considering each of the 30 patients is included in the two study interventions (SS and CS). For the study site (SS) procedures, dexamethasone was administered as a mixture (2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone) intra-space. In the control site (CS) procedures, a regular standard inferior alveolar nerve block was administered, and dexamethasone was given as intramuscular injection. The plasma dexamethasone determination was done in venous blood 30- and 60-min post injection using high performance liquid chromatography (HPLC). The clinical parameters like pain; swelling; and mouth opening on the first, third, and seventh post-operative day were analyzed and compared. No significant difference was found in the clinical parameters assessed; comparative evaluation showed less swelling in the SS interventions. The plasma concentration of dexamethasone for the CS interventions was 226 ± 47 ng/ml at 30-min and 316 ± 81.6 ng/ml at 60-min post injection, and for SS, it was 221 ± 81.6 ng/ml at 30-min and 340 ± 105 ng/ml at 60-min post injection. On inter-site (CS and SS) comparison, no statistically significant difference was ascertained in dexamethasone plasma concentration at 30-min post injection (P = 0.77) and at 60-min post injection. (P = 0.32). Intra-space (pterygomandibular space) administration of dexamethasone can achieve statistically similar plasma concentration of the drug as when the same dose is administered intramuscularly with demonstration of similar clinical effects.

Protective Effect of Intravitreal Administration of Exosomes Derived from Mesenchymal Stem Cells on Retinal Ischemia.

PubMed

Moisseiev, Elad; Anderson, Johnathon D; Oltjen, Sharon; Goswami, Mayank; Zawadzki, Robert J; Nolta, Jan A; Park, Susanna S

2017-10-01

Exosomes derived from human mesenchymal stem cells (hMSCs) cultured under hypoxic conditions contain proteins and growth factors that promote angiogenesis. This study investigated the effect of intravitreal administration of these exosomes on retinal ischemia using a murine model. Oxygen-induced retinopathy (OIR) was induced by exposing one-week-old male C57BL/6J mice to 5 days of 75% hyperoxic conditioning, and returning to room air. After hyperoxic conditioning, the right eye of each mouse was injected intravitreally with 1 µl saline or exosomes derived from hMSCs and compared to control mice of the same age raised in room air without OIR injected intravitreally with saline. Two weeks post-injection, fluorescein angiography (FA) and phase-variance optical coherence tomography angiography (pvOCTA) were used to assess retinal perfusion. Retinal thickness was determined by OCT. The extent of retinal neovascularization was quantitated histologically by counting vascular nuclei on the retinal surface. Among eyes with OIR, intravitreal exosome treatment partially preserved retinal vascular flow in vivo and reduced associated retinal thinning; retinal thickness on OCT was 111.1 ± 7.4µm with saline versus 132.1 ± 11.6µm with exosome, p < 0.001. Retinal neovascularization among OIR eyes was reduced with exosome treatment when compared to saline-treated eyes (7.75 ± 3.68 versus 2.68 ± 1.35 neovascular nuclei per section, p < 0.0001). No immunogenicity or ocular/systemic adverse effect was associated with intravitreal exosome treatment. Intravitreal administration of exosomes derived from hMSCs was well tolerated without immunosuppression and decreased the severity of retinal ischemia in this murine model. This appealing novel non-cellular therapeutic approach warrants further exploration.

CXC chemokine KC fails to induce neutrophil infiltration and neoangiogenesis in a mouse model of myocardial infarction.

PubMed

Oral, Hasan; Kanzler, Isabella; Tuchscheerer, Nancy; Curaj, Adelina; Simsekyilmaz, Sakine; Sönmez, Tolga Taha; Radu, Eugen; Postea, Otilia; Weber, Christian; Schuh, Alexander; Liehn, Elisa A

2013-07-01

Chemokines and neutrophils, known as important players in the inflammatory cascade, also contribute to heart tissue recovery and scar formation after myocardial infarction (MI). The objective of this study was to determine the importance of ELR-containing CXC chemokine KC in neutrophil infiltration and neoangiogenesis, in a mouse model of chronic MI. MI was induced in mice divided in four groups: control (untreated), anti-KC "later" (anti-KC antibody injections started 4 days after MI and then delivered every 72 hours for 3 weeks, to inhibit angiogenesis), anti-KC "earlier" (anti-KC antibody injections 1 day before and 1 day after MI, to block neutrophil infiltration), anti-KC (anti-KC antibody injections 1 day before and 1 day after MI, and then every 72 hours for 3 weeks). The efficiency of the anti-KC treatment was determined by the measurement of KC serum concentration and immunofluorescence staining, in each of the four groups. Surprisingly, we did not find any difference in neutrophil infiltration in the infarcted area between untreated and treated animals. Moreover, the heart function, infarct size, and neoangiogenesis were not different between the four groups. As expected, a comparable anti-CXCR2 treatment of mice before and after MI was able to significantly reduce neutrophil infiltration into the infarcted area and angiogenesis, but also to reduce the infarction size after long or "later" treatment. The major finding of our study is that KC, a potent neutrophil chemoattractant and an established angiogenic factor, failed to interfere in the post-infarction inflammatory response, in wound healing and scar formation after MI. Therefore, these aspects need to be carefully taken into account when devising therapeutic strategies for myocardial infarction and ischemic cardiomyopathy. Copyright © 2013 Elsevier Ltd. All rights reserved.

A pH- and temperature-responsive bioresorbable injectable hydrogel based on polypeptide block copolymers for the sustained delivery of proteins in vivo.

PubMed

Turabee, Md Hasan; Thambi, Thavasyappan; Duong, Huu Thuy Trang; Jeong, Ji Hoon; Lee, Doo Sung

2018-02-27

Sustained delivery of protein therapeutics is limited owing to the fragile nature of proteins. Despite its great potential, delivery of proteins without any loss of bioactivity remains a challenge in the use of protein therapeutics in the clinic. To surmount this shortcoming, we report a pH- and temperature-responsive in situ-forming injectable hydrogel based on comb-type polypeptide block copolymers for the controlled delivery of proteins. Polypeptide block copolymers, composed of hydrophilic polyethylene glycol (PEG), temperature-responsive poly(γ-benzyl-l-glutamate) (PBLG), and pH-responsive oligo(sulfamethazine) (OSM), exhibit pH- and temperature-induced sol-to-gel transition behavior in aqueous solutions. Polypeptide block copolymers were synthesized by combining N-carboxyanhydride-based ring-opening polymerization and post-functionalization of the chain-end using N-hydroxy succinimide ester activated OSM. The physical properties of polypeptide-based hydrogels were tuned by varying the composition of temperature- and pH-responsive PBLG and OSM in block copolymers. Polypeptide block copolymers were non-toxic to human embryonic kidney cells at high concentrations (2000 μg mL -1 ). Subcutaneous administration of polypeptide block copolymer sols formed viscoelastic gel instantly at the back of Sprague-Dawley (SD) rats. The in vivo gels exhibited sustained degradation and were found to be bioresorbable in 6 weeks without any noticeable inflammation at the injection site. Anionic characteristics of hydrogels allow efficient loading of a cationic model protein, lysozyme, through electrostatic interaction. Lysozyme-loaded polypeptide block copolymer sols readily formed a viscoelastic gel in vivo and sustained lysozyme release for at least a week. Overall, the results demonstrate an elegant approach to control the release of certain charged proteins and open a myriad of therapeutic possibilities in protein therapeutics.

Intra-articular glucocorticoid injections in patients with juvenile idiopathic arthritis in a Singapore hospital.

PubMed

Leow, Olivia Min Yi; Lim, Lee Kean; Ooi, Pei Ling; Shek, Lynette Pei Chi; Ang, Elizabeth You Ning; Son, Mary Beth

2014-05-01

This study aimed to evaluate the efficacy and safety of intra-articular glucocorticoid (IAG) injections in our institution in children with juvenile idiopathic arthritis (JIA). This is a retrospective assessment of IAG injections performed by the Department of Paediatrics, National University Hospital, Singapore, from October 2009 to October 2011. A total of 26 procedures were evaluated for efficacy, considering parameters such as clinical response, changes in systemic medication, length of time between repeat injections, safety, consent-taking, pre- and post-procedural advice, compliance with aseptic technique, and post-procedural complications. A total of 26 IAG injections of triamcinolone hexacetonide were administered over 17 occasions (i.e. patient encounters) to ten patients with JIA during the study period. After the injections, clinical scoring by a paediatric rheumatologist showed overall improvement by an average of 2.62 points out of 15. Besides six patient encounters that had an increase in systemic medication on the day of the injection, five required an increase within six months post injection, two required no adjustments, and one resulted in a decrease in medications. In all, 21 injections did not require subsequent injections. The mean interval between repeat injections was 7.8 months. Cutaneous side effects were noted in three anatomically difficult joints. Medical documentation with regard to patient progress was found to be lacking. As per the recommendations of the American College of Rheumatology, we safely used IAG injections as the first-line therapy in our group of patients with oligoarticular JIA, and/or as an adjunct to systemic therapy in our patients with JIA.

Intra-articular glucocorticoid injections in patients with juvenile idiopathic arthritis in a Singapore hospital

PubMed Central

Leow, Olivia Min Yi; Lim, Lee Kean; Ooi, Pei Ling; Shek, Lynette Pei Chi; Ang, Elizabeth You Ning; Son, Mary Beth

2014-01-01

INTRODUCTION This study aimed to evaluate the efficacy and safety of intra-articular glucocorticoid (IAG) injections in our institution in children with juvenile idiopathic arthritis (JIA). METHODS This is a retrospective assessment of IAG injections performed by the Department of Paediatrics, National University Hospital, Singapore, from October 2009 to October 2011. A total of 26 procedures were evaluated for efficacy, considering parameters such as clinical response, changes in systemic medication, length of time between repeat injections, safety, consent-taking, pre- and post-procedural advice, compliance with aseptic technique, and post-procedural complications. RESULTS A total of 26 IAG injections of triamcinolone hexacetonide were administered over 17 occasions (i.e. patient encounters) to ten patients with JIA during the study period. After the injections, clinical scoring by a paediatric rheumatologist showed overall improvement by an average of 2.62 points out of 15. Besides six patient encounters that had an increase in systemic medication on the day of the injection, five required an increase within six months post injection, two required no adjustments, and one resulted in a decrease in medications. In all, 21 injections did not require subsequent injections. The mean interval between repeat injections was 7.8 months. Cutaneous side effects were noted in three anatomically difficult joints. Medical documentation with regard to patient progress was found to be lacking. CONCLUSION As per the recommendations of the American College of Rheumatology, we safely used IAG injections as the first-line therapy in our group of patients with oligoarticular JIA, and/or as an adjunct to systemic therapy in our patients with JIA. PMID:24862747

Abobotulinum - a toxin injection in patients with refractory idiopathic detrusor overactivity: injections in detrusor, trigone and bladder neck or prostatic urethra, versus detrusor - only injections

PubMed Central

Emami, Maryam; Shadpour, Pejman; Kashi, Amir H.; Choopani, Masoud; Zeighami, Mohammadreza

2017-01-01

ABSTRACT Purpose: To evaluate if the injections of abobotulinum-A toxin in trigone and bladder neck/prostatic urethra in addition to detrusor provides better symptoms relief and urodynamic findings in patients with idiopathic detrusor overactivity (IDO) refractory to medical treatment. Materials and Methods: A total of 74 patients with IDO refractory to anticholinergics received injections in detrusor, trigone and bladder neck/prostatic urethra (Group A, N=36) versus detrusor only injections (Group B, N=38) of abobotulinum-A toxin. All patients were evaluated by a standard overactive bladder symptom score (OABSS) questionnaire and cystometrography before and 6 weeks after the operation. OABSS questionnaire was also completed 20 weeks after the operation. Results: The magnitude of OABSS reduction from baseline to 6 weeks after operation in groups A and B patients was 13.4±2.2 versus 11.7±2.1 (p=0.001). Cystometry results were similar in both groups except for higher volume at urgent desire to void in Group B patients (p <0.001). The mean±SD change in residual volume in Group A at 6 weeks after the operation was −4.8±28.6mL (p=0.33) compared to 21.3±16.9mL in Group B patients (p <0.001). Conclusions: In patients with IDO, adding trigone, and bladder neck/prostatic urethra as sites of abobotulinum- A toxin injection produces greater reductions in OABSS score and less residual urine volume but a lower volume at urgent desire to void in comparison with detrusor only injections. PMID:28727385

Correcting Nasojugal Groove with Autologous Cultured Fibroblast Injection: A Pilot Study.

PubMed

Moon, Kyung-Chul; Lee, Hyun-Su; Han, Seung-Kyu; Chung, Ho-Yun

2018-06-01

A new commercial drug that contains autologous cultured fibroblasts has been developed and approved by the United States Food and Drug Administration for improving the appearance of nasolabial folds. However, the treatment requires three sessions every 3-6 weeks. It is known that the skin overlying the nasojugal groove is thinner, and the wrinkle is generally shallower than nasolabial folds. Therefore, we hypothesized that the nasojugal groove could be improved by just one treatment session. Therefore, the purpose of this study was to evaluate the efficacy and safety of autologous cultured fibroblast injection to correct nasojugal grooves. Forty-six subjects with nasojugal grooves were enrolled in this study. They were injected with autologous cultured fibroblasts or placebo in one session. Blinded evaluators and subjects assessed the efficacy using a validated wrinkle assessment scale at 4, 12, and 24 weeks after the injection. Information of adverse events was collected at each visit. Based on the evaluators' assessment at 24 weeks after the injection, 76% of subjects treated with autologous cultured fibroblasts showed improvement whereas 0% of subjects treated with placebo showed improvement (P < 0.0001). Based on self-assessment at 24 weeks after the injection, 72% of subjects treated with autologous cultured fibroblasts and 45% of subjects treated with placebo showed improvement (P = 0.0662). There were no serious adverse events related to autologous cultured fibroblast injection. Autologous cultured fibroblast injection might be effective and safe to correct nasojugal grooves. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Application of an In Vivo Hepatic Triacylglycerol Production Method in the Setting of a High-Fat Diet in Mice

PubMed Central

Ono-Moore, Kikumi D.; Ferguson, Matthew; Blackburn, Michael L.; Issafras, Hassan; Adams, Sean H.

