Computerized Tomography-Guided Paracentesis: An Effective Alternative to Bedside Paracentesis?

PubMed

Gaduputi, Vinaya; Tariq, Hassan; Chandrala, Chaitanya; Sakam, Sailaja; Abbas, Naeem; Chilimuri, Sridhar

2017-02-01

Ascites remains the most common cause of hospitalization among patients with decompensated cirrhosis. Paracentesis is a relatively safe procedure with low complication rates. Computerized tomography (CT)-guided therapeutic paracentesis could be a safe and effective alternative to unaided or aided (ultrasonogram-guided) bedside paracentesis. In this retrospective study, we aimed to compare the efficacy, safety, and cost-effectiveness of CT-guided paracentesis with bedside paracentesis. The period of study was from 2002 to 2012. All patients with cirrhosis who underwent therapeutic paracentesis were included in the study. These patients were divided into two groups. Group I consisted of patients who underwent CT-guided pigtail catheter insertion with ascitic fluid drainage. Group II consisted of patients who underwent beside therapeutic paracentesis after localization of fluid either by physical examination or sonographic localization. We measured the efficacy of CT-guided paracentesis and bedside paracentesis in terms of volume of fluid removed, length of stay, discharge doses of diuretics (spironolactone and furosemide) and number of days to readmission for symptomatic ascites. We also computed the cost-effectiveness of CT-guided therapeutic paracentesis when compared to a bedside procedure. Fischer exact test was used to analyze the distribution of categorical data and unpaired t -test was used for comparison of means. There were a total of 546 unique patients with diagnosed cirrhosis who were admitted to the hospital with symptomatic ascites and underwent therapeutic paracentesis. Two hundred and forty-seven patients underwent CT-guided paracentesis, while 272 patients underwent bedside paracentesis. There was significant inverse correlation between the amount of ascitic fluid removed and total length of stay in the hospital. We found that the volume of fluid removed via a CT-guided pigtail insertion and drainage (2.72 ± 2.02 L) is significantly higher when compared to fluid removed via bedside paracentesis (1.94 ± 1.69). We also found that the interval time period between two successive therapeutic paracenteses was significantly longer for CT group (106.56 ± 75.2 days) when compared to the bedside group (25.57 ± 7.68 days). CT-guided paracentesis with pigtail catheter insertion and drainage is a clinically effective, cheap and safe alternative to conventional bedside paracentesis.

A study of the differential effects of Tomm's questioning styles on therapeutic alliance.

PubMed

Ryan, D; Carr, A

2001-01-01

To replicate and extend Dozier's (1992) test of Tomm's hypothesis about the differential effects of questioning styles on therapeutic alliance, an analogue study was conducted. Twenty-eight family triads, each including a son and his parents, viewed four videotaped, simulated family therapy scenarios in which Tomm's four questioning styles were separately portrayed. Participants were asked to identify with the client whose role corresponded to theirs (that is, father, mother, or son) and, on the basis of this, to rate the client's alliance with the therapist. They were also asked to rate the overall alliance between the family and the therapist. Finally, having viewed all four scenarios, they were invited to rate comparatively the quality of the therapeutic alliance across the four questioning styles. Compared with strategic and lineal questioning styles, circular and reflexive questions led to higher ratings of therapeutic alliance on all three measures. The results of this study support Tomm's hypothesis that questioning styles based on circular assumptions lead to a better therapeutic alliance at an individual and systemic level than do questions based on lineal assumptions.

Effects of Kinesio taping and exercise on forward head posture.

PubMed

Shih, Hsu-Sheng; Chen, Shu-Shi; Cheng, Su-Chun; Chang, Hsun-Wen; Wu, Pei-Rong; Yang, Jin-Shiou; Lee, Yi-Shuang; Tsou, Jui-Yi

2017-01-01

Little is known about the effects of Kinesio taping and therapeutic exercise on correcting forward head posture. To compare Kinesio taping versus therapeutic exercise for forward head posture on static posture, dynamic mobility and functional outcomes. Sixty subjects (31 women, 29 men) with forward head postures participated in this study. They were randomly assigned to either one of the three groups: (1) exercise group (n = 20), (2) taping group (n = 20), and (3) control groups (n = 20). The horizontal forward displacement (HFD) between ear lobe and acromion process, upper cervical and lower cervical angle (UCA, LCA), active range of motion (AROM) of cervical spine, and neck disability index (NDI) were measured before and after a 5-week intervention, and a 2-week follow-up. Data were analyzed by means of a mixed design repeated-measures ANOVA. Both taping and exercise groups showed significant improvements in HFD compared with the control group at post-treatment and follow-up. Compared with the control group, the exercise group exhibited significant improvements in the LCA and the side bending AROM at post-treatment. Both Kinesio taping and therapeutic exercise improve forward head posture after intervention and a 2-week follow-up. The effectiveness of therapeutic exercise is better than taping.

Comparison of the therapeutic dose of warfarin in HIV-infected and HIV-uninfected patients: a study of clinical practice.

PubMed

Jackson, B S; Mokoena, T

2017-02-08

People infected with HIV are prone to venous thrombosis. Treatment of thrombosis is primarily with warfarin. No studies have addressed the effects of HIV infection on warfarin dose. The aims of this study were to determine whether the therapeutic dose of warfarin and induction time to therapeutic dose in HIV-infected patients differ from that in HIV-uninfected patients. A prospective and retrospective descriptive study of induction time to therapeutic warfarin dose, as well as of ambulant therapeutic warfarin dose, was performed. HIV-infected and HIV-uninfected patients being treated after deep venous thrombosis with or without pulmonary embolism were compared. Sex and use of antiretroviral drugs (ARVs) were also compared in the groups. 234 patients were entered into the study. Induction time to therapeutic warfarin dose did not differ between the 2 groups. The mean therapeutic dose of warfarin was higher in the HIV-infected than the HIV-uninfected group: 6.06 vs 5.72 mg/day, but this was not statistically significant (p=0.29). There was no difference in therapeutic warfarin dose between ARV-naïve groups-HIV-uninfected and HIV-infected patients not on ARVs. There appears to be little effect of HIV infection on warfarin dosing. Warfarin therapy should be administered conventionally in HIV-infected patients. 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/.

He-Ne ILLLI used for brain trauma: a clinical observation of 46 cases

NASA Astrophysics Data System (ADS)

Yang, Da-Ke; Ru, Zheng-Guo; Ge, Sheng-Li; Shuo, Wei-Lan

1998-11-01

With the background that ILLLI can lower the viscosity of blood, improve the microcirculation, we investigated and compared the therapeutic effect of conventional drug therapy and ILLLI combined drug therapy for brain trauma. We found that ILLLI combined drug therapy could effectively alleviate some symptoms such as headache, vertigo, nausea, vomiting, blurred vision, anorexia caused by brain trauma. the therapeutic effect of treated group was prior to control group.

[Psychic aspects of the premenstrual dysphoric disorders. New therapeutic strategies: our experience with Vitex agnus castus].

PubMed

Ciotta, L; Pagano, I; Stracquadanio, M; Di Leo, S; Andò, A; Formuso, C

2011-06-01

The premenstrual dysphoric disorder (PMDD) is one of the main problems of the premenstrual phase. It consists of symptoms that sometimes invalidate the scope of employment, social and psycho-affective of patients, requiring thus a diagnostic and therapeutic approach as detailed and accurate as possible. The therapeutic strategies available for this disease are many, but recently the emphasis has been on Vitex agnus castus (VAC), considered by many as evidence drug of choice for both PMS and for the PMDD, being with satisfactory therapeutic properties and small side effects. Our study evaluated a group of patients suffering from PMDD and the clinical efficacy of treatment with VAC (and compared the effectiveness of the results of a more homogeneous group of patients treated with fluoxetine). This study confirms the data reported in the literature regarding the effectiveness of VAC therapy with no side effects.

Rational evaluation of the therapeutic effect and dosimetry of auger electrons for radionuclide therapy in a cell culture model.

PubMed

Shinohara, Ayaka; Hanaoka, Hirofumi; Sakashita, Tetsuya; Sato, Tatsuhiko; Yamaguchi, Aiko; Ishioka, Noriko S; Tsushima, Yoshito

2018-02-01

Radionuclide therapy with low-energy auger electron emitters may provide high antitumor efficacy while keeping the toxicity to normal organs low. Here we evaluated the usefulness of an auger electron emitter and compared it with that of a beta emitter for tumor treatment in in vitro models and conducted a dosimetry simulation using radioiodine-labeled metaiodobenzylguanidine (MIBG) as a model compound. We evaluated the cellular uptake of 125 I-MIBG and the therapeutic effects of 125 I- and 131 I-MIBG in 2D and 3D PC-12 cell culture models. We used a Monte Carlo simulation code (PHITS) to calculate the absorbed radiation dose of 125 I or 131 I in computer simulation models for 2D and 3D cell cultures. In the dosimetry calculation for the 3D model, several distribution patterns of radionuclide were applied. A higher cumulative dose was observed in the 3D model due to the prolonged retention of MIBG compared to the 2D model. However, 125 I-MIBG showed a greater therapeutic effect in the 2D model compared to the 3D model (respective EC 50 values in the 2D and 3D models: 86.9 and 303.9 MBq/cell), whereas 131 I-MIBG showed the opposite result (respective EC 50 values in the 2D and 3D models: 49.4 and 30.2 MBq/cell). The therapeutic effect of 125 I-MIBG was lower than that of 131 I-MIBG in both models, but the radionuclide-derived difference was smaller in the 2D model. The dosimetry simulation with PHITS revealed the influence of the radiation quality, the crossfire effect, radionuclide distribution, and tumor shape on the absorbed dose. Application of the heterogeneous distribution series dramatically changed the radiation dose distribution of 125 I-MIBG, and mitigated the difference between the estimated and measured therapeutic effects of 125 I-MIBG. The therapeutic effect of 125 I-MIBG was comparable to that of 131 I-MIBG in the 2D model, but the efficacy was inferior to that of 131 I-MIBG in the 3D model, since the crossfire effect is negligible and the homogeneous distribution of radionuclides was insufficient. Thus, auger electrons would be suitable for treating small-sized tumors. The design of radiopharmaceuticals with auger electron emitters requires particularly careful consideration of achieving a homogeneous distribution of the compound in the tumor.

Peak experiences and the afterglow phenomenon: when and how do therapeutic effects of hallucinogens depend on psychedelic experiences?

PubMed

Majić, Tomislav; Schmidt, Timo T; Gallinat, Jürgen

2015-03-01

Interest in the therapeutic potential of psychedelic substances has recently resumed. During an early phase of human psychedelic research, their therapeutic application in different pathologies had been suggested, and the first evidence for efficacy was provided. The range of recent clinical applications of psychedelics spans from cluster headaches and obsessive-compulsive disorder to addiction and the treatment of fear and anxiety in patients suffering from terminal illness, indicating potentially different therapeutic mechanisms. A variety of approaches in psychotherapy emphasize subjective experiences, such as so-called peak experiences or afterglow phenomena, as differentially mediating therapeutic action. This review aims to re-evaluate earlier and recent concepts of how psychedelic substances may exert beneficial effects. After a short outline of neurophenomenological aspects, we discuss different approaches to how psychedelics are used in psychotherapy. Finally, we summarize evidence for the relationship between subjective experiences and therapeutic success. While the distinction between pharmacological and psychological action obviously cannot be clear-cut, they do appear to contribute differently from each other when their effects are compared with regard to pathologies. © The Author(s) 2015.

Comparison of Adipose-Derived and Bone Marrow Mesenchymal Stromal Cells in a Murine Model of Crohn's Disease.

PubMed

Xie, Minghao; Qin, Huabo; Luo, Qianxin; He, Xiaosheng; He, Xiaowen; Lan, Ping; Lian, Lei

2017-01-01

Mesenchymal stromal cells (MSCs) have been used in the treatment of Crohn's disease (CD) because of the immunomodulatory ability. The aim of this study was to investigate the therapeutic effect of adipose-derived MSCs (AD-MSCs) and to compare the therapeutic effect of AD-MSCs with that of bone marrow MSCs (BM-MSCs) in a murine model of CD. Murine colitis model of CD was created by trinitrobenzene sulfonic acid (TNBS). Twelve hours after treatment with TNBS, the mouse model was injected with MSCs intraperitoneally. Real-time polymerase chain reaction and immunohistochemistry staining were used to measure the expression levels of inflammatory cytokines in colonic tissues to investigate the therapeutic effect of AD-MSCs. The ten-day survival was recorded after infusion of MSCs. Intraperitoneal injection of MSCs alleviated the clinical and histopathologic severity of intestinal inflammation, and improved the survival of the TNBS-induced mouse model of CD. AD-MSCs could effectively increase the expression of interleukin-10 and reduce the secretion of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-12, and vascular endothelial growth factor. The mucosal injury was repaired by AD-MSCs. These effects were comparable between AD-MSCs and BM-MSCs. The therapeutic effect appears similar between AD-MSCs and BM-MSCs in treating CD. AD-MSCs may be a potential alternative of cell-based therapy for CD.

Increased expression of pigment epithelium-derived factor in aged mesenchymal stem cells impairs their therapeutic efficacy for attenuating myocardial infarction injury‡

PubMed Central

Liang, Hongliang; Hou, Huiyuan; Yi, Wei; Yang, Guodong; Gu, Chunhu; Lau, Wayne Bond; Gao, Erhe; Ma, Xinliang; Lu, Zifan; Wei, Xufeng; Pei, Jianming; Yi, Dinghua

2013-01-01

Aims Mesenchymal stem cells (MSCs) can ameliorate myocardial infarction (MI) injury. However, older-donor MSCs seem less efficacious than those from younger donors, and the contributing underlying mechanisms remain unknown. Here, we determine how age-related expression of pigment epithelium-derived factor (PEDF) affects MSC therapeutic efficacy for MI. Methods and results Reverse transcriptase–polymerized chain reaction  and enzyme-linked immunosorbent assay analyses revealed dramatically increased PEDF expression in MSCs from old mice compared to young mice. Morphological and functional experiments demonstrated significantly impaired old MSC therapeutic efficacy compared with young MSCs in treatment of mice subjected to MI. Immunofluorescent staining demonstrated that administration of old MSCs compared with young MSCs resulted in an infarct region containing fewer endothelial cells, vascular smooth muscle cells, and macrophages, but more fibroblasts. Pigment epithelium-derived factor overexpression in young MSCs impaired the beneficial effects against MI injury, and induced cellular profile changes in the infarct region similar to administration of old MSCs. Knocking down PEDF expression in old MSCs improved MSC therapeutic efficacy, and induced a cellular profile similar to young MSCs administration. Studies in vitro showed that PEDF secreted by MSCs regulated the proliferation and migration of cardiac fibroblasts. Conclusions This is the first evidence that paracrine factor PEDF plays critical role in the regulatory effects of MSCs against MI injury. Furthermore, the impaired therapeutic ability of aged MSCs is predominantly caused by increased PEDF secretion. These findings indicate PEDF as a promising novel genetic modification target for improving aged MSC therapeutic efficacy. PMID:21606086

Cisplatin encapsulated nanoparticle as a therapeutic agent for anticancer treatment

NASA Astrophysics Data System (ADS)

Eka Putra, Gusti Ngurah Putu; Huang, Leaf; Hsu, Yih-Chih

2016-03-01

The knowledge of manipulating size of biomaterials encapsulated drug into nano-scale particles has been researched and developed in treating cancer. Cancer is the second worldwide cause of death, therefore it is critical to treat cancers challenging with therapeutic modality of various mechanisms. Our preliminary investigation has studied cisplatin encapsulated into lipid-based nanoparticle and examined the therapeutic effect on xenografted animal model. We used mice with tumor volume ranging from 195 to 214 mm3 and then few mice were grouped into three groups including: control (PBS), lipid platinum chloride (LPC) nanoparticles and CDDP (cis-diamminedichloroplatinum(II) at dose of 3mg cisplatin /kg body weight. The effect of the treatment was observed for 12 days post-injection. It showed that LPC NPs demonstrated a better therapeutic effect compared to CDDP at same 3mg cisplatin/kg drug dose of tumor size reduction, 96.6% and 11.1% respectively. In addition, mouse body weight loss of LPC, CDDP and PBS treated group are 12.1%, 24.3% and 1.4%. It means that by compared to CDDP group, LPC group demonstrated less side effect as not much reduction of body weight have found. Our findings have shown to be a potential modality to further investigate as a feasible cancer therapy modality.

Therapeutic touch and postoperative pain: a Rogerian research study.

PubMed

Meehan, T C

1993-01-01

This article details Meehan's research study concerning the conceptualization of therapeutic touch within Rogers' science of unitary human beings and an investigation of the effects of therapeutic touch on pain experience in postoperative patients. Using a single trial, single-blind, three-group design, 108 postoperative patients were randomly assigned to receive one of the following: therapeutic touch, a placebo control intervention which mimicked therapeutic touch, or the standard intervention of a narcotic analgesic. Using a visual analogue scale, pain was measured before and one hour following intervention. The hypothesis, that therapeutic touch would significantly decrease postoperative pain compared to the placebo control intervention, was not supported. Secondary analyses suggest that therapeutic touch may decrease patients' need for analgesic medication. Implications for further research and practice are suggested.

Comparative study of therapeutic effects of PPI and H2RA on ulcers during continuous aspirin therapy

PubMed Central

Nema, Hiroaki; Kato, Mototsugu

2010-01-01

AIM: To compare the therapeutic effects of proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) on gastroduodenal ulcers under continuous use of low-dose aspirin. METHODS: Sixty patients who had a gastroduodenal ulcer on screening endoscopy but required continuous use of low-dose aspirin were randomly assigned to receive PPI (lansoprazole 30 mg, n = 30) or H2RA (famotidine 40 mg or if famotidine had been administered before assignment, ranitidine 300 mg, n = 30). The therapeutic effects were evaluated by endoscopy after 8-wk treatment. The presence or absence of Helicobacter pylori (H. pylori) was determined by urea breath test before treatment. Abdominal symptoms were compared with the gastrointestinal symptom rating scale (GSRS) questionnaire before and after treatment. RESULTS: Twenty-six patients in the PPI group and 26 patients in the H2RA group, excluding dropouts, were analyzed. There were no significant differences in median age, sex, underlying disease, smoking status, H. pylori infection, prevalence of ulcers before treatment, and lesion site between the two groups. The therapeutic effects were endoscopically evaluated as healed in 23 patients (88.5%) and not healed in 3 patients in the PPI group and as healed in 22 patients (84.6%) and not healed in 4 patients in the H2RA group. Abdominal symptoms before treatment were uncommon in both groups; the GSRS scores were not significantly reduced after treatment as compared with before treatment. CONCLUSION: The healing rate of gastroduodenal ulcers during continuous use of low-dose aspirin was greater than 80% in both the PPI group and the H2RA group, with no significant difference between the two groups. PMID:21072898

Assembled nanomedicines as efficient and safe therapeutics for articular inflammation.

PubMed

Che, Ling; Zhou, Jianzhi; Li, Shuhui; He, Hongmei; Zhu, Yuxuan; Zhou, Xing; Jia, Yi; Liu, Yao; Zhang, Jianxiang; Li, Xiaohui

2012-12-15

Highly efficient nanomedicines were successfully fabricated by the indomethacin (IND) directed self-assembly of β-cyclodextrin (β-CD)-conjugated polyethyleneimine (PEI-CD), taking advantage of the multiple interactions between drug and polymer. These nanoscaled assemblies exhibited spherical shape and positively charged surface. Compared with the commercial tablet, the relative oral bioavailability of IND-nanomedicines was significantly enhanced. Evaluation based on either carrageenan-induced paw edema or complete Freund's adjuvant (CFA)-induced arthritis suggested the newly developed nanomedicines were more effective than raw IND or IND tablet in terms of prophylactic effect and therapeutic activity. Even the low dose of nanomedicines offered the comparable results to those of control groups at the high dosage in most cases. Moreover, the nanoformulation exhibited ameliorated gastrointestinal stimulation. All these positive results indicated that this type of nanomedicines might serve as a highly efficient and effective delivery nanoplatform for the oral delivery of water-insoluble therapeutics. Copyright © 2012 Elsevier B.V. All rights reserved.

[Preclinical prognosis of pyracetam and picamilon safety based on acute toxicity data].

PubMed

Bugaeva, L I; Spasov, A A; Verovskiĭ, V E; Iezhitsa, I N

2003-01-01

A comparative acute toxicity test of the nootropic drugs piracetam and picamilon was performed on rats. The study was based on the principles of integral evaluation of the drug effect upon the functional and behavioral state of animals. It was found that the conventional therapeutic index does not coincide with the actual therapeutic activity range. Piracetam and picamilon, while exhibiting significantly different toxicity, are characterized by approximately equal ranges of the therapeutic activity.

Opportunities and Challenges in Using Studies without a Control Group in Comparative Effectiveness Reviews

ERIC Educational Resources Information Center

Paulus, Jessica K.; Dahabreh, Issa J.; Balk, Ethan M.; Avendano, Esther E.; Lau, Joseph; Ip, Stanley

2014-01-01

When examining the evidence on therapeutic interventions to answer a comparative effectiveness research question, one should consider all studies that are informative on the interventions' causal effects. "Single group studies" evaluate outcomes longitudinally in cohorts of subjects who are managed with a single treatment strategy.…

[Identification of novel therapeutically effective antibiotics using silkworm infection model].

PubMed

Hamamoto, Hiroshi; Urai, Makoto; Paudel, Atmika; Horie, Ryo; Murakami, Kazuhisa; Sekimizu, Kazuhisa

2012-01-01

Most antibiotics obtained by in vitro screening with antibacterial activity have inappropriate properties as medicines due to their toxicity and pharmacodynamics in animal bodies. Thus, evaluation of the therapeutic effects of these samples using animal models is essential in the crude stage. Mammals are not suitable for therapeutic evaluation of a large number of samples due to high costs and ethical issues. We propose the use of silkworms (Bombyx mori) as model animals for screening therapeutically effective antibiotics. Silkworms are infected by various pathogenic bacteria and are effectively treated with similar ED(50) values of clinically used antibiotics. Furthermore, the drug metabolism pathways, such as cytochrome P450 and conjugation systems, are similar between silkworms and mammals. Silkworms have many advantages compared with other infection models, such as their 1) low cost, 2) few associated ethical problems, 3) adequate body size for easily handling, and 4) easier separation of organs and hemolymph. These features of the silkworm allow for efficient screening of therapeutically effective antibiotics. In this review, we discuss the advantages of the silkworm model in the early stages of drug development and the screening results of some antibiotics using the silkworm infection model.

[Clinical observation on fuzhong (supporting the middle-jiao) manipulation of tuina for infantile anorexia].

PubMed

Wang, Yuan-Yuan; Liu, Xiao-Ying

2014-01-01

To observe clinical therapeutic effect of fuzhong (supporting the middle-jiao) manipulation of tuina for infantile anorexia. Eighty-one children with anorexia were treated with fuzhong manipulation, including abdominal kneading, acupressure at Zhongwan (CV 12), Lanmen (Extra), Tianshu (ST 25), Zusanli (ST 36), Sanyinjiao (SP 6), spine pinching, warm moxibustion and warm scraping with supporting-yang cupping, three times a week, six times as a session. Onset time, therapeutic effect and TCM symptom scores before and after treatment were observed after two sessions and differences of therapeutic effect among different patterns were compared. Seventy-two children had the effect in one session while 41 children had the effect within half of a session. 38 cases were clinically cured, 15 cases were markedly effective, 23 cases were effective and 5 cases were failed. The total effective rate was 93.8%. Compared with before treatment, TCM symptom scores, including appetite, food intake, complexion and defecation, were all obviously improved after treatment (all P < 0.001). The clinical cured rate was 45.2% (19/42) in the pattern of dysfunction of spleen in transportation, 45.8% (11/24) in the pattern of qi deficiency of spleen and stomach, 50.0% (4/8) in the pattern of yin deficiency of spleen and stomach, 57.1% (4/7) in the pattern of liver sufficiency and spleen insufficiency, which had no obvious differences among different patterns (all P > 0.05). The fuzhong manipulation of tuina has quick onset time and satisfied clinical therapeutic effect, which could obviously improve symptoms and is fit for different patterns of infantile anorexia.

Experimental motion sickness - Efficacy of transdermal scopolamine plus ephedrine

NASA Technical Reports Server (NTRS)

Graybiel, A.; Cramer, D. B.; Wood, C. D.

1981-01-01

A double-blind, placebo-controlled study compared the efficacy of transdermal therapeutic system-scopolamine administered alone and combined with ephedrine sulfate given orally in doses of 12.5, 25, and 50 mg. Eight normal male students were exposed to stressful accelerations in a slow-rotation room after receiving 10 apparently identical treatments comprising the four drugs and six placebos. Efficacy of the drug was defined in terms of the placebo range and categorized as beneficial, inconsequential, or detrimental. None of the effects was detrimental. Overall beneficial effects were 60% for transdermal therapeutic system-scopolamine (plus placebo) and 57% for the three transdermal therapeutic system-scopolamine plus ephedrine combinations.

The Cannabis Dilemma: A Review of Its Associated Risks and Clinical Efficacy.

PubMed

Zhang, Melvyn Weibin; Ho, Roger C M

2015-01-01

Cannabis, also known as marijuana, has 9-tetrahydrocannabinol as the main constituent. There has been strict legislation governing the utilization of cannabis locally and worldwide. However, there has been an increasing push to make cannabis legalized, in view of its potential medical and therapeutic effects, for various medical disorders ranging from development disorders to cancer treatment, and being an adjunctive medication for various neurological conditions. It is the aim of this review paper to explore the evidence base for its proposed therapeutic efficacy and to compare the evidence base supporting its proposed therapeutic efficacy with its known and well-researched medical and psychiatric side effects.

[Therapeutic effect of early applying hydrotherapy with Chinese drugs on children hypoxic ischemic encephalopathy].

PubMed

Ma, Yun-Zhi; Zhai, Hong-Yin; Su, Chun-Ya

2009-02-01

To observe the therapeutic effect of hydrotherapy with Chinese drugs (HT-C) in early intervention on children hypoxic ischemic encephalopathy (HIE). HIE children were assigned to the treatment group and the control group, 50 in each, at random depending on the willingness of patients' parents. Both groups received the conventional functional training, according to the "0 -3-year-old early intervention outline", but for the treatment group, HT-C was applied additionally. Indexes for quality of sleep, gross motor function, severity of spasm and intellectual development were observed and compared before and after treatment to assess the therapeutic effects. Therapeutic effect in the treatment group was better than that in the control group in all the indexes observed, showing statistical significance (all P <0.05). Early intervention of HT-C could improve clinical symptom, promote the functional recovery and intellectual development in children HIE, and also could reduce or prevent the sequelae occurrence of the nervous system in them.

Effect of therapeutic class on counseling in community pharmacies.

PubMed

Vainio, Kirsti K; Airaksinen, Marja S A; Hyykky, Tarja T; Enlund, K Hannes

2002-05-01

To assess the effect and importance of the therapeutic class of a drug as a determinant for verbal counseling by community pharmacists. Direct external observations (n = 1431) of pharmacist-customer interactions at the point of delivery of prescription medicines were conducted in 7 community pharmacies in Finland. Trained observers noted whether the pharmacist provided information on directions for use, mode of action, and adverse effects. To examine factors associated with counseling, a multiple logistic regression analysis was constructed, with the dependent variable being counseling of any of the 3 observed topics. In addition to therapeutic class, other independent variables were the pharmacy; pharmacist's age, gender, and degree; and the customer's age, gender, previous use of medicine, and question asking. Provision of counseling differed significantly according to therapeutic classes. Counseling on any of the 3 observed topics was most likely to be provided for customers with antibiotics (80%) and least likely for customers with gynecologic preparations (18%). Differences between therapeutic classes remained statistically significant when the effects of the other variables were controlled for. Other significant predictors for any verbal counseling were the pharmacy, customer's previous use of the medicine, and question asking. Therapeutic class is an important variable that should be included in further studies and considered when comparing studies on patient counseling in community pharmacies.

Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats.

PubMed

Omori, Yoshinori; Honmou, Osamu; Harada, Kuniaki; Suzuki, Junpei; Houkin, Kiyohiro; Kocsis, Jeffery D

2008-10-21

The systemic injection of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has therapeutic benefits after cerebral artery occlusion in rats, and may have multiple therapeutic effects at various sites and times within the lesion as the cells respond to a particular pathological microenvironment. However, the comparative therapeutic benefits of multiple injections of hMSCs at different time points after cerebral artery occlusion in rats remain unclear. In this study, we induced middle cerebral artery occlusion (MCAO) in rats using intra-luminal vascular occlusion, and infused hMSCs intravenously at a single 6 h time point (low and high cell doses) and various multiple time points after MCAO. From MRI analyses lesion volume was reduced in all hMSC cell injection groups as compared to serum alone injections. However, the greatest therapeutic benefit was achieved following a single high cell dose injection at 6 h post-MCAO, rather than multiple lower cell infusions over multiple time points. Three-dimensional analysis of capillary vessels in the lesion indicated that the capillary volume was equally increased in all of the cell-injected groups. Thus, differences in functional outcome in the hMSC transplantation subgroups are not likely the result of differences in angiogenesis, but rather from differences in neuroprotective effects.

[Animal experiment comparison of the therapeutic efficacy of tumor excision with a scalpel or with a CO2 laser in subcutaneously implanted Lewis lung cancer].

PubMed

Mahn, H R; Nowak, C; Audring, H; Liebetruth, J; Lindenau, K F

1982-02-01

An animal experimental study was carried out in order to compare the therapeutical value of two different surgical methods for excising the subcutaneous implanted Lewis lung carcinoma - tumor excision with scalpel or with carbon dioxide laser. The radicalism of operation methods, the survival time, and the tumor local recurrences were performed. The therapeutic effectivity of tumor excision with the carbon dioxide laser is more favourable than the scalpel method.

Fluoroscopically Guided Diagnostic and Therapeutic Intra-Articular Sacroiliac Joint Injections: A Systematic Review.

PubMed

Kennedy, David J; Engel, Andrew; Kreiner, D Scott; Nampiaparampil, Devi; Duszynski, Belinda; MacVicar, John

2015-08-01

To assess the validity of fluoroscopically guided diagnostic intra-articular injections of local anesthetic and effectiveness of intra-articular steroid injections in treating sacroiliac joint (SIJ) pain. Systematic review. Ten reviewers independently assessed 45 publications on diagnostic validity or effectiveness of fluoroscopically guided intra-articular SIJ injections. For diagnostic injections, the primary outcome was validity; for therapeutic injections, analgesia. Secondary outcomes were also described. Of 45 articles reviewed, 39 yielded diagnostic data on physical exam findings, provocation tests, and SIJ injections for diagnosing SIJ pain, and 15 addressed therapeutic effectiveness. When confirmed by comparative local anesthetic blocks with a high degree of pain relief, no single physical exam maneuver predicts response to diagnostic injections. When at least three physical exam findings are present, sensitivity, and specificity increases significantly. The prevalence of SIJ pain is likely 20-30% among patients that have suspected SIJ pain based on history and physical examination. This estimate may be higher in certain subgroups such as the elderly and fusion patients. Two randomized controlled trials and multiple observational studies supported the effectiveness of therapeutic sacroiliac joint injections. Based on this literature, it is unclear whether image-guided intra-articular diagnostic injections of local anesthetic predict positive responses to therapeutic agents. The overall quality of evidence is moderate for the effectiveness of therapeutic SIJ injections. Wiley Periodicals, Inc.

[Peloid therapy. An overview of the empirical status and evidence of mud therapy].

PubMed

Beer, A-M; Fetaj, S; Lange, U

2013-08-01

Numerous peloids for balneotherapy are currently available but in terms of effects and efficacy therapeutic peat has been studied best. Recent studies revealed that both thermal and physical effects of therapeutic peat are comparable and synergistic. The thermal effects of all types of peat used are approximately the same but chemical effects differ. These results have to been taken into account in future peloid analyses and indications and contraindications of mud therapy have to be reviewed in this respect. Some hypothetical aspects of these chemical effects have to be investigated in future clinical studies but clinical experience with mud therapy allows preliminary conclusions to be drawn. This statement is especially supported by recent molecular investigations. Knowledge about the chemical effects is also necessary for planning, defining and designing clinical studies and patients groups. Exemplarily, the therapeutic use of peat in rheumatic diseases and for fertility treatment will be demonstrated.

Monomeric CH3: A Small, Stable Antibody Domain with Therapeutic Promise | Poster

Cancer.gov

By Ashley DeVine, Staff Writer Antibody domains are emerging as promising biopharmaceuticals because of their relatively small size compared to full-sized antibodies, which are too large to effectively penetrate tumors and bind to sterically restricted therapeutic targets. In an article published in The Journal of Biological Chemistry, Tianlei Ying, Ph.D., Dimiter Dimitrov,

Comparative effectiveness of antihypertensive therapeutic classes and treatment strategies in the initiation of therapy in primary care patients: a Distributed Ambulatory Research in Therapeutics Network (DARTNet) study.

PubMed

Bronsert, Michael R; Henderson, William G; Valuck, Robert; Hosokawa, Patrick; Hammermeister, Karl

2013-01-01

Few comparative effectiveness studies of treatment strategies using antihypertensive therapeutic classes in hypertension control have been assessed in a primary care environment. The objectives are to compare the effectiveness of common antihypertensive therapeutic classes initiated as monotherapy and of fixed-dose combinations (FDCs), free-equivalent combinations (FECs), and monotherapy on hypertension control. This article reports observational comparative effectiveness analyses of data electronically extracted from electronic health records. The study population consisted of 8,676 patients with an incident prescription for an antihypertensive agent of a total of 79,176 patients receiving antihypertensive therapy in 33 geographically diverse primary care clinics. The main measures were reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) and rates of attaining goals per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7). There were small, clinically insignificant differences in blood pressure reductions between the monotherapy classes. Higher rates of blood pressure control were obtained when patients were initiated on an angiotensin-converting enzyme inhibitor than a thiazide or thiazide-like diuretic (47.8% vs 39.9%) or a β-blocker versus a thiazide (45.9% vs 39.9%). Patients initiated on FDCs had significantly larger reductions in blood pressure than patients initiated on FECs (-17.3 vs -12.0 mm Hg SBP; -10.1 vs -6.0 mm Hg DBP) or monotherapy (-17.3 vs -13.6 mm Hg SBP; -10.1 vs -7.9 mm Hg DBP). Rates of attaining JNC7 goals also were better for FDCs than FECs (57.2% vs 42.5%) and for FDCs versus monotherapy (57.2% vs 44.9%). Patients initiated on angiotensin-converting enzyme inhibitors and β-blockers had slightly higher rates of blood pressure control. The use of FDCs as initial therapy is more effective in the control of hypertension than monotherapy or FECs.

Development and Characterization of Methylene Blue Oleate Salt-Loaded Polymeric Nanoparticles and their Potential Application as a Treatment for Glioblastoma

PubMed Central

Castañeda-Gill, JM; Ranjan, AP; Vishwanatha, JK

2017-01-01

Glioblastoma (GBM) is an aggressive, grade IV brain tumor that develops from astrocytes located within the cerebrum, resulting in poor prognosis and survival rates following an accepted treatment regimen of surgery, radiation, and temozolomide. Thus, development of new therapeutics is necessary. During the last two decades, methylene blue (MB) has received increased attention as a potential neurotherapeutic due to its duality in brain cancers and neurodegenerative diseases. While MB is capable of easily permeating the blood-brain barrier, its therapeutic concentrations in GBM are known to induce off-target cytotoxicity and thus, another mode of drug delivery must be considered. To this end, encapsulation of formerly unusable compounds into nanoparticles (NPs) made from the biodegradable/biocompatible, FDA approved co-polymer poly (lactide-co-glycolide) (PLGA) has been more commonplace when developing novel therapeutics. In this study, we formulated and characterized Pluronic F68-coated PLGA NPs containing a sodium oleate conjugate of MB (MBOS) via solvent displacement. Conjugation of sodium oleate to MB was shown to reduce its release from PLGA NPs compared to unmodified MB, leading to potential improvements in drug accumulation and therapeutic effectiveness. Our drug-loaded NP preparations, which were ~170 nm in size and had drug loading values of ~2%, were shown to reduce cell viability and cell compartment-specific, as well as overall cell, functions equivalenty, if not more so, when compared to free drug in two GBM cell lines. Following bio-distribution analysis of free MBOS compared to its nano-encapsulated counterpart, drug-loaded NPs were shown to more effectively permeate the BBB, which could lead to improvements in therapeutic effectiveness upon further examination in a tumor-bearing mouse model. Based on these results, we believe that the further development and eventual utilization of this nanoformulation could lead to an effective GBM therapy that could extend patient survival rates. PMID:29034126

A systematic approach to identify therapeutic effects of natural products based on human metabolite information.

PubMed

Noh, Kyungrin; Yoo, Sunyong; Lee, Doheon

2018-06-13

Natural products have been widely investigated in the drug development field. Their traditional use cases as medicinal agents and their resemblance of our endogenous compounds show the possibility of new drug development. Many researchers have focused on identifying therapeutic effects of natural products, yet the resemblance of natural products and human metabolites has been rarely touched. We propose a novel method which predicts therapeutic effects of natural products based on their similarity with human metabolites. In this study, we compare the structure, target and phenotype similarities between natural products and human metabolites to capture molecular and phenotypic properties of both compounds. With the generated similarity features, we train support vector machine model to identify similar natural product and human metabolite pairs. The known functions of human metabolites are then mapped to the paired natural products to predict their therapeutic effects. With our selected three feature sets, structure, target and phenotype similarities, our trained model successfully paired similar natural products and human metabolites. When applied to the natural product derived drugs, we could successfully identify their indications with high specificity and sensitivity. We further validated the found therapeutic effects of natural products with the literature evidence. These results suggest that our model can match natural products to similar human metabolites and provide possible therapeutic effects of natural products. By utilizing the similar human metabolite information, we expect to find new indications of natural products which could not be covered by previous in silico methods.

A novel albumin nanocomplex containing both small interfering RNA and gold nanorods for synergetic anticancer therapy

NASA Astrophysics Data System (ADS)

Choi, Jin-Ha; Hwang, Hai-Jin; Shin, Seung Won; Choi, Jeong-Woo; Um, Soong Ho; Oh, Byung-Keun

2015-05-01

Therapeutic nanocomplexes have been extensively developed for the effective treatment of aggressive cancers because of their outstanding versatility, easy manipulation, and low cytotoxicity. In this study, we describe the synthesis of a novel bovine serum albumin (BSA)-based nanocomplex harboring both Bcl-2-specific small interfering RNA (siRNA) and gold (Au) nanorods (siRNA and rods encapsulated in BSA; SREB) with the aim of developing a targeted breast cancer therapeutic. The SREB complexes contained 2 × 105 siRNA molecules and eight Au nanorods per BSA complex and were successively functionalized with polyethylene glycol (PEG) and anti-ErbB-2 antibodies to facilitate active targeting. The synergetic therapeutic activity originating from the two components effectively induced cell death (~80% reduction in viability compared with control cells) in target breast cancer cells after a single dose of laser irradiation. Intracellular SREB nanocomplex decomposition by proteolytic enzymes resulted in simultaneous RNA interference and thermal ablation, thus leading to apoptosis in the targeted cancer cells. Moreover, these therapeutic effects were sustained for approximately 72 hours. The intrinsic biocompatibility, multifunctionality, and potent in vitro anticancer properties of these SREB nanocomplexes indicate that they have great therapeutic potential for in vivo targeted cancer therapy, in addition to other areas of nanomedicine.Therapeutic nanocomplexes have been extensively developed for the effective treatment of aggressive cancers because of their outstanding versatility, easy manipulation, and low cytotoxicity. In this study, we describe the synthesis of a novel bovine serum albumin (BSA)-based nanocomplex harboring both Bcl-2-specific small interfering RNA (siRNA) and gold (Au) nanorods (siRNA and rods encapsulated in BSA; SREB) with the aim of developing a targeted breast cancer therapeutic. The SREB complexes contained 2 × 105 siRNA molecules and eight Au nanorods per BSA complex and were successively functionalized with polyethylene glycol (PEG) and anti-ErbB-2 antibodies to facilitate active targeting. The synergetic therapeutic activity originating from the two components effectively induced cell death (~80% reduction in viability compared with control cells) in target breast cancer cells after a single dose of laser irradiation. Intracellular SREB nanocomplex decomposition by proteolytic enzymes resulted in simultaneous RNA interference and thermal ablation, thus leading to apoptosis in the targeted cancer cells. Moreover, these therapeutic effects were sustained for approximately 72 hours. The intrinsic biocompatibility, multifunctionality, and potent in vitro anticancer properties of these SREB nanocomplexes indicate that they have great therapeutic potential for in vivo targeted cancer therapy, in addition to other areas of nanomedicine. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr00211g

Nanomedicine strategies for targeting skin inflammation.

PubMed

Abdel-Mottaleb, Mona Ma; Try, Celine; Pellequer, Yann; Lamprecht, Alf

2014-08-01

Topical treatment of skin diseases is an attractive strategy as it receives high acceptance from patients, resulting in higher compliance and therapeutic outcomes. Recently, the use of variable nanocarriers for dermal application has been widely explored, as they offer several advantages compared with conventional topical preparations, including higher skin penetration, controlled and targeted drug delivery and the achievement of higher therapeutic effects. This article will focus on skin inflammation or dermatitis as it is one of the most common skin problems, describing the different types and causes of dermatitis, as well as the typical treatment regimens. The potential use of nanocarriers for targeting skin inflammation and the achievement of higher therapeutic effects using nanotechnology will be explored.

Therapeutic effects of nandrolone and testosterone in adult male HIV patients with AIDS wasting syndrome (AWS): a randomized, double-blind, placebo-controlled trial.

PubMed

Sardar, Partha; Jha, Ayan; Roy, Deeptarka; Majumdar, Uddalak; Guha, Pradipta; Roy, Sabyasachi; Banerjee, Ramtanu; Banerjee, Amit Kumar; Bandyopadhyay, Dipanjan

2010-01-01

We aimed to compare therapeutic effects of intramuscular (IM) nandrolone decanoate and IM testosterone enanthate in male HIV patients with AIDS wasting syndrome (AWS) with placebo control. In this randomized, double-blind, placebo-controlled, 12-week trial, 104 patients with AWS who satisfied our inclusion criteria were randomly allotted in a 2:2:1 ratio to the 3 intervention groups: nandrolone, testosterone, and placebo. We administered 150 mg nandrolone and 250 mg testosterone (both IM, biweekly). The primary outcome measure was a comparison of absolute change in weight at 12 weeks between the nandrolone decanoate, testosterone, and placebo groups. Intent-to-treat analysis was done. The nandrolone group recorded maximum mean increase in weight (3.20 kg; post hoc P < .01 compared to placebo). Body mass index (BMI) of subjects in the nandrolone group had a significantly greater increase (mean = 1.28) compared to both testosterone (post hoc P < .05) and placebo (post hoc P < .01). Waist circumference and triceps skinfold thickness of patients on nandrolone showed similar results. Nandrolone also ensured a better quality of life. Patients with low testosterone level (<3 ng/mL) benefited immensely from nandrolone therapy, which increased their weight and BMI significantly compared to placebo (P < .05). Our trial demonstrates the superior therapeutic effects of nandrolone in male AWS patients, including the androgen deficient.

Subjective and physiological effects after controlled Sativex and oral THC administration.

PubMed

Karschner, E L; Darwin, W D; McMahon, R P; Liu, F; Wright, S; Goodwin, R S; Huestis, M A

2011-03-01

Sativex is a cannabis-plant extract delivering nearly 1:1 Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and "good drug effects" with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses.

Economic evaluations in pain management: principles and methods.

PubMed

Asche, Carl V; Seal, Brian; Jackson, Kenneth C; Oderda, Gary M

2006-01-01

This paper describes how investigators may design, conduct, and report economic evaluations of pharmacotherapy for pain and symptom management. Because economic evaluation of therapeutic interventions is becoming increasingly important, there is a need for guidance on how economic evaluations can be optimally conducted. The steps required to conduct an economic evaluation are described to provide this guidance. Economic evaluations require two or more therapeutic interventions to be compared in relation to costs and effects. There are five types of economic evaluations, based on analysis of: (1) cost-effectiveness, (2) cost-utility, (3) cost-minimization, (4) cost-consequence, and (5) cost-benefit analyses. The six required steps are: identify the perspective of the study; identify the alternatives that will be compared; identify the relevant costs and effects; determine how to collect the cost and effect data; determine how to perform calculation for cost and effects data; and determine the manner in which to depict the results and draw comparisons.

[Therapeutic qualities of a lente preparation of swine insulins manufactured by Pharmachem].

PubMed

Andreev, D; Bozadzhieva, E; Pampulov, L; Penchev, I; Uzunova, B

1977-01-01

The therapeutic effect of swine insulin preparation Lente, "Pharmachim" production was studied in 50 diabetics. Its hypoglycemizing activitis compared with that of standardized insulin Lente--"Novo", extract of bovine pancreas. The Bulgarian preparation was found to be very similar to the preparation Lente-Novo in its pharma-codynamic properties and could successfully be used in the diabetes melitus treatment. Insulin Lente Pharmachim is presumed to have lower antigenicity as an extract of swine pancreas, which is actually its great advantage for the therapeutic practice.

Therapeutic hypothermia in patients following traumatic brain injury: a systematic review.

PubMed

Dunkley, Steven; McLeod, Anne

2017-05-01

The efficacy of therapeutic hypothermia in adult patients with traumatic brain injury is not fully understood. The historical use of therapeutic hypothermia at extreme temperatures was associated with severe complications and led to it being discredited. Positive results from animal studies using milder temperatures led to renewed interest. However, recent studies have not convincingly demonstrated the beneficial effects of therapeutic hypothermia in practice. This review aims to answer the question: in adults with a severe traumatic brain injury (TBI), does the use of therapeutic hypothermia compared with normothermia affect neurological outcome? Systematic review. Four major electronic databases were searched, and a hand search was undertaken using selected key search terms. Inclusion and exclusion criteria were applied. The studies were appraised using a systematic approach, and four themes addressing the research question were identified and critically evaluated. A total of eight peer-reviewed studies were found, and the results show there is some evidence that therapeutic hypothermia may be effective in improving neurological outcome in adult patients with traumatic brain injury. However, the majority of the trials report conflicting results. Therapeutic hypothermia is reported to be effective at lowering intracranial pressure; however, its efficacy in improving neurological outcome is not fully demonstrated. This review suggests that therapeutic hypothermia had increased benefits in patients with haematoma-type injuries as opposed to those with diffuse injury and contusions. It also suggests that cooling should recommence if rebound intracranial hypertension is observed. Although the data indicates a trend towards better neurological outcome and reduced mortality rates, higher quality multi-centred randomized controlled trials are required before therapeutic hypothermia is implemented as a standard adjuvant therapy for treating traumatic brain injury. Therapeutic hypothermia can have a positive impact on patient outcome, but more research is required. © 2016 British Association of Critical Care Nurses.

Comparison of Estimates between Cohort and Case-Control Studies in Meta-Analyses of Therapeutic Interventions: A Meta-Epidemiological Study.

PubMed

Lanza, Amy; Ravaud, Philippe; Riveros, Carolina; Dechartres, Agnes

2016-01-01

Observational studies are increasingly being used for assessing therapeutic interventions. Case-control studies are generally considered to have greater risk of bias than cohort studies, but we lack evidence of differences in effect estimates between the 2 study types. We aimed to compare estimates between cohort and case-control studies in meta-analyses of observational studies of therapeutic interventions by using a meta-epidemiological study. We used a random sample of meta-analyses of therapeutic interventions published in 2013 that included both cohort and case-control studies assessing a binary outcome. For each meta-analysis, the ratio of estimates (RE) was calculated by comparing the estimate in case-control studies to that in cohort studies. Then, we used random-effects meta-analysis to estimate a combined RE across meta-analyses. An RE < 1 indicated that case-control studies yielded larger estimates than cohort studies. The final analysis included 23 meta-analyses: 138 cohort and 133 case-control studies. Treatment effect estimates did not significantly differ between case-control and cohort studies (combined RE 0.97 [95% CI 0.86-1.09]). Heterogeneity was low, with between-meta-analysis variance τ2 = 0.0049. Estimates did not differ between case-control and prospective or retrospective cohort studies (RE = 1.05 [95% CI 0.96-1.15] and RE = 0.99 [95% CI, 0.83-1.19], respectively). Sensitivity analysis of studies reporting adjusted estimates also revealed no significant difference (RE = 1.03 [95% CI 0.91-1.16]). Heterogeneity was also low for these analyses. We found no significant difference in treatment effect estimates between case-control and cohort studies assessing therapeutic interventions.

The effect of therapeutic touch on behavioral symptoms of persons with dementia.

PubMed

Woods, Diana Lynn; Craven, Ruth F; Whitney, Joie

2005-01-01

Approximately 80% of nursing home residents who suffer from Alzheimer's disease and related dementia develop behavioral symptoms of dementia. Given the deleterious side effects of pharmacologic therapy in this population there is an urgent need for clinical trials of nonpharmacologic interventions. To examine the effect of therapeutic touch on the frequency and intensity of behavioral symptoms of dementia. A randomized, double-blind, three-group experimental study: experimental (therapeutic touch), placebo (placebo therapeutic touch), and control (usual care). Fifty-seven residents, aged 67 to 93 years, exhibiting behavioral symptoms of dementia, were randomized to one of the three groups within each of three Special Care Units within three Long-Term Care facilities in a western Canadian province. Behavioral observation was completed every 20 minutes from 8:00AM to 6:00PM for three days pre-intervention and for three days post-intervention by trained observers who were blind to group assignment. The intervention consisted of therapeutic touch given twice daily for 5-7 minutes for three days between 10:00AM and 11:30PM and between 3:00PM and 4:30PM (N = 57). The main outcome variable was overall behavioral symptoms of dementia, consisting of six categories of behaviors: manual manipulation (restlessness), escape restraints, searching and wandering, tapping and banging, pacing and walking, and vocalization. Analysis of variance (ANOVA) (F = 3.331, P = .033) and the Kruskal-Wallis test (chi2 = 6.661, P = .036) indicated a significant difference in overall behavioral symptoms of dementia, manual manipulation and vocalization when the experimental group was compared to the placebo and control groups. The experimental (significant) was more effective in decreasing behavioral symptoms of dementia than usual care, while the placebo group indicated a decreasing trend in behavioral symptoms of dementia compared to usual care. Therapeutic touch offers a nonpharmacological, clinically relevant modality that could be used to decrease behavioral symptoms of dementia, specifically manual manipulation (restlessness) and vocalization, two prevalent behaviors.

IL17/IL17RA as a Novel Signaling Axis Driving Mesenchymal Stem Cell Therapeutic Function in Experimental Autoimmune Encephalomyelitis.

PubMed

Kurte, Mónica; Luz-Crawford, Patricia; Vega-Letter, Ana María; Contreras, Rafael A; Tejedor, Gautier; Elizondo-Vega, Roberto; Martinez-Viola, Luna; Fernández-O'Ryan, Catalina; Figueroa, Fernando E; Jorgensen, Christian; Djouad, Farida; Carrión, Flavio

2018-01-01

The therapeutic effect of mesenchymal stem cells (MSCs) in multiple sclerosis (MS) and the experimental autoimmune encephalomyelitis (EAE) model has been well described. This effect is, in part, mediated through the inhibition of IL17-producing cells and the generation of regulatory T cells. While proinflammatory cytokines such as IFNγ, TNFα, and IL1β have been shown to enhance MSCs immunosuppressive function, the role of IL17 remains poorly elucidated. The aim of this study was, therefore, to investigate the role of the IL17/IL17R pathway on MSCs immunoregulatory effects focusing on Th17 cell generation in vitro and on Th17-mediated EAE pathogenesis in vivo . In vitro , we showed that the immunosuppressive effect of MSCs on Th17 cell proliferation and differentiation is partially dependent on IL17RA expression. This was associated with a reduced expression level of MSCs immunosuppressive mediators such as VCAM1, ICAM1, and PD-L1 in IL17RA -/- MSCs as compared to wild-type (WT) MSCs. In the EAE model, we demonstrated that while WT MSCs significantly reduced the clinical scores of the disease, IL17RA -/- MSCs injected mice exhibited a clinical worsening of the disease. The disability of IL17RA -/- MSCs to reduce the progression of the disease paralleled the inability of these cells to reduce the frequency of Th17 cells in the draining lymph node of the mice as compared to WT MSCs. Moreover, we showed that the therapeutic effect of MSCs was correlated with the generation of classical Treg bearing the CD4 + CD25 + Foxp3 + signature in an IL17RA-dependent manner. Our findings reveal a novel role of IL17RA on MSCs immunosuppressive and therapeutic potential in EAE and suggest that the modulation of IL17RA in MSCs could represent a novel method to enhance their therapeutic effect in MS.

Fenetylline: therapeutic use, misuse and/or abuse.

PubMed

Kristen, G; Schaefer, A; von Schlichtegroll, A

1986-06-01

Fenetylline (CAPTAGON) is included in a list of compounds to be considered by a World Health Organization (WHO) Expert Committee in April 1985 for possible international scheduling under the Convention on Psychotropic Substances, 1971. For over 23 years, this central stimulant has been used therapeutically in hyperkinetic children and other indications in place of amphetamines and other central stimulants with higher risk levels. In good correspondence with recent animal data fenetylline also shows significant qualitative and quantitative differences compared to amphetamine in man. It has few adverse side effects, a lower abuse potential and little actual abuse compared to amphetamine. Thus its benefit/risk assessment is substantially more favourable than that of other central stimulants. For proper therapeutic use of the substance, prescription status is or should be required by national authorities.

Hierarchical Micro/Nano-Porous Acupuncture Needles Offering Enhanced Therapeutic Properties

NASA Astrophysics Data System (ADS)

in, Su-Ll; Gwak, Young S.; Kim, Hye Rim; Razzaq, Abdul; Lee, Kyeong-Seok; Kim, Hee Young; Chang, Suchan; Lee, Bong Hyo; Grimes, Craig A.; Yang, Chae Ha

2016-10-01

Acupuncture as a therapeutic intervention has been widely used for treatment of many pathophysiological disorders. For achieving improved therapeutic effects, relatively thick acupuncture needles have been frequently used in clinical practice with, in turn, enhanced stimulation intensity. However due to the discomforting nature of the larger-diameter acupuncture needles there is considerable interest in developing advanced acupuncture therapeutical techniques that provide more comfort with improved efficacy. So motivated, we have developed a new class of acupuncture needles, porous acupuncture needles (PANs) with hierarchical micro/nano-scale conical pores upon the surface, fabricated via a simple and well known electrochemical process, with surface area approximately 20 times greater than conventional acupuncture needles. The performance of these high-surface-area PANs is evaluated by monitoring the electrophysiological and behavioral responses from the in vivo stimulation of Shenmen (HT7) points in Wistar rats, showing PANs to be more effective in controlling electrophysiological and behavioral responses than conventional acupuncture needles. Comparative analysis of cocaine induced locomotor activity using PANs and thick acupuncture needles shows enhanced performance of PANs with significantly less pain sensation. Our work offers a unique pathway for achieving a comfortable and improved acupuncture therapeutic effect.

Hierarchical Micro/Nano-Porous Acupuncture Needles Offering Enhanced Therapeutic Properties

PubMed Central

In, Su-ll; Gwak, Young S.; Kim, Hye Rim; Razzaq, Abdul; Lee, Kyeong-Seok; Kim, Hee Young; Chang, SuChan; Lee, Bong Hyo; Grimes, Craig A.; Yang, Chae Ha

2016-01-01

Acupuncture as a therapeutic intervention has been widely used for treatment of many pathophysiological disorders. For achieving improved therapeutic effects, relatively thick acupuncture needles have been frequently used in clinical practice with, in turn, enhanced stimulation intensity. However due to the discomforting nature of the larger-diameter acupuncture needles there is considerable interest in developing advanced acupuncture therapeutical techniques that provide more comfort with improved efficacy. So motivated, we have developed a new class of acupuncture needles, porous acupuncture needles (PANs) with hierarchical micro/nano-scale conical pores upon the surface, fabricated via a simple and well known electrochemical process, with surface area approximately 20 times greater than conventional acupuncture needles. The performance of these high-surface-area PANs is evaluated by monitoring the electrophysiological and behavioral responses from the in vivo stimulation of Shenmen (HT7) points in Wistar rats, showing PANs to be more effective in controlling electrophysiological and behavioral responses than conventional acupuncture needles. Comparative analysis of cocaine induced locomotor activity using PANs and thick acupuncture needles shows enhanced performance of PANs with significantly less pain sensation. Our work offers a unique pathway for achieving a comfortable and improved acupuncture therapeutic effect. PMID:27713547

The short-term effects of TENS plus therapeutic ultrasound combinations in chronic neck pain.

PubMed

Sayilir, Selcuk

2018-05-01

To investigate the effects of TENS plus therapeutic ultrasound combinations on symptom relief, physical functionality, perceived stress levels, daytime sleepiness and neck mobility in patients with chronic neck pain (CNP). A total of 64 patients were divided into two groups as the TENS plus ultrasound group (n = 39) and the control CNP group (n = 25). The therapy comprised TENS and therapeutic ultrasound applications for 10 sessions. The control subjects were discouraged from using analgesics but were allowed to use paracetamol daily, if necessary. The Neck Disability Index (NDI), Epworth Sleepiness Scale (ESS), Perceived Stress Scale (PSS), visual analog scale (VAS) and tragus-wall/chin-manubrium distances were recorded at the baseline and after therapy. Significant improvements were detected in the TENS plus ultrasound group compared to the control CNP subjects in respect of VAS, PSS and NDI scores after the TENS plus therapeutic ultrasound therapies (all p < 0.05). The combination of therapeutic ultrasound plus TENS can be an effective modality for relieving pain/stress levels and improving functionality in the short-term of CNP. Copyright © 2018 Elsevier Ltd. All rights reserved.

Latent cytokines for targeted therapy of inflammatory disorders.

PubMed

Mullen, Lisa; Adams, Gill; Layward, Lorna; Vessillier, Sandrine; Annenkov, Alex; Mittal, Gayatri; Rigby, Anne; Sclanders, Michelle; Baker, David; Gould, David; Chernajovsky, Yuti

2014-01-01

The use of cytokines as therapeutic agents is important, given their potent biological effects. However, this very potency, coupled with the pleiotropic nature and short half-life of these molecules, has limited their therapeutic use. Strategies to increase the half-life and to decrease toxicity are necessary to allow effective treatment with these molecules. A number of strategies are used to overcome the natural limitations of cytokines, including PEGylation, encapsulation in liposomes, fusion to targeting peptides or antibodies and latent cytokines. Latent cytokines are engineered using the latency-associated peptide of transforming growth factor-β to produce therapeutic cytokines/peptides that are released only at the site of disease by cleavage with disease-induced matrix metalloproteinases. The principles underlying the latent cytokine technology are described and are compared to other methods of cytokine delivery. The potential of this technology for developing novel therapeutic strategies for the treatment of diseases with an inflammatory-mediated component is discussed. Methods of therapeutic cytokine delivery are addressed. The latent cytokine technology holds significant advantages over other methods of drug delivery by providing simultaneously increased half-life and localised drug delivery without systemic effects. Cytokines that failed clinical trials should be reassessed using this delivery system.

Comparing drug classification systems.

PubMed

Mahoney, Anne; Evans, Jonathan

2008-11-06

An essential quality of drug classification systems is the ability to assign medications to a structured hierarchy for categories such as mechanism of action, physiological effects, and therapeutic indications. No single classification system can meet all of these needs; however, there should be consistency among those that group by the same underlying principals. We discovered discrepancies in how drugs with multiple therapeutic indications are classified among four widely used schemas.

Effect and Feasibility of Therapeutic Hypothermia in Patients with Hemorrhagic Stroke: A Systematic Review and Meta-Analysis.

PubMed

Yao, Zhong; You, Chao; He, Min

2018-03-01

Therapeutic hypothermia (TH) has shown good results in experimental models of hemorrhagic stroke. The clinical application of TH, however, remains controversial, since reports regarding its therapeutic effect are inconsistent. We conducted a systematic review based on Preferred Reporting Items for Systematic Reviews and Meta-analyses comparing TH with a control group in terms of mortality, poor outcome, delayed cerebral ischemia (DCI), and specific complications. The subgroup analyses were stratified by study type, country, mean age, hemorrhage type, cooling method, treatment duration, rewarming velocity, and follow-up time. Nine studies were included, most of which were of moderate quality. The overall effect demonstrated insignificant differences in mortality (risk ratio [RR] 0.78; 95% confidence interval [CI] 0.58-1.06; P = 0.11) and poor outcome rate (RR 0.89; 95% CI 0.70-1.12; P = 0.32) between TH and the control group. However, sensitivity analyses, after we omitted 1 study, achieved a statistically significant difference in poor outcome favoring TH. Moreover, in the subgroup analyses, the results derived from randomized studies revealed that TH significantly reduced poor outcomes (RR 0.40; 95% CI 0.22-0.74; P = 0.003). In addition, TH significantly reduced DCI compared with control (RR 0.61; 95% CI 0.40-0.93; P = 0.02). The incidence of specific complications (rebleeding, pneumonia, sepsis, arrhythmia, and hydrocephalus) between the 2 groups were comparable and did not reach significant difference. The overall effect showed TH did not significantly reduce mortality and poor outcomes but led to a decreased incidence of DCI. Compared with control, TH resulted in comparable incidences of specific complications. Copyright © 2018 Elsevier Inc. All rights reserved.

[Observation on therapeutic effect of chronic fatigue syndrome treated with coiling dragon needling and moving cupping on back].

PubMed

Xu, Wei; Zhou, Ri-Hua; Li, Lei; Jiang, Ming-Wei

2012-03-01

To compare the differences of therapeutic effect of chronic fatigue syndrome treated with the combined therapy of coiling dragon needling and cupping on back and the western medicine therapy with Prednisone. Seventy-two cases were randomly divided into an acupuncture and cupping group (37 cases) and a Prednisone group (35 cases). In acupuncture and cupping group, Jiaji (EX-B 2) points of T1--L5 were applied with coiling dragon needling (once a day), combined with moving cupping on back (once every two days); in Prednisone group, Prednisone tablets were orally taken for 10 mg at 8:00 am. Seven days made one course, and 2 courses were carried on totally. FS-14 scale and BELL's chronic fatigue syndrome integral table were applied to evaluate the fatigue degree of patients before and after treatment, and the therapeutic effects of both groups were compared. After one course of treatment, the BELL's scores of both groups were obviously improved (both P < 0.01), but there was no significant difference between groups (P > 0.05); after two courses of treatment, the BELL's score in acupuncture and cupping group improved more obviously than that in Prednisone group, and the total effective rate of 91.9% (34/37) in acupuncture and cupping group was superior to that of 71.4% (25/35) in Prednisone group (P < 0.05). The therapeutic effect of chronic fatigue syndrome treated with coiling dragon needling and moving cupping on back is positive, superior to that of Prednisone with oral administration.

[Cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of rheumatoid arthritis].

PubMed

Salinas-Escudero, Guillermo; Vargas-Valencia, Juan; García-García, Erika Gabriela; Munciño-Ortega, Emilio; Galindo-Suárez, Rosa María

2013-01-01

to conduct cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of moderate or severe rheumatoid arthritis in patients with previous unresponse to immune selective anti-inflammatory derivatives failure. a pharmacoeconomic model based on decision analysis to assess the clinical outcome after giving etanercept, infliximab, adalimumab or tocilizumab to treat moderate or severe rheumatoid arthritis was employed. Effectiveness of medications was assessed with improvement rates of 20 % or 70 % of the parameters established by the American College of Rheumatology (ACR 20 and ACR 70). the model showed that etanercept had the most effective therapeutic response rate: 79.7 % for ACR 20 and 31.4 % for ACR 70, compared with the response to other treatments. Also, etanercept had the lowest cost ($149,629.10 per patient) and had the most cost-effective average ($187,740.40 for clinical success for ACR 20 and $476,525.80 for clinical success for ACR 70) than the other biologic therapies. we demonstrated that treatment with etanercept is more effective and less expensive compared to the other drugs, thus making it more efficient therapeutic option both in terms of means and incremental cost-effectiveness ratios for the treatment of rheumatoid arthritis.

The therapeutic effect of negative pressure in treating femoral head necrosis in rabbits.

PubMed

Zhang, Yin-gang; Wang, Xuezhi; Yang, Zhi; Zhang, Hong; Liu, Miao; Qiu, Yushen; Guo, Xiong

2013-01-01

Because negative pressure can stimulate vascular proliferation, improve blood circulation and promote osteogenic differentiation of bone marrow stromal cells, we investigated the therapeutic effect of negative pressure on femoral head necrosis (FHN) in a rabbit model. Animals were divided into four groups (n = 60/group): [1] model control, [2] core decompression, [3] negative pressure and [4] normal control groups. Histological investigation revealed that at 4 and 8 weeks postoperatively, improvements were observed in trabecular bone shape, empty lacunae and numbers of bone marrow hematopoietic cells and fat cells in the negative pressure group compared to the core decompression group. At week 8, there were no significant differences between the negative pressure and normal control groups. Immunohistochemistry staining revealed higher expression of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) in the femoral heads in the negative pressure group compared with the core decompression group. Transmission electron microscopy revealed that cell organelles were further developed in the negative pressure group compared with the core decompression group. Microvascular ink staining revealed an increased number of bone marrow ink-stained blood vessels, a thicker vascular lumen and increased microvascular density in the negative pressure group relative to the core decompression group. Real-time polymerase chain reaction revealed that expression levels of both VEGF and BMP-2 were higher in the negative pressure group compared with the core decompression group. In summary, negative pressure has a therapeutic effect on FHN. This effect is superior to core decompression, indicating that negative pressure is a potentially valuable method for treating early FHN.

The Therapeutic Effect of Negative Pressure in Treating Femoral Head Necrosis in Rabbits

PubMed Central

Zhang, Yin-gang; Wang, Xuezhi; Yang, Zhi; Zhang, Hong; Liu, Miao; Qiu, Yushen; Guo, Xiong

2013-01-01

Because negative pressure can stimulate vascular proliferation, improve blood circulation and promote osteogenic differentiation of bone marrow stromal cells, we investigated the therapeutic effect of negative pressure on femoral head necrosis (FHN) in a rabbit model. Animals were divided into four groups (n = 60/group): [1] model control, [2] core decompression, [3] negative pressure and [4] normal control groups. Histological investigation revealed that at 4 and 8 weeks postoperatively, improvements were observed in trabecular bone shape, empty lacunae and numbers of bone marrow hematopoietic cells and fat cells in the negative pressure group compared to the core decompression group. At week 8, there were no significant differences between the negative pressure and normal control groups. Immunohistochemistry staining revealed higher expression of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) in the femoral heads in the negative pressure group compared with the core decompression group. Transmission electron microscopy revealed that cell organelles were further developed in the negative pressure group compared with the core decompression group. Microvascular ink staining revealed an increased number of bone marrow ink-stained blood vessels, a thicker vascular lumen and increased microvascular density in the negative pressure group relative to the core decompression group. Real-time polymerase chain reaction revealed that expression levels of both VEGF and BMP-2 were higher in the negative pressure group compared with the core decompression group. In summary, negative pressure has a therapeutic effect on FHN. This effect is superior to core decompression, indicating that negative pressure is a potentially valuable method for treating early FHN. PMID:23383276

Induced Hypothermia Does Not Harm Hemodynamics after Polytrauma: A Porcine Model

PubMed Central

Mommsen, Philipp; Pfeifer, Roman; Mohr, Juliane; Ruchholtz, Steffen; Flohé, Sascha; Fröhlich, Matthias; Keibl, Claudia; Seekamp, Andreas; Witte, Ingo

2015-01-01

Background. The deterioration of hemodynamics instantly endangers the patients' life after polytrauma. As accidental hypothermia frequently occurs in polytrauma, therapeutic hypothermia still displays an ambivalent role as the impact on the cardiopulmonary function is not yet fully understood. Methods. We have previously established a porcine polytrauma model including blunt chest trauma, penetrating abdominal trauma, and hemorrhagic shock. Therapeutic hypothermia (34°C) was induced for 3 hours. We documented cardiovascular parameters and basic respiratory parameters. Pigs were euthanized after 15.5 hours. Results. Our polytrauma porcine model displayed sufficient trauma impact. Resuscitation showed adequate restoration of hemodynamics. Induced hypothermia had neither harmful nor major positive effects on the animals' hemodynamics. Though heart rate significantly decreased and mixed venous oxygen saturation significantly increased during therapeutic hypothermia. Mean arterial blood pressure, central venous pressure, pulmonary arterial pressure, and wedge pressure showed no significant differences comparing normothermic trauma and hypothermic trauma pigs during hypothermia. Conclusions. Induced hypothermia after polytrauma is feasible. No major harmful effects on hemodynamics were observed. Therapeutic hypothermia revealed hints for tissue protective impact. But the chosen length for therapeutic hypothermia was too short. Nevertheless, therapeutic hypothermia might be a useful tool for intensive care after polytrauma. Future studies should extend therapeutic hypothermia. PMID:26170533

The effect of corticosteroid versus platelet-rich plasma injection therapies for the management of lateral epicondylitis: A systematic review

PubMed Central

Ben-Nafa, Walid; Munro, Wendy

2018-01-01

Introduction: Lateral epicondylitis is a common musculoskeletal disorder of the upper limb. Corticosteroid injection has been widely used as a major mode of treatment. However, better understanding of the pathophysiology of the disease led to a major change in treating the disease, with new options including platelet-rich plasma (PRP) are currently used. Objectives/research aim: To systematically evaluate the effect of corticosteroid versus PRP injections for the treatment of LE. Hypothesis: PRP injections provide longer-term therapeutic effect and less rate of complications compared to corticosteroid injection. Level of evidence: Level 2 evidence (4 included studies are of level 1 evidence, 1 study of level 2 evidence). Design: Systematic Review (according to PRISMA guidelines). Methods: Eleven databases used to search for relevant primary studies comparing the effects of corticosteroid and PRP injections for the treatment of LE. Quality appraisal of studies performed using Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, CASP Randomised Controlled Trial Checklist, and SIGN Methodology Checklist 2. Results: 732 papers were identified. Five randomised controlled trials (250 Patients) met the inclusion criteria. Clinical findings: Corticosteroid injections provided rapid symptomatic improvement with maximum effect at 6/8/8 weeks before symptoms recurrence, whereas PRP showed slower ongoing improvements up to 24/52/104 weeks(3 studies). Corticosteroid showed more rapid symptomatic improvement of symptoms compared to PRP up to the study end-point of 3 months(1 study). Comparable therapeutic effects of corticosteroid and PRP were observed at 6 weeks(1 study). Ultrasonographic Findings: (1) Doppler activity decreased more significantly in patients who received corticosteroid compared to PRP. (2) Reduced tendon thickness and more patients with cortical erosion noted in corticosteroid group whereas increased tendon thickness and less number of patients with common extensor tendon tears noted in PRP group. (3) Fewer patients reported Probe-induced tenderness and oedema in the common extensor tendon in both corticosteroid and PRP groups (2 studies). Conclusion: Corticosteroid injections provide rapid therapeutic effect in the short-term with recurrence of symptoms afterwards, compared to the relatively slower but longer-term effect of platelet-rich plasma. PMID:29561260

Adverse reactions to methylphenidate treatment for attention-deficit/hyperactivity disorder: structure and associations with clinical characteristics and symptom control.

PubMed

Sonuga-Barke, Edmund J S; Coghill, David; Wigal, Timothy; DeBacker, Marc; Swanson, James

2009-12-01

Methylphenidate (MPH)-related adverse events are well characterized. Their predictors and their relationship with therapeutic effects are less well understood. Here we examine these issues in relation to two long-acting formulations. Comparison of Methylphenidates in the Analog Classroom Setting (COMACS) was made in a large (n = 184) placebo-controlled trial comparing Equasym XL/Metadate CD, Concerta, and placebo (PLA) using a Laboratory School protocol. Therapeutic effects were measured using direct observation, scores on a simple math productivity task and parent ratings. Parents also completed the Barkley Stimulant Side Effect Rating Scale (BSSERS). The BSSERS had six factors: Emotionality, sleep/appetite, disengaged, dizzy, uninterested, and aches. Treatment effects were seen only for emotionality (which improved) and sleep and appetite (which worsened). Adverse events were not predictable from personal and clinical characteristics of patients. Sleep/appetite adverse events were not associated with therapeutic effects. Improvements in attention-deficit/hyperactivity disorder (ADHD) and emotionality were correlated. The results support a narrow conceptualization of MPH adverse events with problems restricted to appetite and sleep. These effects were not predictable on the basis of available information and may be due to an underlying mechanism rather distinct from those determining therapeutic effects.

Subjective and Physiological Effects After Controlled Sativex and Oral THC Administration

PubMed Central

Karschner, EL; Darwin, WD; McMahon, RP; Liu, F; Wright, S; Goodwin, RS; Huestis, MA

2013-01-01

Sativex is a cannabis-plant extract delivering nearly 1:1 Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and “good drug effects” with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses. PMID:21289620

Therapeutic alliance in a randomized clinical trial for bulimia nervosa

PubMed Central

Accurso, Erin C.; Fitzsimmons-Craft, Ellen E.; Ciao, Anna; Cao, Li; Crosby, Ross D.; Smith, Tracey L.; Klein, Marjorie H.; Mitchell, James E.; Crow, Scott J.; Wonderlich, Stephen A.; Peterson, Carol B.

2015-01-01

Objective This study examined the temporal relation between therapeutic alliance and outcome in two treatments for bulimia nervosa (BN). Method Eighty adults with BN symptoms were randomized to 21 sessions of integrative cognitive-affective therapy (ICAT) or enhanced cognitive-behavioral therapy (CBT-E). Bulimic symptoms (i.e., frequency of binge eating and purging) were assessed at each session and post-treatment. Therapeutic alliance (Working Alliance Inventory) was assessed at sessions 2, 8, 14, and post-treatment. Repeated-measures analyses using linear mixed models with random intercepts were conducted to determine differences in alliance growth by treatment and patient characteristics. Mixed-effects models examined the relation between alliance and symptom improvement. Results Overall, patients in both treatments reported strong therapeutic alliances. Regardless of treatment, greater therapeutic alliance between (but not within) subjects predicted greater reductions in bulimic behavior; reductions in bulimic behavior also predicted improved alliance. Patients with higher depression, anxiety, or emotion dysregulation had a stronger therapeutic alliance in CBT-E than ICAT, while those with more intimacy problems had greater improvement in therapeutic alliance in ICAT compared to CBT-E. Conclusions Therapeutic alliance has a unique impact on outcome, independent of the impact of symptom improvement on alliance. Within- and between-subject effects revealed that changes in alliance over time did not predict symptom improvement, but rather that individuals who had a stronger alliance overall had better bulimic symptom outcomes. These findings indicate that therapeutic alliance is an important predictor of outcome in the treatment of BN. PMID:25894667

Therapeutic alliance in a randomized clinical trial for bulimia nervosa.

PubMed

Accurso, Erin C; Fitzsimmons-Craft, Ellen E; Ciao, Anna; Cao, Li; Crosby, Ross D; Smith, Tracey L; Klein, Marjorie H; Mitchell, James E; Crow, Scott J; Wonderlich, Stephen A; Peterson, Carol B

2015-06-01

This study examined the temporal relation between therapeutic alliance and outcome in two treatments for bulimia nervosa (BN). Eighty adults with BN symptoms were randomized to 21 sessions of integrative cognitive-affective therapy (ICAT) or enhanced cognitive-behavioral therapy (CBT-E). Bulimic symptoms (i.e., frequency of binge eating and purging) were assessed at each session and posttreatment. Therapeutic alliance (Working Alliance Inventory) was assessed at Sessions 2, 8, 14, and posttreatment. Repeated-measures analyses using linear mixed models with random intercepts were conducted to determine differences in alliance growth by treatment and patient characteristics. Mixed-effects models examined the relation between alliance and symptom improvement. Overall, patients in both treatments reported strong therapeutic alliances. Regardless of treatment, greater therapeutic alliance between (but not within) subjects predicted greater reductions in bulimic behavior; reductions in bulimic behavior also predicted improved alliance. Patients with higher depression, anxiety, or emotion dysregulation had a stronger therapeutic alliance in CBT-E than ICAT, while those with more intimacy problems had greater improvement in therapeutic alliance in ICAT compared to CBT-E. Therapeutic alliance has a unique impact on outcome, independent of the impact of symptom improvement on alliance. Within- and between-subjects effects revealed that changes in alliance over time did not predict symptom improvement, but rather that individuals who had a stronger alliance overall had better bulimic symptom outcomes. These findings indicate that therapeutic alliance is an important predictor of outcome in the treatment of BN. (c) 2015 APA, all rights reserved).

Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease.

PubMed

Taravini, Irene R; Larramendy, Celia; Gomez, Gimena; Saborido, Mariano D; Spaans, Floor; Fresno, Cristóbal; González, Germán A; Fernández, Elmer; Murer, Mario G; Gershanik, Oscar S

2016-02-01

Whether the treatment of Parkinson's disease has to be initiated with levodopa or a D2 agonist like pramipexole remains debatable. Levodopa is more potent against symptoms than D2 agonists, but D2 agonists are less prone to induce motor complications and may have neuroprotective effects. Although regulation of plastic changes in striatal circuits may be the key to their different therapeutic potential, the gene expression patterns induced by de novo treatments with levodopa or D2 agonists are currently unknown. By studying the whole striatal transcriptome in a rodent model of early stage Parkinson's disease, we have identified the gene expression patterns underlying therapeutically comparable chronic treatments with levodopa or pramipexole. Despite the overall relatively small size of mRNA expression changes at the level of individual transcripts, our data show a robust and complete segregation of the transcript expression patterns induced by both treatments. Moreover, transcripts related to oxidative metabolism and mitochondrial function were enriched in levodopa-treated compared to vehicle-treated and pramipexole-treated animals, whereas transcripts related to olfactory transduction pathways were enriched in both treatment groups compared to vehicle-treated animals. Thus, our data reveal the plasticity of genetic striatal networks possibly contributing to the therapeutic effects of the most common initial treatments for Parkinson's disease, suggesting a role for oxidative stress in the long term complications induced by levodopa and identifying previously overlooked signaling cascades as potentially new therapeutic targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fluoxetine treatment is effective in a rat model of childhood-induced post-traumatic stress disorder.

PubMed

Ariel, Lior; Inbar, Sapir; Edut, Schachaf; Richter-Levin, Gal

2017-11-30

Although selective serotonin reuptake inhibitors (SSRIs) are first-line treatment for post-traumatic stress disorder (PTSD) patients, their therapeutic efficacy is limited. Childhood adversities are considered a risk factor for developing PTSD in adulthood but may trigger PTSD without additional trauma in some individuals. Nevertheless, just as childhood is considered a vulnerable period it may also be an effective period for preventive treatment. Using a rat model of childhood-induced PTSD, pre-pubertal stress (juvenile stress, JVS), we compared the therapeutic effects of fluoxetine and examined the effectiveness of 1 month of fluoxetine treatment following JVS and into adulthood compared to treatment in adulthood. Since not all individuals develop PTSD following a trauma, comparing only group means is not the adequate type of analysis. We employed a behavioral profiling approach, which analyzes individual differences compared to the normal behavior of a control group. Animals exposed to JVS exhibited a higher proportion of affected animals as measured using the elevated plus maze 8 weeks after JVS. Fluoxetine treatment following the JVS significantly decreased the proportion of affected animals as measured in adulthood. Fluoxetine treatment in adulthood was not effective. The results support the notion that childhood is not only a vulnerable period but also an effective period for preventive treatment.

Therapeutic indications and other use-case-driven updates in the drug ontology: anti-malarials, anti-hypertensives, opioid analgesics, and a large term request.

PubMed

Hogan, William R; Hanna, Josh; Hicks, Amanda; Amirova, Samira; Bramblett, Baxter; Diller, Matthew; Enderez, Rodel; Modzelewski, Timothy; Vasconcelos, Mirela; Delcher, Chris

2017-03-03

The Drug Ontology (DrOn) is an OWL2-based representation of drug products and their ingredients, mechanisms of action, strengths, and dose forms. We originally created DrOn for use cases in comparative effectiveness research, primarily to identify historically complete sets of United States National Drug Codes (NDCs) that represent packaged drug products, by the ingredient(s), mechanism(s) of action, and so on contained in those products. Although we had designed DrOn from the outset to carefully distinguish those entities that have a therapeutic indication from those entities that have a molecular mechanism of action, we had not previously represented in DrOn any particular therapeutic indication. In this work, we add therapeutic indications for three research use cases: resistant hypertension, malaria, and opioid abuse research. We also added mechanisms of action for opioid analgesics and added 108 classes representing drug products in response to a large term request from the Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM) project. The net result is a new version of DrOn, current to May 2016, that represents three major therapeutic classes of drugs and six new mechanisms of action. A therapeutic indication of a drug product is represented as a therapeutic function in DrOn. Adverse effects of drug products, as well as other therapeutic uses for which the drug product was not designed are dispositions. Our work provides a framework for representing additional therapeutic indications, adverse effects, and uses of drug products beyond their design. Our work also validated our past modeling decisions for specific types of mechanisms of action, namely effects mediated via receptor and/or enzyme binding. DrOn is available at: http://purl.obolibrary.org/obo/dron.owl . A smaller version without NDCs is available at: http://purl.obolibrary.org/obo/dron/dron-lite.owl.

ApoE3 mediated polymeric nanoparticles containing curcumin: apoptosis induced in vitro anticancer activity against neuroblastoma cells.