2016-01-01

High-fat (HF) diets typically promote diet-induced obesity (DIO) and metabolic dysfunction (i.e., insulin resistance, hypertriglyceridemia, and hepatic steatosis). Dysfunction of triacylglycerol (TAG) metabolism may contribute to the development of hepatic steatosis, via increased de novo lipogenesis or repackaging of circulating nonesterified fatty acids (NEFAs). Hepatic TAG production (HTP) rate can be assessed through injecting mice with nonionic detergents that inhibit tissue lipoprotein lipase. Potential confounding effects of detergent-based HTP tests (HTPTs) used in longitudinal studies—including the impact on food intake, energy balance, and weight gain—have not been reported. To examine this, male C57BL/6J mice were fed a 10% or 60% kcal diet. After 4 weeks, the mice underwent an HTPT via poloxamer 407 intraperitoneal injections (1000 mg/kg). Weight gain, energy intake, and postabsorptive TAG levels normalized 7–10 days post-HTPT. The post-HTPT recovery of body weight and energy intake suggest that, in metabolic phenotyping studies, any additional sample collection should occur at least 7–10 days after the HTPT to reduce confounding effects. Diet-specific effects on HTP were also observed: HF-fed mice had reduced HTP, plasma TAG, and NEFA levels compared to controls. In conclusion, the current study highlights the procedural and physiological complexities associated with studying lipid metabolism using a HTPT in the DIO mouse model. PMID:28036028

Image-guided Interstitial Photodynamic Therapy for Squamous Cell Carcinomas: Preclinical investigation

PubMed Central

Sajisevi, Mirabelle; Rigual, Nestor R; Bellnier, David A.; Seshadri, Mukund

2014-01-01

Objective Photodynamic therapy (PDT) is a clinically approved minimally invasive treatment for cancer. In this preclinical study, using an imaging-guided approach, we examined the potential utility of PDT in the management of bulky squamous cell carcinomas (SCCs). Methods To mimic bulky oropharyngeal cancers seen in the clinical setting, intramuscular SCCs were established in six-to-eight week old female C3H mice. Animals were injected with the photosensitizer, 2-[hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH; 0.4 μmol/kg, i.v.) and tumors were illuminated 24 hours post injection with 665 nm light. PDT as a single treatment modality was administered by surface illumination or by interstitial placement of fibers (iPDT). Magnetic resonance imaging was used to guide treatment and assess tumor response to PDT along with correlative histopathologic assessment. Results Interstitial HPPH-PDT resulted in a marked change on T2 maps 24 hours post treatment compared to untreated controls or transcutaneous illumination. Corresponding apparent diffusion coefficient maps also showed hyperintense areas in tumors following iPDT suggestive of effective photodynamic cell kill. Histologic sections (H&E) confirmed presence of extensive tumor necrosis following iPDT. Conclusions These results highlight the potential utility of PDT in the treatment of bulky oropharyngeal cancers. The findings of our study also demonstrate the utility of MRI as a non-invasive tool for mapping of early tissue response to PDT. PMID:25750858

Brain Glucose Transporter (Glut3) Haploinsufficiency Does Not Impair Mouse Brain Glucose Uptake

PubMed Central

Stuart, Charles A.; Ross, Ian R.; Howell, Mary E. A.; McCurry, Melanie P.; Wood, Thomas G.; Ceci, Jeffrey D.; Kennel, Stephen J.; Wall, Jonathan

2011-01-01

Mouse brain expresses three principle glucose transporters. Glut1 is an endothelial marker and is the principal glucose transporter of the blood-brain barrier. Glut3 and Glut6 are expressed in glial cells and neural cells. A mouse line with a null allele for Glut3 has been developed. The Glut3−/− genotype is intrauterine lethal by seven days post-coitis, but the heterozygous (Glut3+/−) littermate survives, exhibiting rapid post-natal weight gain, but no seizures or other behavioral aberrations. At twelve weeks of age, brain uptake of tail vein-injected 3H-2-deoxy glucose in Glut3+/− mice was not different from Glut3+/+ littermates, despite 50% less Glut3 protein expression in the brain. The brain uptake of injected 18F-2-fluoro-2-deoxy glucose was similarly not different from Glut3+/− littermates in the total amount, time course, or brain imaging in the Glut3+/− mice. Glut1 and Glut6 protein expressions evaluated by immunoblots were not affected by the diminished Glut3 expression in the Glut3+/− mice. We conclude that a 50% decrease in Glut3 is not limiting for the uptake of glucose into the mouse brain, since Glut3 haploinsufficiency does not impair brain glucose uptake or utilization. PMID:21316350

Application of an In Vivo Hepatic Triacylglycerol Production Method in the Setting of a High-Fat Diet in Mice.

PubMed

Ono-Moore, Kikumi D; Ferguson, Matthew; Blackburn, Michael L; Issafras, Hassan; Adams, Sean H

2016-12-28

High-fat (HF) diets typically promote diet-induced obesity (DIO) and metabolic dysfunction (i.e., insulin resistance, hypertriglyceridemia, and hepatic steatosis). Dysfunction of triacylglycerol (TAG) metabolism may contribute to the development of hepatic steatosis, via increased de novo lipogenesis or repackaging of circulating nonesterified fatty acids (NEFAs). Hepatic TAG production (HTP) rate can be assessed through injecting mice with nonionic detergents that inhibit tissue lipoprotein lipase. Potential confounding effects of detergent-based HTP tests (HTPTs) used in longitudinal studies-including the impact on food intake, energy balance, and weight gain-have not been reported. To examine this, male C57BL/6J mice were fed a 10% or 60% kcal diet. After 4 weeks, the mice underwent an HTPT via poloxamer 407 intraperitoneal injections (1000 mg/kg). Weight gain, energy intake, and postabsorptive TAG levels normalized 7-10 days post-HTPT. The post-HTPT recovery of body weight and energy intake suggest that, in metabolic phenotyping studies, any additional sample collection should occur at least 7-10 days after the HTPT to reduce confounding effects. Diet-specific effects on HTP were also observed: HF-fed mice had reduced HTP, plasma TAG, and NEFA levels compared to controls. In conclusion, the current study highlights the procedural and physiological complexities associated with studying lipid metabolism using a HTPT in the DIO mouse model.

Effect of antisense oligonucleotides against cholesteryl ester transfer protein on the development of atherosclerosis in cholesterol-fed rabbits.

PubMed

Sugano, M; Makino, N; Sawada, S; Otsuka, S; Watanabe, M; Okamoto, H; Kamada, M; Mizushima, A

1998-02-27

Cholesteryl ester transfer protein (CETP) is the enzyme that facilitates the transfer of cholesteryl ester from high density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoproteins. However, the exact role of CETP in the development of atherosclerosis has not been determined. In the present study, we examined the effect of the suppression of increased plasma CETP by intravenous injection with antisense oligodeoxynucleotides (ODNs) against CETP targeted to the liver on the development of atherosclerosis in rabbits fed a cholesterol diet. The ODNs against rabbit CETP were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method to regulate liver gene expression. Twenty-two male Japanese White rabbits were used in the experiment. Eighteen animals were fed a standard rabbit chow supplemented with 0.3% cholesterol throughout the experiment for 16 weeks. At 8 weeks, they were divided into three groups (six animals in each group), among which the plasma total and HDL cholesterol concentrations did not significantly change. The control group received nothing, the sense group were injected with the sense ODNs complex, and the antisense group were injected with the antisense ODNs complex, respectively, for subsequent 8 weeks. ASOR. poly(L-lysine) ODNs complex were injected via the ear veins twice a week. Four animals were fed a standard rabbit diet for 16 weeks. The total cholesterol concentrations and the CETP mass in the animals injected with antisense ODNs were all significantly decreased in 12 and 16 weeks compared with those injected with sense ODNs and the control animals. The HDL cholesterol concentrations measured by the precipitation assay did not significantly change among the groups fed a cholesterol diet, and triglyceride concentrations did not significantly change in the four groups. However, at the end of the study, when the HDL cholesterol concentrations were measured after the isolation by ultracentrifugation and a column chromotography, they were significantly higher in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. A reduction of CETP mRNA and an increase of LDL receptor mRNA in the liver were observed in the animals injected with antisense ODNs compared with those injected with sense ODNs and the control animals. Aortic cholesterol contents and the aortic percentage lesion to total surface area were significantly lower in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. These findings showed for the first time that suppression of increased plasma CETP by the injection with antisense ODNs against CETP coupled to ASOR carrier molecules targeted to the liver could thus inhibit the atherosclerosis possibly by decreasing the plasma LDL + very low density lipoprotein (VLDL) cholesterol in cholesterol-fed rabbits.

Body Mass Index, Overweight, and Obesity in Swedish Women Born Post-term.

PubMed

Derraik, José G B; Lundgren, Maria; Cutfield, Wayne S; Ahlsson, Fredrik

2016-07-01

There is increasing evidence that post-term birth (≥42 weeks of gestation) is associated with adverse long-term outcomes. We assessed whether women born post-term displayed increased risk of overweight and obesity in adulthood. Data were collected at first antenatal visit (~10-12 weeks of gestation) on singleton Swedish women aged ≥18 years in 1991-2009 (mean age 26.1 years), who were born post-term (n = 27 153) or at term (37-41 weeks of gestation; n = 184 245). Study outcomes were evaluated for continuous associations with gestational age. Stratified analyses were carried out comparing women born post-term or at term. Analyses were also run with a 2-week buffer between groups to account for possible errors in gestational age estimation, comparing women born very post-term (≥43 weeks of gestation; n = 5761) to those born within a narrower term window (38-40 weeks of gestation; n = 130 110). Increasing gestational age was associated with greater adult weight and body mass index (BMI). Stratified analyses showed that women born post-term were 0.5 kg heavier and had BMI 0.2 kg/m(2) greater than those born at term. Differences were more marked between women born very post-term (≥43 weeks) vs. a narrower term group (38-40 weeks): 1.0 kg and 0.3 kg/m(2) . The adjusted relative risks of overweight/obesity and obesity in women born very post-term were 1.13 and 1.12 times higher, respectively, than in those born at term. Post-term birth is associated with greater BMI and increased risk of overweight and obesity in adulthood, particularly among women born ≥43 weeks of gestation. © 2016 John Wiley & Sons Ltd.

Effects of VPS extract of Coriolus versicolor on cancer of the large intestine using a serial sacrifice technique.

PubMed

Toth, Bela; Coles, Melissa; Lynch, James

2006-01-01

VPS, a hot water extract of the Coriolus versicolor mushroom, was given at a 2% dose level in the diet of female Swiss Webster CFW outbred mice in a serial sacrifice experiment. The mice were also administered either 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) as ten weekly subcutaneous (s.c) injections of 20 microg/g body weight or physiological saline (PS) as ten weekly (s.c) injections of 0.01 ml/g body weight. The animals were sacrificed at 26 weeks or 35 weeks after the first injection of 1,2-DMH or PS. The number of mice with large intestinal tumors and the total number of these tumors were: Group I (1,2-DMH), 29 and 438; Group 2 (VPS + 1,2-DMH), 29 and 344; Group 3 (VPS + PS), 0 and 0; and Group 4 (PS), I and 1, in the mice sacrificed at 26 weeks. The corresponding tumor incidences in mice sacrificed at 35 weeks were: Group 1 (1,2-DMH), 30 and 323; Group 2 (VPS + 1,2-DMH), 29 and 521; Group 3 (VPS + PS), 1 and 2; and Group 4 (PS), 0 and 0. Histopathologically, the tumors were diagnosed as polypoid adenomas and adenocarcinomas of the cecum, colon and rectum. Contrary to expectations, the VPS treatment enhanced the development of large intestinal tumors induced by 1,2-DMH in animals sacrificed at 35 weeks after the first injection of the carcinogen.

Evisceration With Injectable Hydrogel Implant in a Rabbit Model.

PubMed

Koreen, Irina V; McClintic, Elysa A; Mott, Ryan T; Stanton, Constance; Yeatts, R Patrick

To determine the safety, durability, and biocompatibility of 2.5% polyacrylamide hydrogel (Aquamid, Specialty European Pharma, Ltd., London, UK) as an injectable viscoelastic implant following evisceration in a rabbit model. The protocol was reviewed and approved by the Wake Forest Institutional Animal Care and Use Committee. Adult New Zealand rabbits underwent cornea-sparing evisceration of the right eye with injection of 2.5% polyacrylamide hydrogel implant. The rabbits were sacrificed after 2 weeks (n = 1), 5 weeks (n = 2), 12 weeks (n = 3), 25 weeks (n = 3), and 1 year (n = 3) to evaluate the implant volume and host reaction to the implant. Both eyes were enucleated and their diameters were measured. The eviscerated eyes were fixed in formalin and processed using routine histopathologic methods to assess inflammatory reaction and vascularization. The implant material was well tolerated with a moderate giant cell reaction seen at 6 weeks that improved over time. Extensive vascularization of the implant was noted starting at 6 weeks. There was excellent maintenance of globe volume that did not diminish over time. The relative diameters of the eviscerated eyes compared with control were 89 ± 6% (mean% ± SD) at 12 weeks (n = 3), 94 ± 2% at 25 weeks (n = 3), and 93 ± 4% at 1 year (n = 3). With further study, injectable 2.5% polyacrylamide hydrogel may provide an excellent alternative to solid orbital implants. The implant material was universally well tolerated and maintained appropriate volume in the orbit for the study period of 1 year. Extensive vascularization of the implant was noted indicating biointegration.

Clinical benefits of incorporating doxycycline into a canine heartworm treatment protocol.

PubMed

Nelson, C Thomas; Myrick, Elizabeth S; Nelson, Thomas A

2017-11-09

The objective of heartworm treatment is to improve the clinical condition of the patient and to eliminate pre-cardiac, juvenile, and adult worm stages with minimal complications. Pulmonary thromboembolisms are an inevitable consequence of worm death and can result in severe pulmonary reactions and even death of the patient. To minimize these reactions, various treatment protocols involving melarsomine, the only adulticidal drug approved by the US Food and Drug Administrations (FDA), in conjunction with macrocyclic lactone heartworm preventives and glucocorticosteroids have been advocated. The discovery of the bacterial endosymbiont Wolbachia in Dirofilaria immitis has led to several experimental studies examining the effects of administering doxycycline to reduce or eliminate Wolbachia organism. These studies have shown a decrease in gross and microscopic pathology of pulmonary parenchyma in experimental heartworm infections pretreated with doxycycline before melarsomine administration. Electronic medical records from a large veterinary practice in northeast Alabama were searched to identify dogs treated for heartworms with melarsomine from January 2005 through December 2012. The search was refined further to select for dogs that met the following criteria: 1) received two or three doses of ivermectin heartworm preventive prior to melarsomine injections, 2) received one injection of melarsomine followed by two injections 4 to 8 weeks later, and 3) were treated with prednisone following melarsomine injections. The dogs were then divided into those that also were treated with doxycycline 10 mg/kg BID for 4 weeks (Group A, n = 47) and those that did not receive doxycycline (Group B, n = 47). The medical notes of all 94 cases were then reviewed for comments concerning coughing, dyspnea, or hemoptysis in the history, physical exam template, or from telephone conversations with clients the week following each visit. Any dog that died within one year of treatment from either cardiovascular or pulmonary problems was noted. Dogs from Group A receiving doxycycline had fewer respiratory complications (6.52%) and heartworm disease-related deaths (0%) than Group B (19.14% and 4.25%, respectively). Although there are not enough cases to indicate statistical significance, the results strongly suggest that including doxycycline into canine heartworm treatment protocols decreases post-treatment complications and mortality in naturally infected clinical cases.

Evaluation of the effectiveness of lumbar interlaminar epidural injections in managing chronic pain of lumbar disc herniation or radiculitis: a randomized, double-blind, controlled trial.

PubMed

Manchikanti, Laxmaiah; Singh, Vijay; Falco, Frank J E; Cash, Kimberly A; Pampati, Vidyasagar

2010-01-01

The pathophysiology of lumbar radicular pain is the subject of ongoing research, with a reported prevalence of sciatica or radiculitis ranging from 1.2% to 43%. Among the numerous non-surgical interventions available, epidural injections are the most commonly performed interventions in the United States in managing chronic low back and lower extremity pain. A randomized, double-blind, controlled trial. An interventional pain management practice, a specialty referral center, a private practice setting in the United States. To evaluate the effectiveness of lumbar interlaminar epidural injections with local anesthetic, with or without steroids, in managing chronic low back and lower extremity pain secondary to disc herniation or radiculitis in providing effective and long-lasting pain relief. Patients were assigned to one of 2 groups with local anesthetic only or with local anesthetic mixed with non-particulate betamethasone. Randomization was performed by computer-generated random allocations sequence by simple randomization. Seventy patients were included in this analysis. Patient outcomes were measured at baseline, 3, 6, and 12 months post-treatment with the Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake. Decrease of > or = 50% of NRS scores and Oswestry scores were considered significant. Significant pain relief (> or = 50%) was seen at 12 months in 74% of patients in Group I and 86% in Group II, and 69% and 83% in ODI scores respectively. Significant differences were noted in pain relief characteristics at 6 months between Group I and Group II (p = 0.001) and functional status improvement was significantly better in Group II at 6 months and 12 months (p = 0.019 and 0.045). The overall average procedures per year were 4.3 in Group I and 4.2 in Group II with an average total relief per year of 42.2 +/- 10.5 weeks in Group I and 41.4 +/- 11.0 weeks in Group II over a period of 52 weeks in the successful group. The study limitations include the lack of a placebo group and the fact that this is a preliminary report of 35 patients in each group. Overall, 74% of patients in Group I without steroids and 86% in Group II with steroids with lumbar disc herniation or radiculitis might benefit from lumbar interlaminar epidural injections.

Comparative Efficacy of Platelet Rich Plasma Injection, Corticosteroid Injection and Ultrasonic Therapy in the Treatment of Periarthritis Shoulder.

PubMed

Kothari, Shashank Yeshwant; Srikumar, Venkataraman; Singh, Neha

2017-05-01

Periarthritis (PA) shoulder characterised by pain and restricted range of motion has a plethora of treatment options with inconclusive evidence. Platelet Rich Plasma (PRP) is an emerging treatment option and its efficacy needs to be examined and compared with other routine interventions. To assess the efficacy of PRP injection and compare it with corticosteroid injection and ultrasonic therapy in the treatment of PA shoulder. Patients with PA shoulder (n=195) were randomised to receive single injection of PRP (2 ml) or corticosteroid (80 mg of methylprednisolone) or ultrasonic therapy (seven sittings in two weeks; 1.5 W/cm 2 , 1 MHz, continuous mode). All participants were also advised to perform a home based 10 minute exercise therapy. The primary outcome measure was active range of motion of the shoulder. Secondary outcome measures used were Visual Analogue Scale (VAS) for pain and a shortened version of Disabilities of the Arm, Shoulder and Hand (QuickDASH) for function. Participants were evaluated at 0, 3, 6 and 12 weeks. Chi-square test, one way and repeated measures of ANOVA tests were used to determine significant differences. PRP treatment resulted in statistically significant improvements over corticosteroid and ultrasonic therapy in active as well as passive range of motion of shoulder, VAS and QuickDASH at 12 weeks. At six weeks, PRP treatment resulted in statistically significant improvements over ultrasonic therapy in VAS and QuickDASH. No major adverse effects were observed. This study demonstrates that single injection of PRP is effective and better than corticosteroid injection or ultrasonic therapy in treatment of PA shoulder.

Impact of the Mass Drug Administration for malaria in response to the Ebola outbreak in Sierra Leone.

PubMed

Aregawi, Maru; Smith, Samuel J; Sillah-Kanu, Musa; Seppeh, John; Kamara, Anitta R Y; Williams, Ryan O; Aponte, John J; Bosman, Andrea; Alonso, Pedro

2016-09-20

As emergency response to the Ebola epidemic, the Government of Sierra Leone and its partners implemented a large-scale Mass Drug Administration (MDA) with artesunate-amodiaquine (ASAQ) covering >2.7 million people in the districts hardest hit by Ebola during December 2014-January 2015. The World Health Organization (WHO) and the National Malaria Control Programme (NMCP) evaluated the impact of the MDA on malaria morbidity at health facilities and the number of Ebola alerts received at District Ebola Command Centres. The coverage of the two rounds of MDA with ASAQ was estimated by relating the number anti-malarial medicines distributed to the estimated resident population. Segmented time-series analysis was applied to weekly data collected from 49 primary health units (PHUs) and 11 hospitals performing malaria parasitological testing during the study period, to evaluate trends of malaria cases and Ebola alerts during the post-MDA weeks compared to the pre-MDA weeks in MDA- and non-MDA-cheifdoms. After two rounds of the MDA, the number of suspected cases tested with rapid diagnostic test (RDT) decreased significantly by 43 % (95 % CI 38-48 %) at week 1 and remained low at week 2 and 3 post-first MDA and at week 1 and 3 post-second MDA; RDT positive cases decreased significantly by 47 % (41-52 %) at week 1 post-first and remained lower throughout all post-MDA weeks; and the RDT test positivity rate (TPR) declined by 35 % (32-38 %) at week 2 and stayed low throughout all post-MDA weeks. The total malaria (clinical + confirmed) cases decreased significantly by 45 % (39-52 %) at week 1 and were lower at week 2 and 3 post-first MDA; and week 1 post-second MDA. The proportion of confirmed malaria cases (out of all-outpatients) fell by 33 % (29-38 %) at week 1 post-first MDA and were lower during all post-MDA weeks. On the contrary, the non-malaria outpatient cases (cases due to other health conditions) either remained unchanged or fluctuated insignificantly. The Ebola alerts decreased by 30 % (13-46 %) at week 1 post-first MDA and much lower during all the weeks post-second MDA. The MDA achieved its goals of reducing malaria morbidity and febrile cases that would have been potentially diagnosed as suspected Ebola cases with increased risk of nosocomial infections. The intervention also helped reduce patient case-load to the severely strained health services at the peak of the Ebola outbreak and malaria transmission. As expected, the effect of the MDA waned in a matter of few weeks and malaria intensity returned to the pre-MDA levels. Nevertheless, the approach was an appropriate public health intervention in the context of the Ebola epidemic even in high malaria transmission areas of Sierra Leone.

The efficacy of multiple versus single hyaluronic acid injections: a systematic review and meta-analysis.

PubMed

Concoff, Andrew; Sancheti, Parag; Niazi, Faizan; Shaw, Peter; Rosen, Jeffrey

2017-12-21

Intra-articular hyaluronic acid (IA-HA) is a common therapy used to treat knee pain and suppress knee inflammation in knee osteoarthritis (OA), typically prescribed in regimens ranging from a single injection to 5 weekly injections given once weekly. We conducted a systematic review to determine the efficacy of IA-HA, with subgroup analyses to explore the differences in knee pain and adverse events (AEs) across different dosing regimens. We conducted a systematic search of the literature to identify studies evaluating IA-HA for the management of knee OA compared to IA-saline. Primary outcome measure was the mean knee pain score at 13 Weeks (3 months) or 26 weeks (6 months). Secondary outcome was the number of treatment-related AEs and treatment-related serious adverse events (SAEs). We evaluated differences in levels of pain and AEs/SAEs between dosing regimens compared to IA-Saline. Thirty articles were included. Overall, IA-HA injections were associated with less knee pain compared to IA-Saline injections for all dosing regimens. 2-4 injections of IA-HA vs. IA-Saline produced the largest effect size at both 3-months and 6-months (Standard mean difference [SMD] = -0.76; -0.98 to -0.53, 95% CI, P < 0.00001, and SMD = -0.36; -0.63 to -0.09 95% CI, P = 0.008, respectively). Additionally, single injection studies yielded a non-significant treatment effect at 3 and 6 months, while ≥5 5 injections demonstrated a significant improvement in pain only at 6 months. Five or more injections of IA-HA were associated with a higher risk of treatment-related AEs compared to IA-Saline (Risk ratio [RR] = 1.67; 1.09 to 2.56 95% CI, p = 0.02), which was a result not seen within the 1 and 2-4 injection subgroups. Overall, 2-4 and ≥5 injection regimens provided pain relief over IA-Saline, while single injection did not. Intra-articular injections of HA used in a 2-4 injection treatment regimen provided the greatest benefit when compared to IA-Saline with respect to pain improvement in patients with knee OA, and was generally deemed safe with few to no treatment-related AEs reported across studies. Future research is needed to directly compare these treatment regimens.

Combination therapy with intra-articular injection of mesenchymal stem cells and articulated joint distraction for repair of a chronic osteochondral defect in the rabbit.

PubMed

Harada, Yohei; Nakasa, Tomoyuki; Mahmoud, Elhussein Elbadry; Kamei, Goki; Adachi, Nobuo; Deie, Masataka; Ochi, Mitsuo

2015-10-01

The present study investigated intra-articular injection of bone-marrow-derived mesenchymal stem cells (MSCs) combined with articulated joint distraction as treatment for osteochondral defects. Large osteochondral defects were created in the weight-bearing area of the medial femoral condyle in rabbit knees. Four weeks after defect creation, rabbits were divided into six groups: control group, MSC group, distraction group, distraction + MSC group, temporary distraction group, and temporary distraction + MSC group. Groups with MSC received intra-articular injection of MSCs. Groups with distraction underwent articulated distraction arthroplasty. Groups with temporary distraction discontinued the distraction after 4 weeks. The rabbits were euthanized at 4, 8, and 12 weeks after treatment except temporary distraction groups which were euthanized at only 12 weeks. Histological scores in the distraction + MSC group were significantly better than in the control, MSC group or distraction group at 4 and 8 weeks, but showed no further improvement. At 12 weeks, the temporary distraction + MSC group showed the best results, demonstrating hyaline cartilage repair with regeneration of the osteochondral junction. In conclusion, joint distraction with intra-articular injection of MSCs promotes early cartilage repair, and compressive loading of the repair tissue after temporary distraction stimulates articular cartilage regeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Hypothalamic AMPK-induced autophagy ameliorates hypercatabolism in septic rats by regulating POMC expression.

PubMed

Cao, Chun; Gao, Tao; Cheng, Yan; Cheng, Minhua; Su, Ting; Xi, Fengchan; Wu, Cuili; Yu, Wenkui

2018-03-18

Hypercatabolism plays a critical role in the pathogenesis of post-critical care debility in critical patients. Central nervous system may exerte a critical role in the regulation of hypercatabolism. However, little is known about the exact mechanisms of the central role. Here, we reported that actived hypothalamic AMP-activated protein kinase (AMPK)-induced autophagy modulated the expression of POMC to ameliorate hypercatabolism in septic rats. Firstly, rats were i.c.v. injected with the lentiviral vector containing shRNA against POMC. Two weeks after injections, rats were intraperitoneally injected with LPS or saline. Twenty-four hours later, blood, skeletal muscle and hypothalamus tissues were obtained. Hypercatabolism markers and neuropeptides expression were detected. Then, rats were injected with AICAR or saline into third ventricle and promptly intraperitoneally injected with LPS or saline. Twenty-four hours after infection, blood, skeletal muscle and hypothalamus tissues were obtained. Hypercatabolism, hypothalamic AMPK-induced autophagy markers and neuropeptides expression were also detected. Results showed that sepsis would decrease the level of hypothalamic autophagy accompany with the alterations of POMC expression and hypercatabolism. Knocking out hypothalamus POMC expression could significantly ameliorate hypercatabolism. Moreover, Central activation of AMPK-induced autophagy pathway via third ventricle injection of AICAR, an AMPK activator, could efficiently ameliorate hypercatabolism as well as attenuate the elevated POMC expression rather than other neuropeptides. Taken together, these results suggested that hypothalamic AMPK-autophagy pathway as a regulatory pathway for POMC expression was essential for hypercatabolism during sepsis. And hypothalamic AMPK-autophagy activation could attenuate the POMC expression to ameliorate hypercatabolism. Pharmaceuticals with the ability of activating hypothalamic AMPK-autophagy pathway may be a therapeutic potential for hypercatabolism in septic patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study.

PubMed

Powell, Jerry; Martinowitz, Uri; Windyga, Jerzy; Di Minno, Giovanni; Hellmann, Andrzej; Pabinger, Ingrid; Maas Enriquez, Monika; Schwartz, Lawrence; Ingerslev, Jørgen

2012-11-01

The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.

Cardiac Stem Cell Hybrids Enhance Myocardial Repair

PubMed Central

Quijada, Pearl; Salunga, Hazel T.; Hariharan, Nirmala; Cubillo, Jonathan D.; El-Sayed, Farid G.; Moshref, Maryam; Bala, Kristin M.; Emathinger, Jacqueline M.; La Torre, Andrea De; Ormachea, Lucia; Alvarez, Roberto; Gude, Natalie A.; Sussman, Mark A.

2015-01-01

Rationale Dual cell transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction improves myocardial repair and performance in large animal models relative to delivery of either cell population. Objective To demonstrate that CardioChimeras (CCs) formed by fusion between CPCs and MSCs have enhanced reparative potential in a mouse model of myocardial infarction relative to individual stem cells or combined cell delivery. Methods and Results Two distinct and clonally derived CCs, CC1 and CC2 were utilized for this study. CCs improved left ventricular anterior wall thickness (AWT) at 4 weeks post injury, but only CC1 treatment preserved AWT at 18 weeks. Ejection fraction was enhanced at 6 weeks in CCs, and functional improvements were maintained in CCs and CPC + MSC groups at 18 weeks. Infarct size was decreased in CCs, whereas CPC + MSC and CPC parent groups remained unchanged at 12 weeks. CCs exhibited increased persistence, engraftment, and expression of early commitment markers within the border zone relative to combinatorial and individual cell population-injected groups. CCs increased capillary density and preserved cardiomyocyte size in the infarcted regions suggesting CCs role in protective paracrine secretion. Conclusions CCs merge the application of distinct cells into a single entity for cellular therapeutic intervention in the progression of heart failure. CCs are a novel cell therapy that improves upon combinatorial cell approaches to support myocardial regeneration. PMID:26228030

Longitudinal in vivo imaging of retinal gliosis in a diabetic mouse model.