PubMed

Mulik, Rohit S; Mönkkönen, Jukka; Juvonen, Risto O; Mahadik, Kakasaheb R; Paradkar, Anant R

2012-11-01

Curcumin, a natural phytoconstituent, is known to be therapeutically effective in the treatment of various cancers such as, breast cancer, lung cancer, pancreatic cancer, brain cancer, etc. However, low bioavailability and photodegradation of curcumin hampers its overall therapeutic efficacy. Anionic polymerization method was employed for the preparation of apolipoprotein-E3 mediated curcumin loaded poly(butyl)cyanoacrylate nanoparticles (ApoE3-C-PBCA) and characterized for size, zeta potential, entrapment efficiency, photostability, morphology, and in vitro release study. ApoE3-C-PBCA were found to be effective against SH-SY5Y neuroblastoma cells compared to curcumin solution (CSSS) and curcumin loaded PBCA nanoparticles (C-PBCA) from in vitro cell culture investigations. Flow cytometry techniques employed for the detection of anticancer activity revealed enhanced activity of curcumin against SH-SY5Y neuroblastoma cells with ApoE3-C-PBCA compared to CSSS and C-PBCA, and apoptosis being the underlying mechanism. Present study revealed that ApoE3-C-PBCA has tremendous potential to develop into an effective therapeutic treatment modality against brain cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

PubMed

Beretta, Simone; Versace, Alessandro; Carone, Davide; Riva, Matteo; Dell'Era, Valentina; Cuccione, Elisa; Cai, Ruiyao; Monza, Laura; Pirovano, Silvia; Padovano, Giada; Stiro, Fabio; Presotto, Luca; Paternò, Giovanni; Rossi, Emanuela; Giussani, Carlo; Sganzerla, Erik P; Ferrarese, Carlo

2017-10-01

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p < 0.001) and higher chance of good functional outcome (OR 4.58, p < 0.001). Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p < 0.001) and lateral (+19.2%; p = 0.016) MCA territory compared to pretreatment during MCA occlusion. Safety indicators were treatment-related mortality and cardiorespiratory effects. The highest efficacy and safety profile was observed for HDT. Our findings suggest that acute modulation of cerebral collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

Immunomodulatory Effects of Deokgu Thermomineral Water Balneotherapy on Oxazolone-Induced Atopic Dermatitis Murine Model

PubMed Central

Lee, Young Bok; Kim, Su Jin; Park, Sae Mi; Lee, Kyung Ho; Han, Hyung Jin; Yu, Dong Soo; Woo, So Youn; Yun, Seong Taek; Hamm, Se-Yeong; Kim, Hong Jig

2016-01-01

Background Although the therapeutic mechanism of balneotherapy for atopic dermatitis has not been clarified, many atopic patients who visit thermomineral springs have shown clinical improvements. Objective This study was aimed to evaluate the immunomodulatory effect of thermomineral water balneotherapy on the atopic dermatitis murine model. Methods The oxazolone-induced atopic dermatitis murine model was used to evaluate the therapeutic effect of balneotherapy with Deokgu thermomineral water compared with distilled water. Histologic evaluation and confocal microscopic imaging were performed to analyze the lesional expression of cluster-of-differentiation (CD)4 and forkhead box p3 (Foxp3). Lesional mRNA expression of interleukin (IL) 33, thymic stromal lymphopoietin (TSLP), and Foxp3 was evaluated by real-time reverse transcription polymerase chain reaction. Results Compared with the distilled water bath group, confocal microscopic evaluation of CD4 and Foxp3 merged images showed increased expression of regulatory T cells in the thermomineral balneotherapy group. The lesional mRNA level of IL-33 showed a reduced trend in the thermomineral balneotherapy group, whereas the level of mRNA of Foxp3 was increased. TSLP showed a decreased trend in both distilled water and thermomineral water bath groups. There was a trend of reduced expression in lesional IL-33 mRNA but increased cell count of CD4+ Foxp3+ regulatory T cells in thermomineral balneotherapy compared with distilled water bath. Conclusion Therefore, thermomineral balneotherapy can be an effective and safe adjuvant therapeutic option for atopic dermatitis. PMID:27081266

Immunomodulatory Effects of Deokgu Thermomineral Water Balneotherapy on Oxazolone-Induced Atopic Dermatitis Murine Model.

PubMed

Lee, Young Bok; Kim, Su Jin; Park, Sae Mi; Lee, Kyung Ho; Han, Hyung Jin; Yu, Dong Soo; Woo, So Youn; Yun, Seong Taek; Hamm, Se-Yeong; Kim, Hong Jig; Kim, Jin-Wou

2016-04-01

Although the therapeutic mechanism of balneotherapy for atopic dermatitis has not been clarified, many atopic patients who visit thermomineral springs have shown clinical improvements. This study was aimed to evaluate the immunomodulatory effect of thermomineral water balneotherapy on the atopic dermatitis murine model. The oxazolone-induced atopic dermatitis murine model was used to evaluate the therapeutic effect of balneotherapy with Deokgu thermomineral water compared with distilled water. Histologic evaluation and confocal microscopic imaging were performed to analyze the lesional expression of cluster-of-differentiation (CD)4 and forkhead box p3 (Foxp3). Lesional mRNA expression of interleukin (IL) 33, thymic stromal lymphopoietin (TSLP), and Foxp3 was evaluated by real-time reverse transcription polymerase chain reaction. Compared with the distilled water bath group, confocal microscopic evaluation of CD4 and Foxp3 merged images showed increased expression of regulatory T cells in the thermomineral balneotherapy group. The lesional mRNA level of IL-33 showed a reduced trend in the thermomineral balneotherapy group, whereas the level of mRNA of Foxp3 was increased. TSLP showed a decreased trend in both distilled water and thermomineral water bath groups. There was a trend of reduced expression in lesional IL-33 mRNA but increased cell count of CD4(+) Foxp3(+) regulatory T cells in thermomineral balneotherapy compared with distilled water bath. Therefore, thermomineral balneotherapy can be an effective and safe adjuvant therapeutic option for atopic dermatitis.

Low power radiofrequency electromagnetic radiation for the treatment of pain due to osteoarthritis of the knee.

PubMed

Alcidi, L; Beneforti, E; Maresca, M; Santosuosso, U; Zoppi, M

2007-01-01

To investigate the analgesic effect of low power radiofrequency electromagnetic radiation (RF) in osteoarthritis (OA) of the knee. In a randomized study on 40 patients the analgesic effect of RF was compared with the effect of transcutaneous electrical nerve stimulation (TENS). RF and TENS applications were repeated every day for a period of 5 days. The therapeutic effect was evaluated by a visual analogue scale (VAS) and by Lequesne's index: tests were performed before, immediately after and 30 days after therapy. RF therapy induced a statistically significant and long lasting decrease of VAS and of Lequesne's index; TENS induced a decrease of VAS and of Lequesne's index which was not statistically significant. A therapeutic effect of RF was therefore demonstrated on pain and disability due to knee OA. This effect was better than the effect of TENS, which is a largely used analgesic technique. Such a difference of the therapeutic effect may be due to the fact that TENS acts only on superficial tissues and nerve terminals, while RF acts increasing superficial and deep tissue temperature.

A single-dose, crossover, placebo- and moxifloxacin-controlled study to assess the effects of neratinib (HKI-272) on cardiac repolarization in healthy adult subjects.

PubMed

Hug, Bruce; Abbas, Richat; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

2010-08-01

Neratinib is an orally administered, small-molecule, irreversible pan-ErbB inhibitor in development for the treatment of ErbB2-positive breast cancer. This study assessed the effects of therapeutic and supratherapeutic neratinib concentrations on cardiac repolarization, in accordance with current regulatory guidance. This was a two-part study in healthy subjects. In part 1, subjects were randomized to receive placebo, 400 mg moxifloxacin, or 240 mg neratinib (therapeutic dose) following a high-fat meal. In part 2, after a washout period, subjects received placebo plus 400 mg ketoconazole or 240 mg neratinib plus ketoconazole (supratherapeutic dose). ANOVA was used to compare the baseline-adjusted QTc interval for neratinib with that of placebo (reference), and for neratinib plus ketoconazole with that of placebo plus ketoconazole (reference). Pharmacokinetic/pharmacodynamic analyses and categorical summaries of interval data were done. Assay sensitivity was evaluated by the effect of moxifloxacin on QTc compared with placebo. Sixty healthy subjects were enrolled in this study. The upper bounds of the 90% confidence interval for baseline-adjusted QTcN (population-specific corrected QT) were 450 milliseconds or change from baseline >30 milliseconds. Moxifloxacin produced a significant increase in QTcN compared with placebo (P < 0.05). Therapeutic and supratherapeutic plasma concentrations of neratinib do not prolong the QTc interval in healthy subjects. (c) 2010 AACR.

Resveratrol regulates hyperglycemia-induced modulations in experimental diabetic animal model.

PubMed

Rehman, Kanwal; Saeed, Kiran; Munawar, Syeda Mehak; Akash, Muhammad Sajid Hamid

2018-06-01

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is associated with variable degrees of glucose intolerance, impaired insulin secretion, insulin resistance and increased hepatic glucose production. The aim of present study was to investigate the therapeutic potentials of resveratrol (RSV) alone and/or in combination with vitamin-E (Vit-E) against hyperglycemia-induced modulations using experimentally alloxan-induced diabetic animal model. Alloxan was used to induce diabetes mellitus in white albino rats and metformin (MF) was used as standard anti-diabetic drug to compare the therapeutic potentials of RSV (alone and/or with Vit-E) by estimating the effect of treatment on glycemia, insulin resistance, liver and kidney function biomarkers, anti-oxidant status, and serum levels of calcium and magnesium. The results of present study indicate the RSV (P < 0.001) alone and/or in combination with Vit-E (P < 0.001) exhibited a highly significant therapeutic potentials by ameliorating the glycemia-induced modulations. Moreover, we also found that RSV in combination with Vit-E also exhibited a better therapeutic effects when compared with that of MF (P < 0.001) and Vit-E (P < 0.05), respectively. Hence, we conclude that RSV alone and/or in combination with Vit-E exhibit its significant therapeutic potentials against hyperglycemia-induced modulations in experimental diabetic animal model and may be one of the most exciting prospect for future treatment of T2DM. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

[Study on effects of low frequency pulse plus auricular point magnetic therapy on electrogastrogram and clinical therapeutic effect in the patient of functional dyspepsia].

PubMed

Wang, Yan-Gang; Yao, Shu-Kun

2007-04-01

To compare therapeutic effects of low frequency pulse plus auricular point magnetic therapy and prepulsid on functional dyspepsia (FD). Fifty cases of FD were randomly divided into a treatment group and a control group. The treatment group were treated with low frequency pulse stimulation on Zhongwan (CV 12), Weishu (BL 21), Neiguan (PC 6), Zusanli (ST 36), with Fenglong (ST 40) and Sanyinjiao (SP 6) selected according to syndrome differentiation, once a day, 30 min each session. The control group were treated with oral administration of prepulsid. Five days constituted one course. The scores of symptoms and parameters of electrogastrogram (EGG) before and after treatment and the therapeutic effect were investigated. After treatment, the symptom scores significantly decreased (P < 0.01), with a significant difference in the decrease of symptom scores between the two groups (P < 0.05); and EGG parameters were improved (P < 0.05). The total effective rate of 93.3% in the treatment group was better than 75.0% in the control group with a significant difference between the two groups (P < 0.05). Low frequency pulse plus auricular point magnetic therapy can significantly improve the clinical symptoms and gastric activities in the patient of FD, with a better therapeutic effect than prepulsid.

Pharmacokinetic parameters explain the therapeutic activity of antimicrobial agents in a silkworm infection model.

PubMed

Paudel, Atmika; Panthee, Suresh; Urai, Makoto; Hamamoto, Hiroshi; Ohwada, Tomohiko; Sekimizu, Kazuhisa

2018-01-25

Poor pharmacokinetic parameters are a major reason for the lack of therapeutic activity of some drug candidates. Determining the pharmacokinetic parameters of drug candidates at an early stage of development requires an inexpensive animal model with few associated ethical issues. In this study, we used the silkworm infection model to perform structure-activity relationship studies of an antimicrobial agent, GPI0039, a novel nitrofuran dichloro-benzyl ester, and successfully identified compound 5, a nitrothiophene dichloro-benzyl ester, as a potent antimicrobial agent with superior therapeutic activity in the silkworm infection model. Further, we compared the pharmacokinetic parameters of compound 5 with a nitrothiophene benzyl ester lacking chlorine, compound 7, that exerted similar antimicrobial activity but had less therapeutic activity in silkworms, and examined the metabolism of these antimicrobial agents in human liver fractions in vitro. Compound 5 had appropriate pharmacokinetic parameters, such as an adequate half-life, slow clearance, large area under the curve, low volume of distribution, and long mean residence time, compared with compound 7, and was slowly metabolized by human liver fractions. These findings suggest that the therapeutic effectiveness of an antimicrobial agent in the silkworms reflects appropriate pharmacokinetic properties.

Is Real-World Evidence Used in P&T Monographs and Therapeutic Class Reviews?

PubMed

Hurwitz, Jason T; Brown, Mary; Graff, Jennifer S; Peters, Loretta; Malone, Daniel C

2017-06-01

Payers are faced with making coverage and reimbursement decisions based on the best available evidence. Often these decisions apply to patient populations, provider networks, and care settings not typically studied in clinical trials. Treatment effectiveness evidence is increasingly available from electronic health records, registries, and administrative claims. However, little is known about when and what types of real-world evidence (RWE) studies inform pharmacy and therapeutic (P&T) committee decisions. To evaluate evidence sources cited in P&T committee monographs and therapeutic class reviews and assess the design features and quality of cited RWE studies. A convenience sample of representatives from pharmacy benefit management, health system, and health plan organizations provided recent P&T monographs and therapeutic class reviews (or references from such documents). Two investigators examined and grouped references into major categories (published studies, unpublished studies, and other/unknown) and multiple subcategories (e.g., product label, clinical trials, RWE, systematic reviews). Cited comparative RWE was reviewed to assess design features (e.g., population, data source, comparators) and quality using the Good ReseArch for Comparative Effectiveness (GRACE) Checklist. Investigators evaluated 565 references cited in 27 monographs/therapeutic class reviews from 6 managed care organizations. Therapeutic class reviews mostly cited published clinical trials (35.3%, 155/439), while single-product monographs relied most on manufacturer-supplied information (42.1%, 53/126). Published RWE comprised 4.8% (21/439) of therapeutic class review references, and none (0/126) of the monograph references. Of the 21 RWE studies, 12 were comparative and assessed patient care settings and outcomes typically not included in clinical trials (community ambulatory settings [10], long-term safety [8]). RWE studies most frequently were based on registry data (6), conducted in the United States (6), and funded by the pharmaceutical industry (5). GRACE Checklist ratings suggested the data and methods of these comparative RWE studies were of high quality. RWE was infrequently cited in P&T materials, even among therapeutic class reviews where RWE is more readily available. Although few P&T materials cited RWE, the comparative RWE studies were generally high quality. More research is needed to understand when and what types of real-world studies can more routinely inform coverage and reimbursement decisions. This project was funded by the National Pharmaceutical Council. Hurwitz, Brown, Peters, and Malone have nothing to disclose. Graff is employed by the National Pharmaceutical Council Part of this study was presented as a poster presentation at the AMCP Managed Care & Specialty Pharmacy 2016 Annual Meeting; April 19-22, 2016; San Francisco, CA. Study concept and design were primarily contributed by Malone and Graff, along with Hurwitz and Brown. All authors participated in data collection, and data interpretation was performed by Malone, Hurwitz, and Graff, with assistance from Brown and Peters. The manuscript was written primarily by Hurwitz and Malone, along with Graff, Brown, and Peters, and revised by Malone, Brown, Peters, Hurwitz, and Graff.

[Cost-effectiveness of local steroid combined with therapeutic exercise in subacromial impingement syndrome].

PubMed

Ramírez-Ortiz, Julio; Mendoza-Eufracio, José Dolores; García-Viveros, María Ricarda; Márquez-Celedonio, Félix Guillermo

2017-01-01

The most common cause of injury is shoulder impingement syndrome. Management includes physical therapy, analgesics, steroids and surgery. The aim of the study was to determine the cost-effectiveness of using steroids combined with therapeutic exercise at home in the chronic impingement syndrome. Clinical trial randomized in 30 people with subacromial impingement syndrome underwent two treatments: steroid and at home rehabilitation booklet evaluated at the first and fourth week through UCLA Shoulder rating scale. We studied 17 men (56.7 %) and 13 women (43.3 %), mean age was 42.87 years. Group 2 earned greater improvement in UCLA Shoulder rating scale 18.87 at baseline and 27.60 at the end. With 30.27 accumulated disability days for group 1, and 14.80 for group 2. The combination of local steroids with therapeutic exercise is more effective clinically and declining disability compared to conventional physical therapy.

Bio-enhancing Effect of Piperine with Metformin on Lowering Blood Glucose Level in Alloxan Induced Diabetic Mice.

PubMed

Atal, Shubham; Atal, Sarjana; Vyas, Savita; Phadnis, Pradeep

2016-01-01

Diabetes mellitus is the most rampant metabolic pandemic of the 21(st) century. Piperine, the chief alkaloid of Piper nigrum (black pepper) is widely used in alternative and complementary therapies has been extensively studied for its bio-enhancing property. To evaluate the bio-enhancing effect of piperine with metformin in lowering blood glucose levels in alloxan-induced diabetic mice. Piperine was isolated from an extract of fruits of P. nigrum. Alloxan-induced (150 mg/kg intraperitoneal) diabetic mice were divided into four groups. Group I (control 2% gum acacia 2 g/100 mL), Group II (metformin 250 mg/kg), Group III (metformin and piperine 250 mg/kg + 10 mg/kg), and Group IV (metformin and piperine 125 mg/kg + 10 mg/kg). All the drugs were administered orally once daily for 28 days. Blood glucose levels were estimated at day 0, day 14, and end of the study (day 28). The combination of piperine with therapeutic dose of metformin (10 mg/kg + 250 mg/kg) showed significantly more lowering of blood glucose level as compared to metformin alone on both 14(th) and 28(th) day (P < 0.05). Piperine in combination with sub-therapeutic dose of metformin (10 mg/kg + 125 mg/kg) showed significantly more lowering of blood glucose as compared to control group and also showed greater lowering of blood glucose as compared to metformin (250 mg/kg) alone. Piperine has the potential to be used as a bio-enhancing agent in combination with metformin which can help reduce the dose of metformin and its adverse effects. Piperine is known for its bioenhancing property. This study evaluates the effect of piperine in combination with oral antidiabetic drug metformin. Drugs were administered for 28 days in alloxan induced diabetic mice and blood glucose lowering effect was seen. Results showed significantly better effect of combination of piperine with therapeutic dose of metformin in comparison to metformin alone. Piperine in combination with subtherapeutic dose of metformin also showed better effect than therapeutic dose of metformin. Piperine, thus shows potential to be used as bioenhancer in combination with metformin.

Simultaneous silencing of ACSL4 and induction of GADD45B in hepatocellular carcinoma cells amplifies the synergistic therapeutic effect of aspirin and sorafenib

PubMed Central

Xia, Hongping; Lee, Kee Wah; Chen, Jianxiang; Kong, Shik Nie; Sekar, Karthik; Deivasigamani, Amudha; Seshachalam, Veerabrahma Pratap; Goh, Brian Kim Poh; Ooi, London Lucien; Hui, Kam M

2017-01-01

Sorafenib is currently the only US Food and Drug Administration (FDA)-approved molecular inhibitor for the systemic therapy of advanced hepatocellular carcinoma (HCC). Aspirin has been studied extensively as an anti-inflammation, cancer preventive and therapeutic agent. However, the potential synergistic therapeutic effects of sorafenib and aspirin on advanced HCC treatment have not been well studied. Drug combination studies and their synergy quantification were performed using the combination index method of Chou-Talalay. The synergistic therapeutic effects of sorafenib and aspirin were evaluated using an orthotopic mouse model of HCC and comprehensive gene profiling analyses were conducted to identify key factors mediating the synergistic therapeutic effects of sorafenib and aspirin. Sorafenib was determined to act synergistically on HCC cells with aspirin in vitro. Using Hep3B and HuH7 HCC cells, it was demonstrated that sorafenib and aspirin acted synergistically to induce apoptosis. Mechanistic studies demonstrated that combining sorafenib and aspirin yielded significant synergistically anti-tumor effects by simultaneously silencing ACSL4 and the induction of GADD45B expression in HCC cells both in vitro and in the orthotopic HCC xenograft mouse model. Importantly, clinical evidence has independently corroborated that survival of HCC patients expressing ACSL4highGADD45Blow was significantly poorer compared to patients with ACSL4lowGADD45Bhigh, thus demonstrating the potential clinical value of combining aspirin and sorafenib for HCC patients expressing ACSL4highGADD45Blow. In conclusion, sorafenib and aspirin provide synergistic therapeutic effects on HCC cells that are achieved through simultaneous silencing of ACSL4 and induction of GADD45B expression. Targeting HCC with ACSL4highGADD45Blow expression with aspirin and sorafenib could provide potential synergistic therapeutic benefits. PMID:28900541

Effects of Real and Recalled Success on Learned Helplessness and Depression

ERIC Educational Resources Information Center

Teasdale, John D.

1978-01-01

The effects of recalling past successes on the deficits in learned helplessness and depression were examined and, for learned helplessness, compared with those of real success. Results suggest real success does not have its therapeutic effects by modifying attributions for failure toward external factors. (Editor)

Comparison the effects of two types of therapeutic exercises Frenkele vs. Swiss ball on the clinical balance measures in patients with type II diabetic neuropathy.

PubMed

Rojhani-Shirazi, Zahra; Barzintaj, Fatemeh; Salimifard, Mohamad Reza

2017-11-01

The number of diabetic patients is increasing in the world. Peripheral neuropathy is the most important problem of diabetes. Neuropathy eventually leads to balance impairment which is the main cause of falling down in these patients However, not sufficient evidences available to compare different protocols for improving balance in diabetic patients. This study aimed to compare the effects of two therapeutic exercises on clinical balance measures in patients with type II diabetic peripheral neuropathy. The study was performed on 60 patients with diabetes categorized randomly into three groups: an intervention group (N=20) that received ball training exercise, another intervention group (N=20) that received Frenkel exercise and a control group (N=20) that received no interventions. Exercise training session was performed for 3 weeks. Then, clinical balance measures were computed in the three groups. Paired t-test and one-way ANOVA were used to analyze the collected data. Both types of therapeutic exercise programs significantly improved balance in single leg stance, star excursion test, and Berg balance scale test (P˂0.05) compared to the control group. Besides, this was more significant in the ball training group (P˂0.05). To improve balance in diabetic neuropathy, Swiss ball exercise is preferred compared to Frenkel training. Copyright © 2016. Published by Elsevier Ltd.

Therapeutic Effects of Topical Tranexamic Acid in Comparison with Hydroquinone in Treatment of Women with Melasma.

PubMed

Atefi, Najmolsadat; Dalvand, Behzad; Ghassemi, Mahammadreza; Mehran, Golnaz; Heydarian, Amir

2017-09-01

Few studies have focused on therapeutic as well as side effects of tranexamic acid (TXA) as a topical drug compared to other topical drugs in treating melasma. The present study aimed to assess and compare the beneficial therapeutic effects and also side effects of local TXA in comparison with hydroquinone in treating women with melasma. This randomized double-blinded clinical trial was performed on 60 women who suffered from melasma and were referred to the skin disorders clinic at the Rasoul-e-Akram hospital in Tehran in 2015. The patients were then randomly assigned via computerized randomization to two groups: group A received TXA%5 (topically twice a day for 12 weeks in the location of the melasma) and group B (received hydroquinone 2% with the same treatment order). Prior to intervention and at 12 weeks after intervention, the intensity and extension of melasma were assessed based on the Melasma Area and Severity Index (MASI) scoring method. The mean MASI score in both treatment groups decreased considerably after completion of treatment and was not significant between the two groups. No side effects were detected in group A, but 10% of those in group B complained of drug-related side effects including erythema and skin irritation (p = 0.131). Regarding the level of patient satisfaction, the patients in group A had a significantly higher level of satisfaction level of 33.3% compared with 6.7% in group B (p = 0.015) (Fig. 9). Multivariate linear regression modeling with the presence of age, history of systemic disorder, drug history, and family history of melasma demonstrated no difference in the mean MASI between the two groups. Topical use of TXA significantly reduced both melanin level and MASI score. Given its high efficiency and low drug side effects, this regimen results in high patient satisfaction compared with topical hydroquinone. IRCT code: IRCT2016040627220N2.

Efficacy of topical latanoprost versus minoxidil and betamethasone valerate on the treatment of alopecia areata.

PubMed

El-Ashmawy, Amal Ahmad; El-Maadawy, Iman Hamed; El-Maghraby, Gamal Mohamed

2018-02-01

Alopecia areata (AA) is one of the most common causes of localized hair loss. There is no universally proven therapy that induces and sustains remission of hair growth in AA. To compare the efficacy and safety of topical latanoprost, minoxidil and betamethasone valerate on hair growth in patients with AA. Hundred patients with AA classified into five groups of 20 treated with: Group I, latanoprost 0.1% lotion; Group II, minoxidil 5% lotion; Group III, betamethasone valerate 0.1% solution; Group IV, combination of latanoprost lotion and betamethasone valerate solution and Group V, a vehicle lotion control group. There was a statistically significant improvement in all therapeutic groups when compared with control group and reduction of severity of alopecia tool score of scalp and beard before and after treatment for all therapeutic groups. Latanoprost, minoxidil and betamethasone valerate are effective and safe in the treatment of patchy AA. The use of latanoprost added to the therapeutic efficacy of topical betamethasone valerate in the treatment of AA and could be an effective adjunctive topical therapy for AA.

[Experimental study on protective effects of HupA in the treatment of isocarbophos poisoning].

PubMed

Liu, Li; Xie, Guang-yun; Wang, Jian; Sun, Jin-xiu

2006-06-01

To investigate the therapeutic and prophylactic efficiency of HupA in mice with acute isocarbophos poisoning, and the protective effects of the HupA on AChE inhibited by isocarbophos. Mice were randomizedly divided into the non-treatment group, the atropine control group, the HupA treatment group and the atropine and HupA combined treatment group. Toxic signs and survival rates were observed and compared among these groups. The AChE activity was monitored in the whole blood, the red cells and brain tissue exposed to isocarbophos in the either treated with HupA or non-treated groups. In HupA treatment group compared with the non-treatment group, toxic signs were significantly decreased and the survival rate was increased. The therapeutic efficiency in the atropine and HupA combined treatment group was better than other groups. After isocarbophos was administered, the AChE activity in the HupA treatment group and the non-treatment group was decreased. However, the AChE activity in the whole blood (1.096 +/- 0.111), (1.262 +/- 0.146), (1.181 +/- 0.353) U/ml, the red cells (0.798 +/- 0.063), (1.000 +/- 0.176), (0.837 +/- 0.331) and the brain tissue (13.739 +/- 2.970), (18.507 +/- 3.466), (10.764 +/- 2.212) U/g in HupA treatment group 0.5, 1 and 2 hours after isocarbophos was administered was significantly higher than those in the non-treatment group (P < 0.05 or P < 0.01). HupA has therapeutic effect on mice with acute isocarbophos poisoning. The protective effect of HupA on blood and brain AChE inhibited by isocarbophos may be one of the mechanisms of the therapeutic effect of HupA in acute Isocarbophos poisoning.

Modelling the cancer growth process by Stochastic Differential Equations with the effect of Chondroitin Sulfate (CS) as anticancer therapeutics

NASA Astrophysics Data System (ADS)

Syahidatul Ayuni Mazlan, Mazma; Rosli, Norhayati; Jauhari Arief Ichwan, Solachuddin; Suhaity Azmi, Nina

2017-09-01

A stochastic model is introduced to describe the growth of cancer affected by anti-cancer therapeutics of Chondroitin Sulfate (CS). The parameters values of the stochastic model are estimated via maximum likelihood function. The numerical method of Euler-Maruyama will be employed to solve the model numerically. The efficiency of the stochastic model is measured by comparing the simulated result with the experimental data.

[Observation on therapeutic effect of three needling method on piriformis injury syndrome].

PubMed

Yang, Jun-xiong; Zhu, Xiao-yi

2008-03-01

To search for an effective needling method for treatment of piriformis injury syndrome. Eighty-two cases were randomly divided into a three needling group and a routine needling group, 41 cases in each group. The three needling group were treated by acupuncture at Huantiao (GB 30), Yanglingquan (GB 34) and Shenmai (BL 62), with needling shallow, middle and deep layers for Huantiao, Yanglingquan, and after acupuncture massage was given at the Foot-Taiyang Channel and the Foot-Shaoyang Channel on lumbosacral region and the affected foot. The routine needling group were treated by routine needling at Huantiao (GB 30), Juliao (GB 29), Chengfu (BL 36), Yanglingquan (GB 34), massage was given also. Their therapeutic effects were compared. The cured rate was 87.8% in the three needling group and 63.4% in the routine needling group, with a significant difference between the two groups (P < 0.05). The therapeutic effect of three needling method on piriformis injury syndrome is better than that of routine needling.

Fractional CO2 laser is an effective therapeutic modality for xanthelasma palpebrarum: a randomized clinical trial.

PubMed

Esmat, Samia M; Elramly, Amany Z; Abdel Halim, Dalia M; Gawdat, Heba I; Taha, Hanaa I

2014-12-01

Xanthelasma palpebrarum (XP) is a common cosmetic concern. Although there is a wide range of therapeutic modalities for XP, there is no general consensus on the optimal treatment for such condition. Compare the efficacy and safety of super pulsed (SP) and fractional CO2 lasers in the treatment of XP. This prospective randomized comparative clinical study included 20 adult patients with bilateral and symmetrical XP lesions. Xanthelasma palpebrarum lesions were randomly assigned to treatment by either single session of ablative SP CO2 laser or 3 to 5 sessions of ablative fractional CO2 laser with monthly intervals. All patients were assessed using digital photography and optical coherence tomography images. Xanthelasma palpebrarum lesions on both sides were successfully removed with significant improvement in size, color, and thickness. Although lesions treated by SP CO2 laser showed significantly better improvement regarding color and thickness of the lesions, downtime and patient satisfaction were significantly better for lesions treated with fractional CO2 laser. Scarring and recurrence were significantly higher in lesions treated by SP CO2 laser. Ablative fractional CO2 laser is an effective and safe therapeutic option for XP with significantly shorter downtime and higher patient satisfaction compared with SP CO2 laser.

Clinical application of a new 0.63- to 0.65-μm pulse diode laser in treating ear, throat, and nose diseases in adults and children

NASA Astrophysics Data System (ADS)

Nasedkin, Alexy N.; Pletnev, A. S.

2001-04-01

An investigation was made of applying a pulsed diode laser emitting at the wavelengths of 0.63 to 0.65 micrometers to treat various otolaryngological diseases, such as rhinosinusitis, acute rhinitis, vasomotor rhinitis, allergic rhinitis, the illness of the lymphoid ring, adenoiditis, chronic tonsillitis, pharyngitis, and catarrhal and suppurative otitis. The therapeutic effect produced by the pulsed diode laser was compared with that of conventional therapeutic lasers. It was found that the pulsed low-intensity laser radiation in the red spectrum region offered a number of advantages over conventional laser therapeutic techniques.

Comparative effectiveness research in hand surgery.

PubMed

Johnson, Shepard P; Chung, Kevin C

2014-08-01

Comparative effectiveness research (CER) is a concept initiated by the Institute of Medicine and financially supported by the federal government. The primary objective of CER is to improve decision making in medicine. This research is intended to evaluate the effectiveness, benefits, and harmful effects of alternative interventions. CER studies are commonly large, simple, observational, and conducted using electronic databases. To date, there is little comparative effectiveness evidence within hand surgery to guide therapeutic decisions. To draw conclusions on effectiveness through electronic health records, databases must contain clinical information and outcomes relevant to hand surgery interventions, such as patient-related outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

IL17/IL17RA as a Novel Signaling Axis Driving Mesenchymal Stem Cell Therapeutic Function in Experimental Autoimmune Encephalomyelitis

PubMed Central

Kurte, Mónica; Luz-Crawford, Patricia; Vega-Letter, Ana María; Contreras, Rafael A.; Tejedor, Gautier; Elizondo-Vega, Roberto; Martinez-Viola, Luna; Fernández-O’Ryan, Catalina; Figueroa, Fernando E.; Jorgensen, Christian; Djouad, Farida; Carrión, Flavio

2018-01-01

The therapeutic effect of mesenchymal stem cells (MSCs) in multiple sclerosis (MS) and the experimental autoimmune encephalomyelitis (EAE) model has been well described. This effect is, in part, mediated through the inhibition of IL17-producing cells and the generation of regulatory T cells. While proinflammatory cytokines such as IFNγ, TNFα, and IL1β have been shown to enhance MSCs immunosuppressive function, the role of IL17 remains poorly elucidated. The aim of this study was, therefore, to investigate the role of the IL17/IL17R pathway on MSCs immunoregulatory effects focusing on Th17 cell generation in vitro and on Th17-mediated EAE pathogenesis in vivo. In vitro, we showed that the immunosuppressive effect of MSCs on Th17 cell proliferation and differentiation is partially dependent on IL17RA expression. This was associated with a reduced expression level of MSCs immunosuppressive mediators such as VCAM1, ICAM1, and PD-L1 in IL17RA−/− MSCs as compared to wild-type (WT) MSCs. In the EAE model, we demonstrated that while WT MSCs significantly reduced the clinical scores of the disease, IL17RA−/− MSCs injected mice exhibited a clinical worsening of the disease. The disability of IL17RA−/− MSCs to reduce the progression of the disease paralleled the inability of these cells to reduce the frequency of Th17 cells in the draining lymph node of the mice as compared to WT MSCs. Moreover, we showed that the therapeutic effect of MSCs was correlated with the generation of classical Treg bearing the CD4+CD25+Foxp3+ signature in an IL17RA-dependent manner. Our findings reveal a novel role of IL17RA on MSCs immunosuppressive and therapeutic potential in EAE and suggest that the modulation of IL17RA in MSCs could represent a novel method to enhance their therapeutic effect in MS. PMID:29760692

Integration of a Community Pharmacy Simulation Program into a Therapeutics Course.

PubMed

Shin, Jaekyu; Tabatabai, Daryush; Boscardin, Christy; Ferrone, Marcus; Brock, Tina

2018-02-01

Objective. To demonstrate the feasibility of integrating the computer simulation, MyDispense, into a therapeutics course and to measure its effects on student perception and learning. Methods. We conducted a prospective study with an experimental phase and an implementation phase. In the first phase, students were randomized to complete a therapeutics case using MyDispense or traditional paper methods in class. In the second phase, all students completed two therapeutic cases using MyDispense in class with the option to complete four additional outside-of-class cases using MyDispense. Students completed pre- and post-tests in class and three surveys. Results. In the experimental phase, mean test scores increased from pre- to post-test for both MyDispense and traditional paper groups, but the difference between the groups was not statistically significant. Students in the traditional paper group reported statistically significant gains in confidence compared to the MyDispense group. In the implementation phase, mean test scores again increased, however, student perception of the use of MyDispense for therapeutics was negative. Completing the optional outside-of-class cases, however, was positively and significantly correlated with the midterm and final examination scores. Conclusion. Implementation of MyDispense in therapeutics may be feasible and has positive effects (eg, correlation with exam scores, capacity for immediate feedback, and potential for effective self-study). With short-term use and in the absence of assessment methods that also require seeking information from patients, students prefer to learn via traditional paper cases.

A novel method for detecting neutralizing antibodies against therapeutic proteins by measuring gene expression.

PubMed

Yu, Yanbin; Piddington, Christopher; Fitzpatrick, Dan; Twomey, Brian; Xu, Ren; Swanson, Steven J; Jing, Shuqian

2006-10-20

The presence of neutralizing antibodies against protein therapeutics is a concern in the biomedical field. Such antibodies not only reduce the efficacy of protein therapeutics, but also impose potential dangers to the patients receiving them. To date, a small number of in vitro cell-based bioassays for detecting neutralizing antibodies against therapeutic proteins have been developed. Most of the existing assays, however, either involve the use of radioactive materials or have limited sensitivities and/or poor specificities. With advances in mRNA profiling and detection techniques, we have established a novel and non-radioactive bioassay system using branched DNA (bDNA) technology for detecting protein-therapeutic neutralizing antibodies in patient serum. Our assay measures the variations of target gene expression that reflect the biologic effect of the therapeutic agent and the capability of the antibodies, if present, to neutralize the therapeutics. Compared with most existing assays, the new assay is more sensitive and specific, and completely eliminates the use of radioactive materials. Application of the new assay system can be widely expanded if new target genes and responding cell lines for other therapeutics are identified or engineered.

Improved Learning Outcomes After Flipping a Therapeutics Module: Results of a Controlled Trial.

PubMed

Lockman, Kashelle; Haines, Stuart T; McPherson, Mary Lynn

2017-12-01

To evaluate the impact on learning outcomes of flipping a pain management module in a doctor of pharmacy curriculum. In a required first-professional-year pharmacology and therapeutics course at the University of Maryland School of Pharmacy, the pain therapeutics content of the pain management module was flipped. This redesign transformed the module from a largely lecture-based, instructor-centered model to a learner-centered model that included a variety of preclass activities and in-class active learning exercises. In spring 2015, the module was taught using the traditional model; in spring 2016, it was taught using the flipped model. The same end-of-module objective structured clinical exam (OSCE) and multiple-choice exam were administered in 2015 to the traditional cohort (TC; n = 156) and in 2016 to the flipped cohort (FC; n = 162). Cohort performance was compared. Learning outcomes improved significantly in the FC: The mean OSCE score improved by 12.33/100 points (P < .0001; 95% CI 10.28-14.38; effect size 1.33), and performance on the multiple-choice exam's therapeutics content improved by 5.07 percentage points (P < .0001; 95% CI 2.56-7.59; effect size 0.45). Student performance on exam items assessing higher cognitive levels significantly improved under the flipped model. Grade distribution on both exams shifted, with significantly more FC students earning an A or B and significantly fewer earning a D or F compared with TC students. Student performance on knowledge- and skill-based assessments improved significantly after flipping the therapeutics content of a pain management module.

Chondromalacia patellae treated by warming needle and rehabilitation training.

PubMed

Qiu, Ling; Zhang, Min; Zhang, Ji; Gao, Le-Nv; Chen, Da-wei; Liu, Jun; She, Jia-yi; Wang, Ling; Yu, Jin-yan; Huang, Le-ping; Bai, Yang

2009-06-01

To observe the effect of warming needle combined with rehabilitation training on chondromalacia patellae in a randomized controlled trial. The 92 cases were randomly divided into a treatment group treated by warming needle plus rehabilitation training (47 cases) and a control group treated by medication plus rehabilitation training (45 cases), and the therapeutic effect was compared after 20 sessions. The pain was relieved more obviously in the treatment group than in the control group (P < 0.05), and the total effective rate was 91.8% and 71.1% respectively (P < 0.01). Warming needle plus rehabilitation training was superior in the therapeutic effect and duration of producing relief of pain to medication plus rehabilitation training in treating chondromalacia patellae.

Fasudil Enhances Therapeutic Efficacy of Neural Stem Cells in the Mouse Model of MPTP-Induced Parkinson's Disease.

PubMed

Li, Yan-Hua; Yu, Jing-Wen; Xi, Jian-Yin; Yu, Wen-Bo; Liu, Jian-Chun; Wang, Qing; Song, Li-Juan; Feng, Ling; Yan, Ya-Ping; Zhang, Guang-Xian; Xiao, Bao-Guo; Ma, Cun-Gen

2017-09-01

Bone marrow-derived neural stem cells (NSCs) are ideal cells for cellular therapy because of their therapeutic potential for repairing and regenerating damaged neurons. However, the optimization of implanted cells and the improvement of microenvironment in the central nervous system (CNS) are still two critical elements for enhancing therapeutic effect. In the current study, we observed the combined therapeutic effect of NSCs with fasudil in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model and explored the possible cellular and molecular mechanisms. The results clearly show that combined treatment of NSCs with fasudil further improves motor capacity of PD mice, thus exerting double effect in treating MPTP-PD. The combined intervention more effectively protected dopaminergic (DA) neurons from loss in the substantia nigra pars compacta (SNpc), which may be associated with the increased number and survival of transplanted NSCs in the brain. Compared with the treatment of fasudil or NSCs alone, the combined intervention more effectively inhibited the activation and aggregation of microglia and astrocytes, displayed stronger anti-inflammatory and antioxidant effects, induced more neurotrophic factor NT-3, and affected the dynamic homeostasis of NMDA and AMPA receptors in MPTP-PD mice. Our study demonstrates that intranasal administration of NSCs, followed by fasudil administration, is a promising cell-based therapy for neuronal lesions.

Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats.

PubMed

Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

2015-04-01

Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vivo delivery and long-term tissue retention of nano-encapsulated sirolimus using a novel porous balloon angioplasty system.

PubMed

Granada, Juan F; Tellez, Armando; Baumbach, William R; Bingham, Brendan; Keng, Yen-Fang; Wessler, Jeffrey; Conditt, Gerard; McGregor, Jennifer; Stone, Gregg; Kaluza, Greg L; Leon, Martin B

2016-08-20

Among antirestenotic compounds, sirolimus displays a superior safety profile compared to paclitaxel, but its pharmacokinetic properties make it a challenging therapeutic candidate for single-time delivery. Herein we evaluate the feasibility of delivery, long-term retention and vascular effects of sirolimus nanoparticles delivered through a novel porous angioplasty balloon in normal porcine arteries and in a swine model of in-stent restenosis (ISR). Sirolimus nanoparticle formulation was delivered via porous balloon angioplasty to 753 coronary artery segments for pharmacokinetic studies and 26 segments for biological effect of sirolimus delivery in different clinical scenarios (de novo [n=8], ISR [n=6] and following stent implantation [n=12]). Sirolimus coronary artery concentrations were above the target therapeutic level of 1 ng/mg after 26 days, and were >100-fold higher in coronary artery treatment sites than in distal myocardium and remote tissues at all time points. At 28 days, reduction in percent stenosis in formulation-treated sites compared to balloon angioplasty treatment was noted in all three clinical scenarios, with the largest effect seen in the de novo study. Local coronary delivery of sirolimus nanoparticles in the porcine model using a novel porous balloon delivery system achieved therapeutic long-term intra-arterial drug levels without significant systemic residual exposure.

Forbearance for fluoxetine: do monoaminergic antidepressants require a number of years to reach maximum therapeutic effect in humans?

PubMed

Fitzgerald, Paul J

2014-07-01

It is of high clinical interest to better understand the timecourse through which psychiatric drugs produce their beneficial effects. While a rough estimate of the time lag between initiating monoaminergic antidepressant therapy and the onset of therapeutic effect in depressed subjects is two weeks, much less is known about when these drugs reach maximum effect. This paper briefly examines studies that directly address this question through long-term antidepressant administration to humans, while also putting forth a simple theoretical approach for estimating the time required for monoaminergic antidepressants to reach maximum therapeutic effect in humans. The theory invokes a comparison between speed of antidepressant drug response in humans and in rodents, focusing on the apparently greater speed in rodents. The principal argument is one of proportions, comparing earliest effects of these drugs in rodents and humans, versus their time to reach maximum effect in these organisms. If the proportionality hypothesis is even coarsely accurate, then applying these values or to some degree their ranges to the hypothesis, may suggest that monoaminergic antidepressants require a number of years to reach maximum effect in humans, at least in some individuals.

Comparison of potential risks of lactic acidosis induction by biguanides in rats.

PubMed

Bando, Kiyoko; Ochiai, Shoko; Kunimatsu, Takeshi; Deguchi, Jiro; Kimura, Juki; Funabashi, Hitoshi; Seki, Takaki

2010-10-01

Lactic acidosis has been considered to be a side effect of some biguanides, after phenformin was withdrawn from the market because of its association with lactic acidosis. The potential of lactic acidosis induced by biguanides at human therapeutic exposure levels, however, has not been examined. Then, we compared the risk of lactic acid at doses providing exposure levels comparable to human therapeutic doses. Metformin and phenformin were orally administered to rats for up to 28 days, and plasma drug concentrations and blood lactic acid levels were examined. Metformin did not elevate lactic acid levels at the dose corresponding to higher systemic drug exposure than human therapeutic level, even for repeated doses. In contrast, phenformin elevated lactic acid levels at the dose corresponding to lower exposure than human therapeutic level, and sustained high levels were observed up to 24h post-dose; furthermore, these changes were enhanced by repeated doses. Direct comparison at each rat equivalent dose clearly indicated that lactic acid levels of phenformin were higher than those of metformin. These non-clinical findings suggest that metformin dose not increase lactic acid levels like phenformin does, and therefore may not increase the risk for lactic acidosis at human therapeutic exposure level. Copyright (c) 2010 Elsevier Inc. All rights reserved.

The combination of FK506 and an anti-CD147 mAb exerts potential therapeutic effects on a mouse model of collagen-induced arthritis.

PubMed

Luan, Jing; Zhang, Kui; Yang, Peng; Zhang, Yang; Feng, Fei; Zhu, Yu-Meng; Zhu, Ping; Chen, Zhi-Nan

2018-05-25

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and excessive T lymphocyte activation plays a critical role in the development of inflammation. CD147 is an antigen related to T cell activation, CD147 blockade exerts beneficial effects on RA. FK506, also known as tacrolimus, exerts strong immunosuppressive effects by inhibiting T cell activation. In this study, RL73 (an anti-mouse CD147 functional-grade purified antibody) and FK506 were co-administered to mice with collagen-induced arthritis (CIA). As expected, the combination of these two drugs produced superior therapeutic effects than either drug alone and enabled the administration of each drug at a lower dose. Moreover, joint damage and destruction were significantly improved in mice injected with both FK506 and RL73 compared with mice injected with either agent alone. These effects might have been observed because the proportions of CD4 + T and CD8 + T cells in the mouse spleen of the combination regimen were clearly decreased compared with each monotherapy. In addition, the proportions of Th2 subsets in the mouse spleen and peripheral blood were clearly increased, and the serum levels of the cytokines interleukin 4 (IL-4) and IL-10 were markedly increased in mice treated with the combination therapy compared with the other groups of mice. The splenic total number of T lymphocytes also showed that the inhibition of T lymphocytes was the most obvious in the combined treatment group. Based on the results from the present study, combining FK506 and the anti-CD147 mAb might be a new practical therapeutic option for the treatment of RA. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparison of the therapeutic effects of tri-iodothyronine and methylprednisolone during early sepsis in laboratory animals.

PubMed

Coskun, F; Saylam, B; Kulah, B; Dolapci, I; Sungur, A; Ozer, M Vasfi

2012-01-01

Despite major advances, the treatment of sepsis is still a challenging problem for surgeons. This study was aimed to compare the therapeutic effects of methylprednisolone and tri-iodothyronine replacement therapy during an early sepsis. Forty male Wistar albino rats weighing 300-340 g were divided into the Control, CLP, CLP/MP, CLP/T3 and CLP/MP/T3 groups. The Control group underwent a sham operation. Only cecal ligation and puncture was performed in the CLP group. The CLP/MP groups received an intramuscular injection of (MP) methylprednisolone (30 mg/kg) at one and half hour before CLP. The CLP/T3 group was given an intraperitoneal (IP) injection of tyroid hormone (T3) 0.4 µg/100 g immediately after CLP. The CLP/MP/T3 group was given IM injection of MP 30 mg/kg before CLP and IP injection of T3 0.4 µg/100 g after CLP. Hemavet changes, blood cultures, peritoneal bacteria content, hormonal alterations and histopathologic changes of intestinal, lung and liver tissue were used to asses the possible therapeutic effects of MP and T3 during early sepsis. A septic insult resulted in significant alterations on hemavet values, free T3, free T4 and cortisol levels, peritoneal bacteria content and intestinal lung and liver tissue samples of the CLP group. Hemavet changes and peritoneal inflammation findings were significantly limited in the CLP/T3 and CLP/MP/T3 groups. Histopathologic changes had no significant difference between the groups during an early sepsis. Compared to the MP replacement therapy, therapeutic effects of T3 replacement therapy have been found significantly more promising (Tab. 1, Fig. 10, Ref. 49).

Therapeutic Benefits and Adverse Effects of Combined Proangiogenic Gene Therapy in Mouse Critical Leg Ischemia.

PubMed

Lebas, Benoît; Galley, Julien; Renaud-Gabardos, Edith; Pujol, Françoise; Lenfant, Françoise; Garmy-Susini, Barbara; Chaufour, Xavier; Prats, Anne-Catherine

2017-04-01

Critical leg ischemia (CLI) represents the ultimate stage of peripheral arterial disease. Despite current surgery advances, patients with CLI have limited therapeutic options. Therapeutic angiogenesis thus appears as a powerful approach, aiming to stimulate vessel formation by angiogenic molecules administration. In this context, combined gene therapy has been proved to be the most efficient. The present study aims to compare, in a preclinical mouse model, the therapeutic benefit of a combination of 2 angiogenic factors fibroblast growth factor 2 (FGF2) and Cyr61 using plasmid and viral vectors, able to generate short- or long-term transgene expression in the leg, respectively. Two therapeutic genes, FGF2 and Cyr61, were introduced into internal ribosome entry site-based expression vectors (FGFiCyr) allowing co-expression of the 2 transgenes. The proangiogenic plasmid pC-FGFiCyr was assessed by intramuscular administration followed by electrotransfer into ischemic legs. To generate long-term transgene expression, the FGFiCyr bicistronic cassette was introduced into an adenoassociated virus-derived vector (rAAV). The rAAV treatment was performed either before or immediately after surgery. Therapeutic effects were analyzed by laser Doppler imaging, clinical score, and angiography. The plasmid pC-FGFiCyr improved revascularization, reperfusion, and clinical score. Surprisingly, when AAV-FGFiCyr was injected 21 or 28 days before surgery, the proangiogenic rAAV was drastically deleterious on all measured parameters. In contrast, when administrated shortly after surgery, AAV-FGFiCyr generated therapeutic benefits, with a significantly better clinical score than after treatment with the plasmid. Therapeutic effects of the angiogenic combination FGF2-Cyr61 is observed with short-term transgene expression, but the treatment is significantly more efficient when a long-term expression viral vector is used. However, the rAAV-FGFiCyr generated therapeutic benefit only when injected in an ischemic leg, whereas the same dose of rAAV exhibited deleterious effects when administrated to healthy animals. These data may contribute to the understanding of the moderate success of proangiogenic treatments in CLI gene therapy clinical assays. Copyright © 2016 Elsevier Inc. All rights reserved.

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed

Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

2011-03-31

Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies.

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed Central

2011-01-01

Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies. PMID:21453539

Comparison of human lung cancer cell radiosensitivity after irradiations with therapeutic protons and carbon ions.

PubMed

Keta, Otilija D; Todorović, Danijela V; Bulat, Tanja M; Cirrone, Pablo Ga; Romano, Francesco; Cuttone, Giacomo; Petrović, Ivan M; Ristić Fira, Aleksandra M

2017-05-01

The aim of this study was to investigate effects of irradiations with the therapeutic proton and carbon ion beams in two non-small cell lung cancers, CRL5876 adenocarcinoma and HTB177 large cell lung carcinoma. The DNA damage response dynamics, cell cycle regulation, and cell death pathway activation were followed. Viability of both cell lines was lower after carbon ions compared to the therapeutic proton irradiations. HTB177 cells showed higher recovery than CRL5876 cells seven days following the treatments, but the survival rates of both cell lines were lower after exposure to carbon ions with respect to therapeutic protons. When analyzing cell cycle distribution of both CRL5876 and HTB177 cells, it was noticed that therapeutic protons predominantly induced G1 arrest, while the cells after carbon ions were arrested in G2/M phase. The results illustrated that differences in the levels of phosphorylated H2AX, a double-strand break marker, exist after therapeutic proton and carbon ion irradiations. We also observed dose- and time-dependent increase in the p53 and p21 levels after applied irradiations. Carbon ions caused larger increase in the quantity of p53 and p21 compared to therapeutic protons. These results suggested that various repair mechanisms were induced in the treated cells. Considering the fact that we have not observed any distinct change in the Bax/Bcl-2 ratio following irradiations, it seemed that different types of cell death were involved in the response to the two types of irradiations that were applied.

Comparison of human lung cancer cell radiosensitivity after irradiations with therapeutic protons and carbon ions

PubMed Central

Keta, Otilija D; Todorović, Danijela V; Bulat, Tanja M; Cirrone, Pablo GA; Romano, Francesco; Cuttone, Giacomo; Petrović, Ivan M

2016-01-01

The aim of this study was to investigate effects of irradiations with the therapeutic proton and carbon ion beams in two non-small cell lung cancers, CRL5876 adenocarcinoma and HTB177 large cell lung carcinoma. The DNA damage response dynamics, cell cycle regulation, and cell death pathway activation were followed. Viability of both cell lines was lower after carbon ions compared to the therapeutic proton irradiations. HTB177 cells showed higher recovery than CRL5876 cells seven days following the treatments, but the survival rates of both cell lines were lower after exposure to carbon ions with respect to therapeutic protons. When analyzing cell cycle distribution of both CRL5876 and HTB177 cells, it was noticed that therapeutic protons predominantly induced G1 arrest, while the cells after carbon ions were arrested in G2/M phase. The results illustrated that differences in the levels of phosphorylated H2AX, a double-strand break marker, exist after therapeutic proton and carbon ion irradiations. We also observed dose- and time-dependent increase in the p53 and p21 levels after applied irradiations. Carbon ions caused larger increase in the quantity of p53 and p21 compared to therapeutic protons. These results suggested that various repair mechanisms were induced in the treated cells. Considering the fact that we have not observed any distinct change in the Bax/Bcl-2 ratio following irradiations, it seemed that different types of cell death were involved in the response to the two types of irradiations that were applied. PMID:27633574

Potent therapeutic effects of shouwu jiangqi decoction on polycystic ovary syndrome with insulin resistance in rats.

PubMed

Wang, Li-hong; Wang, Xu; Yu, Xi-zhong; Xu, Wen-ting

2016-02-01

To investigate the effect of Shouwu Jiangqi Decoction (SJD) on polycystic ovary syndrome (PCOS) with insulin resistance (IR) in rats and to explore the underlining molecular mechanisms. A total of 51 female Sprague-Dawley rats were randomly divided into 6 groups: control group (n=7), model group (n=8), SJD high-dose group (n=9), SJD medium-dose group (n=9), SJD low-dose group (n=9) and DMBG group (n=9). Radioimmunoassay was used to measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations and qRT-PCR and western blot were used to examine the expression levels of mRNA and protein respectively of insulin receptor substrate 1 (IRS-1) and phosphatidylinositide 3-kinases (PI3K) p85α in different groups. FSH level significantly decreased in the model group compared with the normal control (P<0.01), and high-dose SJD and DMBG can significantly increase FSH level (P<0.01). LH level showed a mild increase without statistic significance in the model group compared with the control and different dosages of SJD had no significance effect on LH level, while DMBG can significantly decrease LH level (P<0.01). Testosterone level significantly increased in the model group compared with the control group (P<0.01), and high-dose SJD and DMBG can significantly decrease testosterone level (P<0.01). The expression of IRS-1 as well as PI3Kp85α were significantly decreased in the model group compared with the normal control group at both mRNA (P<0.001) and protein (P<0.01) level, and both high-dose SJD and DMBG can enhance IRS-1 and PI3K expression (P<0.05). SJD has potent therapeutic effects on PCOS with IR in rats. The therapeutic effects of SJD on IR and ovulatory dysfunction are probably achieved through correcting the defective insulin signaling transduction.

Therapeutic touch for anxiety disorders.

PubMed

Robinson, J; Biley, F C; Dolk, H

2007-07-18

Anxiety disorders are a common occurrence in today's society. There is interest from the community in the use of complementary therapies for anxiety disorders. This review examined the currently available evidence supporting the use of therapeutic touch in treating anxiety disorders. To examine the efficacy and adverse effects of therapeutic touch for anxiety disorders. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References) (search date 13/01/06), the Controlled Trials website and Dissertation Abstracts International. Searches of reference lists of retrieved papers were also carried out and experts in the field were contacted. Inclusion criteria included all published and unpublished randomised and quasi-randomised controlled trials comparing therapeutic touch with sham (mimic) TT, pharmacological therapy, psychological treatment, other treatment or no treatment /waiting list. The participants included adults with an anxiety disorder defined by the Diagnostic and Statistical Manual (DSM-IV),the International Classification of Diseases (ICD-10), validated diagnostic instruments, or other validated clinician or self-report instruments. Two review authors independently applied inclusion criteria. Further information was sought from trialists where papers contained insufficient information to make a decision about eligibility. No randomised or quasi-randomised controlled trials of therapeutic touch for anxiety disorders were identified. Given the high prevalence of anxiety disorders and the current paucity of evidence on therapeutic touch in this population, there is a need for well conducted randomised controlled trials to examine the effectiveness of therapeutic touch for anxiety disorders.

Comparisons of Cognitive, Music, and Imagery Techniques on Anxiety Reduction with University Students.

ERIC Educational Resources Information Center

Russell, Lori A.

1992-01-01

Investigated effectiveness of imagery, music, and cognitive therapeutic techniques in reducing anxiety among 78 anxious college students. Found that familiar-sedative music plus imagery was most effective technique in reducing state anxiety compared to music, a cognitive intervention, or control group. (Author/NB)

Misinterpreting the therapeutic effects of small interfering RNA caused by immune stimulation.

PubMed

Robbins, Marjorie; Judge, Adam; Ambegia, Ellen; Choi, Catherine; Yaworski, Ed; Palmer, Lorne; McClintock, Kevin; MacLachlan, Ian

2008-10-01

Activation of innate immunity has direct effects in modulating viral replication, tumor growth, angiogenesis, and inflammatory and other immunological processes. It is now established that unmodified siRNA can activate this innate immune response and therefore there is real potential for siRNA to elicit nonspecific therapeutic effects in a wide range of disease models. Here we demonstrate that in a murine model of influenza infection, the antiviral activity of siRNA is due primarily to immune stimulation elicited by the active siRNA duplexes and is not the result of therapeutic RNA interference (RNAi) as previously reported. We show that the misinterpretation stems from the use of a particular control green fluorescent protein (GFP) siRNA that we identify as having unusually low immunostimulatory activity compared with the active anti-influenza siRNA. Curiously, this GFP siRNA has served as a negative control for a surprising number of groups reporting therapeutic effects of siRNA. The inert immunologic profile of the GFP sequence was unique among a broad panel of published siRNAs, all of which could elicit significant interferon induction from primary immune cells. This panel included eight active siRNAs against viral, angiogenic, and oncologic targets, the reported therapeutic efficacy of which was based on comparison with the nonimmunostimulatory GFP siRNA. These results emphasize the need for researchers to anticipate, monitor, and adequately control for siRNA-mediated immune stimulation and calls into question the interpretation of numerous published reports of therapeutic RNAi in vivo. The use of chemically modified siRNA with minimal immunostimulatory capacity will help to delineate more accurately the mechanism of action underlying such studies.

Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease.

PubMed

Grafton, S T; Turner, R S; Desmurget, M; Bakay, R; Delong, M; Vitek, J; Crutcher, M

2006-04-25

To test whether therapeutic unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to normalization in the pattern of brain activation during movement execution and control of movement extent. Six patients with PD were imaged off medication by PET during performance of a visually guided tracking task with the DBS voltage programmed for therapeutic (effective) or subtherapeutic (ineffective) stimulation. Data from patients with PD during ineffective stimulation were compared with a group of 13 age-matched control subjects to identify sites with abnormal patterns of activation. Conjunction analysis was used to identify those areas in patients with PD where activity normalized when they were treated with effective stimulation. For movement execution, effective DBS caused an increase of activation in the supplementary motor area (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation also induced reductions of movement related "overactivity" compared with healthy subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent with the notion that many areas are recruited to compensate for ineffective motor initiation. Normalization of activity related to the control of movement extent was associated with reductions of activity in primary motor cortex, SMA, and basal ganglia. Effective subthalamic nucleus stimulation leads to task-specific modifications with appropriate recruitment of motor areas as well as widespread, nonspecific reductions of compensatory or competing cortical activity.

Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats.

PubMed

Figueiró-Filho, Ernesto Antonio; Aydos, Ricardo Dutra; Senefonte, Flávio Renato de Almeida; Ferreira, Cristiane Munaretto; Pereira, Erica Freire de Vasconcelos; Oliveira, Vanessa Marcon de; Menezes, Giovanna Pádoa de; Bósio, Marco Antonio Costa

2014-07-01

To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A p<0.05 was considered statistically significant. We did not observe statistically significant differences between groups when comparing the average weight of the foetuses and placentas, rate of female VS males, rates of pre-implantation loss (RPL), rates of efficiency implantation (REI), rates of post-implantation loss (RPIL) and rates of foetal viability (RFV). There was no significant effect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats.

Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia　- The SCELTA Trial.

PubMed

Liotta, Francesco; Annunziato, Francesco; Castellani, Sergio; Boddi, Maria; Alterini, Brunetto; Castellini, Giovanni; Mazzanti, Benedetta; Cosmi, Lorenzo; Acquafresca, Manlio; Bartalesi, Filippo; Dilaghi, Beatrice; Dorigo, Walter; Graziani, Gabriele; Bartolozzi, Benedetta; Bellandi, Guido; Carli, Giulia; Bartoloni, Alessandro; Fargion, Aaron; Fassio, Filippo; Fontanari, Paolo; Landini, Giancarlo; Lucente, Eleonora A M; Michelagnoli, Stefano; Orsi Battaglini, Carolina; Panigada, Grazia; Pigozzi, Clara; Querci, Valentina; Santarlasci, Veronica; Parronchi, Paola; Troisi, Nicola; Baggiore, Cristiana; Romagnani, Paola; Mannucci, Edoardo; Saccardi, Riccardo; Pratesi, Carlo; Gensini, Gianfranco; Romagnani, Sergio; Maggi, Enrico

2018-05-25

The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC) autotransplantation in critical limb ischemia (CLI) has been reported. Variable proportions of circulating monocytes express low levels of CD34 (CD14 + CD34 low cells) and behave in vitro as endothelial progenitor cells (EPCs). The aim of the present randomized clinical trial was to compare the safety and therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral blood by immunomagnetic selection of CD14 + and CD34 + cells) or BM-MNC were injected into the gastrocnemius of the affected limb in 23 and 17 patients, respectively. After a mean of 25.2±18.6-month follow-up, both groups showed significant and progressive improvement in muscle perfusion (primary endpoint), rest pain, consumption of analgesics, pain-free walking distance, wound healing, quality of life, ankle-brachial index, toe-brachial index, and transcutaneous PO 2 . In ECEPC-treated patients, there was a positive correlation between injected CD14 + CD34 low cell counts and the increase in muscle perfusion. The safety profile was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the number of deaths and major amputations was lower compared with eligible untreated patients and historical reference patients. This study supports previous trials showing the efficacy of BM-MNC autotransplantation in CLI patients and demonstrates comparable therapeutic efficacy between BM-MNC and EPEPCs.

Inhibition of HIV Fusion with Multivalent Gold Nanoparticles

PubMed Central

Bowman, Mary-Catherine; Ballard, T. Eric; Ackerson, Christopher J.; Feldheim, Daniel L.; Margolis, David M.; Melander, Christian

2010-01-01

The design and synthesis of a multivalent gold nanoparticle therapeutic is presented. SDC-1721, a fragment of the potent HIV inhibitor TAK-779, was synthesized and conjugated to 2.0 nm diameter gold nanoparticles. Free SDC-1721 had no inhibitory effect on HIV infection; however, the (SDC-1721)-gold nanoparticle conjugates displayed activity comparable to that of TAK-779. This result suggests that multivalent presentation of small molecules on gold nanoparticle surfaces can convert inactive drugs into potent therapeutics. PMID:18473457

Safety and Toxicology of Cannabinoids.

PubMed

Sachs, Jane; McGlade, Erin; Yurgelun-Todd, Deborah

2015-10-01

There is extensive research on the safety, toxicology, potency, and therapeutic potential of cannabis. However, uncertainty remains facilitating continued debate on medical and recreational cannabis policies at the state and federal levels. This review will include a brief description of cannabinoids and the endocannabinoid system; a summary of the acute and long-term effects of cannabis; and a discussion of the therapeutic potential of cannabis. The conclusions about safety and efficacy will then be compared with the current social and political climate to suggest future policy directions and general guidelines.

Multiple polysaccharide-drug complex-loaded liposomes: A unique strategy in drug loading and cancer targeting.

PubMed

Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Gupta, Biki; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2017-10-01

In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer-drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical. The targeted liposome exhibited a specific receptor-mediated endocytic uptake in cancer cells. The enhanced cellular uptake of TL-DDAC resulted in a significantly better anticancer effect in resistant and sensitive breast cancer cells compared to that of the free drugs. Specifically, DOX and CIS at a molar ratio of 1:1 exhibited better therapeutic performance compared to that of other combinations. The combination of an anthracycline-based topoisomerase II inhibitor (DOX) and a platinum compound (CIS) resulted in significantly higher cell apoptosis (early and late) in both types of cancer cells. In conclusion, treatment with DS-DOX and AL-CIS based combination liposomes modified with transferrin (TL-DDAC) was an effective cancer treatment strategy. Further investigation in clinically relevant animal models is warranted to prove the therapeutic efficacy of this unique strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of a sustained fluoride delivery system.

PubMed

Baturina, Olga; Tufekci, Eser; Guney-Altay, Ozge; Khan, Shadeed M; Wnek, Gary E; Lindauer, Steven J

2010-11-01

To develop a novel delivery system by which fluoride incorporated into elastomeric rings, such as those used to ligate orthodontic wires, will be released in a controlled and constant manner. Polyethylene co-vinyl acetate (PEVA) was used as the model elastomer. Samples (N = 3) were prepared by incorporating 0.02 to 0.4 g of sodium fluoride (NaF) into previously prepared PEVA solution. Another group of samples prepared in the same manner were additionally dip-coated in PEVA to create an overcoat. Fluoride release studies were conducted in vitro using an ion selective electrode over a period of 45 days. The amount of fluoride released was compared to the optimal therapeutic dose of 0.7 microg F(-)/ring/d. Only coated samples with the highest fluoride content (group D, 0.4 g of NaF) were able to release fluoride at therapeutic levels. When fluoride release from coated and uncoated samples with the same amount of NaF were compared, it was shown that the dip-coating technique resulted in a fluoride release in a controlled manner while eliminating the initial burst effect. This novel fluoride delivery matrix provided fluoride release at a therapeutically effective rate and profile.

Development of Novel Antibiotic Lysocin E Identified by Silkworm Infection Model.

PubMed

Hamamoto, Hiroshi; Sekimizu, Kazuhisa

2017-01-01

In this symposium, we reported the identification and mechanistic analysis of a novel antibiotic named lysocin E. Lysocin E was identified by screening for therapeutic effectiveness in a silkworm Staphylococcus aureus infection model. The advantages of the silkworm infection model for screening and purification of antibiotics from the culture supernatant of soil bacteria are: 1) low cost; 2) no ethical issues; 3) convenient for evaluation of the therapeutic effectiveness of antibiotics; and 4) pharmacokinetics similar to those of mammals. Lysocin E has remarkable features compared with known antibiotics such as a novel mechanism of action and target. Here, we summarize our reports presented in this symposium.

Studying the Immunomodulatory Effects of Small Molecule Ras Inhibitors in Animal Models of Rheumatoid Arthritis

DTIC Science & Technology

2017-10-01

methotrexate (MTX) provides a superior protective effect compared to monotherapy. (iii) In the AIA model the FTS derivative, F-FTS, showed higher...therapeutic efficacy compared to FTS. (iv) The functional genomics studies showed that FTS therapy inhibits the in vivo TH17 immune response. (v) FTS semi... Description shall include pertinent data and graphs in sufficient detail to explain any significant results achieved. A succinct description of the

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

Bostroem, P.A.

In order to evaluate the therapeutic effects of metoprolol, nifedipine, and their combination, 11 patients with secondary angina pectoris and with thallium tomographic findings indicating coronary artery disease were studied before and after these three treatment regimes in a single-blind cross-over study. The therapeutic effect was measured by standardized working test and isotope angiocardiography, which enabled evaluation of left ventricular ejection fraction, stroke volume, and phase analysis of left ventricular contraction. Treatment with metoprolol and combination therapy increased work performance. Ejection fraction did not differentiate the treatment regimes, whereas stroke volume was significantly lower at work and heart rate highermore » at rest and at work during nifedipine treatment compared to either metoprolol or combination treatment (p less than 0.05). Cardiac output was significantly reduced during nifedipine and metoprolol treatment during work (p less than 0.05). Phase improved after all therapeutic regimes, but reached significance only during the metoprolol treatment period at rest (p less than 0.05).« less

Experiences of women with stress-related ill health in a therapeutic gardening program.

PubMed

Eriksson, Therese; Westerberg, Yvonne; Jonsson, Hans

2011-12-01

Stress-related ill health, e.g. burnout, is of great concern worldwide. Effective rehabilitation programs need to be developed and their therapeutic aspects understood. To explore and describe how women with stress-related ill health who are on sick leave experience the rehabilitation process in a therapeutic garden and how these experiences connect to their everyday lives. This longitudinal study used methods from grounded theory. Five women completed three semi-structured interviews at three weekly intervals during rehabilitation and one interview three months after. Data were analyzed using a constant comparative approach. A secure environment facilitated engagement in activities that provided feelings of enjoyment. These experiences inspired participants to add enjoyable activities in their everyday lives, contributing to occupational balance, despite worries of not be able to continue performing enjoyable activities. Implications. Effective rehabilitation programs need to focus on enjoyable activities in a protective environment to support achievement of occupational balance.

Therapeutic effects of metformin and laparoscopic ovarian drilling in treatment of clomiphene and insulin-resistant polycystic ovary syndrome.

PubMed

Wang, Xiao-Hong; Wang, Jun-Qing; Xu, Yan; Huang, Li-Ping

2015-05-01

To compare the therapeutic effects of metformin (Met) and laparoscopic ovarian drilling (LOD) in clomiphene and insulin-resistant patients with polycystic ovary syndrome (CIRPCOS). A total of 110 patients were randomly divided into two groups. One group was administered Met (n = 55), while the other group underwent LOD (n = 55). Rates of ovulation, pregnancy, and abortion were compared between both groups. Rates of normal menstruation, ovulation, and pregnancy in the LOD group were higher than in the Met group: 76.4% (42/55) vs. 58.2% (32/55), P < 0.04; 50.8% (11/258) vs. 33.5% (94/281), P < 0.001; 38.2% (21/55) vs. 20.0% (11/55), P < 0.03. The difference in the early abortion rate between both groups was not statistically significant. Although Met can significantly improve a patient's insulin resistance, we found that in patients diagnosed with CIRCPOS, LOD can be much more effective in improving rates of normal menstruation, ovulation, and pregnancy.

Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics.

PubMed

Zhou, Xing; Zhao, Yang; Chen, Siyu; Han, Songling; Xu, Xiaoqiu; Guo, Jiawei; Liu, Mengyu; Che, Ling; Li, Xiaohui; Zhang, Jianxiang

2016-08-08

Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N-isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics.

The effect of therapeutic touch on behavioral symptoms and cortisol in persons with dementia.

PubMed

Woods, Diana Lynn; Beck, Cornelia; Sinha, Karabi

2009-06-01

Between 75-90% of nursing home (NH) residents with dementia develop behavioral symptoms (BSD) which may be associated with a stress response. Therapeutic touch has been shown to decrease restlessness in NH residents, however the mechanism is unknown. The purpose of this randomized controlled trial (RCT) was to examine the effect of therapeutic touch on BSD and basal cortisol levels among NH residents with dementia. Using a double blind experimental interrupted time series ABAB design, 65 participants were assigned to one of three groups. The experimental group received therapeutic touch with contact on the neck and shoulders delivered twice daily for 3 days (administered over 2 separate treatment periods); the placebo group received a mimic treatment identical in appearance, and the control group received routine care. Study outcomes were BSD, measured by the modified Agitated Behavior Rating Scale (mABRS), and salivary cortisol levels, measured by enzyme-linked immunosorbent assay (ELISA). 64 residents, aged 67-93 years (M = 85.5, SD = 5.50), completed the study. Restlessness was significantly reduced in the experimental group compared to the control group (p = 0.03). There was a significant difference in morning cortisol variability among groups across time periods (<0.0001). Findings suggest that therapeutic touch may be effective for management of symptoms like restlessness coupled with stress reduction. At a time when cost containment is a consideration in health care, therapeutic touch is an intervention that is non-invasive, readily learned, and can provide a non-pharmacologic alternative for selected persons with BSD. Copyright 2009 S. Karger AG, Basel.

Bio-enhancing Effect of Piperine with Metformin on Lowering Blood Glucose Level in Alloxan Induced Diabetic Mice

PubMed Central

Atal, Shubham; Atal, Sarjana; Vyas, Savita; Phadnis, Pradeep

2016-01-01

Background: Diabetes mellitus is the most rampant metabolic pandemic of the 21st century. Piperine, the chief alkaloid of Piper nigrum (black pepper) is widely used in alternative and complementary therapies has been extensively studied for its bio-enhancing property. Objective: To evaluate the bio-enhancing effect of piperine with metformin in lowering blood glucose levels in alloxan-induced diabetic mice. Materials and Methods: Piperine was isolated from an extract of fruits of P. nigrum. Alloxan-induced (150 mg/kg intraperitoneal) diabetic mice were divided into four groups. Group I (control 2% gum acacia 2 g/100 mL), Group II (metformin 250 mg/kg), Group III (metformin and piperine 250 mg/kg + 10 mg/kg), and Group IV (metformin and piperine 125 mg/kg + 10 mg/kg). All the drugs were administered orally once daily for 28 days. Blood glucose levels were estimated at day 0, day 14, and end of the study (day 28). Results: The combination of piperine with therapeutic dose of metformin (10 mg/kg + 250 mg/kg) showed significantly more lowering of blood glucose level as compared to metformin alone on both 14th and 28th day (P < 0.05). Piperine in combination with sub-therapeutic dose of metformin (10 mg/kg + 125 mg/kg) showed significantly more lowering of blood glucose as compared to control group and also showed greater lowering of blood glucose as compared to metformin (250 mg/kg) alone. Conclusion: Piperine has the potential to be used as a bio-enhancing agent in combination with metformin which can help reduce the dose of metformin and its adverse effects. SUMMARY Piperine is known for its bioenhancing property. This study evaluates the effect of piperine in combination with oral antidiabetic drug metformin. Drugs were administered for 28 days in alloxan induced diabetic mice and blood glucose lowering effect was seen. Results showed significantly better effect of combination of piperine with therapeutic dose of metformin in comparison to metformin alone. Piperine in combination with subtherapeutic dose of metformin also showed better effect than therapeutic dose of metformin. Piperine, thus shows potential to be used as bioenhancer in combination with metformin. PMID:26941537

Prophylactic or therapeutic administration of Agaricus blazei Murill is effective in treatment of murine visceral leishmaniasis.

PubMed

Valadares, Diogo G; Duarte, Mariana C; Ramírez, Laura; Chávez-Fumagalli, Miguel A; Martins, Vivian T; Costa, Lourena E; Lage, Paula S; Ribeiro, Tatiana G; Castilho, Rachel O; Fernandes, Ana Paula; Régis, Wiliam C B; Soto, Manuel; Tavares, Carlos A P; Coelho, Eduardo A F

2012-10-01

The present study aimed to investigate the in vitro antileishmanial activity of five fractions obtained from Agaricus blazei water extract (AbM), namely, Fab1, Fab2, Fab3, Fab4, and Fab5; and use the selected leishmanicidal fraction to treat BALB/c mice infected with Leishmania chagasi. A curve dose-titration was performed to obtain the concentration to be test in infected animals. In this context, Fab5 fraction and AbM were used in the doses of 20 and 100 mg/kg/day, respectively, with the product been administered once a day. The effect induced by a chemo-prophylactic regimen, based on the administration Fab5 fraction and AbM 5 days before infection, and maintained for an additional 20 days post-infection was compared to a therapeutic regimen, in which the compounds were administered from 0 to 20 days of infection. Control animals were either treated with amphotericin B deoxycholate (AmpB) or received distilled water. All groups were followed up for 10 weeks post-infection, when parasitological and immunological parameters were analyzed. The Fab5 presented the best results of in vitro leishmanicidal activity. In the in vivo experiments, the use of Fab5 or AbM, as compared to control groups, resulted in significant reduced parasite burdens in the liver, spleen, and draining lymph nodes of the infected animals, as compared to control groups. A Type 1 immune response was observed in the Fab5 or AbM treated animals. No significant toxicity was observed. The chemo-prophylactic regimen proved to be more effective to induce theses responses. In this context, the data presented in this study showed the potential of the purified Fab5 fraction of AbM as a therapeutic alternative to treat visceral leishmaniasis. In addition, it can be postulated that this fraction can be also employed in a chemo-prophylactic regimen associated or not with other therapeutic products. Copyright © 2012 Elsevier Inc. All rights reserved.

Dynamic contrast-enhanced perfusion area-detector CT assessed with various mathematical models: Its capability for therapeutic outcome prediction for non-small cell lung cancer patients with chemoradiotherapy as compared with that of FDG-PET/CT.

PubMed

Ohno, Yoshiharu; Fujisawa, Yasuko; Koyama, Hisanobu; Kishida, Yuji; Seki, Shinichiro; Sugihara, Naoki; Yoshikawa, Takeshi

2017-01-01

To directly compare the capability of dynamic first-pass contrast-enhanced (CE-) perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy. Fifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR+PR) and 2) stable or progressive disease (SD+PD). Pulmonary arterial and systemic arterial perfusions and total perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor perfusion with the single-input maximum slope method, and SUV max , and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared. The step-wise regression test showed that therapeutic effect (r 2 =0.63, p=0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial perfusion, total perfusion, and SUV max . Mean overall survival showed a significant difference for total perfusion (p=0.003) and systemic arterial perfusion (p=0.04). Dynamic first-pass CE-perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Effects of Rigid Scapular Taping on the Subacromial Space in Athletes With and Without Rotator Cuff Tendinopathy: A Randomized-Controlled Study.

PubMed

Leong, Hio Teng; Fu, Siu Ngor

2018-02-21

Reduction of the subacromial space (SAS) during arm elevation may contribute to rotator cuff tendinopathy. The effects of scapular taping on the SAS in athletes with and without RC tendinopathy is unknown. To investigate the immediate effects of scapular taping on the SAS in athletes with and without RC tendinopathy. Randomized-controlled with repeated measures. University laboratory. Forty-three male volleyball players (17 asymptomatic and 26 with RC tendinopathy, mean age = 22.9±3.5 years) participated in the study. Three scapular taping protocols - no taping (control), taping with tension (therapeutic taping) and taping without tension (sham taping). Ultrasound measurements of the SAS with the arm at 0° and 60° of shoulder abduction, and the change in the SAS between 0° and 60° of shoulder abduction (SAS 0°-60° ) were calculated. Athletes with RC tendinopathy demonstrated larger SAS with therapeutic taping at 60° of shoulder abduction (6.9±1.9 mm vs. 5.8±1.7 mm, mean difference = 1.1 mm, 95% CI = -1.80 - -0.39, p=0.002) when compared to the no taping condition. The tendinopathy group also showed less reduction in the SAS with therapeutic taping during SAS 0°-60° (2.0±1.4 mm vs. 2.8±1.4 mm, p=0.023) when compared to the no taping condition. When tape was applied to the scapula in asymptomatic athletes, our results showed a relatively small increase in the SAS with therapeutic taping during arm resting at 0° of abduction when compared to the no taping condition (8.7±0.9 mm vs. 8.3±0.8 mm, mean difference = 0.4 mm, 95% CI = -0.71 - -0.11, p=0.008). Athletes with RC tendinopathy demonstrated less reduction of the SAS with rigid scapular taping during early arm abduction. Such observation was not evidenced in asymptomatic athletes.

[Principles of controlled clinical trials].

PubMed

Martini, P

1962-01-01

The recovery of the patient should be facilitated as the result of therapeutic research. The basic rule for every therapeutic-clinical trial mist involve a comparison of therapeutic approaches. In acute conditions, such as acute infectious diseases, infarcts, etc., comparisons should be made between two or more groups: the collective therapeutic comparison = the between patients trial. The formation of groups, to be compared one with the other can be justified only if one is reasonably sure that a pathogenic condition indeed exists. In chronic diseases, which extend essentially unchanged over a lengthy period but are nevertheless reversible, therapeutic comparisons may be made between two or more time intervals within the course of the disease in the same individual. This type of therapeutic trial rests primarily upon a (refined!) type of specious reasoning and secondarily, upon modified statistics: the individual therapeutic comparison = the within patient trial. The collective therapeutic comparison, on the one hand, and the individual therapeutic comparison on the other, overlap somewhat in scope. The immediate therapeutic effect is not always an indication of its true value, which may become evident only upon long-term treatment. The short-term trials of therapeutic regimens in an individual must, therefore, be frequently supplemented by long-term trials which can only be carried out by comparing two groups. For many clinical investigations, therefore, the joint efforts of numerous hospitals are absolutely necessary. The second basic rule of therapeutic research is the elimination of secondary causes. The difficulties introduced by these secondary considerations are far greater in therapeutic trials carried out on ambulatory patients than has been hitherto realized. In order to remove subjective secondary causes, the author demanded, in 1931, the use of hidden or illusory media (placebos, dummies) that is, unconscious causative agents. The double blind procedure is indispensible in all experiments, especially where psychological processes and problems are of foremost importance. Therefore, it is absolutely necessary that convincing tests be finally carried out with the double blind procedure on the one hand, and the simple blind procedure on the other in order to determine the range and limitations of both. Therapeutic research of the future is threatened by the hazard of self-satisfaction which produces a sense of accomplishment merely as the result of obeying formal conditions and of following formal standards of accuracy.

Forty cases of gastrointestinal neurosis treated by acupunture.

PubMed

Zhao, Yaping; Ding, Min; Wang, Yanjun

2008-03-01

To compare the therapeutic effect of acupuncture for gastrointestinal neurosis with that of oral remedy. Eighty cases were randomly divided into the following 2 groups. In the treatment group, acupuncture was given for one month at the main points of Zhongwan (CV 12), Zusanli (ST 36), Taichong (LR 3) and Shenmen (HT 7), with the auxiliary points selected according to TCM differentiation. In the control group, Domperidone was orally administered for one month. The total effective rate was 92.5% in the treatment group and 75.0% in the control group, with a significant difference between the 2 groups (chi2 = 4.423, P < 0.05). Acupuncture was superior to the oral remedy in therapeutic effects. Acupuncture may show better results for gastrointestinal neurosis and with less toxic side effects.

Prophylactic compared with therapeutic ibuprofen analgesia in first-trimester medical abortion: a randomized controlled trial.