PubMed

Kumar, Saravana; Zhuo, Lang

2010-10-01

In this study, we visualize and quantify retinal gliosis in vivo for monitoring early diabetic retinopathy (DR) in a transgenic mouse model. Onset of diabetes was triggered via intraperitoneal injection of streptozotocin (STZ) into transgenic F1 hybrid (FVB/N × C57BL/6J) mice expressing green fluorescent protein (GFP) under the control of glial fibrillary acidic protein (GFAP) promoter. Retinal glial cells are imaged once pre-STZ treatment followed by weekly post-STZ imaging for five weeks using a confocal scanning laser ophthalmoscope. Mice develop diabetes one week after STZ induction as confirmed from the high blood glucose levels (>13.9 mmol/L). A significant increase is observed in the GFAP-GFP transgene expression from astrocytic cell bodies and processes as early as week 5 for the STZ-treated mice. Retinal astrocytes also undergo hyperplasia progressively from week 0 to 5. This precedes any structural abnormalities to the retinal vasculature. Immunohistochemistry (IHC) on retinal sections as well as quantitative RT-PCR of endogenous and transgene GFAP mRNA supports our in vivo observation. Our in vivo data correlates with clinical reports with regards to retinal gliosis-related inflammatory response during early diabetic retinopathy. This opens up the possibility of using in vivo molecular imaging of retinal glial cells as a platform for monitoring the efficacy of anti-DR drug candidates which intervene at an early stage.

Follow-up of cortical activity and structure after lesion with laser speckle imaging and magnetic resonance imaging in nonhuman primates

NASA Astrophysics Data System (ADS)

Peuser, Jörn; Belhaj-Saif, Abderraouf; Hamadjida, Adjia; Schmidlin, Eric; Gindrat, Anne-Dominique; Völker, Andreas Charles; Zakharov, Pavel; Hoogewoud, Henri-Marcel; Rouiller, Eric M.; Scheffold, Frank

2011-09-01

The nonhuman primate model is suitable to study mechanisms of functional recovery following lesion of the cerebral cortex (motor cortex), on which therapeutic strategies can be tested. To interpret behavioral data (time course and extent of functional recovery), it is crucial to monitor the properties of the experimental cortical lesion, induced by infusion of the excitotoxin ibotenic acid. In two adult macaque monkeys, ibotenic acid infusions produced a restricted, permanent lesion of the motor cortex. In one monkey, the lesion was monitored over 3.5 weeks, combining laser speckle imaging (LSI) as metabolic readout (cerebral blood flow) and anatomical assessment with magnetic resonance imaging (T2-weighted MRI). The cerebral blood flow, measured online during subsequent injections of the ibotenic acid in the motor cortex, exhibited a dramatic increase, still present after one week, in parallel to a MRI hypersignal. After 3.5 weeks, the cerebral blood flow was strongly reduced (below reference level) and the hypersignal disappeared from the MRI scan, although the lesion was permanent as histologically assessed post-mortem. The MRI data were similar in the second monkey. Our experiments suggest that LSI and MRI, although they reflect different features, vary in parallel during a few weeks following an excitotoxic cortical lesion.

Corticosteroid injection for adhesive capsulitis in primary care: a systematic review of randomised clinical trials

PubMed Central

Koh, Kim Hwee

2016-01-01

Adhesive capsulitis is a common cause of shoulder pain and limited movement. The objectives of this review were to assess the efficacy and safety of corticosteroid injections for adhesive capsulitis and to evaluate the optimum dose and anatomical site of injections. PubMed and CENTRAL databases were searched for randomised trials and a total of ten trials were included. Results revealed that corticosteroid injection is superior to placebo and physiotherapy in the short-term (up to 12 weeks). There was no difference in outcomes between corticosteroid injection and oral nonsteroidal anti-inflammatory drugs at 24 weeks. Dosages of intra-articular triamcinolone 20 mg and 40 mg showed identical outcomes, while subacromial and glenohumeral corticosteroid injections had similar efficacy. The use of corticosteroid injections is also generally safe, with infrequent and minor side effects. Physicians may consider corticosteroid injection to treat adhesive capsulitis, especially in the early stages when pain is the predominant presentation. PMID:27570870

Corticosteroid injection for adhesive capsulitis in primary care: a systematic review of randomised clinical trials.

PubMed

Koh, Kim Hwee

2016-12-01

Adhesive capsulitis is a common cause of shoulder pain and limited movement. The objectives of this review were to assess the efficacy and safety of corticosteroid injections for adhesive capsulitis and to evaluate the optimum dose and anatomical site of injections. PubMed and CENTRAL databases were searched for randomised trials and a total of ten trials were included. Results revealed that corticosteroid injection is superior to placebo and physiotherapy in the short-term (up to 12 weeks). There was no difference in outcomes between corticosteroid injection and oral nonsteroidal anti-inflammatory drugs at 24 weeks. Dosages of intra-articular triamcinolone 20 mg and 40 mg showed identical outcomes, while subacromial and glenohumeral corticosteroid injections had similar efficacy. The use of corticosteroid injections is also generally safe, with infrequent and minor side effects. Physicians may consider corticosteroid injection to treat adhesive capsulitis, especially in the early stages when pain is the predominant presentation. Copyright: © Singapore Medical Association.

Determination of the toxicity of intravitreal minocycline in rabbit eyes.

PubMed

Falavarjani, Khalil Ghasemi; Pourhabibi, Arash; Aghdam, Kaveh Abri; Hosseini, Seyed Bagher; Modarres, Mehdi; Pazouki, Abdolreza; Khanamiri, Hossein Nazari

2016-09-01

To evaluate the retinal toxicity of intravitreal minocycline in rabbit eyes. Intravitreal injection of minocycline with concentrations of 1000, 500, 250, 125 and 62.5 μg in 0.1 ml was performed in 10 New Zealand albino rabbits. Each concentration was injected into two rabbit eyes. For each dose, normal saline was injected in one contralateral eye and the other fellow eye remained non-injected. Electrophysiologic testing was performed before and 4 weeks after injections. The eyes were enucleated 4 weeks after injections and examined using light microscopy. The clinical examination was unremarkable after injections. Electroretinography recordings were significantly affected at all doses in at least one of the a- or b-waves of photopic or scotopic responses. Histopathologic examination revealed marked atrophy and loss of integrity in all retinal layers in all minocycline injected eyes. Contralateral eyes were normal. In our study, intravitreal minocycline was toxic to the retina in albino rabbits even at a concentration of 62.5 µg/0.1 ml.

The effect of platelet-rich plasma injection on lateral epicondylitis following failed conservative management.

PubMed

Brkljac, Milos; Kumar, Shyam; Kalloo, Dale; Hirehal, Kiran

2015-12-01

We assessed the effect PRP injection on pain and function in patients with lateral epicondylitis where conservative management had failed. We prospectively reviewed 34 patients. The mean follow-up was 26 weeks (range 6-114 weeks). We used the Oxford Elbow Score (OES) and progression to surgery to assess outcomes. 88.2% improved their OES. 8.8% reported symptom progression. One patient had no change. No patients suffered adverse reactions. Two patients underwent an open release procedure. One had the injection repeated. An injection of PRP improves pain and function in patients suffering from LE where conservative management has failed.

Efficacy of Combined Ultrasound-Guided Steroid Injection and Splinting in Patients With Carpal Tunnel Syndrome: A Randomized Controlled Trial.

PubMed

Wang, Jia-Chi; Liao, Kwong-Kum; Lin, Kon-Ping; Chou, Chen-Liang; Yang, Tsui-Fen; Huang, Yu-Fang; Wang, Kevin A; Chiu, Jan-Wei

2017-05-01

To compare the effectiveness of local steroid injection plus splinting with that of local steroid injection alone using clinical and electrophysiological parameters in patients with carpal tunnel syndrome (CTS). Randomized controlled study with 12 weeks of follow-up. Tertiary care center. Volunteer sample of patients (N=52) diagnosed with CTS. Participants were randomly assigned to the steroid injection group (n=26) or the steroid injection-plus-splinting group (n=26). Patients of both groups received ultrasound-guided steroid injection with 1mL of 10mg (10mg/mL) triamcinolone acetonide (Shincort) and 1mL of 2% lidocaine hydrochloride (Xylocaine). Participants in the second group also wore a volar splint in the neutral position while sleeping and also during daytime whenever possible for the 12-week intervention period. Participants were evaluated before the treatment and at 6 and 12 weeks after the onset of treatment. The primary outcome measure was Boston Carpal Tunnel Questionnaire scores. The secondary outcome measures were as follows: scores on the visual analog scale for pain; electrophysiological parameters, including median nerve distal motor latency, sensory nerve conduction velocity (SNCV), and compound muscle action potential and sensory nerve action potential (SNAP) amplitudes; and patient's subjective impression of improvement. At 12-week follow-up, improvements in symptom severity and functional status scores on the Boston Carpal Tunnel Questionnaire as well as SNCV and SNAP amplitudes were greater in the group that received steroid injection combined with splinting than in the group that received steroid injection alone. The between-group difference was .48 points (95% confidence interval [CI], .09-.88 points; P=.032) in the Symptom Severity Scale score, .37 points (95% CI, .06-.67 points; P=.019) in the Functional Status Scale score, 3.38m/s (95% CI, 0.54-6.22m/s; P=.015) in the SNCV amplitude, and 3.21μV (95% CI, 0.00-6.46μV; P=.025) in the SNAP amplitude. In people with CTS, steroid injection combined with splinting resulted in modestly greater reduction of symptoms, superior functional recovery, and greater improvement in nerve function at 12-week follow-up as compared with steroid injection alone. However, these small differences are of unclear clinical significance. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Brain-midgut short neuropeptide F mechanism that inhibits digestive activity of the American cockroach, Periplaneta americana upon starvation.

PubMed

Mikani, Azam; Wang, Qiu-Shi; Takeda, Makio

2012-03-01

Immunohistochemical reactivity against short neuropeptide F (sNPF) was observed in the brain-corpus cardiacum and midgut paraneurons of the American cockroach, Periplaneta americana. Four weeks of starvation increased the number of sNPF-ir cells in the midgut epithelium but the refeeding decreased the number in 3h. Dramatic rises in sNPF contents in the midgut epithelium and hemolymph of roaches starved for 4 weeks were confirmed by ELISA. Starvation for 4 weeks reduced α-amylase, protease and lipase activities in the midgut of P. americana but refeeding restored these to high levels. Co-incubation of dissected midgut with sNPF at physiological concentrations inhibited α-amylase, protease and lipase activities. sNPF injection into the hemocoel led to a decrease in α-amylase, protease and lipase activities, whereas PBS injection had no effects. The injection of d-(+)-trehalose and l-proline into the hemocoel of decapitated adult male cockroaches that had been starved for 4 weeks had no effect on these digestive enzymes. However, injection into the hemocoel of head-intact starved cockroaches stimulated digestive activity. Injection of d-(+)-trehalose and l-proline into the lumen of decapitated cockroaches that had been starved for 4 weeks increased enzymes activities and suppressed sNPF in the midgut. Our data indicate that sNPF from the midgut paraneurons suppresses α-amylase, protease and lipase activities during starvation. Injection of d-(+)-trehalose/l-proline into the hemocoel of head-intact starved cockroach decreased the hemolymph sNPF content, which suggests that sNPF could be one of the brain factors, demonstrating brain-midgut interplay in the regulation of digestive activities and possibly nutrition-associated behavioral modifications. Copyright © 2011 Elsevier Inc. All rights reserved.

Golimumab, a human antibody to tumour necrosis factor α given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study

PubMed Central

Keystone, E C; Genovese, M C; Klareskog, L; Hsia, E C; Hall, S T; Miranda, P C; Pazdur, J; Bae, S-C; Palmer, W; Zrubek, J; Wiekowski, M; Visvanathan, S; Wu, Z; Rahman, M U

2009-01-01

Objective: The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. Methods: Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n  =  133), golimumab 100 mg injections plus placebo capsules (group 2, n  =  133), golimumab 50 mg injections plus methotrexate capsules (group 3, n  =  89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n  =  89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24. Results: The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively. Conclusion: The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function. PMID:19066176

Conservative Treatment of Ankle Osteoarthritis: Can Platelet-Rich Plasma Effectively Postpone Surgery?

PubMed

Repetto, Ilaria; Biti, Besmir; Cerruti, Paola; Trentini, Roberto; Felli, Lamberto

Osteoarthritis is the most common and disabling of the orthopedic diseases. Currently, the conservative treatment of osteoarthritis is limited to symptomatic treatment, whose goal is to improve function and pain control. Ankle osteoarthritis is relatively uncommon, in contrast to osteoarthritis of the hip and knee, and the therapeutic options (both pharmacologic and surgical) are limited, with surgery providing poorer and less predictable results. The effectiveness of platelet-rich plasma injections for osteoarthritis is still controversial, especially so for ankle arthritis, owing to the lack of evidence in the present data. We retrospectively evaluated the mid- to long-term clinical results (mean follow-up of 17.7 months) for platelet-rich plasma injections in 20 patients (20 ankles) with ankle osteoarthritis. We evaluated the presence of pain using the visual analog scale, function using the Foot and Ankle Disability Index, and subjective satisfaction. The pre- and post-treatment scores, obtained from the clinical records and from telephone interviews during the follow-up period, were compared using the Student t test. We found a strong positive effect for 4 platelet-rich plasma injections (injected once a week) on pain (p = .0001) and function (p = .001), with 80% of patients very satisfied and satisfied, and only 2 patients (10%) required surgery because of early treatment failure. These results suggest that the use of platelet-rich plasma injection is a valid and safe alternative to postpone the need for surgery. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Chronic low-grade postoperative endophthalmitis in a child with Marfan syndrome

PubMed Central

Khurram Butt, Darakhshanda; Scott, Robert A; Upendran, Muralidharan R

2017-01-01

This case report describes a 9-year-old male who presented to the emergency department with 2 days’ history of left painful red eye. On initial examination, his outside medical records indicated that he had bilateral subluxated lenses and had undergone left eye lensectomy with glued intrascleral fixation of an intraocular lens 8 weeks earlier. Vision in left eye was poor from first postoperative day but with no undue pain or redness, and poor vision was attributed to possible vitreous bleed. Subsequent postoperative course was uneventful. He was discharged from ophthalmic care on topical steroids and antibiotic drops, one week postsurgery. The eye was healing well until he developed pain, for which ophthalmic care was sought. He underwent anterior chamber tap with intravitreal injections. Aqueous samples were positive for Staphylococcus aureus DNA by polymerase chain reaction. Post vitrectomy and implant removal, his recovery was good and vision improved to 0.50 LogMar with aphakic correction. PMID:29180908

One Minute, Sub-One-Watt Photothermal Tumor Ablation Using Porphysomes, Intrinsic Multifunctional Nanovesicles

PubMed Central

Jin, Cheng S.; Lovell, Jonathan F.; Zheng, Gang

2013-01-01

We recently developed porphysomes as intrinsically multifunctional nanovesicles. A photosensitizer, pyropheophorbide α, was conjugated to a phospholipid and then self-assembled to liposome-like spherical vesicles. Due to the extremely high density of porphyrin in the porphyrin-lipid bilayer, porphysomes generated large extinction coefficients, structure-dependent fluorescence self-quenching, and excellent photothermal efficacy. In our formulation, porphysomes were synthesized using high pressure extrusion, and displayed a mean particle size around 120 nm. Twenty-four hr post-intravenous injection of porphysomes, the local temperature of the tumor increased from 30 °C to 62 °C rapidly upon one minute exposure of 750 mW (1.18 W/cm2), 671 nm laser irradiation. Following the complete thermal ablation of the tumor, eschars formed and healed within 2 weeks, while in the control groups the tumors continued to grow and all reached the defined end point within 3 weeks. These data show how porphysomes can be used as potent photothermal therapy (PTT) agents. PMID:24084712

Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs.

PubMed

Guarnieri, Michael; Tyler, Betty M; Detolla, Louis; Zhao, Ming; Kobrin, Barry

2014-01-01

Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Drug implants can retain significant and unintended reservoirs of drugs.

Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

PubMed Central

Guarnieri, Michael; Tyler, Betty M.; DeTolla, Louis; Zhao, Ming; Kobrin, Barry

2014-01-01

Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs. PMID:24459402

Completion of five years of safe CO2 injection and transition into the post-closure phase at the Ketzin pilot site

NASA Astrophysics Data System (ADS)

Martens, Sonja; Moeller, Fabian; Streibel, Martin; Liebscher, Axel; Ketzin Group

2014-05-01

The injection of CO2 at the Ketzin pilot site in Germany ended after five years in August 2013. We present the key results from site operation and outline future activities within the post-closure phase. From June 2008 onwards, a total amount of 67 kt of CO2 was safely injected into a saline aquifer (Upper Triassic sandstone) at a depth of 630 m - 650 m. The CO2 used was mainly of food grade quality (purity > 99.9%). In addition, 1.5 kt of CO2 from the pilot capture facility "Schwarze Pumpe" (power plant CO2 with purity > 99.7%) was injected in 2011. During regular operation, the CO2 was pre-heated on-site to 45°C before injection in order to avoid pressure build-up within the reservoir. During the final months of injection a "cold-injection" experiment with a stepwise decrease of the injection temperature down to 10°C was conducted between March and July 2013. In summer 2013, the injection of a mixture of 95% CO2 and 5% N2 was also tested. After ceasing the injection in August the injection facility and pipeline were removed in December 2013. Geological storage of CO2 at the Ketzin pilot site has so far proceeded in a safe and reliable manner. As a result of one of the most comprehensive R&D programs worldwide, a combination of different geochemical and geophysical monitoring methods is able to detect even small quantities of CO2 and map their spatial extent. After the cessation of CO2 injection a series of activities and further investigations are involved in the post-closure phase. The aim is that Ketzin will for the first time ever close the complete life-time cycle of a CO2 storage site at pilot scale. The five wells (1 injection/observation well, 4 pure observation wells) will be successively abandoned within the next few years while monitoring is continuing. The partial plugging of one observation well in the reservoir section was already completed in fall 2013. The new four-years project COMPLETE (CO2 post-injection monitoring and post-closure phase at the Ketzin pilot site) started in January 2014. Activities within COMPLETE include R&D work on well integrity, post-closure monitoring as well as two field experiments. One is a back-production test of the CO2 aiming at information on the physicochemical properties of the back-produced CO2 as well as the pressure response of the reservoir. The other experiment will focus on brine injection into the CO2 storage reservoir in order to study e.g. the residual gas saturation. Public outreach has been a key element for the project from the very beginning and accompanies the research on CO2 storage at Ketzin since 2004. Thus dissemination (e.g. www.co2ketzin.de) and activities at the visitor centre at the pilot site will continue within COMPLETE and along the entire life cycle of the Ketzin project.

Alternative early life vaccination programs for companion animals.

PubMed

Poulet, H

2007-07-01

An experimental challenge study of multicomponent vaccination of kittens is reported. Seven-to-nine week old, specific pathogen-free kittens received two injections (4 weeks apart) of non-adjuvanted, multicomponent vaccine formulated at the minimum protective dose. Kittens were challenged at 4 weeks or 1 year post-vaccination with individual infectious agents. Vaccination induced complete protection against challenge from feline parvovirus on both occasions, but at 1 year, the protection against feline herpesvirus, feline calicivirus and Chlamydophila felis was not as strong as 4 weeks after vaccination. This demonstration of a decline in protective immunity at the normal time of administration of the first booster vaccine suggests that earlier administration of this booster (at 4-6 months of age) may provide better protection. The effect of maternally derived antibody (MDA) on kitten vaccination was determined by conducting an identical experiment but with kittens born to queens vaccinated during pregnancy. Serum antibody titres to specific vaccine components were measured in these kittens on day 0 (time of first vaccination), day 28 (time of second vaccination) and day 42. There was heterogeneity in transfer of MDA to kittens within a litter, and between litters. MDA may neutralize the serological response of kittens on the first, and occasionally the second, occasion of vaccination when vaccination is performed at 8 and 12 weeks of age. This finding underpins recent recommendations that the final vaccination in the primary series be administered at 16 weeks of age.

[Intra-articular injections of triamcinolone hexacetonide in rheumatoid arthritis: short and long-term improvement predictors].

PubMed

Furtado, Rita Nely Vilar; Machado, Flavia Soares; Luz, Karine Rodrigues da; Santos, Marla Francisca dos; Konai, Monique Sayuri; Lopes, Roberta Vilela; Natour, Jamil

2015-01-01

Identify good response predictors to intra-articular injection (IAI) with triamcinolone hexacetonide (TH). This study was carried out in rheumatoid arthritis (RA) patients (American College of Rheumatology criteria) submitted to IAI (mono, pauci or polyarticular injection). A "blinded" observer prospectively evaluated joints at one week (T1), four weeks (T4), twelve weeks (T12) and 24 weeks (T24) after IAI. Outcome measurements included Visual Analogue Scale (0-10 cm) at rest, in movement and for swollen joints. Clinical, demographic and variables related to injection at baseline were analyzed according to IAI response. We studied 289 patients with RA (635 joints) with a mean age of 48.7 years (±10.68), 48.5% of them Caucasians, VAS for global pain=6.52 (±1.73). Under univariate analysis, the variables relating the best responses following IAI (improvement > 70%) were: "elbow and metacarpophalangeal (MCP) IAI, and functional class II". Under multivariate analysis, "males" and "non-whites" were the predictors with the best response to IAI at T4, while "elbow and MCP IAI", "polyarticular injection", "use of methotrexate" and "higher total dose of TH" obtained the best response at T24. Several predictors of good response to IAI in patients with RA were identified. The best-response predictors for TH IAI of long term were "apply elbow and MCP IAI" and "apply polyarticular injection". Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

In vivo cartilage formation using chondrogenic-differentiated human adipose-derived mesenchymal stem cells mixed with fibrin glue.

PubMed

Jung, Sung-No; Rhie, Jong Won; Kwon, Ho; Jun, Young Joon; Seo, Je-Won; Yoo, Gyeol; Oh, Deuk Young; Ahn, Sang Tae; Woo, Jihyoun; Oh, Jieun

2010-03-01

Human adipose-derived mesenchymal stem cells (MSCs) were differentiated into chondrogenic MSCs, and fibrin glue was used together to explore the feasibility of whether cartilages can be generated in vivo by injecting the differentiated cells. Mesenchymal stem cells extracted from human adipose were differentiated into chondrogenic MSCs, and such differentiated cells mixed with fibrin glue were injected subcutaneously into the back of the nude mouse. In addition to visual evaluation of the tissues formed after 4, 8, and 12 weeks, hematoxylin-eosin staining, Masson trichrome staining, measurement of glycosaminoglycan concentration using dimethylmethylene blue, agreecan through reverse transcriptase-polymerase chain reaction, type II collagen, and expression of SOX-9 were verified. Moreover, the results were compared with 2 groups of controls: 1 control group that received only injection of chondrogenic-differentiated MSC and the supporting control group that received only fibrin glue injection. For the experimental group, cartilage-like tissues were formed after 4, 8, and 12 weeks. Formation of cartilage tissues was not observed in any of 4, 8, and 12 weeks of the control group. The supporting control group had only a small structure formation after 4 weeks, but the formed structure was completely decomposed by the 8th and 12th weeks. The range of staining dramatically increased with time at 4, 8, and 12 weeks in Masson trichrome staining. The concentration of glycosaminoglycan also increased with time. The increased level was statistically significant with more than 3 times more after 8 weeks compared with 4 weeks and more than 2 times more after 12 weeks compared with 8 weeks. Also, in reverse transcriptase-polymerase chain reaction at 4, 8, and 12 weeks, all results expressed a cartilage-specific gene called aggrecan, type II collagen, and SOX-9. The study verified that the chondrogenic-differentiated MSCs derived from human adipose tissues with fibrin glue can proliferate and form new cartilage. Our findings suggest that formation of cartilages in vivo is possible.

Indirect comparisons of efficacy and weekly factor consumption during continuous prophylaxis with recombinant factor VIII Fc fusion protein and conventional recombinant factor VIII products.

PubMed

Iorio, A; Krishnan, S; Myrén, K J; Lethagen, S; McCormick, N; Yermakov, S; Karner, P

2017-05-01

Recombinant factor VIII (rFVIII) products with extended half-lives have the potential to improve adherence and outcomes in haemophilia beyond the results obtained with conventional rFVIII products. In the absence of head-to-head comparisons, annualized bleed rates (ABRs) and weekly factor consumption with rFVIII Fc fusion protein (rFVIIIFc) and conventional rFVIII products were indirectly compared using studies of continuous prophylaxis. A systematic literature review was conducted to identify studies of rFVIII products for comparison with rFVIIIFc in the continuous prophylactic treatment of previously treated adolescents and adults with moderate and severe haemophilia A. Mean ABRs were compared between rFVIIIFc and individual rFVIII studies and between rFVIIIFc and a pooled measure for rFVIII estimated by meta-analysis. Comparisons of factor consumption were based on mean or median weekly factor consumption. Results from seven studies of conventional rFVIII products (injections 2-4 times week -1 ) were compared with rFVIIIFc (injections 1.4-2.4 times week -1 ). The pooled mean ABR for rFVIII products was significantly higher compared with rFVIIIFc (difference = 2.0; P = 0.007). Compared with most rFVIII studies, the reported weekly factor consumption was lower with rFVIIIFc [mean differences = 15.5-21.8 IU kg -1 week -1 (17-26%); median differences = 12.7-29.8 IU kg -1 week -1 (16-37%)]. In one comparison, mean weekly factor consumption with rFVIII was significantly lower but mean ABR was significantly higher than rFVIIIFc. Prophylaxis with rFVIIIFc may be associated with improved bleeding rates and lower weekly factor consumption than more frequently injected rFVIII products. Relative to rFVIII products with similar bleeding rates, results indicate that rFVIIIFc is associated with reduced weekly factor consumption while requiring fewer prescribed injections. © 2017 John Wiley & Sons Ltd.

Interferon Beta-1a Subcutaneous Injection

MedlinePlus

... course of disease where symptoms flare up from time to time) of multiple sclerosis (MS, a disease in which ... under the skin). It is usually injected three times a week. You should inject this medication on ...

Implications of poly(N-isopropylacrylamide)-g-poly(ethylene glycol) with codissolved brain-derived neurotrophic factor injectable scaffold on motor function recovery rate following cervical dorsolateral funiculotomy in the rat

PubMed Central

Grous, Lauren Conova; Vernengo, Jennifer; Jin, Ying; Himes, B. Timothy; Shumsky, Jed S.; Fischer, Itzhak; Lowman, Anthony

2016-01-01

Object In a follow-up study to their prior work, the authors evaluated a novel delivery system for a previously established treatment for spinal cord injury (SCI), based on a poly(N-isopropylacrylamide) (PNIPAAm), lightly cross-linked with a polyethylene glycol (PEG) injectable scaffold. The primary aim of this work was to assess the recovery of both spontaneous and skilled forelimb function following a cervical dorsolateral funiculotomy in the rat. This injury ablates the rubrospinal tract (RST) but spares the dorsal and ventral corticospinal tract and can severely impair reaching and grasping abilities. Methods Animals received an implant of either PNIPAAm-g-PEG or PNIPAAm-g-PEG + brain-derived neurotrophic factor (BDNF). The single-pellet reach-to-grasp task and the staircase-reaching task were used to assess skilled motor function associated with reaching and grasping abilities, and the cylinder task was used to assess spontaneous motor function, both before and after injury. Results Because BDNF can stimulate regenerating RST axons, the authors showed that animals receiving an implant of PNIPAAm-g-PEG with codissolved BDNF had an increased recovery rate of fine motor function when compared with a control group (PNIPAAm-g-PEG only) on both a staircase-reaching task at 4 and 8 weeks post-SCI and on a single-pellet reach-to-grasp task at 5 weeks post-SCI. In addition, spontaneous motor function, as measured in the cylinder test, recovered to preinjury values in animals receiving PNIPAAm-g-PEG + BDNF. Fluorescence immunochemistry indicated the presence of both regenerating axons and BDA-labeled fibers growing up to or within the host-graft interface in animals receiving PNIPAAm-g-PEG + BDNF. Conclusions Based on their results, the authors suggest that BDNF delivered by the scaffold promoted the growth of RST axons into the lesion, which may have contributed in part to the increased recovery rate. PMID:23581453

Concentration of ofloxacin in canine prostate tissue and prostate fluid after intraprostatic injection of biodegradable sustained-releasing microspheres containing ofloxacin.