PubMed

Raymond, Elizabeth G; Weaver, Mark A; Louie, Karmen S; Dean, Gillian; Porsch, Lauren; Lichtenberg, E Steve; Ali, Rose; Arnesen, Michelle

2013-09-01

To compare the effectiveness of two oral analgesic regimens in first-trimester medical abortion. We randomly assigned 250 participants undergoing first-trimester abortion with mifepristone and misoprostol at three clinics to two ibuprofen regimens: therapeutic (800 mg every 4-6 hours as needed for pain) or prophylactic (800 mg starting 1 hour before the misoprostol dose, then every 4-6 hours for 48 hours regardless of pain, then as needed). We asked each participant to record her maximum pain on a scale of 0-10 daily thereafter. Of participants assigned to the prophylactic and therapeutic regimens, 111 of 123 (90%) and 117 of 127 (92%), respectively, provided follow-up data. More than 80% of the participants in each group complied with their assigned treatment. Participants in the prophylactic group used substantially more ibuprofen than those in the therapeutic group (median of nine and four tablets, respectively). The mean maximum pain score was 7.1 in the prophylactic group and 7.3 in the therapeutic group (standard deviations 2.5 and 2.2, respectively); the difference was not statistically significant (P=.87, adjusted for site). Duration of pain, verbal pain ratings reported at follow-up, and use of other analgesics did not differ significantly by group (all P>.05). No significant benefit of the prophylactic regimen was apparent in any population subgroup. Abortion failure and ibuprofen side effects in the two groups were similar. We found no evidence that prophylactic administration of ibuprofen reduces pain severity or duration in first-trimester medical abortion. The average pain severity experienced by participants using both regimens was high. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01457521. I.

Therapeutic effects of lornoxicam-loaded nanomicellar formula in experimental models of rheumatoid arthritis.

PubMed

Helmy, Hebatullah Samy; El-Sahar, Ayman E; Sayed, Rabab H; Shamma, Rehab Nabil; Salama, Alaa Hamed; Elbaz, Eman Maher

2017-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease treated by nonsteroidal anti-inflammatory drugs (NSAIDs) including lornoxicam (LX). Nanocarriers have been used to increase the efficacy and reduce the side effects of various drugs. The objective of the present study was to compare the therapeutic efficacy of systemic administration of lornoxicam-loaded nanomicellar formula (LX-NM) with that of free LX. The LX-loaded mixed polymeric nanomicellar formula was prepared by direct equilibrium technique. Two rat models were used in the study: carrageenan-induced acute edema and Freund's complete adjuvant (FCA)-induced chronic arthritis. The inhibitory effect of LX-NM on carrageenan-induced edema was higher than free LX for the same dose (1.3 mg/kg, i.p.). LX-NM (0.325 mg/kg, i.p.) produced effects comparable to that of diclofenac, which served as a standard. In the FCA model, daily treatment with LX-NM (0.325 mg/kg, i.p.) starting on day 14 significantly reduced the percentage of edema and increased weight growth. However, the same dose of LX failed to confer any significant change. Additionally, LX-NM significantly attenuated the rise of tumor necrosis factor-α (TNF-α), interleukin-1β, prostaglandin E2, nuclear factor-κβ, malondialdehyde and nitric oxide serum levels. In contrast, LX failed to show any significant reduction in elevated serum biomarkers except for TNF-α. LX-NM is an alternative delivery system that is simply prepared at low costs. It showed a superior therapeutic efficacy against RA compared to free LX. Thus, LX-NM can be considered as a promising candidate for treatment of RA and similar inflammatory disorders.

Do observational studies using propensity score methods agree with randomized trials? A systematic comparison of studies on acute coronary syndromes

PubMed Central

Dahabreh, Issa J.; Sheldrick, Radley C.; Paulus, Jessica K.; Chung, Mei; Varvarigou, Vasileia; Jafri, Haseeb; Rassen, Jeremy A.; Trikalinos, Thomas A.; Kitsios, Georgios D.

2012-01-01

Aims Randomized controlled trials (RCTs) are the gold standard for assessing the efficacy of therapeutic interventions because randomization protects from biases inherent in observational studies. Propensity score (PS) methods, proposed as a potential solution to confounding of the treatment–outcome association, are widely used in observational studies of therapeutic interventions for acute coronary syndromes (ACS). We aimed to systematically assess agreement between observational studies using PS methods and RCTs on therapeutic interventions for ACS. Methods and results We searched for observational studies of interventions for ACS that used PS methods to estimate treatment effects on short- or long-term mortality. Using a standardized algorithm, we matched observational studies to RCTs based on patients’ characteristics, interventions, and outcomes (‘topics’), and we compared estimates of treatment effect between the two designs. When multiple observational studies or RCTs were identified for the same topic, we performed a meta-analysis and used the summary relative risk for comparisons. We matched 21 observational studies investigating 17 distinct clinical topics to 63 RCTs (median = 3 RCTs per observational study) for short-term (7 topics) and long-term (10 topics) mortality. Estimates from PS analyses differed statistically significantly from randomized evidence in two instances; however, observational studies reported more extreme beneficial treatment effects compared with RCTs in 13 of 17 instances (P = 0.049). Sensitivity analyses limited to large RCTs, and using alternative meta-analysis models yielded similar results. Conclusion For the treatment of ACS, observational studies using PS methods produce treatment effect estimates that are of more extreme magnitude compared with those from RCTs, although the differences are rarely statistically significant. PMID:22711757

Intra-articular hyaluronic acid in the treatment of knee osteoarthritis: a Canadian evidence-based perspective

PubMed Central

Bhandari, Mohit; Bannuru, Raveendhara R.; Babins, Eric M.; Martel-Pelletier, Johanne; Khan, Moin; Raynauld, Jean-Pierre; Frankovich, Renata; Mcleod, Deanna; Devji, Tahira; Phillips, Mark; Schemitsch, Emil H.; Pelletier, Jean-Pierre

2017-01-01

Osteoarthritis (OA) is a chronic condition characterized by a loss of joint cartilage and is a major cause of disability in Canada, with an estimated CN$195 billion annual cost. Knee OA leads to persistent pain and loss of function, and treatment goals primarily focus on symptom relief and retention of function. Intra-articular hyaluronic acid (IAHA) has therapeutic benefits, and numerous recently published meta-analyses (MAs) and commentaries have highlighted new evidence on the role of IAHA therapy for knee OA. A diverse, multidisciplinary group of specialists met independently in closed sessions to review findings from eight MAs with literature search end dates no earlier than 2012 to address controversies surrounding IAHA therapy for mild-to-moderate knee OA within the Canadian treatment context. Outcomes from a total of eight MAs were reviewed, and consistent and statistically significant improvements in pain, function and stiffness up to 26 weeks were found with IAHA therapy compared with IA placebo or controls, regardless of MA size or trial quality. These findings are in line with those of a Cochrane review, another recent systematic review and patient satisfaction survey. Overall, three MAs reported outcomes based on molecular weight (MW), with the two reporting effect sizes showing significantly improved pain outcomes for higher compared with lower MW HAs. Recent evidence suggests that HA therapy is well tolerated with no increased risk of serious adverse events compared with placebo and the full therapeutic effect of IAHA therapy appears to have considerable clinical importance, consisting of the combined IA placebo and HA therapeutic effects. IAHA therapy is a well-tolerated and effective option for patients with mild-to-moderate knee OA failing first-line pharmacological therapy. PMID:28932293

Feasibility Study of an Interactive Multimedia Electronic Problem Solving Treatment Program for Depression: A Preliminary Uncontrolled Trial

PubMed Central

Berman, Margit I.; Jr., Jay C. Buckey; Hull, Jay G.; Linardatos, Eftihia; Song, Sueyoung L.; McLellan, Robert K.; Hegel, Mark T.

2014-01-01

Computer-based depression interventions lacking live therapist support have difficulty engaging users. This study evaluated the usability, acceptability, credibility, therapeutic alliance and efficacy of a stand-alone multimedia, interactive, computer-based Problem Solving Treatment program (ePST™) for depression. The program simulated live treatment from an expert PST therapist, and delivered 6 ePST™ sessions over 9 weeks. Twenty-nine participants with moderate-severe symptoms received the intervention; 23 completed a mini mally adequate dose of ePST™ (at least 4 sessions). Program usability, acceptability, credibility, and therapeutic alliance were assessed at treatment midpoint and endpoint. Depressive symptoms and health-related functioning were assessed at baseline, treatment midpoint (4 weeks), and study endpoint (10 weeks). Depression outcomes and therapeutic alliance ratings were also compared to previously published research on live PST and computer-based depression therapy. Participants rated the program as highly usable, acceptable, and credible, and reported a therapeutic alliance with the program comparable to that observed in live therapy. Depressive symptoms improved significantly over time. These findings also provide preliminary evidence that ePST™ may be effective as a depression treatment. Larger clinical trials with diverse samples are indicated. PMID:24680231

Prophylactic versus therapeutic amnioinfusion for oligohydramnios in labour.

PubMed

Novikova, Natalia; Hofmeyr, G Justus; Essilfie-Appiah, George

2012-09-12

Amnioinfusion aims to relieve umbilical cord compression during labour by infusing a liquid into the uterine cavity. The objective of this review was to assess the effects of prophylactic amnioinfusion for women in labour with oligohydramnios, but not fetal heart deceleration, compared with therapeutic amnioinfusion only if fetal heart rate decelerations or thick meconium-staining of the liquor occur. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2012). Randomised trials comparing prophylactic amnioinfusion in women in labour with oligohydramnios but not fetal heart rate deceleration in labour with therapeutic amnioinfusion. The authors assessed trial quality and extracted data. One randomized trial of 116 women was included. No differences were found in the rate of caesarean section (risk ratio 1.29, 95% confidence interval 0.60 to 2.74). There were no differences in cord arterial pH, oxytocin augmentation, neonatal pneumonia or postpartum endometritis. Prophylactic amnioinfusion was associated with increased intrapartum fever (risk ratio 3.48, 95% confidence interval 1.21 to 10.05). There appears to be no advantage of prophylactic amnioinfusion over therapeutic amnioinfusion carried out only when fetal heart rate decelerations or thick meconium-staining of the liquor occur.

Prophylactic versus therapeutic amnioinfusion for oligohydramnios in labour.

PubMed

Hofmeyr, G J

2000-01-01

Amnioinfusion aims to relieve umbilical cord compression during labour by infusing a liquid into the uterine cavity. The objective of this review was to assess the effects of prophylactic amnioinfusion for oligohydramnios compared with therapeutic amnioinfusion only if fetal heart rate decelerations or thick meconium-staining of the liquor occur. The Cochrane Pregnancy and Childbirth Group trials register and Cochrane Controlled Trials Register were searched. Date of last search: October 1997. Randomised trials comparing prophylactic with therapeutic amnioinfusion in women with oligohydramnios but not fetal heart rate deceleration in labour. The reviewer assessed trial quality and extracted data. Two studies of 285 women were included. No differences were found in the rate of caesarean section (relative risk 0.98, 95% confidence interval 0.58 to 1.66), or forceps delivery. There were no difference in Apgar scores, cord arterial pH, oxytocin augmentation, meconium aspiration, neonatal pneumonia or postpartum endometritis. Prophylactic amnioinfusion was associated with increased intrapartum fever (relative risk 3.48, 95% confidence interval 1.21 to 10.05). There appears to be no advantage of prophylactic amnioinfusion over therapeutic amnioinfusion carried out only when fetal heart rate decelerations or thick meconium-staining of the liquor occur.

Cognitive enhancing effects of rTMS administered to the prefrontal cortex in patients with depression: A systematic review and meta-analysis of individual task effects.

PubMed

Martin, Donel M; McClintock, Shawn M; Forster, Jane J; Lo, Tin Yan; Loo, Colleen K

2017-11-01

Repetitive transcranial magnetic stimulation (rTMS) is an approved therapeutic treatment of major depressive disorder and has increasing clinical use throughout the world. However, it remains unclear whether an rTMS course for depression may also produce cognitive enhancement. In a recent meta-analysis of sham-controlled randomized controlled studies (RCTs) conducted in patients with neuropsychiatric conditions, no evidence was found for generalized cognitive enhancing effects across cognitive domains with active compared to sham rTMS. Notwithstanding, there remains the possibility of cognitive effects following an rTMS course that are more highly specific, for example, in specific clinical conditions, or at the individual task level. This study aimed to determine whether a therapeutic rTMS course in patients with depression is associated with cognitive enhancing effects at the task level. A systematic review and meta-analysis of outcomes on individual neuropsychological tasks from sham-controlled RCTs where an rTMS course was administered to the dorsolateral prefrontal cortex (DLPFC) in patients with depression. Eighteen studies met the inclusion criteria. Active rTMS treatment showed no specific enhancing effects on the majority of cognitive tasks. Modest effect size improvements with active compared to sham rTMS treatment were found for performance on the Trail Making Test Parts A (g = 0.28, 95% CI = 0.06-0.50) and B (g = 0.26, 95% CI = 0.06-0.47). A therapeutic rTMS course administered to the prefrontal cortex for depression may produce modest cognitive enhancing effects specific to psychomotor speed, visual scanning, and set-shifting ability. © 2017 Wiley Periodicals, Inc.

A novel glycogen synthase kinase-3 inhibitor optimized for acute myeloid leukemia differentiation activity

PubMed Central

Stetson, Lindsay; Ignatz-Hoover, James; Moreton, Stephen; Chakrabarti, Amit; Xia, Zhiqiang; Karan, Goutam; de Lima, Marcos; Agrawal, Mukesh K; Wald, David N

2016-01-01

Standard therapies used for the treatment of Acute Myeloid Leukemia (AML) are cytotoxic agents that target rapidly proliferating cells. Unfortunately, this therapeutic approach has limited efficacy and significant toxicity and the majority of AML patients still die of their disease. In contrast to the poor prognosis of most AML patients, most individuals with a rare subtype of AML, Acute Promyelocytic Leukemia (APL), can be cured by differentiation therapy using regimens containing all-trans retinoic acid. GSK3 has previously been identified as a therapeutic target in AML where its inhibition can lead to the differentiation and growth arrest of leukemic cells. Unfortunately, existing GSK3 inhibitors lead to suboptimal differentiation activity making them less useful as clinical AML differentiation agents. Here we describe the discovery of a novel GSK3 inhibitor, GS87. GS87 was discovered in efforts to optimize GSK3 inhibition for AML differentiation activity. Despite GS87's dramatic ability to induce AML differentiation, kinase profiling reveals its high specificity in targeting GSK3 as compared to other kinases. GS87 demonstrates high efficacy in a mouse AML model system and unlike current AML therapeutics, exhibits little effect on normal bone marrow cells. GS87 induces potent differentiation by more effectively activating GSK3-dependent signaling components including MAPK signaling as compared to other GSK3 inhibitors. GS87 is a novel GSK3 inhibitor with therapeutic potential as a differentiation agent for non-promyelocytic AML. PMID:27196775

Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.

PubMed

Langenickel, Thomas H; Jordaan, Pierre; Petruck, Jesika; Kode, Kiran; Pal, Parasar; Vaidya, Soniya; Chandra, Priya; Rajman, Iris

2016-08-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization. This randomized double-blind crossover study in healthy male subjects compared the effect of therapeutic and supratherapeutic doses of LCZ696 with placebo and moxifloxacin 400 mg (open-label treatment) as positive control. The primary assessment was mean baseline- and placebo-corrected QTcF (∆∆QTcF; Fridericia correction). Additional assessments included the ∆∆QTcB (Bazett's correction), PR interval, QRS duration, heart rate (HR), LCZ696 pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and safety. Of the 84 subjects enrolled, 81 completed the study. The maximum upper bound of the two-sided 90 % confidence interval for ∆∆QTcF for LCZ696 400 mg and 1200 mg were <10 ms, and assay sensitivity was confirmed with moxifloxacin. No relevant treatment-emergent changes were observed in any of the ECG-derived parameters with LCZ696 or placebo, and the incidence of adverse events was comparable among the treatment groups. Single therapeutic and supratherapeutic doses of LCZ696 did not affect cardiac repolarization as defined by the E14 ICH guidelines.

Sentence-Level Movements in Parkinson's Disease: Loud, Clear, and Slow Speech

ERIC Educational Resources Information Center

Kearney,Elaine; Giles, Renuka; Haworth, Brandon; Faloutsos, Petros; Baljko, Melanie; Yunusova, Yana

2017-01-01

Purpose: To further understand the effect of Parkinson's disease (PD) on articulatory movements in speech and to expand our knowledge of therapeutic treatment strategies, this study examined movements of the jaw, tongue blade, and tongue dorsum during sentence production with respect to speech intelligibility and compared the effect of varying…

Comparative effects of copper sulfate or potassium permanganate on channel catfish concurrently infected with Flavobacterium columnare and Ichthyobodo necator

USDA-ARS?s Scientific Manuscript database

An opportunistic study was conducted to determine the effects of two chemical therapeutants on channel catfish (CCF) Ictalurus punctatus concurrently infected Flavobacterium columnare and Ichthyobodo necator. Copper sulfate (CuSO4) and potassium permanganate (KMnO4) were investigated for their abil...

Effectiveness of 308-nm Excimer Laser Therapy in Treating Alopecia Areata, Determined by Examining the Treated Sides of Selected Alopecic Patches.

PubMed

Byun, Ji Won; Moon, Jong Hyuk; Bang, Chan Yl; Shin, Jeonghyun; Choi, Gwang Seong

2015-01-01

Some studies have reported the use of 308-nm excimer laser therapy for treating alopecia areata (AA); however, the effectiveness of this therapy on a theoretical basis has not yet been comparatively analyzed. To determine the therapeutic effect of excimer laser therapy on AA. One alopecic patch was divided into control and treated sides in 10 patients with AA. Then, 308-nm excimer laser therapy was administered twice a week for 12 weeks. Photograph and phototrichogram analyses were performed. Photographic assessments by both dermatologists and individuals of the general population showed objective improvements after excimer laser therapy. On the treated side, the hair count and hair diameter had statistically increased after treatment. However, only the hair diameter was found to be significantly high in the treated half when it was compared with the control side. The 308-nm excimer laser has a therapeutic effect on AA, which is proven by photograph and phototrichogram analysis by a side-by-side comparison. © 2015 S. Karger AG, Basel.

Breviscapine Injection Improves the Therapeutic Effect of Western Medicine on Angina Pectoris Patients.

PubMed

Wang, Chuan; Li, Yafeng; Gao, Shoucui; Cheng, Daxin; Zhao, Sihai; Liu, Enqi

2015-01-01

To evaluate the beneficial and adverse effects of breviscapine injection in combination with Western medicine on the treatment of patients with angina pectoris. The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, the China National Knowledge Infrastructure, the Wanfang Database, the Chongqing VIP Information Database and the China Biomedical Database were searched to identify randomized clinical trials (RCTs) that evaluated the effects of Western medicine compared to breviscapine injection plus Western medicine on angina pectoris patients. The included studies were analyzed using RevMan 5.1.0 software. The literature search yielded 460 studies, wherein 16 studies matched the selection criteria. The results showed that combined therapy using Breviscapine plus Western medicine was superior to Western medicine alone for improving angina pectoris symptoms (OR=3.77, 95% Cl: 2.76~5.15) and also resulted in increased electrocardiogram (ECG) improvement (OR=2.77, 95% Cl: 2.16~3.53). The current evidence suggests that Breviscapine plus Western medicine achieved a superior therapeutic effect compared to Western medicine alone.

Breviscapine Injection Improves the Therapeutic Effect of Western Medicine on Angina Pectoris Patients

PubMed Central

Wang, Chuan; Li, Yafeng; Gao, Shoucui; Cheng, Daxin; Zhao, Sihai; Liu, Enqi

2015-01-01

To evaluate the beneficial and adverse effects of breviscapine injection in combination with Western medicine on the treatment of patients with angina pectoris. The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, the China National Knowledge Infrastructure, the Wanfang Database, the Chongqing VIP Information Database and the China Biomedical Database were searched to identify randomized clinical trials (RCTs) that evaluated the effects of Western medicine compared to breviscapine injection plus Western medicine on angina pectoris patients. The included studies were analyzed using RevMan 5.1.0 software. The literature search yielded 460 studies, wherein 16 studies matched the selection criteria. The results showed that combined therapy using Breviscapine plus Western medicine was superior to Western medicine alone for improving angina pectoris symptoms (OR =3.77, 95% Cl: 2.76~5.15) and also resulted in increased electrocardiogram (ECG) improvement (OR=2.77, 95% Cl: 2.16~3.53). The current evidence suggests that Breviscapine plus Western medicine achieved a superior therapeutic effect compared to Western medicine alone. PMID:26052709

[The phenomenon of attachment to parents, the duration of therapeutic remissions and autoaggressive behavior among inpatients with alcohol addiction].

PubMed

Fedotov, I A; Shustov, D I

2016-01-01

To determine the role of phenomenon of attachment to parents in the formation of therapeutic remission and the relationship between attachment styles and autoaggressive behavior in patients with alcohol addiction (AA). Sixty-two patients with AA and 30 controls were examined. Insecure attachment styles were most frequents in AA patients that indicated a role of attachment pathology in the development of the disease. Higher frequency of secure and preoccupied styles were noted in patients with AA with the duration of therapeutic remissions more than one year compared to those with shorter duration. No effect of duration of therapeutic remission on autoaggressive behavior was found in patients who did not receive special treatment. In AA patients, avoidant style was correlated with autoaggression in family and professional spheres, and high-anxious style was correlated with classical autoaggression in the form of antisocial behavior.

Therapeutic Horseback Riding Outcomes of Parent-Identified Goals for Children with Autism Spectrum Disorder: An ABA′ Multiple Case Design Examining Dosing and Generalization to the Home and Community

PubMed Central

Baird, Joanne M.; Kim, Young Joo; Rajora, Kuwar B.; D’Silva, Delma; Podolinsky, Lin; Mazefsky, Carla; Minshew, Nancy

2014-01-01

We examined whether different doses of therapeutic riding influenced parent-nominated target behaviors of children with autism spectrum disorder (ASD) (a) during the session (b) at home, and (c) in the community. We used a single subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5 times/week. Three boys with ASD, 6–8 years of age participated, and counts of target behaviors were collected in each setting and phase of the study. Compared to Baseline, 70 % of the target behaviors were better during Intervention and improvement was retained in 63 % of the behaviors during Withdrawal. Increased doses of therapeutic riding were significant for magnitude of change, and the effect of the therapeutic riding sessions generalized to home and community. PMID:24091469

Handout on Health: Osteoporosis

MedlinePlus

... well, studies are comparing the effectiveness of different therapeutic approaches. Prevention Studies Researchers continue to explore the impact of nutritional status on bone health and fracture risk. Scientists are examining the impact of physical activity levels on bone health and are developing ...

Inhibitory Effects of Culinary Herbs and Spices on the Growth of HCA-7 Colorectal Cancer Cells and Their COX-2 Expression.

PubMed

Jaksevicius, Andrius; Carew, Mark; Mistry, Calli; Modjtahedi, Helmout; Opara, Elizabeth I

2017-09-21

It is unclear if the anti-inflammatory properties of culinary herbs and spices (CHS) are linked to their ability to inhibit Colorectal cancer cell (CRC) growth. Furthermore, their therapeutic potential with regards to CRC is unknown. The aim of this study was to establish if the inhibition of HCA-7 CRC cell growth by a selection of culinary herbs and spices (CHS) is linked to the inhibition of the cells' cyclooxygenase-2 (COX-2 )expression, and to investigate their therapeutic potential. CHS inhibited the growth of Human colon adenocarcinoma-7 (HCA-7) cells; the order of potency was turmeric, bay leaf, ginger, sage, and rosemary; their combinations had a synergistic or additive effect on cell growth inhibition. CHS also inhibited COX-2 expression and activity; this action was comparable to that of the specific COX-2 inhibitor Celecoxib. Coincident with COX-2 inhibition was the accumulation of cells in the sub G1 phase of the HCA-7's cell cycle and, using bay leaf and turmeric, the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP). This latter effect showed that the effect of these CHS on growth arrest was irreversible, and was comparable to that of the caspase activator Etoposide. This study provides evidence of a link between the inhibition of HCA-7 growth, and its COX-2 expression, by CHS, and their therapeutic potential.

Inhibitory Effects of Culinary Herbs and Spices on the Growth of HCA-7 Colorectal Cancer Cells and Their COX-2 Expression

PubMed Central

Jaksevicius, Andrius; Carew, Mark; Mistry, Calli

2017-01-01

It is unclear if the anti-inflammatory properties of culinary herbs and spices (CHS) are linked to their ability to inhibit Colorectal cancer cell (CRC) growth. Furthermore, their therapeutic potential with regards to CRC is unknown. The aim of this study was to establish if the inhibition of HCA-7 CRC cell growth by a selection of culinary herbs and spices (CHS) is linked to the inhibition of the cells’ cyclooxygenase-2 (COX-2 )expression, and to investigate their therapeutic potential. CHS inhibited the growth of Human colon adenocarcinoma-7 (HCA-7) cells; the order of potency was turmeric, bay leaf, ginger, sage, and rosemary; their combinations had a synergistic or additive effect on cell growth inhibition. CHS also inhibited COX-2 expression and activity; this action was comparable to that of the specific COX-2 inhibitor Celecoxib. Coincident with COX-2 inhibition was the accumulation of cells in the sub G1 phase of the HCA-7’s cell cycle and, using bay leaf and turmeric, the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP). This latter effect showed that the effect of these CHS on growth arrest was irreversible, and was comparable to that of the caspase activator Etoposide. This study provides evidence of a link between the inhibition of HCA-7 growth, and its COX-2 expression, by CHS, and their therapeutic potential. PMID:28934138

[Observation on the therapeutic effect of Lamivudin on chronic hepatitis B].

PubMed

Wen, Xiaofeng; Li, Xuemei; Xie, Houyu; Chen, Nian; Zeng, Wenfeng; Ru, Haiyun; Cui, Xaioping; Tang, Zhongmin

2002-12-01

To observe the therapeutic effect of Lamivudine on controlling hepatitis B virus DNA replication. The liver disease patients were divided into two groups, the treated group (n=64) was given Lamivudine 100 mg once a day for one year and was additionally given liver protection drugs according to their liver function, while the control group (n=30) was given common liver protection drugs. The blood routine test, liver function and the viral markers were detected at defined times. The results showed that after one year treatment of chronic hepatitis B with Lamivudine, the recovery rate of ALT was 90.7%, the negative conversion rate of HBV DNA was 73.1% showing a significant difference as compared with the control group (P<0.05). The negative seroconversion rate of HBeAg was 50%, HBeAg/anti HBe changing rate was 38.2%, that had no significant different as compared with the control group (P<0.05). The percentage for disease relapse and second elevation of ALT was 3.1% in therapeutic group that was significantly different from that of the control group (P<0.05). Two cases with severe hepatitis in the treated group were all alive. Lamivudine could effectively control HBV DNA replication, making ALT normal, it also could decrease the relapse rate of chronic hepatitis B and raise the survival rate of the patients with liver disease.

A Randomized Comparative Trial on the Therapeutic Efficacy of Topical Aloe vera and Calendula officinalis on Diaper Dermatitis in Children

PubMed Central

Panahi, Yunes; Sharif, Mohamad Reza; Sharif, Alireza; Beiraghdar, Fatemeh; Zahiri, Zahra; Amirchoopani, Golnoush; Marzony, Eisa Tahmasbpour; Sahebkar, Amirhossein

2012-01-01

Introduction. Diaper dermatitis (DD) is a common inflammatory disorder among children and infants. The objective of the present randomized and double-blind trial was to compare the therapeutic efficacies of Aloe vera cream and Calendula officinalis ointment on the frequency and severity of DD in children. Methods. Sixty-six infants with DD (aged < 3 years) were randomized to receive either Aloe cream (n = 32) or Calendula ointment (n = 34). Infants were treated with these drugs 3 times a day for 10 days. The severity of dermatitis was graded at baseline as well as at the end of trial using a 5-point scale. The adverse effects of study medications were assessed during the trial. Results. Although improvement in the severity of DD was observed in both treatment groups (P < 0.001), patients receiving Calendula ointment had significantly fewer rash sites compared to Aloe group (P = 0.001). No adverse effect was reported from either of the medications. Discussion. The evidence from this study suggests that topical Aloe and in particular Calendula could serve as safe and effective treatment for the treatment of diaper dermatitis in infants. PMID:22606064

A randomized comparative trial on the therapeutic efficacy of topical aloe vera and Calendula officinalis on diaper dermatitis in children.

PubMed

Panahi, Yunes; Sharif, Mohamad Reza; Sharif, Alireza; Beiraghdar, Fatemeh; Zahiri, Zahra; Amirchoopani, Golnoush; Marzony, Eisa Tahmasbpour; Sahebkar, Amirhossein

2012-01-01

Diaper dermatitis (DD) is a common inflammatory disorder among children and infants. The objective of the present randomized and double-blind trial was to compare the therapeutic efficacies of aloe vera cream and Calendula officinalis ointment on the frequency and severity of DD in children. Sixty-six infants with DD (aged < 3 years) were randomized to receive either aloe cream (n = 32) or Calendula ointment (n = 34). Infants were treated with these drugs 3 times a day for 10 days. The severity of dermatitis was graded at baseline as well as at the end of trial using a 5-point scale. The adverse effects of study medications were assessed during the trial. Although improvement in the severity of DD was observed in both treatment groups (P < 0.001), patients receiving Calendula ointment had significantly fewer rash sites compared to aloe group (P = 0.001). No adverse effect was reported from either of the medications. The evidence from this study suggests that topical aloe and in particular Calendula could serve as safe and effective treatment for the treatment of diaper dermatitis in infants.

Does therapeutic hypothermia reduce acute kidney injury among term neonates with perinatal asphyxia?--a randomized controlled trial.

PubMed

Tanigasalam, Vasanthan; Bhat, Vishnu; Adhisivam, Bethou; Sridhar, M G

2016-01-01

The objective of this study is to evaluate whether therapeutic hypothermia reduces the incidence of acute kidney injury (AKI) among term neonates perinatal asphyxia. This randomized controlled trial conducted in a tertiary care teaching hospital, south India included 120 term neonates with perinatal asphyxia who were randomized to receive either therapeutic hypothermia or standard supportive care. Renal parameters of neonates in both the groups were monitored and AKI was ascertained as per Acute Kidney Injury Network criteria. The incidence of AKI was less in therapeutic hypothermia group compared to standard treatment group (32% versus 60%, p < 0.05). The incidence of Stages 1, 2, and 3 AKI was 22%, 5%, and 5% in therapeutic hypothermia group compared with 52%, 5%, and 3%, respectively, in the standard treatment group. The mortality was less in therapeutic hypothermia group compared with the standard treatment group (26% versus 50%, p < 0.05). Therapeutic hypothermia reduces the incidence and severity of AKI among term neonates with perinatal asphyxia.

5-HT1a activation in PO/AH area induces therapeutic hypothermia in a rat model of intracerebral hemorrhage

PubMed Central

Liang, Tan; Chen, Qianwei; Li, Qiang; Li, Rongwei; Tang, Jun; Hu, Rong; Zhong, Jun; Ge, Hongfei; Liu, Xin; Hua, Feng

2017-01-01

Therapeutic hypothermia is widely applied as a neuroprotective measure on intracerebral hemorrhage (ICH). However, several clinical trials regarding physical hypothermia encountered successive failures because of its side-effects in recent years. Increasing evidences indicate that chemical hypothermia that targets hypothalamic 5-HT1a has potential to down-regulate temperature set point without major side-effects. Thus, this study examined the efficacy and safety of 5-HT1a stimulation in PO/AH area for treating ICH rats. First, the relationship between head temperature and clinical outcomes was investigated in ICH patients and rat models, respectively. Second, the expression and distribution of 5-HT1a receptor in PO/AH area was explored by using whole-cell patch and confocal microscopy. In the meantime, the whole-cell patch was subsequently applied to investigate the involvement of 5-HT1a receptors in temperature regulation. Third, we compared the efficacy between traditional PH and 5-HT1a activation-induced hypothermia for ICH rats. Our data showed that more severe perihematomal edema (PHE) and neurological deficits was associated with increased head temperature following ICH. 5-HT1a receptor was located on warm-sensitive neurons in PO/AH area and 8-OH-DPAT (5-HT1a receptor agonist) significantly enhanced the firing rate of warm-sensitive neurons. 8-OH-DPAT treatment provided a steadier reduction in brain temperature without a withdrawal rebound, which also exhibited a superior neuroprotective effect on ICH-induced neurological dysfunction, white matter injury and BBB damage compared with physical hypothermia. These findings suggest that chemical hypothermia targeting 5-HT1a receptor in PO/AH area could act as a novel therapeutic manner against ICH, which may provide a breakthrough for therapeutic hypothermia. PMID:29088731

Therapeutic touch affects DNA synthesis and mineralization of human osteoblasts in culture.

PubMed

Jhaveri, Ankur; Walsh, Stephen J; Wang, Yatzen; McCarthy, MaryBeth; Gronowicz, Gloria

2008-11-01

Complementary and alternative medicine (CAM) techniques are commonly used in hospitals and private medical facilities; however, the effectiveness of many of these practices has not been thoroughly studied in a scientific manner. Developed by Dr. Dolores Krieger and Dora Kunz, Therapeutic Touch is one of these CAM practices and is a highly disciplined five-step process by which a practitioner can generate energy through their hands to promote healing. There are numerous clinical studies on the effects of TT but few in vitro studies. Our purpose was to determine if Therapeutic Touch had any effect on osteoblast proliferation, differentiation, and mineralization in vitro. TT was performed twice a week for 10 min each on human osteoblasts (HOBs) and on an osteosarcoma-derived cell line, SaOs-2. No significant differences were found in DNA synthesis, assayed by [(3)H]-thymidine incorporation at 1 or 2 weeks for SaOs-2 or 1 week for HOBs. However, after four TT treatments in 2 weeks, TT significantly (p = 0.03) increased HOB DNA synthesis compared to controls. Immunocytochemistry for Proliferating Cell Nuclear Antigen (PCNA) confirmed these data. At 2 weeks in differentiation medium, TT significantly increased mineralization in HOBs (p = 0.016) and decreased mineralization in SaOs-2 (p = 0.0007), compared to controls. Additionally, Northern blot analysis indicated a TT-induced increase in mRNA expression for Type I collagen, bone sialoprotein, and alkaline phosphatase in HOBs and a decrease of these bone markers in SaOs-2 cells. In conclusion, Therapeutic Touch appears to increase human osteoblast DNA synthesis, differentiation and mineralization, and decrease differentiation and mineralization in a human osteosarcoma-derived cell line. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

[Comparison of the effects of BI-6, a new asymmetric bipyridine oxime, with HI-6 oxime and obidoxime in combination with atropine on soman and fosdrine toxicity in mice].

PubMed

Kassa, J

1999-01-01

The therapeutic efficacy of the new asymmetric bispyridinium oxime BI-6 against acute toxicity of the highly toxic organophosphate soman and the organophosphorus insecticide fosdrin by means of affecting the LD50 values of these noxiores substances was compared with the effect of the hitherto most perspective oxime HI-6 and the classic obidoxime always in combination with the identical dose of atropine. At the equimolar level the effect of oxime BI-6 against fosdrin completely equals the effects of both oximes HI-6 and obidoxime. The effect of oxime BI-6 against soman is even more marked than the effect of HI-6 but this difference is not statistically significant. On the other hand, at the equi-effective level, the effect of oxime BI-6 against soman is statistically significantly lower than the effect of HI-6, and against fosdrin it is even lower than the effect of both remaining oximes. The effects of the new oxime BI-6 equal, or slightly exceed the therapeutic effect of HI-6 but at the equimolar level only. At the equi-effective level which respects the toxicity of the oxime and is therefore more important for practical use, it is a therapeutically weaker reactivator of acetylcholinesterase than HI-6.

Comparative Therapeutic Effects of Minocycline Treatment and Bone Marrow Mononuclear Cell Transplantation following Striatal Stroke

PubMed Central

Souza, Celice C.; da Silva, Michelle Castro; Lopes, Rosana Telma; Cardoso, Marcelo M.; Santos, Adriano Guimarães; dos Santos, Ijair Rogério

2017-01-01

We explored the comparative effects of minocycline treatment and intrastriatal BMMC transplantation after experimental striatal stroke in adult rats. Male Wistar adult rats were divided as follows: saline-treated (N = 5), minocycline-treated (N = 5), and BMMC-transplanted (N = 5) animals. Animals received intrastriatal microinjections of 80 pmol of endothelin-1 (ET-1). Behavioral tests were performed at 1, 3, and 7 days postischemia. Animals were treated with minocycline (50 mg/kg, i.p.) or intrastriatal transplants of 106 BMMCs at 24 h postischemia. Animals were perfused at 7 days after ischemic induction. Coronal sections were stained with cresyl violet for gross histopathological analysis and immunolabeled for the identification of neuronal bodies (NeuN), activated microglia/macrophages (ED1), and apoptotic cells (active caspase-3). BMMC transplantation and minocycline reduced the number of ED1+ cells (p < 0.05, ANOVA-Tukey), but BMMC afforded better results. Both treatments afforded comparable levels of neuronal preservation compared to control (p > 0.05). BMMC transplantation induced a higher decrease in the number of apoptotic cells compared to control and minocycline treatment. Both therapeutic approaches improved functional recovery in ischemic animals. The results suggest that BMMC transplantation is more effective in modulating microglial activation and reducing apoptotic cell death than minocycline, although both treatments are equally efficacious on improving neuronal preservation. PMID:28713482

Comparative Therapeutic Effects of Minocycline Treatment and Bone Marrow Mononuclear Cell Transplantation following Striatal Stroke.

PubMed

Souza, Celice C; da Silva, Michelle Castro; Lopes, Rosana Telma; Cardoso, Marcelo M; de Souza, Lucas Lacerda; Santos, Adriano Guimarães; Dos Santos, Ijair Rogério; Franco, Edna C S; Gomes-Leal, Walace

2017-01-01

We explored the comparative effects of minocycline treatment and intrastriatal BMMC transplantation after experimental striatal stroke in adult rats. Male Wistar adult rats were divided as follows: saline-treated ( N = 5), minocycline-treated ( N = 5), and BMMC-transplanted ( N = 5) animals. Animals received intrastriatal microinjections of 80 pmol of endothelin-1 (ET-1). Behavioral tests were performed at 1, 3, and 7 days postischemia. Animals were treated with minocycline (50 mg/kg, i.p.) or intrastriatal transplants of 106 BMMCs at 24 h postischemia. Animals were perfused at 7 days after ischemic induction. Coronal sections were stained with cresyl violet for gross histopathological analysis and immunolabeled for the identification of neuronal bodies (NeuN), activated microglia/macrophages (ED1), and apoptotic cells (active caspase-3). BMMC transplantation and minocycline reduced the number of ED1+ cells ( p < 0.05, ANOVA-Tukey), but BMMC afforded better results. Both treatments afforded comparable levels of neuronal preservation compared to control ( p > 0.05). BMMC transplantation induced a higher decrease in the number of apoptotic cells compared to control and minocycline treatment. Both therapeutic approaches improved functional recovery in ischemic animals. The results suggest that BMMC transplantation is more effective in modulating microglial activation and reducing apoptotic cell death than minocycline, although both treatments are equally efficacious on improving neuronal preservation.

Therapeutic Symptomatic Strategies in the Parasomnias.

PubMed

Manni, Raffaele; Toscano, Gianpaolo; Terzaghi, Michele

2018-06-05

The purpose of this review was to discuss the currently available pharmacologic and non-pharmacologic treatment options for parasomnias. Recent pathophysiological findings about sleep structure in parasomnias helped understanding several drug mechanisms of action. Serotoninergic theory accounts for the effect of serotoninergic drugs. Study about spectral analysis of sleep showed the effect of clonazepam on spectral bands. Cannabinoids proved to be effective in some of parasomnias, as in many other neurological disorders. A series of therapeutic strategies were analyzed and compared. Benzodiazepines, antidepressant drugs, and L-5-hydroxytryptophan may be beneficial in DOA. SSRI and topiramate are effective in SRED. RBD responds to clonazepam, melatonin, and to a lesser extent to dopaminergic and anticholinergic agents. Prazosin and cannabinoids are effective in nightmare disorder. Sleep paralysis may respond to antidepressant agents. Tricyclic antidepressant may be effective in sleep-related hallucinations and exploding head syndrome. Sleep enuresis may be successfully treated with desmopressin, anticholinergic drugs, and imipramine.

Effects of video-based therapy preparation targeting experiential acceptance or the therapeutic alliance.

PubMed

Johansen, Ayna B; Lumley, Mark; Cano, Annmarie

2011-06-01

Preparation for psychotherapy may enhance the psychotherapeutic process, reduce drop-outs, and improve outcomes, but the effective mechanisms of such preparation are poorly understood. Previous studies have rarely targeted specific processes that are associated with positive therapy outcomes. This randomized experiment compared the effects of preparatory videos that targeted either the Therapeutic Alliance, Experiential Acceptance, or a Control video on early therapeutic process variables in 105 patients seen in individual therapy. Participants watched the videos just before their first therapy session. No significant differences were found between the Alliance and Experiential Acceptance videos on patient recommendations, immediate affective reactions, or working alliance and attrition after the first session. However, the Therapeutic Alliance video produced an immediate increase in negative mood relative to the Control video, whereas the Experiential acceptance video produced a slight increase in positive mood relative to the Alliance video. Surprisingly, patients who viewed the Alliance video were rated significantly lower than the control group on therapist-rated alliance after the first session. These findings suggest there may be specific process effects in the early phase of treatment based on the type of pretraining material used, and also indicate that video-based pretraining efforts could be counterproductive. Furthermore, this research contributes to the literature by providing insights into methodological considerations for future work on the use of technology in psychotherapy and challenges associated with preparing people for successful psychotherapy.

Testing the Effectiveness of Therapeutic Showering in Labor.

PubMed

Stark, Mary Ann

: Therapeutic showering is a holistic nursing intervention that is often available and supports physiologic labor. The purpose of this study was to compare the effectiveness of therapeutic showering with usual care during active labor. Research questions were as follows: Are there significant differences between women who showered 30 minutes during active labor and those who received usual labor care in anxiety, tension, relaxation, pain, discomfort, and coping? Is there a difference in use of obstetric interventions between groups? A convenience sample of healthy low-risk women in active labor was recruited (N = 32). A pretest posttest control group repeated-measures design was used. Participants were randomized to treatment group (n = 17), who showered for 30 minutes, or to control group (n = 14) who received usual labor care. Women evaluated pain, discomfort, anxiety, tension, coping, and relaxation at enrollment, again 15 minutes after entering the shower or receiving usual care, then again 30 minutes after entering the shower or receiving usual care. Chart reviews after delivery recorded obstetric interventions. The showering group had statistically significant decreases in pain, discomfort, anxiety and tension, and significant increase in relaxation. There were no differences in use of obstetric interventions. Therapeutic showering was effective in reducing pain, discomfort, anxiety, and tension while improving relaxation and supporting labor in this sample.

Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice

PubMed Central

Huang, Yan-Feng; Qu, Chang; Xu, Lie-Qiang; Su, Zi-Ren; Zeng, Hui-Fang; Zheng, Lin; Yi, Tie-Gang; Li, Hui-Lin; Chen, Jian-Ping

2018-01-01

Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC. PMID:29538417

Validating the Effectiveness of Switching the Vancomycin TDM Analysis Software Based on the Predictive Accuracy.

PubMed

Imai, Shungo; Yamada, Takehiro; Ishiguro, Nobuhisa; Miyamoto, Takenori; Kagami, Keisuke; Tomiyama, Naoki; Niinuma, Yusuke; Nagasaki, Daisuke; Suzuki, Koji; Yamagami, Akira; Kasashi, Kumiko; Kobayashi, Masaki; Iseki, Ken

2017-01-01

Based on the predictive performance in our previous study, we switched the therapeutic drug monitoring (TDM) analysis software for dose setting of vancomycin (VCM) from "Vancomycin MEEK TDM analysis software Ver2.0" (MEEK) to "SHIONOGI-VCM-TDM ver.2009" (VCM-TDM) in January 2015. In the present study, our aim was to validate the effectiveness of the changing VCM TDM analysis software in initial dose setting of VCM. The enrolled patients were divided into two groups, each having 162 patients in total, who received VCM with the initial dose set using MEEK (MEEK group) or VCM-TDM (VCM-TDM group). We compared the rates of attaining the therapeutic range (trough value; 10-20 μg/mL) of serum VCM concentration between the groups. Multivariate logistic regression analysis was performed to confirm that changing the VCM TDM analysis software was an independent factor related to attaining the therapeutic range. Switching the VCM TDM analysis software from MEEK to VCM-TDM improved the rate of attaining the therapeutic range by 21.6% (MEEK group: 42.6% vs. VCM-TDM group: 64.2%, p<0.01). Patient age ≥65 years, concomitant medication (furosemide) and the TDM analysis software used VCM-TDM were considered to be independent factors for attaining the therapeutic range. These results demonstrated the effectiveness of switching the VCM TDM analysis software from MEEK to VCM-TDM for initial dose setting of VCM.

Therapeutic Effect of External Application of Ligustrazine Combined with Holistic Nursing on Pressure Sores.

PubMed

Niu, Junzhi; Han, Lin; Gong, Fen

2016-08-15

BACKGROUND This study aimed to explore the therapeutic effect of external application of ligustrazine combined with holistic nursing on pressure sores, as well as the underlying mechanism. MATERIAL AND METHODS From February 2014 to March 2015, a total of 32 patients with Phase II and Phase III pressure sores were enrolled and randomly assigned to an experimental group or a control group. The clinical data were comparable between the 2 groups. In addition to holistic nursing, the patients in the experimental group received 4 weeks of continuous external application of ligustrazine, whereas patients in the control group received compound clotrimazole cream. Therapeutic effect and healing time were recorded. HaCaT cells were used as an in vitro model for mechanism analysis of the effect of ligustrazine in treating pressure sores. After culturing with different concentrations of ligustrazine or the inhibitor of AKT (LY294002) for 72 h, cell viability, clone formation numbers, and levels of phosphatidyl inositol 3-kinase (PI3K), p-AKT, and p-mammalian target of rapamycin (mTOR) were determined. RESULTS Compared to the control group, the total effective rate in the experimental group was significantly higher, and the healing time was significantly reduced. Cell viability and clone formation numbers were significantly upregulated by ligustrazine in a dose-dependent manner. Both the cell viability and clone formation numbers were significantly inhibited by application of LY294002. CONCLUSIONS Our results suggest that ligustrazine combined with holistic nursing is an effective treatment of pressure sores. The protective effect may be associated with the promotion of cell growth by activation of the PI3K/AKT pathway.

Therapeutic Effect of External Application of Ligustrazine Combined with Holistic Nursing on Pressure Sores

PubMed Central

Niu, Junzhi; Han, Lin; Gong, Fen

2016-01-01

Background This study aimed to explore the therapeutic effect of external application of ligustrazine combined with holistic nursing on pressure sores, as well as the underlying mechanism. Material/Methods From February 2014 to March 2015, a total of 32 patients with Phase II and Phase III pressure sores were enrolled and randomly assigned to an experimental group or a control group. The clinical data were comparable between the 2 groups. In addition to holistic nursing, the patients in the experimental group received 4 weeks of continuous external application of ligustrazine, whereas patients in the control group received compound clotrimazole cream. Therapeutic effect and healing time were recorded. HaCaT cells were used as an in vitro model for mechanism analysis of the effect of ligustrazine in treating pressure sores. After culturing with different concentrations of ligustrazine or the inhibitor of AKT (LY294002) for 72 h, cell viability, clone formation numbers, and levels of phosphatidyl inositol 3-kinase (PI3K), p-AKT, and p-mammalian target of rapamycin (mTOR) were determined. Results Compared to the control group, the total effective rate in the experimental group was significantly higher, and the healing time was significantly reduced. Cell viability and clone formation numbers were significantly upregulated by ligustrazine in a dose-dependent manner. Both the cell viability and clone formation numbers were significantly inhibited by application of LY294002. Conclusions Our results suggest that ligustrazine combined with holistic nursing is an effective treatment of pressure sores. The protective effect may be associated with the promotion of cell growth by activation of the PI3K/AKT pathway. PMID:27523814

Medicinal use of cannabis: history and current status.

PubMed

Kalant, H

2001-01-01

To provide an overview of the history and pharmacology of cannabis in relation to current scientific knowledge concerning actual and potential therapeutic uses of cannabis preparations and pure cannabinoids. The literature on therapeutic uses of cannabis and cannabinoids was assessed with respect to type of study design, quality and variability of data, independent replications by the same or other investigators, magnitude of effects, comparison with other available treatments and reported adverse effects. The results of this review were also compared with those of major international reviews of this topic in the past five years. Pure tetrahydrocannabinol and several analogues have shown significant therapeutic benefits in the relief of nausea and vomiting, and stimulation of appetite in patients with wasting syndrome. Recent evidence clearly demonstrates analgesic and anti-spasticity effects that will probably prove to be clinically useful. Reduction of intraocular pressure in glaucoma and bronchodilation in asthma are not sufficiently strong, long lasting or reliable to provide a valid basis for therapeutic use. The anticonvulsant effect of cannabidiol is sufficiently promising to warrant further properly designed clinical trials. There is still a major lack of long term pharmacokinetic data and information on drug interactions. For all the present and probable future uses, pure cannabinoids, administered orally, rectally or parenterally, have been shown to be effective, and they are free of the risks of chronic inflammatory disease of the airways and upper respiratory cancer that are associated with the smoking of crude cannabis. Smoking might be justified on compassionate grounds in terminally ill patients who are already accustomed to using cannabis in this manner. Future research will probably yield new synthetic analogues with better separation of therapeutic effects from undesired psychoactivity and other side effects, and with solubility properties that may permit topical administration in the eye, or aerosol inhalation for rapid systemic effect without the risks associated with smoke inhalation.

Lingual vs. labial fixed orthodontic appliances: systematic review and meta-analysis of treatment effects.

PubMed

Papageorgiou, Spyridon N; Gölz, Lina; Jäger, Andreas; Eliades, Theodore; Bourauel, Christoph

2016-04-01

The aim of this systematic review was to compare the therapeutic and adverse effects of lingual and labial orthodontic fixed appliances from clinical trials on human patients in an evidence-based manner. Randomized and prospective non-randomized clinical trials comparing lingual and labial appliances were included. Risk of bias within and across studies was assessed using the Cochrane tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random-effects meta-analyses were conducted, followed by subgroup and sensitivity analyses. Six electronic databases were searched from inception to July 2015, without limitations. A total of 13 papers pertaining to 11 clinical trials were included with a total of 407 (34% male/66% female) patients. Compared with labial appliances, lingual appliances were associated with increased overall oral discomfort, increased speech impediment (measured using auditory analysis), worse speech performance assessed by laypersons, increased eating difficulty, and decreased intermolar width. On the other hand, lingual appliances were associated with increased intercanine width and significantly decreased anchorage loss of the maxillary first molar during space closure. Based on existing trials, there is insufficient evidence to make robust recommendations for lingual fixed orthodontic appliances regarding their therapeutic or adverse effects, as the quality of evidence was low. © 2016 Eur J Oral Sci.

Effects of hypothermia on pharmacokinetics and pharmacodynamics: a systematic review of preclinical and clinical studies.

PubMed

van den Broek, Marcel P H; Groenendaal, Floris; Egberts, Antoine C G; Rademaker, Carin M A

2010-05-01

Examples of clinical applications of therapeutic hypothermia in modern clinical medicine include traumatic cardiac arrest, ischaemic stroke and, more recently, acute perinatal asphyxia in neonates. The exact mechanism of (neuro)protection by hypothermia is unknown. Since most enzymatic processes exhibit temperature dependency, it can be expected that therapeutic hypothermia may cause alterations in both pharmacokinetic and pharmacodynamic parameters, which could result in an increased risk of drug toxicity or therapy failure. Generalizable knowledge about the effect of therapeutic hypothermia on pharmacokinetics and pharmacodynamics could lead to more appropriate dosing and thereby prediction of clinical effects. This article reviews the evidence on the influence of therapeutic hypothermia on individual pharmacokinetic and pharmacodynamic parameters. A literature search was conducted within the PubMed, Embase and Cochrane databases from January 1965 to September 2008, comparing pharmacokinetic and/or pharmacodynamic parameters in hypothermia and normothermia regarding preclinical (animal) and clinical (human) studies. During hypothermia, pharmacokinetic parameters alter, resulting in drug and metabolite accumulation in the plasma for the majority of drugs. Impaired clearance is the most striking effect. Based on impaired clearance, dosages should be decreased considerably, especially for drugs with a low therapeutic index. Hypothetically, high-clearance compounds are affected more than low-clearance compounds because of the additional effect of impaired hepatic blood flow. The volume of distribution also changes, which may lead to therapy failure when it increases and could lead to toxicity when it decreases. The pH-partitioning hypothesis could contribute to the changes in the volumes of distribution for weak bases and acids, depending on their acid dissociation constants and acid-base status. Pharmacodynamic parameters may also alter, depending on the hypothermic regimen, drug target location, pharmacological mechanism and metabolic pathway of inactivation. The pharmacological response changes when target sensitivity alters. Rewarming patients to normothermia can also result in toxicity or therapy failure. The integrated effect of hypothermia on pharmacokinetic and pharmacodynamic properties of individual drugs is unclear. Therefore, therapeutic drug monitoring is currently considered essential for drugs with a low therapeutic index, drugs with active metabolites, high-clearance compounds and drugs that are inactivated by enzymes at the site of effect. Because most of the studies (74%) included in this review contain preclinical data, clinical pharmacokinetic/pharmacodynamic studies are essential for the development of substantiated dose regimens to avoid toxicity and therapy failure in patients treated with hypothermia.

Psilocybin--summary of knowledge and new perspectives.

PubMed

Tylš, Filip; Páleníček, Tomáš; Horáček, Jiří

2014-03-01

Psilocybin, a psychoactive alkaloid contained in hallucinogenic mushrooms, is nowadays given a lot of attention in the scientific community as a research tool for modeling psychosis as well as due to its potential therapeutic effects. However, it is also a very popular and frequently abused natural hallucinogen. This review summarizes all the past and recent knowledge on psilocybin. It briefly deals with its history, discusses the pharmacokinetics and pharmacodynamics, and compares its action in humans and animals. It attempts to describe the mechanism of psychedelic effects and objectify its action using modern imaging and psychometric methods. Finally, it describes its therapeutic and abuse potential. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Conclusions of the expert panel: importance of erlotinib as a second-line therapeutic option

PubMed Central

Castagnari, Aldo

2008-01-01

During the Experts Meeting on Lung Cancer, participants emphasized the usefulness of erlotinib as second-line therapy for lung cancer. They noted that, although there are no comparative studies, erlotinib could be as effective as docetaxel and pemetrexed in second-line therapy. Regarding the toxicity profile of each of these drugs – one of the key issues considered in the meeting – specialists pointed out how important it is to clearly identify existing differences in this issue. Each drug has different degrees of toxicity, and this information is crucial at the time of choosing the therapeutic regimen. Erlotinib treatment could be an effective option for second-line therapy. PMID:18831720

Comparison between neurostimulation techniques repetitive transcranial magnetic stimulation vs electroconvulsive therapy for the treatment of resistant depression: patient preference and cost-effectiveness.

PubMed

Magnezi, Racheli; Aminov, Emanuel; Shmuel, Dikla; Dreifuss, Merav; Dannon, Pinhas

2016-01-01

Major depressive disorder (MDD) is a common disorder, widely distributed in the population, and is often associated with severe symptoms and functional impairment. It has been estimated that 30% of MDD patients do not benefit adequately from therapeutic interventions, including pharmacotherapy and psychotherapy. Treatment-resistant depression (TRD) is generally defined as a failure to achieve remission, despite therapeutic interventions. The most effective treatment alternatives for TRD are hospitalization, electroconvulsive therapy (ECT), and transcranial magnetic stimulation (TMS). Here we compared the clinical effectiveness of ECT and TMS, including success rates, patient responses, side-effect profiles, and financial worthiness. We found that ECT (P<0.0001) was more effective than TMS (P<0.012) (not statistically significant in group effect) in TRD patients. However, ECT patients reported a higher percentage of side effects (P<0.01) and the TMS treatment scored better in terms of patient preference. The cost benefit of ECT was higher than that of TMS (US$2075 vs US$814). Patient's preferences for treatment could be more intense in the TMS, if the TMS is included in the Health Maintenance Organization's service list. We propose that both of these treatment options should be available in psychiatric wards, thus expanding the therapeutic toolkit for TRD.

A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Crighton, Gemma L; Estcourt, Lise J; Wood, Erica M; Trivella, Marialena; Doree, Carolyn; Stanworth, Simon

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in thrombocytopenic patients with bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004 and updated in 2012 that addressed four separate questions: therapeutic-only versus prophylactic platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. We have now split this review into four smaller reviews looking at these questions individually; this review is the first part of the original review. Objectives To determine whether a therapeutic-only platelet transfusion policy (platelet transfusions given when patient bleeds) is as effective and safe as a prophylactic platelet transfusion policy (platelet transfusions given to prevent bleeding, usually when the platelet count falls below a given trigger level) in patients with haematological disorders undergoing myelosuppressive chemotherapy or stem cell transplantation. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 23 July 2015. Selection criteria RCTs involving transfusions of platelet concentrates prepared either from individual units of whole blood or by apheresis, and given to prevent or treat bleeding in patients with malignant haematological disorders receiving myelosuppressive chemotherapy or undergoing HSCT. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Main results We identified seven RCTs that compared therapeutic platelet transfusions to prophylactic platelet transfusions in haematology patients undergoing myelosuppressive chemotherapy or HSCT. One trial is still ongoing, leaving six trials eligible with a total of 1195 participants. These trials were conducted between 1978 and 2013 and enrolled participants from fairly comparable patient populations. We were able to critically appraise five of these studies, which contained separate data for each arm, and were unable to perform quantitative analysis on one study that did not report the numbers of participants in each treatment arm. Overall the quality of evidence per outcome was low to moderate according to the GRADE approach. None of the included studies were at low risk of bias in every domain, and all the studies identified had some threats to validity. We deemed only one study to be at low risk of bias in all domains other than blinding. Two RCTs (801 participants) reported at least one bleeding episode within 30 days of the start of the study. We were unable to perform a meta-analysis due to considerable statistical heterogeneity between studies. The statistical heterogeneity seen may relate to the different methods used in studies for the assessment and grading of bleeding. The underlying patient diagnostic and treatment categories also appeared to have some effect on bleeding risk. Individually these studies showed a similar effect, that a therapeutic-only platelet transfusion strategy was associated with an increased risk of clinically significant bleeding compared with a prophylactic platelet transfusion policy. Number of days with a clinically significant bleeding event per participant was higher in the therapeutic-only group than in the prophylactic group (one RCT; 600 participants; mean difference 0.50, 95% confidence interval (CI) 0.10 to 0.90; moderate-quality evidence). There was insufficient evidence to determine whether there was any difference in the number of participants with severe or life-threatening bleeding between a therapeutic-only transfusion policy and a prophylactic platelet transfusion policy (two RCTs; 801 participants; risk ratio (RR) 4.91, 95% CI 0.86 to 28.12; low-quality evidence). Two RCTs (801 participants) reported time to first bleeding episode. As there was considerable heterogeneity between the studies, we were unable to perform a meta-analysis. Both studies individually found that time to first bleeding episode was shorter in the therapeutic-only group compared with the prophylactic platelet transfusion group. There was insufficient evidence to determine any difference in all-cause mortality within 30 days of the start of the study using a therapeutic-only platelet transfusion policy compared with a prophylactic platelet transfusion policy (two RCTs; 629 participants). Mortality was a rare event, and therefore larger studies would be needed to establish the effect of these alternative strategies. There was a clear reduction in the number of platelet transfusions per participant in the therapeutic-only arm (two RCTs, 991 participants; standardised mean reduction of 0.50 platelet transfusions per participant, 95% CI −0.63 to −0.37; moderate-quality evidence). None of the studies reported quality of life. There was no evidence of any difference in the frequency of adverse events, such as transfusion reactions, between a therapeutic-only and prophylactic platelet transfusion policy (two RCTs; 991 participants; RR 1.02, 95% CI 0.62 to 1.68), although the confidence intervals were wide. Authors’ conclusions We found low- to moderate-grade evidence that a therapeutic-only platelet transfusion policy is associated with increased risk of bleeding when compared with a prophylactic platelet transfusion policy in haematology patients who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT. There is insufficient evidence to determine any difference in mortality rates and no evidence of any difference in adverse events between a therapeutic-only platelet transfusion policy and a prophylactic platelet transfusion policy. A therapeutic-only platelet transfusion policy is associated with a clear reduction in the number of platelet components administered. PMID:26422767

Optimal therapies of a virus replication model with pharmacological delays based on reverse transcriptase inhibitors and protease inhibitors

NASA Astrophysics Data System (ADS)

Pei, Yongzhen; Li, Changguo; Liang, Xiyin

2017-11-01

A short delay in the pharmacological effect on account of the time required for drug absorption, distribution, and penetration into target cells after application of any anti-viral drug, is defined by the pharmacological delay (Herz et al 1996 Proc. Natl Acad. Sci. USA 93 7247-51). In this paper, a virus replication model with Beddington-DeAngelis incidence rate and the pharmacological and intracellular delays is presented to describe the treatment to cure the virus infection. The optimal controls represent the efficiency of reverse transcriptase inhibitors and protease inhibitors in suppressing viral production and prohibiting new infections. Due to the fact that both the control and state variables contain delays, we derive a necessary conditions for our optimal problem. Based on these results, numerical simulations are implemented not only to show the optimal therapeutic schedules for different infection and release rates, but also to compare the effective of three treatment programs. Furthermore, comparison of therapeutic effects under different maximum tolerable dosages is shown. Our research indicates that (1) the proper and specific treatment program should be determined according to the infection rates of different virus particles; (2) the optimal combined drug treatment is the most efficient; (3) the appropriate proportion of medicament must be formulated during the therapy due to the non-monotonic relationship between maximum tolerable dosages and therapeutic effects; (4) the therapeutic effect is advantageous when the pharmacological delay is considered.

[Observation on therapeutic effect of acupuncture combined with chinese herbs on polycystic ovary syndrome of kidney deficiency and phlegm stasis type].

PubMed

Shi, Yin; Feng, Hui-jun; Liu, Hui-rong; Zhu, Dan

2009-02-01

To observe the clinical therapeutic effect of acupuncture combined with Chinese herbs on polycystic ovary syndrome of kidney deficiency and phlegm stasis type and probe into the mechanism. Sixty-three cases of polycystic ovary syndrome of kidney deficiency and phlegm stasis type were randomly divided in to a combined acupuncture and Chinese herb group (n=32) treated with acupuncture at Qihai (CV 6), Guanyuan (CV 4), et al. and oral administration of Chinese herbs, and a simple Chinese herb group (n=31) treated with oral administration of the same Chinese herbs as in the combined acupuncture and Chinese herb group. The therapeutic effects and changes of follicle stimulating hormone (FSH), luteotropic hormone (LH), testosterone (T) and LH/FSH were compared between the two groups. The total effective rate was 93.8% in the combined acupuncture and Chinese herb group and 80.6% in the simple Chinese herb group, the former being significantly better than the latter (P < 0.05). The decrease of T in the combined acupuncture and Chinese herb group was significantly su perior to that in the simple Chinese herb group (P < 0.01). Acupuncture combined with Chinese herb therapy is superior to the simple Chinese herb in the clinical therapeutic effect on polycystic ovary syndrome of kidney deficiency and phlegm stasis type and decrease of T level, indicating this method is a better one for polycystic ovary syndrome of kidney deficiency and phlegm stasis type.

Recent advances in chirally pure proton pump inhibitors.

PubMed

Pai, Vikas; Pai, Nitin

2007-08-01

Chirality is a ubiquitous natural phenomenon resulting because of a differential spatial orientation of molecules around its chiral centre. This leads to the existence of two or more spatially dissimilar forms, known as stereoisomers or enantiomers, which are non-superimposable images of each other and may significantly differ from each other with respect to pharmacokinetic and pharmacodynamic properties and molecular interaction. Thus one isomer may offer significant pharmacokinetic and therapeutic advantages as compared to the other isomer or the racemic mixture (mixture containing both enantiomers). Proton pump inhibitors are a class of drugs which have been very effective in the management of acid-related disorders. The proton pumps currently available in the market including omeprazole, pantoprazole, rabeprazole and lansoprazole are racemic mixtures of the S and R isomers. Chirally pure forms of proton pump inhibitors show a superior metabolic and pharmacokinetic profile as compared to their racemates. The therapeutic efficacy is also superior to the parent racemate. This has been clearly demonstrated with the development of esomeprazole- the S-isomer of omeprazole. S-pantoprazole and dexrabeprazole also offer therapeutic advantages as compared to racemic pantoprazole and racemic rabeprazole respectively. This article reviews the chiral developments in the proton pump inhibitors and their clinical applications.

Impact of a driver intervention program on DWI recidivism and problem drinking

DOT National Transportation Integrated Search

1985-12-01

This was a natural history study comparing the effects of a brief jail sentence, suspended sentence/fine, or a therapeutic intervention known as The Weekend Intervention Program (WIP) on drunk driving recidivism and alcohol-related crashes, Offenders...

Monomeric CH3: A Small, Stable Antibody Domain with Therapeutic Promise | Poster

Cancer.gov

By Ashley DeVine, Staff Writer Antibody domains are emerging as promising biopharmaceuticals because of their relatively small size compared to full-sized antibodies, which are too large to effectively penetrate tumors and bind to sterically restricted therapeutic targets. In an article published in The Journal of Biological Chemistry, Tianlei Ying, Ph.D., Dimiter Dimitrov, Ph.D., and their colleagues in the Protein Interactions Group, Cancer and Inflammation Program, Center for Cancer Research, reported their design of a novel antibody domain, monomeric CH3 (mCH3).

Drug-device trials for infectious diseases: CDRH perspective.

PubMed

Meier, Kristen L; Gitterman, Steven

2011-05-01

Assessing the performance of new diagnostic tests for infectious diseases has traditionally focused on comparing the new assay against a reference standard such as culture. In this paper, we suggest that clinical trial designs with both a diagnostic and therapeutic component may be necessary to evaluate the safety and effectiveness of nonmicrobiologically based assays, with a specific emphasis on the test/marker-stratified design. General design challenges for trials of infectious diseases that simultaneously study both diagnostic and therapeutic components (eg, both devices and drugs) are also discussed.

Therapeutic whole-body hypothermia reduces mortality in severe traumatic brain injury if the cooling index is sufficiently high: meta-analyses of the effect of single cooling parameters and their integrated measure.

PubMed

Olah, Emoke; Poto, Laszlo; Hegyi, Peter; Szabo, Imre; Hartmann, Petra; Solymar, Margit; Petervari, Erika; Balasko, Marta; Habon, Tamas; Rumbus, Zoltan; Tenk, Judit; Rostas, Ildiko; Weinberg, Jordan; Romanovsky, Andrej A; Garami, Andras

2018-04-21

Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the mortality of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure inter-study homogeneity. We extracted data on TBI severity, body temperature, mortality, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but inter-study heterogeneity was high. On the contrary, by meta-analysis of RCTs which were homogenous with regards to statistical, clinical designs and precisely reported the cooling protocol, we showed decreased odds ratio for mortality in therapeutic hypothermia compared to no cooling. As independent factors, milder and longer cooling, and rewarming at < 0.25°C/h were associated with better outcome. Therapeutic hypothermia was beneficial only if the cooling index (measure of combination of cooling parameters) was sufficiently high. We conclude that high methodological and statistical inter-study heterogeneity could underlie the contradictory results obtained in previous studies. By analyzing methodologically homogenous studies, we show that cooling improves the outcome of severe TBI and this beneficial effect depends on certain cooling parameters and on their integrated measure, the cooling index.

[Atomoxetine and piracetam in the treatment of attention deficit hyperactivity disorder in children].

PubMed

Zavadenko, N N; Suvorinova, N Iu

2008-01-01

Therapeutic effect of atomoxetine and piracetam has been assessed in the open controlled study included 42 patients with attention deficit hyperactivity disorder (ADHD), aged from 6 to 13 years. Group 1 (16 patients) received atomoxetine (strattera) in daily dosage 0,8-1,2 mg/kg as a monotherapy for 6 weeks. Patients of group 2 (14 children) received piracetam as a monotherapy in daily dosage 50-70 mg/kg for 6 weeks. No pharmacological therapy was conducted in group 3 (a control one) which included 12 patients with ADHD. The high effectiveness of both atomoxetine and piracetam has been shown. However, comparing to piracetam, the therapeutic effect of atomoxetine was reached earlier (two weeks after the beginning of therapy) and was more pronounced for all components of syndromes.

A Multimodal System with Synergistic Effects of Magneto-Mechanical, Photothermal, Photodynamic and Chemo Therapies of Cancer in Graphene-Quantum Dot-Coated Hollow Magnetic Nanospheres

PubMed Central

Wo, Fangjie; Xu, Rujiao; Shao, Yuxiang; Zhang, Zheyu; Chu, Maoquan; Shi, Donglu; Liu, Shupeng

2016-01-01

In this study, a multimodal therapeutic system was shown to be much more lethal in cancer cell killing compared to a single means of nano therapy, be it photothermal or photodynamic. Hollow magnetic nanospheres (HMNSs) were designed and synthesized for the synergistic effects of both magneto-mechanical and photothermal cancer therapy. By these combined stimuli, the cancer cells were structurally and physically destroyed with the morphological characteristics distinctively different from those by other therapeutics. HMNSs were also coated with the silica shells and conjugated with carboxylated graphene quantum dots (GQDs) as a core-shell composite: HMNS/SiO2/GQDs. The composite was further loaded with an anticancer drug doxorubicin (DOX) and stabilized with liposomes. The multimodal system was able to kill cancer cells with four different therapeutic mechanisms in a synergetic and multilateral fashion, namely, the magnetic field-mediated mechanical stimulation, photothermal damage, photodynamic toxicity, and chemotherapy. The unique nanocomposites with combined mechanical, chemo, and physical effects will provide an alternative strategy for highly improved cancer therapy efficiency. PMID:26941842

A Multimodal System with Synergistic Effects of Magneto-Mechanical, Photothermal, Photodynamic and Chemo Therapies of Cancer in Graphene-Quantum Dot-Coated Hollow Magnetic Nanospheres.

PubMed

Wo, Fangjie; Xu, Rujiao; Shao, Yuxiang; Zhang, Zheyu; Chu, Maoquan; Shi, Donglu; Liu, Shupeng

2016-01-01

In this study, a multimodal therapeutic system was shown to be much more lethal in cancer cell killing compared to a single means of nano therapy, be it photothermal or photodynamic. Hollow magnetic nanospheres (HMNSs) were designed and synthesized for the synergistic effects of both magneto-mechanical and photothermal cancer therapy. By these combined stimuli, the cancer cells were structurally and physically destroyed with the morphological characteristics distinctively different from those by other therapeutics. HMNSs were also coated with the silica shells and conjugated with carboxylated graphene quantum dots (GQDs) as a core-shell composite: HMNS/SiO2/GQDs. The composite was further loaded with an anticancer drug doxorubicin (DOX) and stabilized with liposomes. The multimodal system was able to kill cancer cells with four different therapeutic mechanisms in a synergetic and multilateral fashion, namely, the magnetic field-mediated mechanical stimulation, photothermal damage, photodynamic toxicity, and chemotherapy. The unique nanocomposites with combined mechanical, chemo, and physical effects will provide an alternative strategy for highly improved cancer therapy efficiency.

Genomic damage induced by 1-MHz ultrasound in vitro.

PubMed

Udroiu, Ion; Marinaccio, Jessica; Bedini, Angelico; Giliberti, Claudia; Palomba, Raffaele; Sgura, Antonella

2018-01-01

Genotoxic effects of therapeutic ultrasound are poorly documented, when compared with the wide use of this physical agent. The aim of this work was to investigate the clastogenic and aneugenic potential of 1 MHz ultrasound, employing intensities (200 and 300 mW/cm 2 ) above the cavitational threshold, but in the range of those normally used in therapeutics. Both normal fibroblasts (AG01522) and tumoral cells (MCF-7) were sonicated. While no effects on viability were noted, significant increases of CREST-negative micronuclei (indicative of clastogenesis) and CREST-positive micronuclei (indicative of aneuploidy) were detected. Clastogenesis was confirmed by increases of γ-H2AX foci, while increases of spindle anomalies confirmed the induction of aneuploidy. Our results confirm previous works that showed ultrasound-induced DNA breakage. Moreover, our experiments show that the known effect of ultrasound-induced damage to microtubules is also able to damage the mitotic spindle and induce aneuploidy. On the overall, this work highlights the importance to further investigate the potential risks related to therapeutics US. Environ. Mol. Mutagen. 59:60-68, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effects of scapular taping on the activity onset of scapular muscles and the scapular kinematics in volleyball players with rotator cuff tendinopathy.

PubMed

Leong, Hio Teng; Ng, Gabriel Yin-Fat; Fu, Siu Ngor

2017-06-01

To examine the effect of scapular taping on the activity onset of scapular muscles and the scapular kinematics during arm elevation in volleyball players with rotator cuff (RC) tendinopathy. Randomized placebo-controlled repeated measures METHODS: Twenty-six male volleyball players with RC tendinopathy (mean age=23.6±3.3years) participated in the study. Electromyography (EMG) activity onset of upper trapezius (UT), middle trapezius (MT), lower trapezius (LT) and serratus anterior (SA) and the three-dimensional scapular kinematics quantified by using an acromial marker cluster method were compared with three scapular taping protocols, namely, no taping, therapeutic taping, and placebo taping. The MT, LT and SA activated significantly earlier in both therapeutic taping (all p<0.005) and placebo taping conditions than no taping conditions (all p<0.002). There was a small increase in the scapular upward rotation when therapeutic taping and no taping conditions were compared (p=0.007). Scapular taping may enhance the neuromotor control of the scapular muscles. Whether it provides adequate support for normal scapular kinematics during arm movement in athletes with RC tendinopathy await for further studies. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Long-Term Therapeutic Effects of Mesenchymal Stem Cells Compared to Dexamethasone on Recurrent Experimental Autoimmune Uveitis of Rats

PubMed Central

Zhang, Lingjun; Zheng, Hui; Shao, Hui; Nian, Hong; Zhang, Yan; Bai, Lingling; Su, Chang; Liu, Xun; Dong, Lijie; Li, Xiaorong; Zhang, Xiaomin

2014-01-01

Purpose. We tested the long-term effects of different regimens of mesenchymal stem cell (MSC) administration in a recurrent experimental autoimmune uveitis (rEAU) model in rats, and compared the efficacy of MSC to that of dexamethasone (DEX). Methods. One or two courses of MSC treatments were applied to R16-specific T cell–induced rEAU rats before or after disease onsets. The DEX injections were given for 7 or 50 days continuously after disease onsets. Clinical appearances were observed until the 50th day after transfer. On the 10th day, T cells from control and MSC groups were analyzed by flow cytometry. Supernatants from the proliferation assay and aqueous humor were collected for cytokine detection. Functions of T cells and APCs in spleens also were studied by lymphocyte proliferation assays. Results. One course of MSC therapy, administered after disease onset, led to a lasting therapeutic effect, with a decreased incidence, reduced mean clinical score, and reduced retinal impairment after 50 days of observation, while multiple courses of treatment did not improve the therapeutic benefit. Although DEX and MSCs equally reduced the severity of the first episode of rEAU, the effect of DEX was shorter lasting, and DEX therapy failed to control the disease even with long periods of treatment. The MSCs significantly decreased T helper 1 (Th1) and Th17 responses, suppressed the function of antigen-presenting cells, and upregulated T regulatory cells. Conclusions. These results suggested that MSCs might be new corticosteroid spring agents, while providing fewer side effects and longer lasting suppressive effects for recurrent uveitis. PMID:25125599

Perceptions of Socratic and non-Socratic presentation of information in cognitive behaviour therapy.

PubMed

Heiniger, Louise E; Clark, Gavin I; Egan, Sarah J

2018-03-01

Socratic Method is a style of inquiry used in cognitive behavioural therapy (CBT) that encourages clients to reflect on their problems and draw conclusions from newly-gained insights. However, assumptions about the superior efficacy of Socratic Method over non-Socratic (didactic) approaches remain largely untested. The aim of this study was to compare the perceived helpfulness of therapists' questions, autonomy supportiveness, likelihood of engaging in therapeutic tasks and preference for Socratic Method versus a didactic approach using a video analogue and ratings of lay observers. The mediating effects of therapeutic alliance and empathy were also examined. Participants (N = 144, mean age = 37, SD = 13) completed an online survey where they rated two videoed therapy analogues. Socratic Method had higher mean scores on perceived helpfulness of therapists' questions, autonomy supportiveness, and likelihood of engaging in therapeutic tasks and preference than didactic presentation. Perceived helpfulness and preference ratings were higher for Socratic Method after accounting for potential confounders. Perceived therapeutic alliance and empathy both mediated the effect of therapy condition on autonomy and engagement. The findings support the use of Socratic Method in CBT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Subconjunctival Delivery of p75NTR Antagonists Reduces the Inflammatory, Vascular, and Neurodegenerative Pathologies of Diabetic Retinopathy.

PubMed

Galan, Alba; Barcelona, Pablo F; Nedev, Hinyu; Sarunic, Marinko V; Jian, Yifan; Saragovi, H Uri

2017-06-01

The p75NTR is a novel therapeutic target validated in a streptozotocin mouse model of diabetic retinopathy. Intravitreal (IVT) injection of small molecule p75NTR antagonist THX-B was therapeutic and resolved the inflammatory, vascular, and neurodegenerative phases of the retinal pathology. To simplify clinical translation, we sought a superior drug delivery method that circumvents risks associated with IVT injections. We compared the pharmacokinetics of a single 40 μg subconjunctival (SCJ) depot to the reported effective 5 μg IVT injections of THX-B. We quantified therapeutic efficacy, with endpoints of inflammation, edema, and neuronal death. The subconjunctival depot affords retinal exposure equal to IVT injection, without resulting in detectable drug in circulation. At week 2 of diabetic retinopathy, the SCJ depot provided therapeutic efficacy similar to IVT injections, with reduced inflammation, reduced edema, reduced neuronal death, and a long-lasting protection of the retinal structure. Subconjunctival injections are a safe and effective route for retinal delivery of p75NTR antagonists. The subconjunctival route offers an advantageous, less-invasive, more compliant, and nonsystemic method to deliver p75NTR antagonists for the treatment of retinal diseases.

Distinguishing rational from irrational applications of pharmacogenetic synergies from the bench to clinical trials.

PubMed

Hucl, Tomas; Gallmeier, Eike; Kern, Scott E

2007-06-01

Single therapeutic agents very often fail in unselected patients. It is therefore commonplace to combine an agent specifically with a selected patient subgroup or with another agent. To support such efforts, it is useful to clarify the distinctions between the terms and the mathematical models used in analyzing combinations. To incorporate molecular disease classifications, the familiar concept of the therapeutic window is modified to define a pharmacogenetic window, which is an unambiguous numerical measure of the magnitude of interaction produced by a combination, and to define a test of pharmacogenetic synergy. In contrast, certain common comparative methods, such as vertical windows (comparing effects at a given dose) and animal models of mutational targets may be dominated by undesirable features. Although this discussion is oriented towards cancer therapy, an extension of these concepts to other comparative biologic assays is feasible and advisable.

Frondoside A potentiates the effects of conventional therapeutic agents in acute leukemia.

PubMed

Sajwani, F H; Collin, P; Adrian, T E

2017-12-01

Acute leukemia is the major cause of mortality in hematological malignancies. Despite improvement of survival with current chemotherapies, patients die from the disease or side-effects of treatment. Thus, new therapeutic agents are needed. Frondoside A is a triterpenoid glycoside originally isolated from the sea cucumber, Cucumaria frondosa that has potent antitumor effects in various cancers. The current study investigated the effects of frondoside A in acute leukemia cell lines alone and in combination with drugs used for this malignancy. This study is the first comparing the efficacy of frondoside A to available conventional drugs. The acute leukemia cell lines used were CCRF-CEM, HL-60 and THP-1. Cells were cultured and treated with different concentrations of vincristine sulphate, asparaginase and prednisolone alone and in combination with frondoside A. The inhibitory concentration 50 (IC 50 ) for each compound was determined for the cell lines. CCRF-CEM cells were very sensitive to frondoside A treatment while HL-60 and THP1 were less sensitive. Frondoside A markedly enhanced the anticancer effects of all of the conventional drugs. Synergistic effects were seen with most of the combinations. Frondoside A may be valuable in the treatment of acute leukemia, particularly when used in combination with current therapeutic drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prediction of polypharmacological profiles of drugs by the integration of chemical, side effect, and therapeutic space.

PubMed

Cheng, Feixiong; Li, Weihua; Wu, Zengrui; Wang, Xichuan; Zhang, Chen; Li, Jie; Liu, Guixia; Tang, Yun

2013-04-22

Prediction of polypharmacological profiles of drugs enables us to investigate drug side effects and further find their new indications, i.e. drug repositioning, which could reduce the costs while increase the productivity of drug discovery. Here we describe a new computational framework to predict polypharmacological profiles of drugs by the integration of chemical, side effect, and therapeutic space. On the basis of our previous developed drug side effects database, named MetaADEDB, a drug side effect similarity inference (DSESI) method was developed for drug-target interaction (DTI) prediction on a known DTI network connecting 621 approved drugs and 893 target proteins. The area under the receiver operating characteristic curve was 0.882 ± 0.011 averaged from 100 simulated tests of 10-fold cross-validation for the DSESI method, which is comparative with drug structural similarity inference and drug therapeutic similarity inference methods. Seven new predicted candidate target proteins for seven approved drugs were confirmed by published experiments, with the successful hit rate more than 15.9%. Moreover, network visualization of drug-target interactions and off-target side effect associations provide new mechanism-of-action of three approved antipsychotic drugs in a case study. The results indicated that the proposed methods could be helpful for prediction of polypharmacological profiles of drugs.

Effect of Polyether Ether Ketone on Therapeutic Radiation to the Spine: A Pilot Study.