PubMed

Bahk, J Y; Hyun, J S; Lee, J Y; Kim, J; Cho, Y H; Lee, J H; Park, J S; Kim, M O

2000-05-01

Excellent treatment results in chronic prostatitis by direct intra-prostatic injection of antibiotic were reported several decades ago with only minimal scientific background. We examined the distribution, in prostatic tissue and fluid, of the antibiotic in canines after intra-prostatic injection of biodegradable sustained-releasing microspheres containing 12 mg. of ofloxacin. A total of 36 male dogs, 12 controls and 24 experimental, older than 2 years, were used. Experimental dogs were given biodegradable sustained releasing microspheres containing ofloxacin 12 mg. and poly(D,L-lactic) acid 28 mg., designed to release over more than a 4 week period. The 12 control animals were divided into 2 groups, and oral ofloxacin 100 mg. was given twice a day for 2 and 4 weeks. The 24 experimental animals were divided into 4 subgroups of 6 dogs each, 4 for prostatic tissue and 2 for prostatic fluid level of ofloxacin determination. Anesthesia was initiated with ketamine HCl and xylazine, and maintained with intermittent ketamine HCl. In the experimental groups, 1 ml. of resolved formula was injected into one lobe of surgically exposed prostates. The concentration of ofloxacin was measured by high performance liquid chromatography (HPLC) of blood, prostatic tissue and prostatic fluid. Pilocarpine 0.5 mg./kg. was used for the collection of the prostatic fluid. The total ofloxacin of controls were 2,800 (2 weeks) and 5,600 (4 weeks) mg. In control groups, tissue concentrations of ofloxacin were relatively even at all segments of prostate, 7.4 +/- 0.8 (2 weeks) and 9.2 +/- 1.1 microg./ml. (4 weeks). The blood level ranged between 3.6 to 5.1 microg./ml. The prostatic fluid level ranged from 3.1 to 5.7 microg. /ml. In the experimental groups, the tissue levels of ofloxacin were 10.5 +/- 3.0 (1 week), 13.8 +/- 4.5 (2 weeks), 7.1 +/- 0.9 (3 weeks) and 7.7 +/- 3.0 microg./ml. (4 weeks) in the injected lobe. The opposite lobes were 8.0 +/- 1.1 (1 week), 10.2 +/- 4.2 (2 weeks), 5. 1 +/- 1.4 (3 weeks) and 7.6 +/- 0.8 (4 weeks) microg./ml. The blood level in the experimental groups ranged between 0.16 to 0.59 microg./ml. The prostate fluid level ranged from 2.9 to 6.1 microg./ml. in 8 dogs. Upon pathologic examination, the microspheres were interposed between prostate stroma and their size was reduced over time. Our study indicates that there is communication between the right and left prostate lobes. Direct injection of biodegradable sustained releasing ofloxacin formula into the prostate may be a substitute for long term antibiotic medication in humans for chronic prostatitis in the future without hurting the minimal inhibitory concentration(MIC)90.

Presence of stem/progenitor cells in the rat penis.

PubMed

Lin, Guiting; Alwaal, Amjad; Zhang, Xiaoyu; Wang, Jianwen; Wang, Lin; Li, Huixi; Wang, Guifang; Ning, Hongxiu; Lin, Ching-Shwun; Xin, Zhongcheng; Lue, Tom F

2015-01-15

Tissue resident stem cells are believed to exist in every organ, and their identification is commonly done using a combination of immunostaining for putative stem cell markers and label-retaining cell (LRC) strategy. In this study, we employed these approaches to identify potential stem cells in the penis. Newborn rats were intraperitoneally injected with thymidine analog, 5-ethynyl-2-deoxyuridine (EdU), and their penis was harvested at 7 h, 3 days, 1 week, and 4 weeks. It was processed for EdU stains and immunofluorescence staining for stem cell markers A2B5, PCNA, and c-kit. EdU-positive cells were counted for each time point and co-localized with each stem cell marker, then isolated and cultured in vitro followed by their characterization using flowcytometry and immunofluorescence. At 7 h post-EdU injection, 410 ± 105.3 penile corporal cells were labeled in each cross-section (∼28%). The number of EdU-positive cells at 3 days increased to 536 ± 115.6, while their percentage dropped to 25%. Progressively fewer EdU-positive cells were present in the sacrificed rat penis at longer time points (1 and 4 weeks). They were mainly distributed in the subtunic and perisinusoidal spaces, and defined as subtunic penile progenitor cells (STPCs) and perisinusoidal penile progenitor cells (PPCs). These cells expressed c-kit, A2B5, and PCNA. After culturing in vitro, only ∼0.324% corporal cells were EdU-labeled LRCs and expressed A2B5/PCNA. Therefore, labeling of penis cells by EdU occurred randomly, and label retaining was not associated with expression of c-kit, A2B5, or PCNA. The penile LRCs are mainly distributed within the subtunic and perisinusoidal space.

Chronic liver injury promotes hepatocarcinoma cells seeding and growth, associated with the infiltration by macrophages.

PubMed

Delire, Bénédicte; Henriet, Patrick; Lemoine, Pascale; Leclercq, Isabelle A; Stärkel, Peter

2018-05-04

Ninety percent of hepatocarcinoma (HCC) develop in a chronically damaged liver. The interactions between non tumor stromal components, especially macrophages, and the cancer cells are still incompletely understood. Our aim was to determine whether a chronically injured liver represents a favorable environment for the seeding and growth of HCC cells, and to evaluate the potential roles of macrophages infiltrated within the tumor. HCC cells were injected into the liver in healthy mice (healthy liver group-HL) and in mice chronically treated with CCl 4 for 7 weeks (CCl 4 7w group). Livers were examined for the presence of tumor 2 weeks post injection. Tumor and non tumor tissues were analyzed for macrophages infiltration, origin (monocytes-derived vs resident macrophages) and polarization state, and matrix metalloproteinases (MMPs) production. Fifty-three percent of mice developed neoplastic lesion in the HL group while a tumor lesion was found in all livers in the CCl 4 7w group. Macrophages infiltrated more deeply the tumors of the CCl 4 7weeks group. Evaluation of factors involved in the recruitment of macrophages and of markers of their polarization state was in favor of prominent infiltration of M2 pro-tumor monocytes-derived macrophages inside the tumors developing in a chronically injured liver. MMP-2 and -9 production, attributed to M2 pro-tumor macrophages, was significantly higher in the tumors of the CCl 4 7w group. Chronic liver damage promotes cancer development in our model. Our results suggest that an injured background favors the infiltration of M2 pro-tumor monocytes-derived macrophages. These secrete MMP-2 and MMP-9 that promote tumor progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Hydraulic distension of the knee: a novel treatment for arthrofibrosis after total knee replacement (case series).

PubMed

Formby, Peter M; Donohue, Michael A; Cannova, Christopher J; Caulfield, J Patrick

2016-06-01

Arthrofibrosis following total knee arthroplasty (TKA) is a common problem, which can be frustrating to both the patient and treating physician and can dramatically compromise post-operative function. Current treatment options for TKA arthrofibrosis include watchful waiting, injections, physical therapy, manipulation under anaesthesia, arthroscopic/open lysis of adhesions and revision surgery. We present a novel technique to treat acute and chronic stiffness following TKA, which we call hydraulic distension. A retrospective pre- and post-operative inpatient and outpatient record review of three patients treated with hydraulic distension for arthrofibrosis following TKA at a single institution. Three patients with a mean age of 74 years (68-78) underwent hydraulic distension of the knee at a mean of 23.4 ± 18.4 months (9 weeks to 36 months) following primary TKA. The mean pre-distension maximum flexion was 86.7 ± 10.4°, and the mean post-distension flexion was 110 ± 13.2° (23.3° increase). The patients maintained a mean 110 ± 20° flexion (23.3° increase) at a mean follow-up of 11.7 months (1 week to 29 months). There were no complications. We present a novel technique for managing arthrofibrosis following TKA that has not been previously reported. This is an effective, safe procedure, with our patients experiencing a mean 23° increased knee flexion at the most recent follow-up. Published 2016. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Effect of High-Volume Injection, Platelet-Rich Plasma, and Sham Treatment in Chronic Midportion Achilles Tendinopathy: A Randomized Double-Blinded Prospective Study.

PubMed

Boesen, Anders Ploug; Hansen, Rudi; Boesen, Morten Ilum; Malliaras, Peter; Langberg, Henning

2017-07-01

Injection therapies are often considered alongside exercise for chronic midportion Achilles tendinopathy (AT), although evidence of their efficacy is sparse. To determine whether eccentric training in combination with high-volume injection (HVI) or platelet-rich plasma (PRP) injections improves outcomes in AT. Randomized controlled trial; Level of evidence, 1. A total of 60 men (age, 18-59 years) with chronic (>3 months) AT were included and followed for 6 months (n = 57). All participants performed eccentric training combined with either (1) one HVI (steroid, saline, and local anesthetic), (2) four PRP injections each 14 days apart, or (3) placebo (a few drops of saline under the skin). Randomization was stratified for age, function, and symptom severity (Victorian Institute of Sports Assessment-Achilles [VISA-A]). Outcomes included function and symptoms (VISA-A), self-reported tendon pain during activity (visual analog pain scale [VAS]), tendon thickness and intratendinous vascularity (ultrasonographic imaging and Doppler signal), and muscle function (heel-rise test). Outcomes were assessed at baseline and at 6, 12, and 24 weeks of follow-up. VISA-A scores improved in all groups at all time points ( P < .05), with greater improvement in the HVI group (mean ± SEM, 6 weeks = 27 ± 3 points; 12 weeks = 29 ± 4 points) versus PRP (6 weeks = 14 ± 4; 12 weeks = 15 ± 3) and placebo (6 weeks = 10 ± 3; 12 weeks = 11 ± 3) at 6 and 12 weeks ( P < .01) and in the HVI (22 ± 5) and PRP (20 ± 5) groups versus placebo (9 ± 3) at 24 weeks ( P < .01). VAS scores improved in all groups at all time points ( P < .05), with greater decrease in HVI (6 weeks = 49 ± 4 mm; 12 weeks = 45 ± 6 mm; 24 weeks = 34 ± 6 mm) and PRP (6 weeks = 37 ± 7 mm; 12 weeks = 41 ± 7 mm; 24 weeks = 37 ± 6 mm) versus placebo (6 weeks = 23 ± 6 mm; 12 weeks = 30 ± 5 mm; 24 weeks = 18 ± 6 mm) at all time points ( P < .05) and in HVI versus PRP at 6 weeks ( P < .05). Tendon thickness showed a significant decrease only in HVI and PRP groups during the intervention, and this was greater in the HVI versus PRP and placebo groups at 6 and 12 weeks ( P < .05) and in the HVI and PRP groups versus the placebo group at 24 weeks ( P < .05). Muscle function improved in the entire cohort with no difference between the groups. Treatment with HVI or PRP in combination with eccentric training in chronic AT seems more effective in reducing pain, improving activity level, and reducing tendon thickness and intratendinous vascularity than eccentric training alone. HVI may be more effective in improving outcomes of chronic AT than PRP in the short term. Registration: NCT02417987 ( ClinicalTrials.gov identifier).

Clinical Outcomes of Intravitreal Preservative-Free Triamcinolone Preparation (Triesence®) for Cystoid Macular Oedema and Inflammation in Patients with Uveitis.

PubMed

Steeples, Laura R; Anand, Nitin; Moraji, Jiten; Jones, Nicholas P

2017-03-20

To assess the outcomes of intravitreal benzyl alcohol-free triamcinolone acetonide suspension in uveitis-related macular oedema. Single-center retrospective cohort study of 66 injections to 44 eyes of 40 patients. Uveitis diagnosis, systemic and local therapy, intraocular pressure (IOP), central retinal thickness (CRT), number of injections, time to re-injection and side-effects were noted during 6-months minimum follow-up. Sixty eight percent of eyes received a single injection. 18% required 2 injections, and 13% received ≥3 injections with mean time to second and third injections of 25.5 and 52.7 weeks, respectively. 90% of injections were unilateral. Mean CRT reduced, and by 12-weeks visual acuity improvement >0.3logMar was achieved in 46%. Cataract progression (47%) and IOP>21 mmHg (45%) were the commonest adverse events. Preservative-free triamcinolone is an additional option for uveitis-related macular oedema, particularly in unilateral cases, with favorable CRT and visual outcomes. Repeat injections may be necessary, and the period of efficacy varies between eyes.

Influence of Delivery Method on Neuroprotection by Bone Marrow Mononuclear Cell Therapy following Ventral Root Reimplantation with Fibrin Sealant

PubMed Central

Barbizan, Roberta; Castro, Mateus V.; Barraviera, Benedito; Ferreira, Rui S.; Oliveira, Alexandre L. R.

2014-01-01

The present work compared the local injection of mononuclear cells to the spinal cord lateral funiculus with the alternative approach of local delivery with fibrin sealant after ventral root avulsion (VRA) and reimplantation. For that, female adult Lewis rats were divided into the following groups: avulsion only, reimplantation with fibrin sealant; root repair with fibrin sealant associated with mononuclear cells; and repair with fibrin sealant and injected mononuclear cells. Cell therapy resulted in greater survival of spinal motoneurons up to four weeks post-surgery, especially when mononuclear cells were added to the fibrin glue. Injection of mononuclear cells to the lateral funiculus yield similar results to the reimplantation alone. Additionally, mononuclear cells added to the fibrin glue increased neurotrophic factor gene transcript levels in the spinal cord ventral horn. Regarding the motor recovery, evaluated by the functional peroneal index, as well as the paw print pressure, cell treated rats performed equally well as compared to reimplanted only animals, and significantly better than the avulsion only subjects. The results herein demonstrate that mononuclear cells therapy is neuroprotective by increasing levels of brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF). Moreover, the use of fibrin sealant mononuclear cells delivery approach gave the best and more long lasting results. PMID:25157845

[Neurotropic effect of B vitamins in the complex treatment of pain syndrome].

PubMed

Shavlovskaya, O A

Combined vitamin preparations in therapeutic doses are used, along with simple analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), muscle and epidural blockade, for the relief of acute pain. It is recommended to use the B vitamin preparation neuromultivit. The tablet form of this preparation contains vitamin thiamine hydrochloride (100 mg), pyridoxine hydrochloride (200 mg), cyanocobalamin (0.2 mg), and injectable form includes thiamine hydrochloride (100mg), pyridoxine hydrochloride (100 mg), cyanocobalamin (1 mg). The efficacy of neuromultivit in a two stage scheme (intramuscular injections of 2 ml daily for 5-10 days with further injections 2-3 times a week for 2-3 weeks at the initial stage and 1 tablet 3 times a day for 4 weeks at the second stage) was shown.

Characterization of sleep-pattern and neuro-immune-endocrine markers at 24 hour post-injection of a single low dose of lipopolysaccharide in male Wistar rats.