PubMed

Jackson, J Benjamin; Crimaldi, Anthony J; Peindl, Richard; Norton, H James; Anderson, William E; Patt, Joshua C

2017-01-01

Cadaveric model. To compare the effect of PEEK versus conventional implants on scatter radiation to a simulated tumor bed in the spine SUMMARY OF BACKGROUND DATA.: Given the highly vasculature nature of the spine, it is the most common place for bony metastases. After surgical treatment of a spinal metastasis, adjuvant radiation therapy is typically administered. Radiation dosing is primarily limited by toxicity to the spinal cord. The scatter effect caused by metallic implants decreases the accuracy of dosing and can unintentionally increase the effective dose seen by the spinal cord. This represents a dose-limiting factor for therapeutic radiation postoperatively. A cadaveric thorax specimen was utilized as a metastatic tumor model with two separate three-level spine constructs (one upper thoracic and one lower thoracic). Each construct was examined independently. All four groups compared included identical posterior instrumentation. The anterior constructs consisted of either: an anterior polyether ether ketone (PEEK) cage, an anterior titanium cage, an anterior bone cement cage (polymethyl methacrylate), or a control group with posterior instrumentation alone. Each construct had six thermoluminescent detectors to measure the radiation dose. The mean dose was similar across all constructs and locations. There was more variability in the upper thoracic spine irrespective of the construct type. The PEEK construct had a more uniform dose distribution with a standard deviation of 9.76. The standard deviation of the others constructs was 14.26 for the control group, 19.31 for the titanium cage, and 21.57 for the cement (polymethyl methacrylate) construct. The PEEK inter-body cage resulted in a significantly more uniform distribution of therapeutic radiation in the spine when compared with the other constructs. This may allow for the application of higher effective dosing to the tumor bed for spinal metastases without increasing spinal cord toxicity with either fractionated or hypofractionated radiotherapy. N/A.

Effects of short-term exposure to environmentally relevant concentrations of different pharmaceutical mixtures on the immune response of the pond snail Lymnaea stagnalis.

PubMed

Gust, M; Fortier, M; Garric, J; Fournier, M; Gagné, F

2013-02-15

Pharmaceuticals are pollutants of potential concern in the aquatic environment where they are commonly introduced as complex mixtures via municipal effluents. Many reports underline the effects of pharmaceuticals on immune system of non target species. Four drug mixtures were tested, and regrouped pharmaceuticals by main therapeutic use: psychiatric (venlafaxine, carbamazepine, diazepam), antibiotic (ciprofloxacine, erythromycin, novobiocin, oxytetracycline, sulfamethoxazole, trimethoprim), hypolipemic (atorvastatin, gemfibrozil, benzafibrate) and antihypertensive (atenolol, furosemide, hydrochlorothiazide, lisinopril). Their effects were then compared with a treated municipal effluent known for its contamination, and its effects on the immune response of Lymnaea stagnalis. Adult L. stagnalis were exposed for 3 days to an environmentally relevant concentration of the four mixtures individually and as a global mixture. Effects on immunocompetence (hemocyte viability and count, ROS and thiol levels, phagocytosis) and gene expression were related to the immune response and oxidative stress: catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), Selenium-dependent glutathione peroxidase (SeGPx), two isoforms of the nitric oxide synthetase gene (NOS1 and NOS2), molluscan defensive molecule (MDM), Toll-like receptor 4 (TLR4), allograft inflammatory factor-1 (AIF) and heat-shock protein 70 (HSP70). Immunocompetence was differently affected by the therapeutic class mixtures compared to the global mixture, which increased hemocyte count, ROS levels and phagocytosis, and decreased intracellular thiol levels. TLR4 gene expression was the most strongly increased, especially by psychiatric mixture (19-fold), while AIF-1, GR and CAT genes were downregulated. A decision tree analysis revealed that the immunotoxic responses caused by the municipal effluent were comparable to those obtained with the global pharmaceutical mixture, and the latter shared similarity with the antibiotic mixture. This suggests that pharmaceutical mixtures in municipal effluents represent a risk for gastropods at the immunocompetence levels and the antibiotic group could represent a model therapeutic class for municipal effluent toxicity studies in L. stagnalis. Copyright © 2013 Elsevier B.V. All rights reserved.

Synergistic effects of FGF-2 and PDGF-BB on angiogenesis and muscle regeneration in rabbit hindlimb ischemia model.

PubMed

Li, Jie; Wei, Yuquan; Liu, Kang; Yuan, Chuang; Tang, Yajuan; Quan, Qingli; Chen, Ping; Wang, Wei; Hu, Huozhen; Yang, Li

2010-07-01

Combinatorial strategy has been used in therapeutic angiogenesis in animal models of peripheral arterial disease (PAD) and coronary artery disease for decades. Previous studies have shown that basic fibroblast growth factor (FGF-2) and platelet-derived growth factor BB (PDGF-BB) proteins together establish functional and stable vascular networks on mouse corneal and also in animal model of hindlimb ischemia. However, the short half life of protein by single injection is not sufficient to achieve effective dosage, repeated and prolonged injection causes systemic toxicity. Here we study the synergistic effects of FGF-2 and PDGF-BB by intramuscular injection of naked plasmid DNA on therapeutic angiogenesis in rabbit model of hindlimb ischemia. We found that transient delivery of FGF-2 and PDGF-BB naked DNA together resulted in greater increases in capillary growth, collateral formation and popliteal blood flow compared with control and single gene delivery. Our data provided novel evidence of beneficial effects of DNA-based FGF-2 and PDFG-BB on muscle repair after ischemic injury. These findings reveal an alternative therapeutic approach in the treatment of ischemic diseases and even in muscular disorders. Copyright 2010. Published by Elsevier Inc.

Association of PAX4 genetic variants with oral antidiabetic drugs efficacy in Chinese type 2 diabetes patients.

PubMed

Chen, M; Hu, C; Zhang, R; Jiang, F; Wang, J; Peng, D; Tang, S; Sun, X; Yan, J; Luo, Y; Bao, Y; Jia, W

2014-10-01

The aim of this study was to investigate the association of PAX4 variants with therapeutic effect of oral antidiabetic drugs in Chinese type 2 diabtes mellitus (T2DM) patients. A total of 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks, and the therapeutic effects were compared. In the rosiglitazone cohort, rs6467136 GA+AA carriers showed greater decrease in 2-h glucose levels (P=0.0063) and higher cumulative attainment rates of target 2-h glucose levels (Plog rank=0.0093) than GG homozygotes. In the subgroup with defective β-cell function, rs6467136 GA+AA carriers exhibited greater decrements of 2-h glucose level and improvement of homeostasis model assessment of insulin resistance (P=0.0143). Moreover, GA+AA carriers were more likely to attain the target fasting and 2-h glucose level (Plog rank=0.0091 and 0.007, respectively). However, these single-nucleotide polymorphisms showed no effect on repaglinide efficacy. In conclusion, PAX4 variant rs6467136 was associated with the therapeutic effect of rosiglitazone in Chinese T2DM patients.

DNA/RNA heteroduplex oligonucleotide for highly efficient gene silencing

PubMed Central

Nishina, Kazutaka; Piao, Wenying; Yoshida-Tanaka, Kie; Sujino, Yumiko; Nishina, Tomoko; Yamamoto, Tsuyoshi; Nitta, Keiko; Yoshioka, Kotaro; Kuwahara, Hiroya; Yasuhara, Hidenori; Baba, Takeshi; Ono, Fumiko; Miyata, Kanjiro; Miyake, Koichi; Seth, Punit P.; Low, Audrey; Yoshida, Masayuki; Bennett, C. Frank; Kataoka, Kazunori; Mizusawa, Hidehiro; Obika, Satoshi; Yokota, Takanori

2015-01-01

Antisense oligonucleotides (ASOs) are recognized therapeutic agents for the modulation of specific genes at the post-transcriptional level. Similar to any medical drugs, there are opportunities to improve their efficacy and safety. Here we develop a short DNA/RNA heteroduplex oligonucleotide (HDO) with a structure different from double-stranded RNA used for short interfering RNA and single-stranded DNA used for ASO. A DNA/locked nucleotide acid gapmer duplex with an α-tocopherol-conjugated complementary RNA (Toc-HDO) is significantly more potent at reducing the expression of the targeted mRNA in liver compared with the parent single-stranded gapmer ASO. Toc-HDO also improves the phenotype in disease models more effectively. In addition, the high potency of Toc-HDO results in a reduction of liver dysfunction observed in the parent ASO at a similar silencing effect. HDO technology offers a novel concept of therapeutic oligonucleotides, and the development of this molecular design opens a new therapeutic field. PMID:26258894

Formulation Development and Evaluation of the Therapeutic Efficacy of Brinzolamide Containing Nanoemulsions

PubMed Central

Mahboobian, Mohammad Mehdi; Seyfoddin, Ali; Rupenthal, Ilva D.; Aboofazeli, Reza; Foroutan, Seyed Mohsen

2017-01-01

Brinzolamide (BZ) is an intraocular pressure reducing agent with low bioavailability. The purpose of the present study was to overcome this issue by development of BZ containing nanoemulsions (NEs) as an ocular drug delivery system with desirable therapeutic efficacy. Brinzolamide NEs were prepared by the spontaneous emulsification method. Based on initial release studies, twelve formulations with the slowest release characteristics were subjected to further physicochemical investigations such as particle size, polydispersity index, pH, refractive index, osmolality and viscosity. The therapeutic efficacy of these formulations was assessed by measuring the intraocular pressure after instillation of the prepared NEs in normotensive albino rabbit eyes. Nanoemulsions with suitable physicochemical properties exhibited high formulation stability under different conditions. more over biological evaluations indicated that using lower drug concentrations in NE formulations (0.4%) had a similar or even better pharmacodynamic effect compared to the commercial suspension with a higher drug concentration (1%). Our findings suggest that NEs could be effectively used as carriers for enhancing the bioavailability of topically applied ophthalmic drugs. PMID:29201076

Efficacy and safety of a multifactor intervention to improve therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): protocol for the ICEPOC study.

PubMed

Barnestein-Fonseca, Pilar; Leiva-Fernández, José; Vidal-España, Francisca; García-Ruiz, Antonio; Prados-Torres, Daniel; Leiva-Fernández, Francisca

2011-02-14

Low therapeutic adherence to medication is very common. Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment. The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is extremely poor according to most studies. The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence. Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients. A randomized controlled clinical trial with 140 COPD diagnosed patients selected by a non-probabilistic method of sampling. Subjects will be randomly allocated into two groups, using the block randomization technique. Every patient in each group will be visited four times during the year of the study. Motivational aspects related to adherence (beliefs and behaviour): group and individual interviews; cognitive aspects: information about illness; skills: inhaled technique training. Reinforcement of the cognitive-emotional aspects and inhaled technique training will be carried out in all visits of the intervention group. Adherence to a prescribed treatment involves a behavioural change. Cognitive, emotional and motivational aspects influence this change and so we consider the best intervention procedure to improve adherence would be a cognitive and emotional strategy which could be applied in daily clinical practice. Our hypothesis is that the application of a multifactor intervention (COPD information, dose reminders and reinforcing audiovisual material, motivational aspects and inhalation technique training) to COPD patients taking inhaled treatment will give a 25% increase in the number of patients showing therapeutic adherence in this group compared to the control group.We will evaluate the effectiveness of this multifactor intervention on patient adherence to inhaled drugs considering that it will be right and feasible to the clinical practice context. Current Controlled Trials ISRCTN18841601.

Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

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

Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.

Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant tomore » the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.« less

Internet-delivered Treatment for Substance Abuse: A Multi-site Randomized Controlled Clinical Trial

PubMed Central

Campbell, Aimee N. C.; Nunes, Edward V.; Matthews, Abigail G.; Stitzer, Maxine; Miele, Gloria M.; Polsky, Daniel; Turrigiano, Eva; Walters, Scott; McClure, Erin A.; Kyle, Tiffany L.; Wahle, Aimee; Van Veldhuisen, Paul; Goldman, Bruce; Babcock, Dean; Stabile, Patricia Quinn; Winhusen, Theresa; Ghitza, Udi E.

2014-01-01

Objective Drug and alcohol abuse constitutes a major public health problem. Computer-delivered interventions have potential to improve access to quality care. The objective of this study was to evaluate the effectiveness of the Therapeutic Education System, an internet-delivered behavioral intervention that includes motivational incentives, as a clinician-extender in the treatment of substance use disorders. Method Adult men and women (N=507) entering 10 outpatient addiction treatment programs were randomly assigned to 12-weeks of treatment-as-usual (n=252) or treatment-as-usual + Therapeutic Education System, whereby the intervention substituted for 2 hours of standard care per week (n=255). Therapeutic Education System consists of 62 computer-interactive modules covering skills for achieving and maintaining abstinence, plus prize-based motivational incentives contingent on abstinence and treatment adherence. Treatment-as-usual consisted of individual and group counseling at the participating programs. Primary outcomes were (1) abstinence from drugs and heavy drinking measured by twice weekly urine drug screens and self-report, and (2) time to drop-out from treatment. Results Compared to treatment-as-usual, those receiving Therapeutic Education System reduced dropout from treatment (Hazard Ratio=0.72 [95% CI, 0.57-0.92], P=.010), and increased abstinence (Odds Ratio=1.62 [95% CI: 1.12-2.35], P=.010), an effect that was more pronounced among patients with a positive urine drug and/or breath alcohol screen at the point of study entry (n=228) (Odds Ratio=2.18 [95% CI: 1.30-3.68], P=.003). Conclusion Internet-delivered interventions, such as Therapeutic Education System, have the potential to expand access and improve addiction treatment outcomes; additional research is needed to assess effectiveness in non-specialty clinical systems and to differentiate the effect of Community Reinforcement Approach and Contingency Management. PMID:24700332

Different in vitro and in vivo profiles of substituted 3-aminopropylphosphinate and 3-aminopropyl(methyl)phosphinate GABA(B) receptor agonists as inhibitors of transient lower oesophageal sphincter relaxation.

PubMed

Lehmann, A; Antonsson, M; Aurell-Holmberg, A; Blackshaw, L A; Brändén, L; Elebring, T; Jensen, J; Kärrberg, L; Mattsson, J P; Nilsson, K; Oja, S S; Saransaari, P; von Unge, S

2012-03-01

Gastro-oesophageal reflux is predominantly caused by transient lower oesophageal sphincter relaxation (TLOSR) and GABA(B) receptor stimulation inhibits TLOSR. Lesogaberan produces fewer CNS side effects than baclofen, which has been attributed to its affinity for the GABA transporter (GAT), the action of which limits stimulation of central GABA(B) receptors. To understand the structure-activity relationship for analogues of lesogaberan (3-aminopropylphosphinic acids), and corresponding 3-aminopropyl(methyl)phosphinic acids, we have compared representatives of these classes in different in vitro and in vivo models. The compounds were characterized in terms of GABA(B) agonism in vitro. Binding to GATs and cellular uptake was done using rat brain membranes and slices respectively. TLOSR was measured in dogs, and CNS side effects were evaluated as hypothermia in mice and rats. 3-Aminopropylphosphinic acids inhibited TLOSR with a superior therapeutic index compared to 3-aminopropyl(methyl)phosphinic acids. This difference was most likely due to differential GAT-mediated uptake into brain cells of the former but not latter. In agreement, 3-aminopropyl(methyl)phosphinic acids were much more potent in producing hypothermia in rats even when administered i.c.v. An enhanced therapeutic window for 3-aminopropylphosphinic acids compared with 3-aminopropyl(methyl)phosphinic acids with respect to inhibition of TLOSR was observed and is probably mechanistically linked to neural cell uptake of the former but not latter group of compounds. These findings offer a platform for discovery of new GABA(B) receptor agonists for the treatment of reflux disease and other conditions where selective peripheral GABA(B) receptor agonism may afford therapeutic effects. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Different in vitro and in vivo profiles of substituted 3-aminopropylphosphinate and 3-aminopropyl(methyl)phosphinate GABAB receptor agonists as inhibitors of transient lower oesophageal sphincter relaxation

PubMed Central

Lehmann, A; Antonsson, M; Aurell-Holmberg, A; Blackshaw, LA; Brändén, L; Elebring, T; Jensen, J; Kärrberg, L; Mattsson, JP; Nilsson, K; Oja, SS; Saransaari, P; von Unge, S

2012-01-01

BACKGROUND AND PURPOSE Gastro-oesophageal reflux is predominantly caused by transient lower oesophageal sphincter relaxation (TLOSR) and GABAB receptor stimulation inhibits TLOSR. Lesogaberan produces fewer CNS side effects than baclofen, which has been attributed to its affinity for the GABA transporter (GAT), the action of which limits stimulation of central GABAB receptors. To understand the structure–activity relationship for analogues of lesogaberan (3-aminopropylphosphinic acids), and corresponding 3-aminopropyl(methyl)phosphinic acids, we have compared representatives of these classes in different in vitro and in vivo models. EXPERIMENTAL APPROACH The compounds were characterized in terms of GABAB agonism in vitro. Binding to GATs and cellular uptake was done using rat brain membranes and slices respectively. TLOSR was measured in dogs, and CNS side effects were evaluated as hypothermia in mice and rats. KEY RESULTS 3-Aminopropylphosphinic acids inhibited TLOSR with a superior therapeutic index compared to 3-aminopropyl(methyl)phosphinic acids. This difference was most likely due to differential GAT-mediated uptake into brain cells of the former but not latter. In agreement, 3-aminopropyl(methyl)phosphinic acids were much more potent in producing hypothermia in rats even when administered i.c.v. CONCLUSIONS AND IMPLICATIONS An enhanced therapeutic window for 3-aminopropylphosphinic acids compared with 3-aminopropyl(methyl)phosphinic acids with respect to inhibition of TLOSR was observed and is probably mechanistically linked to neural cell uptake of the former but not latter group of compounds. These findings offer a platform for discovery of new GABAB receptor agonists for the treatment of reflux disease and other conditions where selective peripheral GABAB receptor agonism may afford therapeutic effects. PMID:21950457

Therapeutic effects of aqueous extracts of Petroselinum sativum on ethylene glycol-induced kidney calculi in rats.

PubMed

Saeidi, Jafar; Bozorgi, Hadi; Zendehdel, Ahmad; Mehrzad, Jamshid

2012-01-01

To investigate the therapeutic effects of the aqueous extract of Petroselinum Sativum aerial parts and roots on kidney calculi. Thirty-six male Wistar rats were randomly assigned into 6 groups and treated for 30 days. Group A served as normal control and group B received 1% ethylene glycol in drinking water. Groups C, D, E, and F received 1% ethylene glycol from day 0 and were used as the treatment subjects. Rats in groups C and D received 200 and 600 mg/kg body weight of aerial parts aqueous extract, respectively, and those in groups E and F received 200 and 600 mg/kg body weight of root aqueous extract in drinking water, respectively, from the 14th day of the experiment. On the 14th and 30th days of the experiment, serum level of magnesium (1.71 ± 0.12 and 3.81 ± 0.25, respectively) decreased significantly while serum level of calcium (10.45 ± 0.26 and 11.33 ± 0.18, respectively) increased significantly in group B compared with the control group (14th day: magnesium = 2.87 ± 0.17 and calcium = 8.80 ± 0.00 and 30th day: magnesium = 6.01 ± 0.00 and calcium = 8.30 ± 0.22; P < .001). In the treatment groups of C, D, E, and F, the number of deposits decreased significantly compared with group B on the 30th day (P < .001). The weight of the kidneys increased significantly in group B (2.01 ± 0.17) compared with the control group (1.52 ± 0.07) and decreased significantly in treatment groups (P < .05). Petroselinum Sativum has a therapeutic effect on calcium oxalate stones in rats with nephrolithiasis and reduces the number of calcium oxalate deposits.

Clinical research and the development of medical therapeutics.

PubMed

Antman, Elliott M

2014-01-01

Clinical research plays a central role in the development of medical therapeutics, but the current system is estimated to take 10-15 years from initial discovery to regulatory approval, at a cost of approximately US$1 billion. Contrast the paths by which 2 anticoagulant options for atrial fibrillation were discovered and ultimately established as treatment options in clinical medicine. Warfarin was discovered by serendipity and compared with placebo in relatively small trials; this was associated with a low cost of development. The new oral anticoagulants were synthesized to provide highly specific, targeted inhibition of critical steps in the coagulation system. They were compared with warfarin for prevention of stroke and systemic embolic events in large, phase 3 trials; this resulted in very expensive development programs. Neither of these paths is desirable for future development of therapeutics. We need to focus on innovative approaches at the preclinical level (systems approach, greater use of inducible pluripotent stem cells, use of novel bioengineering platforms) and clinical trial level (adaptive design, greater use of new and emerging technology). Focusing on disruptive innovations for development of medical therapeutics has the potential to bring us closer to the goal of precision medicine where safer, more effective treatments are discovered in a more efficient system.

Detection of Post-Therapeutic Effects in Breast Carcinoma Using Hard X-Ray Index of Refraction Computed Tomography - A Feasibility Study.

PubMed

Grandl, Susanne; Sztrókay-Gaul, Anikó; Mittone, Alberto; Gasilov, Sergey; Brun, Emmanuel; Bravin, Alberto; Mayr, Doris; Auweter, Sigrid D; Hellerhoff, Karin; Reiser, Maximilian; Coan, Paola

2016-01-01

Neoadjuvant chemotherapy is the state-of-the-art treatment in advanced breast cancer. A correct visualization of the post-therapeutic tumor size is of high prognostic relevance. X-ray phase-contrast computed tomography (PC-CT) has been shown to provide improved soft-tissue contrast at a resolution formerly restricted to histopathology, at low doses. This study aimed at assessing ex-vivo the potential use of PC-CT for visualizing the effects of neoadjuvant chemotherapy on breast carcinoma. The analysis was performed on two ex-vivo formalin-fixed mastectomy samples containing an invasive carcinoma removed from two patients treated with neoadjuvant chemotherapy. Images were matched with corresponding histological slices. The visibility of typical post-therapeutic tissue changes was assessed and compared to results obtained with conventional clinical imaging modalities. PC-CT depicted the different tissue types with an excellent correlation to histopathology. Post-therapeutic tissue changes were correctly visualized and the residual tumor mass could be detected. PC-CT outperformed clinical imaging modalities in the detection of chemotherapy-induced tissue alterations including post-therapeutic tumor size. PC-CT might become a unique diagnostic tool in the prediction of tumor response to neoadjuvant chemotherapy. PC-CT might be used to assist during histopathological diagnosis, offering a high-resolution and high-contrast virtual histological tool for the accurate delineation of tumor boundaries.

Continuous positive airway pressure and liver enzymes in obstructive sleep apnoea: data from a randomized controlled trial.

PubMed

Kohler, Malcolm; Pepperell, Justin C T; Davies, Robert J O; Stradling, John R

2009-01-01

Obstructive sleep apnoea syndrome (OSAS) has been suggested to be an independent risk factor for non-alcoholic fatty liver disease (NAFLD), possibly via intermittent hypoxia that influences blood pressure, lipid levels and insulin resistance, factors themselves known to cause NAFLD. In observational studies, OSAS has been associated with elevated levels of liver enzymes. Continuous positive airway pressure (CPAP) is the treatment for OSAS, but the effects of CPAP on liver enzymes have not been studied in a randomized controlled trial. To determine if 4 weeks of CPAP influence alanine-aminotransferase (ALT) and aspartate-aminotranferase (AST) levels. 94 patients with moderate-to-severe OSAS were randomized to therapeutic or sub-therapeutic CPAP treatment. Plasma ALT and AST were measured before and after 4 weeks of CPAP. Results are means +/- SD. ALT levels decreased from 39.1 +/- 26.3 to 30.3 +/- 16.4 IU/l in patients treated with therapeutic CPAP, but also decreased from 36.9 +/- 20.7 to 31.5 +/- 16.5 IU/l in patients treated with sub-therapeutic CPAP (difference between mean changes -3.4, 95% CI -7.8 to 1.0 IU/l, p = 0.13 between groups). AST levels did not change significantly with therapeutic CPAP (from 29.1 +/- 14.7 to 30.2 +/- 13.6 IU/l), nor with sub-therapeutic CPAP (from 28.2 +/- 16.2 to 29.5 +/- 12.6 IU/l; difference between mean changes -0.2, 95% CI -3.0 to 2.6 IU/l, p = 0.87 between groups). Four weeks of active CPAP has no beneficial effect on aminotransferase levels when compared to sub-therapeutic CPAP in patients with OSAS. Therefore, CPAP does not seem to improve biochemical markers of potential NAFLD in OSAS patients.

Immunologic properties and therapeutic efficacy of a multivalent epitope-based vaccine against four Helicobacter pylori adhesins (urease, Lpp20, HpaA, and CagL) in Mongolian gerbils.

PubMed

Guo, Le; Yin, Runting; Xu, Guangxian; Gong, Xiaojuan; Chang, Zisong; Hong, Dantong; Liu, Hongpeng; Ding, Shuqin; Han, Xuebo; Li, Yuan; Tang, Feng; Liu, Kunmei

2017-12-01

Therapeutic vaccination is a desirable alternative for controlling Helicobacter pylori (H. pylori) infection. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and adhesins, which are on the surface of H. pylori, play a pivotal role in binding to human gastric mucosa. In the present study, we constructed a multivalent epitope-based vaccine named CFAdE with seven carefully selected antigenic fragments from four H. pylori adhesins (urease, Lpp20, HpaA and CagL). The specificity, immunogenicity and ability to produce neutralizing antibodies of CFAdE were evaluated in BALB/c mice. After that, its therapeutic efficacy and protective immune mechanisms were explored in H. pylori-infected Mongolian gerbils. The results indicated that CFAdE could induce comparatively high levels of specific antibodies against urease, Lpp20, HpaA and CagL. Additionally, oral therapeutic immunization with CFAdE plus polysaccharide adjuvant (PA) significantly decreased H. pylori colonization compared with oral immunization with urease plus PA, and the protection was correlated with IgG and sIgA antibody and antigen-specific CD4 + T cells. This study indicated that the multivalent epitope-based vaccine, which targeted multiple adhesins in adherence of H. pylori to the gastric mucosa, is more effective than the univalent vaccine targeting urease only. This multivalent epitope-based vaccine may be a promising therapeutic candidate vaccine against H. pylori infection. © 2017 John Wiley & Sons Ltd.

A novel high mobility group box 1 neutralizing chimeric antibody attenuates drug‐induced liver injury and postinjury inflammation in mice

PubMed Central

Lea, Jonathan D.; Sowinska, Agnieszka; Ottosson, Lars; Fürst, Camilla Melin; Steen, Johanna; Aulin, Cecilia; Clarke, Joanna I.; Kipar, Anja; Klevenvall, Lena; Yang, Huan; Palmblad, Karin; Park, B. Kevin; Tracey, Kevin J.; Blom, Anna M.; Andersson, Ulf

2016-01-01

Acetaminophen (APAP) overdoses are of major clinical concern. Growing evidence underlines a pathogenic contribution of sterile postinjury inflammation in APAP‐induced acute liver injury (APAP‐ALI) and justifies development of anti‐inflammatory therapies with therapeutic efficacy beyond the therapeutic window of the only current treatment option, N‐acetylcysteine (NAC). The inflammatory mediator, high mobility group box 1 (HMGB1), is a key regulator of a range of liver injury conditions and is elevated in clinical and preclinical APAP‐ALI. The anti‐HMGB1 antibody (m2G7) is therapeutically beneficial in multiple inflammatory conditions, and anti‐HMGB1 polyclonal antibody treatment improves survival in a model of APAP‐ALI. Herein, we developed and investigated the therapeutic efficacy of a partly humanized anti‐HMGB1 monoclonal antibody (mAb; h2G7) and identified its mechanism of action in preclinical APAP‐ALI. The mouse anti‐HMGB1 mAb (m2G7) was partly humanized (h2G7) by merging variable domains of m2G7 with human antibody‐Fc backbones. Effector function‐deficient variants of h2G7 were assessed in comparison with h2G7 in vitro and in preclinical APAP‐ALI. h2G7 retained identical antigen specificity and comparable affinity as m2G7. 2G7 treatments significantly attenuated APAP‐induced serum elevations of alanine aminotransferase and microRNA‐122 and completely abrogated markers of APAP‐induced inflammation (tumor necrosis factor, monocyte chemoattractant protein 1, and chemokine [C‐X‐C motif] ligand 1) with prolonged therapeutic efficacy as compared to NAC. Removal of complement and/or Fc receptor binding did not affect h2G7 efficacy. Conclusion: This is the first report describing the generation of a partly humanized HMGB1‐neutralizing antibody with validated therapeutic efficacy and with a prolonged therapeutic window, as compared to NAC, in APAP‐ALI. The therapeutic effect was mediated by HMGB1 neutralization and attenuation of postinjury inflammation. These results represent important progress toward clinical implementation of HMGB1‐specific therapy as a means to treat APAP‐ALI and other inflammatory conditions. (Hepatology 2016;64:1699‐1710). PMID:27474782

Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors

PubMed Central

De Witt, Michelle; Gamble, Alexander; Hanson, Derek; Markowitz, Daniel; Powell, Caitlin; Al Dimassi, Saleh; Atlas, Mark; Boockvar, John; Ruggieri, Rosamaria; Symons, Marc

2017-01-01

The microtubule inhibitor vincristine is currently used to treat a variety of brain tumors, including low-grade glioma and anaplastic oligodendroglioma. Vincristine, however, does not penetrate well into brain tumor tissue, and moreover, it displays dose-limiting toxicities, including peripheral neuropathy. Mebendazole, a Food and Drug Administration–approved anthelmintic drug with a favorable safety profile, has recently been shown to display strong therapeutic efficacy in animal models of both glioma and medulloblastoma. Importantly, appropriate formulations of mebendazole yield therapeutically effective concentrations in the brain. Mebendazole has been shown to inhibit microtubule formation, but it is not known whether its potency against tumor cells is mediated by this inhibitory effect. To investigate this, we examined the effects of mebendazole on GL261 glioblastoma cell viability, microtubule polymerization and metaphase arrest, and found that the effective concentrations to inhibit these functions are very similar. In addition, using mebendazole as a seed for the National Cancer Institute (NCI) COMPARE program revealed that the top-scoring drugs were highly enriched in microtubule-targeting drugs. Taken together, these results indicate that the cell toxicity of mebendazole is indeed caused by inhibiting microtubule formation. We also compared the therapeutic efficacy of mebendazole and vincristine against GL261 orthotopic tumors. We found that mebendazole showed a significant increase in animal survival time, whereas vincristine, even at a dose close to its maximum tolerated dose, failed to show any efficacy. In conclusion, our results strongly support the clinical use of mebendazole as a replacement for vincristine for the treatment of brain tumors. PMID:28386621

Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability.

PubMed

Li, Bailong; Li, Cheng; Zhu, Mo; Zhang, Youjun; Du, Jicong; Xu, Yang; Liu, Bin; Gao, Fu; Liu, Hu; Cai, Jianming; Yang, Yanyong

2017-01-01

Radiation therapy is an important treatment for thoracic cancer; however, side effects accompanied with radiotherapy lead to limited tumor control and a decline in patient quality of life. Among these side effects, radiation-induced lung injury (RILI) is the most serious and common. Hence, an effective remedy for RILI is needed. Mesenchymal stromal cells (MSCs) are multipotent adult stem cells that have been demonstrated to be an effective treatment in some disease caused by tissue damage. However, unlike other injuries, RILI received limited therapeutic effects from implanted MSCs due to local hypoxia and extensive reactive oxygen species (ROS) in irradiated lungs. Since the poor survival of MSCs is primarily due to hypoxia and ROS generation, we hypothesize that persistent and adaptive hypoxia treatment induces enhanced resistance to hypoxic stress in implanted MSC. The aim of this study is to investigate whether persistent and adaptive hypoxia treatment of bmMSCs prior to their transplantation in injured mice enhanced survival and improved curative effects in RILI. Primary bmMSCs were obtained from the marrow of six-week-old male C57BL6/J mice and were cultured either under normoxic conditions (21% O2) or hypoxic conditions (2.5% O2). Mice were injected with normoxia/hypoxia MSCs after thoracic irradiation (20 Gy). The therapeutic effects of MSCs on RILI were assessed by pathological examinations that included H&E staining, Masson staining and α-SMA staining; meanwhile, inflammatory factors were measured using an ELISA. The morphology of MSCs in vitro was recorded using a microscope and identified by flow cytometry, cell viability was measured using the CCK-8 assay, the potential for proliferation was detected by the EdU assay, and ROS levels were measured using a ROS fluorogenic probe. In addition, HIF-1α and several survival pathway proteins (Akt, p-Akt, Caspase-3) were also detected by western blotting. Implanted MSCs alleviated both early radiation-induced pneumonia and late pulmonary fibrosis. However, hypoxia MSCs displayed a more pronounced therapeutic effect compared to normoxia MSCs. Compared to normoxia MSCs, the hypoxia MSCs demonstrated greater cell viability, an enhanced proliferation potential, decreased ROS levels and increased resistance to hypoxia and ROS stress. In addition, hypoxia MSCs achieved higher activation levels of HIF-1α and Akt, and HIF-1α played a critical role in the development of resistance. Hypoxia enhances the therapeutic effect of mesenchymal stromal cells on radiation-induced lung injury by promoting MSC proliferation and improving their antioxidant ability, mediated by HIF-1α. © 2017 The Author(s). Published by S. Karger AG, Basel.

Developmental Therapeutics Consortium report on study design effects on trial outcomes in chronic myeloid leukaemia.

PubMed

Giles, Francis; Mahon, François-Xavier; Gjertsen, Bjorn; Swords, Ronan; Labar, Boris; Turkina, Anna; Rosti, Gianantonio

2012-09-01

Tyrosine kinase inhibitors (TKIs) have dramatically changed the treatment of chronic myeloid leukaemia (CML). Results from ongoing phase 3 trials with nilotinib [Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd)] and dasatinib [Dasatinib Versus Imatinib Study in Treatment-Naive CML-CP Patients (DASISION)] in newly diagnosed patients with CML in chronic phase have demonstrated that these TKIs resulted in significant improvements in responses vs. imatinib. The Developmental Therapeutics Consortium (DTC) systematically reviewed the published literature to provide a comparative analysis of the ENESTnd and DASISION trial designs and data reported on each study. The recent approval of nilotinib and dasatinib based on these two pivotal studies offers physicians the option to optimise frontline treatment based on a patient's comorbidities, risk factors and tolerability profiles. Although nilotinib and dasatinib provide effective therapeutic options for the frontline treatment of CML, the lack of an evidenced-based, side-by-side comparison makes it difficult to directly compare these agents. Despite potential bias from differences in patient populations and study design, indirect cross-trial comparisons to determine the relative effectiveness of these agents will be performed by physicians. This DTC report provides a comprehensive summary of the study designs, protocols and results of the ENESTnd and DASISION trials, which will assist physicians in making informed decisions on the best treatment approach for their patients. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

Changes in the Vaginal Microenvironment with Metronidazole Treatment for Bacterial Vaginosis in Early Pregnancy

PubMed Central

Balkus, Jennifer; Agnew, Kathy; Lawler, Richard; Hitti, Jane

2009-01-01

Abstract Objective Bacterial vaginosis (BV) is associated with preterm delivery, but there is little evidence that treatment improves pregnancy outcomes. We examined whether oral or vaginal metronidazole treatment for BV in early pregnancy was more effective in restoring the normal vaginal environment. Methods This was a randomized controlled trial comparing oral and intravaginal metronidazole for treatment of BV in early pregnancy (<20 weeks). Vaginal samples collected at baseline and 4 weeks after treatment were evaluated using gram stain, culture, colorimetric detection of sialidase, and immunoassay for measurement of proinflammatory cytokines interleukins-1β, -6, -8 (IL-1β, IL-6, IL-8) and secretory leukocyte protease inhibitor (SLPI). We compared the effect of treatment between groups (using chi-square and t test) and within individuals (McNemar's test). Results Of 126 subjects, 108 (86%) completed follow-up (55 oral, 53 intravaginal). Of the study population, 34% achieved therapeutic cure, and this was not different between treatment groups. BV-associated bacteria were significantly reduced in both groups, but few subjects regained colonization with protective lactobacilli. Among women who achieved therapeutic cure, the level of IL-1β dropped significantly (p < 0.001) and SLPI increased (p = 0.003). More women in the vaginal treatment group had undetectable sialidase after treatment (p = 0.013). Conclusions Treatment with oral or intravaginal metronidazole in early pregnancy reduced colonization with BV-associated bacteria but was not effective in achieving therapeutic cure or in restoring healthy vaginal lactobacilli. PMID:19951217

Therapeutic, prophylactic, untoward, and contraceptive effects of combined oral contraceptives: catholic teaching, natural law, and the principle of double effect when deciding to prescribe and use.

PubMed

Casey, Murray Joseph; Salzman, Todd A

2014-01-01

Combined oral contraceptives (COC) have been demonstrated to have significant benefits for the treatment and prevention of disease. These medications also are associated with untoward health effects, and they may be directly contraceptive. Prescribers and users must compare and weigh the intended beneficial health effects against foreseeable but unintended possible adverse effects in their decisions to prescribe and use. Additionally, those who intend to abide by Catholic teachings must consider prohibitions against contraception. Ethical judgments concerning both health benefits and contraception are approached in this essay through an overview of the therapeutic, prophylactic, untoward, and contraceptive effects of COC and discussion of magisterial and traditional Catholic teachings from natural law. Discerning through the principle of double effect, proportionate reason, and evidence gathered from the sciences, medical and moral conclusions are drawn that we believe to be fully compliant with good medicine and Catholic teaching.

Comparing the Cost Effectiveness of Non-vitamin K Antagonist Oral Anticoagulants with Well-Managed Warfarin for Stroke Prevention in Atrial Fibrillation Patients at High Risk of Bleeding.

PubMed

Hospodar, Alexa R; Smith, Kenneth J; Zhang, Yuting; Hernandez, Inmaculada

2018-05-09

Several studies have compared the cost effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin using results from clinical trials evaluating NOACs. However, the time in therapeutic range (TTR) of warfarin groups ranged across clinical trials, and all were below the therapeutic goal of 70%. We compared the cost effectiveness of edoxaban 60 mg, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, rivaroxaban 20 mg, and well-managed warfarin with a TTR of 70% in preventing stroke among patients with atrial fibrillation at high risk of bleeding. For the six treatments, we used a Markov state-transition model to quantify lifetime costs in $US and effectiveness in quality-adjusted life-years (QALYs). We simulated relative risk ratios of clinical events with each NOAC versus warfarin with a TTR of 70% using published regression models that predict how the incidence of thrombotic or hemorrhagic events changes for each unit change in TTR. We re-ran our analysis for two other estimates of TTR: 65 and 75%. Treatment with edoxaban 60 mg cost $US127,520/QALY gained compared with warfarin with a TTR of 70% and cost $US41,860/QALY gained compared with warfarin with a TTR of 65%. However, warfarin with a TTR of 75% was more effective and less expensive than all NOACs. For three levels of TTR, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, and rivaroxaban 20 mg were dominated strategies. The comparative cost effectiveness of edoxaban and warfarin is highly sensitive to TTR. At the $US100,000/QALY willingness-to-pay threshold, our results suggest that warfarin is the most cost-effective treatment for patients who can achieve a TTR of 70%.

[Acupuncture combined with magnetic therapy for treatment of temple-jaw joint dysfunction].

PubMed

Wang, Xiao-Hui; Zhang, Wen

2009-04-01

To compare clinical therapeutic effects of acupuncture combined with magnetic therapy and simple magnetic therapy on temple-jaw joint dysfunction. Eighty-two cases were randomly divided into an observation group (n = 52) and a control group (n = 30). The observation group was treated with acupuncture at Xiaguan (ST 7), Jiache (ST 6), Hegu (LI 4), etc. and AL-2 low frequency electromagnetic comprehensive treatment instrument; the control group was treated with AL-2 low frequency electromagnetic comprehensive treatment instrument. The cured and markedly effective rate of 90.4% in the observation group was significantly better than 66.7% in the control group (P < 0.01), and the total effective rate of 98.1% in the observation group was significantly better than 86.7% in the control group (P < 0.05). The therapeutic effect of acupuncture combined with magnetic therapy is significantly better than that of the simple magnetic therapy on temple-jaw joint dysfunction.

The Therapeutic Effect of Zuogui Wan in Gestational Diabetes Mellitus Rats

PubMed Central

Feng, Qianjin; Niu, Xin; Liu, Xinshe; Xu, Kaixia; Yang, Xiangzhu; Wang, Huifeng

2014-01-01

In this experiment, we established an animal model of gestational diabetes mellitus rats using streptozotocin. Using the rat model of GDM, the pregnant rats in 1-19d were divided into three groups: (1) Zuogui Wan gestational diabetes mellitus group (group I, n = 12), (2) gestational diabetes mellitus rats as the control group (group II, n = 11), and (3) rats of normal pregnancy group (group III, n = 11). Compared with gestational diabetes mellitus rats as the control group, Zuogui Wan can change the indexes of fasting blood glucose, body weight, total cholesterol, insulin, and metabolism cage index significantly in Zuogui Wan gestational diabetes mellitus group. We can conclude that Zuogui Wan has the therapeutic effect on gestational diabetes mellitus. PMID:25136475

Comparing individual preferences for four meditation techniques: Zen, Vipassana (Mindfulness), Qigong, and Mantra.

PubMed

Burke, Adam

2012-01-01

A significant number of studies have been published examining the mind-body effects of meditation and its clinical efficacy. There are very few studies, however, which directly compare different meditation methods with each other to explore potentially distinct mechanisms and effects, and no studies comparing individual preferences for different methods. As preference is seen as an important factor in consumer healthcare decision making, greater understanding of this aspect is needed as meditation becomes a more widely used therapeutic modality. For this reason a pilot study was conducted to compare four meditation techniques for personal preference. A within-subjects comparison design was employed. A convenience sample of 247 undergraduate university students participated in the study. Participants learned two open observing meditation techniques-Vipassana (Mindfulness) and Zen, and two focused attention techniques-Mantra and Qigong Visualization, practicing one method per week. At the end of a six-week training period participants ranked the four meditation methods in order of personal preference. Ranking of subjective preference of meditations practiced. A within subjects comparison revealed that significantly more participants chose Vipassana or Mantra meditation as their preferred techniques compared with Qigong Visualization and Zen. This study provides information on differences in preference for type of meditation. As the benefits of meditation accrue over time, selecting a method that motivates sustained practice is a critical objective if therapeutic effects are to be achieved. Copyright © 2012 Elsevier Inc. All rights reserved.

Intravenous application of HI-6 salts (dichloride and dimethansulphonate) in pigs: comparison with pharmacokinetics profile after intramuscular administration.

PubMed

Zdarova Karasova, Jana; Zemek, Filip; Kunes, Martin; Kvetina, Jaroslav; Chladek, Jaroslav; Jun, Daniel; Bures, Jan; Tachecí, Ilja; Kuca, Kamil

2013-01-01

Oxime HI-6 is an acetylcholinesterase reactivator therapeutically efficient against nerve agents. Because of their physico-chemical properties, oximes are typically applied intramuscularly (i.m.). This route of administration has also some disadvantages, and alternative strategies ought to be examined. We evaluated the pharmacokinetic profiles of two HI-6 salts after their intravenous (i.v.) administration, and compare the results with the known pharmacokinetics after i.m. administration. Pigs were administered with HI-6 salts (i.v), either HI-6 dichloride (10.71 mg/kg) or molar equivalent HI-6 dimethansulphonate (13.59 mg/kg). Doses of the HI-6 salts corresponded with a standard HI-6 dichloride dose in one autoinjector (500 mg) and were recalculated for one kilogram of body weight. The main pharmacokinetic parameters are comparable after i.v. and i.m. HI-6 administration. The compared pharmacokinetic parameters were half-life, terminal rate constant, mean residence time of the molecule in the body, clearance, and the apparent volume in the terminal phase. The bioavailability after i.m. administration was comparable with that of i.v.; these results suggest that the oxime is well released from the muscle depot. Significant differences were found in parameters Cmax and Tmax which are important in cases of emergency when rapidity and bioavailability are paramount for the success of treatment. I.v. administration should solve the problem of rapid clearance. Infusion or bolus administration may be considered as a logical subsequent step in oxime treatment strategy. The main advantage is in maintenance of an effective therapeutic plasma concentration, a more easily achievable effective therapeutic concentration, and fewer local adverse reactions.

Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer.

PubMed

Xiao, Jie; Xu, Xiaobo; Li, Xiao; Li, Yanli; Liu, Guobing; Tan, Hui; Shen, Hua; Shi, Hongcheng; Cheng, Dengfeng

2016-09-30

The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188 ReO₄ - or 188 Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188 Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188 Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed compared with other groups. Thus, 188 Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.

Comparing the effects of repetitive transcranial magnetic stimulation and electroconvulsive therapy in the treatment of depression: a systematic review and meta-analysis.

PubMed

Micallef-Trigona, Beppe

2014-01-01

Electroconvulsive therapy (ECT) is the longest standing psychiatric treatment available and has unequivocal benefit in severe depression. However this treatment comes with a number of side effects such as memory impairment. On the other hand, Repetitive Transcranial Magnetic Stimulation (rTMS) is a relatively new form of treatment which has been shown to be efficacious in patients suffering from a number of psychopathologies, including severe depression, with few reported side effects. Due to its potential therapeutic efficacy and lack of side effects, rTMS has gained traction in the treatment of depression, with a number of authors keen to see it take over from ECT. However, it is not clear whether rTMS represents a therapeutic alternative to ECT. This meta-analysis will therefore compare the "gold standard" treatment for severe depression, with the relatively new but promising rTMS. A literature search will be performed with the intention to include all randomised clinical trials. The null hypothesis is that there is no difference in the antidepressant efficacy between the two types of treatment modalities. Statistical analysis of Hamilton Depression Rating Scale (HDRS) scores will be performed.

Management of Myofascial Pain of Upper Trapezius: A Three Group Comparison Study

PubMed Central

Kannan, Priya

2012-01-01

It is important to identify the most effective therapeutic modality in the management of myofascial trigger points (MTPt). Thus we aimed to study the effect of therapeutic ultrasound, laser and ischemic compression in reducing pain and improving cervical range of motion among patients with MTPt. Experimental study comparing three groups was designed as a 5 days trial, a co-relational design was considered. Outcome measures: VAS for pain, provocative pain test using “soft tissue tenderness grading scheme” and active cervical lateral flexion using inch tape. Methods- Patients were divided into 3 groups, Gr 1 underwent treatment using therapeutic ultrasound, Gr 2 with therapeutic laserand Gr 3 with ischemic compression. Assessments were done on day 1 and day 5 of treatment respectively. Results: ANOVA revealed improvement among all 3 groups as statistically significant difference (p<0.05) between the start and end of trial. Analysis using Chi square test shows a statistically significant difference in the improvement between laser and the other 2 groups. Mean difference in the change of scores between the assessments showed laser therapy to have a tendency towards progressive improvement over the treatment period and a better improvement than the other 2 groups. Weconclude that laser can be used as an effective treatment regimen in the management of myofascial trigger points thereby reducing disability caused due to musculoskeletal pathology. PMID:22980377

Data-driven analysis of biomedical literature suggests broad-spectrum benefits of culinary herbs and spices.

PubMed

Rakhi, N K; Tuwani, Rudraksh; Mukherjee, Jagriti; Bagler, Ganesh

2018-01-01

Spices and herbs are key dietary ingredients used across cultures worldwide. Beyond their use as flavoring and coloring agents, the popularity of these aromatic plant products in culinary preparations has been attributed to their antimicrobial properties. Last few decades have witnessed an exponential growth of biomedical literature investigating the impact of spices and herbs on health, presenting an opportunity to mine for patterns from empirical evidence. Systematic investigation of empirical evidence to enumerate the health consequences of culinary herbs and spices can provide valuable insights into their therapeutic utility. We implemented a text mining protocol to assess the health impact of spices by assimilating, both, their positive and negative effects. We conclude that spices show broad-spectrum benevolence across a range of disease categories in contrast to negative effects that are comparatively narrow-spectrum. We also implement a strategy for disease-specific culinary recommendations of spices based on their therapeutic tradeoff against adverse effects. Further by integrating spice-phytochemical-disease associations, we identify bioactive spice phytochemicals potentially involved in their therapeutic effects. Our study provides a systems perspective on health effects of culinary spices and herbs with applications for dietary recommendations as well as identification of phytochemicals potentially involved in underlying molecular mechanisms.

Data-driven analysis of biomedical literature suggests broad-spectrum benefits of culinary herbs and spices

PubMed Central

Mukherjee, Jagriti

2018-01-01

Spices and herbs are key dietary ingredients used across cultures worldwide. Beyond their use as flavoring and coloring agents, the popularity of these aromatic plant products in culinary preparations has been attributed to their antimicrobial properties. Last few decades have witnessed an exponential growth of biomedical literature investigating the impact of spices and herbs on health, presenting an opportunity to mine for patterns from empirical evidence. Systematic investigation of empirical evidence to enumerate the health consequences of culinary herbs and spices can provide valuable insights into their therapeutic utility. We implemented a text mining protocol to assess the health impact of spices by assimilating, both, their positive and negative effects. We conclude that spices show broad-spectrum benevolence across a range of disease categories in contrast to negative effects that are comparatively narrow-spectrum. We also implement a strategy for disease-specific culinary recommendations of spices based on their therapeutic tradeoff against adverse effects. Further by integrating spice-phytochemical-disease associations, we identify bioactive spice phytochemicals potentially involved in their therapeutic effects. Our study provides a systems perspective on health effects of culinary spices and herbs with applications for dietary recommendations as well as identification of phytochemicals potentially involved in underlying molecular mechanisms. PMID:29813110

Effect of high intensity focused ultrasound (HIFU) in conjunction with a nanomedicines-microbubble complex for enhanced drug delivery.

PubMed

Han, Hyounkoo; Lee, Hohyeon; Kim, Kwangmeyung; Kim, Hyuncheol

2017-11-28

Although nanomedicines have been intensively investigated for cancer therapy in the past, poor accumulation of nanomedicines in tumor sites remains a serious problem. Therefore, a novel drug delivery system is required to enhance accumulation and penetration of nanomedicines at the tumor site. Recently, high-intensity focused ultrasound (HIFU) has been highlighted as a non-invasive therapeutic modality, and showed enhanced therapeutic efficacy in combination with nanomedicines. Cavitation effect induced by the combination of HIFU and microbubbles results in transiently enhanced cell membrane permeability, facilitating improved drug delivery efficiency into tumor sites. Therefore, we introduce the acoustic cavitation and thermal/mechanical effects of HIFU in conjunction with microbubble to overcome the limitation of conventional drug delivery. The cavitation effect maximized by the strong acoustic energy of HIFU induced the preferential accumulation of nanomedicine locally released from the nanomedicines-microbubble complex in the tumor. In addition, the mechanical effect of HIFU allowed the accumulated nanomedicines to penetrate into deeper tumor region. The preferential accumulation and deeper penetration of nanomedicines by HIFU showed enhanced therapeutic efficacy, compared to low frequency ultrasound (US). These overall results demonstrate that the strategy combined nanomedicines-microbubble complex with HIFU is a promising tools for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Encouraging Legal Help Seeking for Victims of Intimate Partner Violence: The Therapeutic Effects of the Civil Protection Order

PubMed Central

Wright, Caroline Vaile; Johnson, Dawn M.

2016-01-01

Civil protective orders (CPOs) are the most widely used justice system remedy for intimate partner violence (IPV), and were implemented to ensure safety and increase victim participation in the justice system. Limited data exists regarding the effectiveness of CPOs; however, theories of therapeutic jurisprudence argue that legal interventions in and of themselves can improve mental health outcomes. To test this hypothesis, we examined the effectiveness of having a CPO issued against one’s abuser at improving the psychological sequelae of exposure to trauma. We used a longitudinal sample of female residents of battered women’s shelters who had experienced IPV (N = 106; 55% African American). One-way analyses of variance using gain scores indicated that PTSD symptoms (effect size ηp2 = .16) and incidents of sexual revictimization (effect size ηp2 = .09) decreased from baseline to 6-months postshelter for women who had a CPO against their most recent abuser compared to women without a CPO. These results support theories of therapeutic jurisprudence, suggesting that having a CPO can improve mental health outcomes. Limitations and clinical implications of our findings are discussed, including arguing for a coordinated service system that incorporates both legal and psychological assistance to improve the mental health of victims of IPV. PMID:23184312

3,3′-Diindolylmethane stimulates exosomal Wnt11 autocrine signaling in human umbilical cord mesenchymal stem cells to enhance wound healing

PubMed Central

Shi, Hui; Xu, Xiao; Zhang, Bin; Xu, Jiahao; Pan, Zhaoji; Gong, Aihua; Zhang, Xu; Li, Rong; Sun, Yaoxiang; Yan, Yongmin; Mao, Fei; Qian, Hui; Xu, Wenrong

2017-01-01

Human umbilical cord-derived mesenchymal stem cells (hucMSCs) are suggested as a promising therapeutic tool in regenerative medicine, however, their efficacy requires improvement. Small molecules and drugs come up to be a convenient strategy in regulating stem cells fate and function. Here, we evaluated 3,3′-diindolylmethane (DIM), a natural small-molecule compound involved in the repairing effects of hucMSCs on a deep second-degree burn injury rat model. HucMSCs primed with 50 μM of DIM exhibited desirable repairing effects compared with untreated hucMSCs. DIM enhanced the stemness of hucMSCs, which was related to the activation of Wnt/β-catenin signaling. β-catenin inhibition impaired the healing effects of DIM-primed hucMSCs (DIM-hucMSCs) in vivo. Moreover, we demonstrated that DIM upregulated Wnt11 expression in hucMSC-derived exosomes. Wnt11 knockdown inhibited β-catenin activation and stemness induction in DIM-hucMSCs and abrogated their therapeutic effects in vivo. Thus, our findings indicate that DIM promotes the stemness of hucMSCs through increased exosomal Wnt11 autocrine signaling, which provides a novel strategy for improving the therapeutic effects of hucMSCs on wound healing. PMID:28529644

Therapeutic alliance in dietetic practice for weight loss: Insights from health coaching.

PubMed

Nagy, Annaliese; McMahon, Anne; Tapsell, Linda; Deane, Frank; Arenson, Danielle

2018-02-13

The psychological construct of 'therapeutic alliance' can be used to better understand the effectiveness of consultations, particularly goal setting for weight management. We analysed audio-recorded health coaching sessions during a weight loss trial to explore relationships between therapeutic alliance and various contextual factors. Audio recordings of 50 health coaching sessions were analysed. After assessing fidelity to the protocol, therapeutic alliance was measured using an adapted Working Alliance Inventory Observer-rated Short Version (WAI-O-S), and examined by (i) identifying relationships between contextual factors and WAI-O-S scores (Spearman's coefficients); (ii) testing the impact of preparatory exercises and body mass index on WAI-O-S scores (one-way analysis of variance and least-squared differences tests) and (iii) comparing differences in WAI-O-S scores based on relationship status, gender and follow-up session completion (independent samples t-tests). Fidelity was high (mean 88%). WAI-O-S total scores ranged from 55 to 70 (out of 84). Session duration was significantly correlated with WAI-O-S component of 'Bond' (r = 0.42, P = 0.002). Those who completed preparatory exercises had significantly higher total WAI-O-S scores, 'Goal' and 'Task' scores. Participants who completed the follow-up session scored significantly higher for 'Goal' compared to no follow-up. Spending more time in a session appears related to increased bonding, a key component of therapeutic alliance. Preparatory work may help build therapeutic alliance and agreement on goals appears to influence follow-up completion. These exploratory findings provide directions for research addressing the professional relationship in dietetic consultations for weight loss. © 2018 Dietitians Association of Australia.

Gynecomastia in Patients with Prostate Cancer: A Systematic Review.

PubMed

Fagerlund, Anders; Cormio, Luigi; Palangi, Lina; Lewin, Richard; Santanelli di Pompeo, Fabio; Elander, Anna; Selvaggi, Gennaro

2015-01-01

Gynecomastia and/or mastodynia is a common medical problem in patients receiving antiandrogen (bicalutamide or flutamide) treatment for prostate cancer; up to 70% of these patients result to be affected; furthermore, this can jeopardise patients' quality of life. To systematically review the quality of evidence of the current literature regarding treatment options for bicalutamide-induced gynecomastia, including efficacy, safety and patients' quality of life. The PubMed, Medline, Scopus, The Cochrane Library and SveMed+ databases were systematically searched between January 1, 2000 and December 31, 2014. All searches were undertaken between January and February 2015. The search phrase used was:"gynecomastia AND treatment AND prostate cancer". Two reviewers assessed 762 titles and abstracts identified. The search and review process was done in accordance with the PRISMA statement. The PICOS (patients, intervention, comparator, outcomes and study design) process was used to specify inclusion criteria. Quality of evidence was rated according to GRADE. Primary outcomes were: treatment effects, number of complications and side effects. Secondary outcome was: Quality of Life. Eleven studies met the inclusion criteria and are analysed in this review. Five studies reported pharmacological intervention with tamoxifen and/or anastrozole, either as prophylactic or therapeutic treatment. Four studies reported radiotherapy as prophylactic and/or therapeutic treatment. Two studies compared pharmacological treatment to radiotherapy. Most of the studies were randomized with varying risk of bias. According to GRADE, quality of evidence was moderate to high. Bicalutamide-induced gynecomastia and/or mastodynia can effectively be managed by oral tamoxifen (10-20 mg daily) or radiotherapy without relevant side effects. Prophylaxis or therapeutic treatment with tamoxifen results to be more effective than radiotherapy.

Gynecomastia in Patients with Prostate Cancer: A Systematic Review

PubMed Central

Cormio, Luigi; Palangi, Lina; Lewin, Richard; Santanelli di Pompeo, Fabio; Elander, Anna

2015-01-01

Introduction Gynecomastia and/or mastodynia is a common medical problem in patients receiving antiandrogen (bicalutamide or flutamide) treatment for prostate cancer; up to 70% of these patients result to be affected; furthermore, this can jeopardise patients’ quality of life. Aims To systematically review the quality of evidence of the current literature regarding treatment options for bicalutamide-induced gynecomastia, including efficacy, safety and patients’ quality of life. Methods The PubMed, Medline, Scopus, The Cochrane Library and SveMed+ databases were systematically searched between January 1, 2000 and December 31, 2014. All searches were undertaken between January and February 2015. The search phrase used was:”gynecomastia AND treatment AND prostate cancer”. Two reviewers assessed 762 titles and abstracts identified. The search and review process was done in accordance with the PRISMA statement. The PICOS (patients, intervention, comparator, outcomes and study design) process was used to specify inclusion criteria. Quality of evidence was rated according to GRADE. Main Outcome Measures Primary outcomes were: treatment effects, number of complications and side effects. Secondary outcome was: Quality of Life. Results Eleven studies met the inclusion criteria and are analysed in this review. Five studies reported pharmacological intervention with tamoxifen and/or anastrozole, either as prophylactic or therapeutic treatment. Four studies reported radiotherapy as prophylactic and/or therapeutic treatment. Two studies compared pharmacological treatment to radiotherapy. Most of the studies were randomized with varying risk of bias. According to GRADE, quality of evidence was moderate to high. Conclusions Bicalutamide-induced gynecomastia and/or mastodynia can effectively be managed by oral tamoxifen (10–20 mg daily) or radiotherapy without relevant side effects. Prophylaxis or therapeutic treatment with tamoxifen results to be more effective than radiotherapy. PMID:26308532

Zirconia-incorporated zinc oxide eugenol has improved mechanical properties and cytocompatibility with human dental pulp stem cells.

PubMed

Jun, Soo Kyung; Kim, Hae-Won; Lee, Hae-Hyoung; Lee, Jung-Hwan

2018-01-01

Zinc oxide eugenol (ZOE) is widely used as a therapeutic dental restorative material. However, ZOE has poor mechanical properties and high cytotoxicity toward human dental pulp stem cells (hDPSCs) due to the release of Zn ions. In this study, zirconia-incorporated ZOE (ZZrOE) was developed to reduce the cytotoxicity and improve the mechanical properties of ZOE with sustained therapeutic effects on inflamed hDPSCs in terms of inflammatory gene expression levels compared with those of the original material. After the setting time and mechanical properties of ZZrOE incorporating varying amounts of zirconia (0, 5, 10, and 20wt% in powder) were characterized, the surface morphology and composition of the resulting ZZrOE materials were investigated. The ions and chemicals released into the cell culture medium from ZOE and ZZrOE (3cm 2 /mL) were measured by inductively coupled plasma atomic emission spectroscopy and gas chromatography, respectively. After testing cytotoxicity against hDPSCs using the above extracts, the therapeutic effects on lipopolysaccharide-inflamed hDPSCs in terms of compromising the upregulation of inflammatory response-related mRNA expression were tested using real-time PCR. ZZrOE 20% exhibited increased compressive strength (∼45%), 3-point flexural strength (∼150%) and hardness (∼75%), as well as a similar setting time (∼90%), compared with those of ZOE. After the rough surface of ZZrOE was observed, significantly fewer released Zn ions and eugenol (∼40% of that from ZOE) were detected in ZZrOE 20%. ZZrOE showed less cytotoxicity because of the lower amount of Zn ions released from ZOE while showing sustained inhibition of inflammatory marker (e.g., interleukin 1β, 6 and 8) mRNA levels. The improved mechanical properties and cytocompatibility, as well as the sustained therapeutic effects on inflamed hDPSCs, were investigated in ZZrOE compared with those of ZOE. Therefore, ZZrOE has the potential to be used as an alternative to ZOE as a dental restorative material. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Comparison of salt with low-dose furosemide and carperitide for treating acute decompensated heart failure: a single-center retrospective cohort study.

PubMed

Okuhara, Yoshitaka; Hirotani, Shinichi; Ando, Tomotaka; Nishimura, Koichi; Orihara, Yoshiyuki; Komamura, Kazuo; Naito, Yoshiro; Mano, Toshiaki; Masuyama, Tohru

2017-04-01

Hypertonic saline with furosemide has been proposed for a long time as an effective therapeutic option for the treatment of acute decompensated heart failure (ADHF). We previously reported the efficacy of continuous infusion of 1.7 % hypertonic saline plus low-dose furosemide in treatment for ADHF. Although this therapeutic strategy can be a useful option for effective decongestion in treatment for ADHF, there is no study that assesses the effect and safety of saline supplementation compared with standard therapy in Japan. The aim of this study was to investigate the efficacy, safety, and cost-effectiveness of 1.7 % hypertonic saline plus low-dose furosemide infusion compared with carperitide. We compared clinical outcomes, adverse events, and cost for patients receiving carperitide (carperitide group) with those for patients receiving 1.7 % hypertonic saline plus low-dose furosemide (salt group) during the initial hospitalization for ADHF. The cost analysis was performed on the basis of the previous report about cost-effectiveness of acute heart failure. A total of 175 ADHF patients received either carperitide (n = 111) or 1.7 % hypertonic saline plus low-dose furosemide infusion (n = 64) as initial treatment. There were no differences in length of hospital stay (27 ± 19 vs. 25 ± 16 day, p = 0.170) and infusion period (7.2 ± 6.1 vs. 8.4 ± 7.5 day, p = 0.474) between the two groups. The incidence of rehospitalization did not differ at 1 month (7.6 vs. 6.6 %, p = 1.000) and 1 year (36.8 vs. 37.7 %, p = 0.907) between the two groups. The Kaplan-Meier curves revealed no significant difference for 1 year all-cause mortality between the two groups (log-rank, p = 0.724). The single hospitalization cost was 95,314 yen lower and the yearly hospitalization cost 125,628 yen lower in the salt group compared with the carperitide group. Thus, intravenous 1.7 % hypertonic saline plus low-dose furosemide infusion is as effective as carperitide in terms of clinical outcome and is a cost-effective therapeutic strategy for the treatment of ADHF.

Herbs in Oral Mucositis

PubMed Central

Baharvand, Maryam; Jafari, Soudeh

2017-01-01

Oral mucositis is an inflammatory mucosal destruction as a result of chemotherapy and/or radiation therapy, which in severe cases can impair patients’ quality of life. Moreover, mucosal infection and/or systemic involvement due to compromised immunity leads to delay or discontinuation of the treatment. Many strategies and agents have been suggested for the management of this condition. Because of their lower side effects compared to chemical drugs, general interest in evaluating therapeutic effects of herbs has been increased intensively. Herbal plants apply their effect through different mechanisms of action: antioxidant, analgesic, anti-inflammatory, antifungal, antiseptic, and anticarcinogenic activity. Recently, various natural agents in plants have been noticed in mucositis, which may improve the symptoms through different interventions. The purpose of this review is to focus on the preventive or therapeutic use of herbal medicine to alleviate oral mucositis. PMID:28511530

Memory-enhancing effect of aspirin is mediated through opioid system modulation in an AlCl3-induced neurotoxicity mouse model

PubMed Central

RIZWAN, SAIMA; IDREES, AYESHA; ASHRAF, MUHAMMAD; AHMED, TOUQEER

2016-01-01

Neurodegenerative disorders such as Alzheimers disease (AD) are multifaceted and there are currently a limited number of therapeutic strategies available to treat them. Aspirin is known to act on multiple therapeutic targets and is a successful anti-inflammatory agent in various tissues. The present study aimed to ascertain the performance of aspirin when employed as a therapeutic agent to treat neurodegeneration on novel targets, including opioid system genes, in an AlCl3-induced neurotoxicity mouse model. The effects of two doses of aspirin (5 and 20 mg/kg aspirin for 12 days) were investigated in an AlCl3-induced neurotoxicity mouse model (150 mg/kg AlCl3 for 12 days). Neurological improvements were assessed through different behavioral tests and the effects of aspirin on opioid system gene expression levels were assessed by reverse transcription-polymerase chain reaction. Both doses resulted in improvements in cognitive behavior. A 5 mg/kg dose of aspirin was revealed to be effective for spatial memory improvement (7.14±0.84 sec), whilst a 20 mg/kg dose was superior for improving extinction learning (7.63±4.04%). Aspirin (5 mg/kg) also significantly improved contextual memory (48.05±10.6%) when compared with the AlCl3-treated group (1.49±0.62%; P<0.001). Aspirin was also observed to significantly decrease δ-opioid receptor expression in the cortex (1.09±0.08 and 1.27±0.08, respectively) at both doses (5 and 20 mg/kg) when compared with the AlCl3-treated group (3.69±1.43; P<0.05). Furthermore, aspirin at 5 mg/kg significantly reduced expression of prodynorphin in the cortex (0.57±0.20) when compared with the AlCl3-treated group (1.95±0.84; P<0.05). Notably, the effect of aspirin was significant in the cortex but not in the hippocampus. In summary, aspirin was effective in ameliorating the AD-like symptoms via the modulation of opioid systems. However, additional studies are required to determine the long term effects of aspirin on such conditions. PMID:27168835

Evaluating a novel oxygenating therapeutic for its potential use in the advancement of wound healing.

PubMed

Gueldner, Jennifer; Zhang, Fan; Zechmann, Bernd; Bruce, Erica D

2017-09-01

Non-gaseous oxygen therapeutics are emerging technologies in regenerative medicine that aim to sidestep the undesirable effects seen in traditional oxygen therapies, while enhancing tissue and wound regeneration. Using a novel oxygenating therapeutic (Ox66™) several in vitro models including fibroblast and keratinocyte monocultures were evaluated for potential drug toxicity, the ability of cells to recover after chemical injury, and cell migration after scratch assay. It was determined that in both cell lines, there was no significant cytotoxicity found after independent treatment with Ox66™. Similarly, after DMSO-induced chemical injury, the health parameters of cells treated with Ox66™ were improved when compared to their untreated counterparts. Particles were also characterized using scanning electron microscopy and electron dispersive spectroscopy both individually and in conjunction with fibroblast growth. The data in this study showed that the novel wound healing therapeutic has potential in advancing the treatment of various types of acute and chronic wounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Team-based learning in therapeutics workshop sessions.

PubMed

Beatty, Stuart J; Kelley, Katherine A; Metzger, Anne H; Bellebaum, Katherine L; McAuley, James W

2009-10-01

To implement team-based learning in the workshop portion of a pathophysiology and therapeutics sequence of courses to promote integration of concepts across the pharmacy curriculum, provide a consistent problem-solving approach to patient care, and determine the impact on student perceptions of professionalism and teamwork. Team-based learning was incorporated into the workshop portion of 3 of 6 pathophysiology and therapeutics courses. Assignments that promoted team-building and application of key concepts were created. Readiness assurance tests were used to assess individual and team understanding of course materials. Students consistently scored 20% higher on team assessments compared with individual assessments. Mean professionalism and teamwork scores were significantly higher after implementation of team-based learning; however, this improvement was not considered educationally significant. Approximately 91% of students felt team-based learning improved understanding of course materials and 93% of students felt teamwork should continue in workshops. Team-based learning is an effective teaching method to ensure a consistent approach to problem-solving and curriculum integration in workshop sessions for a pathophysiology and therapeutics course sequence.

The route of administration influences the therapeutic index of an anti-proNGF neutralizing mAb for experimental treatment of Diabetic Retinopathy.

PubMed

Barcelona, Pablo F; Galan, Alba; Nedev, Hinyu; Jian, Yifan; Sarunic, Marinko V; Saragovi, H Uri

2018-01-01

Many neurodegenerative retinal diseases are treated with monoclonal antibodies (mAb) delivered by invasive intravitreal injection (IVT). In Diabetic Retinopathy there is a scarcity of effective agents that can be delivered using non-invasive methods, and there are significant challenges in the validation of novel therapeutic targets. ProNGF represents a potential novel target, and IVT administration of a function-blocking anti-proNGF mAb is therapeutic in a mouse model of DR. We therefore compared invasive IVT to less invasive systemic intravenous (IV) and local subconjunctival (SCJ) administration, for therapy of Diabetic Retinopathy. The IV and SCJ routes are safe, afford sustained pharmacokinetics and tissue penetration of anti-proNGF mAb, and result in long-term therapeutic efficacy that blocks retinal inflammation, edema, and neuronal death. SCJ may be a more convenient and less-invasive approach for ophthalmic use and may enable reduced frequency of intervention for the treatment of retinal pathologies.

Analytical interference in the therapeutic drug monitoring of methotrexate.

PubMed

Oudart, Jean-Baptiste; Marquet, Benjamin; Feliu, Catherine; Gozalo, Claire; Djerada, Zoubir; Millart, Hervé

2016-06-01

High-dose of methotrexate chemotherapy is used in the treatment of some tumors. It presents several side effects that required therapeutic drug monitoring, which is commonly performed on 24, 48 and 72h after the beginning of the methotrexate infusion. Treatment of overexposure to methotrexate is based on injection of carboxypeptidase G2, which specifically degrades methotrexate into inactive metabolite: DAMPA. FPIA immunoassay on TDx automated analyzer (Abbott™) was used for therapeutic drug monitoring of methotrexate. This immunoassay presented a significant cross-reactivity between methotrexate and DAMPA, which widely overestimate the residual concentration compared to the gold standard HPLC/MS. TDx automated analyzer was substituted by a new immunoassay on Architect automated analyzer (Abbott™). However, this immunoassay has the same cross-reactivity, which needs to be careful when monitoring methotrexate after an injection of carboxypeptidase G2. In order to determine the most suitable assay for the therapeutic drug monitoring of methotrexate, the knowledge of injection of carboxypeptidase G2 remains essential.

Comparison of the efficiency of transplantation of bone marrow multipotent mesenchymal stromal cells cultured under normoxic and hypoxic conditions and their conditioned media on the model of acute lung injury.

PubMed

Chailakhyan, R K; Aver'yanov, A V; Zabozlaev, F G; Sobolev, P A; Sorokina, A V; Akul'shin, D A; Gerasimov, Yu V

2014-05-01

The therapeutic efficiency of intravenous injection of rat bone marrow multipotent mesenchymal stromal cells grown under conditions of normoxia and hypoxia (3% O2) and conditioned media from these cultures were compared on the rat model of acute lung injury induced by intraperitoneal injection of lipopolysaccharide. The best therapeutic efficiency was demonstrated by cells grown under hypoxic conditions. The effect of conditioned media was less pronounced and did not depend on the culturing conditions.

Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

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

Fossa, Anthony A., E-mail: anthony.fossa@icardiac.com; Wisialowski, Todd A.; Cremers, Thomas

2012-11-01

Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure ofmore » arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular safety and efficacy more adequately address therapeutic index ► Similar paradigms may exist with other centrally and peripherally acting drugs.« less

Superior therapeutic efficacy of nab-paclitaxel over cremophor-based paclitaxel in locally advanced and metastatic models of human pancreatic cancer.

PubMed

Rajeshkumar, N V; Yabuuchi, Shinichi; Pai, Shweta G; Tong, Zeen; Hou, Shihe; Bateman, Scott; Pierce, Daniel W; Heise, Carla; Von Hoff, Daniel D; Maitra, Anirban; Hidalgo, Manuel

2016-08-09

Albumin-bound paclitaxel (nab-paclitaxel, nab-PTX) plus gemcitabine (GEM) combination has demonstrated efficient antitumour activity and statistically significant overall survival of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) compared with GEM monotherapy. This regimen is currently approved as a standard of care treatment option for patients with metastatic PDAC. It is unclear whether cremophor-based PTX combined with GEM provide a similar level of therapeutic efficacy in PDAC. We comprehensively explored the antitumour efficacy, effect on metastatic dissemination, tumour stroma and survival advantage following GEM, PTX and nab-PTX as monotherapy or in combination with GEM in a locally advanced, and a highly metastatic orthotopic model of human PDAC. Nab-PTX treatment resulted in significantly higher paclitaxel tumour plasma ratio (1.98-fold), robust stromal depletion, antitumour efficacy (3.79-fold) and survival benefit compared with PTX treatment. PTX plus GEM treatment showed no survival gain over GEM monotherapy. However, nab-PTX in combination with GEM decreased primary tumour burden, metastatic dissemination and significantly increased median survival of animals compared with either agents alone. These therapeutic effects were accompanied by depletion of dense fibrotic tumour stroma and decreased proliferation of carcinoma cells. Notably, nab-PTX monotherapy was equivalent to nab-PTX plus GEM in providing survival advantage to mice in a highly aggressive metastatic PDAC model, indicating that nab-PTX could potentially stop the progression of late-stage pancreatic cancer. Our data confirmed that therapeutic efficacy of PTX and nab-PTX vary widely, and the contention that these agents elicit similar antitumour response was not supported. The addition of PTX to GEM showed no survival advantage, concluding that a clinical combination of PTX and GEM may unlikely to provide significant survival advantage over GEM monotherapy and may not be a viable alternative to the current standard-of-care nab-PTX plus GEM regimen for the treatment of PDAC patients.

Comparative Effectiveness Research Through a Collaborative Electronic Reporting Consortium.

PubMed

Fiks, Alexander G; Grundmeier, Robert W; Steffes, Jennifer; Adams, William G; Kaelber, David C; Pace, Wilson D; Wasserman, Richard C

2015-07-01

The United States lacks a system to use routinely collected electronic health record (EHR) clinical data to conduct comparative effectiveness research (CER) on pediatric drug therapeutics and other child health topics. This Special Article describes the creation and details of a network of EHR networks devised to use clinical data in EHRs for conducting CER, led by the American Academy of Pediatrics Pediatric Research in Office Settings (PROS). To achieve this goal, PROS has linked data from its own EHR-based "ePROS" network with data from independent practices and health systems across the United States. Beginning with 4 of proof-of-concept retrospective CER studies on psychotropic and asthma medication use and side effects with a planned full-scale prospective CER study on treatment of pediatric hypertension, the Comparative Effectiveness Research Through Collaborative Electronic Reporting (CER(2)) collaborators are developing a platform to advance the methodology of pediatric pharmacoepidemiology. CER(2) will provide a resource for future CER studies in pediatric drug therapeutics and other child health topics. This article outlines the vision for and present composition of this network, governance, and challenges and opportunities for using the network to advance child health and health care. The goal of this network is to engage child health researchers from around the United States in participating in collaborative research using the CER(2) database. Copyright © 2015 by the American Academy of Pediatrics.

Decline in placebo-controlled trial results suggests new directions for comparative effectiveness research.

PubMed

Olfson, Mark; Marcus, Steven C

2013-06-01

The Affordable Care Act offers strong support for comparative effectiveness research, which entails comparisons among active treatments, to provide the foundation for evidence-based practice. Traditionally, a key form of research into the effectiveness of therapeutic treatments has been placebo-controlled trials, in which a specified treatment is compared to placebo. These trials feature high-contrast comparisons between treatments. Historical trends in placebo-controlled trials have been evaluated to help guide the comparative effectiveness research agenda. We investigated placebo-controlled trials reported in four leading medical journals between 1966 and 2010. We found that there was a significant decline in average effect size or average difference in efficacy (the ability to produce a desired effect) between the active treatment and placebo. On average, recently studied treatments offered only small benefits in efficacy over placebo. A decline in effect sizes in conventional placebo-controlled trials supports an increased emphasis on other avenues of research, including comparative studies on the safety, tolerability, and cost of treatments with established efficacy.

JIM-13-0560 R1: Propensity scores for confounder adjustment when assessing the effects of medical interventions using non-experimental study designs

PubMed Central

Stürmer, Til; Wyss, Richard; Glynn, Robert J.; Brookhart, M. Alan

2014-01-01

Treatment effects, especially when comparing two or more therapeutic alternatives as in comparative effectiveness research, are likely to be heterogeneous across age, gender, co-morbidities, and co-medications. Propensity scores (PSs), an alternative to multivariable outcome models to control for measured confounding, have specific advantages in the presence of heterogeneous treatment effects. Implementing PSs using matching or weighting allows us to estimate different overall treatment effects in differently defined populations. Heterogeneous treatment effects can also be due to unmeasured confounding concentrated in those treated contrary to prediction. Sensitivity analyses based on PSs can help to assess such unmeasured confounding. PSs should be considered a primary or secondary analytic strategy in non-experimental medical research, including pharmacoepidemiology and non-experimental comparative effectiveness research. PMID:24520806

A cool approach to reducing electrode-induced trauma: Localized therapeutic hypothermia conserves residual hearing in cochlear implantation.

PubMed

Tamames, Ilmar; King, Curtis; Bas, Esperanza; Dietrich, W Dalton; Telischi, Fred; Rajguru, Suhrud M

2016-09-01

The trauma caused during cochlear implant insertion can lead to cell death and a loss of residual hair cells in the cochlea. Various therapeutic approaches have been studied to prevent cochlear implant-induced residual hearing loss with limited success. In the present study, we show the efficacy of mild to moderate therapeutic hypothermia of 4 to 6 °C applied to the cochlea in reducing residual hearing loss associated with the electrode insertion trauma. Rats were randomly distributed in three groups: control contralateral cochleae, normothermic implanted cochleae and hypothermic implanted cochleae. Localized hypothermia was delivered to the middle turn of the cochlea for 20 min before and after implantation using a custom-designed probe perfused with cooled fluorocarbon. Auditory brainstem responses (ABRs) were recorded to assess the hearing function prior to and post-cochlear implantation at various time points up to 30 days. At the conclusion of the trials, inner ears were harvested for histology and cell count. The approach was extended to cadaver temporal bones to study the potential surgical approach and efficacy of our device. In this case, the hypothermia probe was placed next to the round window niche via the facial recess or a myringotomy. A significant loss of residual hearing was observed in the normothermic implant group. Comparatively, the residual hearing in the cochleae receiving therapeutic hypothermia was significantly conserved. Histology confirmed a significant loss of outer hair cells in normothermic cochleae receiving the surgical trauma when compared to the hypothermia treated group. In human temporal bones, a controlled and effective cooling of the cochlea was achieved using our approach. Collectively, these results suggest that therapeutic hypothermia during cochlear implantation may reduce traumatic effects of electrode insertion and improve conservation of residual hearing. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease.

PubMed

Jayawardena, Dulari; Anbazhagan, Arivarasu N; Guzman, Grace; Dudeja, Pradeep K; Onyuksel, Hayat

2017-11-06

Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine, with increasing incidence worldwide. At present, the management of IBD is an unmet medical need due to the ineffectiveness of currently available drugs in treating all patients, and there is strong demand for novel therapeutics. In this regard, vasoactive intestinal peptide, a potent anti-inflammatory endogenous hormone, has shown promise in managing multiple immune disorders in animal models. However, when administered in the free form, VIP undergoes rapid degradation in vivo, and with continuous infusion, it causes severe dose limiting side effects. To overcome these barriers, we have developed a superior mode to deliver VIP in its native form, using sterically stabilized micelles (VIP-SSM). Our previous studies demonstrated that, VIP, when administered in SSM, prevented joint damage and inflammation in a mouse model of rheumatoid arthritis at a significantly lower dose than the free peptide, completely abrogating the serious side effect of hypotension associated with VIP. In the current study, we demonstrate the therapeutic benefit of VIP-SSM over free peptide in reversing severe colitis associated with IBD. First, we conducted preliminary studies with dextran sulfate sodium (DSS) induced colitis in mice, to determine the effectiveness of VIP administered on alternate days in reducing disease severity. Thereafter, a single intra peritoneal injection of VIP-SSM or the free peptide was used to determine its therapeutic effect on the reversal of colitis and associated diarrhea. The results demonstrated that when administered on alternate days, both VIP-SSM and VIP were capable of alleviating DSS colitis in mice. However, when administered as a single dose, in a therapeutic setting, VIP-SSM showed superior benefits compared to the free peptide in ameliorating colitis phenotype. Namely, the loss of solid fecal pellets and increased fluid accumulation in colon resulting from DSS insult was abrogated in VIP-SSM treated mice and not with free VIP. Furthermore, reduced protein and mRNA levels of the major chloride bicarbonate exchanger, down regulated in adenoma (DRA), seen with DSS was reversed with VIP-SSM, but not with the free peptide. Similarly, VIP-SSM treatment significantly reduced the elevated mRNA levels of pro-inflammatory cytokines and showed significant histologic recovery when compared to mice treated with free VIP. Therefore, these results demonstrated that as a single dose, the anti-inflammatory and antidiarrheal effects of VIP can be achieved effectively when administered as a nanomedicine. Therefore, we propose VIP-SSM to be developed as a potential therapeutic tool for treating ulcerative colitis, a type of IBD.

Hypoxic-Ischemic Encephalopathy-Associated Liver Fatty Degeneration and the Effects of Therapeutic Hypothermia in Newborn Piglets.

PubMed

Kubo, Hiroyuki; Shimono, Ryuichi; Nakamura, Shinji; Koyano, Kosuke; Jinnai, Wataru; Yamato, Satoshi; Yasuda, Saneyuki; Nakamura, Makoto; Tanaka, Aya; Fujii, Takayuki; Kanenishi, Kenji; Chiba, Yoichi; Miki, Takanori; Kusaka, Takashi; Ueno, Masaki

2017-01-01

Although liver can be injured under the hypoxic-ischemic encephalopathy (HIE) condition, there is currently no histopathological evidence. Therapeutic hypothermia is used to protect the brain; however, the therapeutic potential for concomitant liver injury is unknown. This study aimed to histopathologically prove HIE-associated liver injury and to investigate the influence of therapeutic hypothermia in a newborn piglet HIE model. Eighteen newborn piglets were divided into 3 groups: control (n = 4), HIE (n = 8), and therapeutic hypothermia (n = 6) groups. The hypoxic insult was induced by decreasing the fraction of inspiratory oxygen from 21 to 2-4% over 40 min while monitoring cerebral blood volume and cerebral hemoglobin oxygen saturation. For therapeutic hypothermia, whole-body cooling at 33-34°C was administered for 24 h after the hypoxic insult. We hematologically and histopathologically investigated the liver injury in all groups. Alanine transaminase and lactate dehydrogenase levels in the HIE group were significantly elevated compared with those in the control group. Micro-lipid droplet accumulation in the periportal zone, but not in the perivenous zone, was significantly greater in the HIE group than in the control group and significantly smaller in the therapeutic hypothermia group than in the HIE group. We demonstrated that micro-lipid droplet accumulation in the cytoplasm of hepatocytes in the periportal zone occurs under the HIE condition and that this accumulation is suppressed by therapeutic hypothermia. © 2016 S. Karger AG, Basel.

Augmented liver targeting of exosomes by surface modification with cationized pullulan.

PubMed

Tamura, Ryo; Uemoto, Shinji; Tabata, Yasuhiko

2017-07-15

Exosomes are membrane nanoparticles containing biological substances that are employed as therapeutics in experimental inflammatory models. Surface modification of exosomes for better tissue targetability and enhancement of their therapeutic ability was recently attempted mainly using gene transfection techniques. Here, we show for the first time that the surface modification of exosomes with cationized pullulan, which has the ability to target hepatocyte asialoglycoprotein receptors, can target injured liver and enhance the therapeutic effect of exosomes. Surface modification can be achieved by a simple mixing of original exosomes and cationized pullulan and through an electrostatic interaction of both substances. The exosomes modified with cationized pullulan were internalized into HepG2 cells in vitro to a significantly greater extent than unmodified ones and this internalization was induced through the asialoglycoprotein receptor that was specifically expressed on HepG2 cells and hepatocytes. When injected intravenously into mice with concanavalin A-induced liver injury, the modified exosomes accumulated in the liver tissue, resulting in an enhanced anti-inflammatory effect in vivo. It is concluded that the surface modification with cationized pullulan promoted accumulation of the exosomes in the liver and the subsequent biological function, resulting in a greater therapeutic effect on liver injury. Exosomes have shown potentials as therapeutics for various inflammatory disease models. This study is the first to show the specific accumulation of exosomes in the liver and enhanced anti-inflammatory effect via the surface modification of exosomes using pullulan, which is specifically recognized by the asialoglycoprotein receptor (AGPR) on HepG2 cells and hepatocytes. The pullulan was expressed on the surface of PKH-labeled exosomes, and it led increased accumulation of PKH into HepG2 cells, whereas the accumulation was canceled by AGPR inhibitor. In the mouse liver injury model, the modification of PKH-labeled exosomes with pullulan enabled increased accumulation of PKH specifically in the injured liver. Furthermore the greater therapeutic effects against the liver injury compared with unmodified original exosomes was observed. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Cost-effectiveness analysis of therapeutic options for chronic hepatitis C genotype 3 infected patients.

PubMed

Gimeno-Ballester, Vicente; Mar, Javier; O'Leary, Aisling; Adams, Róisín; San Miguel, Ramón

2017-01-01

This study provides a cost-effectiveness analysis of therapeutic strategies for chronic hepatitis C genotype 3 infected patients in Spain. A Markov model was designed to simulate the progression in a cohort of patients aged 50 years over a lifetime horizon. Sofosbuvir (SOF) plus peginterferon and ribavirin for 12 weeks was a cost-effective option when compared to standard of care (SoC) in the treatment of both 'moderate fibrosis' and 'cirrhotic' patients. Incremental cost-effectiveness ratios were €35,276/QALY and €18,374/QALY respectively. ICERs for SOF plus daclatasvir (DCV) regimens versus SoC were over the threshold limit considered, at €56,178/QALY and €77,378/QALY for 'moderate fibrosis' and 'cirrhotic' patients respectively. Addition of SOF to IFN-based regimens for genotype 3 was cost-effective for both 'moderate fibrosis' and 'cirrhotic' patients. IFN-free options including SOF and DCV association required price reductions lower than the list prices to be considered cost-effective.

The effectiveness of alternative planned durations of residential drug abuse treatment.

PubMed Central

McCusker, J; Vickers-Lahti, M; Stoddard, A; Hindin, R; Bigelow, C; Zorn, M; Garfield, F; Frost, R; Love, C; Lewis, B

1995-01-01

Randomized controlled trials were conducted at two residential drug abuse treatment facilities to compare programs that differed in planned duration. One trial compared a 6-month and a 12-month therapeutic community program (n = 184), and the second compared a 3-month and a 6-month relapse prevention program (n = 444). Retention rates over comparable time periods differed minimally by planned treatment duration, and the longer programs had lower completion rates. There was no effect in either trial of planned treatment duration on changes in psychosocial variables between admission and exit or on rates or patterns of drug use at follow-up between 2 and 6 months after exit. PMID:7573630

Health care provider communication: an empirical model of therapeutic effectiveness.

PubMed

Chochinov, Harvey M; McClement, Susan E; Hack, Thomas F; McKeen, Nancy A; Rach, Amanda M; Gagnon, Pierre; Sinclair, Shane; Taylor-Brown, Jill

2013-05-01

Patients who are facing life-threatening and life-limiting cancer almost invariably experience psychological distress. Responding effectively requires therapeutic sensitivity and skill. In this study, we examined therapeutic effectiveness within the setting of cancer-related distress with the objective of understanding its constituent parts. Seventy-eight experienced psychosocial oncology clinicians from 24 health care centers across Canada were invited to participate in 3 focus groups each. In total, 29 focus groups were held over 2 years, during which clinicians articulated the therapeutic factors deemed most helpful in mitigating patient psychosocial distress. The content of each focus group was summarized into major themes and was reviewed with participants to confirm their accuracy. Upon completion of the focus groups, workshops were held in various centers, eliciting participant feedback on an empirical model of therapeutic effectiveness based on the qualitative analysis of focus group data. Three primary, interrelated therapeutic domains emerged from the data, forming a model of optimal therapeutic effectiveness: 1) personal growth and self-care (domain A), 2) therapeutic approaches (domain B), and 3) creation of a safe space (domain C). Areas of domain overlap were identified and labeled accordingly: domain AB, therapeutic humility; domain BC, therapeutic pacing; and domain AC, therapeutic presence. This empirical model provides detailed insights regarding the elements and pedagogy of effective communication and psychosocial care for patients who are experiencing cancer-related distress. Copyright © 2012 American Cancer Society.

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

PubMed Central

Gimona, Mario; Pachler, Karin; Laner-Plamberger, Sandra; Schallmoser, Katharina; Rohde, Eva

2017-01-01

Extracellular vesicles (EVs) derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC)-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path. PMID:28587212

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use.

PubMed

Gimona, Mario; Pachler, Karin; Laner-Plamberger, Sandra; Schallmoser, Katharina; Rohde, Eva

2017-06-03

Extracellular vesicles (EVs) derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC)-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.

Effect of therapeutic interchange on medication reconciliation during hospitalization and upon discharge in a geriatric population

PubMed Central

Wang, Jessica S.; Fogerty, Robert L.

2017-01-01

Background Therapeutic interchange of a same class medication for an outpatient medication is a widespread practice during hospitalization in response to limited hospital formularies. However, therapeutic interchange may increase risk of medication errors. The objective was to characterize the prevalence and safety of therapeutic interchange. Methods and findings Secondary analysis of a transitions of care study. We included patients over age 64 admitted to a tertiary care hospital between 2009–2010 with heart failure, pneumonia, or acute coronary syndrome who were taking a medication in any of six commonly-interchanged classes on admission: proton pump inhibitors (PPIs), histamine H2-receptor antagonists (H2 blockers), hydroxymethylglutaryl CoA reductase inhibitors (statins), angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and inhaled corticosteroids (ICS). There was limited electronic medication reconciliation support available. Main measures were presence and accuracy of therapeutic interchange during hospitalization, and rate of medication reconciliation errors on discharge. We examined charts of 303 patients taking 555 medications at time of admission in the six medication classes of interest. A total of 244 (44.0%) of medications were therapeutically interchanged to an approved formulary drug at admission, affecting 64% of the study patients. Among the therapeutically interchanged drugs, we identified 78 (32.0%) suspected medication conversion errors. The discharge medication reconciliation error rate was 11.5% among the 244 therapeutically interchanged medications, compared with 4.2% among the 311 unchanged medications (relative risk [RR] 2.75, 95% confidence interval [CI] 1.45–5.19). Conclusions Therapeutic interchange was prevalent among hospitalized patients in this study and elevates the risk for potential medication errors during and after hospitalization. Improved electronic systems for managing therapeutic interchange and medication reconciliation may be valuable. PMID:29049325

The therapeutic effect of artesunate on rosacea through the inhibition of the JAK/STAT signaling pathway.

PubMed

Li, Ting; Zeng, Qingwen; Chen, Xingming; Wang, Guojiang; Zhang, Haiqing; Yu, Aihua; Wang, Hairui; Hu, Yang

2018-06-01

Acne rosacea is a type of chronic dermatosis with the characteristics of erubescence, angiotelectasis and pustule formation. However, current treatment methods are limited due to the side effects. Artesunate demonstrated a promising therapeutic efficacy with a high safety margin. HaCaT cells were treated with antibacterial peptide LL‑37 to simulate rosacea caused by Demodex folliculorum (D. folliculorum) infection. Cell Counting kit 8 and flow cytometry assays were performed to measure cellular proliferation, apoptosis, the stage of the cell cycle and reactive oxygen species generation in order to determine the level of cell damage. Then the damaged cells were treated with different concentrations of artesunate and doxycycline to determine the therapeutic effect of artesunate. Pro‑inflammatory cytokines tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑6, IL‑8 and C‑C motif chemokine 2 (MCP‑1) were measured using an ELISA, while western blotting was used to detect the expression of Janus kinase 2 (JAK2) and signal transducer and transcription activator (STAT3). As a result, LL‑37 treated HaCaT cells decreased in cell viability, had an increased apoptotic rate and cell cycle arrest, indicating that cell damage caused by rosacea was simulated. In addition, upregulated concentrations of the pro‑inflammatory cytokines TNF‑α, IL‑6, IL‑8 and MCP‑1 were attenuated in the artesunate group in a dose‑dependent fashion, indicating the therapeutic effect of artesunate. Furthermore, higher concentrations of artesunate exhibited an improved effect compared with the doxycycline group. In addition, increased expression levels of JAK2 and STAT3 following treatment with LL‑37 suggested that rosacea caused by D. folliculorum infection may lead to inflammation through the JAK/STAT signaling pathway. In conclusion, the potential mechanism by which damage occurs in rosacea was revealed and a promising therapeutic method against rosacea was demonstrated.

Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice.

PubMed

Tsuji, Takumi; Okuno, Satoshi; Kuroda, Ayano; Hamazaki, Junya; Chikami, Takuma; Sakurai, Sakura; Yoshida, Yuya; Banno, Rie; Fujita, Tetsuro; Kohno, Takeyuki

2016-04-01

The increasing incidence and prevalence of atopic dermatitis (AD) demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of immunomodulator FTY720 ointment (fingolimod) for mite-induced intractable AD using an NC/Nga mouse model. Female NC/Nga mice that developed severe AD were divided into four groups: (1) FTY720 (0.001% FTY720 ointment), (2) tacrolimus (tacrolimus hydrate ointment) (3) betamethasone (betamethasone ointment), and (4) ointment base (hydrophilic petrolatum), all of which received treatment six times per week. Therapeutic efficacy after two weeks was evaluated in terms of AD severity, histochemical observations (epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration), transepidermal water loss (TEWL), and epidermal barrier function (filaggrin expression). Betamethasone treatment showed little effect, confirming that the AD was intractable. In the FTY720 group, AD improved significantly compared with the ointment base group, as did epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration. In contrast, AD in the tacrolimus and betamethasone groups did not improve significantly, nor did epidermal hypertrophy or mast cell accumulation. Furthermore, in the FTY720 group, TEWL decreased significantly compared with the ointment base group, and filaggrin expression significantly increased compared with the betamethasone and ointment base groups. FTY720 ointment is a promising candidate for treatment of intractable AD. These findings also provide the first evidence that FTY720 ointment ameliorates epidermal barrier function. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Improved Antitumor Activity of a Therapeutic Melanoma Vaccine through the Use of the Dual COX-2/5-LO Inhibitor Licofelone.

PubMed

Neumann, Silke; Shirley, Simon A; Kemp, Roslyn A; Hook, Sarah M

2016-01-01

Immune-suppressive cell populations impair antitumor immunity and can contribute to the failure of immune therapeutic approaches. We hypothesized that the non-steroidal anti-inflammatory drug licofelone, a dual cyclooxygenase-2/5-LO inhibitor, would improve therapeutic melanoma vaccination by reducing immune-suppressive cell populations. Therefore, licofelone was administered after tumor implantation, either alone or in combination with a peptide vaccine containing a long tyrosinase-related protein 2-peptide and the adjuvant α-galactosylceramide, all formulated into cationic liposomes. Mice immunized with the long-peptide vaccine and licofelone showed delayed tumor growth compared to mice given the vaccine alone. This protection was associated with a lower frequency of immature myeloid cells (IMCs) in the bone marrow (BM) and spleen of tumor-inoculated mice. When investigating the effect of licofelone on IMCs in vitro , we found that the prostaglandin E 2 -induced generation of IMCs was decreased in the presence of licofelone. Furthermore, pre-incubation of BM cells differentiated under IMC-inducing conditions with licofelone reduced the secretion of cytokines interleukin (IL)-10 and -6 upon lipopolysaccharides (LPS) stimulation as compared to untreated cells. Interestingly, licofelone increased IL-6 and IL-10 secretion when administered after the LPS stimulus, demonstrating an environment-dependent effect of licofelone. Our findings support the use of licofelone to reduce tumor-promoting cell populations.

Disintegrable NIR Light Triggered Gold Nanorods Supported Liposomal Nanohybrids for Cancer Theranostics.

PubMed

Chauhan, Deepak S; Prasad, Rajendra; Devrukhkar, Janhavi; Selvaraj, Kaliaperumal; Srivastava, Rohit

2018-05-16

In this work, facile synthesis and application of targeted, dual therapeutic gold nanorods-liposome (GNR-Lipos) nanohybrid for imaging guided photothermal therapy and chemotherapy is investigated. The dual therapeutic GNR-Lipos nanohybrid consists of GNR supported, and doxorubicin (DOX) loaded liposome. GNRs not only serve as a photothermal agent and increase the drug release in intracellular environment of cancer cells, but also provide mechanical strength to liposomes by being decorated both inside and outside of bilayer surfaces. The designed nanohybrid shows a remarkable response for synergistic chemophotothermal therapy compared to only chemotherapy or photothermal therapy. The NIR response, efficient uptake by the cells, disintegration of GNR-Lipos nanohybrid, and synergistic therapeutic effect of photothermal and chemotherapy over breast cancer cells MDA-MB-231 are studied for the better development of a biocompatible nanomaterial based multifunctional cancer theranostic agent.

Life on the line: the therapeutic potentials of computer-mediated conversation.

PubMed

Miller, J K; Gergen, K J

1998-04-01

In what ways are computer networking practices comparable to face-to-face therapy? With the exponential increase in computer-mediated communication and the increasing numbers of people joining topically based computer networks, the potential for grass-roots therapeutic (or antitherapeutic) interchange is greatly augmented. Here we report the results of research into exchanges on an electronic bulletin board devoted to the topic of suicide. Over an 11-month period participants offered each other valuable resources in terms of validation of experience, sympathy, acceptance, and encouragement. They also asked provocative questions and furnished broad-ranging advice. Hostile entries were rare. However, there were few communiques that parallel the change-inducing practices more frequent within many therapeutic settings. In effect, on-line dialogues seemed more sustaining than transforming. Further limits and potentials of on-line communication are explored.

Human small bowel as a useful tool to investigate smooth muscle effects of potential therapeutics in organophosphate poisoning.

PubMed

Marquart, Katharina; Prokopchuk, Olga; Worek, Franz; Thiermann, Horst; Martignoni, Marc E; Wille, Timo

2018-09-01

Isolated organs proofed to be a robust tool to study effects of (potential) therapeutics in organophosphate poisoning. Small bowel samples have been successfully used to reveal smooth muscle relaxing effects. In the present study, the effects of obidoxime, TMB-4, HI-6 and MB 327 were investigated on human small bowel tissue and compared with rat data. Hereby, the substances were tested in at least seven different concentrations in the jejunum or ileum both pre-contracted with carbamoylcholine. Additionally, the cholinesterase activity of native tissue was determined. Human small intestine specimens showed classical dose response-curves, similar to rat tissue, with MB 327 exerting the most potent smooth muscle relaxant effect in both species (human EC 50 =0.7×10 -5 M and rat EC 50 =0.7×10 -5 M). The AChE activity for human and rat samples did not differ significantly (rat jejunum=1351±166 mU/mg wet weight; rat ileum=1078±123 mU/mg wet weight; human jejunum=1030±258 mU/mg wet weight; human ileum=1293±243 mU/mg wet weight). Summarizing, our isolated small bowel setup seems to be a solid tool to investigate the effects of (potential) therapeutics on pre-contracted smooth muscle, with data being transferable between rat and humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Functionalized bioengineered spider silk spheres improve nuclease resistance and activity of oligonucleotide therapeutics providing a strategy for cancer treatment.

PubMed

Kozlowska, Anna Karolina; Florczak, Anna; Smialek, Maciej; Dondajewska, Ewelina; Mackiewicz, Andrzej; Kortylewski, Marcin; Dams-Kozlowska, Hanna

2017-09-01

Cell-selective delivery and sensitivity to serum nucleases remain major hurdles to the clinical application of RNA-based oligonucleotide therapeutics, such as siRNA. Spider silk shows great potential as a biomaterial due to its biocompatibility and biodegradability. Self-assembling properties of silk proteins allow for processing into several different morphologies such as fibers, scaffolds, films, hydrogels, capsules and spheres. Moreover, bioengineering of spider silk protein sequences can functionalize silk by adding peptide moieties with specific features including binding or cell recognition domains. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel oligonucleotide delivery system that can be utilized to improve pharmacokinetics of RNA-based therapeutics, such as CpG-siRNA. The MS2 bioengineered silk was functionalized with poly-lysine domain (KN) to generate hybrid silk MS2KN. CpG-siRNA efficiently bound to MS2KN in contrary to control MS2. Both MS2KN complexes and spheres protected CpG-siRNA from degradation by serum nucleases. CpG-siRNA molecules encapsulated into MS2KN spheres were efficiently internalized and processed by TLR9-positive macrophages. Importantly, CpG-STAT3siRNA loaded in silk spheres showed delayed and extended target gene silencing compared to naked oligonucleotides. The prolonged Stat3 silencing resulted in the more pronounced downregulation of interleukin 6 (IL-6), a proinflammatory cytokine and upstream activator of STAT3, which limits the efficacy of TLR9 immunostimulation. Our results demonstrate the feasibility of using spider silk spheres as a carrier of therapeutic nucleic acids. Moreover, the modified kinetic and activity of the CpG-STAT3siRNA embedded into silk spheres is likely to improve immunotherapeutic effects in vivo. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel oligonucleotide delivery system that can be utilized to improve pharmacokinetics of RNA-based therapeutics. Although, the siRNA constructs have already given very promising results in the cancer therapy, the in vivo application of RNA-based oligonucleotide therapeutics still is limited due to their sensitivity to serum nucleases and some toxicity. We propose a carrier for RNA-based therapeutics that is made of bioengineered spider silk. We showed that functionalized bioengineered spider silk spheres not only protected RNA-based therapeutics from degradation by serum nucleases, but what is more important the embedding of siRNA into silk spheres delayed and extended target gene silencing compared with naked oligonucleotides. Moreover, we showed that plain silk spheres did not have unspecific effect on target gene levels proving not only to be non-cytotoxic but also very neutral vehicles in terms of TLR9/STAT3 activation in macrophages. We demonstrated advantages of novel delivery technology in safety and efficacy comparing with delivery of naked CpG-STAT3siRNA therapeutics. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Improved efficacy of therapeutic vaccination with viable human umbilical vein endothelial cells against murine melanoma by introduction of OK432 as adjuvant.

PubMed

Xu, Maolei; Xing, Yun; Zhou, Ling; Yang, Xue; Yao, Wenjun; Xiao, Wen; Ge, Chiyu; Ma, Yanjun; Yang, Jie; Wu, Jie; Cao, Rongyue; Li, Taiming; Liu, Jingjing

2013-06-01

Vaccination with xenogeneic or syngeneic endothelial cells targeting tumor angiogenesis is effective for inhibiting tumor growth. OK432, an effective adjuvant, was mixed with viable human umbilical vein endothelial cells (HUVECs) to prepare a novel HUVECs-OK432 vaccine, which could have an improved therapeutic efficacy. In this study, HUVECs-OK432 was administrated in mice by subcutaneous injection in a therapeutic procedure. The results showed that a stronger HUVEC-specific Abs and cytotoxic T lymphocyte immune response were elicited, which resulted in significant inhibition on the growth of B16F10 melanoma and remarkably prolonged survival of B16F10 melanoma-bearing mice compared with HUVECs. Besides, parallel results were obtained in vitro showing a stronger inhibition of HUVEC proliferation by immune sera of HUVECs-OK432 than that of HUVECs. Moreover, histochemistry and immunohistochemistry analysis showed that HUVECs-OK432 induced large areas of continuous necrosis within tumors and significantly reduced the vessel density, correlating well with the extent of tumor inhibition. Our present results suggest that OK432 could be employed as an effective adjuvant for HUVEC vaccines and therefore should be useful for adjuvant immunotherapy of cancer.

CSC-3436 switched tamoxifen-induced autophagy to apoptosis through the inhibition of AMPK/mTOR pathway.

PubMed

Wu, Sheng-Tang; Sun, Guang-Huan; Cha, Tai-Lung; Kao, Chien-Chang; Chang, Sun-Yran; Kuo, Sheng-Chu; Way, Tzong-Der

2016-08-15

Triple-negative breast cancer (TNBC) lacks specific therapeutic target and limits to chemotherapy and is essential to develop novel therapeutic regimens. Increasing studies indicated that tamoxifen, a selective estrogen receptor modulators (SERMs), has anti-tumor therapeutic effect in estrogen receptor α (ERα)-negative tumor. Here, we determined whether autophagy was activated by tamoxifen in TNBC cells. Moreover, CSC-3436 displayed strong and selective growth inhibition on cancer cells. Next, we investigated the anti-proliferation effect of combination of CSC-3436 plus tamoxifen on cell death in TNBC cells. Our study found that tamoxifen induces autophagy in TNBC cells. Endoplasmic reticulum stress and AMPK/mTOR contributed tamoxifen-induced autophagy. Interestingly, in combination treatment with CSC-3436 enhanced the anti-proliferative effect of tamoxifen. We found that CSC-3436 switched tamoxifen-induced autophagy to apoptosis via cleavage of ATG-5. Moreover, AMPK/mTOR pathway may involve in CSC-3436 switched tamoxifen-induced autophagy to apoptosis. The combination of tamoxifen and CSC-3436 produced stronger tumor growth inhibition compared with CSC-3436 or tamoxifen alone treatments in vivo. These data indicated that CSC-3436 combined with tamoxifen may be a potential approach for treatment TNBC.

Cyclodextrins: improving the therapeutic response of analgesic drugs: a patent review.

PubMed

de Oliveira, Makson G B; Guimarães, Adriana G; Araújo, Adriano A S; Quintans, Jullyana S S; Santos, Márcio R V; Quintans-Júnior, Lucindo J

2015-01-01

Cyclodextrins (CDs) are cyclic oligosaccharides that have recently been recognized as useful tools for optimizing the delivery of such problematic drugs. CDs can be found in at least 35 pharmaceutical products, such as anticancer agents, analgesic and anti-inflammatory drugs. Besides, several studies have demonstrated that CD-complexed drugs could provide benefits in solubility, stability and also improve pharmacological response when compared with the drug alone. The patent search was conducted in the databases WIPO, Espacenet, USPTO, Derwent and INPI, using the keywords cyclodextrin, pain and its related terms (analgesia, hyperalgesia, hypernociception, nociception, antinociception, antinociceptive). We found 442 patents. Criteria such as the complexation of analgesic agents and evidence of improvement of the therapeutic effect were indispensable for the inclusion of the patent. So, 18 patents were selected. We noticed that some patents are related to the complexation of opioids, NSAIDs, as well as natural products, in different types of CDs. The use of CDs creates the prospect of developing new therapeutic options for the most effective treatment of painful conditions, allowing a reduction of dosage of analgesic drugs and the occurrence of side effects. Thus, CDs can be an important tool to improve the efficacy and pharmacological profile of analgesic drugs.

Lessons Learned from Gemcitabine: Impact of Therapeutic Carrier Systems and Gemcitabine's Drug Conjugates on Cancer Therapy.

PubMed

Dyawanapelly, Sathish; Kumar, Animesh; Chourasia, Manish K

2017-01-01

Currently, drug delivery systems have a high impact in cancer therapy and are receiving more attention than conventional cancer treatment modalities. Compared with current cancer therapies, gemcitabine (2', 2'-difluoro-2'-deoxycytidine) has been proven to be an effective chemotherapeutic agent against pancreatic, colon, bladder, breast, ovarian, non-small-cell lung, and head and neck cancers in combination with other anticancer agents. To improve the safety and efficacy of cytotoxic drugs, several drug delivery systems have been explored. This review outlines the recent work directed toward gemcitabine delivery systems for cancer therapy, including aerosols, polymeric nanoparticles, liposomes, microparticles, carbon nanotubes, and multifunctional theranostic nanomedicines. It also provides insight into the design and development of gemcitabine conjugation for safe and effective cancer therapy. Despite the clinical promises of gemcitabine, many therapeutic challenges remain. Specifically, its therapeutic use in cancer chemotherapy is impeded by a short biological half-life, caused by its rapid metabolism, and resistance due to increased expression of ribonucleotide reductase. In our opinion, many research investigations have contributed to improve the selectivity and efficacy of gemcitabine. This combined approach of drug delivery systems and gemcitabine conjugates has shown promising efficacy in preclinical models and significant potential for future clinical cancer-therapeutic applications. Also, these strategies overcome most of the aforementioned limits of gemcitabine.

Enhanced Analgesic Responses After Preferential Delivery of Morphine and Fentanyl to the Olfactory Epithelium in Rats

PubMed Central

Hoekman, John D.; Ho, Rodney J.Y.

2011-01-01

Background Centrally acting opioid analgesics such as morphine and fentanyl are effective, but their efficacy is often limited by a delayed response or side effects resulting from systemic first-pass before reaching the brain and the central nervous system (CNS). It is generally accepted that drugs applied to the nasal cavity can directly access the brain and the CNS, which could provide therapeutic advantages such as rapid onset and lower systemic exposure. The olfactory region of the nasal cavity has been implicated in facilitating this direct nose-to-CNS transfer. If the fraction of opioid administered to the olfactory region could be improved, there could be a larger fraction of drug directly delivered to the CNS, mediating greater therapeutic benefit. Methods We have developed a pressurized olfactory delivery (POD) device to consistently and non-invasively deposit a majority of drug on the olfactory region of the nasal cavity in Sprague-Dawley rats. Using the tail-flick latency test and analysis of plasma and CNS tissue drug exposure, we compared distribution and efficacy of the opioids morphine and fentanyl administered to the nasal olfactory region with the POD device or the nasal respiratory region with nose drops or systemically via intraperitoneal (IP) injection. Results Compared to nose drop, POD administration of morphine resulted in significantly higher overall therapeutic effect (AUCeffect) without a significant increase in plasma drug exposure (AUCplasma). POD delivery of morphine resulted in a nose-to-CNS direct transport percentage of 38–55%. POD delivery of fentanyl led to a faster (5 min vs. 10 min) and more intense analgesic effect compared to nasal respiratory administration. Unlike IP injection or nose drop administration, both morphine and fentanyl given by the POD device to olfactory nasal epithelium exhibited clockwise [plasma] versus effect hysteresis after nasal POD administration, consistent with direct nose-to-CNS drug transport mechanism. Conclusions Deposition of opioids to the olfactory region within the nasal cavity could have a significant impact on drug distribution and pharmacodynamic effect, and thus should be considered into account in future nasally administered opioid studies. PMID:21709146

A novel ventricular restraint device (ASD) repetitively deliver Salvia miltiorrhiza to epicardium have good curative effects in heart failure management.

PubMed

Naveed, Muhammad; Wenhua, Li; Gang, Wang; Mohammad, Imran Shair; Abbas, Muhammad; Liao, Xiaoqian; Yang, Mengqi; Zhang, Li; Liu, Xiaolin; Qi, Xiaoming; Chen, Yineng; Jiadi, Lv; Ye, Linlan; Zhijie, Wang; Ding, Chen Ding; Feng, Yu; Xiaohui, Zhou

2017-11-01

A novel ventricular restraint is the non-transplant surgical option for the management of an end-stage dilated heart failure (HF). To expand the therapeutic techniques we design a novel ventricular restraint device (ASD) which has the ability to deliver a therapeutic drug directly to the heart. We deliver a Traditional Chinese Medicine (TCM) Salvia miltiorrhiza (Danshen Zhusheye) through active hydraulic ventricular support drug delivery system (ASD) and we hypothesize that it will show better results in HF management than the restraint device and drug alone. SD rats were selected and divided into five groups (n=6), Normal, HF, HF+SM (IV), HF+ASD, HF+ASD+SM groups respectively. Post myocardial infarction (MI), electrocardiography (ECG) showed abnormal heart function in all groups and HF+ASD+SM group showed a significant therapeutic improvement with respect to other treatment HF, HF+ASD, and HF+SM (IV) groups on day 30. The mechanical functions of the heart such as heart rate, LVEDP, and LVSP were brought to normal when treated with ASD+SM and show significant (P value<0.01) compared to other groups. BNP significantly declines in HF+ASD+SM group animals compared with other treatment groups. Masson's Trichrome staining was used to study histopathology of cardiac myocytes and quantification of fibrosis was assessed. The large blue fibrotic area was observed in HF, HF+ASD, and HF+SM (IV) groups while HF+ASD+SM showed negligible fibrotic myocyte at the end of study period (30days). This study proves that novel ASD device augments the therapeutic effect of the drug and delivers Salvia miltiorrhiza to the cardiomyocytes significantly as well as provides additional support to the dilated ventricle by the heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Reduction in hSOD1 copy number significantly impacts ALS phenotype presentation in G37R (line 29) mice: implications for the assessment of putative therapeutic agents.

PubMed

Zwiegers, Pierre; Lee, Grace; Shaw, Christopher A

2014-08-08

In vivo animal models of familial amyotrophic lateral sclerosis (fALS) are widely used to delineate the potential role that genetic mutations play in the neurodegenerative process. While these models are extensively used for establishing the safety and efficacy of putative therapeutics during pre-clinical development, effective clinical translation of pharmacological interventions has been largely unsuccessful. In this report we compare a recent cohort of G37R (line 29) mice generated from mating wild-type females with transgenic males obtained commercially to a previous set of offspring produced with transgenic male breeders from a colony established at a local collaborator's facility. Commercially derived progeny presented with a tightly clustered genomic signature for the mutant human superoxide dismutase1 transgene (hSOD1) locus, and exhibited a greater than two-fold reduction in the number of transgene copies present in the genome compared to offspring derived locally. Decrease in transgene levels corresponded with delayed ALS progression and a significant increase in overall lifespan (146%). These results highlight some key challenges inherent to the use of G37R (line 29) animals in pre-clinical studies for the development of ALS therapeutics. Without stringent assessment of mutant SOD1 copy number/protein levels, heterogeneity of transgene levels within cohorts may influence the behavioural and pathological presentation of disease and thus calls to question the validity of any detected therapeutic effects. Nuanced changes in mutant SOD1 copy number that currently remain unreported may undermine research endeavours, delay efforts for clinical translation, and compromise the rigor of animal studies by limiting reproducibility amongst research groups.

Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence.

PubMed

Durcan, Laura; Clarke, William A; Magder, Laurence S; Petri, Michelle

2015-11-01

Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists recommend weight-based dosing while some other specialists advocate height-based "ideal body weight" dosing. Patients were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis, the dose was 200 mg after each session, and in renal insufficiency it was 200 mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the effect of measurement and counseling on adherence, we compared the proportion of patients with a level of 500 ng/ml or higher based on the number of prior assessments. The proportion of patients with HCQ levels in the therapeutic range differed significantly by age, sex, and Vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were therapeutic, and by the third measurement this increased to 80% (p ≤ 0.0001). There was a trend toward higher disease activity with lower HCQ levels. Renal failure dosing led to suboptimum levels. We show that weight-based dosing (max 400 mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling, and repeated testing can increase adherence rates.

Applying a soft-robotic glove as assistive device and training tool with games to support hand function after stroke: Preliminary results on feasibility and potential clinical impact.

PubMed

Prange-Lasonder, Gerdienke B; Radder, Bob; Kottink, Anke I R; Melendez-Calderon, Alejandro; Buurke, Jaap H; Rietman, Johan S

2017-07-01

Recent technological developments regarding wearable soft-robotic devices extend beyond the current application of rehabilitation robotics and enable unobtrusive support of the arms and hands during daily activities. In this light, the HandinMind (HiM) system was developed, comprising a soft-robotic, grip supporting glove with an added computer gaming environment. The present study aims to gain first insight into the feasibility of clinical application of the HiM system and its potential impact. In order to do so, both the direct influence of the HiM system on hand function as assistive device and its therapeutic potential, of either assistive or therapeutic use, were explored. A pilot randomized clinical trial was combined with a cross-sectional measurement (comparing performance with and without glove) at baseline in 5 chronic stroke patients, to investigate both the direct assistive and potential therapeutic effects of the HiM system. Extended use of the soft-robotic glove as assistive device at home or with dedicated gaming exercises in a clinical setting was applicable and feasible. A positive assistive effect of the soft-robotic glove was proposed for pinch strength and functional task performance 'lifting full cans' in most of the five participants. A potential therapeutic impact was suggested with predominantly improved hand strength in both participants with assistive use, and faster functional task performance in both participants with therapeutic application.

The Molecular Phenotype of Endocapillary Proliferation: Novel Therapeutic Targets for IgA Nephropathy

PubMed Central

John, Rohan; Grone, Elisabeth; Porubsky, Stefan; Gröne, Hermann-Josef; Herzenberg, Andrew M.; Scholey, James W.; Hladunewich, Michelle; Cattran, Daniel C.

2014-01-01

IgA nephropathy (IgAN) is a clinically and pathologically heterogeneous disease. Endocapillary proliferation is associated with higher risk of progressive disease, and clinical studies suggest that corticosteroids mitigate this risk. However, corticosteroids are associated with protean cellular effects and significant toxicity. Furthermore the precise mechanism by which they modulate kidney injury in IgAN is not well delineated. To better understand molecular pathways involved in the development of endocapillary proliferation and to identify novel specific therapeutic targets, we evaluated the glomerular transcriptome of microdissected kidney biopsies from 22 patients with IgAN. Endocapillary proliferation was defined according to the Oxford scoring system independently by 3 nephropathologists. We analyzed mRNA expression using microarrays and identified transcripts differentially expressed in patients with endocapillary proliferation compared to IgAN without endocapillary lesions. Next, we employed both transcription factor analysis and in silico drug screening and confirmed that the endocapillary proliferation transcriptome is significantly enriched with pathways that can be impacted by corticosteroids. With this approach we also identified novel therapeutic targets and bioactive small molecules that may be considered for therapeutic trials for the treatment of IgAN, including resveratrol and hydroquinine. In summary, we have defined the distinct molecular profile of a pathologic phenotype associated with progressive renal insufficiency in IgAN. Exploration of the pathways associated with endocapillary proliferation confirms a molecular basis for the clinical effectiveness of corticosteroids in this subgroup of IgAN, and elucidates new therapeutic strategies for IgAN. PMID:25133636

[Therapeutic regimens for treating bacterial vaginosis in pregnant women].

PubMed

Borisov, I; Dimitrova, V; Mazneĭkova, V; Shopova, E

1999-01-01

The study comprises 128 pregnant women examined at different gestational weeks. The diagnosis of bacterial vaginosis was made using: a) the complex clinical criteria--vaginal discharge, vaginal pH, amine test and "clue cells" b) Nugent scoring system c) Spiegel criteria. Two therapeutic regimens were compared--intravaginal 2% clindamycin creme (Dalacin V) 5 g three consecutive days and intravaginal metronidazole (Flagyl) 500 mg once daily for 5 consecutive days. Control examination was carried out 5-7 days after completion of therapy using the same protocol. 28 women from the first group and 31 women from the second group had the control examination. Bacterial vaginosis was eradicated in 93% of women using intravaginal clindamycin and in 87% of women using intravaginal metronidazole. Both regimes were more effective compared to treatment with oral ampicillin for 7 days, where the cure rate was 62%.

Levonorgestrel-releasing intrauterine system vs oral progestins for non-atypical endometrial hyperplasia: a systematic review and metaanalysis of randomized trials.

PubMed

Abu Hashim, Hatem; Ghayaty, Essam; El Rakhawy, Mohamed

2015-10-01

We sought to evaluate the therapeutic efficacy of levonorgestrel-releasing intrauterine system (LNG-IUS) with oral progestins for treatment of non-atypical endometrial hyperplasia (EH). Searches were conducted on PubMed, SCOPUS, and CENTRAL databases to August 2014, and reference lists of relevant articles were screened. The search was limited to articles conducted on human beings and females. The PRISMA Statement was followed. Seven randomized controlled trials (n = 766 women) were included. Main outcome measures were the therapeutic effect rate (histological response) after 3, 6, 12, and 24 months of treatment; rate of irregular vaginal bleeding; and the hysterectomy rate per woman randomized. The Cochrane Collaboration risk of bias tool was used for quality assessment. Metaanalysis was performed with fixed effects model. LNG-IUS achieved a highly significant therapeutic response rate compared with oral progestins after 3 months of treatment (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.39-3.82; P = .001, 5 trials, I(2) = 0%, n = 376), after 6 months of treatment (OR, 3.16; 95% CI, 1.84-5.45; P < .00001, 4 trials, I(2) = 0%, n = 397), after 12 months of treatment (OR, 5.73; 95% CI, 2.67-12.33; P < .00001, 2 trials, I(2) = 0%, n = 224), and after 24 months of treatment (OR, 7.46; 95% CI, 2.55-21.78; P = .0002, 1 trial, n = 104). Subgroup analysis showed evidence of highly significant therapeutic response following LNG-IUS compared with oral progestins for non-atypical simple as well as complex EH (OR, 2.51; 95% CI, 1.14-5.53; P = .02, 6 trials, I(2) = 0%, n = 290; and OR, 3.31; 95% CI, 1.62-6.74; P = .001, 4 trials, I(2) = 0%, n = 216, respectively). Compared with oral progestins, LNG-IUS achieved significantly fewer hysterectomies (OR, 0.26; 95% CI, 0.15-0.45; P < .00001, 3 trials, n = 362, I² = 42%). No difference was observed in the rate of irregular vaginal bleeding between both groups (OR, 1.12; 95% CI, 0.54-2.32; P = .76, 2 trials, n = 207, I² = 77%). Funnel plot analysis was not performed because of the relatively small number of included studies. For treatment of non-atypical EH, LNG-IUS achieves higher therapeutic effect rates and lower hysterectomy rates than oral progestins and should be offered as an alternative to oral progestins in these cases. Copyright © 2015 Elsevier Inc. All rights reserved.

[Socio-ecological study of the therapeutic milieu in a modern rehabilitation centre (author's transl)].

PubMed

Heftner, E; Höller, H

1978-11-01

The article presents a data survey carried out by means of a questionnaire, the "ward atmosphere scale" described by Moos (1966--1974), U.S.A. In Austria, the effects of socio-ecological influences are examined for the first time at the rehabilitation centre in Hochegg. The data refer to autumn 1975. At that time attempts were made at Hochegg rehabilitation centre to develop a staff-centred guidance style and a client-centred therapeutic milieu in the sense of a therapeutic community. The patients were offered therapeutic programmes which were to the greatest possible degree tailored to their individual needs whilst not interferring with the patients' spontaneity and personal initiative. The analysis of the variables used in Hochegg are illustrated and compared with the mean values of the American results. It is pointed out that studies of existing conditions performed in an endeavour to create more human working conditions, are met with disapprouval. The first results of the survey are intended to be used as the basis for the improvement of the questionnaire and are helpful in decision-making regarding the development of therapeutic styles which meet the needs of the patient, regarding staff management and architectural influences.

Identification of potent biodegradable adjuvants that efficiently break self-tolerance--a key issue in the development of therapeutic vaccines.

PubMed

Ringvall, Maria; Huijbers, Elisabeth J M; Ahooghalandari, Parvin; Alekseeva, Ludmila; Andronova, Tatyana; Olsson, Anna-Karin; Hellman, Lars

2009-12-10

Monoclonal antibodies are used successfully in the treatment of many human disorders. However, these antibodies are expensive and have in many countries put a major strain on the health care economy. Therapeutic vaccines, directed against the same target molecules, may offer a solution to this problem. Vaccines usually involve lower amount of recombinant protein, approximately 10,000-20,000 times less, which is significantly more cost effective. Attempts to develop such therapeutic vaccines have also been made. However, their efficacy has been limited by the lack of potent immunostimulatory compounds, adjuvants, for human use. To address this problem we have conducted a broad screening for adjuvants that can enhance the efficacy of therapeutic vaccines, whilst at the same time being non-toxic and biodegradable. We have now identified adjuvants that show these desired characteristics. A combination of Montanide ISA720 and phosphorothioate stabilized CpG stimulatory DNA, induced similar or even higher anti-self-antibody titers compared to Freund's adjuvant, currently the most potent, but also toxic, adjuvant available. This finding removes one of the major limiting factors in the field and facilitates the development of a broad range of novel therapeutic vaccines.

Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arctigenin and arctiin from Arctium lappa L.

PubMed

Gao, Qiong; Yang, Mengbi; Zuo, Zhong

2018-05-01

Arctigenin (AR) and its glycoside, arctiin, are two major active ingredients of Arctium lappa L (A lappa), a popular medicinal herb and health supplement frequently used in Asia. In the past several decades, bioactive components from A lappa have attracted the attention of researchers due to their promising therapeutic effects. In the current article, we aimed to provide an overview of the pharmacology of AR and arctiin, focusing on their anti-inflammatory effects, pharmacokinetics properties and clinical efficacies. Compared to acrtiin, AR was reported as the most potent bioactive component of A lappa in the majority of studies. AR exhibits potent anti-inflammatory activities by inhibiting inducible nitric oxide synthase (iNOS) via modulation of several cytokines. Due to its potent anti-inflammatory effects, AR may serve as a potential therapeutic compound against both acute inflammation and various chronic diseases. However, pharmacokinetic studies demonstrated the extensive glucuronidation and hydrolysis of AR in liver, intestine and plasma, which might hinder its in vivo and clinical efficacy after oral administration. Based on the reviewed pharmacological and pharmacokinetic characteristics of AR, further pharmacokinetic and pharmacodynamic studies of AR via alternative administration routes are suggested to promote its ability to serve as a therapeutic agent as well as an ideal bioactive marker for A lappa.

Blended Interventions to Change Behavior in Patients With Chronic Somatic Disorders: Systematic Review.

PubMed

Kloek, Corelien; Bossen, Daniël; de Bakker, Dinny H; Veenhof, Cindy; Dekker, Joost

2017-12-21

Blended behavior change interventions combine therapeutic guidance with online care. This new way of delivering health care is supposed to stimulate patients with chronic somatic disorders in taking an active role in their disease management. However, knowledge about the effectiveness of blended behavior change interventions and how they should be composed is scattered. This comprehensive systematic review aimed to provide an overview of characteristics and effectiveness of blended behavior change interventions for patients with chronic somatic disorders. We searched for randomized controlled trials published from 2000 to April 2017 in PubMed, Embase, CINAHL, and Cochrane Central Register of Controlled Trials. Risk of bias was assessed using the Cochrane Collaboration tool. Study characteristics, intervention characteristics, and outcome data were extracted. Studies were sorted based on their comparison group. A best-evidence synthesis was conducted to summarize the effectiveness. A total of 25 out of the 29 included studies were of high quality. Most studies (n=21; 72%) compared a blended intervention with no intervention. The majority of interventions focused on changing pain behavior (n=17; 59%), and the other interventions focused on lifestyle change (n=12; 41%). In addition, 26 studies (90%) focused on one type of behavior, whereas 3 studies (10%) focused on multiple behaviors. A total of 23 studies (79%) mentioned a theory as basis for the intervention. The therapeutic guidance in most studies (n=18; 62%) was non face-to-face by using email, phone, or videoconferencing, and in the other studies (partly), it was face-to-face (n=11; 38%). In 26 studies (90%), the online care was provided via a website, and in 3 studies (10%) via an app. In 22 studies (76%), the therapeutic guidance and online care were integrated instead of two separate aspects. A total of 26 outcome measures were included in the evidence synthesis comparing blended interventions with no intervention: for the coping strategy catastrophizing, we found strong evidence for a significant effect. In addition, 1 outcome measure was included in the evidence synthesis comparing blended interventions with face-to-face interventions, but no evidence for a significant effect was found. A total of 6 outcome measures were included in the evidence synthesis comparing blended interventions with online interventions, but no evidence for a significant effect was found. Blended behavior change interventions for patients with chronic somatic disorders show variety in the type of therapeutic guidance, the type of online care, and how these two delivery modes are integrated. The evidence of the effectiveness of blended interventions is inconsistent and nonsignificant for most outcome measures. Future research should focus on which type of blended intervention works for whom. ©Corelien Kloek, Daniël Bossen, Dinny H de Bakker, Cindy Veenhof, Joost Dekker. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 21.12.2017.

Early neuroprotection after cardiac arrest.

PubMed

Dell'anna, Antonio M; Scolletta, Sabino; Donadello, Katia; Taccone, Fabio S

2014-06-01

Many efforts have been made in the last decades to improve outcome in patients who are successfully resuscitated from sudden cardiac arrest. Despite some advances, postanoxic encephalopathy remains the most common cause of death among those patients and several investigations have focused on early neuroprotection in this setting. Therapeutic hypothermia is the only strategy able to provide effective neuroprotection in clinical practice. Experimental studies showed that therapeutic hypothermia was even more effective when it was started immediately after the ischemic event. In human studies, the use of prehospital hypothermia was able to reduce the time to target temperature but did not result in higher survival rate or neurological recovery in patients with out-of-hospital cardiac arrest, when compared with standard in-hospital therapeutic hypothermia. Thus, intra-arrest hypothermia (i.e., initiated during cardiopulmonary resuscitation) may be a valid alternative to improve the effectiveness of therapeutic hypothermia in this setting; however, more clinical data are needed to demonstrate any potential benefit of such intervention on neurological outcome. Together with cooling, early hemodynamic optimization should be considered to improve cerebral perfusion in cardiac arrest patients and minimize any secondary brain injury. Nevertheless, only scarce data are available on the impact of early hemodynamic optimization on the development of organ dysfunction and neurological recovery in such patients. Some new protective strategies, including inhaled gases (i.e., xenon, argon, nitric oxide) and intravenous drugs (i.e., erythropoietin) are emerging in experimental studies as promising tools to improve neuroprotection, especially when combined with therapeutic hypothermia. Early cooling may contribute to enhance neuroprotection after cardiac arrest. Hemodynamic optimization is mandatory to avoid cerebral hypoperfusion in this setting. The combination of such interventions with other promising neuroprotective strategies should be evaluated in future large clinical studies.

Bifidobacterium breve as a delivery vector of IL-24 gene therapy for head and neck squamous cell carcinoma in vivo.

PubMed

Wang, L; Vuletic, I; Deng, D; Crielaard, W; Xie, Z; Zhou, K; Zhang, J; Sun, H; Ren, Q; Guo, C

2017-11-01

Beneficial bacteria are becoming ever more popular gene delivery method for hypoxia-tumor targeting in vivo. In this study we investigated the therapeutic effect of new recombinant Bifidobacterium breve strain expressing interleukin (IL)-24 gene (B. breve-IL24) on head and neck tumor xenograft in mice. Briefly, B. breve transformants were obtained through electro-transformation. Bacteria-tumor-targeting ability were analyzed in vivo over different time points (1, 3 and 7 days post-bacteria injection). Furthermore, the therapeutic effect of bacteria on tumor cells in vivo were analyzed as follows: 30 Balb/c nude mice bearing subcutaneous tumor were randomly divided in three groups (Drug group, green fluorescent protein (GFP) group and Saline group). The therapy lasted for 2 weeks and included B. breve-IL24 administration via tail vein for Drug group, B. breve-GFP for GFP group and phosphate buffered saline for Saline group. The tumor growth was monitored using standard caliper technique, while the apoptosis induction in vivo was analyzed by Real-time Positron Emission Tomography/Computed Tomography (PET/CT) imaging ([18F]-ML-10 tracer). At the end of the experiment, tumor tissues were collected and analyzed by western blotting. Briefly, our results suggested that our new recombinant bacterium has the capability of targeting tumor tissue in vivo. As for the therapeutic effect, our new strain has revealed to be a promising therapeutic approach against tumor growth in vivo. Briefly, higher tumor growth inhibition and higher tumor cell apoptosis induction were observed in Drug group compared with the GFP and Saline groups. To conclude, a new recombinant strain B. breve-IL24 offers a novel, safe and clinically acceptable therapeutic approach for tumor therapy in vivo.

A pilot study of the comparative efficacy of 100 Hz magnetic seizure therapy and electroconvulsive therapy in persistent depression.

PubMed

Fitzgerald, Paul B; Hoy, Kate E; Elliot, David; McQueen, Susan; Wambeek, Lenore E; Chen, Leo; Clinton, Anne Maree; Downey, Glenn; Daskalakis, Zafiris J

2018-05-01

Magnetic seizure therapy (MST) is a novel brain stimulation technique that uses a high-powered transcranial magnetic stimulation device to produce therapeutic seizures. Preliminary MST studies have found antidepressant effects in the absence of cognitive side effects but its efficacy compared to electroconvulsive therapy (ECT) remains unclear. The aim of this study was to investigate the therapeutic efficacy and cognitive profile of MST compared to standard right unilateral ECT treatment. Thirty-seven patients completed a course of at least nine ECT or MST treatments in a randomized double-blind protocol. Assessments of depression severity and cognition were performed before and after treatment. No difference in the antidepressant effectiveness between the treatments was seen across any of the clinical outcome measures, although the overall response rates in both groups were quite low. In regards to cognition, following MST there were significant improvements in tests of psychomotor speed, verbal memory, and cognitive inhibition, with no reductions in cognitive performance. Following ECT there was significant improvement in only one of the cognitive inhibition tasks. With respect to the between-group comparisons, the MST group showed a significantly greater improvement on psychomotor speed than ECT. MST showed similar efficacy to right unilateral ECT in patients with treatment-resistant depression without cognitive side effects but in a sample that was only of sufficient size to demonstrate relatively large differences in response between the two groups. Future research should aim to optimize the methods of MST administration and compare its efficacy to ECT in large randomized controlled trials. © 2018 Wiley Periodicals, Inc.

A comparison of the COG and MCNP codes in computational neutron capture therapy modeling, Part II: gadolinium neutron capture therapy models and therapeutic effects.

PubMed

Wangerin, K; Culbertson, C N; Jevremovic, T

2005-08-01

The goal of this study was to evaluate the COG Monte Carlo radiation transport code, developed and tested by Lawrence Livermore National Laboratory, for gadolinium neutron capture therapy (GdNCT) related modeling. The validity of COG NCT model has been established for this model, and here the calculation was extended to analyze the effect of various gadolinium concentrations on dose distribution and cell-kill effect of the GdNCT modality and to determine the optimum therapeutic conditions for treating brain cancers. The computational results were compared with the widely used MCNP code. The differences between the COG and MCNP predictions were generally small and suggest that the COG code can be applied to similar research problems in NCT. Results for this study also showed that a concentration of 100 ppm gadolinium in the tumor was most beneficial when using an epithermal neutron beam.

Autoradiographic and biochemical observations on the distribution of non-steroid anti-inflammatory drugs.

PubMed

Rainsford, K D; Schweitzer, A; Brune, K

1981-04-01

A comparison has been made of the distribution of some new radioactively-labelled non-steroid anti-inflammatory (NSAI) drugs or pro-drugs with their respective progenitors and/or standard acidic NSAI drugs (i.e. aspirin, indomethacin and phenylbutazone), using whole body autoradiography and scintillation counting. The object of this study was to establish if the distribution of these new NSAI drugs may contribute to changes in their side-, or therapeutic effects compared with the older drugs. All the NSAI drugs accumulated in those tissues wherein the principle therapeutic and side-effects are manifest. The accumulation in inflamed tissues occurs regardless of the structural type of NSAI drugs, i.e. with specific accumulation occurring in this tissue of the acidic drugs or their acidic metabolites. New aspects of the distribution of the acetyl moiety of aspirin are reported which may be significant in relation to the side-effects induced by this drug.

[Observation on non-invasive electrode pulse electric stimulation for treatment of Bell's palsy].

PubMed

Guo, Qing-Hua; Yan, Jian-Zhen; Yan, Wu-Shen; Xiao, Mei-Zhen

2006-12-01

To explore non-invasive therapy for treatment of Bell palsy. Two hundred and seventy-six were randomly divided into two groups, a treatment group and a control group, 138 cases in each group. The treatment group were treated with non-invasive electrode pulse electric stimulation at Taiyang (EX-HN 5), Sibai (ST 2), Qianzheng (Extra), Dicang (ST 4), and the control group with routine medicine (prednisone, dibazol, vitamine B complex and Qianzheng Powder), once each day, 10 days constituting one course. After two courses, their therapeutic effects were compared. The cured rate and the effective rate were 83.3% and 99.3% in the treatment group, and 48.5% and 88.4% in the control group respectively with a significant difference between the two groups (P < 0.05). Non-invasive electrode pulse electric stimulation at facial points has obvious therapeutic effect on Bell palsy.

Pharmaceutical, biological, and clinical properties of botulinum neurotoxin type A products.

PubMed

Frevert, Jürgen

2015-03-01

Botulinum neurotoxin injections are a valuable treatment modality for many therapeutic indications and have revolutionized the field of aesthetic medicine so that they are the leading cosmetic procedure performed worldwide. Studies show that onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA are comparable in terms of clinical efficacy. Differences between the products relate to the botulinum neurotoxin complexes, specific biological potency, and their immunogenicity. Protein complex size and molecular weight have no effect on biological activity, stability, distribution, or side effect profile. Complexing proteins and inactive toxin (toxoid) content increase the risk of neutralizing antibody formation, which can cause secondary treatment failure, particularly in chronic disorders that require frequent injections and long-term treatment. These attributes could lead to differences in therapeutic outcomes, and, given the widespread aesthetic use of these three neurotoxin products, physicians should be aware of how they differ to ensure their safe and effective use.

Hypothermia as an Adjunct Therapy to Vesicant-induced Skin Injury

PubMed Central

Sawyer, Thomas W; Nelson, Peggy

2008-01-01

Objective: The notion that cooling vesicant-exposed tissue may ameliorate or prevent resultant injury is not a novel concept. During both World Wars, studies were conducted that investigated this potential mode of therapy with sulfur mustard and seemed to conclude that there might be merit in pursuing this research direction. However, it does not appear that these studies were followed up vigorously, and the literature that describes this work is not readily accessible. In this report, we compare the toxicities of lewisite and sulfur mustard in vitro and in vivo and also provide an overview of historical and recent work on the effect of temperature on the toxicity of these vesicating chemical warfare agents.Methods: Tissue culture and animal studies were utilized to examine the effects of hypothermia on vesicant-induced toxicity. Results: Cytotoxicity was either significantly delayed (lewisite) or prevented (sulfur mustard) when cultures were maintained at 25°C. However, the effects of hypothermia on sulfur mustard–induced cell death were reversible when the cells were returned to 37°C. Despite these in vitro results, animal studies demonstrated that the therapeutic cooling of both mustard sulfur–exposed and lewisite-exposed skin resulted in dramatic and permanent protection against injury. Cooling also increased the therapeutic window in which drugs were effective against vesicant agents in tissue culture and lewisite-induced skin injury. Conclusions: The simple and noninvasive application of cooling measures may not only provide significant therapeutic relief to vesicant-exposed skin but also increase the therapeutic window in which medical countermeasures against vesicant agents are useful. PMID:18516227

Whole-Body Cryotherapy in Athletes: From Therapy to Stimulation. An Updated Review of the Literature.

PubMed

Lombardi, Giovanni; Ziemann, Ewa; Banfi, Giuseppe

2017-01-01

Nowadays, whole-body cryotherapy is a medical physical treatment widely used in sports medicine. Recovery from injuries (e.g., trauma, overuse) and after-season recovery are the main purposes for application. However, the most recent studies confirmed the anti-inflammatory, anti-analgesic, and anti-oxidant effects of this therapy by highlighting the underlying physiological responses. In addition to its therapeutic effects, whole-body cryotherapy has been demonstrated to be a preventive strategy against the deleterious effects of exercise-induced inflammation and soreness. Novel findings have stressed the importance of fat mass on cooling effectiveness and of the starting fitness level on the final result. Exposure to the cryotherapy somehow mimics exercise, since it affects myokines expression in an exercise-like fashion, thus opening another possible window on the therapeutic strategies for metabolic diseases such as obesity and type 2 diabetes. From a biochemical point of view, whole-body cryotherapy not always induces appreciable modifications, but the final clinical output (in terms of pain, soreness, stress, and post-exercise recovery) is very often improved compared to either the starting condition or the untreated matched group. Also, the number and the frequency of sessions that should be applied in order to obtain the best therapeutic results have been deeply investigated in the last years. In this article, we reviewed the most recent literature, from 2010 until present, in order to give the most updated insight into this therapeutic strategy, whose rapidly increasing use is not always based on scientific assumptions and safety standards.

Medicinal Plants for Management of Gastroesophageal Reflux Disease: A Review of Animal and Human Studies.

PubMed

Salehi, Mehdi; Karegar-Borzi, Hossein; Karimi, Mehrdad; Rahimi, Roja

2017-02-01

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disease that causes troublesome symptoms and/or complications. The major therapeutic strategy for GERD focuses mainly on symptom alleviation using proton pump inhibitors (PPIs), which does not produce a perfect response in all patients. An approach with new therapeutic agents for GERD seems to be essential. The aim of this study was to review animal and human studies investigating the effect of medicinal plants in GERD as well as mechanisms underlying their therapeutic effects. Medline, Scopus, and Cochrane Central Register of Controlled Trials were searched for animal or human studies. The data collected covered January 1966-October 2015. A total of 22 studies were included in this review, of which nine were animal studies and 13 were human studies. Ceratonia siliqua as a medicinal plant and rikkunshito as a multicomponent herbal preparation were the most frequently studied herbal medicines in GERD. Antioxidant and anti-inflammatory activities were the main mechanisms demonstrated in animal studies for ameliorating the effects of medicinal plants in GERD. Other mechanisms include downregulation of genes encoding inflammatory proteins, improvement of barrier function and gastric mucus, a decrease in gastric acid, and induction of tonic contractions of the lower esophageal sphincter. All herbal preparations used in human studies have led to the alleviation of symptoms related to GERD. Myrtus communis and Cydonia oblonga showed marked reduction in GERD symptoms comparable to omeprazole. The therapeutic effect of Cydonia oblonga persisted after discontinuation of the drug. Tongjlang and rikkunshito showed therapeutic effects for non-erosive reflux disease (NERD) where PPIs failed to show a promising effect. Studies on Ceratonia siliqua have been solely focused on regurgitation in infants, and a remarkable decrease in the number of regurgitations was demonstrated. The multiple mechanisms of action of medicinal plants in GERD other than anti-secretory properties appear to provide more efficient treatment and helped to manage the histopathological changes associated with this disorder. Further studies are needed to understand the effects of medicinal plants on GERD better.

[Effects of pamidronate disodium (Bonin) combined with chemotherapy on bone pain in multiple myeloma].

PubMed

Leng, Yun; Chen, Shi-lun; Shi, Hong-zhi

2002-10-01

Objective. To evaluate the therapeutic effects of Disodium Pamidronate (Bonin) on bone pain in multiple myeloma. Method. 18 patients received only chemotherapy and 16 patients with addition of Bonin were compared. Result. The bone pain was significantly relieved both in chemotherapy alone group and in the combination group of Bonin with chemotherapy after treatment (P<0.01, as compared with before therapy). However, the effects of combination group were more dramatical than that of the other group (P<0.05). No obvious side-effects were observed except mild fever in one patient in the combination group. Conclusion. Bonin, as a safe and effective Bisphosphonates preparation, could relieve bone pain in multiple myeloma more effectively when combined with chemotherapy.

Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists.

PubMed

de Koning, M L Y; Fischer, K; de Laat, B; Huisman, A; Ninivaggi, M; Schutgens, R E G

2017-05-01

Essentials It is unknown if hemophilia patients with atrial fibrillation need anticoagulation. Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared. Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR). In non-severe hemophilia, 33% had higher ETP than therapeutic INR and may need anticoagulation. Click to hear Dr Negrier's perspective on global assays for assessing coagulation SUMMARY: Background It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKAs) to the same extent as the normal population. Objective To compare hemostatic potential in hemophilia patients and patients on VKAs using thrombin generation (TG). Methods In this cross-sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII < 1%, n = 15) and non-severe (FVIII 1-50%, n = 118) hemophilia A, 97 patients on a VKA with an international normalized ratio (INR) ≥ 1.5 and healthy controls. Endogenous thrombin potential (ETP) (nm*min) was compared according to FVIII level (< 1%, 1-19% and 20-50%) with healthy controls and patients with sub-therapeutic INR (1.5-1.9) and therapeutic INR (≥ 2.0). Medians and interquartile ranges (IQRs) were calculated. Results Compared with healthy controls (898 [IQR 803-1004]), both hemophilia patients and patients on VKAs had lower median ETPs at 304 (196-449) and 176 (100-250), respectively. ETP was quite similar in severe hemophilia patients (185 [116-307]) and patients with a therapeutic INR (156 [90-225]). Compared with patients with therapeutic INR, ETP in patients with FVIII 1-19% and patients with FVIII 20-50% was higher at 296 (203-430) and 397 (219-632), respectively. All patients with therapeutic INR had an ETP < 400. Considering this threshold, 93% of severe hemophilia patients, 70% of patients with FVIII 1-19% and 52% of patients with FVIII 20-50% had an ETP < 400. Conclusion In severe hemophilia patients, TG was comparable to that in patients with a therapeutic INR. In one-third of non-severe hemophilia patients, TG was higher. These results suggest that anticoagulation therapy should be considered in a substantial proportion of non-severe hemophilia patients. © 2017 International Society on Thrombosis and Haemostasis.

3D culture of Her2+ breast cancer cells promotes AKT to MAPK switching and a loss of therapeutic response.

PubMed

Gangadhara, Sharath; Smith, Chris; Barrett-Lee, Peter; Hiscox, Stephen

2016-06-01

The Her2 receptor is overexpressed in up to 25 % of breast cancers and is associated with a poor prognosis. Around half of Her2+ breast cancers also express the estrogen receptor and treatment for such tumours can involve both endocrine and Her2-targeted therapies. However, despite preclinical data supporting the effectiveness of these agents, responses can vary widely in the clinical setting. In light of the increasing evidence pointing to the interplay between the tumour and its extracellular microenvironment as a significant determinant of therapeutic sensitivity and response here we investigated the impact of 3D matrix culture of breast cancer cells on their therapeutic sensitivity. A 3D Matrigel-based culture system was established and optimized for the growth of ER+/Her2+ breast cancer cell models. Growth of cells in response to trastuzumab and endocrine agents in 3D culture versus routine monolayer culture were assessed using cell counting and Ki67 staining. Endogenous and trastuzumab-modulated signalling pathway activity in 2D and 3D cultures were assessed using Western blotting. Breast cancer cells in 3D culture displayed an attenuated response to both endocrine agents and trastuzumab compared with cells cultured in traditional 2D monolayers. Underlying this phenomenon was an apparent matrix-induced shift from AKT to MAPK signalling; consequently, suppression of MAPK in 3D cultures restores therapeutic response. These data suggest that breast cancer cells in 3D culture display a reduced sensitivity to therapeutic agents which may be mediated by internal MAPK-mediated signalling. Targeting of adaptive pathways that maintain growth in 3D culture may represent an effective strategy to improve therapeutic response clinically.

Pan-RAF and MEK vertical inhibition enhances therapeutic response in non-V600 BRAF mutant cells.

PubMed

Molnár, Eszter; Rittler, Dominika; Baranyi, Marcell; Grusch, Michael; Berger, Walter; Döme, Balázs; Tóvári, József; Aigner, Clemens; Tímár, József; Garay, Tamás; Hegedűs, Balázs

2018-05-08

Currently, there are no available targeted therapy options for non-V600 BRAF mutated tumors. The aim of this study was to investigate the effects of RAF and MEK concurrent inhibition on tumor growth, migration, signaling and apoptosis induction in preclinical models of non-V600 BRAF mutant tumor cell lines. Six BRAF mutated human tumor cell lines CRL5885 (G466 V), WM3629 (D594G), WM3670 (G469E), MDAMB231 (G464 V), CRL5922 (L597 V) and A375 (V600E as control) were investigated. Pan-RAF inhibitor (sorafenib or AZ628) and MEK inhibitor (selumetinib) or their combination were used in in vitro viability, video microscopy, immunoblot, cell cycle and TUNEL assays. The in vivo effects of the drugs were assessed in an orthotopic NSG mouse breast cancer model. All cell lines showed a significant growth inhibition with synergism in the sorafenib/AZ628 and selumetinib combination. Combination treatment resulted in higher Erk1/2 inhibition and in increased induction of apoptosis when compared to single agent treatments. However, single selumetinib treatment could cause adverse therapeutic effects, like increased cell migration in certain cells, selumetinib and sorafenib combination treatment lowered migratory capacity in all the cell lines. Importantly, combination resulted in significantly increased tumor growth inhibition in orthotropic xenografts of MDAMB231 cells when compared to sorafenib - but not to selumetinib - treatment. Our data suggests that combined blocking of RAF and MEK may achieve increased therapeutic response in non-V600 BRAF mutant tumors.

A Novel Resolvin-Based Strategy for Limiting Acetaminophen Hepatotoxicity

PubMed Central

Patel, Suraj J; Luther, Jay; Bohr, Stefan; Iracheta-Vellve, Arvin; Li, Matthew; King, Kevin R; Chung, Raymond T; Yarmush, Martin L

2016-01-01

Objectives: Acetaminophen (APAP)-induced hepatotoxicity is a major cause of morbidity and mortality. The current pharmacologic treatment for APAP hepatotoxicity, N-acetyl cysteine (NAC), targets the initial metabolite-driven injury but does not directly affect the host inflammatory response. Because of this, NAC is less effective if given at later stages in the disease course. Resolvins, a novel group of lipid mediators shown to attenuate host inflammation, may be a therapeutic intervention for APAP hepatotoxicity. Methods: The temporal patterns of liver injury and neutrophil activation were investigated in a murine model of APAP hepatotoxicity. In addition, the effect of neutrophil depletion and resolvin administration on the severity of liver injury induced by APAP was studied. In vitro studies to investigate the mechanism of resolvin effect on hepatocyte injury and neutrophil adhesion were performed. Results: We demonstrate that hepatic neutrophil activation occurs secondary to the initial liver injury induced directly by APAP. We also show that neutrophil depletion attenuates APAP-induced liver injury, and administration of resolvins hours after APAP challenge not only attenuates liver injury, but also extends the therapeutic window eightfold compared to NAC. Mechanistic in vitro analysis highlights resolvins' ability to inhibit neutrophil attachment to endothelial cells in the presence of the reactive metabolite of APAP. Conclusions: This study highlights the ability of resolvins to protect against APAP-induced liver injury and extend the therapeutic window compared to NAC. Although the mechanism for resolvin-mediated hepatoprotection is likely multifactorial, inhibition of neutrophil infiltration and activation appears to play an important role. PMID:26986653

[Prophylactic and therapeutic effect of oxymatrine on D-galactosamine-induced rat liver fibrosis].

PubMed

Yang, Wenzhuo; Zeng, Minde; Fan, Zhuping; Mao, Yimin; Song, Yulin; Jia, Yitao; Lu, Lungen; Chen, Cheng Wei; Peng, Yan Shen; Zhu, Hong Yin

2002-06-01

To investigate the prophylactic and therapeutic effect of oxymatrine on experimental liver fibrosis and to reveal its mechanism. By establishing D-galactosamine-induced rat liver fibrosis model, we observed the effect of oxymatrine on serum and tissue biochemical indexes, content of liver hydroxyline, expression of TGF?1 mRNA and changes of tissue pathology. There was a decline of liver hydroxyline and serum AST and ALT in oxymatrine group compared to those of the D-GalN group. The hydroxyline content in oxymatrine pretreatment group was (0.50 0.11)mug/mg compared with (0.99 0.14)mug/mg in D-GalN group (t=8.366, P<0.01). The content in oxymatrine treatment group was (0.44 0.04)mug/mg compared with 0.70 0.06 in D-GalN group (t=9.839, P<0.01). The SOD activity was (149.81 15.28) NU/mg in oxymatrine pretreatment group and (95.22 16.33) NU/mg in the model group (t=7.309, P<0.01); (157.68 19.54) NU/mg in the treatment group compared with (119.88 14.94) NU/mg in the model group (t=4.348, P<0.01). MDA in the pretreatment group was (2.06 0.17) nmol/mg, lower than (4.57 0.37) nmol/mg in the model group (t=17.529, P<0.01). In the treatment group, it was (1.76 0.24)nmol/mg, lower than (3.10 0.17) nmol/mg in the model group (t=12.697, P<0.01). TGF?1 mRNA reduced in the pretreatment and treatment groups as compared with that in the model group (0.21 0.01 vs 0.50 0.01, t=48.665, P<0.01; 0.18 0.02 vs 0.38 0.01, t=22.464, P<0.01). Electron microscopy showed that oxymatrine group had milder hepatocyte degeneration and less fibrosis accumulation than did the model group. Microscopy revealed wide septa expansion from the portal area to the central venous, piecemeal and confluent necrosis and pseudo-nodular formation in part of the lobular in the model group. While in oxymatrine group these lesions were much improved. Oxymatrine shows prophylactic and therapeutic effect in D-galactosamine induced rat liver fibrosis. This is partly by protecting hepatocyte and suppressing fibrosis accumulation through anti-lipoperoxidation.

Therapeutic effects of selective atrioventricular node vagal stimulation in atrial fibrillation and heart failure.

PubMed

Zhang, Youhua; Popović, Zoran B; Kusunose, Kenya; Mazgalev, Todor N

2013-01-01

Atrial fibrillation (AF) and heart failure (HF) frequently coexist. We have previously demonstrated that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during AF. Due to withdrawal of vagal activity in HF, the therapeutic effects of AVN-VS may be compromised in the combined condition of AF and HF. Accordingly, this study was designed to evaluate the therapeutic effects of AVN-VS to control ventricular rate in AF and HF. A combined model of AF and HF was created by implanting a dual chamber pacemaker in 24 dogs. A newly designed bipolar electrode was inserted into the ganglionic AVN fat pad and connected to a nerve stimulator for delivering AVN-VS. In all dogs, HF was induced by high rate ventricular pacing at 220 bpm for 4 weeks. AF was then induced and maintained by rapid atrial pacing at 600 bpm after discontinuation of ventricular pacing. These HF + AF dogs were randomized into control (n = 9) and AVN-VS (n = 15) groups. In the latter group, vagal stimulation (310 μs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. Compared with the control, AVN-VS had a consistent effect on ventricular rate slowing (by >50 bpm, all P < 0.001) during the entire 6-month observation period that was associated with left ventricular functional improvement. Moreover, AVN-VS was well tolerated by the treated animals. AVN-VS achieved consistent rate slowing, which was associated with improved ventricular function in a canine AF and HF model. Thus, AVN-VS may be a novel, effective therapeutic option in the combined condition of AF and HF. © 2012 Wiley Periodicals, Inc.

[Preventive and therapeutic effect of genetic vaccine based on recombinant alpha virus against mouse mastocytoma P815].

PubMed

Ni, Bing; Yang, Ri-gao; Li, Yan-qiu; Wu, Yu-zhang

2004-01-01

To explore the immunological effect of genetic vaccine based on alpha-virus and to seek out better forms of gene vaccines. Expression plasmid P1A/pSMART2a and packaging plasmid helper were cotransfected into mammalian 293 cells by calcium phosphate precipitation method and high level of recombinant alpha-virus P1A/SFV was prepared. Following identification of rSFV and its expression, BALB/c mice were inoculated with rSFV, and the production of antigen-specific antibody and the cytotoxic effect of CTLs were determined. In the preventive and therapeutic experiments, the percents of tumor-free and of survival mice immunized with rSFV were observed. The recombinant SFV could express correctly in cultured cells. After being inoculated into the mice, rSFV could prime stronger CTL response than that in control mice. When the ratio of E/T cells was 100:1, the (51)Cr release rate reached 75%. No antibody could be detected in mice from all groups. The immunological effect of P1A/SFV among all groups was the best in both preventive and therapeutic experiment within experimental deadline. On 60th day in preventive experiment, the percent of tumor-free animal in P1A/SFV group reached 60%, whereas that was only 20% in P1A/pCI-neogroup. On 60th day in therapeutic experiment, survival rate of mice in P1A/SFV group reached 50%, but only 10% mice could survive in all control groups. Compared with common gene vaccines, the genetic vaccine based on recombinant SFV has the best immunological effect, which provides some new strategies for clinical genetic therapy of tumors.

The Effect of Brief Exposure to Sub-Therapeutic Concentrations of Chlorhexidine Digluconate on the Susceptibility of Staphylococci to Platelet Microbicidal Protein.

PubMed

Ivanov, Iuri B; Gritsenko, Viktor A; Kuzmin, Michael D

2015-06-01

Antiseptic agents are widely used in hospitals and are essential when prevention and control of nosocomial infections is required. It is necessary to consider several aspects that affect the biocide activity because they have direct impact on the nosocomial infection rate. Organisms belonging to the Staphylococcus genus are involved in such infections and chlorhexidine digluconate (CHXD) is one of the most used antiseptic agents for human and animal health. In the context of such infections, anti-bacterial peptides have been isolated from platelets and have been termed platelet microbicidal proteins (PMP). Platelet microbicidal proteins have been shown to enhance the bacterial inhibitory activities of sub-therapeutic concentrations of antibiotics. The main objective of this study was to investigate the effect of brief exposure to different sub-therapeutic concentrations of CHXD on the susceptibility of staphylococci to PMP. The influence of brief exposure to three different sub-therapeutic concentrations of CHXD (0.005%, 0.0025%, and 0.00125%) on the subsequent staphylocidal effect of PMP was evaluated. Among all clinical staphylococcal strains studied, all isolates were considered to be resistant to the bactericidal action of PMP. Exposure of staphylococci to CHXD prior to PMP resulted in significantly increased staphylococcal killing compared with the killing achieved with PMP alone. This enhanced effect was most marked for concentrations of CHXD of 0.005%. The combined data indicate that PMP exerts cooperative bactericidal effect with CHXD. The anti-staphylococcal PMP and CHXD synergistic activity in vitro demonstrated in the present study make these molecules potentially useful for preventing endovascular catheter-associated infections. Future research based on animal and human models is needed to elucidate the in vivo efficacies and toxicities and utility in clinical practice.

A variant of PSMD6 is associated with the therapeutic efficacy of oral antidiabetic drugs in Chinese type 2 diabetes patients.

PubMed

Chen, Miao; Hu, Cheng; Zhang, Rong; Jiang, Feng; Wang, Jie; Peng, Danfeng; Tang, Shanshan; Sun, Xue; Yan, Jing; Wang, Shiyun; Wang, Tao; Bao, Yuqian; Jia, Weiping

2015-05-29

The PSMD6 variant rs831571 has been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of this variant with therapeutic effects of oral antidiabetic drugs in Chinese T2DM patients. 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks, and the therapeutic effects were compared. In the rosiglitazone cohort, rs831571 showed significant associations with fasting plasma glucose (FPG), 2-h glucose and decrement of glycated haemoglobin (HbA1c) levels after 24 weeks of treatment (P = 0.0368, 0.0468 and 0.0247, respectively). The C allele was significantly associated with a better attainment of FPG at 24 and 32 weeks (P = 0.0172 and 0.0257, respectively). Survival analyses showed CC homozygotes were more likely to attain a standard FPG level (P = 0.0654). In the repaglinide cohort, rs831571 was significantly associated with decreased HbA1c levels after 24 weeks of treatment, the homeostatic model assessment of insulin resistance and fasting insulin level after 48 weeks of treatment with repaglinide (P = 0.0096, 0235 and 0.0212, respectively). In conclusion, we observed that the PSMD6 variant rs831571 might be associated with the therapeutic effects of rosiglitazone and repaglinide in Chinese T2DM patients. However, these findings need to be confirmed in the future.

A variant of PSMD6 is associated with the therapeutic efficacy of oral antidiabetic drugs in Chinese type 2 diabetes patients

PubMed Central

Chen, Miao; Hu, Cheng; Zhang, Rong; Jiang, Feng; Wang, Jie; Peng, Danfeng; Tang, Shanshan; Sun, Xue; Yan, Jing; Wang, Shiyun; Wang, Tao; Bao, Yuqian; Jia, Weiping

2015-01-01

The PSMD6 variant rs831571 has been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of this variant with therapeutic effects of oral antidiabetic drugs in Chinese T2DM patients. 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks, and the therapeutic effects were compared. In the rosiglitazone cohort, rs831571 showed significant associations with fasting plasma glucose (FPG), 2-h glucose and decrement of glycated haemoglobin (HbA1c) levels after 24 weeks of treatment (P = 0.0368, 0.0468 and 0.0247, respectively). The C allele was significantly associated with a better attainment of FPG at 24 and 32 weeks (P = 0.0172 and 0.0257, respectively). Survival analyses showed CC homozygotes were more likely to attain a standard FPG level (P = 0.0654). In the repaglinide cohort, rs831571 was significantly associated with decreased HbA1c levels after 24 weeks of treatment, the homeostatic model assessment of insulin resistance and fasting insulin level after 48 weeks of treatment with repaglinide (P = 0.0096, 0235 and 0.0212, respectively). In conclusion, we observed that the PSMD6 variant rs831571 might be associated with the therapeutic effects of rosiglitazone and repaglinide in Chinese T2DM patients. However, these findings need to be confirmed in the future. PMID:26024304

Effect of therapeutic footwear on foot reulceration in patients with diabetes: a randomized controlled trial.

PubMed

Reiber, Gayle E; Smith, Douglas G; Wallace, Carolyn; Sullivan, Katrina; Hayes, Shane; Vath, Christy; Maciejewski, Matthew L; Yu, Onchee; Heagerty, Patrick J; LeMaster, Joseph

2002-05-15

Many people with diabetes experience lower-limb ulcers. Footwear has been implicated as a primary cause of foot ulcers, yet research is limited on the efficacy of shoe and insert combinations to prevent reulceration. To determine whether extra-depth and -width therapeutic shoes used with 2 types of inserts reduce reulceration in diabetic individuals with a history of foot ulcer. Randomized clinical trial of 400 diabetes patients with history of foot ulcer in 2 Washington State health care organizations who did not require custom shoes for foot deformity and were enrolled between August 1997 and December 1998 and followed up for 2 years. Data collected at regular intervals documented physical, foot, and diabetes characteristics; footwear use; foot lesions; and ulcers. Participants were randomly assigned to receive 3 pairs of therapeutic shoes and 3 pairs of customized medium-density cork inserts with a neoprene closed-cell cover (n = 121); to receive 3 pairs of therapeutic shoes and 3 pairs of prefabricated, tapered polyurethane inserts with a brushed nylon cover (n = 119); or to wear their usual footwear (controls; n = 160). Foot reulceration, compared among the 3 groups. Two-year cumulative reulceration incidence across the 3 groups was low: 15% in the cork-insert group, 14% in the prefabricated-insert group, and 17% in controls. In the intent-to-treat analysis, patients assigned to therapeutic shoes did not have a significantly lower risk of reulceration compared with controls (risk ratio [RR] for the cork-insert group, 0.88; 95% confidence interval [CI], 0.51-1.52 and RR the for prefabricated-insert group, 0.85; 95% CI, 0.48-1.48). All ulcer episodes in patients assigned to therapeutic shoes and 88% wearing nonstudy shoes occurred in patients with foot insensitivity. This study of persons without severe foot deformity does not provide evidence to support widespread dispensing of therapeutic shoes and inserts to diabetic patients with a history of foot ulcer. Study shoes and custom cork or preformed polyurethane inserts conferred no significant ulcer reduction compared with control footwear. This study suggests that careful attention to foot care by health care professionals may be more important than therapeutic footwear but does not negate the possibility that special footwear is beneficial in persons with diabetes who do not receive such close attention to foot care by their health care providers or in individuals with severe foot deformities.

[Therapeutic effect of cervical Jiaji electroacupuncture on postoperative intractable hiccup of liver neoplasms].