PubMed

Nachón-García, Francisco; Hurtado-Alvarado, Gabriela; Acosta-Hernández, Mario E; Peña-Escudero, Carolina; Priego-Fernández, Sergio; Alvarez-Herrera, Samantha; Becerril-Villanueva, Enrique; Pérez-Sánchez, Gilberto; Pavón, Lenin; García-García, Fabio

2018-07-15

The long-term effect of immune system activation by a low dose of lipopolysaccharide on neuro-immune-endocrine regulation is unclear. Sleep, neurotransmitter concentrations, TNF-α, and corticosterone levels were evaluated in male Wistar rats implanted with conventional sleep recordings. In this work, we found that REM sleep was reduced in the first 4 h post-injection, without affecting the total sleep time, while adrenaline concentration was reduced in the hippocampus at 24 h post-injection of LPS. Our results demonstrated that, although the acute immune response was not evident 24 h after the injection of LPS, it was able to promote the reduction of AD in the hippocampus, which may explain in part the depressive behavior reported in rodents following LPS administration. Copyright © 2018 Elsevier B.V. All rights reserved.

High-throughput high-volume nuclear imaging for preclinical in vivo compound screening§.

PubMed

Macholl, Sven; Finucane, Ciara M; Hesterman, Jacob; Mather, Stephen J; Pauplis, Rachel; Scully, Deirdre; Sosabowski, Jane K; Jouannot, Erwan

2017-12-01

Preclinical single-photon emission computed tomography (SPECT)/CT imaging studies are hampered by low throughput, hence are found typically within small volume feasibility studies. Here, imaging and image analysis procedures are presented that allow profiling of a large volume of radiolabelled compounds within a reasonably short total study time. Particular emphasis was put on quality control (QC) and on fast and unbiased image analysis. 2-3 His-tagged proteins were simultaneously radiolabelled by 99m Tc-tricarbonyl methodology and injected intravenously (20 nmol/kg; 100 MBq; n = 3) into patient-derived xenograft (PDX) mouse models. Whole-body SPECT/CT images of 3 mice simultaneously were acquired 1, 4, and 24 h post-injection, extended to 48 h and/or by 0-2 h dynamic SPECT for pre-selected compounds. Organ uptake was quantified by automated multi-atlas and manual segmentations. Data were plotted automatically, quality controlled and stored on a collaborative image management platform. Ex vivo uptake data were collected semi-automatically and analysis performed as for imaging data. >500 single animal SPECT images were acquired for 25 proteins over 5 weeks, eventually generating >3500 ROI and >1000 items of tissue data. SPECT/CT images clearly visualized uptake in tumour and other tissues even at 48 h post-injection. Intersubject uptake variability was typically 13% (coefficient of variation, COV). Imaging results correlated well with ex vivo data. The large data set of tumour, background and systemic uptake/clearance data from 75 mice for 25 compounds allows identification of compounds of interest. The number of animals required was reduced considerably by longitudinal imaging compared to dissection experiments. All experimental work and analyses were accomplished within 3 months expected to be compatible with drug development programmes. QC along all workflow steps, blinding of the imaging contract research organization to compound properties and automation provide confidence in the data set. Additional ex vivo data were useful as a control but could be omitted from future studies in the same centre. For even larger compound libraries, radiolabelling could be expedited and the number of imaging time points adapted to increase weekly throughput. Multi-atlas segmentation could be expanded via SPECT/MRI; however, this would require an MRI-compatible mouse hotel. Finally, analysis of nuclear images of radiopharmaceuticals in clinical trials may benefit from the automated analysis procedures developed.

Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure

DOE PAGES

Tyler, Christina R.; Noor, Shahani; Young, Tamara; ...

2018-01-27

The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O 3) exposure in aged mice, where increased blood brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C 57BL/6 male mice, aged 8-10 weeks or 12–18 months were exposed to either filtered air (FA) or 1.0 ppm O 3 for 4 hours; animals received a single IP injection of sodium fluorescein (FSCN) 20 hours post-exposure. One-hour post-FSCN injection, animals were transcardially perfused for immunohistochemical analysis of BBB permeability. β-amyloid protein expression wasmore » assessed via ELISA. Flow cytometric characterization of infiltrating immune cells, including neutrophils, macrophages, and microglia populations was performed 20 hours post-O 3 exposure. Flow cytometry analysis of brains revealed increased microglia “activation” and presentation of CD11b, F4/80 and MHCII in aged animals relative to younger ones; these age-induced differences were potentiated by acute O 3 exposure. Cortical and limbic regions in aged brains had increased reactive microgliosis and β-amyloid protein expression after O 3 insult. The aged cerebellum was particularly vulnerable to acute O 3 exposure with increased populations of infiltrating neutrophils, peripheral macrophages/monocytes, and Ly6C + inflammatory monocytes after insult, which were not significantly increased in the young cerebellum. O 3 exposure increased the penetration of FSCN beyond the BBB, the infiltration of peripheral immune cells, and reactive gliosis of microglia. Furthermore, the aged BBB is vulnerable to insult and becomes highly penetrable in response to O 3 exposure, leading to greater neuroinflammatory outcomes.« less

Human SolCD39 Inhibits Injury-induced Development of Neointimal Hyperplasia

PubMed Central

Drosopoulos, Joan H. F.; Kraemer, Rosemary; Shen, Hao; Upmacis, Rita K.; Marcus, Aaron J.; Musi, Elgilda

2010-01-01

SUMMARY Blood platelets provide the initial response to vascular endothelial injury, becoming activated as they adhere to the injured site. Activated platelets recruit leukocytes, and initiate proliferation and migration of vascular smooth muscle cells (SMC) within the injured vessel wall, leading to development of neointimal hyperplasia. Endothelial CD39/NTPDase1 and recombinant solCD39 rapidly metabolize nucleotides, including stimulatory ADP released from activated platelets, thereby suppressing additional platelet reactivity. Using a murine model of vascular endothelial injury, we investigated whether circulating human solCD39 could reduce platelet activation and accumulation, thus abating leukocyte infiltration and neointimal formation following vascular damage. Intraperitoneally-administered solCD39 ADPase activity in plasma peaked 1 hr post-injection, with an elimination half-life of 43 hr. Accordingly, mice were administered solCD39 or saline 1 hr prior to vessel injury, then either sacrificed 24 hr post-injury or treated with solCD39 or saline (3X weekly) for an additional 18 days. 24 hr post-injury, solCD39-treated mice displayed a reduction in platelet activation and recruitment, P-selectin expression, and leukocyte accumulation in the arterial lumen. Furthermore, repeated administration of solCD39 modulated the late stage of vascular injury by suppressing leukocyte deposition, macrophage infiltration and SMC proliferation/migration, resulting in abrogation of neointimal thickening. In contrast, injured femoral arteries of saline-injected mice exhibited massive platelet thrombus formation, marked P-selectin expression, and leukocyte infiltration. Pronounced neointimal growth with macrophage and SMC accretion was also observed (intimal-to-medial area ratio 1.56±0.34 at 19 days). Thus, systemic administration of solCD39 profoundly affects injury-induced cellular responses, minimizing platelet deposition and leukocyte recruitment, and suppressing neointimal hyperplasia. PMID:20024507

Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tyler, Christina R.; Noor, Shahani; Young, Tamara

The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O 3) exposure in aged mice, where increased blood brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C 57BL/6 male mice, aged 8-10 weeks or 12–18 months were exposed to either filtered air (FA) or 1.0 ppm O 3 for 4 hours; animals received a single IP injection of sodium fluorescein (FSCN) 20 hours post-exposure. One-hour post-FSCN injection, animals were transcardially perfused for immunohistochemical analysis of BBB permeability. β-amyloid protein expression wasmore » assessed via ELISA. Flow cytometric characterization of infiltrating immune cells, including neutrophils, macrophages, and microglia populations was performed 20 hours post-O 3 exposure. Flow cytometry analysis of brains revealed increased microglia “activation” and presentation of CD11b, F4/80 and MHCII in aged animals relative to younger ones; these age-induced differences were potentiated by acute O 3 exposure. Cortical and limbic regions in aged brains had increased reactive microgliosis and β-amyloid protein expression after O 3 insult. The aged cerebellum was particularly vulnerable to acute O 3 exposure with increased populations of infiltrating neutrophils, peripheral macrophages/monocytes, and Ly6C + inflammatory monocytes after insult, which were not significantly increased in the young cerebellum. O 3 exposure increased the penetration of FSCN beyond the BBB, the infiltration of peripheral immune cells, and reactive gliosis of microglia. Furthermore, the aged BBB is vulnerable to insult and becomes highly penetrable in response to O 3 exposure, leading to greater neuroinflammatory outcomes.« less

Naringin treatment induces neuroprotective effects in a mouse model of Parkinson's disease in vivo, but not enough to restore the lesioned dopaminergic system.

PubMed

Kim, Heung Deok; Jeong, Kyoung Hoon; Jung, Un Ju; Kim, Sang Ryong

2016-02-01

We recently reported that treatment with naringin, a major flavonoid found in grapefruit and citrus fruits, attenuated neurodegeneration in a rat model of Parkinson's disease (PD) in vivo. In order to investigate whether its effects are universally applied to a different model of PD and whether its treatment induces restorative effects on the lesioned nigrostriatal dopaminergic (DA) projection, we observed the effects of pre-treatment or post-treatment with naringin in a mouse model of PD. For neuroprotective effects, 6-hydroxydopamine (6-OHDA) was unilaterally injected into the striatum of mouse brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. Our results showed that naringin protected the nigrostriatal DA projection from 6-OHDA-induced neurotoxicity. Moreover, similar to the effects in rat brains, this treatment induced the activation of mammalian target of rapamycin complex 1 (mTORC1), which is well known as an important survival factor for DA neurons, and inhibited microglial activation in the substantia nigra (SN) of mouse brains treated with 6-OHDA. However, there was no significant change of DA phenotypes in the SN and striatum post-treated with naringin compared with 6-OHDA-lesioned mice, despite the treatment being continued for 12 weeks. These results suggest that post-treatment with naringin alone may not be enough to restore the nigrostriatal DA projection in a mouse model of PD. However, our results apparently suggest that naringin is a beneficial natural product to prevent DA degeneration, which is involved in PD. Copyright © 2015 Elsevier Inc. All rights reserved.

Autologous bone marrow stem cell transplantation attenuates hepatocyte apoptosis in a rat model of ex vivo liver resection and liver autotransplantation.

PubMed

Xu, Tubing; Wang, Xiaojun; Chen, Geng; He, Yu; Bie, Ping

2013-10-01

To investigate the efficacy of autologous bone marrow stem cell (BMSC) transplantation in the treatment of hepatic injury in ex vivo liver resection and liver autotransplantation (ELRLA). Rat hepatic fibrosis was induced by intraperitoneal injection of 50% CCl4-olive oil solution at a dose of 2 mL/kg twice weekly for 4 wk. ELRLA was performed 3 d post the last injection of CCl4. Six rats in each group were killed 12, 24, 48, 72, and 168 h after the operation. Hepatocyte apoptosis was determined by TUNEL assay. The expression of Bcl-2, Bax, transforming growth factor (TGF) β1, TGFβ1 receptor1/2, and phosphorylated p38 MAPK were determined by Western blot. Autologous BMSC transplantation significantly inhibited the increase of alanine aminotransferease and aspartate aminotransferase at 12, 24, and 48 h post operation and attenuated ELRLA-induced hepatocyte apoptosis. In BMSC-treated rats, the expression of Bcl-2 was significantly upregulated, whereas there were no obvious changes in Bax level. The expression of TGFβ1 was significantly upregulated in the rat liver after the surgery. Autologous BMSC transplantation significantly downregulated the TGFβ1 levels at 48, 72, and 168 h post surgery. However, autologous BMSC transplantation showed little effect on the levels of TGFβ receptor 1/2 at all the time points observed. Furthermore, autologous BMSC transplantation significantly inhibited the activation of p38 MAPK. Autologous BMSC transplantation may reduce ELRLA-induced liver injury and improve survival rates in hepatic fibrosis rats. Autologous BMSC transplantation may be useful to improve the outcome of patients who undergo ELRLA. Copyright © 2013 Elsevier Inc. All rights reserved.

Measuring persistent temporomandibular joint nociception in rats and two mice strains.

PubMed

Kramer, Phillip R; Kerins, Carolyn A; Schneiderman, Emet; Bellinger, Larry L

2010-04-19

Temporomandibular joint (TMJ) pain has been reported to last for prolonged periods in humans. In rodents a variety of methods have been used to measure TMJ nociception, but for most of these methods the period of measurement has been minutes to a couple of hours. In addition, most measurement protocols required restraint or training of the animal. Previous studies from our laboratory demonstrated that feeding behavior, particularly meal duration, was an indicator of TMJ nociception in unrestrained and untrained male and female Sprague-Dawley rats for up to two days. In this study, we first found that injection of complete Freund's adjuvant (CFA) into the TMJ of rats significantly lengthened meal duration for 19 days and also decreased meal frequency for 42 days. Interestingly, the meal duration varied significantly from day to day within the 19 day period. TMJ interleukin-1 beta (IL-1 beta) and calcitonin gene-related peptide (CGRP) were significantly elevated in the TMJ tissues of CFA-injected animals and the level of these markers was attenuated as the meal duration decreased with time. Control animals injected with saline into the TMJ or CFA into the knee did not show a significant lengthening in meal duration but did show a decrease in meal frequency. In a second study, DBA/1LacJ mice given TMJ CFA injections showed a significantly lengthened meal duration on four of the seven days measured using end-of-the meal definition of 5 or 10 min. No other meal pattern changed significantly. Two days post-CFA injection, the DBA/1LacJ mice showed significantly elevated interleukin-6 (IL-6), but not elevated IL-1 beta. Seven days post-injection, both IL-6 and IL-1 beta were significantly elevated. No change in CGRP was detected. In this study C57Bl/6 mice also received TMJ CFA injections, but they did not show a lengthening in any meal pattern or significant increases in IL-1 beta, IL-6 or CGRP. Our data show, for the first time, that meal duration can be used to measure CFA-induced nociception in the TMJ over the course of several weeks in unrestrained rats and for up to seven days in the DBA/1LacJ mouse strain. In addition, C57Bl/6 mice are resistant to CFA-induced TMJ nociception at the same dose used in the DBA/1LacJ mice. (c) 2010 Elsevier Inc. All rights reserved.

Increased anxiety in rats after 3,4-methylenedioxymethamphetamine: association with serotonin depletion.