PubMed

Zhang, S K; Gao, W B; Liu, Y; He, H

2018-02-23

Objective: To evaluate the therapeutic effect of cervical Jiaji electroacupuncture on postoperative intractable hiccup of liver neoplasms. Methods: A total of 39 patients with postoperative intractable hiccup of liver neoplasms in The First Affiliated Hospital of Heilongjiang University of Chinese Medicine from May 2013 to May 2017 were collected and divided into 2 groups randomly. The electroacupuncture group included 20 cases, the control group included 19 cases. Patients in the electroacupuncture group were treated by cervical Jiaji electroacupuncture (located in C3-5, sympathetic ganglion), while the control group were treated by metoclopramide combined with chlorpromazine for three days. The therapeutic effects of two groups were compared and the onset time were recorded. Results: Total effective rates of electroacupuncture group and control group were 95.0% and 47.4%, respectively. The onset time in electroacupuncture group and control group were (14.8±3.3) h and (30.5±3.1) h, respectively ( P <0.01). Ten cases who resisted the control treatment were then treated by electroacupuncture for 3 days, 6 cases were recovered, 3 cases became better, while 1 case demonstrated no response. No serious adverse reactions were appeared in each group. Conclusion: Cervical Jiaji electroacupuncture is an effective and safe treatment for postoperative intractable hiccup of liver neoplasms, and it can be used as a remedy for intractable hiccup patients who don't respond to drug treatment.

A comparative evaluation of the chelators H4octapa and CHX-A″-DTPA with the therapeutic radiometal (90)Y.

PubMed

Price, Eric W; Edwards, Kimberly J; Carnazza, Kathryn E; Carlin, Sean D; Zeglis, Brian M; Adam, Michael J; Orvig, Chris; Lewis, Jason S

2016-09-01

To compare the radiolabeling performance, stability, and practical efficacy of the chelators CHX-A″-DTPA and H4octapa with the therapeutic radiometal (90)Y. The bifunctional chelators p-SCN-Bn-H4octapa and p-SCN-Bn-CHX-A″-DTPA were conjugated to the HER2-targeting antibody trastuzumab. The resulting immunoconjugates were radiolabeled with (90)Y to compare radiolabeling efficiency, in vitro and in vivo stability, and in vivo performance in a murine model of ovarian cancer. High radiochemical yields (>95%) were obtained with (90)Y-CHX-A″-DTPA-trastuzumab and (90)Y-octapa-trastuzumab after 15min at room temperature. Both (90)Y-CHX-A″-DTPA-trastuzumab and (90)Y-octapa-trastuzumab exhibited excellent in vitro and in vivo stability. Furthermore, the radioimmunoconjugates displayed high tumoral uptake values (42.3±4.0%ID/g for (90)Y-CHX-A″-DTPA-trastuzumab and 30.1±7.4%ID/g for (90)Y-octapa-trastuzumab at 72h post-injection) in mice bearing HER2-expressing SKOV3 ovarian cancer xenografts. Finally, (90)Y radioimmunotherapy studies performed in tumor-bearing mice demonstrated that (90)Y-CHX-A″-DTPA-trastuzumab and (90)Y-octapa-trastuzumab are equally effective therapeutic agents, as treatment with both radioimmunoconjugates yielded substantially decreased tumor growth compared to controls. Ultimately, this work demonstrates that the acyclic chelators CHX-A″-DTPA and H4octapa have comparable radiolabeling, stability, and in vivo performance, making them both suitable choices for applications requiring (90)Y. Copyright © 2016 Elsevier Inc. All rights reserved.

Early effects of duloxetine on emotion recognition in healthy volunteers

PubMed Central

Bamford, Susan; Penton-Voak, Ian; Pinkney, Verity; Baldwin, David S; Munafò, Marcus R; Garner, Matthew

2015-01-01

The serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine is an effective treatment for major depression and generalised anxiety disorder. Neuropsychological models of antidepressant drug action suggest therapeutic effects might be mediated by the early correction of maladaptive biases in emotion processing, including the recognition of emotional expressions. Sub-chronic administration of duloxetine (for two weeks) produces adaptive changes in neural circuitry implicated in emotion processing; however, its effects on emotional expression recognition are unknown. Forty healthy participants were randomised to receive either 14 days of duloxetine (60 mg/day, titrated from 30 mg after three days) or matched placebo (with sham titration) in a double-blind, between-groups, repeated-measures design. On day 0 and day 14 participants completed a computerised emotional expression recognition task that measured sensitivity to the six primary emotions. Thirty-eight participants (19 per group) completed their course of tablets and were included in the analysis. Results provide evidence that duloxetine, compared to placebo, may reduce the accurate recognition of sadness. Drug effects were driven by changes in participants’ ability to correctly detect subtle expressions of sadness, with greater change observed in the placebo relative to the duloxetine group. These effects occurred in the absence of changes in mood. Our preliminary findings require replication, but complement recent evidence that sadness recognition is a therapeutic target in major depression, and a mechanism through which SNRIs could resolve negative biases in emotion processing to achieve therapeutic effects. PMID:25759400

Anti-Inflammatory Effects of Rebamipide Eyedrop Administration on Ocular Lesions in a Murine Model of Primary Sjögren's Syndrome

PubMed Central

Arakaki, Rieko; Eguchi, Hiroshi; Yamada, Akiko; Kudo, Yasusei; Iwasa, Akihiko; Enkhmaa, Tserennadmid; Hotta, Fumika; Mitamura-Aizawa, Sayaka; Mitamura, Yoshinori; Hayashi, Yoshio; Ishimaru, Naozumi

2014-01-01

Background Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren's syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown. Methods and Finding Reb eyedrops were administered to the murine model of SS aged 4–8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment. Conclusion Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces. PMID:24866156

Magnetic Seizure Therapy for Unipolar and Bipolar Depression: A Systematic Review

PubMed Central

Cretaz, Eric; Brunoni, André R.

2015-01-01

Objective. Magnetic seizure therapy (MST) is a novel, experimental therapeutic intervention, which combines therapeutic aspects of electroconvulsive therapy (ECT) and transcranial magnetic stimulation, in order to achieve the efficacy of the former with the safety of the latter. MST might prove to be a valuable tool in the treatment of mood disorders, such as major depressive disorder (MDD) and bipolar disorder. Our aim is to review current literature on MST. Methods. OVID and MEDLINE databases were used to systematically search for clinical studies on MST. The terms “magnetic seizure therapy,” “depression,” and “bipolar” were employed. Results. Out of 74 studies, 8 met eligibility criteria. There was considerable variability in the methods employed and samples sizes were small, limiting the generalization of the results. All studies focused on depressive episodes, but few included patients with bipolar disorder. The studies found reported significant antidepressant effects, with remission rates ranging from 30% to 40%. No significant cognitive side effects related to MST were found, with a better cognitive profile when compared to ECT. Conclusion. MST was effective in reducing depressive symptoms in mood disorders, with generally less side effects than ECT. No study focused on comparing MST to ECT on bipolar depression specifically. PMID:26075100

Adoptive transfer of induced-Treg cells effectively attenuates murine airway allergic inflammation.

PubMed

Xu, Wei; Lan, Qin; Chen, Maogen; Chen, Hui; Zhu, Ning; Zhou, Xiaohui; Wang, Julie; Fan, Huimin; Yan, Chun-Song; Kuang, Jiu-Long; Warburton, David; Togbe, Dieudonnée; Ryffel, Bernhard; Zheng, Song-Guo; Shi, Wei

2012-01-01

Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4(+)FoxP3(+)) and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma.

Adoptive Transfer of Induced-Treg Cells Effectively Attenuates Murine Airway Allergic Inflammation

PubMed Central

Chen, Maogen; Chen, Hui; Zhu, Ning; Zhou, Xiaohui; Wang, Julie; Fan, Huimin; Yan, Chun-Song; Kuang, Jiu-Long; Warburton, David; Togbe, Dieudonnée; Ryffel, Bernhard; Zheng, Song-Guo; Shi, Wei

2012-01-01

Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4+FoxP3+) and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma. PMID:22792275

Effect of antimicrobial compounds tylosin and chlortetracycline during batch anaerobic swine manure digestion.

PubMed

Stone, James J; Clay, Sharon A; Zhu, Zhenwei; Wong, Kwok L; Porath, Laura R; Spellman, Garth M

2009-10-01

Tylosin and chlortetracycline (CTC) are antimicrobial chemicals that are fed to >45% of the US swine herds at therapeutic and sub-therapeutic dosages to enhance growth rates and treat swine health problems. These compounds are poorly absorbed during digestion so that the bioactive compound or metabolites are excreted. This study investigated the degradation and stabilization of swine manure that contained no additives and compared the observed processes with those of manure containing either tylosin or CTC. The batch anaerobic incubation lasted 216 days. The breakdown of insoluble organic matter through anaerobic hydrolysis reactions was faster for manure containing CTC compared with tylosin or no-antimicrobial treatments. Volatile fatty acid (VFA) accumulation, including acetate, butyrate, and propionate, was greater for CTC-containing manure compared to tylosin and no-antimicrobial treatments. The relative abundance of two aceticlastic methanogens, Methanosaetaceae and Methanosarcinaceae spp., were less for CTC manure than manure with no-antimicrobial treatment. In addition, generation of methane and carbon dioxide was inhibited by 27.8% and 28.4%, respectively, due to the presence of CTC. Tylosin effects on manure degradation were limited, however the relative abundance of Methanosarcinaceae spp. was greater than found in the CTC or no-antimicrobial manures. These data suggest that acetate and other C-1 VFA compounds would be effectively utilized during methanogenesis in the presence of tylosin.

Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis.

PubMed

Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon

2015-02-01

Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.

Antipsychotic profile of cannabidiol and rimonabant in an animal model of emotional context processing in schizophrenia.

PubMed

Levin, Raquel; Almeida, Valeria; Peres, Fernanda Fiel; Calzavara, Mariana Bendlin; da Silva, Neide Derci; Suiama, Mayra Akimi; Niigaki, Suzy Tamie; Zuardi, Antonio Waldo; Hallak, Jaime Eduardo Cecilio; Crippa, Jose Alexandre; Abílio, Vanessa Costhek

2012-01-01

Clinical and neurobiological findings suggest that cannabinoids and their receptors are implicated in schizophrenia. Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa plant, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects. We have recently reported that spontaneously hypertensive rats (SHR) present a deficit in contextual fear conditioning (CFC) that is specifically ameliorated by antipsychotics and aggravated by proschizophrenia manipulations. These results led us to suggest that the CFC deficit presented by SHR could be used as a model to study emotional processing impairment in schizophrenia. The aim of this study is to evaluate the effects of CBD and rimonabant (CB1 receptor antagonist) on the contextual fear conditioning in SHR and Wistar rats (WR). Rats were submitted to CFC task after treatment with different doses of CBD (experiment 1) and rimonabant (experiment 2). In experiment 1, SHR showed a decreased freezing response when compared to WR that was attenuated by 1 mg/kg CBD. Moreover, all CBD-treated WR presented a decreased freezing response when compared to control rats. In experiment 2, SHR showed a decreased freezing response when compared to WR that was attenuated by 3 mg/kg rimonabant. Our results suggest a potential therapeutical effect of CBD and rimonabant to treat the emotional processing impairment presented in schizophrenia. In addition, our results reinforce the anxiolytic profile of CBD.

Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance

PubMed Central

Liu, Meilian; Xiang, Ruihua; Wilk, Sarah Ann; Zhang, Ning; Sloane, Lauren B.; Azarnoush, Kian; Zhou, Lijun; Chen, Hongzhi; Xiang, Guangda; Walter, Christi A.; Austad, Steven N.; Musi, Nicolas; DeFronzo, Ralph A.; Asmis, Reto; Scherer, Philipp E.; Dong, Lily Q.; Liu, Feng

2012-01-01

The antidiabetic and antiatherosclerotic effects of adiponectin make it a desirable drug target for the treatment of metabolic and cardiovascular diseases. However, the adiponectin-based drug development approach turns out to be difficult due to extremely high serum levels of this adipokine. On the other hand, a significant correlation between adiponectin multimerization and its insulin-sensitizing effects has been demonstrated, suggesting a promising alternative therapeutic strategy. Here we show that transgenic mice overexpressing disulfide bond A oxidoreductase-like protein in fat (fDsbA-L) exhibited increased levels of total and the high-molecular-weight form of adiponectin compared with wild-type (WT) littermates. The fDsbA-L mice also displayed resistance to diet-induced obesity, insulin resistance, and hepatic steatosis compared with WT control mice. The protective effects of DsbA-L overexpression on diet-induced insulin resistance, but not increased body weight and fat cell size, were significantly decreased in adiponectin-deficient fDsbA-L mice (fDsbA-L/Ad−/−). In addition, the fDsbA-L/Ad−/− mice displayed greater activity and energy expenditure compared with adiponectin knockout mice under a high-fat diet. Taken together, our results demonstrate that DsbA-L protects mice from diet-induced obesity and insulin resistance through adiponectin-dependent and independent mechanisms. In addition, upregulation of DsbA-L could be an effective therapeutic approach for the treatment of obesity and its associated metabolic disorders. PMID:22807031

Validity, Significance, Strengths, Limitations, and Evidentiary Value of Real-World Clinical Data for Combination Therapy in Alzheimer's Disease: Comparison of Efficacy and Effectiveness Studies

PubMed Central

Atri, Alireza; Rountree, Susan D.; Lopez, Oscar L.; Doody, Rachelle S.

2012-01-01

Background Randomized controlled efficacy trials (RCTs), the scientific gold standard, are required for regulatory approval of Alzheimer's disease (AD) interventions, yet provide limited information regarding real-world therapeutic effectiveness. Objective: To compare the nature of evidence regarding the combination of approved AD treatments from RCTs versus long-term observational controlled studies (LTOCs). Methods Comparisons of strengths, limitations, and evidence level for monotherapy [cholinesterase inhibitor (ChEI) or memantine] and combination therapy (ChEI + memantine) in RCTs versus LTOCs. Results RCTs examined highly selected populations over months. LTOCs collected data across multiple AD stages in large populations over many years. RCTs and LTOCs show similar patterns favoring combination over monotherapy over placebo/no treatment. Long-term combination therapy compared to monotherapy reduced cognitive and functional decline and delayed time to nursing home admission. Persistent treatment was associated with slower decline. While LTOCs used control groups, adjusted for multiple covariates, had higher external validity, and favorable ethical, practical and cost considerations, their limitations included potential selection bias due to lack of placebo comparisons and randomization. Conclusions Naturalistic LTOCs provide complementary long-term level II evidence to complement level I evidence from short-term RCTs regarding therapeutic effectiveness in AD that may otherwise be unobtainable. A coordinated strategy/consortium to pool LTOC data from multiple centers to estimate long-term comparative effectiveness, risks/benefits, and costs of AD treatments is needed. PMID:22327239

Increasing nerve agent treatment efficacy by P-glycoprotein inhibition.

PubMed

Joosen, Marloes J A; Vester, Stefanie M; Hamelink, Jouk; Klaassen, Steven D; van den Berg, Roland M

2016-11-25

One of the shortcomings of current treatment of nerve agent poisoning is that not all drugs effectively penetrate the blood-brain barrier (BBB), whereas most nerve agents easily do. P-glycoprotein (Pgp) efflux transporters at the BBB may contribute to this aspect. It was previously shown that Pgp inhibition by tariquidar enhanced the efficacy of nerve agent treatment when administered as a pretreatment. In the present study soman-induced seizures were also substantially prevented when the animals were intravenously treated with tariquidar post-poisoning, in addition to HI-6 and atropine. In these animals, approximately twice as much AChE activity was present in their brain as compared to control rats. The finding that tariquidar did not affect distribution of soman to the brain indicates that the potentiating effects were a result of interactions of Pgp inhibition with drug distribution. In line with this, atropine appeared to be a substrate for Pgp in in vitro studies in a MDR1/MDCK cell model. This indicates that tariquidar might induce brain region specific effects on atropine distribution, which could contribute to the therapeutic efficacy increase found. Furthermore, the therapeutic enhancement by tariquidar was compared to that of the less specific and less potent Pgp inhibitor cyclosporine A. This compound appeared to induce a protective effect similar to tariquidar. In conclusion, treatment with a Pgp inhibitor resulted in enhanced therapeutic efficacy of HI-6 and atropine in a soman-induced seizure model in the rat. The mechanism underlying these effects should be further investigated. To that end, the potentiating effect of nerve agent treatment should be addressed against a broader range of nerve agents, for oximes and atropine separately, and for those at lower doses. In particular when efficacy against more nerve agents is shown, a Pgp inhibitor such as tariquidar might be a valid addition to nerve agent antidotes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Immunohistochemical detection of a potential molecular therapeutic target for canine hemangiosarcoma

PubMed Central

ADACHI, Mami; HOSHINO, Yuki; IZUMI, Yusuke; TAKAGI, Satoshi

2015-01-01

Canine hemangiosarcoma (HSA) is a progressive malignant neoplasm of dogs for which there is currently no effective treatment. A recent study suggested that receptor tyrosine kinases (RTKs), the PI3K/Akt/m-TOR and MAPK pathways are all activated in canine and human HSA. The aim of the present study was to investigate the overexpression of these proteins by immunohistochemistry in canine splenic HSA to identify potential molecular therapeutic targets. A total of 10 splenic HSAs and two normal splenic samples surgically resected from dogs were sectioned and stained with hematoxylin and eosin for histological diagnosis or analyzed using immunohistochemistry. The expression of RTKs, c-kit, VEGFR-2 and PDGFR-2, as well as PI3K/Akt/m-TOR and MEK was higher in canine splenic HSAs compared to normal spleens. These proteins may therefore be potential therapeutic targets in canine splenic HSA. PMID:26685984

Immunohistochemical detection of a potential molecular therapeutic target for canine hemangiosarcoma.

PubMed

Adachi, Mami; Hoshino, Yuki; Izumi, Yusuke; Takagi, Satoshi

2016-05-03

Canine hemangiosarcoma (HSA) is a progressive malignant neoplasm of dogs for which there is currently no effective treatment. A recent study suggested that receptor tyrosine kinases (RTKs), the PI3K/Akt/m-TOR and MAPK pathways are all activated in canine and human HSA. The aim of the present study was to investigate the overexpression of these proteins by immunohistochemistry in canine splenic HSA to identify potential molecular therapeutic targets. A total of 10 splenic HSAs and two normal splenic samples surgically resected from dogs were sectioned and stained with hematoxylin and eosin for histological diagnosis or analyzed using immunohistochemistry. The expression of RTKs, c-kit, VEGFR-2 and PDGFR-2, as well as PI3K/Akt/m-TOR and MEK was higher in canine splenic HSAs compared to normal spleens. These proteins may therefore be potential therapeutic targets in canine splenic HSA.

Extravasation of a therapeutic dose of 131I-metaiodobenzylguanidine: prevention, dosimetry, and mitigation.

PubMed

Bonta, Dacian V; Halkar, Raghuveer K; Alazraki, Naomi

2011-09-01

After the extravasation of a therapeutic dose of (131)I-metaiodobenzylguanidine that produced a radiation burn to a patient's forearm, we instituted a catheter placement verification protocol. Before therapy infusion, proper placement is verified by administering 37 MBq of (99m)Tc-pertechnetate through the catheter, and monitoring activity at the administration site and on the contralateral extremity. A dosimetric model describing both high-rate and low-rate dose components was developed and predicted that the basal epidermal layer received a radiation dose consistent with the observed moist desquamation radiation skin toxicity. No extravasation incidents have occurred since the verification procedure was instituted. To protect against radiation injury from extravasation of therapeutic radionuclides, test administration of a small (99m)Tc dose with probe monitoring of comparable sites in both upper extremities appears to be an effective preventive measure.

Office-based procedures for diagnosis and treatment of esophageal pathology.

PubMed

Wellenstein, David J; Schutte, Henrieke W; Marres, Henri A M; Honings, Jimmie; Belafsky, Peter C; Postma, Gregory N; Takes, Robert P; van den Broek, Guido B

2017-09-01

Diagnostic and therapeutic office-based procedures under topical anesthesia are emerging in the daily practice of laryngologists and head and neck surgeons. Since the introduction of the transnasal esophagoscope, office-based procedures for the esophagus are increasingly performed. We conducted a systematic review of literature on office-based procedures under topical anesthesia for the esophagus. Transnasal esophagoscopy is an extensively investigated office-based procedure. This procedure shows better patient tolerability and equivalent accuracy compared to conventional transoral esophagoscopy, as well as time and cost savings. Secondary tracheoesophageal puncture, esophageal dilatation, esophageal sphincter injection, and foreign body removal are less investigated, but show promising results. With the introduction of the transnasal esophagoscope, an increasing number of diagnostic and therapeutic office-based procedures for the esophagus are possible, with multiple advantages. Further investigation must prove the clinical feasibility and effectiveness of the therapeutic office-based procedures. © 2017 Wiley Periodicals, Inc.

Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptosis in human colon carcinoma cells.

PubMed

Waghela, Bhargav N; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy.

Pelvic floor muscle rehabilitation for patients with lifelong premature ejaculation: a novel therapeutic approach.

PubMed

Pastore, Antonio L; Palleschi, Giovanni; Fuschi, Andrea; Maggioni, Cristina; Rago, Rocco; Zucchi, Alessandro; Costantini, Elisabetta; Carbone, Antonio

2014-06-01

Premature ejaculation is the most common male sexual disorder. The aim of the study was to evaluate the possible therapeutic role of pelvic floor muscle rehabilitation in patients affected by lifelong premature ejaculation. We treated 40 men with lifelong premature ejaculation, reporting, a baseline intravaginal ejaculatory latency time (IELT) ≤ 1 min, with 12-week pelvic floor muscle rehabilitation. At the end of the rehabilitation, mean IELTs were calculated to evaluate the effectiveness of the therapy. At the end of the treatment, 33 (82.5%) of the 40 patients gained control of their ejaculatory reflex, with a mean IELT of 146.2 s (range: 123.6-152.4 s). A total of 13 out of 33 (39%) patients were evaluated at 6 months follow up, and they maintained a significant IELT (112.6 s) compared with their initial IELT (mean 39.8 s). The results obtained in our subjects treated with pelvic floor rehabilitation are promising. This therapy represents an important cost reduction compared with the standard treatment (selective serotonin reuptake inhibitors). Based on the present data, we propose pelvic floor muscle rehabilitation as a new, viable therapeutic option for the treatment of premature ejaculation.

Short-duration therapeutic massage reduces postural upper trapezius muscle activity.

PubMed

Domingo, Antoinette R; Diek, Melissa; Goble, Kathleen M; Maluf, Katrina S; Goble, Daniel J; Baweja, Harsimran S

2017-01-18

Massage therapy has historically been used as a therapeutic treatment to help reduce pain and promote relaxation. The aim of this study was to investigate the effect of therapeutic massage on the upper trapezius muscles, which are commonly associated with increased muscle tension. This was a randomized crossover study. Seventeen healthy individuals (nine women; 24.5±4.0 years) participated in the study. All individuals participated in two sessions that were held 24 h apart. In one of the sessions, the participants received a moderate pressure massage applied to the shoulders and neck. In the other session, participants sat quietly. The order of the sessions was counterbalanced across participants. Muscle activity, as measured by surface electromyography, of the upper trapezius muscles was recorded. The amount of muscle activity change following massage was compared with the change in muscle activity following quiet sitting. Muscle activity of the upper trapezius reduced significantly (19.3%; P=0.004) following massage compared with muscle activity following quiet sitting (1.0%). Our findings suggest that short-duration moderate pressure massage leads to a reduction in upper trapezius muscle activity. This result has potential implications for clinical populations such as those with chronic neck pain.

Therapeutic Options in Idiopathic Burning Mouth Syndrome: Literature Review

PubMed Central

Miziara, Ivan; Chagury, Azis; Vargas, Camila; Freitas, Ludmila; Mahmoud, Ali

2014-01-01

Introduction Burning mouth syndrome (BMS) is characterized by a burning sensation in the tongue, palate, lips, or gums of no well-defined etiology. The diagnosis and treatment for primary BMS are controversial. No specific laboratory tests or diagnostic criteria are well established, and the diagnosis is made by excluding all other possible disorders. Objective To review the literature on the main treatment options in idiopathic BMS and compare the best results of the main studies in 15 years. Data Synthesis We conducted a literature review on PubMed/MEDLINE, SciELO, and Cochrane-BIREME of work in the past 15 years, and only selected studies comparing different therapeutic options in idiopathic BMS, with preference for randomized and double-blind controlled studies. Final Comments Topical clonazepam showed good short-term results for the relief of pain, although this was not presented as a definitive cure. Similarly, α-lipoic acid showed good results, but there are few randomized controlled studies that showed the long-term results and complete remission of symptoms. On the other hand, cognitive therapy is reported as a good and lasting therapeutic option with the advantage of not having side effects, and it can be combined with pharmacologic therapy. PMID:25992157

Biologically Targeted Therapeutics in Pediatric Brain Tumors

PubMed Central

Nageswara Rao, Amulya A.; Scafidi, Joseph; Wells, Elizabeth M.; Packer, Roger J.

2013-01-01

Pediatric brain tumors are often difficult to cure and involve significant morbidity when treated with traditional treatment modalities, including neurosurgery, conventional chemotherapy, and radiotherapy. During the past two decades, a clearer understanding of tumorigenesis, molecular growth pathways, and immune mechanisms in the pathogenesis of cancer has opened up promising avenues for therapy. Pediatric clinical trials with novel biologic agents are underway to treat various pediatric brain tumors, including high and low grade gliomas and embryonal tumors. As the therapeutic potential of these agents undergoes evaluation, their toxicity profiles are also becoming better understood. These agents have potentially better central nervous system penetration and lower toxicity profiles compared with conventional chemotherapy. In infants and younger children, biologic agents may prove to be of equal or greater efficacy compared with traditional chemotherapy and radiation therapy, and may reduce the deleterious side effects of traditional therapeutics on the developing brain. Molecular pathways implicated in pediatric brain tumors, agents that target these pathways, and current clinical trials are reviewed. Associated neurologic toxicities will be discussed subsequently. Considerable work is needed to establish the efficacy of these agents alone and in combination, but pediatric neurologists should be aware of these agents and their rationale. PMID:22490764

Biologically targeted therapeutics in pediatric brain tumors.

PubMed

Nageswara Rao, Amulya A; Scafidi, Joseph; Wells, Elizabeth M; Packer, Roger J

2012-04-01

Pediatric brain tumors are often difficult to cure and involve significant morbidity when treated with traditional treatment modalities, including neurosurgery, conventional chemotherapy, and radiotherapy. During the past two decades, a clearer understanding of tumorigenesis, molecular growth pathways, and immune mechanisms in the pathogenesis of cancer has opened up promising avenues for therapy. Pediatric clinical trials with novel biologic agents are underway to treat various pediatric brain tumors, including high and low grade gliomas and embryonal tumors. As the therapeutic potential of these agents undergoes evaluation, their toxicity profiles are also becoming better understood. These agents have potentially better central nervous system penetration and lower toxicity profiles compared with conventional chemotherapy. In infants and younger children, biologic agents may prove to be of equal or greater efficacy compared with traditional chemotherapy and radiation therapy, and may reduce the deleterious side effects of traditional therapeutics on the developing brain. Molecular pathways implicated in pediatric brain tumors, agents that target these pathways, and current clinical trials are reviewed. Associated neurologic toxicities will be discussed subsequently. Considerable work is needed to establish the efficacy of these agents alone and in combination, but pediatric neurologists should be aware of these agents and their rationale. Copyright © 2012 Elsevier Inc. All rights reserved.

Therapeutic and prophylactic utility of the memory-enhancing drug donepezil hydrochloride on cognition of patients undergoing electroconvulsive therapy: a randomized controlled trial.

PubMed

Prakash, Jyoti; Kotwal, Atul; Prabhu, Hra

2006-09-01

Substantial progress has been made in identifying how the treatment parameters used in electroconvulsive therapy (ECT) impact its cognitive side effects. However, there is limited information regarding the role of memory enhancers in post-ECT cognitive disturbances. We evaluated the therapeutic and prophylactic efficacy of the memory-enhancing drug donepezil hydrochloride on cognition of patients undergoing ECT. A triple blind (the study subjects, clinician assessing the cognition, and the data analyst were unaware of subject allocation for trial assessment) randomized controlled trial was carried out in a General Hospital Psychiatry Unit. Subjects were randomized into 2 groups. One group received ECT with placebo, whereas the other group received ECT and donepezil (a memory-enhancing drug). Study participants were assessed in post-ECT period to analyze cognitive deficits and to compare the differences in 2 groups, as regards recovery of various aspects of cognition. The post-ECT recovery of various components of cognition was more rapid in patients using donepezil as compared to those not given donepezil (P < 0.05). This significant improvement in recovery time among patients receiving donepezil bears therapeutic implication in immediate post-ECT cognitive deficits.

Brief Christian and Non-Christian Rational-Emotive Therapy with Depressed Christian Clients: An Exploratory Study.

ERIC Educational Resources Information Center

Johnson, W. Brad; Ridley, Charles R.

1992-01-01

Operationalized brief "Christian" form of rational-emotive therapy (CRET) and compared therapeutic efficacy of CRET with standard version of brief rational-emotive therapy (RET). Findings from depressed Christian clients (n=10) indicated that both treatments were effective in reducing depression and automatic negative thoughts whereas only CRET…

Deconstructing Pediatric Depression Trials: An Analysis of the Effects of Expectancy and Therapeutic Contact

ERIC Educational Resources Information Center

Rutherford, Bret R.; Sneed, Joel R.; Tandler, Jane M.; Rindskopf, David; Peterson, Bradley S.; Roose, Steven P.

2011-01-01

Objective: This study investigated how study type, mean patient age, and amount of contact with research staff affected response rates to medication and placebo in acute antidepressant trials for pediatric depression. Method: Data were extracted from nine open, four active comparator, and 18 placebo-controlled studies of antidepressants for…

Comparing Voice-Therapy and Vocal-Hygiene Treatments in Dysphonia Using a Limited Multidimensional Evaluation Protocol

ERIC Educational Resources Information Center

Rodriguez-Parra, Maria J.; Adrian, Jose A.; Casado, Juan C.

2011-01-01

Purpose: This study evaluates the effectiveness of two different programs of voice-treatment on a heterogeneous group of dysphonic speakers and the stability of therapeutic progress for longterm follow-up post-treatment period, using a limited multidimensional protocol of evaluation. Method: Forty-two participants with voice disorders were…

Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria gonorrhoeae, Hawaii, USA.

PubMed

Papp, John R; Abrams, A Jeanine; Nash, Evelyn; Katz, Alan R; Kirkcaldy, Robert D; O'Connor, Norman P; O'Brien, Pamela S; Harauchi, Derek H; Maningas, Eloisa V; Soge, Olusegun O; Kersh, Ellen N; Komeya, Alan; Tomas, Juval E; Wasserman, Glenn M; Kunimoto, Gail Y; Trees, David L; Whelen, A Christian

2017-05-01

During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options.

A PHARMACOKINETIC-PHARMACODYNAMIC MODEL FOR GENE-REGULATED PROSTATE MAINTENANCE: COMPARING THE EFFECTS OF CASTRATION WITH ANTIANDROGEN EXPOSURE IN THE RAT

EPA Science Inventory

Antiandrogens affect prostate maintenance in two ways. Androgen antagonists, such as the fungicide vinclozolin, act as competitive ligands for the androgen receptor (AR). Enzyme inhibitors, such as the therapeutic drug Finasteride, inhibit the enzyme 5 -reductase (5 R) from metab...

Randomized Clinical Trial: The Use of SpeechEasy® in Stuttering Treatment

ERIC Educational Resources Information Center

Ritto, Ana Paula; Juste, Fabiola Staróbole; Stuart, Andrew; Kalinowski, Joseph; de Andrade, Claudia Regina Furquim

2016-01-01

Background: Numerous studies have demonstrated the benefit of devices delivering altered auditory feedback (AAF) as a therapeutic alternative for those who stutter. Aims: The effectiveness of a device delivering AAF (SpeechEasy®) was compared with behavioural techniques in the treatment of stuttering in a randomized clinical trial. Methods &…

Anti-SEMA3A Antibody: A Novel Therapeutic Agent to Suppress GBM Tumor Growth.

PubMed

Lee, Jaehyun; Shin, Yong Jae; Lee, Kyoungmin; Cho, Hee Jin; Sa, Jason K; Lee, Sang-Yun; Kim, Seok-Hyung; Lee, Jeongwu; Yoon, Yeup; Nam, Do-Hyun

2017-11-10

Glioblastoma (GBM) is classified as one of the most aggressive and lethal brain tumor. Great strides have been made in understanding the genomic and molecular underpinnings of GBM, which translated into development of new therapeutic approaches to combat such deadly disease. However, there are only few therapeutic agents that can effectively inhibit GBM invasion in a clinical framework. In an effort to address such challenges, we have generated anti-SEMA3A monoclonal antibody as a potential therapeutic antibody against GBM progression. We employed public glioma datasets, Repository of Molecular Brain Neoplasia Data and The Cancer Genome Atlas, to analyze SEMA3A mRNA expression in human GBM specimens. We also evaluated for protein expression level of SEMA3A via tissue microarray (TMA) analysis. Cell migration and proliferation kinetics were assessed in various GBM patient-derived cells (PDCs) and U87-MG cell-line for SEMA3A antibody efficacy. GBM patient-derived xenograft (PDX) models were generated to evaluate tumor inhibitory effect of anti-SEMA3A antibody in vivo. By combining bioinformatics and TMA analysis, we discovered that SEMA3A is highly expressed in human GBM specimens compared to non-neoplastic tissues. We developed three different anti-SEMA3A antibodies, in fully human IgG form, through screening phage-displayed synthetic antibody library using a classical panning method. Neutralization of SEMA3A significantly reduced migration and proliferation capabilities of PDCs and U87-MG cell-line in vitro. In PDX models, treatment with anti-SEMA3A antibody exhibited notable tumor inhibitory effect through down-regulation of cellular proliferative kinetics and tumor-associated macrophages recruitment. In present study, we demonstrated tumor inhibitory effect of SEMA3A antibody in GBM progression and present its potential relevance as a therapeutic agent in a clinical framework.

Protective and therapeutic effects of an extract mixture of alder tree, labiate herb, milk thistle green bean-rice bran fermentation, and turnip against ethanol-induced toxicity in the rat

PubMed Central

Baek, Min-Won; Seok, Seung-Hyeok; Lee, Hui-Young; Kim, Dong Jae; Lee, Byoung-Hee; Ahn, Young-Tae; Lim, Kwang-Sei; Huh, Chul-Sung

2008-01-01

An herbal extract mixture and yogurt added to the herbal extract mixture were tested for their protective and therapeutic effects on ethanol-induced liver injury. The herbal extract mixture, yogurt and commercial drugs were used for treatment for two weeks prior to administering a single oral dose of ethanol (3 g/kg body weight). The herbal extract mixture and yogurt added to the herbal extract mixture were found to provide protection against ethanol-induced toxicity comparable to the commercial drug treatment, according to the serum and histopathological analysis. It was also shown that co-treatment with herbal extract mixture and yogurt against a triple oral dose of ethanol (2 g/kg body weight, over one week) provided protection against ethanol toxicity. After the initial set of experiments, the herbal extract mixture and yogurt treatments were extended for three more weeks. When compared to the positive control, further treatment with both the herbal extract and yogurt significantly reduced liver injury and resulted in a lower grade of lipid deposition. PMID:18296886

Study on force mechanism for therapeutic effect of pushing manipulation with one-finger meditation base on similarity analysis of force and waveform.

PubMed

Fang, Lei; Fang, Min; Guo, Min-Min

2016-12-27

To reveal the force mechanism for therapeutic effect of pushing manipulation with one-finger meditation. A total of 15 participants were recruited in this study and assigned to an expert group, a skilled group and a novice group, with 5 participants in each group. Mechanical signals were collected from a biomechanical testing platform, and these data were further observed via similarity analysis and cluster analysis. Comparing the force waveforms of manipulation revealed that the manipulation forces were similar between the expert group and the skilled group (P>0.05). The mean value of vertical force was 9.8 N, and 95% CI rang from 6.37 to 14.70 N, but there were significant differences compared with the novice group (P<0.05). The result of overall similarity coefficient cluster analysis showed that two kinds of manipulation forces curves were existed between the expert group and the skilled group. Pushing manipulation with one-finger meditation is a kind of light stimulation manipulation on the acupoint, and force characteristics of double waveforms continuously alternated during manual operation.

Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome

PubMed Central

Becerra, Lino; Sava, Simona; Simons, Laura E.; Drosos, Athena M.; Sethna, Navil; Berde, Charles; Lebel, Alyssa A.; Borsook, David

2014-01-01

Pediatric complex regional pain syndrome (P-CRPS) offers a unique model of chronic neuropathic pain as it either resolves spontaneously or through therapeutic interventions in most patients. Here we evaluated brain changes in well-characterized children and adolescents with P-CRPS by measuring resting state networks before and following a brief (median = 3 weeks) but intensive physical and psychological treatment program, and compared them to matched healthy controls. Differences in intrinsic brain networks were observed in P-CRPS compared to controls before treatment (disease state) with the most prominent differences in the fronto-parietal, salience, default mode, central executive, and sensorimotor networks. Following treatment, behavioral measures demonstrated a reduction of symptoms and improvement of physical state (pain levels and motor functioning). Correlation of network connectivities with spontaneous pain measures pre- and post-treatment indicated concomitant reductions in connectivity in salience, central executive, default mode and sensorimotor networks (treatment effects). These results suggest a rapid alteration in global brain networks with treatment and provide a venue to assess brain changes in CRPS pre- and post-treatment, and to evaluate therapeutic effects. PMID:25379449

Uncertainty of High Intensity Therapeutic Ultrasound (HITU) Field Characterization with Hydrophones: Effects of Nonlinearity, Spatial Averaging, and Complex Sensitivity

PubMed Central

Liu, Yunbo; Wear, Keith A.; Harris, Gerald R.

2017-01-01

Reliable acoustic characterization is fundamental for patient safety and clinical efficacy during high intensity therapeutic ultrasound (HITU) treatment. Technical challenges, such as measurement uncertainty and signal analysis still exist for HITU exposimetry using ultrasound hydrophones. In this work, four hydrophones were compared for pressure measurement: a robust needle hydrophone, a small PVDF capsule hydrophone and two different fiber-optic hydrophones. The focal waveform and beam distribution of a single element HITU transducer (1.05 MHz and 3.3 MHz) were evaluated. Complex deconvolution between the hydrophone voltage signal and frequency-dependent complex sensitivity was performed to obtain pressure waveform. Compressional pressure, rarefactional pressure, and focal beam distribution were compared up to 10.6/−6.0 MPa (p+ and p−) (1.05 MHz) and 20.65/−7.20 MPa (3.3 MHz). In particular, the effects of spatial averaging, local nonlinear distortion, complex deconvolution and hydrophone damage thresholds were investigated. This study showed an uncertainty of no better than 10–15% on hydrophone-based HITU pressure characterization. PMID:28735734

Research and application of absorbable screw in orthopedics: a clinical review comparing PDLLA screw with metal screw in patients with simple medial malleolus fracture.

PubMed

Tang, Jin; Hu, Jin-feng; Guo, Wei-chun; Yu, Ling; Zhao, Sheng-hao

2013-01-01

To observe the therapeutic effect of absorbable screw in medial malleolus fracture and discuss its clinical application in orthopedics. A total of 129 patients with simple medial malleolus fracture were studied. Among them, 64 patients were treated with poly-D, L-lactic acid (PDLLA) absorbable screws, while the others were treated with metal screws. All the patients were followed up for 12-20 months (averaged 18.4 months) and the therapeutic effect was evaluated according to the American Orthopaedic Foot and Ankle Society clinical rating systems. In absorbable screw group, we obtained excellent and good results in 62 cases (96.88%); in steel screw group, 61 cases (93.85%) achieved excellent and good results. There was no significant difference between the two groups. In the treatment of malleolus fracture, absorbable screw can achieve the same result compared with metal screw fixation. Absorbable screw is preferred due to its advantages of safety, cleanliness and avoiding the removal procedure associated with metallic implants.

Variation of High-Intensity Therapeutic Ultrasound (HITU) Pressure Field Characterization: Effects of Hydrophone Choice, Nonlinearity, Spatial Averaging and Complex Deconvolution.

PubMed

Liu, Yunbo; Wear, Keith A; Harris, Gerald R

2017-10-01

Reliable acoustic characterization is fundamental for patient safety and clinical efficacy during high-intensity therapeutic ultrasound (HITU) treatment. Technical challenges, such as measurement variation and signal analysis, still exist for HITU exposimetry using ultrasound hydrophones. In this work, four hydrophones were compared for pressure measurement: a robust needle hydrophone, a small polyvinylidene fluoride capsule hydrophone and two fiberoptic hydrophones. The focal waveform and beam distribution of a single-element HITU transducer (1.05 MHz and 3.3 MHz) were evaluated. Complex deconvolution between the hydrophone voltage signal and frequency-dependent complex sensitivity was performed to obtain pressure waveforms. Compressional pressure (p + ), rarefactional pressure (p - ) and focal beam distribution were compared up to 10.6/-6.0 MPa (p + /p - ) (1.05 MHz) and 20.65/-7.20 MPa (3.3 MHz). The effects of spatial averaging, local non-linear distortion, complex deconvolution and hydrophone damage thresholds were investigated. This study showed a variation of no better than 10%-15% among hydrophones during HITU pressure characterization. Published by Elsevier Inc.

Long-Acting Phospholipid Gel of Exenatide for Long-Term Therapy of Type II Diabetes.

PubMed

Hu, Mei; Zhang, Yu; Xiang, Nanxi; Zhong, Ying; Gong, Tao; Zhang, Zhi-Rong; Fu, Yao

2016-06-01

This study aimed to develop a sustained-release formulation of exenatide (EXT) for the long-term therapeutic efficacy in the treatment of type II diabetes. In this study, we present an injectable phospholipid gel by mixing biocompatible phospholipid S100, medium chain triglyceride (MCT) with 85% (w/w) ethanol. A systemic pre-formulation study has been carried out to improve the stability of EXT during formulation fabrication. With the optimized formulation, the pharmacokinetic profiles in rats were studied and two diabetic animal models were employed to evaluate the therapeutic effect of EXT phospholipid gel via a single subcutaneous injection versus repeated injections of normal saline and EXT solution. With optimized formulation, sustained release of exenatide in vivo for over three consecutive weeks was observed after one single subcutaneous injection. Moreover, the pharmacodynamic study in two diabetic models justified that the gel formulation displayed a comparable hypoglycemic effect and controlled blood glucose level compared with exenatide solution treated group. EXT-loaded phospholipid gel represents a promising controlled release system for long-term therapy of type II diabetes.

Therapeutic potential of choline magnesium trisalicylate as an alternative to aspirin for patients with bleeding tendencies.

PubMed

Danesh, B J; Saniabadi, A R; Russell, R I; Lowe, G D

1987-12-01

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p less than 0.005), AA (p less than 0.01) and spontaneous aggregation (p less than 0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

Effect of Misalignment between Hospital and Provincial Formularies on Medication Discrepancies at Discharge: PPITS (Proton Pump Inhibitor Therapeutic Substitution) Study

PubMed Central

Chua, Doson; Chu, Eric; Lo, Angela; Lo, Melissa; Pataky, Fruzina; Tang, Linda; Bains, Ajay

2012-01-01

Background Medication discrepancies may occur on admission, transfer, or discharge from hospital. Therapeutic interchange within a drug class is a common practice in hospitals, and orders for specific proton pump inhibitors (PPIs) are often substituted with the hospital’s formulary PPI through therapeutic interchange protocols. Rabeprazole is the PPI on the formulary of the British Columbia PharmaCare program. However, different PPIs may appear on the formularies of the province’s hospitals. This misalignment and use of therapeutic interchange may lead to increased rates of medication discrepancies at the time of discharge. Objective To evaluate the effect of formulary misalignment for PPIs between St Paul’s Hospital in Vancouver and the British Columbia PharmaCare program and use of therapeutic interchange on the occurrence of medication discrepancies at discharge. Methods A cohort chart review was performed to compare discharge discrepancy rates for PPI orders between 2 periods: June 2006 to June 2008, when the same PPI appeared on the hospital and provincial formularies, and July 2008 to July 2010, when the designated PPIs differed between the hospital and provincial formularies. Data for the first study period were used to establish the baseline discharge discrepancy rate, and data for the later period represented the discharge discrepancy rate in the presence of misalignment between the hospital and PharmaCare formularies. Results The discharge discrepancy rate for PPIs was 27.3% (24/88) when the 2 formularies were aligned and 49.1% (81/165) when the formularies were misaligned. This represents an absolute increase of 21.8 percentage points in the risk of discharge discrepancies (95% confidence interval 9.8–33.9 percentage points; p < 0.001) when the hospital and provincial formularies were misaligned and the hospital’s therapeutic interchange protocol was used. Conclusions Misalignment between the PPIs specified in the hospital and provincial formularies, combined with use of therapeutic interchange, was associated with a significant increase in medication discrepancies at discharge. PMID:22529401

[A consensual therapeutic recommendation for type 2 diabetes mellitus by the Slovak Diabetes Society (2018)].

PubMed

Martinka, Emil; Uličiansky, Vladimír; Mokáň, Marián; Tkáč, Ivan; Galajda, Peter; Dókušová, Silvia; Schroner, Zbynek

2018-01-01

Type 2 diabetes mellitus is a heterogeneous medical condition involving multiple pathophysiological mechanisms. Its successful treatment requires an individualized approach and frequently combined therapy with utilizing its effect on multiple levels. Current possibilities enable the employment of such procedures to an incomparably greater extent than before. The effects of different classes of oral antidiabetic drugs on the reduction of glycemia and HbA1c is mutually comparable. However differences are observed in the proportions of patients who met the required criteria, regarding the increase in weight, incidence of hypoglycemia as well as the effect on cardiovascular, renal or oncologic morbidity and mortality, and severity of specific adverse effects, potential risks and contraindications. The presented text provides the reader with the information about the Consensual therapeutic algorithm for the treatment of type 2 diabetes mellitus in compliance with SPC, the ADA/EASD amended indicative limitations and recommendations, formulated by the Committee of the Slovak Diabetes Society.Key words: biguanides - gliflozins - gliptins - glitazones - GLP-1-receptor agonists - insulin - sulfonylurea.

Novel genipin crosslinked atorvastatin loaded sericin nanoparticles for their enhanced antihyperlipidemic activity.

PubMed

Kanoujia, Jovita; Singh, Mahendra; Singh, Pooja; Saraf, Shubhini A

2016-12-01

The objective of this study was to demonstrate the therapeutic as well as biopolymer like characteristics of naturally occurring sericin protein for development of nanoparticulate system of atorvastatin (Atr) to improve therapeutic effect and to reduce toxicity. The sericin encapsulated atorvastatin nanoparticles (Seri-Atr NPs) were prepared by desolvation method utilizing genipin (Gn) as a natural and nontoxic crosslinker. The optimized NPs exhibited small particle size (166±0.30nm), high entrapment efficiency (91±0.69%) and uniform spherical shape with sustained release profile. Moreover, the results of pharmacokinetic studies indicated an increase in AUC0-∞ of NPs (1189.74±52.3hng/ml) compared with Atr (501.84±66hng/ml). The cellular uptake of NPs suggested an interaction of negatively charged particles with the cell surface and considerable reduction in systemic toxicity. Histopathology studies also demonstrated the therapeutic potential of sericin and cytocompatibility. Hence, genipin crosslinked sericin based nanoparticles represents a promising nanoplatform for improved therapeutic efficiency of Atr. Copyright © 2016 Elsevier B.V. All rights reserved.

Team-based Learning in Therapeutics Workshop Sessions

PubMed Central

Kelley, Katherine A.; Metzger, Anne H.; Bellebaum, Katherine L.; McAuley, James W.

2009-01-01

Objectives To implement team-based learning in the workshop portion of a pathophysiology and therapeutics sequence of courses to promote integration of concepts across the pharmacy curriculum, provide a consistent problem-solving approach to patient care, and determine the impact on student perceptions of professionalism and teamwork. Design Team-based learning was incorporated into the workshop portion of 3 of 6 pathophysiology and therapeutics courses. Assignments that promoted team-building and application of key concepts were created. Assessment Readiness assurance tests were used to assess individual and team understanding of course materials. Students consistently scored 20% higher on team assessments compared with individual assessments. Mean professionalism and teamwork scores were significantly higher after implementation of team-based learning; however, this improvement was not considered educationally significant. Approximately 91% of students felt team-based learning improved understanding of course materials and 93% of students felt teamwork should continue in workshops. Conclusion Team-based learning is an effective teaching method to ensure a consistent approach to problem-solving and curriculum integration in workshop sessions for a pathophysiology and therapeutics course sequence. PMID:19885069

Dual delivery of biological therapeutics for multimodal and synergistic cancer therapies.

PubMed

Jang, Bora; Kwon, Hyokyoung; Katila, Pramila; Lee, Seung Jin; Lee, Hyukjin

2016-03-01

Cancer causes >8.2 million deaths annually worldwide; thus, various cancer treatments have been investigated over the past decades. Among them, combination drug therapy has become extremely popular, and treatment with more than one drug is often necessary to achieve appropriate anticancer efficacy. With the development of nanoformulations and nanoparticulate-based drug delivery, researchers have explored the feasibility of dual delivery of biological therapeutics to overcome the current drawbacks of cancer therapy. Compared with the conventional single drug therapy, dual delivery of therapeutics has provided various synergistic effects in addition to offering multimodality to cancer treatment. In this review, we highlight and summarize three aspects of dual-delivery systems for cancer therapy. These include (1) overcoming drug resistance by the dual delivery of chemical drugs with biological therapeutics for synergistic therapy, (2) targeted and controlled drug release by the dual delivery of drugs with stimuli-responsive nanomaterials, and (3) multimodal theranostics by the dual delivery of drugs and molecular imaging probes. Furthermore, recent developments, perspectives, and new challenges regarding dual-delivery systems for cancer therapy are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

THC therapeutic research by independent and state-sponsored investigators: a historical review.

PubMed

Scigliano, J A

1981-01-01

A brief history of the control and use of cannabis in the United States is presented. Essential to the discussion are the federal law: the Marihuana Tax Stamp Act of 1937; the Controlled Substances Act of 1970; and the Federal Food, Drug and Cosmetic Act of 1962. On mandate of Congress in 1968, initial studies were directed to determine effects of long-term use in man. The annual reporting of the status of "Marihuana and Health" was established. In the early 1970s, the scope of research was broadened to include evaluation of THC for use in certain medical conditions. Interest in therapeutic research may have been influenced by anecdotal reports of benefit for nausea and vomiting of cancer chemotherapy and for elevated intraocular pressure of glaucoma, by the lobbying for laws to legalize marihuana by special interest groups, and by the passage of state "Controlled Substances Therapeutic Research" acts (CSTRA). A listing of approved INDs in four therapeutic categories, a chart comparing the components of laws passed by 25 states, and a bibliography of suggested reading for further contact with the subject matter are included.

Bioresponsive release of insulin-like growth factor-I from its PEGylated conjugate.

PubMed

Braun, Alexandra C; Gutmann, Marcus; Mueller, Thomas D; Lühmann, Tessa; Meinel, Lorenz

2018-06-10

PEGylation of protein ligands, the attachment of polyethylene glycol (PEG) polymers to a therapeutic protein, increases therapeutics' half-life but frequently comes at the cost of reduced bioactivity. We are now presenting a bioinspired strategy leading out of this dilemma. To this end, we selected a position within insulin-like growth factor I (IGF-I) for decoration with a PEG 30kDa -modified protease-sensitive peptide linker (PSL) using a combination of enzymatic and chemical bioorthogonal coupling strategies. The PSL sequence responded to matrix metalloproteinases (MMP) to provide a targeted release in diseased tissue. The IGF-PSL-PEG conjugate had different binding protein affinity, cell proliferation, and endocytosis patterns as compared to the wild type. Exposure of the conjugate to elevated levels of activated MMPs, as present in inflamed tissues, fully reestablished the wild type properties through effective PSL cleavage. In conclusion, this bioinspired approach provided a blueprint for PEGylated therapeutics combining the pharmacokinetic advantages of PEGylation, while locally restoring the full suite of biological potential of therapeutics. Copyright © 2018 Elsevier B.V. All rights reserved.

The relationship between adult attachment style and therapeutic alliance in individual psychotherapy: a meta-analytic review.

PubMed

Diener, Marc J; Monroe, Joel M

2011-09-01

The present study examined the relationship between adult attachment style and therapeutic alliance in individual psychotherapy. Search procedures yielded 17 independent samples (total N = 886, average n = 52, standard deviation = 24) for inclusion in the meta-analysis. Results indicated that greater attachment security was associated with stronger therapeutic alliances, whereas greater attachment insecurity was associated with weaker therapeutic alliances, with an overall weighted effect size of r = .17, p < .001 (95% confidence interval = .10-.23). Publication bias analyses did not indicate any cause for concern regarding the results. The data were not demonstrably heterogeneous (Q = 6.10, df = 16, p = .99), and all between-study moderator analyses were nonsignificant (p values > .10) with the exception of the source of alliance ratings; results indicated that patient-rated alliance demonstrated a significantly larger relationship with attachment compared with therapist-rated alliance (Qbetween = 3.95, df = 1, p = .047). Implications for clinical practice and future research are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved). (c) 2011 APA, all rights reserved.

Therapeutic Mechanisms of Bile Acids and Nor-Ursodeoxycholic Acid in Non-Alcoholic Fatty Liver Disease.

PubMed

Steinacher, Daniel; Claudel, Thierry; Trauner, Michael

2017-01-01

Non-alcoholic fatty liver disease is one of the most rapidly rising clinical problems in the 21st century. So far no effective drug treatment has been established to cure this disease. Bile acids (BAs) have a variety of signaling properties, which can be used therapeutically for modulating hepatic metabolism and inflammation. A side-chain shorted derivative of ursodeoxycholic acid (UDCA) is 24 nor-ursodeoxycholic acid (NorUDCA) and it represents a new class of drugs for treatment of liver diseases. NorUDCA has unique biochemical and therapeutic properties, since it is relatively resistant to conjugation with glycine or taurine compared to UDCA. NorUDCA undergoes cholehepatic shunting, resulting in ductular targeting, bicarbonate-rich hypercholeresis, and cholangiocyte protection. Furthermore, it showed anti-fibrotic, anti-inflammatory, and anti-lipotoxic properties in several animal models. As such, NorUDCA is a promising new approach in the treatment of cholestatic and metabolic liver diseases. This review is a summary of current BA-based therapeutic approaches in the treatment of the fatty liver disease. © 2017 S. Karger AG, Basel.

Targeting Murine Mesenchymal Stem Cells to Kidney Injury Molecule-1 Improves Their Therapeutic Efficacy in Chronic Ischemic Kidney Injury.

PubMed

Zou, Xiangyu; Jiang, Kai; Puranik, Amrutesh S; Jordan, Kyra L; Tang, Hui; Zhu, Xiangyang; Lerman, Lilach O

2018-05-01

Mesenchymal stem cells (MSC) have been experimentally used for kidney repair, but modest retention limits their efficacy. Cell-surface coating allows modulating MSC homing and interaction with target cells. We coated mouse adipose tissue-derived MSC with antibodies directed against kidney injury molecule-1 (ab-KIM1), which is upregulated in injured kidneys, and tested the hypothesis that this would enhance their therapeutic effects in ischemic kidney injury. Untreated MSC, ab-KIM1-coated MSC (KIM-MSC), or vehicle, were injected systemically into the carotid artery of 2-kidneys, 1-clip mice 2 weeks after surgery. MSC retention in different organs was explored 24 hours, 48 hours, or 2 weeks after injection. Renal volume, perfusion, and oxygenation were studied 2 weeks after injection using magnetic resonance imaging in vivo, and renal inflammation, apoptosis, capillary density, and fibrosis ex vivo. The ab-KIM1 coating had little effect on MSC viability or proliferation. The stenotic kidney showed upregulated KIM1 expression, selective homing, and greater retention of KIM-MSC compared to untreated MSC and compared to other organs. KIM-MSC-injected mice improved renal perfusion and capillary density, and attenuated oxidative damage, apoptosis, and fibrosis compared to mice treated with vehicle or with native MSC. In conclusion, MSC coating with ab-KIM1 increased their retention in the ischemic kidney and enhanced their therapeutic efficacy. This novel method may be useful to selectively target injured kidneys, and supports further development of strategies to enhance cell-based treatment of ischemic kidney injury. Stem Cells Translational Medicine 2018;7:394-403. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Assessment of the effect of Allium sativum on serum nitric oxide level and hepatic histopathology in experimental cystic echinococcosis in mice.

PubMed

Ali, Nehad Mahmoud; Ibrahim, Ayman Nabil; Ahmed, Naglaa Samier

2016-09-01

The current study was carried out to evaluate the prophylactic and therapeutic effects of Allium sativum on experimental cystic echinococcosis by measuring the serum nitric oxide level and studying hepatic histopathological changes. The experimental animals were divided into five groups, ten mice in each, group (I): prophylactic; group (II): therapeutic; group (III): prophylactic and therapeutic; group (IV): infected nontreated; group (V): non infected non treated. The results showed that serum nitric oxide was significantly increased as a result of infection in all infected groups compared to group V. Statistical significant difference was noted in serum nitrate level in group I at 1st and 8th week post infection compared to the same time interval in group IV. In group II, statistical significance was noticed only at the 1st week post infection. Statistical significant difference was noted in serum nitrate level in group III at 1st, 4th, 6th and 8th week post infection compared to same time interval in group IV. Hydatid cysts developed in livers of mice of group IV as early as 4 weeks of infection while no cysts were found in groups I,II and III. Histopathologically there were moderate pathological changes in group I and group II as hepatocytes showed moderate steatosis, moderate venous congestion and inflammatory cellular infiltrate with foci of degeneration and necrosis. While livers of mice of group III showed mild steatosis, mild venous congestion, mild inflammatory cellular infiltrate, no necrosis and no biliary hyperplasia. Accordingly, that garlic (Allium sativum) may be a promising phototherapeutic agent for cystic echinococcosis.

Age of the Donor Reduces the Ability of Human Adipose-Derived Stem Cells to Alleviate Symptoms in the Experimental Autoimmune Encephalomyelitis Mouse Model

PubMed Central

Scruggs, Brittni A.; Semon, Julie A.; Zhang, Xiujuan; Zhang, Shijia; Bowles, Annie C.; Pandey, Amitabh C.; Imhof, Kathleen M.P.; Kalueff, Allan V.; Gimble, Jeffrey M.

2013-01-01

There is a significant clinical need for effective therapies for primary progressive multiple sclerosis, which presents later in life (i.e., older than 50 years) and has symptoms that increase in severity without remission. With autologous mesenchymal stem cell therapy now in the early phases of clinical trials for all forms of multiple sclerosis (MS), it is necessary to determine whether autologous stem cells from older donors have therapeutic effectiveness. In this study, the therapeutic efficacy of human adipose-derived mesenchymal stem cells (ASCs) from older donors was directly compared with that of cells from younger donors for disease prevention. Mice were induced with chronic experimental autoimmune encephalomyelitis (EAE) using the myelin oligodendrocyte glycoprotein35–55 peptide and treated before disease onset with ASCs derived from younger (<35 years) or older (>60 years) donors. ASCs from older donors failed to ameliorate the neurodegeneration associated with EAE, and mice treated with older donor cells had increased central nervous system inflammation, demyelination, and splenocyte proliferation in vitro compared with the mice receiving cells from younger donors. Therefore, the results of this study demonstrated that donor age significantly affects the ability of human ASCs to provide neuroprotection, immunomodulation, and/or remyelination in EAE mice. The age-related therapeutic differences corroborate recent findings that biologic aging occurs in stem cells, and the differences are supported by evidence in this study that older ASCs, compared with younger donor cells, secrete less hepatocyte growth factor and other bioactive molecules when stimulated in vitro. These results highlight the need for evaluation of autologous ASCs derived from older patients when used as therapy for MS. PMID:24018793

The use of cell-sheet technique eliminates arrhythmogenicity of skeletal myoblast-based therapy to the heart with enhanced therapeutic effects.

PubMed

Narita, Takuya; Shintani, Yasunori; Ikebe, Chiho; Kaneko, Masahiro; Harada, Narumi; Tshuma, Nomathamsanqa; Takahashi, Kunihiko; Campbell, Niall G; Coppen, Steven R; Yashiro, Kenta; Sawa, Yoshiki; Suzuki, Ken

2013-09-20

Clinical application of skeletal myoblast transplantation has been curtailed due to arrhythmogenicity and inconsistent therapeutic benefits observed in previous studies. However, these issues may be solved by the use of a new cell-delivery mode. It is now possible to generate "cell-sheets" using temperature-responsive dishes without artificial scaffolds. This study aimed to validate the safety and efficacy of epicardial placement of myoblast-sheets (myoblast-sheet therapy) in treating heart failure. After coronary artery ligation in rats, the same numbers of syngeneic myoblasts were transplanted by intramyocardial injection or cell-sheet placement. Continuous radio-telemetry monitoring detected increased ventricular arrhythmias, including ventricular tachycardia, after intramyocardial injection compared to the sham-control, while these were abolished in myoblast-sheet therapy. This effect was conjunct with avoidance of islet-like cell-cluster formation that disrupts electrical conduction, and with prevention of increased arrhythmogenic substrates due to exaggerated inflammation. Persistent ectopic donor cells were found in the lung only after intramyocardial injection, strengthening the improved safety of myoblast-sheet therapy. In addition, myoblast-sheet therapy enhanced cardiac function, corresponding to a 9.2-fold increase in donor cell survival, compared to intramyocardial injection. Both methods achieved reduced infarct size, decreased fibrosis, attenuated cardiomyocyte hypertrophy, and increased neovascular formation, in association with myocardial upregulation of a group of relevant molecules. The pattern of these beneficial changes was similar between two methods, but the degree was more substantial after myoblast-sheet therapy. The cell-sheet technique enhanced safety and therapeutic efficacy of myoblast-based therapy, compared to the current method, thereby paving the way for clinical application. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The significance of compliance and persistence in the treatment of diabetes, hypertension and dyslipidaemia: a review

PubMed Central

Cramer, J A; Benedict, Á; Muszbek, N; Keskinaslan, A; Khan, Z M

2008-01-01

Objectives To review studies of patient compliance/persistence with cardiovascular or antidiabetic medication published since the year 2000; to compare the methods used to measure compliance/persistence across studies; to compare reported compliance/persistence rates across therapeutic classes and to assess whether compliance/persistence correlates with clinical outcomes. Methods English language papers published between January 2000 and November 2005 investigating patient compliance/persistence with cardiovascular or antidiabetic medication were identified through searches of the MEDLINE and EMBASE databases. Definitions and measurements of compliance/persistence were compared across therapeutic areas using contingency tables. Results Of the 139 studies analysed, 32% focused on hypertension, 27% on diabetes and 13% on dyslipidaemia. The remainder covered coronary heart disease and cardiovascular disease (CVD) in general. The most frequently reported measure of compliance was the 12-month medication possession ratio (MPR). The overall mean MPR was 72%, and the MPR did not differ significantly between treatment classes (range: 67–76%). The average proportion of patients with an MPR of > 80% was 59% overall, 64% for antihypertensives, 58% for oral antidiabetics, 51% for lipid-lowering agents and 69% in studies of multiple treatments, again with no significant difference between treatment classes. The average 12-month persistence rate was 63% and was similar across therapeutic classes. Good compliance had a positive effect on outcome in 73% of the studies examining clinical outcomes. Conclusions Non-compliance with cardiovascular and antidiabetic medication is a significant problem, with around 30% of days ‘on therapy’ not covered by medication and only 59% of patients taking medication for more than 80% of their days ‘on therapy’ in a year. Good compliance has a positive effect on clinical outcome, suggesting that the management of CVD may be improved by improving patient compliance. PMID:17983433

Targeting Murine Mesenchymal Stem Cells to Kidney Injury Molecule‐1 Improves Their Therapeutic Efficacy in Chronic Ischemic Kidney Injury

PubMed Central

Zou, Xiangyu; Jiang, Kai; Puranik, Amrutesh S.; Jordan, Kyra L.; Tang, Hui

2018-01-01

Abstract Mesenchymal stem cells (MSC) have been experimentally used for kidney repair, but modest retention limits their efficacy. Cell‐surface coating allows modulating MSC homing and interaction with target cells. We coated mouse adipose tissue‐derived MSC with antibodies directed against kidney injury molecule‐1 (ab‐KIM1), which is upregulated in injured kidneys, and tested the hypothesis that this would enhance their therapeutic effects in ischemic kidney injury. Untreated MSC, ab‐KIM1‐coated MSC (KIM‐MSC), or vehicle, were injected systemically into the carotid artery of 2‐kidneys, 1‐clip mice 2 weeks after surgery. MSC retention in different organs was explored 24 hours, 48 hours, or 2 weeks after injection. Renal volume, perfusion, and oxygenation were studied 2 weeks after injection using magnetic resonance imaging in vivo, and renal inflammation, apoptosis, capillary density, and fibrosis ex vivo. The ab‐KIM1 coating had little effect on MSC viability or proliferation. The stenotic kidney showed upregulated KIM1 expression, selective homing, and greater retention of KIM‐MSC compared to untreated MSC and compared to other organs. KIM‐MSC‐injected mice improved renal perfusion and capillary density, and attenuated oxidative damage, apoptosis, and fibrosis compared to mice treated with vehicle or with native MSC. In conclusion, MSC coating with ab‐KIM1 increased their retention in the ischemic kidney and enhanced their therapeutic efficacy. This novel method may be useful to selectively target injured kidneys, and supports further development of strategies to enhance cell‐based treatment of ischemic kidney injury. Stem Cells Translational Medicine 2018;7:394–403 PMID:29446551

Monte Carlo simulations for angular and spatial distributions in therapeutic-energy proton beams

NASA Astrophysics Data System (ADS)

Lin, Yi-Chun; Pan, C. Y.; Chiang, K. J.; Yuan, M. C.; Chu, C. H.; Tsai, Y. W.; Teng, P. K.; Lin, C. H.; Chao, T. C.; Lee, C. C.; Tung, C. J.; Chen, A. E.

2017-11-01

The purpose of this study is to compare the angular and spatial distributions of therapeutic-energy proton beams obtained from the FLUKA, GEANT4 and MCNP6 Monte Carlo codes. The Monte Carlo simulations of proton beams passing through two thin targets and a water phantom were investigated to compare the primary and secondary proton fluence distributions and dosimetric differences among these codes. The angular fluence distributions, central axis depth-dose profiles, and lateral distributions of the Bragg peak cross-field were calculated to compare the proton angular and spatial distributions and energy deposition. Benchmark verifications from three different Monte Carlo simulations could be used to evaluate the residual proton fluence for the mean range and to estimate the depth and lateral dose distributions and the characteristic depths and lengths along the central axis as the physical indices corresponding to the evaluation of treatment effectiveness. The results showed a general agreement among codes, except that some deviations were found in the penumbra region. These calculated results are also particularly helpful for understanding primary and secondary proton components for stray radiation calculation and reference proton standard determination, as well as for determining lateral dose distribution performance in proton small-field dosimetry. By demonstrating these calculations, this work could serve as a guide to the recent field of Monte Carlo methods for therapeutic-energy protons.

Topical Application of Eupatilin Ameliorates Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice.

PubMed

Lee, Ji Hyun; Lee, Ye Jin; Lee, Jun Young; Park, Young Min

2017-02-01

Atopic dermatitis (AD) is an inflammatory skin disorder with severe pruritus. Despite advancements in medicine, therapeutic treatments for AD are still limited. Eupatilin (5,7-dihydroxy-30,40,6-trimethoxyflavone) is one of the lipophilic flavonoids from Artemisia umbelliformis Lam. and Artemisia genipi Weber. Although it has been reported to act a role in improving inflammation, its action on AD is uncertain. In this study, we examined the role of eupatilin on AD-like skin lesions in NC/Nga mice. 2,4-dinitrochlorobenzene was repeatedly applied to the ear of NC/Nga mice to produce AD-like skin lesions. Eupatilin (1%, once a day for 5 consecutive days/week) was applied topically for four weeks for the evaluation of its therapeutic effects. 1% eupatilin cream significantly reduced the clinical severity score of AD-like lesions, compared to the vehicle ( p <0.005). A histopathological analysis revealed that 1% eupatilin cream significantly decreased the mast cell infiltration as well as inflammatory cell infiltration, compared to the vehicle ( p <0.005). We showed that 1% eupatilin cream significantly reduced the expression of thymic stromal lymphopoietin, tumor necrosis factor-α, interleukin-4, and interleukin-19, but not interferon-γ, compared to the vehicle ( p <0.005). Considering the therapeutic reaction of eupatilin on AD-like lesions as in this study, the substance has a promising to be an adjuvant topical agent for the control of AD.

Mannosylated thiolated polyethylenimine nanoparticles for the enhanced efficacy of antimonial drug against Leishmaniasis.

PubMed

Sarwar, Hafiz S; Ashraf, Sehreen; Akhtar, Sohail; Sohail, Muhammad F; Hussain, Syed Z; Rafay, Muhammad; Yasinzai, Masoom; Hussain, Irshad; Shahnaz, Gul

2018-01-01

Our aim was to inhibit trypanothione reductase (TR) and P-gp efflux pump of Leishmania by the use of thiolated polymers. Thus, increasing the intracellular accumulation and therapeutic effectiveness of antimonial compounds. Mannosylated thiolated chitosan and mannosylated thiolated chitosan-polyethyleneimine graft were synthesized and characterized. Meglumine antimoniate-loaded nanoparticles were prepared and evaluated for TR and P-gp efflux pump inhibition, biocompatibility, macrophage uptake and antileishmanial potential. Thiomers inhibited TR with Ki 2.021. The macrophage uptake was 33.7- and 18.9-fold higher with mannosylated thiolated chitosan-polyethyleneimine graft and mannosylated thiolated chitosan nanoparticles, respectively, as compared with the glucantime. Moreover, the in vitro antileishmanial activity showed 14.41- and 7.4-fold improved IC 50 for M-TCS-g-PEI and M-TCS, respectively as compared with glucantime. These results encouraged the concept that TR and P-gp inhibition by the use of thiomers improves the therapeutic efficacy of antimonial drugs.

Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors

NASA Astrophysics Data System (ADS)

Dixit, Suraj; Novak, Thomas; Miller, Kayla; Zhu, Yun; Kenney, Malcolm E.; Broome, Ann-Marie

2015-01-01

Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to untargeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.

Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors

PubMed Central

Dixit, Suraj; Novak, Thomas; Miller, Kayla; Zhu, Yun; Kenney, Malcolm E.

2015-01-01

Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to un-targeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging. PMID:25519743

(131)I-MIBG radionuclide therapy is safe and cost-effective in the control of symptoms of the carcinoid syndrome.

PubMed

Pathirana, A A; Vinjamuri, S; Byrne, C; Ghaneh, P; Vora, J; Poston, G J

2001-06-01

The standard treatment used to control the symptoms of carcinoid syndrome (CS) involves subcutaneous injections of the somatostatin analogue octreotide. This is expensive (US $8000--16,000 per year), and treatment may be for many years. The aim of this study was to evaluate the efficacy and cost-effectiveness of our experience over the last 5 years with 1-131-labelled metaiodobenzylguanidine (MIBG) radionuclide therapy in the palliation of patients with CS. A consecutive series of 20 symptomatic patients (referred between 1994 and 1999) with CS were evaluated. Fifteen of them underwent(123)I-MIBG scanning. Of the 13 patients with significant tracer uptake in metastatic deposits compared to background, 12 underwent a course of therapeutic(131)I-MIBG (one patient refused). Symptoms, biochemical markers, CT scans, follow-up(123)I-MIBG scans, and the requirement for octreotide were used to assess outcome of treatment. Costs of(131)I-MIBG and octreotide treatments were compared. MIBG treatment was well tolerated in all with only transient side-effects. Ten patients showed a measurable clinical improvement. Seven had a complete clinical response. The mean duration of response was 15.4 months. Octreotide was not required or was reduced in eight patients. Treatment with(131)I-MIBG resulted in a saving of US $1000 per patient, with effective symptom control, when compared to octreotide. 1-131 MIBG therapy is a safe and cost-effective therapeutic option to successfully control symptoms in patients with carcinoid syndrome. Copyright Harcourt Publishers Limited.

Effect of a therapeutic maximum allowable cost (MAC) program on the cost and utilization of proton pump inhibitors in an employer-sponsored drug plan in Canada.

PubMed

Mabasa, Vincent H; Ma, Johnny

2006-06-01

Therapeutic maximum allowable cost (MAC) is a managed care intervention that uses reference pricing in a therapeutic class or category of drugs or an indication (e.g., heartburn). Therapeutic MAC has not been studied in Canada or the United States. The proton pump inhibitor (PPI) rabeprazole was used as the reference drug in this therapeutic MAC program based on prices for PPIs in the province of Ontario. No PPI is available over the counter in Canada. To evaluate the utilization and anticipated drug cost savings for PPIs in an employer-sponsored drug plan in Canada that implemented a therapeutic MAC program for PPIs. An employer group with an average of 6,300 covered members, which adopted the MAC program for PPIs in June 2003, was compared with a comparison group comprising the book of business throughout Canada (approximately 5 million lives) without a PPI MAC program (non-MAC group). Pharmacy claims for PPIs were identified using the first 6 characters of the generic product identifier (GPI 492700) for a 36-month period from June 1, 2002, through May 31, 2005. The primary comparison was the year prior to the intervention (from June 1, 2002, through May 31, 2003) and the first full year following the intervention (June 1, 2004, through May 31, 2005). Drug utilization was evaluated by comparing the market share of each of the PPIs for the 2 time periods and by the days of PPI therapy per patient per year (PPPY) and days of therapy per prescription (Rx). Drug cost was defined as the cost of the drug (ingredient cost), including allowable provincial pharmacy markup but excluding pharmacy dispense fee. Cost savings were calculated from the allowed drug cost per claim, allowed cost per day, and allowed cost PPPY. (All amounts are in Canadian dollars.) The MAC intervention group experienced an 11.7% reduction in the average cost per day of PPI drug therapy, from 2.14 US dollars in the preperiod to 1.89 US dollars in the postperiod, compared with a 3.7% reduction in the comparison group (2.16 US dollars vs. 2.08 US dollars). Utilization dropped by 11.9% in the intervention group, from 166.7 days of PPI drug therapy PPPY to 146.9 days PPPY, compared with an increase of 7.9% in the comparison group, from 136.1 days to 146.8 days PPPY. The combined effect of the decrease in drug cost per day and utilization was a 22.1% reduction in allowed drug cost PPPY in the intervention (MAC) group (from 357 US dollars to 278 US dollars PPPY) versus a 4.1% increase in the comparison group (from 293 US dollars to 305 US dollars PPPY). A MAC program for PPIs for one employer in Canada was associated with savings for the drug plan sponsor of approximately 8% in actual drug cost per day of therapy compared with the comparison group. Total savings after consideration of utilization was approximately 26% for the intervention group versus the comparison group.

Relieving Pain using Dose-Extending Placebos: A Scoping Review

PubMed Central

Colloca, Luana; Enck, Paul; DeGrazia, David

2017-01-01

Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Importantly, provided that nondisclosure is pre-authorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated. PMID:27023425

[Therapeutic effects of the integrated acupuncture and Chinese herbal medicine on reflux esophagitis].

PubMed

Zhang, Wan; Li, Bolin; Sun, Jianhui; Wang, Zhikun; Zhang, Nana; Shi, Fang; Pei, Lin

2017-07-12

To compare the differences in the clinical therapeutic effects on reflux esophagitis among the combined therapy of huazhuo jiedu jiangni decoction (the decoction for resolving the turbid, detoxification and reducing the pathologic upward qi in short) and acupuncture, omeprazole and Chinese herbal medicine. Ninety patients were randomized into 3 groups, 4 cases of them were dropped off. Finally, there were 29 cases in the combined therapy group with acupuncture and the decoction, 29 cases in the western medication group and 28 cases in the Chinese herbal medicine group in the statistical analysis. In the combined therapy group with acupuncture and the decoction, the decoction was prescribed recurrence rate. The therapeutic effects are better than the simple application of either Chinese herbal medicine or omeprazole. for oral administration. Additionally, acupuncture was applied to Neiguan (PC 6), Zusanli (ST 36), Zhongwan (CV 12), Ganshu (BL 18), Danshu (BL 19) and Taichong (LR 3). The decoction was applied one dose a day and acupuncture was once a day. In the western medication group, omeprazole capsules, 20 mg were prescribed for oral administration, twice a day. In the Chinese herbal medicine group, the decoction was simply applied. The treatment was 8 weeks in the 3 groups and the follow-up visit was 6 months. The score of reflux disorder questionnaire (RDQ) and the changes in esophageal mucosa under gastroscope were observed before and after treatment; the clinical therapeutic effects and recurrence rate were evaluated in the 3 groups. In 4 and 8 weeks of treatment, RDQ scores in the 3 groups were all reduced as compared with those before treatment (all P <0.05). In 4 weeks of treatment, RDQ score in the combined therapy group with acupuncture and Chinese herbal medicine was lower than that in the western medication group ( P <0.05). In 8 weeks of treatment, RDQ score in the combined therapy group with acupuncture and Chinese herbal medicine was lower than those in the western medication group and the Chinese herbal medicine group (both P <0.05). In follow-up visit for 6 months, the recurrence rate in the combined therapy group with acupuncture and the decoction was lower than those in the other two groups (both P <0.05). In 8 weeks of treatment, the total effective rate for clinical symptoms and that observed under gastroscope in the combined therapy group with acupuncture and the decoction were all better than those in the western medication group and the Chinese herbal medicine group (all P <0.05). The combined therapy of huazhuo jiedu jiangni decoction and acupuncture achieve the definite therapeutic effects on reflux esophagitis, relieve the symptoms, protect gastric mucosa and reduce the.

Inhibition of West Nile Virus replication by retrovirus-delivered small interfering RNA in human neuroblastoma cells.

PubMed

Yang, Yongbo; Wu, Chengxiang; Wu, Jianguo; Nerurkar, Vivek R; Yanagihara, Richard; Lu, Yuanan

2008-05-01

West Nile virus (WNV) has been responsible for the largest outbreaks of arboviral encephalitis in U.S. history. No specific drug is currently available for the effective treatment of WNV infection. To exploit RNA interference as a potential therapeutic approach, a Moloney murine leukemia virus-based retrovirus vector was used to effectively deliver WNV-specific small interfering RNA (siRNA) into human neuroblastoma HTB-11 cells. Viral plaque assays demonstrated that transduced cells were significantly refractory to WNV replication, as compared to untransduced control cells (P < 0.05), which correlated with the reduced expression of target viral genes and respective viral proteins. Therefore, retrovirus-mediated delivery of siRNA for gene silencing can be used to study the specific functions of viral genes associated with replication and may have potential therapeutic applications.

Preferential cephalic redistribution of left ventricular cardiac output during therapeutic hypothermia for perinatal hypoxic-ischemic encephalopathy

PubMed Central

Hochwald, Ori; Jabr, Mohammed; Osiovich, Horacio; Miller, Steven P.; McNamara, Patrick J.; Lavoie, Pascal M.

2015-01-01

Objective To determine the relationship between left ventricular cardiac output (LVCO), superior vena cava (SVC) flow, and brain injury during whole-body therapeutic hypothermia. Study design Sixteen newborns with moderate or severe hypoxic-ischemic encephalopathy were studied using echocardiography during and immediately after therapeutic hypothermia. Measures were also compared with 12 healthy newborns of similar postnatal age. Newborns undergoing therapeutic hypothermia also had a cerebral magnetic resonance imaging as part of routine clinical care on postnatal day 3–4. Results LVCO was markedly reduced (mean+/−SD: 126+/−38 mL/kg/min) during therapeutic hypothermia, whereas SVC flow was maintained within expected normal values (88+/− 27 mL/kg/min) such that it represented 70% of the LVCO. The reduction in LVCO during therapeutic hypothermia was mainly accounted by a reduction in heart rate (99 +/− 13 BPM versus 123 +/− 17 BPM; p<0.001) compared to immediately post-warming, in the context of myocardial dysfunction. Neonates with documented brain injury on MRI showed higher SVC flow pre-rewarming, compared to newborns without brain injury (p=0.013). Conclusion Newborns with perinatal hypoxic-ischemic encephalopathy showed a preferential systemic-to cerebral redistribution of cardiac blood flow during whole-body therapeutic hypothermia, which may reflect a lack of cerebral vascular adaptation in newborns with more severe brain injury. PMID:24582011

Preferential cephalic redistribution of left ventricular cardiac output during therapeutic hypothermia for perinatal hypoxic-ischemic encephalopathy.