PubMed

Gurtman, Clint G; Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; McGregor, Iain S

2002-06-20

The long-term behavioural and neurotoxic effects of 3,4-methlyenedioxymethampthetamine (MDMA, "Ecstasy") were examined in rats. Rats were given MDMA (5 mg/kg i.p. once per hour for 4 h) or vehicle injections on each of two consecutive days at an ambient temparature of 28 degrees C. MDMA caused acute hyperthermia and locomotor hyperactivity on both days. Four and six weeks after drug administration the rats previously treated with MDMA showed elevated levels of anxiety-like behaviour in the emergence and social interaction tests, respectively. At 9 weeks post-MDMA, the rats displayed an increase in anxiety on the elevated plus-maze test relative to controls. Ten weeks following treatment the rats were killed and their brains dissected and neurotramitter content analysed using High Performance Liquid Chromotography (HPLC). Rats previously given MDMA showed significantly decreased 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the amygdala, hippocampus and striatum relative to controls. This 5-HT depletion may have a causal role in producing increased anxiety-like behaviours in MDMA-treated rats. These results are consistent with human studies suggesting that exposure to high doses of MDMA may predispose to long-term psychological problems such as anxiety and depression.

[Comparative study on four kinds of assessment methods of post-marketing safety of Danhong injection].

PubMed

Li, Xuelin; Tang, Jinfa; Meng, Fei; Li, Chunxiao; Xie, Yanming

2011-10-01

To study the adverse reaction of Danhong injection with four kinds of methods, central monitoring method, chart review method, literature study method and spontaneous reporting method, and to compare the differences between them, explore an appropriate method to carry out post-marketing safety evaluation of traditional Chinese medicine injection. Set down the adverse reactions' questionnaire of four kinds of methods, central monitoring method, chart review method, literature study method and collect the information on adverse reactions in a certain period. Danhong injection adverse reaction information from Henan Province spontaneous reporting system was collected with spontaneous reporting method. Carry on data summary and descriptive analysis. Study the adverse reaction of Danhong injection with four methods of central monitoring method, chart review method, literature study method and spontaneous reporting method, the rates of adverse events were 0.993%, 0.336%, 0.515%, 0.067%, respectively. Cyanosis, arrhythmia, hypotension, sweating, erythema, hemorrhage dermatitis, rash, irritability, bleeding gums, toothache, tinnitus, asthma, elevated aminotransferases, constipation, pain are new discovered adverse reactions. The central monitoring method is the appropriate method to carry out post-marketing safety evaluation of traditional Chinese medicine injection, which could objectively reflect the real world of clinical usage.

Comparative Efficacy of Platelet Rich Plasma Injection, Corticosteroid Injection and Ultrasonic Therapy in the Treatment of Periarthritis Shoulder

PubMed Central

Srikumar, Venkataraman; Singh, Neha

2017-01-01

Introduction Periarthritis (PA) shoulder characterised by pain and restricted range of motion has a plethora of treatment options with inconclusive evidence. Platelet Rich Plasma (PRP) is an emerging treatment option and its efficacy needs to be examined and compared with other routine interventions. Aim To assess the efficacy of PRP injection and compare it with corticosteroid injection and ultrasonic therapy in the treatment of PA shoulder. Materials and Methods Patients with PA shoulder (n=195) were randomised to receive single injection of PRP (2 ml) or corticosteroid (80 mg of methylprednisolone) or ultrasonic therapy (seven sittings in two weeks; 1.5 W/cm2, 1 MHz, continuous mode). All participants were also advised to perform a home based 10 minute exercise therapy. The primary outcome measure was active range of motion of the shoulder. Secondary outcome measures used were Visual Analogue Scale (VAS) for pain and a shortened version of Disabilities of the Arm, Shoulder and Hand (QuickDASH) for function. Participants were evaluated at 0, 3, 6 and 12 weeks. Chi-square test, one way and repeated measures of ANOVA tests were used to determine significant differences. Results PRP treatment resulted in statistically significant improvements over corticosteroid and ultrasonic therapy in active as well as passive range of motion of shoulder, VAS and QuickDASH at 12 weeks. At six weeks, PRP treatment resulted in statistically significant improvements over ultrasonic therapy in VAS and QuickDASH. No major adverse effects were observed. Conclusion This study demonstrates that single injection of PRP is effective and better than corticosteroid injection or ultrasonic therapy in treatment of PA shoulder. PMID:28658861

Microplasmin-Induced Posterior Vitreous Detachment Affects Vitreous Oxygen Levels

PubMed Central

Quiram, Polly A.; Leverenz, Victor R.; Baker, Robert M.; Dang, Loan; Giblin, Frauk J.; Trese, Michael T.

2009-01-01

Purpose To determine if enzymatic induction of a posterior vitreous detachment (PVD) and/or vitreous liquefaction affects O2 concentration in the vitreous cavity in animals with vascularized and avascular retinal circulations. Methods Either microplasmin or hyaluronidase was injected intravitreally into guinea pigs (avascular retinal circulation), brown Norway rats (vascularized retinal circulation without fovea), or cats (vascularized retinal circulation with fovea) with the contralateral eye used as a control. One to 2 weeks post injection, vitreal oxygen concentration was measured using a highly sensitive, platinum-based fluorophore O2 sensor. In addition, control and microplasmin-injected rats, guinea pigs, and cats were exposed to 100% oxygen and vitreal O2 levels were measured over time. Scanning electron microscopy (SEM) was used to evaluate the vitreoretinal interface for the presence of a PVD. Results In animals with a vascularized retinal circulation (brown Norway rats and cats), intravitreal injection of microplasmin with induction of a PVD significantly increased baseline O2 concentration in the vitreous cavity compared to hyaluronidase injected eyes and controls in rats (35, 25, and 23 mm Hg, P < 0.001 and P < 0.001, respectively) and cats (26, 18, and 16 mm Hg, P < 0.01 and P < 0.001, respectively). Interestingly, intravitreal injection of hyaluronidase (vitreous liquefaction without induction of a PVD) did not significantly increase vitreal O2 levels in any of the animal species (P > 0.1). Upon exposure to 100% oxygen by facemask, microplasmin injected animals showed a rapid increase in vitreal oxygen levels compared to hyaluronidase injected animals and controls, indicating that the presence of a PVD allows rapid O2 exchange within the vitreous cavity. Similarly, once O2 was discontinued, the O2 concentration decreased in a similarly rapid rate. SEM showed smooth retinal surfaces in microplasmin-injected cat eyes, indicating the presence of a PVD which was not present in hyaluronidase injected or control eyes. Conclusion The results suggest that enzymatic-assisted PVD with microplasmin increases vitreal O2 levels and increases the rate of O2 exchange within the vitreous cavity. PMID:18040251

Prospective randomized controlled trial comparing standard analgesia with combined intra-operative cystic plate and port-site local anesthesia for post-operative pain management in elective laparoscopic cholecystectomy.

PubMed

Protic, Mladjan; Veljkovic, Radovan; Bilchik, Anton J; Popovic, Ana; Kresoja, Milana; Nissan, Aviram; Avital, Itzhak; Stojadinovic, Alexander

2017-02-01

Various mechanisms, including somatic and visceral nociceptive stimulation, have been suggested as a cause for pain after laparoscopic cholecystectomy (LC). We therefore conducted a prospective randomized controlled trial (PRCT) to evaluate whether somatovisceral pain blockade reduces pain after LC. Analgesic efficacy of multimodal analgesia is superior to standard analgesia for patients undergoing elective LC for symptomatic cholelithiasis. Specifically, topical cystic plate and port-site injection with 0.25 % bupivacaine significantly reduces pain after LC. This study was designed as single-blinded PRCT. This study was conducted in an academic medical center. Between February and May 2010 we randomly assigned 63 patients with symptomatic cholelithiasis in a 1:1 ratio to non-opioid/opioid analgesic combinations (Control Group, n = 32) and non-opioid/opioid analgesic combinations plus topical 0.25 % bupivacaine onto the cystic plate and local 0.25 % bupivacaine port-site injection, post-LC (Study Group, n = 31). Primary endpoint was patient-reported pain 1, 4, 6, 12, 24 h and 1 week post-LC using the Visual Analog Scale (VAS 0-10). Study groups were comparable clinicopathologically. There were no adverse events. A statistically significant reduction in mean pain score was apparent in Study Group patients in comparison with Control Group (mean VAS 4.83 ± 2.33 vs. 6.80 ± 1.87; p < 0.001) at all early (1-6 h) post-operative time points following LC. This PRCT shows significantly improved pain control with somatovisceral pain blockade over non-opioid/opioid analgesic combinations following LC for symptomatic cholelithiasis. For centers not utilizing adjunctive local anesthetic for LC, this topical use of bupivacaine may improve patient comfort during recovery. This trial was registered on www.ClinicalTrials.gov NCT# 01972620.

Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats

PubMed Central

Zhou, Feng; Hui, Yu; Xin, Hua; Xu, Yong-De; Lei, Hong-En; Yang, Bi-Cheng; Guan, Rui-Li; Li, Meng; Hou, Jian-Quan; Xin, Zhong-Cheng

2017-01-01

This study aimed to explore the therapeutic effects of adipose-derived stem cells (ADSCs)-based microtissues (MTs) on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg kg−1), and 8 weeks later, the determined diabetic rats randomly received intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs, or MTs. Another eight normal rats equally got IC injection of PBS. MTs were generated with a hanging drop method, and the injected cells were tracked in ADSC- and MT-injected rats. Four weeks after the treatments, intracavernous pressure (ICP), histopathological changes in corpus cavernosum (CC), and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. The results showed that MTs expressed vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and tumor necrosis factor-stimulated gene-6 (TSG-6). MTs injection had a higher retention than ADSCs injection and MTs treatment improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle, and endothelial contents in diabetic rats, ameliorated local inflammation in CC better. Thus, our findings demonstrate that IC injection of MTs improves erectile function and histopathological changes in STZ-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors. PMID:27345005

Functional Ability Improved in Essential Tremor by IncobotulinumtoxinA Injections Using Kinematically Determined Biomechanical Patterns – A New Future

PubMed Central

Samotus, Olivia; Rahimi, Fariborz; Lee, Jack; Jog, Mandar

2016-01-01

Objective Effective treatment for functional disability caused by essential tremor is a significant unmet need faced by many clinicians today. Current literature regarding focal therapy by botulinum toxin type A (BoNT-A) injections uses fixed dosing regimens, which cannot be individualized, provides only limited functional benefit and unacceptable muscle weakness commonly occurs. This 38-week open label study, the longest to-date, demonstrates how kinematic technology addressed all these issues by guiding muscle selection. Method Participants (n = 24) were assessed at weeks 0, 6, 16, 22, 32, and 38 and injected with incobotulinumtoxinA at weeks 0, 16, and 32. Clinical assessments including UPDRS tremor items, Fahn-Tolosa-Marin (FTM) tremor rating scale assessing tremor severity, writing and functional ability, quality of life questionnaire (QUEST) and objective kinematic assessments were completed at every visit. Participants performed two postural and two weight-bearing scripted tasks with motion sensors placed over the wrist, elbow and shoulder joints. These sensors captured angular tremor amplitude (RMS units) and acceleration joint motion that was segmented into directional components: flexion-extension (F/E), pronation-supination and radial-ulnar at the wrist, F/E at the elbow, and F/E and adduction-abduction at the shoulder. Injection parameters were determined using kinematics, followed by the clinician’s determination of which muscles would contribute to the specific upper limb tremor biomechanics and dosing per participant. Results Multi-joint biomechanical recordings allowed individualized muscle selection and showed significant improvement in whole-arm function, FTM parts A-C scores, at week 6 which continued throughout the study. By week 38, the total FTM score statistically significantly reduced from 16.2±4.6 at week 0 to 9.5±6.3 (p<0.0005). UPDRS item 21 score rating action tremor was significantly reduced from 2.6±0.5 at week 0 to 1.6±1.1 (p = 0.01) at week 32. Quality of life (QUEST) significantly improved from 40.3±15.8 at week 0 to 31.1±15.3 (p = 0.035) at week 32 and to 27.8±15.3 (p = 0.028) at week 38. Kinematics provided an objective, secondary outcome measure, which showed a significant decrease in tremor amplitude in the wrist and shoulder joints (p<0.05). Eight participants (40%) self-reported mild weakness in injected muscles but had no interference in arm function. Conclusion Kinematic tremor assessments provide the injector unique insight to objectively individualize and personalize injection parameters demonstrating BoNT-A effectively alleviates functional disability caused by essential tremor. Kinematic technology is a promising method for standardizing assessments and for focal upper limb tremor treatment. Trial Registration ClinicalTrials.gov NCT02427646 PMID:27101283

[Influence of undernutrition in the lactating cow on ovulation induction by serum gonadotropins (PMSG) during the post-partum period].

PubMed

Gauthier, D; Yaouanc, A; Cochaud, J; Mauléon, P

1981-01-01

Two experiments were carried out to assess the influence of undernutrition on postpartum ovulation in nursing Charolais cows after PMSG injection. In each experiment, the nursing cows were divided into 2 groups: one fed at a low nutritional level and the other at a normal nutritional level. In the first experiment, 19 animals were injected on post-partum days 15 and 30 with 600 IU of PMSG; in the second experiment, 34 received the same injection on post-partum day 54 after 9 days of priming with a Norgestomet implant. On post-partum day 15, only one cow in each group ovulated. At post-partum day 30, 1 out of 8 cows at the low nutritional plane ovulated vs 5 out of 9 at the normal nutritional plane (P less than 0.05). Likewise, on post-partum day 54, 5 out of 14 cows at the low nutritional plane ovulated vs 17 out of 17 at the normal nutritional level (P less than 0.05). Therefore, there is a time during the post-partum period when the nursing cow ovary does not respond to PMSG by ovulation. The length of this time is increased by undernutrition.

Frequency of booster injections of allergoids.

PubMed

Norman, P S; Creticos, P S; Marsh, D G

1990-01-01

In 1982, 43 ragweed-sensitive patients receiving maintenance injections of full doses of ragweed allergoid were selected for a study of the immunologic and clinical efficacy of booster injections only four times a year. These patients had participated for 2 to 7 years as part of a trial of mixes of up to four allergoids to common pollens in the mid-Atlantic area tailored to each patient's skin test sensitivity. They were divided into a group (21 patients) to receive injections every 3 months and a group (22 patients) to receive injections about every 6 weeks (eight injections per year). Patients were rerandomized after 1 year so that half of each original group switched to the alternate treatment, and this program was continued until after the ragweed season of 1985. Thirty-four patients were still under study the last year. Doses, per injection, were 100 allergoid units (1 allergoid unit equals 100 PNU) of each allergen in the mixture. Symptom scores during the 8 weeks of each of the four ragweed seasons were not significantly higher in the 3-month treated group. IgG antibody levels to Amb a I (antigen E) were followed until early 1984 and were not significantly different in the two groups, even though the 6-week treated patients received a two times higher cumulative dose per year. Rates of local and systemic reactions (percent of injections eliciting reactions) were not different in the groups, which means that the 3-month treated group had about half as many reactions by virtue of taking half as many injections.(ABSTRACT TRUNCATED AT 250 WORDS)