PubMed

Hochwald, Ori; Jabr, Mohammad; Osiovich, Horacio; Miller, Steven P; McNamara, Patrick J; Lavoie, Pascal M

2014-05-01

To determine the relationship between left ventricular cardiac output (LVCO), superior vena cava (SVC) flow, and brain injury during whole-body therapeutic hypothermia. Sixteen newborns with moderate or severe hypoxic-ischemic encephalopathy were studied using echocardiography during and immediately after therapeutic hypothermia. Measures were also compared with 12 healthy newborns of similar postnatal age. Newborns undergoing therapeutic hypothermia also had cerebral magnetic resonance imaging as part of routine clinical care on postnatal day 3-4. LVCO was markedly reduced (mean ± SD 126 ± 38 mL/kg/min) during therapeutic hypothermia, whereas SVC flow was maintained within expected normal values (88 ± 27 mL/kg/min) such that SVC flow represented 70% of the LVCO. The reduction in LVCO during therapeutic hypothermia was mainly accounted by a reduction in heart rate (99 ± 13 vs 123 ± 17 beats/min; P < .001) compared with immediately postwarming in the context of myocardial dysfunction. Neonates with brain injury on magnetic resonance imaging had higher SVC flow prerewarming, compared with newborns without brain injury (P = .013). Newborns with perinatal hypoxic-ischemic encephalopathy showed a preferential systemic-to-cerebral redistribution of cardiac blood flow during whole-body therapeutic hypothermia, which may reflect a lack of cerebral vascular adaptation in newborns with more severe brain injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Hydroxychloroquine Blood Levels in SLE: Clarifying dosing controversies and improving adherence

PubMed Central

Durcan, Laura; Clarke, William A; Magder, Laurence S.; Petri, Michelle

2015-01-01

OBJECTIVES Hydroxychloroquine is used for its effect on systemic lupus erythematosus (SLE) disease activity and long-term benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is dosing controversy; rheumatologists recommend weight-based, while ophthalmologists advocate height-based ‘ideal body weight’ dosing. METHODS Patients were prescribed hydroxychloroquine not to exceed 6.5mg/kg (max400mg/day). In hemodialysis, the dose was 200mg after each session, in renal insufficiency it was 200mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the impact of measurement and counseling on adherence, we compared the proportion of patients with a level of 500ng/ml or higher based on how many prior assessments the patient had. RESULTS The proportion of patients with hydroxychloroquine levels in the therapeutic range differed significantly by age, gender and vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, sub-therapeutic and therapeutic levels, disease activity decreased (SLEDAI 2.92, 2.36 and 2.20)(P=0.04, for trend). At first, 56% were therapeutic and by the third measurement this increased to 80% (p =<0.0001). CONCLUSION There was a trend towards higher disease activity with lower hydroxychloroquine levels. Renal failure dosing led to sub-optimum levels. We show that weight-based dosing (max 400mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling and repeated testing can increase adherences rates. PMID:26428205

Secondary Release of Exosomes from Astrocytes Contributes to the Increase in Neural Plasticity and Improvement of Functional Recovery after Stroke in Rats Treated with Exosomes Harvested from MicroRNA 133b-Overexpressing Multipotent Mesenchymal Stromal Cells

PubMed Central

Xin, Hongqi; Wang, Fengjie; Li, Yanfeng; Lu, Qing-E; Cheung, Wing Lee; Zhang, Yi; Zhang, Zheng Gang; Chopp, Michael

2017-01-01

We previously demonstrated that multipotent mesenchymal stromal cells (MSCs) that overexpress microRNA 133b (miR-133b) significantly improve functional recovery in rats subjected to middle cerebral artery occlusion (MCAO) compared with naive MSCs and that exosomes generated from naive MSCs mediate the therapeutic benefits of MSC therapy for stroke. Here we investigated whether exosomes isolated from miR-133b-overexpressing MSCs (Ex-miR-133b+) exert amplified therapeutic effects. Rats subjected to 2 h of MCAO were intra-arterially injected with Ex-miR-133b+, exosomes from MSCs infected by blank vector (Ex-Con), or phosphate-buffered saline (PBS) and were sacrificed 28 days after MCAO. Compared with the PBS treatment, both exosome treatment groups exhibited significant improvement of functional recovery. Ex-miR-133b+ treatment significantly increased functional improvement and neurite remodeling/brain plasticity in the ischemic boundary area compared with the Ex-Con treatment. Treatment with Ex-miR-133b+ also significantly increased brain exosome content compared with Ex-Con treatment. To elucidate mechanisms underlying the enhanced therapeutic effects of Ex-miR-133b+, astrocytes cultured under oxygen- and glucose-deprived (OGD) conditions were incubated with exosomes harvested from naive MSCs (Ex-Naive), miR-133b downregulated MSCs (Ex-miR-133b−), and Ex-miR-133b+. Compared with the Ex-Naive treatment, Ex-miR-133b+ significantly increased exosomes released by OGD astrocytes, whereas Ex-miR-133b− significantly decreased the release. Also, exosomes harvested from OGD astrocytes treated with Ex-miR-133b+ significantly increased neurite branching and elongation of cultured cortical embryonic rat neurons compared with the exosomes from OGD astrocytes subjected to Ex-Con. Our data suggest that exosomes harvested from miR-133b-overexpressing MSCs improve neural plasticity and functional recovery after stroke with a contribution from a stimulated secondary release of neurite-promoting exosomes from astrocytes. PMID:27677799

Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils.

PubMed

Guo, Le; Yang, Hua; Tang, Feng; Yin, Runting; Liu, Hongpeng; Gong, Xiaojuan; Wei, Jun; Zhang, Ying; Xu, Guangxian; Liu, Kunmei

2017-01-01

Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori ( H. pylori ) infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori , remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP), heat shock protein 60 (HSP60) and H. pylori adhesin A (HpaA) was constructed based on mucosal adjuvant cholera toxin B subunit (CTB), Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA 27-53 , UreA 183-203 , HpaA 132-141 , and HSP60 189-203 ), and also the epitope-rich regions of urease B subunit (UreB 158-251 and UreB 321-385 ) predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori -infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB 158-172 , UreB 181-195 , UreB 211-225 , UreB 349-363 , HpaA 132-141 , and HSP60 189-203 ). In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4 + T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to H. pylori . These results indic ate that a multivalent epitope-based vaccine including Th and B cell epitopes from various H. pylori antigens could be a promising candidate against H. pylori infection.

Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils

PubMed Central

Guo, Le; Yang, Hua; Tang, Feng; Yin, Runting; Liu, Hongpeng; Gong, Xiaojuan; Wei, Jun; Zhang, Ying; Xu, Guangxian; Liu, Kunmei

2017-01-01

Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori (H. pylori) infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori, remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP), heat shock protein 60 (HSP60) and H. pylori adhesin A (HpaA) was constructed based on mucosal adjuvant cholera toxin B subunit (CTB), Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA27–53, UreA183–203, HpaA132–141, and HSP60189–203), and also the epitope-rich regions of urease B subunit (UreB158–251 and UreB321–385) predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori-infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB158–172, UreB181–195, UreB211–225, UreB349–363, HpaA132–141, and HSP60189–203). In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4+ T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to H. pylori. These results indic ate that a multivalent epitope-based vaccine including Th and B cell epitopes from various H. pylori antigens could be a promising candidate against H. pylori infection. PMID:28824883

[Comparison of the therapeutic effects of electroacupuncture and probiotics combined with deanxit in treating diarrhea-predominant irritable bowel syndrome].

PubMed

Chen, Yue-Hua; Chen, Xing-Kui; Yin, Xiao-Jun

2012-05-01

To study and compare the therapeutic effects of electroacupuncture and probiotics combine Deanxit in treating diarrhea predominant irritable bowel syndrome (D-IBS). Totally 64 D-IBS patients accompanied with anxiety and/or depression were randomly assigned to the Western medicine group (Group A) and the electroacupuncture (EA) group (Group B), 30 patients in Group A and 34 patients in Group B. Patients in Group A took Bacillus licheniformis and Deanxit, while those in Group B received EA. Four weeks consisted of one therapeutic course. Three-month follow-up was carried out. The scoring for the digestive tract symptoms, HAMA score, and HAMD score were evaluated before and after treatment. The recurrence in the 3-month follow-up was also observed. The total effect rate was 86.67% in Group A and 88.24% in Group B with no statistical difference between the two groups (P > 0.05). There was statistical difference in the scoring for the digestive tract symptoms, HAMA score, and HAMD score (P < 0.05, P < 0.01). There was no statistical difference in the improvement of defecation frequency score, HAMA score, HAMD score between the two groups after treatment (P > 0.05). Better effects on improving abdominal pain score and abdominal distention score was obtained in Group B (P < 0.01), while better effects on improving the stool form score and mucus score were obtained in Group A (P < 0.01). There was no statistical difference in the recurrence rate between the two groups within the two-month follow-up (P > 0.05). The recurrence rate within the 3-month follow-up was obviously lower in Group B than in Group A (P < 0.05). EA and Western medicine (probiotics combined Deanxit) could effectively treat D-IBS patients accompanied with anxiety and/or depression. Both of them had different superiorities in improving symptoms. But EA had better long-term therapeutic effects.

Nanoparticle delivery of chemosensitizers improve chemotherapy efficacy without incurring additional toxicity

NASA Astrophysics Data System (ADS)

Caster, Joseph M.; Sethi, Manish; Kowalczyk, Sonya; Wang, Edina; Tian, Xi; Nabeel Hyder, Sayed; Wagner, Kyle T.; Zhang, Ying-Ao; Kapadia, Chintan; Man Au, Kin; Wang, Andrew Z.

2015-01-01

Chemosensitizers can improve the therapeutic index of chemotherapy and overcome treatment resistance. Successful translation of chemosensitizers depends on the development of strategies that can preferentially deliver chemosensitizers to tumors while avoiding normal tissue. We hypothesized that nanoparticle (NP) formulation of chemosensitizers can improve their delivery to tumors which can in turn improve their therapeutic index. To demonstrate the proof of principle of this approach, we engineered NP formulations of two chemosensitizers, the PI3-kindase inhibitor wortmanin (Wtmn) and the PARP inhibitor olaparib. NP Wtmn and NP olaparib were evaluated as chemosensitizers using lung cancer cells and breast cancer cells respectively. We found Wtmn to be an efficient chemosensitizer in all tested lung-cancer cell lines reducing tumor cell growth between 20 and 60% compared to drug alone. NP formulation did not decrease its efficacy in vitro. Olaparib showed less consistent chemosensitization as a free drug or in NP formulation. NP Wtmn was further evaluated as a chemosensitizer using mouse models of lung cancer. We found that NP Wtmn is an effective chemosensitizer and more effective than free Wtmn showing a 32% reduction in tumor growth compared to free Wtmn when given with etoposide. Importantly, NP Wtmn was able to sensitize the multi-drug resistant H69AR cells to etoposide. Additionally, the combination of NP Wtmn and etoposide chemotherapy did not significantly increase toxicity. The present study demonstrates the proof of principle of using NP formulation of chemosensitizing drugs to improve the therapeutic index of chemotherapy.

Protocol for an HTA report: Does therapeutic writing help people with long-term conditions? Systematic review, realist synthesis and economic modelling

PubMed Central

Meads, C; Nyssen, O P; Wong, G; Steed, L; Bourke, L; Ross, C A; Hayman, S; Field, V; Lord, J; Greenhalgh, T; Taylor, S J C

2014-01-01

Introduction Long-term medical conditions (LTCs) cause reduced health-related quality of life and considerable health service expenditure. Writing therapy has potential to improve physical and mental health in people with LTCs, but its effectiveness is not established. This project aims to establish the clinical and cost-effectiveness of therapeutic writing in LTCs by systematic review and economic evaluation, and to evaluate context and mechanisms by which it might work, through realist synthesis. Methods Included are any comparative study of therapeutic writing compared with no writing, waiting list, attention control or placebo writing in patients with any diagnosed LTCs that report at least one of the following: relevant clinical outcomes; quality of life; health service use; psychological, behavioural or social functioning; adherence or adverse events. Searches will be conducted in the main medical databases including MEDLINE, EMBASE, PsycINFO, The Cochrane Library and Science Citation Index. For the realist review, further purposive and iterative searches through snowballing techniques will be undertaken. Inclusions, data extraction and quality assessment will be in duplicate with disagreements resolved through discussion. Quality assessment will include using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data synthesis will be narrative and tabular with meta-analysis where appropriate. De novo economic modelling will be attempted in one clinical area if sufficient evidence is available and performed according to the National Institute for Health and Care Excellence (NICE) reference case. PMID:24549165

Network Meta-Analysis Comparing the Efficacy of Therapeutic Treatments for Bronchiolitis in Children.

PubMed

Guo, Caili; Sun, Xiaomin; Wang, Xiaowen; Guo, Qing; Chen, Dan

2018-01-01

This study aims to compare placebo (PBO) and 7 therapeutic regimens-namely, bronchodilator agents (BAs), hypertonic saline (HS), BA ± HS, corticosteroids (CS), epinephrine (EP), EP ± CS, and EP ± HS-to determine the optimal bronchiolitis treatment. We plotted networks using the curative outcome of several studies and specified the relations among the experiments by using mean difference, standardized mean difference, and corresponding 95% credible interval. The surface under the cumulative ranking curve (SUCRA) was used to separately rank each therapy on clinical severity score (CSS) and length of hospital stay (LHS). This network meta-analysis included 40 articles from 1995 to 2016 concerning the treatment of bronchiolitis in children. All 7 therapeutic regimens displayed no significant difference to PBO with regard to CSS in our study. Among the 7 therapies, BA performed better than CS. As for LHS, EP and EP ± HS had an advantage over PBO. Moreover, EP and EP ± HS were also more efficient than BA. The SUCRA results showed that EP ± CS is most effective, and EP ± HS is second most effective with regard to CSS. With regard to LHS, EP ± HS ranked first, EP ± CS ranked second, and EP ranked third. We recommend EP ± CS and EP ± HS as the first choice for bronchiolitis treatment in children because of their outstanding performance with regard to CSS and LHS. © 2017 American Society for Parenteral and Enteral Nutrition.

Protocol for an HTA report: Does therapeutic writing help people with long-term conditions? Systematic review, realist synthesis and economic modelling.

PubMed

Meads, C; Nyssen, O P; Wong, G; Steed, L; Bourke, L; Ross, C A; Hayman, S; Field, V; Lord, J; Greenhalgh, T; Taylor, S J C

2014-02-18

Long-term medical conditions (LTCs) cause reduced health-related quality of life and considerable health service expenditure. Writing therapy has potential to improve physical and mental health in people with LTCs, but its effectiveness is not established. This project aims to establish the clinical and cost-effectiveness of therapeutic writing in LTCs by systematic review and economic evaluation, and to evaluate context and mechanisms by which it might work, through realist synthesis. Included are any comparative study of therapeutic writing compared with no writing, waiting list, attention control or placebo writing in patients with any diagnosed LTCs that report at least one of the following: relevant clinical outcomes; quality of life; health service use; psychological, behavioural or social functioning; adherence or adverse events. Searches will be conducted in the main medical databases including MEDLINE, EMBASE, PsycINFO, The Cochrane Library and Science Citation Index. For the realist review, further purposive and iterative searches through snowballing techniques will be undertaken. Inclusions, data extraction and quality assessment will be in duplicate with disagreements resolved through discussion. Quality assessment will include using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data synthesis will be narrative and tabular with meta-analysis where appropriate. De novo economic modelling will be attempted in one clinical area if sufficient evidence is available and performed according to the National Institute for Health and Care Excellence (NICE) reference case.

Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Therapy in Women with Stage I-III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue.

PubMed

Lötzke, Désirée; Wiedemann, Florian; Rodrigues Recchia, Daniela; Ostermann, Thomas; Sattler, Daniel; Ettl, Johannes; Kiechle, Marion; Büssing, Arndt

2016-01-01

This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neo)adjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI) (n = 45) or for a physical exercise intervention (PEI) (n = 47). Measurements were obtained before (t 0) and after the intervention (t 1) as well as 3 months after finishing intervention (t 2) using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p < 0.05) but not under YI (t 0 to t 2). Regarding quality of life (EORTC QLQ-C30) a direct effect (t 0 to t 1; p < 0.001) of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p < 0.001) were observed at both t 1 and t 2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t 1 nor for t 2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase.

Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Therapy in Women with Stage I–III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue

PubMed Central

Lötzke, Désirée; Wiedemann, Florian; Rodrigues Recchia, Daniela; Ostermann, Thomas; Sattler, Daniel; Ettl, Johannes; Kiechle, Marion; Büssing, Arndt

2016-01-01

This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neo)adjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI) (n = 45) or for a physical exercise intervention (PEI) (n = 47). Measurements were obtained before (t 0) and after the intervention (t 1) as well as 3 months after finishing intervention (t 2) using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p < 0.05) but not under YI (t 0 to t 2). Regarding quality of life (EORTC QLQ-C30) a direct effect (t 0 to t 1; p < 0.001) of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p < 0.001) were observed at both t 1 and t 2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t 1 nor for t 2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase. PMID:27019663

[Therapeutic effect of double fill nine tastes soup in treating recurrent respiratory infection (RRI) and change of immune function in children].

PubMed

Wang, Youcheng; Zhang, Lijuan; Hu, Guohua; Wang, Menghe; Tang, Xiaoyuan; Guo, Hui; Shi, Yimei; Chen, Shufang; Shi, Changchun

2012-04-01

To investigate the therapeutic effect of double fill nine tastes soup in treating children recurrent respiratory infection (RRTI) and the change of immune function. 77 RRTI patients were randomly selected into observation and control groups. The observation group was treated with Chinese medicine- double fill nine tastes soup,water frying points 2 times oral. The control was treated with transfer factor oral liquid,every 10 mL,2 times daily oral. Treatment periods were both two months. IgA, IgG, IgM and IL-12, TNF-alpha, INF-gamma were detected before and after treatment to assess the clinical effects and the changes of immune factors, meanwhile, a health group was established. Before treatment, compared with the health group, the serum IgA, IgG, IgM, IgE, IL-12, TNF-alpha, IFN-gamma in both groups were significantly different (P < 0.01). After treatment, the ratio of IgA, IgG, Ig M, IL-12, TNF-alpha, IFN-gamma in two groups were significantly different (P < 0.01). Compared with the recurrence rate and clinical effects, the observation group was better than control, and the differences were significant (P < 0.01). Double fill nine tastes soup has significant effects in treating recurrent respiratory infection (RRI) and enhance the immune function in children.

Prolonged analgesic effect of PLGA-encapsulated bee venom on formalin-induced pain in rats.

PubMed

Jeong, Injae; Kim, Beom-Soo; Lee, Hyejung; Lee, Kang-Min; Shim, Insop; Kang, Sung-Keel; Yin, Chang-Shick; Hahm, Dae-Hyun

2009-10-01

To enhance the medicinal activity of bee venom (BV) acupuncture, bee venom was loaded into biodegradable poly(D,L-lactide-co-glycolide) nanoparticles (BV-PLGA-NPs) by a water-in-oil-in-water-emulsion/solvent-evaporation technique. Rat formalin tests were performed after subcutaneous injection of BV-PLGA-NPs to the Zusanli acupuncture point (ST36) at 0.5, 1, 2, 6, 12, 24, and 48 h before plantar injection of 2% formalin. BV-PLGA-NPs treatment showed comparable analgesic activity to typical BV acupuncture during the late phase, compared with saline-treated controls, and the analgesic effect lasted for 12h. PLGA-encapsulation was also effective in alleviating the edema induced by allergens in bee venom. These results indicate that PLGA-encapsulation provided a more prolonged effect of BV acupuncture treatment, while maintaining a comparable therapeutic effect.

Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications.

PubMed

Kraehenmann, Rainer

2017-01-01

A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or 'classical' psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,Ndimethyltryptamine), and ayahuasca - a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams, and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Research literature related to psychedelics and dreaming is reviewed, and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelicassisted therapy will be provided. Common features between psychedelic states and night dreams include perception, mental imagery, emotion activation, fear memory extinction, and sense of self and body. Differences between these two states are related to differential perceptual input from the environment, clarity of consciousness and meta-cognitive abilities. Therefore, psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness. The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications

PubMed Central

Kraehenmann, Rainer

2017-01-01

Background: A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or ‘classical’ psychedelics such as the prototypical psychedelic drug lysergic acid diethylamide (LSD) psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Methods: Research literature related to psychedelics and dreaming is reviewed and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelic-assisted therapy will be provided. Results: Common features between psychedelic states and night dreams include perception mental imagery emotion activation fear memory extinction and sense of self and body. Differences between these two states are related to differential perceptual input from the environment clarity of consciousness and meta-cognitive abilities. Therefore psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness Conclusion: The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. PMID:28625125

Systematic review and meta-analysis of the diagnostic and therapeutic role of water-soluble contrast agent in adhesive small bowel obstruction.

PubMed

Branco, B C; Barmparas, G; Schnüriger, B; Inaba, K; Chan, L S; Demetriades, D

2010-04-01

This meta-analysis assessed the diagnostic and therapeutic role of water-soluble contrast agent (WSCA) in adhesive small bowel obstruction (SBO). PubMed, Embase and Cochrane databases were searched systematically. The primary outcome in the diagnostic role of WSCA was its ability to predict the need for surgery. In the therapeutic role, the following were evaluated: resolution of SBO without surgery, time from admission to resolution, duration of hospital stay, complications and mortality. To assess the diagnostic role of WSCA, pooled estimates of sensitivity, specificity, positive and negative predictive values, and likelihood ratios were derived. For the therapeutic role of WSCA, weighted odds ratio (OR) and weighted mean difference (WMD) were obtained. Fourteen prospective studies were included. The appearance of contrast in the colon within 4-24 h after administration had a sensitivity of 96 per cent and specificity of 98 per cent in predicting resolution of SBO. WSCA administration was effective in reducing the need for surgery (OR 0.62; P = 0.007) and shortening hospital stay (WMD -1.87 days; P < 0.001) compared with conventional treatment. Water-soluble contrast was effective in predicting the need for surgery in patients with adhesive SBO. In addition, it reduced the need for operation and shortened hospital stay. Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Therapeutic efficacy of the combination of doxorubicin-loaded liposomes with inertial cavitation generated by confocal ultrasound in AT2 Dunning rat tumour model.

PubMed

Mestas, Jean-Louis; Fowler, R Andrew; Evjen, Tove J; Somaglino, Lucie; Moussatov, Alexei; Ngo, Jacqueline; Chesnais, Sabrina; Røgnvaldsson, Sibylla; Fossheim, Sigrid L; Nilssen, Esben A; Lafon, Cyril

2014-09-01

The combination of liposomal doxorubicin (DXR) and confocal ultrasound (US) was investigated for the enhancement of drug delivery in a rat tumour model. The liposomes, based on the unsaturated phospholipid dierucoylphosphocholine, were designed to be stable during blood circulation in order to maximize accumulation in tumour tissue and to release drug content upon US stimulation. A confocal US setup was developed for delivering inertial cavitation to tumours in a well-controlled and reproducible manner. In vitro studies confirm drug release from liposomes as a function of inertial cavitation dose, while in vivo pharmacokinetic studies show long blood circulation times and peak tumour accumulation at 24-48 h post intravenous administration. Animals injected 6 mg kg(-1) liposomal DXR exposed to US treatment 48 h after administration show significant tumour growth delay compared to control groups. A liposomal DXR dose of 3 mg kg(-1), however, did not induce any significant therapeutic response. This study demonstrates that inertial cavitation can be generated in such a fashion as to disrupt drug carrying liposomes which have accumulated in the tumour, and thereby increase therapeutic effect with a minimum direct effect on the tissue. Such an approach is an important step towards a therapeutic application of cavitation-induced drug delivery and reduced chemotherapy toxicity.

Treatment with endotracheal therapeutics after sarin microinstillation inhalation exposure increases blood cholinesterase levels in guinea pigs.

PubMed

Che, Magnus M; Song, Jian; Oguntayo, Samuel; Doctor, Bhupendra P; Rezk, Peter; Perkins, Michael W; Sciuto, Alfred M; Nambiar, Madhusoodana P

2012-05-01

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were measured in the blood and tissues of animals that are treated with a number of endotracheally aerosolized therapeutics for protection against inhalation toxicity to sarin. Therapeutics included, aerosolized atropine methyl bromide (AMB), scopolamine or combination of AMB with salbutamol, sphingosine 1-phosphate, keratinocyte growth factor, adenosine A1 receptor antisense oligonucleotide (EPI2010), 2,3-diacetyloxybenzoic acid (2,3 DABA), oxycyte, and survanta. Guinea pigs exposed to 677.4 mg/m(3) or 846.5 mg/m(3) (1.2 LCt(50)) sarin for 4 min using a microinstillation inhalation exposure technique and treated 1 min later with the aerosolized therapeutics. Treatment with all therapeutics significantly increased the survival rate with no convulsions throughout the 24 h study period. Blood AChE activity determined using acetylthiocholine as substrate showed 20% activity remaining in sarin-exposed animals compare to controls. In aerosolized AMB and scopolamine-treated animals the remaining AChE activity was significantly higher (45-60%) compared to sarin-exposed animals (p < 0.05). Similarly, treatment with all the combination therapeutics resulted in significant increase in blood AChE activity in comparison to sarin-exposed animals although the increases varied between treatments (p < 0.05). BChE activity was increased after treatment with aerosolized therapeutics but was lesser in magnitude compared to AChE activity changes. Various tissues showed elevated AChE activity after therapeutic treatment of sarin-exposed animals. Increased AChE and BChE activities in animals treated with nasal therapeutics suggest that enhanced breathing and reduced respiratory toxicity/lung injury possibly contribute to rapid normalization of chemical warfare nerve agent inhibited cholinesterases.

Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors.

PubMed

Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin'ichi; Aoki, Yoshitsugu

2016-01-01

Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD.

Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors

PubMed Central

Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin’ichi; Aoki, Yoshitsugu

2016-01-01

Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD. PMID:27621596

Clinicians' perspectives of therapeutic alliance in face-to-face and telepractice speech-language pathology sessions.

PubMed

Freckmann, Anneka; Hines, Monique; Lincoln, Michelle

2017-06-01

To investigate the face validity of a measure of therapeutic alliance for paediatric speech-language pathology and to determine whether a difference exists in therapeutic alliance reported by speech-language pathologists (SLPs) conducting face-to-face sessions, compared with telepractice SLPs or in their ratings of confidence with technology. SLPs conducting telepractice (n = 14) or face-to-face therapy (n = 18) completed an online survey which included the Therapeutic Alliance Scales for Children - Revised (TASC-r) (Therapist Form) to rate clinicians' perceptions of rapport with up to three clients. Participants also reported their overall perception of rapport with each client and their comfort with technology. There was a strong correlation between TASC-r total scores and overall ratings of rapport, providing preliminary evidence of TASC-r face validity. There was no significant difference between TASC-r scores for telepractice and face-to-face therapy (p = 0.961), nor face-to-face and telepractice SLPs' confidence with familiar (p = 0.414) or unfamiliar technology (p = 0.780). The TASC-r may be a promising tool for measuring therapeutic alliance in speech-language pathology. Telepractice does not appear to have a negative effect on rapport between SLPs and paediatric clients. Future research is required to identify how SLPs develop rapport in telepractice.

A clinical assay for the measurement of milrinone in plasma by HPLC mass spectrometry.

PubMed

Chihoho, B; Sage, A B; Smolenski, R T; Vazir, A; Rose, M L; Banner, N R; Leaver, N V

2012-05-01

Milrinone is a bipyridine phosphodiesterase inhibitor with positive inotropic and vasodilatory effects. As interest in longer term use of intravenous therapy increases, it becomes essential to monitor its plasma concentration owing to a narrow therapeutic range, an increased half-life in renal failure and toxicity associated with high levels. A high-performance liquid chromatography (HPLC) method with mass (MS) detection using a triple quadrupole mass spectrometer is presented. The method was compared with the UV/HPLC method and validated according to current international guidelines. Coefficients of variation of less than 7.5% were obtained across the therapeutic range and 18.3% at 2.4 ng/mL, the lower limit of quantitation. Plasma from 13 cardiac surgery patients receiving standard intravenous doses of milrinone were measured. Eight patients achieved therapeutic milrinone levels within 3-4 h post start of infusion, one was borderline sub-therapeutic and four patients achieved levels that were above the upper limit of the therapeutic range and potentially toxic. This method offers high sensitivity, is rapid, easy to use and requires minimal amount of sample. We believe this method could become the reference procedure for clinical monitoring of milrinone and help to improve the safety of the use of this drug in patients with cardiac failure. Copyright © 2011 John Wiley & Sons, Ltd.

Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis.

PubMed

Ahn, Julie; Bishop, Justin A; Akpeng, Belinda; Pai, Sara I; Best, Simon R A

2015-02-01

Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid-IL2Rgamma(null) (NSG) mouse. The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control. We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis. © The Author(s) 2014.

Investigation of Color in a Fusion Protein Using Advanced Analytical Techniques: Delineating Contributions from Oxidation Products and Process Related Impurities.

PubMed

Song, Hangtian; Xu, Jianlin; Jin, Mi; Huang, Chao; Bongers, Jacob; Bai, He; Wu, Wei; Ludwig, Richard; Li, Zhengjian; Tao, Li; Das, Tapan K

2016-04-01

Discoloration of protein therapeutics has drawn increased attention recently due to concerns of potential impact on quality and safety. Investigation of discoloration in protein therapeutics for comparability is particularly challenging primarily for two reasons. First, the description of color or discoloration is to certain extent a subjective characteristic rather than a quantitative attribute. Secondly, the species contributing to discoloration may arise from multiple sources and are typically present at trace levels. Our purpose is to development a systematic approach that allows effective identification of the color generating species in protein therapeutics. A yellow-brown discoloration event observed in a therapeutic protein was investigated by optical spectroscopy, ultra-performance liquid chromatography, and mass spectrometry (MS). Majority of the color generating species were identified as oxidatively modified protein. The location of the oxidized amino acid residues were identified by MS/MS. In addition, the impact of process-related impurities co-purified from media on discoloration was also investigated. Finally a semi-quantitative scale to estimate the contribution of each color source is presented, which revealed oxidized peptides are the major contributors. A systematic approach was developed for identification of the color generating species in protein therapeutics and for estimation of the contribution of each color source.

Cells as advanced therapeutics: State-of-the-art, challenges, and opportunities in large scale biomanufacturing of high-quality cells for adoptive immunotherapies.

PubMed

Dwarshuis, Nate J; Parratt, Kirsten; Santiago-Miranda, Adriana; Roy, Krishnendu

2017-05-15

Therapeutic cells hold tremendous promise in treating currently incurable, chronic diseases since they perform multiple, integrated, complex functions in vivo compared to traditional small-molecule drugs or biologics. However, they also pose significant challenges as therapeutic products because (a) their complex mechanisms of actions are difficult to understand and (b) low-cost bioprocesses for large-scale, reproducible manufacturing of cells have yet to be developed. Immunotherapies using T cells and dendritic cells (DCs) have already shown great promise in treating several types of cancers, and human mesenchymal stromal cells (hMSCs) are now extensively being evaluated in clinical trials as immune-modulatory cells. Despite these exciting developments, the full potential of cell-based therapeutics cannot be realized unless new engineering technologies enable cost-effective, consistent manufacturing of high-quality therapeutic cells at large-scale. Here we review cell-based immunotherapy concepts focused on the state-of-the-art in manufacturing processes including cell sourcing, isolation, expansion, modification, quality control (QC), and culture media requirements. We also offer insights into how current technologies could be significantly improved and augmented by new technologies, and how disciplines must converge to meet the long-term needs for large-scale production of cell-based immunotherapies. Copyright © 2017 Elsevier B.V. All rights reserved.

The Antimalarial Effect of Curcumin Is Mediated by the Inhibition of Glycogen Synthase Kinase-3β.

PubMed

Ali, Amatul Hamizah; Sudi, Suhaini; Basir, Rusliza; Embi, Noor; Sidek, Hasidah Mohd

2017-02-01

Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3β and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3β.

Effect of OSA on hypoxic and inflammatory markers during CPAP withdrawal: Further evidence from three randomized control trials.

PubMed

Turnbull, Chris D; Rossi, Valentina A; Santer, Peter; Schwarz, Esther I; Stradling, John R; Petousi, Nayia; Kohler, Malcolm

2017-05-01

Obstructive sleep apnoea (OSA) is associated with cardiovascular disease. Intermittent hypoxia, endothelial dysfunction and adipose tissue-mediated inflammation have all been linked to cardiovascular disease in OSA. We therefore explored the effect of OSA on relevant associated blood markers: adrenomedullin (ADM), endocan, endothelin-1 (ET-1), resistin and vascular endothelial growth factor (VEGF). Patients with OSA, established on and compliant with continuous positive airways pressure (CPAP) therapy for >1 year were included from three randomized controlled trials, conducted at two centres. Patients were randomized to either continued therapeutic CPAP or sham CPAP (CPAP withdrawal) for 2 weeks. Blood markers were measured at baseline and at 14 days and the treatment effect between sham CPAP and therapeutic CPAP was analysed. A total of 109 patients were studied (therapeutic CPAP n = 54, sham CPAP n = 55). Sham CPAP was associated with a return of OSA (between-group difference in oxygen desaturation index (ODI) 36.0/h, 95% CI 29.9-42.2, P < 0.001). Sham CPAP was associated with a reduction in ADM levels at 14 days (-26.0 pg/mL, 95% CI -47.8 to -4.3, P = 0.02), compared to therapeutic CPAP. Return of OSA was not associated with changes in endocan, ET-1, resistin or VEGF. Whilst CPAP withdrawal was associated with return of OSA, it was associated with an unexpected significant reduction in the vasodilator ADM and not with expected increases in hypoxia-induced markers, markers of endothelial function or resistin. We propose that the vascular effects occurring in OSA may be brought about by other mechanisms, perhaps partly through a reduction in ADM. © 2016 Asian Pacific Society of Respirology.

Therapeutic Effect of CD4+CD25+ Regulatory T Cells Amplified In Vitro on Experimental Autoimmune Neuritis in Rats.

PubMed

Wang, Feng-Jie; Cui, Dan; Qian, Wei-Dong

2018-05-14

This study aimed to explore whether the adoptive transfusion of autologous CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) has a therapeutic effect on Experimental autoimmune neuritis (EAN) model rats, and it provides new experimental and theoretical bases for the immunotherapy of Guillain-Barre syndrome (GBS). CD4+CD25+ Tregs were sorted from the spleens of rats using immunomagnetic bead separation techniques combined with flow cytometry. Their in vitro inhibitory function was determined using a lymphocyte proliferation inhibition test, and their purity was confirmed by flow cytometry. Cells were stimulated using CD3/CD28 monoclonal antibodies and were cultured in culture medium containing interleukin 2 (IL-2), transforming growth factor-β (TGF-β) and rapamycin. After 15 days of amplification, CD4+CD25+ Tregs were collected and transfused into EAN model rats. Changes in the pathology and electron microscopical morphology of rat sciatic nerves in the normal group, untreated group, low-dose group (2 × 107) and high-dose group (4 × 107) were observed, and the expression of CD4+CD25+FOXP3 in peripheral blood in the four groups of rats was detected by flow cytometry. Compared with rats in the untreated group, rats in the treatment groups had significantly reduced infiltration of inflammatory cells in the sciatic nerve, as well as myelin and axonal damage. Additionally, the CD4+CD25+ Tregs levels in peripheral blood were significantly higher than those in the untreated group (P< 0. 05). Moreover, the therapeutic effect became more significant with an increase in the dose of adoptive transfusion. Adoptive transfusion of CD4+CD25+ Tregs into EAN model rats has significant therapeutic effects. © 2018 The Author(s). Published by S. Karger AG, Basel.

Darbepoetin alfa therapeutic interchange protocol for anemia in dialysis.

PubMed

Brophy, Donald F; Ripley, Elizabeth Bd; Kockler, Denise R; Lee, Seina; Proeschel, Lori A

2005-11-01

Erythropoiesis-stimulating proteins, such as erythropoietin alfa and darbepoetin alfa, have positively impacted anemia management. These medications improve patient outcomes and quality of life. Their costs, however, remain a major barrier for health systems. To evaluate the development, implementation, and cost-effectiveness of an inpatient therapeutic interchange protocol for erythropoiesis-stimulating proteins at a large, tertiary care, university-affiliated health system. Virginia Commonwealth University Health System (VCUHS) developed and implemented a therapeutic interchange program to convert therapy for all inpatients undergoing dialysis from erythropoietin alfa to darbepoetin alfa for treatment of chronic kidney disease-related anemia. An evaluation of the economic impact of this program on drug expenditures over a fiscal quarter (2003) was conducted using historical comparator data (2002). Preliminary evaluation of the program demonstrated cost-savings and reduced drug utilization of erythropoiesis-stimulating proteins in hospitalized dialysis patients. For the first quarter of 2003 compared with the first quarter of 2002, VCUHS realized a cost-savings of nearly 10,000 US dollars, which was related to the program's aggressive screening procedure. When these data were normalized for equal numbers of patients in each group receiving one of the drugs, the actual cost-savings was over 2000 US dollars. These cost-savings are largely due to reduced utilization of these expensive biotechnology products with implementation of a dosing protocol. VCUHS has successfully developed and implemented a darbepoetin alfa therapeutic interchange protocol for hospitalized dialysis patients. This has translated into reduced use of erythropoiesis-stimulating proteins, resulting in cost-savings for the health system.

Synthetic hepcidin from fish: Uptake and protection against Vibrio anguillarum in sea bass (Dicentrarchus labrax).

PubMed

Álvarez, Claudio Andrés; Acosta, Félix; Montero, Daniel; Guzmán, Fanny; Torres, Elisa; Vega, Belinda; Mercado, Luis

2016-08-01

The generation of a variety of new therapeutic agents to control and reduce the effects of pathogen in aquaculture is urgently needed. The antimicrobial peptides (AMPs) are one of the major components of the innate defenses and typically have broad-spectrum antimicrobial activity. However, absorption and distributions of exogenous AMPs for therapeutics application on farmed fish species need to be studied. Previous studies in our laboratory have shown the properties of hepcidin as an effective antimicrobial peptide produced in fish in response to LPS and iron. Therefore, we decided to investigate the antimicrobial activity of four synthetic variants of hepcidin against Vibrio anguillarum in vitro, and using the more effective peptide we demonstrated the pathogen's ability to protect against the infection in European Sea bass. Additionally the uptake of this peptide after ip injection was demonstrated, reaching its distribution organs such as intestine, head kidney, spleen and liver. The synthetic peptide did not show cytotoxic effects and significantly reduced the accumulated mortalities percentage (23.5%) compared to the European Sea bass control (72.5%) at day 21. In conclusion, synthetic hepcidin shows antimicrobial activity against V. anguillarum and the in vivo experiments suggest that synthetic hepcidin was distributed trough the different organs in the fish. Thus, synthetic hepcidin antimicrobial peptide could have high potential for therapeutic application in farmed fish species. Copyright © 2016 Elsevier Ltd. All rights reserved.

Therapeutic effect of budesonide/formoterol, montelukast and N-acetylcysteine for bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

PubMed

Kim, Sei Won; Rhee, Chin Kook; Kim, Yoo Jin; Lee, Seok; Kim, Hee Je; Lee, Jong Wook

2016-05-26

Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) is currently treated with systemic corticosteroids despite poor efficacy and side effects. This study investigated the therapeutic effect of budesonide/formoterol, montelukast and n-acetylcysteine, which are suggested as treatment options for BOS after HSCT. After diagnosis of BOS, 61 patients were treated with budesonide/formoterol, montelukast and n-acetylcysteine for 3 months. Pulmonary function test and COPD assessment test (CAT) were performed before and after the combination therapy. Therapeutic response was evaluated by changes in forced expiratory volume in 1 s (FEV1) or CAT score. After 3 months of combination treatment, mean FEV1 increased by 220 mL (p < 0.001) and residual volume decreased by 200 mL (p =0 .005). Median CAT score also significantly decreased from 15.5 to 11.0 (p = 0.001). The overall response rate to combination therapy was 82 %. Comparing the no-response group and the response group, the forced vital capacity (% predicted) decline between pre-HSCT and BOS diagnosis was significantly greater in the response group (p = 0.036). Combination treatment with budesonide/formoterol, montelukast and n-acetylcysteine significantly improved lung function and respiratory symptoms in patients with BOS after allogeneic HSCT without serious side effects.

Cannabis for therapeutic purposes: patient characteristics, access, and reasons for use.

PubMed

Walsh, Zach; Callaway, Robert; Belle-Isle, Lynne; Capler, Rielle; Kay, Robert; Lucas, Philippe; Holtzman, Susan

2013-11-01

The authorized and unauthorized use of cannabis for therapeutic purposes (CTP) has increased dramatically in recent years, and physicians have called for further research to better clarify the parameters of effective and appropriate use. We report findings from a large cross-sectional study of the use of CTP in Canada and compare use across medical conditions and across authorized and unauthorized users. We examined cannabis use history, medical conditions and symptoms, patterns of current use of CTP, modes of access and perceived effectiveness among 628 self-selected Canadians consumers of CTP. Participants were recruited from medical cannabis dispensaries and from organizations that assist users of CTP. Patients reported using cannabis to treat multiple symptoms, with sleep, pain, and anxiety being the most common. Cannabis was perceived to provide effective symptoms relief across medical conditions. Patterns of use were also consistent across medical conditions. Notable differences were observed with regard to modes of access. Across medical conditions respondents reported using cannabis to effectively address diverse symptoms. Results indicate a substantial disconnect between the therapeutic use of cannabis and research on the risks and benefits of such use; particularly with regard to the anxiolytic and sedative use of cannabis. Authorized and unauthorized users exhibited few meaningful differences with regard to medical conditions and patterns of use, but faced substantial differences regarding access. Copyright © 2013 Elsevier B.V. All rights reserved.

Health Care Provider Communication

PubMed Central

Chochinov, Harvey M; McClement, Susan E; Hack, Thomas F; McKeen, Nancy A; Rach, Amanda M; Gagnon, Pierre; Sinclair, Shane; Taylor-Brown, Jill

2013-01-01

BACKGROUND Patients who are facing life-threatening and life-limiting cancer almost invariably experience psychological distress. Responding effectively requires therapeutic sensitivity and skill. In this study, we examined therapeutic effectiveness within the setting of cancer-related distress with the objective of understanding its constituent parts. METHODS Seventy-eight experienced psychosocial oncology clinicians from 24 health care centers across Canada were invited to participate in 3 focus groups each. In total, 29 focus groups were held over 2 years, during which clinicians articulated the therapeutic factors deemed most helpful in mitigating patient psychosocial distress. The content of each focus group was summarized into major themes and was reviewed with participants to confirm their accuracy. Upon completion of the focus groups, workshops were held in various centers, eliciting participant feedback on an empirical model of therapeutic effectiveness based on the qualitative analysis of focus group data. RESULTS Three primary, interrelated therapeutic domains emerged from the data, forming a model of optimal therapeutic effectiveness: 1) personal growth and self-care (domain A), 2) therapeutic approaches (domain B), and 3) creation of a safe space (domain C). Areas of domain overlap were identified and labeled accordingly: domain AB, therapeutic humility; domain BC, therapeutic pacing; and domain AC, therapeutic presence. CONCLUSIONS This empirical model provides detailed insights regarding the elements and pedagogy of effective communication and psychosocial care for patients who are experiencing cancer-related distress. [See editorial on pages 000–000, this issue.] Cancer 2013. © 2013 American Cancer Society. PMID:23341092

Rheumatoid arthritis treatment with TNF inhibitors and alternative procedures in case of its failure – results of the Polish survey in the context of EULAR recommendations

PubMed Central

Dębowska, Grażyna; Spytek, Joanna; Tłustochowicz, Witold

2015-01-01

Introduction According to the European League Against Rheumatism (EULAR), rheumatoid arthritis (RA) treatment aims to achieve remission or low disease activity (LDA) within 6 months. In Poland, despite the existence of the National Health Fund Drug Program (NHF-DP), data on the effects of treatment with biological agents in patients with RA are not publicly available. Also we cannot compare registers from other countries with the Polish results because the rules of the therapeutic program in Poland impose restrictions that do not exist in other countries. For this reason, the data will not be comparable, but the results of the currently used regimen for biological treatment in Poland should be analyzed and compared with the recommendations of the European EULAR as a contribution to further discussion. Objectives To determine the tumor necrosis factor α (TNF-α) inhibitor treatment patterns in RA patients in Poland, to evaluate the frequency and causes of treatment failure as well as post-failure recommendations, and to compare Polish clinical practice enforced by the therapeutic program with the EULAR recommendations. Material and methods The data on 895 RA patients were retrospectively collected from routine medical records. A questionnaire was completed only once for each patient. Results After 3 months of treatment with a TNF-α inhibitor, the therapeutic target was achieved in 72% of patients: 4% in remission, 8% LDA, and 60% with moderate disease activity (MDA); after 9 months, 46% had reached the target: 16% in remission, 30% with LDA. An average of 49% of patients presented with MDA or high disease activity (HDA), thus requiring treatment modification. Treatment failure was confirmed in 14% of patients and a modified therapy administered: rituximab (72%) or adalimumab (20%). The most common cause of failure was inefficacy of treatment (70%). Conclusions In the Polish therapeutic program, despite the persistence of MDA or HDA, the treatment with TNF inhibitors rarely qualifies as ineffective and therefore is seldom modified by switching to another biologic drug. As long as the initiation of treatment and its modifications are enforced by the NHF-DP and not the recommendations of EULAR, treatment may be less effective and paradoxically cost-intensive. Therefore, it seems obvious that it is necessary to change and adapt the NHF-DP requirements to European standards. PMID:27407248

Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis.

PubMed

Zhu, Yu; Wang, Yuchen; Zhao, Bizeng; Niu, Xin; Hu, Bin; Li, Qing; Zhang, Juntao; Ding, Jian; Chen, Yunfeng; Wang, Yang

2017-03-09

Osteoarthritis (OA) is the most common joint disease worldwide. In the past decade, mesenchymal stem cells (MSCs) have been used widely for the treatment of OA. A potential mechanism of MSC-based therapies has been attributed to the paracrine secretion of trophic factors, in which exosomes may play a major role. In this study, we aimed to compare the effectiveness of exosomes secreted by synovial membrane MSCs (SMMSC-Exos) and exosomes secreted by induced pluripotent stem cell-derived MSCs (iMSC-Exos) on the treatment of OA. Induced pluripotent stem cell-derived MSCs and synovial membrane MSCs were characterized by flow cytometry. iMSC-Exos and SMMSC-Exos were isolated using an ultrafiltration method. Tunable resistive pulse-sensing analysis, transmission electron microscopy, and western blots were used to identify exosomes. iMSC-Exos and SMMSC-Exos were injected intra-articularly in a mouse model of collagenase-induced OA and the efficacy of exosome injections was assessed by macroscopic, histological, and immunohistochemistry analysis. We also evaluated the effects of iMSC-Exos and SMMSC-Exos on proliferation and migration of human chondrocytes by cell-counting and scratch assays, respectively. The majority of iMSC-Exos and SMMSC-Exos were approximately 50-150 nm in diameter and expressed CD9, CD63, and TSG101. The injection of iMSC-Exos and SMMSC-Exos both attenuated OA in the mouse OA model, but iMSC-Exos had a superior therapeutic effect compared with SMMSC-Exos. Similarly, chondrocyte migration and proliferation were stimulated by both iMSC-Exos and SMMSC-Exos, with iMSC-Exos exerting a stronger effect. The present study demonstrated that iMSC-Exos have a greater therapeutic effect on OA than SMMSC-Exos. Because autologous iMSCs are theoretically inexhaustible, iMSC-Exos may represent a novel therapeutic approach for the treatment of OA.

The Effect of Ursolic Acid on Leishmania (Leishmania) amazonensis Is Related to Programed Cell Death and Presents Therapeutic Potential in Experimental Cutaneous Leishmaniasis

PubMed Central

Yamamoto, Eduardo S.; Campos, Bruno L. S.; Jesus, Jéssica A.; Laurenti, Márcia D.; Ribeiro, Susan P.; Kallás, Esper G.; Rafael-Fernandes, Mariana; Santos-Gomes, Gabriela; Silva, Marcelo S.; Sessa, Deborah P.; Lago, João H. G.; Levy, Débora; Passero, Luiz F. D.

2015-01-01

Among neglected tropical diseases, leishmaniasis is one of the most important ones, affecting more than 12 million people worldwide. The available treatments are not well tolerated, and present diverse side effects, justifying the search for new therapeutic compounds. In the present study, the activity of ursolic acid (UA) and oleanolic acid (OA) were assayed in experimental cutaneous leishmaniasis (in vitro and in vivo). Promastigote forms of L. amazonensis were incubated with OA and UA for 24h, and effective concentration 50% (EC50) was estimated. Ultraestructural alterations in Leishmania amazonensis promastigotes after UA treatment were evaluated by transmission electron microscopy, and the possible mode of action was assayed through Annexin V and propidium iodide staining, caspase 3/7 activity, DNA fragmentation and transmembrane mitochondrial potential. The UA potential was evaluated in intracellular amastigotes, and its therapeutic potential was evaluated in L. amazonensis infected BALB/c mice. UA eliminated L. amazonensis promastigotes with an EC50 of 6.4 μg/mL, comparable with miltefosine, while OA presented only a marginal effect on promastigote forms at 100 μg/mL. The possible mechanism by which promastigotes were eliminated by UA was programmed cell death, independent of caspase 3/7, but it was highly dependent on mitochondria activity. UA was not toxic for peritoneal macrophages from BALB/c mice, and it was able to eliminate intracellular amastigotes, associated with nitric oxide (NO) production. OA did not eliminate amastigotes nor trigger NO. L. amazonensis infected BALB/c mice submitted to UA treatment presented lesser lesion size and parasitism compared to control. This study showed, for the first time, that UA eliminate promastigote forms through a mechanism associated with programed cell death, and importantly, was effective in vivo. Therefore, UA can be considered an interesting candidate for future tests as a prototype drug for the treatment of cutaneous leishmaniasis. PMID:26674781

Albumin nanoparticles with synergistic antitumor efficacy against metastatic lung cancers.

PubMed

Kim, Bomi; Seo, Bohyung; Park, Sanghyun; Lee, Changkyu; Kim, Jong Oh; Oh, Kyung Taek; Lee, Eun Seong; Choi, Han-Gon; Youn, Yu Seok

2017-10-01

Albumin nanoparticles are well-known as effective drug carriers used to deliver hydrophobic chemotherapeutic agents. Albumin nanoparticles encapsulating curcumin and doxorubicin were fabricated using slightly modified nanoparticle albumin-bound (nab™) technology, and the synergistic effects of these two drugs were examined. Albumin nanoparticles encapsulating curcumin, doxorubicin, and both curcumin and doxorubicin were prepared using a high pressure homogenizer. The sizes of albumin nanoparticles were ∼130nm, which was considered to be suitable for the EPR (enhanced permeability and retention) effect. Albumin nanoparticles gradually released drugs over a period of 24h without burst effect. To confirm the synergistic effect of two drugs, in vitro cytotoxicity assay was performed using B16F10 melanoma cells. The cytotoxic effect on B16F10 melanoma cells was highest when co-treated with both curcumin and doxorubicin compared to single treatment of either curcumin and doxorubicin. The combined index calculated by medium-effect equation was 0.6069, indicating a synergistic effect. Results of confocal laser scanning microscopy and fluorescence-activated cell sorting corresponded to results from an in vitro cytotoxicity assay, indicating synergistic cytotoxicity induced by both drugs. A C57BL/6 mouse model induced by B16F10 lung metastasis was used to study in vivo therapeutic effects. When curcumin and doxorubicin were simultaneously treated, the metastatic melanoma mass in the lungs macroscopically decreased compared to curcumin or doxorubicin alone. Albumin nanoparticles encapsulating two anticancer drugs were shown to have an effective therapeutic result and would be an excellent way to treat resistant lung cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

Platelet lysate enhances synovial fluid multipotential stromal cells functions: Implications for therapeutic use.

PubMed

Altaie, Ala; Baboolal, Thomas G; Wall, Owen; Jones, Elena; McGonagle, Dennis

2018-03-01

Although intra-articular injection of platelet products is increasingly used for joint regenerative approaches, there are few data on their biological effects on joint-resident multipotential stromal cells (MSCs), which are directly exposed to the effects of these therapeutic strategies. Therefore, this study investigated the effect of platelet lysate (PL) on synovial fluid-derived MSCs (SF-MSCs), which in vivo have direct access to sites of cartilage injury. SF-MSCs were obtained during knee arthroscopic procedures (N = 7). Colony forming unit-fibroblast (CFU-F), flow-cytometric phenotyping, carboxyfluorescein succinimidyl ester-based immunomodulation for T-cell and trilineage differentiation assays were performed using PL and compared with standard conditions. PL-enhanced SF-MSC (PL-MSC) proliferation as CFU-F colonies was 1.4-fold larger, and growing cultures had shorter population-doubling times. PL-MSCs and fetal calf serum (FCS)-MSCs had the same immunophenotype and similar immunomodulation activities. In chondrogenic and osteogenic differentiation assays, PL-MSCs produced 10% more sulfated-glycosaminoglycan (sGAG) and 45% less Ca ++ compared with FCS-MSCs, respectively. Replacing chondrogenic medium transforming growth factor-β3 with 20% or 50% PL further increased sGAG production of PL-MSCs by 69% and 95%, respectively, compared with complete chondrogenic medium. Also, Dulbecco's Modified Eagle's Medium high glucose (HG-DMEM) plus 50% PL induced more chondrogenesis compared with HG-DMEM plus 10% FCS and was comparable to complete chondrogenic medium. This is the first study to assess SF-MSC responses to PL and provides biological support to the hypothesis that PL may be capable of modulating multiple functional aspects of joint resident MSCs with direct access to injured cartilage. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Modeling shifts in the rate and pattern of subthalamopallidal network activity during deep brain stimulation.

PubMed

Hahn, Philip J; McIntyre, Cameron C

2010-06-01

Deep brain stimulation (DBS) of the subthlamic nucleus (STN) represents an effective treatment for medically refractory Parkinson's disease; however, understanding of its effects on basal ganglia network activity remains limited. We constructed a computational model of the subthalamopallidal network, trained it to fit in vivo recordings from parkinsonian monkeys, and evaluated its response to STN DBS. The network model was created with synaptically connected single compartment biophysical models of STN and pallidal neurons, and stochastically defined inputs driven by cortical beta rhythms. A least mean square error training algorithm was developed to parameterize network connections and minimize error when compared to experimental spike and burst rates in the parkinsonian condition. The output of the trained network was then compared to experimental data not used in the training process. We found that reducing the influence of the cortical beta input on the model generated activity that agreed well with recordings from normal monkeys. Further, during STN DBS in the parkinsonian condition the simulations reproduced the reduction in GPi bursting found in existing experimental data. The model also provided the opportunity to greatly expand analysis of GPi bursting activity, generating three major predictions. First, its reduction was proportional to the volume of STN activated by DBS. Second, GPi bursting decreased in a stimulation frequency dependent manner, saturating at values consistent with clinically therapeutic DBS. And third, ablating STN neurons, reported to generate similar therapeutic outcomes as STN DBS, also reduced GPi bursting. Our theoretical analysis of stimulation induced network activity suggests that regularization of GPi firing is dependent on the volume of STN tissue activated and a threshold level of burst reduction may be necessary for therapeutic effect.

Effect of intravascular irradiation of He-Ne laser on cerebral infarction: Hemorrheology and apoptosis

NASA Astrophysics Data System (ADS)

Zhu, Jian; Liang, Min-yi; Cao, Hao-cai; Li, Xiao-Yuan; Li, Shao-ming; Li, Shun-hao; Li, Wen-qi; Zhang, Jin-hong; Liu, Lei; Lai, Jian-hong

2005-07-01

Objective: To explore the efficacy of He-Ne laser intravascular irradiation on infarction and hemorrheology. To observe the effects of intravascular low level He-Ne laser irradiation (ILLLI) of blood on cell proliferation, apoptosis and chromosome in lymphocyte from cerebral infarction Methods: Seventy cases with cerebral infarction were randomly divided into groups control group (35 cases) treated only with common drugs and therapeutic group (35 cases) treated besides common drugs also by He-Ne laser intravascular irradiation. Their hemorrheology index and treatment results were observed and compared. The blood lymphocytes of cerebral infarction were cultured before and after treatment. After that, the mitosis index (MI), cell kinetics index (CKI), sister-chromatid exchanges (SCE) frequencies and apoptosis were determined. Results The therapeutic group was better than the control one. The effective rate in the therapeutic group was 88.6%, in the control one was 65.7%. The viscosity and fibrinogen, etc were better than that in the control group with significant difference (P<0.01). The lymphocyte proliferation index was significantly two increased than the control one (P>0.05) in cerebral infarction patients after treatment; The CKI of lymphocytes had no obvious difference among groups (P>0.05) SCE frequencies of lymphocytes had no statistic significance between control group and ILLLI on (P>0.05). It showed the apoptosis rate of lymphocytes in cerebral infarction patients after ILLLI treatment increased significantly compared with the control group, (P<0.001). There was a significant difference of apoptosis rate of lymphocytes in cerebral infarction patients than the control (P<0.001). Conclusions: During the He-Ne laser intravascular irradiation of the cerebral infarction, the low level He-Ne by ILLLI can increase the proliferation of lymphocytes, and can induce lymphocytes to apoptosis, but has no mutagenicity of cells.

[A comparison of the effect of oral captopril and nicardipine in hypertensive crisis].

PubMed

Addad, Faouzi; Ferjani, Hayet; Chaabani, Abdelghani; Jelliti, Mounir; Gamra, Habib; Makni, Hatem; Khaldoun, Ben Hamda; Dridi, Zohra; Ben Farhat, Mohamed

2008-02-01

Hypertensive crisis is defined as a severe elevation in blood pressure (BP) without target organ injury. There are few data about the efficacy and safety of comparative oral antihypertensive drugs. To compare the efficacy and safety of oral captopril (25 mg) and nicardipine (20 mg) in hypertensive crisis. This prospective, randomized study included 50 patients attended at the emergency department with a hypertensive crisis (arterial blood pressure of at least 180/110 mmHg without target organ damage confirmed after 15 min of rest. Systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) were assessed at several intervals during 4 h after the drug administration. Therapeutic success was defined by a SBP< or =160 and DBP< or =90 mmHg two hours after drug administration. The initial clinical characteristics as age, sex, initial systolic and diastolic BP and HR were no different in the two groups. BP levels started to significantly decrease within 15 minutes. At 2 hours, SBP and DBP dropped were similar in captopril group and nicardipine group,respectively to 162/94 vs 161/89 mmHg; p=ns. The therapeutic success at the second hour has been obtained in 68% of cases in the two groups. Age >70 years was a predictor's factor of therapeutic failure in the captopril group. Heart rate significantly dropped after 30 min in the captopril group (82.3 +/- 11.8 vs 77.6 +/- 12.7 c/min; p=0.037). This effect was maintained over four hours. There were no side effects in this study. Oral captopril or nicardipine are efficacy and safe in the treatment of hypertensive crisis.

Cost-effectiveness of medical nutrition therapy and therapeutically designed meals for older adults with cardiovascular disease.

PubMed

Troyer, Jennifer L; McAuley, William J; McCutcheon, Megan E

2010-12-01

Many older adults experience hyperlipidemia and hypertension, but there is little information about whether medical nutrition therapy (MNT) or therapeutic meals have independent or joint beneficial effects on older adults with these diagnoses. To assess the cost-effectiveness of MNT and therapeutic meals for older adults with hyperlipidemia and/or hypertension. A 1-year prospective four-arm controlled randomized community-based clinical trial. Participants were people ages 60 years or older residing in community settings who were medically diagnosed with either hypertension or hyperlipidemia. They were recruited through a number of venues beginning in May 2003. The 321 eligible individuals were assigned to one of four arms: (a) a literature control group, (b) a therapeutic meal group that received seven diagnosis-appropriate therapeutic meals a week, (c) an MNT group, and (d) an MNT-plus-therapeutic meal group. The outcome measure was quality-adjusted life-years (QALYs). Costs included both intervention and medical costs. Estimations of separate models of costs and QALYs facilitated the construction of incremental cost-effectiveness ratios. Net benefit analysis produced the probability that each intervention was cost-effective given different values for society's willingness to pay for a QALY. Therapeutic meals are cost-effective. Using the net benefit approach and a willingness to pay of $109,000 per QALY, the probability that the therapeutic meal delivery program is cost-effective is 95% and for MNT the probability is 90%. However, the combination of MNT and therapeutic meals did not have an independent significant effect on QALYs. Results inform the debate about extending Medicare funding for MNT to individuals with hypertension and hyperlipidemia. Future research should include more individuals who are not currently receiving medications for these diseases. Copyright © 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria gonorrhoeae, Hawaii, USA

PubMed Central

Papp, John R.; Abrams, A. Jeanine; Nash, Evelyn; Katz, Alan R.; Kirkcaldy, Robert D.; O’Connor, Norman P.; O’Brien, Pamela S.; Harauchi, Derek H.; Maningas, Eloisa V.; Soge, Olusegun O.; Kersh, Ellen N.; Komeya, Alan; Tomas, Juval E.; Wasserman, Glenn M.; Kunimoto, Gail Y.; Trees, David L.

2017-01-01

During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options. PMID:28418303

The Evaluation of Filmed Excerpts of Rogers, Perls, and Ellis by Beginning Counselor Trainees

ERIC Educational Resources Information Center

Kelly, F. Donald; Byrne, Thomas P.

1977-01-01

Students (N=29) viewed three stimulus films and rated therapeutic effectiveness of the therapists. Students were subsequently rank-ordered on the basis of skill development and assigned to one of three groups (high, middle, or low.) Results revealed an overall higher evaluation for Rogers as compared to either Perls or Ellis. (Author)

Integrating Microtissues in Nanofiber Scaffolds for Regenerative Nanomedicine

PubMed Central

Keller, Laetitia; Wagner, Quentin; Offner, Damien; Eap, Sandy; Musset, Anne-Marie; Arruebo, Manuel; Kelm, Jens M.; Schwinté, Pascale; Benkirane-Jessel, Nadia

2015-01-01

A new generation of biomaterials focus on smart materials incorporating cells. Here, we describe a novel generation of synthetic nanofibrous implant functionalized with living microtissues for regenerative nanomedicine. The strategy designed here enhances the effectiveness of therapeutic implants compared to current approaches used in the clinic today based on single cells added to the implant. PMID:28793604

Therapeutic and Transmission-Blocking 
Efficacy of Dihydroartemisinin/Piperaquine and Chloroquine against Plasmodium vivax Malaria, Cambodia.

PubMed

Popovici, Jean; Vantaux, Amelie; Primault, Lyse; Samreth, Reingsey; Piv, Eak Por; Bin, Sophalai; Kim, Saorin; Lek, Dysoley; Serre, David; Menard, Didier

2018-08-17

We assessed the efficacy of standard 3-day courses of chloroquine and dihydroartemisinin/piperaquine against Plasmodium vivax malaria. Compared with chloroquine, dihydroartemisinin/piperaquine was faster in clearing asexual P. vivax parasites and blocking human-to-mosquito transmission. This drug combination was also more effective in preventing potential recurrences for >2 months.

Treatment of obese asthma in a mouse model by simvastatin is associated with improving dyslipidemia and decreasing leptin level.

PubMed

Han, Wei; Li, Jun; Tang, Huaping; Sun, Lixin

2017-03-04

Obesity can cause or worsen asthma. Compared with common asthma, obese asthma is difficult to control. Statins are effective serum cholesterol-lowering agents in clinical practice, and they also have anti-inflammatory properties, which in theory are potentially beneficial in asthma. Many studies have shown that simvastatin has good therapeutic effect in animal models of asthma. However, the therapeutic effect and action mechanism of simvastatin for obese asthma remain unclear. Leptin, a satiety hormone, is in positive correlation with total body fat mass and may also play a significant role in the pathogenesis of asthma. In this study, we use the method of high-fat diet and ovalbumin (OVA) sensitization and challenge to establish the mouse model of obesity and asthma, and find that obese asthmatic mice has higher levels of glucose, lipid and leptin in serum, and neutrophil percentage in bronchoalveolar lavage fluid (BALF), and more severe airway inflammation and structural changes in lung tissues than non-obese asthmatic mice, and respond poorly to dexamethasone treatment, which indicates that obese asthma might belong to steroid-resistant (SR) asthma. Simvastatin treatment reduces the levels of glucose, lipid, leptin and neutrophil percentage, and improves airway inflammation and remodeling, which can be as a potential therapeutic target used in the treatment of obese asthma in humans. Correlation analysis shows that there is positive correlation between neutrophil percentage and serum leptin/cholesterol level, which indicates that the therapeutic efficacy of simvastatin on obese asthma might be associated with improving dyslipidemia and decreasing leptin level. Copyright © 2017 Elsevier Inc. All rights reserved.

Therapeutic efficacy of atypical antipsychotic drugs by targeting multiple stress-related metabolic pathways

PubMed Central

Cai, H L; Jiang, P; Tan, Q Y; Dang, R L; Tang, M M; Xue, Y; Deng, Y; Zhang, B K; Fang, P F; Xu, P; Xiang, D X; Li, H D; Yao, J K

2017-01-01

Schizophrenia (SZ) is considered to be a multifactorial brain disorder with defects involving many biochemical pathways. Patients with SZ show variable responses to current pharmacological treatments of SZ because of the heterogeneity of this disorder. Stress has a significant role in the pathophysiological pathways and therapeutic responses of SZ. Atypical antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic–pituitary–adrenal (HPA) axis and exert therapeutic effects on stress by targeting the prefrontal cortex (PFC) and hippocampus. To evaluate the effects of AAPDs (such as clozapine, risperidone and aripiprazole) on stress, we compared neurochemical profile variations in the PFC and hippocampus between rat models of chronic unpredictable mild stress (CUMS) for HPA axis activation and of long-term dexamethasone exposure (LTDE) for HPA axis inhibition, using an ultraperformance liquid chromatography–mass spectrometry (UPLC–MS/MS)-based metabolomic approach and a multicriteria assessment. We identified a number of stress-induced biomarkers comprising creatine, choline, inosine, hypoxanthine, uric acid, allantoic acid, lysophosphatidylcholines (LysoPCs), phosphatidylethanolamines (PEs), corticosterone and progesterone. Specifically, pathway enrichment and correlation analyses suggested that stress induces oxidative damage by disturbing the creatine–phosphocreatine circuit and purine pathway, leading to excessive membrane breakdown. Moreover, our data suggested that the AAPDs tested partially restore stress-induced deficits by increasing the levels of creatine, progesterone and PEs. Thus, the present findings provide a theoretical basis for the hypothesis that a combined therapy using adenosine triphosphate fuel, antioxidants and omega-3 fatty acids as supplements may have synergistic effects on the therapeutic outcome following AAPD treatment. PMID:28509906

Amodiaquine failure associated with erythrocytic glutathione in Plasmodium falciparum malaria

PubMed Central

Zuluaga, Lina; Pabón, Adriana; López, Carlos; Ochoa, Aleida; Blair, Silvia

2007-01-01

Objective To establish the relationship between production of glutathione and the therapeutic response to amodiaquine (AQ) monotherapy in Plasmodium falciparum non-complicated malaria patients. Methodology Therapeutic response to AQ was evaluated in 32 patients with falciparum malaria in two townships of Antioquia, Colombia, and followed-up for 28 days. For every patient, total glutathione and enzymatic activity (glutathione reductase, GR, and γ-glutamylcysteine synthetase, γ-GCS) were determined in parasitized erythrocytes, non-infected erythrocytes and free parasites, on the starting day (day zero, before ingestion of AQ) and on the day of failure (in case of occurrence). Results There was found an AQ failure of 31.25%. Independent of the therapeutic response, on the starting day and on the day of failure, lower total glutathione concentration and higher GR activities in parasitized erythrocytes were found, compared with non-infected erythrocytes (p < 0.003). In addition, only on the day of failure, γ-GCS activity of parasitized erythrocytes was higher, compared with that of healthy erythrocytes (p = 0.01). Parasitized and non-parasitized erythrocytes in therapeutic failure patients (TF) had higher total glutathione on the starting day compared with those of adequate clinical response (ACR) (p < 0.02). Parasitized erythrocytes of TF patients showed lower total glutathione on the failure day, compared with starting day (p = 0.017). No differences was seen in the GR and γ-GCS activities by compartment, neither between the two therapeutic response groups nor between the two treatment days. Conclusion This study is a first approach to explaining P. falciparum therapeutic failure in humans through differences in glutathione metabolism in TF and ACR patients. These results suggest a role for glutathione in the therapeutic failure to antimalarials. PMID:17451604

Evaluation of multidensity orthotic materials used in footwear for patients with diabetes.

PubMed

Foto, J G; Birke, J A

1998-12-01

Selected combinations of multidensity orthotic materials were tested under simulated walking conditions found in the forefoot of diabetic patients. Materials were compared for therapeutic effectiveness by their stress/strain properties and dynamic compression set. Results showed that all of the multidensity materials experienced losses in performance throughout the testing period of 100,000 cycles, with the greatest losses occurring within the first 10,000 cycles. Of the materials tested, Poron + Plastazote #2 and Spenco + Microcel Puff Lite had the highest dynamic material strain and the lowest dynamic compression set over 100,000 cycles. In comparison, these are better multidensity combinations than the others tested to use as therapeutic orthoses in footwear for diabetic patients.

Therapeutic mild hypothermia improves early outcomes in rats subjected to severe sepsis.

PubMed

Ding, Wu; Shen, Yuehong; Li, Qiang; Jiang, Shouyin; Shen, Huahao

2018-04-15

Therapeutic hypothermia has shown beneficial effects in sepsis. This study focused on its mechanism. Sixteen male Sprague-Dawley rats underwent cecal ligation and perforation and subsequently were treated with either hypothermia (HT; body temperature cooled and maintained at 34 °C by ice pad for 10 h; n = 8) or normothermia (NT; n = 8). Three additional rats underwent sham surgery. The body temperatures of the sham-operated and NT groups were maintained at 38 °C with a thermal pad. After the hypothermia treatment, the HT rats were rewarmed for 2 h. The groups were compared for circulating cytokines (IL-6, IL-10), lactate, high mobility group box-1 protein (HMGB1), and lung and intestinal lesions. Animals were observed for 24 h. Compared with the sham-operated group, the 2 sepsis group rats had significantly higher circulating IL-6, HMGB1, and lactate levels, and tissue injury. In the HT rats, the levels of IL-6, HMGB1, and lactate, the lung wet-to-dry ratio, and lung and intestinal damage were significantly lower than that of the NT group. Circulating IL-10 levels increased significantly after 12 h in the sepsis groups compared with sham animals, while that of the NT and HT groups were comparable. The survival rates of the NT and HT rats were also comparable. Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema. These results suggest that mild hypothermia has potential as a therapy in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.

Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice.

PubMed

Jadeja, Ravirajsinh N; Urrunaga, Nathalie H; Dash, Suchismita; Khurana, Sandeep; Saxena, Neeraj Kumar

2015-09-01

Withaferin-A (WA) has anti-oxidant activities however, its therapeutic potential in acetaminophen (APAP) hepatotoxicity is unknown. We performed a proof-of-concept study to assess the therapeutic potential of WA in a mouse model that mimics APAP-induced liver injury (AILI) in humans. Overnight fasted C57BL/6NTac (5-6 wk. old) male mice received 200 mg/kg APAP intraperitoneally (i.p.). After 1 h mice were treated with 40 mg/kg WA or vehicle i.p., and euthanized 4 and 16 h later; their livers were harvested and serum collected for analysis. At 4 h, compared to vehicle-treated mice, WA-treated mice had reduced serum ALT levels, hepatocyte necrosis and intrahepatic hemorrhage. All APAP-treated mice had reduced hepatic glutathione (GSH) levels however, reduction in GSH was lower in WA-treated when compared to vehicle-treated mice. Compared to vehicle-treated mice, livers from WA-treated mice had reduced APAP-induced JNK activation, mitochondrial Bax translocation, and nitrotyrosine generation. Compared to vehicle-treated mice, WA-treated mice had increased hepatic up-regulation of Nrf2, Gclc and Nqo1, and down-regulation of Il-6 and Il-1β. The hepatoprotective effect of WA persisted at 16 h. Compared to vehicle-treated mice, WA-treated mice had reduced hepatocyte necrosis and hepatic expression of Il-6, Tnf-α and Il-1β, increased hepatic Gclc and Nqo1 expression and GSH levels, and reduced lipid peroxidation. Finally, in AML12 hepatocytes, WA reduced H₂O₂-induced oxidative stress and necrosis by preventing GSH depletion. Collectively, these data show mechanisms whereby WA reduces necrotic hepatocyte injury, and demonstrate that WA has therapeutic potential in AILI. Copyright © 2015 Elsevier Inc. All rights reserved.

Integrating School-Based and Therapeutic Conflict Management Models at School.

ERIC Educational Resources Information Center

D'Oosterlinck, Franky; Broekaert, Eric

2003-01-01

Explores the possibility of integrating school-based and therapeutic conflict management models, comparing two management models: a school-based conflict management program, "Teaching Students To Be Peacemakers"; and a therapeutic conflict management program, "Life Space Crisis Intervention." The paper concludes that integration might be possible…

Low-intensity blue-enriched white light (750 lux) and standard bright light (10,000 lux) are equally effective in treating SAD. A randomized controlled study.

PubMed

Meesters, Ybe; Dekker, Vera; Schlangen, Luc J M; Bos, Elske H; Ruiter, Martine J

2011-01-28

Photoreceptor cells containing melanopsin play a role in the phase-shifting effects of short-wavelength light. In a previous study, we compared the standard light treatment (SLT) of SAD with treatment using short-wavelength blue-enriched white light (BLT). Both treatments used the same illuminance (10,000 lux) and were equally highly effective. It is still possible, however, that neither the newly-discovered photoreceptor cells, nor the biological clock play a major role in the therapeutic effects of light on SAD. Alternatively, these effects may at least be partly mediated by these receptor cells, which may have become saturated as a result of the high illuminances used in the therapy. This randomized controlled study compares the effects of low-intensity BLT to those of high-intensity SLT. In a 22-day design, 22 patients suffering from a major depression with a seasonal pattern (SAD) were given light treatment (10,000 lux) for two weeks on workdays. Subjects were randomly assigned to either of the two conditions, with gender and age evenly distributed over the groups. Light treatment either consisted of 30 minutes SLT (5000 °K) with the EnergyLight® (Philips, Consumer Lifestyle) with a vertical illuminance of 10,000 lux at eye position or BLT (17,000 °K) with a vertical illuminance of 750 lux using a prototype of the EnergyLight® which emitted a higher proportion of short-wavelengths. All participants completed questionnaires concerning mood, activation and sleep quality on a daily basis. Mood and energy levels were also assessed on a weekly basis by means of the SIGH-SAD and other assessment tools. On day 22, SIGH-SAD ratings were significantly lower than on day 1 (SLT 65.2% and BLT 76.4%). On the basis of all assessments no statistically significant differences were found between the two conditions. With sample size being small, conclusions can only be preliminary. Both treatment conditions were found to be highly effective. The therapeutic effects of low-intensity blue-enriched light were comparable to those of the standard light treatment. Saturation effects may play a role, even with a light intensity of 750 lux. The therapeutic effects of blue-enriched white light in the treatment of SAD at illuminances as low as 750 lux help bring light treatment for SAD within reach of standard workplace and educational lighting systems.

[Clinical observation on idiopathic tinnitus treated with acupuncture, buzhong yiqi tang and cizhu wan].

PubMed

Chen, Surong; Tan, Xuming; Fei, Lanbo; Xiang, Xiande

2018-04-12

To observe the differences in the clinical therapeutic effects on idiopathic tinnitus between the combined therapy with acupuncture and the modified formula of buzhong yiqi tang and cizhu wan and the simple administration of the modified formula of buzhong yiqi tang and cizhu wan . A total of 60 patients were randomized into a combined treatment group and an herbal medicine group, 30 cases in each one and 2 cases dropped out in the herbal medicine group. In the combined treatment group, acupuncture was given at the local acupoints for tinnitus, such as Yifeng (TE 17), penetrating needling technique from Ermen (TE 21) to Tinggong (SI 19) and Tinghui (GB 2) combined with the scalp acupuncture [the vertigo-auditory area, Baihui (GV 20)] and the oral administration of the modified formula of buzhong yiqi tang and cizhu wan . In the herbal medicine group, the oral administration of the modified formula of buzhong yiqi tang and cizhu wan was only applied. The treatment was given once a day in each group, 5 times a week for acupuncture and 7 times a week for the oral administration of herbal medicine. Totally, the treatment for 6 weeks was required in the two groups. Before and after treatment, the tinnitus severity score (TSS) and the score of tinnitus handicap inventory (THI) were observed and the clinical therapeutic effects were compared between the two groups. After treatment, the TSS and THI scores reduced as compared with those before treatment in the two groups (all P <0.05). The scores in the combined treatment group were lower than those in the herbal medicine group (both P <0.05). The total effective rate in the combined treatment group was 93.3% (28/30), better than 67.9% (19/28) in the herbal medicine group ( P <0.05). The combined treatment with scalp acupuncture, acupuncture around the ear and the modified formula of buzhong yiqi tang and cizhu wan achieve the superior therapeutic effects on idiopathic tinnitus as compared with the simple oral administration of the modified formula of buzhong yiqi tang and cizhu wan .

The Sea Urchin Embryo, an Invertebrate Model for Mammalian Developmental Neurotoxicity, Reveals Multiple Neurotransmitter Mechanisms for Effects of Chlorpyrifos: Therapeutic Interventions and a Comparison with the Monoamine Depleter, Reserpine

PubMed Central

Buznikov, Gennady A.; Nikitina, Lyudmila A.; Rakić, Ljubiša M.; Miloševi, Ivan; Bezuglov, Vladimir V.; Lauder, Jean M.; Slotkin, Theodore A.

2007-01-01

Lower organisms show promise for the screening of neurotoxicants that might target mammalian brain development. Sea urchins use neurotransmitters as embryonic growth regulatory signals, so that adverse effects on neural substrates for mammalian brain development can be studied in this simple organism. We compared the effects of the organophosphate insecticide, chlorpyrifos in sea urchin embryos with those of the monoamine depleter, reserpine, so as to investigate multiple neurotransmitter mechanisms involved in developmental toxicity and to evaluate different therapeutic interventions corresponding to each neurotransmitter system. Whereas reserpine interfered with all stages of embryonic development, the effects of chlorpyrifos did not emerge until the mid-blastula stage. After that point, the effects of the two agents were similar. Treatment with membrane permeable analogs of the monoamine neurotransmitters, serotonin and dopamine, prevented the adverse effects of either chlorpyrifos or reserpine, despite the fact that chlorpyrifos works simultaneously through actions on acetylcholine, monoamines and other neurotransmitter pathways. This suggests that different neurotransmitters, converging on the same downstream signaling events, could work together or in parallel to offset the developmental disruption caused by exposure to disparate agents. We tested this hypothesis by evaluating membrane permeable analogs of acetylcholine and cannabinoids, both of which proved effective against chlorpyrifos- or reserpine-induced teratogenesis. Invertebrate test systems can provide both a screening procedure for mammalian neuroteratogenesis and may uncover novel mechanisms underlying developmental vulnerability as well as possible therapeutic approaches to prevent teratogenesis. PMID:17720543

Antioxidant effect of aqueous extract of four plants with therapeutic potential on gynecological diseases; Semen persicae, Leonurus cardiaca, Hedyotis diffusa, and Curcuma zedoaria.

PubMed

Ji, Shaojian; Fattahi, Amir; Raffel, Nathalie; Hoffmann, Inge; Beckmann, Matthias W; Dittrich, Ralf; Schrauder, Michael

2017-11-25

Little information is available concerning antioxidant effects of plant teas (water boiled) which are used more commonly in traditional Chinese medicine than other extracts. Thus, we addressed this issue by evaluating the ability of teas from four different plants with therapeutic potential on gynecological diseases. The aqueous extracts of Semen persicae, Leonurus cardiaca, Hedyotis diffusa, and Curcuma zedoaria rhizome were prepared and then their effects on copper-induced low-density lipoprotein cholesterol (LDL-C) oxidation were evaluated by spectrophotometric method. Density gradient ultracentrifugation method was recruited to isolate LDL-C from healthy individuals. Our results showed that adding 10, 20, and 30 µl S. persicae could increase the lag phase duration of LDL-C oxidation compared with control reaction 12, 21, and 33%, respectively. The most effective delay (87%) was observed when 30 µl H. diffusa was added to the reaction. In cases of L. cardiaca and C. zedoaria, we found no significant influence on the lag phase duration (p > 0.05). Moreover, our findings about starting point of the decomposition phase were almost in parallel with the lag phase results, as 30 µl of S. persicae or H. diffusa teas could significantly increase the initiation time of decomposition (p < 0.05). In conclusion our results showed that both S. persicae and H. diffusa teas and not L. cardiaca and C. zedoaria could have medicinal therapeutic effects partly through direct oxidation prevention.

Drug use to resistance exercise-induced fatigue based on diclofenac diethylamine emulgel efficacy analysis.

PubMed

Gu, Qi

2017-05-01

In this paper, the author study on the effect of drug treatment on sports injury, and makes a comparative analysis of drug effects. In sports, the incidence of various types of injuries is increasing, especially in muscle injury. In the experiment, we compared the effects of three different drugs on the treatment and relief of muscle loss. After 3 weeks, the average optical density of desmin in muscle fiber positive region have decreased, as xiaotong plaster (0.4708±0.0126), votalin (0.5124±0.0264) and placebo (0.3856±0.0312). It has a certain effect to promote the repair and regeneration of desmin expression by drugs. Through the analysis of the effect of drug intervention on sports injury repair, we can effectively improve the therapeutic effect of sports injury.

The Therapeutic Effect of the Antitumor Drug 11beta and Related Molecules on Polycystic Kidney Disease

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0364 TITLE: The Therapeutic Effect of the Antitumor Drug 11beta and Related Molecules on Polycystic Kidney Disease...SUBTITLE The Therapeutic Effect of the Antitumor Drug 11beta and Related Molecules on Polycystic Kidney Disease 5a. CONTRACT NUMBER 5b. GRANT NUMBER...synthetic multifunctional compounds as therapeutics for polycystic kidney disease (PKD). In collaboration with the Essigmann lab at MIT, we have

The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol

PubMed Central

2010-01-01

Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Methods Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-over, repeat-dose study. Results Pharmacokinetic parameters for ibuprofen and paracetamol were similar for the combination and monotherapy tablets (values falling within the 80% to 125% acceptable bioequivalence range) except for the rate of absorption of paracetamol from the combination (tmax), which was significantly faster compared with monotherapy (median difference 10 minutes; p < 0.05). Mean plasma concentrations of both drugs were higher, earlier, following administration of the combination tablet compared with monotherapy. Mean plasma levels at 10 and 20 minutes were 6.64 μg.mL-1 and 16.81 μg.mL-1, respectively, for ibuprofen from the combination, compared with 0.58 μg.mL-1 and 9.00 μg.mL-1, respectively, for monotherapy. For paracetamol, mean plasma levels at 10 and 20 minutes were 5.43 μg.mL-1 and 14.54 μg.mL-1, respectively, for the combination compared with 0.33 μg.mL-1 and 9.19 μg.mL-1, respectively, for monotherapy. The rate of absorption of both ibuprofen and paracetamol was significantly delayed when the combination tablet was administered in the fed versus fasted state; median delay was 25 minutes for ibuprofen (p > 0.05) and 55 minutes for paracetamol (p < 0.001). The pharmacokinetic parameters were comparable irrespective of whether the combination tablet was given twice or three times daily; systemic exposure was, however, approximately 1.4 times greater for both drugs when given three times daily. Conclusions Administration of ibuprofen and paracetamol in a fixed-dose combination tablet does not significantly alter the pharmacokinetic profiles of either drug, except for enhancing the rate of paracetamol absorption, offering potential therapeutic benefits in relation to the onset of analgesia. Concentrations of both drugs reached previously reported therapeutic levels when the combination tablet was administrated in the fed or fasted state. Three times daily dosing may offer enhanced therapeutic effect for longer than twice daily dosing. PMID:20602760

Experimental and early investigational drugs for androgenetic alopecia.

PubMed

Guo, Hongwei; Gao, Wendi Victor; Endo, Hiromi; McElwee, Kevin John

2017-08-01

Treatments for androgenetic alopecia constitute a multi-billion-dollar industry, however, currently available therapeutic options have variable efficacy. Consequently, in recent years small biotechnology companies and academic research laboratories have begun to investigate new or improved treatment methods. Research and development approaches include improved formulations and modes of application for current drugs, new drug development, development of cell-based treatments, and medical devices for modulation of hair growth. Areas covered: Here we review the essential pathways of androgenetic alopecia pathogenesis and collate the current and emerging therapeutic strategies using journal publications databases and clinical trials databases to gather information about active research on new treatments. Expert opinion: We propose that topically applied medications, or intra-dermal injected or implanted materials, are preferable treatment modalities, minimizing side effect risks as compared to systemically applied treatments. Evidence in support of new treatments is limited. However, we suggest therapeutics which reverse the androgen-driven inhibition of hair follicle signaling pathways, such as prostaglandin analogs and antagonists, platelet-rich plasma (PRP), promotion of skin angiogenesis and perfusion, introduction of progenitor cells for hair regeneration, and more effective ways of transplanting hair, are the likely near future direction of androgenetic alopecia treatment development.

Potential savings from an evidence-based consumer-oriented public education campaign on prescription drugs.

PubMed

Donohue, Julie M; Fischer, Michael A; Huskamp, Haiden A; Weissman, Joel S

2008-10-01

To estimate potential savings associated with the Consumer Reports Best Buy Drugs program, a national educational program that provides consumers with price and effectiveness information on prescription drugs. National data on 2006 prescription sales and retail prices paid for angiotensin-converting enzyme inhibitors (ACEIs), β-blockers, calcium channel blockers, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-coA) reductase inhibitors (statins). We converted national data on aggregate unit sales of drugs in the four classes to defined daily doses (DDD) and estimated a range of potential savings from generic and therapeutic substitution. We estimated that $2.76 billion, or 7.83 percent of sales, could be saved if use of the drugs recommended by the educational program was increased. The recommended drugs' prices were 15-65 percent lower per DDD than their therapeutic alternatives. The majority (57.4 percent) of potential savings would be achieved through therapeutic substitution. Substantial savings can be achieved through greater use of comparatively effective and lower cost drugs recommended by a national consumer education program. However, barriers to dissemination of consumer-oriented drug information must be addressed before savings can be realized. © Health Research and Educational Trust.

Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro✩

PubMed Central

Secor, Eric R.; Singh, Anurag; Guernsey, Linda A.; McNamara, Jeff T.; Zhan, Lijun; Maulik, Nilanjana; Thrall, Roger S.

2009-01-01

Bromelain (Br), an extract from pineapple stem with cysteine protease activity, exerts anti-inflammatory effects in a number of inflammatory models. We have previously shown that Br treatment decreased activated CD4+ T cells and has a therapeutic role in an ovalbumin-induced murine model of allergic airway disease. The current study was designed to determine the effect of Br on CD4+ T cell activation, specifically the expression of CD25 in vitro. CD25 is up regulated upon T cell activation, found as a soluble fraction (sCD25) and is a therapeutic target in inflammation, autoimmunity and allergy. Br treatment of anti-CD3 stimulated CD4+ T cells reduced CD25 expression in a dose and time dependent manner. This reduction of CD25 was dependent on the proteolytic action of Br as the addition of E64 (a cysteine protease inhibitor) abrogated this response. The concentration of sCD25 was increased in supernatants of Br treated activated CD4+ T cells as compared to control cells, suggesting that Br proteolytically cleaved cell-surface CD25. This novel mechanism of action identifies how Br may exert its therapeutic benefits in inflammatory conditions. PMID:19162239

Potential Savings from an Evidence-Based Consumer-Oriented Public Education Campaign on Prescription Drugs

PubMed Central

Donohue, Julie M; Fischer, Michael A; Huskamp, Haiden A; Weissman, Joel S

2008-01-01

Objective To estimate potential savings associated with the Consumer Reports Best Buy Drugs program, a national educational program that provides consumers with price and effectiveness information on prescription drugs. Data Sources National data on 2006 prescription sales and retail prices paid for angiotensin-converting enzyme inhibitors (ACEIs), β-blockers, calcium channel blockers, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-coA) reductase inhibitors (statins). Study Design We converted national data on aggregate unit sales of drugs in the four classes to defined daily doses (DDD) and estimated a range of potential savings from generic and therapeutic substitution. Principal Findings We estimated that $2.76 billion, or 7.83 percent of sales, could be saved if use of the drugs recommended by the educational program was increased. The recommended drugs’ prices were 15–65 percent lower per DDD than their therapeutic alternatives. The majority (57.4 percent) of potential savings would be achieved through therapeutic substitution. Conclusions Substantial savings can be achieved through greater use of comparatively effective and lower cost drugs recommended by a national consumer education program. However, barriers to dissemination of consumer-oriented drug information must be addressed before savings can be realized. PMID:18479406

Balloon enteroscopy versus spiral enteroscopy for small-bowel disorders: a systematic review and meta-analysis.

PubMed

Baniya, Ramkaji; Upadhaya, Sunil; Subedi, Subash Chandra; Khan, Jahangir; Sharma, Prabin; Mohammed, Tabrez Shaik; Bachuwa, Ghassan; Jamil, Laith H

2017-12-01

Two novel enteroscopic procedures, balloon enteroscopy and spiral enteroscopy, have revolutionized the diagnostic and therapeutic approach to small-bowel disorders. These disorders that historically required surgical interventions are now investigated and managed nonsurgically. Only a few weakly powered studies have compared the outcomes of spiral enteroscopy and balloon enteroscopy. We conducted a systematic review and meta-analysis to compare the efficacy and safety of these 2 procedures. PubMed, Cochrane Library, Scopus, and clinicaltrials.gov databases were searched for all studies published up to January 12, 2017 comparing the efficacy and safety of balloon enteroscopy (single or double) and spiral enteroscopy. Primary outcomes of interest were diagnostic and therapeutic success rates. Other outcomes included procedure length, depth of maximal insertion (DMI), rate of complete enteroscopy, and adverse events. We calculated Odds ratios (ORs) for categorical variables and mean difference (MD) for continuous variables. The Mantel-Haenszel method was used to analyze the data. Fixed and random effect models were used for <50% heterogeneity and >50% heterogeneity, respectively. Eight studies met the inclusion criteria for this meta-analysis. A total of 615 procedures were analyzed, which included 394 balloon enteroscopy and 221 spiral enteroscopy procedures. There were no significant differences in diagnostic and therapeutic success rates (OR, 1.27; 95% confidence interval [CI], .86-1.88; P = .22; and OR, 1.23; 95% CI, .82-1.84; P = .32, respectively) between the 2 procedures. Similarly, DMI was not significantly different between the 2 groups (MD, 26.29; 95% CI, 20.92-73.49; P = .28). However, the procedure time was significantly shorter for the spiral enteroscopy group compared with the balloon enteroscopy group (MD, 11.26; 95% CI, 2.72-19.79; P = .010). A subgroup analysis comparing double balloon enteroscopy with spiral enteroscopy yielded similar results. Both procedures achieved similar diagnostic and therapeutic outcomes and with similar depth of insertion. Spiral enteroscopy has the benefit of shorter procedural time. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.

PubMed

Zhang, Yan; Yang, Yang; Zhang, Guang-Zhu; Gao, Mou; Ge, Guang-Zhi; Wang, Qin-Qin; Ji, Xin-Chao; Sun, Yi-Lin; Zhang, Hong-Tian; Xu, Ru-Xiang

2016-10-01

Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma. Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neurological severity scores (mNSS). A comparative study of therapeutic effects between SI and intraperitoneal injection of edaravone (IP) involved in cerebral edema, blood-brain barrier (BBB) permeability, hematoma absorption, inflammatory response and neuronal apoptosis. Compared with IP, the mNSS was significantly (P < 0.05) improved by SI; cerebral edema and BBB permeability were dramatically ameliorated (P < 0.05); IL-4 and IL-10 levels increased, but IL-1β and TNF-α levels significantly decreased; neuron apoptosis decreased markedly (P < 0.05); and caspase-3 and Bax expression significantly dropped, but Bcl-2 increased in SI group (P < 0.05). SI markedly improved neurological deficits in ICH rat models via antiinflammatory and antiapoptosis mechanisms and promoted M2-type microglia differentiation. SI was effective in rats with collagenase-induced ICH. © 2016 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.

PubMed

Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

2016-02-01

Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. © The Author(s) 2015.

THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the sub-chronic PCP model of schizophrenia

PubMed Central

Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

2017-01-01

Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the CSF levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared to THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. PMID:26510449

The comparison of the effectiveness of conventional therapeutic exercises and Pilates on pain and function in patients with knee osteoarthritis.

PubMed

Mazloum, Vahid; Rabiei, Pouya; Rahnama, Nader; Sabzehparvar, Elnaz

2018-05-01

The aim of this study was to investigate the effectiveness of two different interventions on pain and disability in patients with knee osteoarthritis (KOA). Forty-one individuals (Mean ± SD: Age 52.1 ± 8.9 years, Height 172.8 ± 6.6 cm, Weight 80.2 ± 6.9 kg) with KOA were randomly allocated into Pilates (N = 14), conventional therapeutic exercise (CTE) (N = 14), and control (N = 13) groups. Joint position sense (JPS), functional performance, pain, and disability were examined using Biodex system, aggregate time of four daily activities, and Lequesne Index. One-Way ANOVA, and Post Hoc Scheffe test were administrated to analyze the data (P < 0.05). There was a significant (P < 0.001) difference between the experimental groups in all measured outcomes compared to the control. While, regarding pain and disability, more significant (P = 0.003) improvement was observed in participants following Pilates training compared to CTE. It seemed that Pilates training was more effective than the CTE to improve pain and disability in individuals with KOA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment Preferences Affect the Therapeutic Alliance: Implications for Randomized Controlled Trials

ERIC Educational Resources Information Center

Iacoviello, Brian M.; McCarthy, Kevin Scott; Barrett, Marna S.; Rynn, Moira; Gallop, Robert; Barber, Jacques P.

2007-01-01

The influence of treatment preferences on the development of the therapeutic alliance was investigated. Seventy-five patients were followed while participating in a randomized controlled trial comparing supportive-expressive psychotherapy with sertraline or pill placebo in the treatment of major depressive disorder. Therapeutic alliance was…

Bioequivalence of isoniazid in a two drug fixed dose combination and in a single drug dosage form.

PubMed

Agrawal, S; Kaul, C L; Panchagnula, R

2001-08-01

To increase the patient compliance and reduce the risk of drug resistant strains, WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tablets as a routine therapeutic regimen in Directly Observed Treatment Shortcourse (DOTS). But the main issue in the use of FDC is the quality of the formulation. At present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin from FDC compared to separate formulations. For the therapeutic effectiveness all the components of the FDCs should be bioavailable at tissue site. Also, the primary and acquired resistance rate of isoniazid is much higher compared to other anti-tubercular drugs. Hence, a comparative bioavailability study of isoniazid from a two drugs FDC compared to a separate formulation was carried out on a group of 12 healthy volunteers. When evaluated by normal or log transformed confidence interval, Two Way ANOVA and Hauschke analysis, the bioequivalence limits for AUC0-8 and AUC0-24 were within 0.8-1.25. For Cmax and Tmax, these limits were within 0.7-1.43. Hence, isoniazid from a FDC formulation was found to be bioequivalent to a separate formulation at same dose levels.

The state-of-play and future of antibody therapeutics.

PubMed

Elgundi, Zehra; Reslan, Mouhamad; Cruz, Esteban; Sifniotis, Vicki; Kayser, Veysel

2017-12-01

It has been over four decades since the development of monoclonal antibodies (mAbs) using a hybridoma cell line was first reported. Since then more than thirty therapeutic antibodies have been marketed, mostly as oncology, autoimmune and inflammatory therapeutics. While antibodies are very efficient, their cost-effectiveness has always been discussed owing to their high costs, accumulating to more than one billion dollars from preclinical development through to market approval. Because of this, therapeutic antibodies are inaccessible to some patients in both developed and developing countries. The growing interest in biosimilar antibodies as affordable versions of therapeutic antibodies may provide alternative treatment options as well potentially decreasing costs. As certain markets begin to capitalize on this opportunity, regulatory authorities continue to refine the requirements for demonstrating quality, efficacy and safety of biosimilar compared to originator products. In addition to biosimilars, innovations in antibody engineering are providing the opportunity to design biobetter antibodies with improved properties to maximize efficacy. Enhancing effector function, antibody drug conjugates (ADC) or targeting multiple disease pathways via multi-specific antibodies are being explored. The manufacturing process of antibodies is also moving forward with advancements relating to host cell production and purification processes. Studies into the physical and chemical degradation pathways of antibodies are contributing to the design of more stable proteins guided by computational tools. Moreover, the delivery and pharmacokinetics of antibody-based therapeutics are improving as optimized formulations are pursued through the implementation of recent innovations in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine.

PubMed

Kress, Hans G

2009-03-01

Buprenorphine was not used widely in clinical practice over many years, mainly due to analgesic potency and clinical safety concerns based on misinterpreted animal data. Contrary to previous concerns, however, no analgesic ceiling effect and no antagonism of combined pure mu-opioid receptor agonists is seen within the therapeutic dose range. In recent studies, buprenorphine could be effectively and safely combined with full mu-agonists, and switching between buprenorphine and another opioid provided comparable pain relief based on equianalgesic doses. Moreover, buprenorphine exerts an antihyperalgesic effect, which is due -- at least in part -- to antagonistic activity at kappa-opioid receptors. Buprenorphine pharmacokinetics are not altered by advanced age or renal dysfunction. In addition, the risk of respiratory depression is lower than with other opioids including morphine, hydromorphone, methadone and fentanyl. Unlike morphine and fentanyl, there is no immunosuppressive activity with buprenorphine at therapeutic analgesic doses. Transdermal buprenorphine has significantly improved the clinical use of the drug, providing continuous buprenorphine release for up to 96 h. In clinical trials, patients receiving transdermal buprenorphine experienced significantly greater pain relief, better sleep, and a reduced need for rescue therapy, compared to placebo. Large-scale post-marketing studies have confirmed the effectiveness of transdermal buprenorphine in treating moderate-to-severe cancer and non-cancer pain including neuropathic syndromes. Finally, the comparably low incidence of CNS adverse events and constipation, and the possibility of use in severe renal dysfunction without a need for dose adjustment make buprenorphine well suited for chronic pain management in at-risk patients, such as diabetics, elderly or renally impaired individuals including those requiring haemodialysis.

Long-term organ protection by doxazosin and/or quinapril as antihypertensive therapy.

PubMed

Gallego-Delgado, Julio; Lazaro, Alberto; Gomez-Garre, Dulcenombre; Osende, Julio I; Gonzalez-Rubio, Maria L; Herraiz, Marta; Manzarbeitia, Félix; Fortes, José; Fernandez-Cruz, Arturo; Egido, Jesús

2006-01-01

Even with optimal blood pressure control, organ protection may also depend on the selected therapeutic regime. Angiotensin-converting enzyme inhibitors have been shown to provide excellent organ protection in hypertension, and may show dose-dependent protective effects. Adrenergic alpha blockers have been associated with an increased rate of heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and Vasodilator-Heart Failure Trial (V-HeFT). This has been related to a proapoptotic effect of this drug in cardiomyocytes. Our purpose is to compare the heart and renal protection of a high quinapril dose, with a combined low quinapril dose plus doxazosin, in an animal model of chronic hypertension. Uninephrectomized spontaneously hypertensive 12-week-old rats were treated for 36 weeks with either quinapril or a combination of doxazosin plus a low quinapril dose. Tight blood pressure control was achieved with both treatments. Renal and cardiac protection was assessed by different parameters, and cardiac apoptosis was evaluated by active caspase-3, apoptotic protein and heat shock protein levels. Untreated hypertensive and normotensive rats were included as controls. Both treatments showed significant heart and renal protection compared with untreated animals. Both therapeutic regimes showed similar protection in renal and cardiac pathology, coronary media fibrosis, myocardial apoptosis and cardiac index. Proteinuria and left ventricular hypertrophy regression were significantly lower in the quinapril group compared with the combined treatment group. Blood pressure control with a high quinapril dose provided higher organ protection than a combined therapy with a lower quinapril dose. This effect was not due to a deleterious effect of doxazosin.

The potential usefulness of the Response Index in positron emission tomography assessing the therapeutic effect of pre-operative chemotherapy for advanced colorectal cancer.

PubMed

Nomura, Masatoshi; Takahashi, Hidekazu; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Matsuda, Chu; Ikenaga, Masakazu; Yamamoto, Hirofumi; Murata, Kohei; Doki, Yuichiro; Mori, Masaki; Mizushima, Tsunekazu

2017-12-01

Pre-operative chemotherapy is an option for patients with local advanced rectal cancer, but the response rate to pre-operative chemotherapy with oxaliplatin is still low. If the therapeutic effect of pre-operative chemotherapy could be assessed, we may be able to convert to surgery early. The purpose of the present study was to validate the correlation between the maximum standardized uptake value (SUV max ) in 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) of the primary tumor and the therapeutic effect of pre-operative chemotherapy in advanced colorectal cancer. Retrospective cohort study from January 2011 to October 2015. We examined 28 patients with pathologically confirmed sigmoid or rectal cancer that underwent pre-operative chemotherapy and surgery. The correlation between Response Index (RI), calculated as (SUV max after chemotherapy)/(SUV max before chemotherapy), and the therapeutic effect on the primary tumor in advanced colorectal cancer. The degree of differentiation (p = 0.04), SUV max in the primary tumor after chemotherapy (p = 0.02), and RI (p = 0.008) were significant predictors of the therapeutic effect in univariate analysis. The areas under the ROC curve constructed with RI and therapeutic effect was 0.77. The optimal cut-off values for the RI in the responder group was < 0.32. RI calculated as (SUV max after chemotherapy)/(SUV max before chemotherapy) in the primary tumor significantly correlated with the therapeutic effect of chemotherapy on advanced colorectal cancer. Thus, RI is potentially useful for predicting the therapeutic effect in advanced colorectal cancer.

A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations

PubMed Central

Thiel, Christoph; Cordes, Henrik; Fabbri, Lorenzo; Aschmann, Hélène Eloise; Baier, Vanessa; Atkinson, Francis; Blank, Lars Mathias; Kuepfer, Lars

2017-01-01

Drug-induced toxicity is a significant problem in clinical care. A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses, in particular within a patient context. Here, a comparative toxicity analysis was performed for fifteen hepatotoxic drugs by evaluating toxic changes reflecting the transition from therapeutic drug responses to toxic reactions at the cellular level. By use of physiologically-based pharmacokinetic modeling, in vitro toxicity data were first contextualized to quantitatively describe time-resolved drug responses within a patient context. Comparatively studying toxic changes across the considered hepatotoxicants allowed the identification of subsets of drugs sharing similar perturbations on key cellular processes, functional classes of genes, and individual genes. The identified subsets of drugs were next analyzed with regard to drug-related characteristics and their physicochemical properties. Toxic changes were finally evaluated to predict both molecular biomarkers and potential drug-drug interactions. The results may facilitate the early diagnosis of adverse drug events in clinical application. PMID:28151932

Comparison of lower limb muscle activation with ballet movements (releve and demi-plie) and general movements (heel rise and squat) in healthy adults.

PubMed

Kim, Min-Ju; Kim, Joong-Hwi

2016-01-01

[Purpose] The aim of this study was to demonstrate therapeutic grounds for rehabilitation exercise approach by comparing and analyzing muscular activities of Ballet movements: the releve movement (RM) and the demi-plie movement (DM). [Methods] Four types of movements such as RM vs. heel rise (HM) and DM vs. squat movement (SM) were randomized and applied in 30 healthy male and female individuals while measuring 10-s lower limb muscular activities (gluteus maximus [GMa], gluteus medius [GMe], rectus femoris [RF], adductor longus [AL], medial gastrocnemius [MG], and lateral gastrocnemius [LG]) by using surface electromyography (EMG). [Results] Significant differences were found in GMa, GMe, AL and MG activities for DM and in all of the six muscles for RM, in particular when the two groups were compared (RM vs HM and DM vs SM). [Conclusion] The RM and DM have a greater effect on lower limb muscular force activities compared to HM and SM and could be recommended as clinical therapeutic exercises for lower limb muscle enhancement.

Comparison of lower limb muscle activation with ballet movements (releve and demi-plie) and general movements (heel rise and squat) in healthy adults

PubMed Central

Kim, Min-Ju; Kim, Joong-Hwi

2016-01-01

[Purpose] The aim of this study was to demonstrate therapeutic grounds for rehabilitation exercise approach by comparing and analyzing muscular activities of Ballet movements: the releve movement (RM) and the demi-plie movement (DM). [Methods] Four types of movements such as RM vs. heel rise (HM) and DM vs. squat movement (SM) were randomized and applied in 30 healthy male and female individuals while measuring 10-s lower limb muscular activities (gluteus maximus [GMa], gluteus medius [GMe], rectus femoris [RF], adductor longus [AL], medial gastrocnemius [MG], and lateral gastrocnemius [LG]) by using surface electromyography (EMG). [Results] Significant differences were found in GMa, GMe, AL and MG activities for DM and in all of the six muscles for RM, in particular when the two groups were compared (RM vs HM and DM vs SM). [Conclusion] The RM and DM have a greater effect on lower limb muscular force activities compared to HM and SM and could be recommended as clinical therapeutic exercises for lower limb muscle enhancement. PMID:26957762

[Formulation and in vitro examination of furosemide-containing suppositories and preliminary experiences of their clinical use].

PubMed

Regdon, G; Fazekas, T; Regdon, G; Selmeczi, B

1997-01-01

Rectal suppositories containing Furosemide (4-Chloro-N-furfuryl-5-sulfamoylanthranilic acid) and Furosemide Sodium were formulated with various suppository bases. The in vitro drug release of Massa Estarinum 299 proved to be the best from among the vehicles having various physical-chemical properties. The diuretic effect of the two suppositories was compared in a prospective, cross-over clinical trial including 8 patients. Both preparations have induced and increase of urine flow, which was comparable to the diuretic effect of the tablet. Thus the possibility of rectal use has been added to the modalities of therapeutic Furosemide administration.

Comparative Effects of Urocortins and Stresscopin on Cardiac Myocyte Contractility

PubMed Central

Makarewich, Catherine A.; Troupes, Constantine D.; Schumacher, Sarah M.; Gross, Polina; Koch, Walter J.; Crandall, David L.; Houser, Steven R.

2015-01-01

Rationale There is a current need for development of new therapies for patients with heart failure. Objective To test the effects of members of the Corticotropin-Releasing Factor (CRF) family of peptides on myocyte contractility to validate them as potential heart failure therapeutics. Methods and Results Adult feline left ventricular myocytes (AFMs) were isolated and contractility was assessed in the presence and absence of CRF peptides Urocortin 2 (UCN2), Urocortin 3 (UCN3), Stresscopin (SCP), and the β-adrenergic agonist isoproterenol (Iso). An increase in fractional shortening and peak Ca2+ transient amplitude was seen in the presence of all CRF peptides. A decrease in Ca2+ decay rate (Tau) was also observed at all concentrations tested. cAMP generation was measured by ELISA in isolated AFMs in response to the CRF peptides and Iso and significant production was seen at all concentrations and time points tested. Conclusions The CRF family of peptides effectively increases cardiac contractility and should be evaluated as potential novel therapeutics for heart failure patients. PMID:26231084

Immunogenicity and therapeutic effects of a Mycobacterium tuberculosis rv2190c DNA vaccine in mice.

PubMed

Liang, Yan; Zhang, Xiaoyan; Bai, Xuejuan; Xiao, Li; Wang, Xiaomei; Zhang, Junxian; Yang, Yourong; Song, Jinying; Wang, Lan; Wu, Xueqiong

2017-02-27

Tuberculosis (TB) is a major global public health problem. New treatment methods on TB are urgently demanded. In this study, Mycobacterium tuberculosis (MTB) rv2190c DNA vaccine was prepared and its immunogenicity and therapeutic effects were evaluated. Non-infected mice immunized with rv2190c DNA or ag85a DNA showed higher levels of interferon-gamma (IFN-γ) in stimulated spleen lymphocyte culture supernatants, and had more Th1 cells and an elevatory ratio of Th1/Th2 immune cells in whole blood, indicating that Th1-type immune response was predominant. Compared with the saline group, ag85a DNA group and rv2190c DNA group in the infected mice decreased the lung colony-forming units (CFUs) by 0.533 and 0.283 log 10 , and spleen CFUs by 0.425 and 0.321 log 10 respectively, and pathological lesion. The rv2190c DNA had some immunotherapeutic effect on TB.

An fMRI study of neural pathways following acupuncture in mild cognitive impairment patients

NASA Astrophysics Data System (ADS)

Feng, Yuanyuan; Bai, Lijun; Wang, Hu; Zhong, Chongguang; You, Youbo; Zhang, Wensheng; Tian, Jie

2012-03-01

While the use of acupuncture as a complementary therapeutic method for treating MCI is popular in certain parts of the world, the underlying mechanism is still elusive. In the current study, we adopted multivariate Granger causality analysis (mGCA) to explore the causal interactions of brain networks involving acupuncture in mild cognitive impairment (MCI) patients compared to healthy controls (HC). The fMRI experiment was performed with two different paradigms: namely, deep acupuncture (DA) and superficial acupuncture (SA) at acupoint KI3. Results demonstrated that deep acupuncture could modulate the abnormal regions in MCI group. These regions are implicated in memory encoding and retrieving. This may relate to the purported therapeutically beneficial effects of acupuncture for the treatment of MCI. However, the most significant causal interactions were found in the sensorimotor regions in HC group. This may because acupuncture has a greater modulatory effect on patients with a pathological imbalance. This paper provides the preliminary neurophysiological evidence for the potential efficacy effect of acupuncture on MCI.

Adjunctive micronutrient supplementation for pulmonary tuberculosis.

PubMed

Armijos, Rodrigo X; Weigel, M Margaret; Chacon, Rocío; Flores, Luis; Campos, Armando

2010-01-01

To assess the effect of micronutrient supplementation on tuberculosis (TB) patient outcomes. The randomized, double-blinded, placebo-controlled study was conducted in pulmonary TB patients undergoing directly observed treatment short course/ tratamiento acortado estrictamente supervisado (TAES/ DOTS) at IMSS in Ciudad Juarez, Chihuahua, Mexico, who were recruited during August 2005-July 2006. Consecutive patients received zinc and vitamin A supplements or matched placebo for four months. Dietary intake, blood zinc and vitamin A, immune response (IFN-gamma,TNF-alpha, and IL-10 mRNA), and sputum smear conversion were measured. The proportion of micronutrient compared to placebo group subjects with a negative sputum smear by month 3 was significantly increased (p= 0.03). This occurred subsequent to increased TNF-alpha and IFN-gamma and decreased IL-10 observed at month 2. Micronutrient supplementation appeared to accelerate the beneficial therapeutic effect of chemotherapy. The earlier elimination of bacilli from sputum was associated with improved zinc status and Th1 immune response. The therapeutic effect of vitamin A was less evident.

An accessible pharmacodynamic transcriptional biomarker for notch target engagement.

PubMed

Tanis, K Q; Podtelezhnikov, A A; Blackman, S C; Hing, J; Railkar, R A; Lunceford, J; Klappenbach, J A; Wei, B; Harman, A; Camargo, L M; Shah, S; Finney, E M; Hardwick, J S; Loboda, A; Watters, J; Bergstrom, D A; Demuth, T; Herman, G A; Strack, P R; Iannone, R

2016-04-01

γ-Secretase mediates amyloid production in Alzheimer's disease (AD) and oncogenic activity of Notch. γ-Secretase inhibitors (GSIs) are thus of interest for AD and oncology. A peripheral biomarker of Notch activity would aid determination of the therapeutic window and dosing regimen for GSIs, given toxicities associated with chronic Notch inhibition. This study examined the effects of GSI MK-0752 on blood and hair follicle transcriptomes in healthy volunteers. The effects of a structurally diverse GSI on rhesus blood and hair follicles were also compared. Significant dose-related effects of MK-0752 on transcription were observed in hair follicles, but not blood. The GSI biomarker identified in follicles exhibited 100% accuracy in a clinical test cohort, and was regulated in rhesus by a structurally diverse GSI. This study identified a translatable, accessible pharmacodynamic biomarker of GSI target engagement and provides proof of concept of hair follicle RNA as a translatable biomarker source. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Consensus Treatment Plans for New-Onset Systemic Juvenile Idiopathic Arthritis

PubMed Central

DeWitt, Esi Morgan; Kimura, Yukiko; Beukelman, Timothy; Nigrovic, Peter A.; Onel, Karen; Prahalad, Sampath; Schneider, Rayfel; Stoll, Matthew L.; Angeles-Han, Sheila; Milojevic, Diana; Schikler, Kenneth N.; Vehe, Richard K.; Weiss, Jennifer E.; Weiss, Pamela; Ilowite, Norman T.; Wallace, Carol A.

2012-01-01

Objective There is wide variation in therapeutic approaches to systemic juvenile idiopathic arthritis (sJIA) among North American rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available for treatment of sJIA can result in better health outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans and standardized assessment schedules for use in clinical practice to facilitate such studies. Methods Case-based surveys were administered to CARRA members to identify prevailing treatments for new-onset sJIA. A 2-day consensus conference in April 2010 employed modified nominal group technique to formulate preliminary treatment plans and determine important data elements for collection. Follow-up surveys were employed to refine the plans and assess clinical acceptability. Results The initial case-based survey identified significant variability among current treatment approaches for new onset sJIA, underscoring the utility of standardized plans to evaluate comparative effectiveness. We developed four consensus treatment plans for the first 9 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The four treatment regimens included glucocorticoids only, or therapy with methotrexate, anakinra or tocilizumab, with or without glucocorticoids. This approach was approved by >78% of CARRA membership. Conclusion Four standardized treatment plans were developed for new-onset sJIA. Coupled with data collection at defined intervals, use of these treatment plans will create the opportunity to evaluate comparative effectiveness in an observational setting to optimize initial management of sJIA. PMID:22290637

[Genome-editing: focus on the off-target effects].

PubMed

He, Xiubin; Gu, Feng

2017-10-25

Breakthroughs of genome-editing in recent years have paved the way to develop new therapeutic strategies. These genome-editing tools mainly include Zinc-finger nucleases (ZFNs), Transcription activator-like effector nucleases (TALENs), and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas-based RNA-guided DNA endonucleases. However, off-target effects are still the major issue in genome editing, and limit the application in gene therapy. Here, we summarized the cause and compared different detection methods of off-targets.

The Clinical Efficacy of Autologous Platelet-Rich Plasma Combined with Ultra-Pulsed Fractional CO2 Laser Therapy for Facial Rejuvenation

PubMed Central

Hui, Qiang; Chang, Peng; Guo, Bingyu; Zhang, Yu

2017-01-01

Abstract Ultra-pulsed fractional CO2 laser is an efficient, precise, and safe therapeutic intervention for skin refreshing, although accompanied with prolonged edema and erythema. In recent years, autologous platelet-rich plasma (PRP) has been proven to promote wound and soft tissue healing and collagen regeneration. To investigate whether the combination of PRP and ultra-pulsed fractional CO2 laser had a synergistic effect on therapy for facial rejuvenation. Totally, 13 facial aging females were treated with ultra-pulsed fractional CO2 laser. One side of the face was randomly selected as experimental group and injected with PRP, the other side acted as the control group and was injected with physiological saline at the same dose. Comprehensive assessment of clinical efficacy was performed by satisfaction scores, dermatologists' double-blind evaluation and the VISIA skin analysis system. After treatment for 3 months, subjective scores of facial wrinkles, skin texture, and skin elasticity were higher than that in the control group. Similarly, improvement of skin wrinkles, texture, and tightness in the experimental group was better compared with the control group. Additionally, the total duration of erythema, edema, and crusting was decreased, in the experimental group compared with the control group. PRP combined with ultra-pulsed fractional CO2 laser had a synergistic effect on facial rejuvenation, shortening duration of side effects, and promoting better therapeutic effect. PMID:27222038

Sex reassignment surgery: a study of 141 Dutch transsexuals.

PubMed

Kuiper, B; Cohen-Kettenis, P

1988-10-01

This is an evaluation of the therapeutic effect of sex reassignment surgery on 36 female-to-male transsexuals and 105 male-to-female transsexuals in the Netherlands. Data were collected by means of structured interviews. The evaluation was made on the basis of subjective data only, that is on what the persons themselves reported on their gender identity, gender role, and physical condition. Allowing for the restrictive methodology of the (ex post facto) study, it is concluded that there is no reason to doubt the therapeutic effect of sex reassignment surgery. No specific differences were found between those who were still in medical treatment and those who had completed treatment. The findings obtained in the female-to-male transsexuals compare favorably with those obtained in male-to-female transsexuals. Finally, the conclusion is drawn that more attention ought to be paid to psychosocial guidance in addition to medical guidance.

Seeking new acne treatment from natural products, devices and synthetic drug discovery.

PubMed

Yang, Ji Hoon; Yoon, Ji Young; Kwon, Hyuck Hoon; Min, Seonguk; Moon, Jungyoon; Suh, Dae Hun

2017-01-01

Despite lots of research on the pathogenesis of acne, the development of new therapeutic agents is still stagnant. Conventional agents which target multiple pathological processes have some serious side effects and this makes seeking new treatment options important for treating acne. As new therapeutic options, researchers are focusing on natural products, synthetic drugs and devices. From natural products, epigallocatechin-3 gallate, lupeol, cannabidiol and Lactobacillus fermented Chamaecyperis obtusa were reported to be possible candidates for novel drugs, targeting multiple pathogenic factors. Synthetic anti- P.acnes agent, nitric oxide nanoparticles and α-mangostin nanoparticles are shown to be effective in acne treatment. Device or procedural methods such as fractional microneedling radiofrequency, cryolysis, photothermolysis and daylight photodynamic therapy have potential as new treatment options for acne. Further large clinical trials comparing these new treatments with existing agents will be necessary in the future.

Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer

NASA Astrophysics Data System (ADS)

Hervault, Aziliz; Thanh, Nguyêl; N. Thé, Kim

2014-09-01

Magnetic nanoparticles have been widely investigated for their great potential as mediators of heat for localised hyperthermia therapy. Nanocarriers have also attracted increasing attention due to the possibility of delivering drugs at specific locations, therefore limiting systematic effects. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia was noticed more than thirty years ago. However, combining magnetic nanoparticles with molecules of drugs in the same nanoformulation has only recently emerged as a promising tool for the application of hyperthermia with combined chemotherapy in the treatment of cancer. The main feature of this review is to present the recent advances in the development of multifunctional therapeutic nanosystems incorporating both magnetic nanoparticles and drugs, and their superior efficacy in treating cancer compared to either hyperthermia or chemotherapy as standalone therapies. The principle of magnetic fluid hyperthermia is also presented.

Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer.

PubMed

Hervault, Aziliz; Thanh, Nguyen Th Kim

2014-10-21

Magnetic nanoparticles have been widely investigated for their great potential as mediators of heat for localised hyperthermia therapy. Nanocarriers have also attracted increasing attention due to the possibility of delivering drugs at specific locations, therefore limiting systematic effects. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia was noticed more than thirty years ago. However, combining magnetic nanoparticles with molecules of drugs in the same nanoformulation has only recently emerged as a promising tool for the application of hyperthermia with combined chemotherapy in the treatment of cancer. The main feature of this review is to present the recent advances in the development of multifunctional therapeutic nanosystems incorporating both magnetic nanoparticles and drugs, and their superior efficacy in treating cancer compared to either hyperthermia or chemotherapy as standalone therapies. The principle of magnetic fluid hyperthermia is also presented.

Sleep enhances exposure therapy.

PubMed

Kleim, B; Wilhelm, F H; Temp, L; Margraf, J; Wiederhold, B K; Rasch, B

2014-05-01

Sleep benefits memory consolidation. Here, we tested the beneficial effect of sleep on memory consolidation following exposure psychotherapy of phobic anxiety. A total of 40 individuals afflicted with spider phobia according to DSM-IV underwent a one-session virtual reality exposure treatment and either slept for 90 min or stayed awake afterwards. Sleep following exposure therapy compared with wakefulness led to better reductions in self-reported fear (p = 0.045, d = 0.47) and catastrophic spider-related cognitions (p = 0.026, d = 0.53) during approaching a live spider, both tested after 1 week. Both reductions were associated with greater percentages of stage 2 sleep. Our results indicate that sleep following successful psychotherapy, such as exposure therapy, improves therapeutic effectiveness, possibly by strengthening new non-fearful memory traces established during therapy. These findings offer an important non-invasive alternative to recent attempts to facilitate therapeutic memory extinction and consolidation processes with pharmacological or behavioral interventions.

A systematic review exploring therapist competence, adherence, and therapy outcomes in individual CBT for children and young people.

PubMed

Rapley, Hannah A; Loades, Maria E

2018-04-22

Whilst the evidence base for cognitive behavioural therapy (CBT) with children and young people is growing, the mechanisms through which these beneficial effects occur are still unclear. This systematic review seeks to appraise the relationship between therapeutic outcomes in CBT and therapist adherence and competence, within the child and adolescent literature. A systematic review was carried out, with five studies identified as meeting the inclusion criteria. The literature is currently small and inconclusive. Amongst the studies reviewed, there were inconsistent findings, with minimal-to-no effect sizes found between adherence, competence, and outcomes. The current paucity of research in this area means that conclusions are currently limited. The role and impact of adherence and competence on therapeutic outcomes remains unclear within individual CBT in a child population. This is comparable with the current adult literature, where findings also remain inconclusive. Further research avenues are discussed.

Seeking new acne treatment from natural products, devices and synthetic drug discovery

PubMed Central

Yoon, Ji Young; Kwon, Hyuck Hoon; Min, Seonguk; Suh, Dae Hun

2017-01-01

ABSTRACT Despite lots of research on the pathogenesis of acne, the development of new therapeutic agents is still stagnant. Conventional agents which target multiple pathological processes have some serious side effects and this makes seeking new treatment options important for treating acne. As new therapeutic options, researchers are focusing on natural products, synthetic drugs and devices. From natural products, epigallocatechin-3 gallate, lupeol, cannabidiol and Lactobacillus fermented Chamaecyperis obtusa were reported to be possible candidates for novel drugs, targeting multiple pathogenic factors. Synthetic anti-P.acnes agent, nitric oxide nanoparticles and α-mangostin nanoparticles are shown to be effective in acne treatment. Device or procedural methods such as fractional microneedling radiofrequency, cryolysis, photothermolysis and daylight photodynamic therapy have potential as new treatment options for acne. Further large clinical trials comparing these new treatments with existing agents will be necessary in the future. PMID:29484092

Pharmacological Effect of Berberine Chloride in Propyl Thiouracil Induced Thyroidal Dysfunction - A Time Bound Study in Female Rats.

PubMed

Maurya, Harikesh; Dhiman, Sheena; Dua, Kamal; Gupta, Gaurav

2016-01-01

The present study is aimed at bringing out the information on the effect of berberine chloride in hyper and hypo thyroidal model with two dose levels. The research article also reviewed details of various existing patents associated with comprehensive compilation regarding the therapeutic application of berberine and related forms. Sixty female wistar rats weighing between 150-250 gm were divided in to 10 groups. The animals were grouped in to solvent control; hypothyroid; hyperthyroid; prophylactic with two different doses of berberine chloride (50 and 100 mg/kg); treatment groups similar to that of the prophylactic and therapeutic group. To substantiate the dose dependent effect of berberine chloride in 6-n-propyL-2-thiouracil (PTU) induced hypothyroidism, lipid profile, thyroid profile, enzymes profiles and blood profiles, in addition to histopathological studies were also carried out. There was no any significant difference in the lipid profile among solvent control, treatment and prophylactic groups. However, there was a significant difference (***p<0.001) in serum triglycerides, LDL and VLDL of hypothyroid group when compound to that of the rest. As far as thyroid profile is concerned, T3 level of berberine chloride (50 mg/kg) treated groups (prophylactic+ treatment) showed a significant rise compared to hypothyroid group. TSH level in prophylactic groups was far higher than the rest of the groups (3.002±0.0192, 1.051±0.0008 against the solvent control, 0.308±0.008). SGOT, SGPT levels were significantly higher with the therapeutic group than that of the normal and hypo-thyroidal group. Blood profile of berberine chloride (100 mg/kg) treated therapeutic group was comparable to that of the solvent control than all other groups. The probable mechanism underlying may be that inactivation of type I 5.-iodothyronine deiodinase (5.DI) enzyme by NF-kB pathway. From the findings of the current study it can be concluded that berberine chloride possesses both thyroid stimulating and suppressing activities depending on its dose, especially berberine chloride 50 mg/kg supports thyroid stimulating property.

Porous Se@SiO2 nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis.

PubMed

Deng, Guoying; Dai, Chenyun; Chen, Jinyuan; Ji, Anqi; Zhao, Jingpeng; Zhai, Yue; Kang, Yingjie; Liu, Xijian; Wang, Yin; Wang, Qiugen

2018-01-01

Methylprednisolone (MPS) is an important drug used in therapy of many diseases. However, osteonecrosis of the femoral head is a serious damage in the MPS treatment. Thus, it is imperative to develop new drugs to prevent the serious side effect of MPS. The potential interferences Se@SiO 2 nanocomposites may have to the therapeutic effect of methylprednisolone (MPS) were evaluated by classical therapeutic effect index of acute respiratory distress syndrome (ARDS), such as wet-to-dry weight ratio, inflammatory factors IL-1β and TNF-α. And oxidative stress species (ROS) index like superoxide dismutase (SOD) and glutathione (GSH) were tested. Then, the protection effects of Se@SiO 2 have in osteonecrosis of the femoral head (ONFH) were evaluated by micro CT, histologic analysis and Western-blot analysis. In the present study, we found that in the rat model of ARDS, Se@SiO 2 nanocomposites induced SOD and GSH indirectly to reduce ROS damage. The wet-to-dry weight ratio of lung was significantly decreased after MPS treatment compared with the control group, whereas the Se@SiO 2 did not affect the reduced wet-to-dry weight ratio of MPS. Se@SiO 2 also did not impair the effect of MPS on the reduction of inflammatory factors IL-1β and TNF-α, and on the alleviation of structural destruction. Furthermore, micro CT and histologic analysis confirmed that Se@SiO 2 significantly alleviate MPS-induced destruction of femoral head. Moreover, compared with MPS group, Se@SiO 2 could increase collagen II and aggrecan, and reduce the IL-1β level in the cartilage of femoral head. In addition, the biosafety of Se@SiO 2 in vitro and in vivo were supported by cell proliferation assay and histologic analysis of main organs from rat models. Se@SiO 2 nanocomposites have a protective effect in MPS-induced ONFH without influence on the therapeutic activity of MPS, suggesting the potential as effective drugs to avoid ONFH in MPS therapy.

Porous Se@SiO2 nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis

PubMed Central

Chen, Jinyuan; Ji, Anqi; Zhao, Jingpeng; Zhai, Yue; Kang, Yingjie; Liu, Xijian; Wang, Yin; Wang, Qiugen

2018-01-01

Background Methylprednisolone (MPS) is an important drug used in therapy of many diseases. However, osteonecrosis of the femoral head is a serious damage in the MPS treatment. Thus, it is imperative to develop new drugs to prevent the serious side effect of MPS. Methods The potential interferences Se@SiO2 nanocomposites may have to the therapeutic effect of methylprednisolone (MPS) were evaluated by classical therapeutic effect index of acute respiratory distress syndrome (ARDS), such as wet-to-dry weight ratio, inflammatory factors IL-1β and TNF-α. And oxidative stress species (ROS) index like superoxide dismutase (SOD) and glutathione (GSH) were tested. Then, the protection effects of Se@SiO2 have in osteonecrosis of the femoral head (ONFH) were evaluated by micro CT, histologic analysis and Western-blot analysis. Results In the present study, we found that in the rat model of ARDS, Se@SiO2 nanocomposites induced SOD and GSH indirectly to reduce ROS damage. The wet-to-dry weight ratio of lung was significantly decreased after MPS treatment compared with the control group, whereas the Se@SiO2 did not affect the reduced wet-to-dry weight ratio of MPS. Se@SiO2 also did not impair the effect of MPS on the reduction of inflammatory factors IL-1β and TNF-α, and on the alleviation of structural destruction. Furthermore, micro CT and histologic analysis confirmed that Se@SiO2 significantly alleviate MPS-induced destruction of femoral head. Moreover, compared with MPS group, Se@SiO2 could increase collagen II and aggrecan, and reduce the IL-1β level in the cartilage of femoral head. In addition, the biosafety of Se@SiO2 in vitro and in vivo were supported by cell proliferation assay and histologic analysis of main organs from rat models. Conclusion Se@SiO2 nanocomposites have a protective effect in MPS-induced ONFH without influence on the therapeutic activity of MPS, suggesting the potential as effective drugs to avoid ONFH in MPS therapy. PMID:29606872

Irinotecan delivery by microbubble-assisted ultrasound - A pilot preclinical study

NASA Astrophysics Data System (ADS)

Escoffre, Jean-Michel; Novell, Anthony; Serrière, Sophie; Bouakaz, Ayache

2012-11-01

Irinotecan is conventionally used for the treatment of colorectal cancer. However, its administration is associated with severe side effects. Targeted drug delivery using ultrasound (US) combined with microbubbles offers new opportunities to increase the therapeutic effectiveness of antitumor treatment and to reduce toxic exposure to healthy tissues. The objective of this study is to investigate the safety and efficacy of in-vivo delivery of irinotecan by microbubble-assisted US in human glioblastoma model (U-87 MG). In order to validate the potential of this new method in-vivo, subcutaneous tumors were implanted in the flank of nude mouse and treated when they reached a volume of 100 mm3. In the first study, the measured volumes with caliper and anatomic ultrasound imaging were compared for the monitoring and the quantification of tumor growth during 27 days. Ultrasound imaging measurements were positively correlated to caliper measurements. The tumor treatment consisted of an i.v. injection of irinotecan (20 mg/kg) followed one hour later by i.v. administration of MM1 microbubble and an US insonation using a single-element transducer operating at 1MHz (400 kPa, 10 kHz PRF 40% DC, 3 min). The therapeutic efficacy was evaluated for 39 days by measuring the tumor volume before and after treatment using a caliper and based on ultrasound images using an 18 MHz probe (Vevo 2100). Our results showed that anatomical ultrasound imaging was as efficient as caliper for the monitoring and the quantification of tumor growth. Moreover, irinotecan delivery by sonoporation induced a significant decrease of glioblastoma tumor volume and an increase of tumor-doubling time compared to the tumor treated by irinotecan alone. In conclusion, this novel therapeutic approach has promising features since it can be used to reduce the injected drug dose and to achieve a better therapeutic efficacy.

Investigation and Manipulation of the Local Microenvironment of Spherical Nucleic Acid Nanoconjugates

NASA Astrophysics Data System (ADS)

Briley, William Edward

For the past several decades, tremendous efforts have been made by many to battle cancer,one of the leading causes of death in the United States and around the world. Unfortunately, the diagnosis and treatment of many genetically-based disorders such as cancer remains very difficult to this day. This is due to the fact that current technologies are unable to adequately differentiate between healthy and diseased cells. In many cases, state-of-the-art diagnostic and therapeutics for genetic disorders rely on targeting downstream effects that may be related to, or influenced by aberrations in gene expression, rather than targeting the up- or down-regulated transcripts themselves. This type of targeting can lead to significant off-target effects, which can translate to false positives for diagnostics, and systemic toxicity for therapeutics. This thesis discusses a nanoparticle-based conjugate which aims to increase the specificity of diagnostics, therapeutics, and biological research platforms by targeting RNA transcripts directly. This nanoconjugate, known as the spherical nucleic acid (SNA) is capable of entering live cells with negligible cytotoxicity and immunogenicity, and binding onto targeted RNA transcripts. Chapter one details the properties and synthesis of the SNA, and discusses how the cell entry/transcript binding capabilities of the SNA can be translated into therapeutic and diagnostic platforms. Chapter two then moves into the therapeutic applications of the SNA, discussing a novel platform known as the Sticky-flare, which is capable of detecting and fluorescently labeling target transcripts for real time analysis. Chapter three then investigates the function of the SNA in a therapeutic application. Specifically, the route that topically applied SNAs take to penetrate through skin is elucidated, and is contextualized by comparing the penetration of SNAs with equivalent linear DNA sequences. Linear nucleic acids are typically not capable of effecting gene regulation via topical application in the way that SNAs have been shown to, and the reasons for this are identified and examined. Finally, chapter five investigates whether super-porous materials such as metal organic frameworks (MOFs) are applicable as SNA cores, specifically I analyze if SNAs with a MOF core maintain the ability to enter cells in a way similar to gold core SNAs. It further investigates the complications of analyzing SNAs with high sedimentation rates (S) in cell culture, and the development of a novel method with which to analyze high-S nanoparticle structures. The conclusion of the thesis then mentions future applications of diagnostic and therapeutic SNAs, and how such nanostructures may play a role in molecular biology, as well as cancer diagnostics and therapeutics.

Pelvic floor muscle rehabilitation for patients with lifelong premature ejaculation: a novel therapeutic approach

PubMed Central

Palleschi, Giovanni; Fuschi, Andrea; Maggioni, Cristina; Rago, Rocco; Zucchi, Alessandro; Costantini, Elisabetta; Carbone, Antonio

2014-01-01

Objectives: Premature ejaculation is the most common male sexual disorder. The aim of the study was to evaluate the possible therapeutic role of pelvic floor muscle rehabilitation in patients affected by lifelong premature ejaculation. Methods: We treated 40 men with lifelong premature ejaculation, reporting, a baseline intravaginal ejaculatory latency time (IELT) ≤ 1 min, with 12-week pelvic floor muscle rehabilitation. Results: At the end of the rehabilitation, mean IELTs were calculated to evaluate the effectiveness of the therapy. At the end of the treatment, 33 (82.5%) of the 40 patients gained control of their ejaculatory reflex, with a mean IELT of 146.2 s (range: 123.6–152.4 s). A total of 13 out of 33 (39%) patients were evaluated at 6 months follow up, and they maintained a significant IELT (112.6 s) compared with their initial IELT (mean 39.8 s). Conclusions: The results obtained in our subjects treated with pelvic floor rehabilitation are promising. This therapy represents an important cost reduction compared with the standard treatment (selective serotonin reuptake inhibitors). Based on the present data, we propose pelvic floor muscle rehabilitation as a new, viable therapeutic option for the treatment of premature ejaculation. PMID:24883105

Cutaneous fungal microbiome: Malassezia yeasts in seborrheic dermatitis scalp in a randomized, comparative and therapeutic trial.

PubMed

Kamamoto, C S L; Nishikaku, A S; Gompertz, O F; Melo, A S; Hassun, K M; Bagatin, E

2017-01-01

Malassezia spp in skin microbiome scalp has been implicated in seborrheic dermatitis pathogenesis. Thus, treatment based in antifungal combined to topical keratolitic agents have been indicated as well as oral isotretinoin as it reduces the sebum production, glandular's size and possesses anti-inflammatory properties. This randomized, comparative and therapeutic trial aimed toper form the genotypic identification of Malassezia species before and after low-dose oral isotretinoin or topical antifungal treatments for moderate to severe seborrhea and/or seborrheic dermatitis on scalp. Scales and sebum of the scalp were seeded in the middle of modified Dixon and incubated at 32°C. For genotypic identification polymerase chain reaction primers for the ITS and D1/D2 ribossomal DNA were used and followed by samples sequencing. The procedure was conducted before and after therapeutic and randomized intervention for moderate to severe seborrhea/seborrheic dermatitis on the scalp, including oral isotretinoin, 10 mg, every other day and anti-seborrheic shampoo (piroctone olamine), over six months. The M. globosa and M. restricta were the most frequent species isolated on the scalp before and after both treatments. Other non- Malassezia species were also identified. The Malassezia spp. were maintained in the scalp after both treatments that were equally effective for the control of seborrhea/seborrheic dermatitis clinical signs.

The therapeutic power of play: examining the play of young children with leukaemia.

PubMed

Gariépy, N; Howe, N

2003-11-01

The therapeutic function of play has been investigated in relation to recognized stressors such as hospitalization, illness and medical treatments for ill children. While medical treatments in the past 30 years have improved survival rates, children's psychological experiences and quality of life during and after their illness have received limited attention. The present study investigated the therapeutic effects of play on 3- to 5-year-old children with leukaemia compared with a control group of healthy children. The participants with leukaemia (n = 11) were from the external oncology clinic of an urban children's hospital; control children (n = 11) attended a day care centre. Measures included children's experience of stress, social and cognitive play behaviours, and daily mood. A series of manova revealed that the children with leukaemia, compared with the control children, engaged in (a) significantly fewer total play behaviours, and in particular less (b) parallel, (c) group and (d) dramatic play. Pearson correlations revealed significant relationships between reports of 'being happy' and play only for children with leukaemia. Quantitative and qualitative analyses revealed a pattern of repetitive play activities week after week for children with leukaemia, but not controls. Findings are discussed in light of the theoretical and practical implications for children undergoing treatment for leukaemia.

Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

PubMed Central

Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

Psychological consequences in pediatric intensive care unit survivors: the neglected outcome.

PubMed

Muranjan, Mamta N; Birajdar, Suresh B; Shah, Henal R; Sundaraman, Preeti; Tullu, Milind S

2008-02-01

To determine whether Pediatric Intensive Care Unit (PICU) hospitalization results in adverse psychological effects and to identify the contributory factors. Level III PICU of a tertiary center. Prospective cohort study. Consecutive patients 5 years or older admitted to PICU for at least 48 hours constituted the study population. Controls were age and sex matched children hospitalized in the pediatric wards for at least 48 hours. Severity of illness was assessed by the Pediatric Risk of Mortality (PRISM) score. Level of therapeutic intervention was determined by the Therapeutic Interventions Scoring System (TISS--76 score). Temperament Measurement Schedule was used to assess the premorbid temperament. Psychological assessment was performed using Impact of Event Scale (IES), Birleson Depression Scale and the Self-Esteem Scale. Follow-up evaluation was done one month after discharge. There were 30 children each in the study and control groups. They had comparable pre-morbid temperament as well as scores on the self-esteem and depression scales. Significantly higher proportion of patients in PICU had intrusive thoughts (43%) as compared to controls (6.7%). Development of intrusive thoughts correlated significantly with the degree of intervention. Demographic parameters, nature of the disease, duration of hospitalization and severity of illness did not correlate with the psychological outcome. One month after discharge, scores in both groups were comparable. Children subjected to therapeutic interventions in the PICU develop transient psychological impairment manifested by experiencing intrusive thoughts that resolve within a month.

[A comparative study of the effectiveness and tolerability of a procedure involving slow dose-escalation of rivastigmine in patients with mild or moderate Alzheimer-type dementia: the SCALEX study].

PubMed

Agüera-Ortiz, L F; Ramos-García, M; Gobartt, A L

To determine and to compare the tolerability and effectiveness of a slow escalation of the dose of rivastigmine in patients with Alzheimer's disease with respect to using it with a faster escalation. We conducted a multi-centre, naturalistic, open-label, randomised trial with 429 hospital outpatients diagnosed with Alzheimer-type dementia (according to DSM-IV and NINCDS-ADRA criteria) and in whom treatment with rivastigmine was clinically indicated. Two study groups were established: slow escalation and fast escalation (in accordance with usual clinical practice); effectiveness and tolerability variables were analysed in the two groups, as was the proportion of patients who reached therapeutic doses (> 6 mg/day). The scores obtained on the CGI, MMSE, NPI and Barthel index scales were analysed, together with adverse events and reactions concerning spontaneous communication, and scores on the UKU scale. The slow escalation group displayed slightly higher percentages of sub-therapeutic anticipated interruptions than the fast escalation group (chi-square test; p < 0.05). On comparing the two treatment groups, no statistically significant differences were observed for the evolution of the scores on the different scales of effectiveness; no statistically significant differences were found between the two groups in the safety and tolerability analyses (chi-square test, exact test; p > 0.05) for most of the parameters that were studied (adverse reactions in spontaneous communication and the modified UKU scale). Slow escalation of the dose of rivastigmine did not display greater effectiveness or tolerability in comparison to an escalation applied in accordance with usual clinical practice.

Continuous positive airway pressure improves sleep and daytime sleepiness in patients with Parkinson disease and sleep apnea.

PubMed

Neikrug, Ariel B; Liu, Lianqi; Avanzino, Julie A; Maglione, Jeanne E; Natarajan, Loki; Bradley, Lenette; Maugeri, Alex; Corey-Bloom, Jody; Palmer, Barton W; Loredo, Jose S; Ancoli-Israel, Sonia

2014-01-01

Obstructive sleep apnea (OSA), common in Parkinson disease (PD), contributes to sleep disturbances and daytime sleepiness. We assessed the effect of continuous positive airway pressure (CPAP) on OSA, sleep, and daytime sleepiness in patients with PD. This was a randomized placebo-controlled, crossover design. Patients with PD and OSA were randomized into 6 w of therapeutic treatment or 3 w of placebo followed by 3 w of therapeutic treatment. Patients were evaluated by polysomnography (PSG) and multiple sleep latency test (MSLT) pretreatment (baseline), after 3 w, and after 6 w of CPAP treatment. Analyses included mixed models, paired analysis, and within-group analyses comparing 3 w to 6 w of treatment. Sleep laboratory. Thirty-eight patients with PD (mean age = 67.2 ± 9.2 y; 12 females). Continuous positive airway pressure. PSG OUTCOME MEASURES: sleep efficiency, %sleep stages (N1, N2, N3, R), arousal index, apnea-hypopnea index (AHI), and % time oxygen saturation < 90% (%time SaO2 < 90%). MSLT outcome measures: mean sleep-onset latency (MSL). There were significant group-by-time interactions for AHI (P < 0.001), % time SaO2 < 90% (P = 0.02), %N2 (P = 0.015) and %N3 (P = 0.014). Subjects receiving therapeutic CPAP showed significant decrease in AHI, %time SaO2 < 90%, %N2, and significant increase in %N3 indicating effectiveness of CPAP in the treatment of OSA, improvement in nighttime oxygenation, and in deepening sleep. The paired sample analyses revealed that 3 w of therapeutic treatment resulted in significant decreases in arousal index (t = 3.4, P = 0.002). All improvements after 3 w were maintained at 6 w. Finally, 3 w of therapeutic CPAP also resulted in overall decreases in daytime sleepiness (P = 0.011). Therapeutic continuous positive airway pressure versus placebo was effective in reducing apnea events, improving oxygen saturation, and deepening sleep in patients with Parkinson disease and obstructive sleep apnea. Additionally, arousal index was reduced and effects were maintained at 6 weeks. Finally, 3 weeks of continuous positive airway pressure treatment resulted in reduced daytime sleepiness measured by multiple sleep latency test. These results emphasize the importance of identifying and treating obstructive sleep apnea in patients with Parkinson disease.

Changes in Transversus Abdominis Muscle Thickness after Lumbo-Pelvic Core Stabilization Training among Chronic Low Back Pain Individuals.

PubMed

Leonard, J H; Paungmali, A; Sitilertpisan, P; Pirunsan, U; Uthaikhup, S

2015-01-01

Lumbo-pelvic core stabilization training (LPST) is one of the therapeutic exercises common in practice for rehabilitation of patients with chronic low back pain. This study was carried out to examine the therapeutic effects of LPST on the muscle thickness of transversus abdominis (TrA) at rest and during contraction among patients with chronic non-specific low back pain. A total of 25 participants (7 males and 18 females) with chronic non-specific low back pain participated in a within-subject, repeated measures, double-blinded, placebo-controlled comparisons trial. The participants received three different types of experimental therapeutic training conditions which includes the lumbo-pelvic core stabilization training (LPST), the placebo treatment with passive cycling (PC) and a controlled intervention with rest (CI). The interventions were carried out by randomization with 48 hours between the sessions. The effectiveness of interventions was studied by measuring the changes in muscle thickness of TrA at rest and during contraction using a real time ultrasonography. Repeated measures ANOVA demonstrated that the LPST provided significant therapeutic benefits as measured by an increase in the muscle thickness of the TrA at rest (p<0.05) and during contraction (p<0.01). The percentage change of the muscle thickness observed during LPST was significantly higher (p<0.01) when compared to the other two experimental training conditions. The findings indicated that the LPST might provide therapeutic benefits by increasing the muscle thickness and function of TrA. Therefore, it is suggested that LPST technique should be considered as part of management program for treatment of low back pain.

Therapeutic Exercise Training to Reduce Chronic Headache in Working Women: Design of a Randomized Controlled Trial.

PubMed

Rinne, Marjo; Garam, Sanna; Häkkinen, Arja; Ylinen, Jari; Kukkonen-Harjula, Katriina; Nikander, Riku

2016-05-01

Cervicogenic headache and migraine are common causes of visits to physicians and physical therapists. Few randomized trials utilizing active physical therapy and progressive therapeutic exercise have been previously published. The existing evidence on active treatment methods supports a moderate effect on cervicogenic headache. The aim of this study is to investigate whether a progressive, group-based therapeutic exercise program decreases the intensity and frequency of chronic headache among women compared with a control group receiving a sham dose of transcutaneous electrical nerve stimulation (TENS) and stretching exercises. A randomized controlled trial with 6-month intervention and follow-up was developed. The participants were randomly assigned to either a treatment group or a control group. The study is being conducted at 2 study centers. The participants are women aged 18 to 60 years with chronic cervicogenic headache or migraine. The treatment group's exercise program consisted of 6 progressive therapeutic exercise modules, including proprioceptive low-load progressive craniocervical and cervical exercises and high-load exercises for the neck muscles. The participants in the control group received 6 individually performed sham TENS treatment sessions. The primary outcome is the intensity of headache. The secondary outcomes are changes in frequency and duration of headache, neck muscle strength, neck and shoulder flexibility, impact of headache on daily life, neck disability, fear-avoidance beliefs, work ability, and quality of life. Between-group differences will be analyzed separately at 6, 12, and 24 months with generalized linear mixed models. In the case of count data (eg, frequency of headache), Poisson or negative binomial regression will be used. The therapists are not blinded. The effects of specific therapeutic exercises on frequency, intensity, and duration of chronic headache and migraine will be reported. © 2016 American Physical Therapy Association.

Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice.

PubMed

Tanaka, Ken-Ichiro; Sato, Keizo; Aoshiba, Kazutetsu; Azuma, Arata; Mizushima, Tohru

2012-06-15

Bronchodilators (such as ipratropium bromide), steroids (such as fluticasone propionate), and newly developed anti-inflammatory drugs (such as roflumilast) are used for patients with chronic obstructive pulmonary disease (COPD). We recently reported that lecithinized superoxide dismutase (PC-SOD) confers a protective effect in mouse models of COPD. We here examined the therapeutic effect of the combined administration of PC-SOD with ipratropium bromide on pulmonary emphysema and compared the effect of PC-SOD to other types of drugs. The severity of emphysema in mice was assessed by various criteria. Lung mechanics (elastance) and respiratory function (ratio of forced expiratory volume in the first 0.05 s to forced vital capacity) were assessed. Administration of PC-SOD by inhalation suppressed elastase-induced pulmonary emphysema, alteration of lung mechanics, and respiratory dysfunction. The concomitant intratracheal administration of ipratropium bromide did not alter the ameliorating effects of PC-SOD. Administration of ipratropium bromide, fluticasone propionate, or roflumilast alone did not suppress the elastase-induced increase in the pulmonary level of superoxide anion, pulmonary inflammatory response, pulmonary emphysema, alteration of lung mechanics, or respiratory dysfunction as effectively as did PC-SOD. PC-SOD, but not the other drugs, showed a therapeutic effect even when the drug was administered after the development of emphysema. PC-SOD also suppressed the cigarette smoke-induced pulmonary inflammatory response and increase in airway resistance. Based on these results, we consider that the inhalation of PC-SOD would be therapeutically beneficial for COPD.

Enhancing cancer therapeutics using size-optimized magnetic fluid hyperthermia

NASA Astrophysics Data System (ADS)

Khandhar, Amit P.; Ferguson, R. Matthew; Simon, Julian A.; Krishnan, Kannan M.

2012-04-01

Magnetic fluid hyperthermia (MFH) employs heat dissipation from magnetic nanoparticles to elicit a therapeutic outcome in tumor sites, which results in either cell death (>42 °C) or damage (<42 °C) depending on the localized rise in temperature. We investigated the therapeutic effect of MFH in immortalized T lymphocyte (Jurkat) cells using monodisperse magnetite (Fe3O4) nanoparticles (MNPs) synthesized in organic solvents and subsequently transferred to aqueous phase using a biocompatible amphiphilic polymer. Monodisperse MNPs, ˜16 nm diameter, show maximum heating efficiency, or specific loss power (watts/g Fe3O4) in a 373 kHz alternating magnetic field. Our in vitro results, for 15 min of heating, show that only 40% of cells survive for a relatively low dose (490 μg Fe/ml) of these size-optimized MNPs, compared to 80% and 90% survival fraction for 12 and 13 nm MNPs at 600 μg Fe/ml. The significant decrease in cell viability due to MNP-induced hyperthermia from only size-optimized nanoparticles demonstrates the central idea of tailoring size for a specific frequency in order to intrinsically improve the therapeutic potency of MFH by optimizing both dose and time of application.

Could EU herbal monographs contribute to Malta's treatment armamentarium?

PubMed

Micallef, B; Attard, E; Serracino-Inglott, A; Borg, J J

2015-03-15

Ten years have passed since Directive 2004/24/EC regulating herbal medicinal products across the EU were published. The directive created the Committee on Herbal Medicinal Products within the European Medicines Agency whose remit includes the creation and publishing of official EU monographs on herbal medicinal products. These monographs include the official uses of the products and their evidence for efficacy and safety. To this effect, we are interested in analysing the potential impact herbal product EU monographs could have on the therapeutic treatment options available for prescribers in Malta. Therefore our aim was two-fold. First, to rationalise the spread of indications of the herbal substances listed in the community herbal monograph inventory and subsequently determine if these herbal substances could potentially contribute to the treatment options available in our local scenario (Malta). 128 EU monographs were analysed resulting in a total of 230 indications which subsequently codified into 42 unique ATC codes. The Malta Medicines List contains 1456 unique ATC codes. Comparative analysis of the Malta Medicines List revealed that the 21 therapeutic areas had 4 or less pharmaceutically used substances (5th level ATC codes) registered and therefore in our opinion are areas with limited therapeutic choice. The following 4 therapeutic areas, A05 bile and liver therapy, A13 tonics, A15 appetite stimulants and D03 preparations for treatment of wounds and ulcers, could potentially benefit from the registration of herbal medicinal products according to the EU herbal monographs. If such registration is effected the aforementioned areas would no longer be considered limited because more than 4 therapeutic choices would be available to prescribers. This study is the first study across the EU to analyse the potential impact of published EU herbal monographs on therapeutic coverage in an EU member state and confirms the notion that herbal products could potentially increase the treatment options available in areas where few medical products have been registered due to Malta's small market size. Copyright © 2015 Elsevier GmbH. All rights reserved.

Effect of Enrofloxacin on Histochemistry, Immunohistochemistry and Molecular Changes in Lamb Articular Cartilage.

PubMed

Khazaeel, Kaveh; Mazaheri, Yazdan; Hashemi Tabar, Mahmood; Najafzadeh, Hossein; Morovvati, Hassan; Ghadrdan, Alireza

2015-01-01

Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections. It is metabolized to ciprofloxacin in the body as active metabolite. Fluoroquinolones change in the articular cartilage, especially with high doses and more than two weeks use. So, due to relatively excessive use of enrofloxacin in mammals and similarity of lambs to human subjects with respect to skeletal activity cycles, this study was done to investigate the effects of enrofloxacin on some cellular and molecular changes in growing lamb articular cartilage to evaluate some possible mechanisms involved these changes. Twelve, 2-month-old male lambs divided into three groups: control group received only normal saline; therapeutic group received 5mg/kg enrofloxacin subcutaneously, daily, for 15 days and toxic group received 35 mg/kg enrofloxacin in the same manner as therapeutic group. Twenty four hours after the last dose, the animals were sacrificed, and their stifle joints were dissected. Sampling from distal femoral and proximal tibial extremities was done quickly for further histological and molecular studies. Collagen-п content was studied with avidin-biotin immunohistochemistry method in different groups. Expression of Sox9 and caspase-3 was evaluated by Real-time PCR. Immunohistochemical changes were included decreases of matrix proteoglycans, carbohydrates, and Collagen-п in the toxic group. Some of these changes were observed in the therapeutic group with less intensity in comparison to the toxic group. Enrofloxacin were significantly decreased (P≤0.05). Sox9 expression in therapeutic and toxic groups compared to control group. But caspase -3 expressions in the toxic group significantly increased (P≤0.0001) with a comparison to other groups, while, between control and therapeutic groups, there were no significant differences. So, it can be concluded that enrofloxacin increases apoptosis in chondrocytes and decreases their numbers. Enrofloxacin use in growing lambs even at recommended therapeutic dose is not completely safe on articular cartilage. Moreover, higher doses of enrofloxacin induce severe changes in lamb articular cartilage.

Differential Therapeutic Outcomes of Community-Based Group Interventions for Women and Children Exposed to Intimate Partner Violence

ERIC Educational Resources Information Center

McWhirter, Paula T.

2011-01-01

Two community-based group therapies, emotion focused versus goal oriented, are compared among women exposed to intimate partner violence (n = 46) and their children (n = 48) aged between 6 and 12 years. A series of repeated measures analyses are employed to evaluate the effects of time from baseline to postintervention following random assignment.…

High-Throughput Fabrication of Nanocomplexes Using 3D-Printed Micromixers.

PubMed

Bohr, Adam; Boetker, Johan; Wang, Yingya; Jensen, Henrik; Rantanen, Jukka; Beck-Broichsitter, Moritz

2017-03-01

3D printing allows a rapid and inexpensive manufacturing of custom made and prototype devices. Micromixers are used for rapid and controlled production of nanoparticles intended for therapeutic delivery. In this study, we demonstrate the fabrication of micromixers using computational design and 3D printing, which enable a continuous and industrial scale production of nanocomplexes formed by electrostatic complexation, using the polymers poly(diallyldimethylammonium chloride) and poly(sodium 4-styrenesulfonate). Several parameters including polymer concentration, flow rate, and flow ratio were systematically varied and their effect on the properties of nanocomplexes was studied and compared with nanocomplexes prepared by bulk mixing. Particles fabricated using this cost effective device were equally small and homogenous but more consistent and controllable in size compared with those prepared manually via bulk mixing. Moreover, each micromixer could process more than 2 liters per hour with unaffected performance and the setup could easily be scaled-up by aligning several micromixers in parallel. This demonstrates that 3D printing can be used to prepare disposable high-throughput micromixers for production of therapeutic nanoparticles. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Efficacy of kinesio taping on isokinetic quadriceps torque in knee osteoarthritis: a double blinded randomized controlled study.

PubMed

Anandkumar, Sudarshan; Sudarshan, Shobhalakshmi; Nagpal, Pratima

2014-08-01

Double blind pre-test post-test control group design. To compare the isokinetic quadriceps torque, standardized stair-climbing task (SSCT) and pain during SSCT between subjects diagnosed with knee osteoarthritis pre and post kinesio tape (KT) application with and without tension. Strength of the quadriceps and torque producing capability is frequently found to be compromised in knee osteoarthritis. The efficacy of KT in improving isokinetic quadriceps torque in knee osteoarthritis is unknown, forming the basis for this study. Forty subjects were randomly allocated to either the experimental (therapeutic KT with tension) or control group (sham KT without tension) with the allocation being concealed. Pre and post test measurements of isokinetic quadriceps torque, SSCT and pain during SSCT were carried out by a blinded assessor. A large effect size with significant improvements in the peak quadriceps torque (concentric and eccentric at angular velocities of 90° per second and 120° per second), SSCT and pain were obtained in the experimental group when compared to the control group. Application of therapeutic KT is effective in improving isokinetic quadriceps torque, SSCT and reducing pain in knee osteoarthritis.

Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease.

PubMed

Hassan, Mubashir; Shahzadi, Saba; Seo, Sung Y; Alashwal, Hany; Zaki, Nazar; Moustafa, Ahmed A

2018-01-01

The design of novel inhibitors to target BACE1 with reduced cytotoxicity effects is a promising approach to treat Alzheimer's disease (AD). Multiple clinical drugs and antibodies such as AZD3293 and Solanezumab are being tested to investigate their therapeutical potential against AD. The current study explores the binding pattern of AZD3293 and Solanezumab against their target proteins such as β-secretase (BACE1) and mid-region amyloid-beta (Aβ) (PDBIDs: 2ZHV & 4XXD), respectively using molecular docking and dynamic simulation (MD) approaches. The molecular docking results show that AZD3293 binds within the active region of BACE1 by forming hydrogen bonds against Asp32 and Lys107 with distances 2.95 and 2.68 Å, respectively. However, the heavy chain of Solanezumab interacts with Lys16 and Asp23 of amyloid beta having bond length 2.82, 2.78, and 3.00 Å, respectively. The dynamic cross correlations and normal mode analyses show that BACE1 depicted good residual correlated motions and fluctuations, as compared to Solanezumab. Using MD, the Root Mean Square Deviation and Fluctuation (RMSD/F) graphs show that AZD3293 residual fluctuations and RMSD value (0.2 nm) was much better compared to Solanezumab (0.7 nm). Moreover, the radius of gyration (Rg) results also depicts the significance of AZD3293 docked complex compared to Solanezumab through residual compactness. Our comparative results show that AZD3293 is a better therapeutic agent for treating AD than Solanezumab.

Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease

PubMed Central

Hassan, Mubashir; Shahzadi, Saba; Seo, Sung Y.; Alashwal, Hany; Zaki, Nazar; Moustafa, Ahmed A.

2018-01-01

The design of novel inhibitors to target BACE1 with reduced cytotoxicity effects is a promising approach to treat Alzheimer's disease (AD). Multiple clinical drugs and antibodies such as AZD3293 and Solanezumab are being tested to investigate their therapeutical potential against AD. The current study explores the binding pattern of AZD3293 and Solanezumab against their target proteins such as β-secretase (BACE1) and mid-region amyloid-beta (Aβ) (PDBIDs: 2ZHV & 4XXD), respectively using molecular docking and dynamic simulation (MD) approaches. The molecular docking results show that AZD3293 binds within the active region of BACE1 by forming hydrogen bonds against Asp32 and Lys107 with distances 2.95 and 2.68 Å, respectively. However, the heavy chain of Solanezumab interacts with Lys16 and Asp23 of amyloid beta having bond length 2.82, 2.78, and 3.00 Å, respectively. The dynamic cross correlations and normal mode analyses show that BACE1 depicted good residual correlated motions and fluctuations, as compared to Solanezumab. Using MD, the Root Mean Square Deviation and Fluctuation (RMSD/F) graphs show that AZD3293 residual fluctuations and RMSD value (0.2 nm) was much better compared to Solanezumab (0.7 nm). Moreover, the radius of gyration (Rg) results also depicts the significance of AZD3293 docked complex compared to Solanezumab through residual compactness. Our comparative results show that AZD3293 is a better therapeutic agent for treating AD than Solanezumab. PMID:29910719

A Comparison of Therapeutic Factors in Two Group Treatment Modalities: Verbal and Art Therapy.

ERIC Educational Resources Information Center

Shechtman, Zipora; Perl-Dekel, Ofra

2000-01-01

Compares therapeutic factors in verbal and art group psychotherapy in a psychiatric day-treatment clinic in Israel. Results only partly support the differences between modalities, but do reveal significant differences between participants with only a few interactions between participants and modalities. All therapeutic factors appear in both…

A meta-analysis of the effect of angiotensin receptor blockers and calcium channel blockers on blood pressure, glycemia and the HOMA-IR index in non-diabetic patients.

PubMed

Yang, Yue; Wei, Ri-bao; Xing, Yue; Tang, Lu; Zheng, Xiao-yong; Wang, Zi-cheng; Gao, Yu-wei; Li, Min-xia; Chen, Xiang-mei

2013-12-01

This study compared the efficacy of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) in the effect of insulin resistance (IR) as assessed using the homeostasis model assessment of insulin resistance (HOMA-IR) in non-diabetic patients. The MEDLINE, EMBASE, and Cochrane Library databases were searched to identify studies published before December 2012 that investigated the use of ARBs and CCBs to determine the effect on the HOMA-IR index in non-diabetics. Parameters on IR and blood pressure were collected. Review Manager 5.2 and Stata 12.0 were used to perform the meta-analysis. Fixed and random effects models were applied to various aspects of the meta-analysis, which assessed the therapeutic effects of the two types of drug using the HOMA-IR index in non-diabetic patients. The meta-analysis included five clinical trials. Patient comparisons before and after treatment with ARBs and CCBs revealed that ARBs reduced the HOMA-IR index (weighted mean difference (WMD) -0.65, 95% confidence interval (CI) -0.93 to -0.38) and fasting plasma insulin (FPI) (WMD -2.01, 95% CI -3.27 to -0.74) significantly more than CCBs. No significant differences in the therapeutic effects of these two types of drug on blood pressure were observed. Given that there are no significant differences in the therapeutic effects of ARBs and CCBs on blood pressure, as ARBs are superior to CCBs in their effect on the HOMA-IR index in non-diabetics, they might be a better choice in hypertension patients without diabetes. © 2013.

Effects of 8 weeks of continuous positive airway pressure on abdominal adiposity in obstructive sleep apnoea.

PubMed

Sivam, Sheila; Phillips, Craig L; Trenell, Michael I; Yee, Brendon J; Liu, Peter Y; Wong, Keith K; Grunstein, Ronald R

2012-10-01

The aim of the present study was to investigate the effect of continuous positive airway pressure (CPAP) treatment on regional adipose tissue distribution in patients with moderate or severe obstructive sleep apnoea. Patients received both therapeutic and sham CPAP in a random order for 2 months each with an intervening 1-month washout. Abdominal subcutaneous, visceral and liver fat were quantified using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Liver enzymes and plasma glucose were also determined. Measurements were obtained at baseline and at the end of both treatment arms. 38 eligible patients were randomly assigned to a treatment order, with 27 patients having complete MRI/MRS data. No significant difference was observed in subcutaneous (-28.6 cm(3); p=0.49) or visceral (-16.8 cm(3); p=0.59) adipose tissue, intrahepatic lipid (-0.2%; p=0.21), or fasting glucose measurements (-0.1 mmol·L(-1); p=0.46) between treatment modalities. Alkaline phosphatase decreased (-3.1 U·L(-1); p=0.02) while on therapeutic CPAP compared with sham CPAP but other liver enzymes, including aspartate aminotransferase (0.3 U·L(-1); p=0.82), alanine aminotransferase (1.34 U·L(-1); p=0.59) and γ-glutamyltransferase (-2.3 U·L(-1); p=0.33), remained unchanged. In this first randomised, sham-controlled trial, there was no change in adipose tissue distribution after 8 weeks of therapeutic CPAP compared with 8 weeks of sham CPAP. Longer duration of CPAP use may be necessary to demonstrate a difference.

A High Throughput Model of Post-Traumatic Osteoarthritis using Engineered Cartilage Tissue Analogs

PubMed Central

Mohanraj, Bhavana; Meloni, Gregory R.; Mauck, Robert L.; Dodge, George R.

2014-01-01

(1) Objective A number of in vitro models of post-traumatic osteoarthritis (PTOA) have been developed to study the effect of mechanical overload on the processes that regulate cartilage degeneration. While such frameworks are critical for the identification therapeutic targets, existing technologies are limited in their throughput capacity. Here, we validate a test platform for high-throughput mechanical injury incorporating engineered cartilage. (2) Method We utilized a high throughput mechanical testing platform to apply injurious compression to engineered cartilage and determined their strain and strain rate dependent responses to injury. Next, we validated this response by applying the same injury conditions to cartilage explants. Finally, we conducted a pilot screen of putative PTOA therapeutic compounds. (3) Results Engineered cartilage response to injury was strain dependent, with a 2-fold increase in GAG loss at 75% compared to 50% strain. Extensive cell death was observed adjacent to fissures, with membrane rupture corroborated by marked increases in LDH release. Testing of established PTOA therapeutics showed that pan-caspase inhibitor (ZVF) was effective at reducing cell death, while the amphiphilic polymer (P188) and the free-radical scavenger (NAC) reduced GAG loss as compared to injury alone. (4) Conclusions The injury response in this engineered cartilage model replicated key features of the response from cartilage explants, validating this system for application of physiologically relevant injurious compression. This study establishes a novel tool for the discovery of mechanisms governing cartilage injury, as well as a screening platform for the identification of new molecules for the treatment of PTOA. PMID:24999113

A systematic review protocol on the effectiveness of therapeutic exercises utilised by physiotherapists to improve function in patients with burns.

PubMed

Mudawarima, Tapfuma; Chiwaridzo, Matthew; Jelsma, Jennifer; Grimmer, Karen; Muchemwa, Faith Chengetayi

2017-10-23

Therapeutic exercises play a crucial role in the management of burn injuries. The broad objective of this review is to systematically evaluate the effectiveness, safety and applicability to low-income countries of therapeutic exercises utilised by physiotherapists to improve function in patients with burns. Population = adults and children/adolescents with burns of any aspect of their bodies. Interventions = any aerobic and/or strength exercises delivered as part of a rehabilitation programme by anyone (e.g. physiotherapists, occupational therapists, nurses, doctors, community workers and patients themselves). Comparators = any comparator. Outcomes = any measure of outcome (e.g. quality of life, pain, muscle strength, range of movement, fear or quality of movement). Settings = any setting in any country. A systematic review will be conducted by two blinded independent reviewers who will search articles on PubMed, CiNAHL, Cochrane library, Medline, Pedro, OTseeker, EMBASE, PsychINFO and EBSCOhost using predefined criteria. Studies of human participants of any age suffering from burns will be eligible, and there will be no restrictions on total body surface area. Only randomised controlled trials will be considered for this review, and the methodological quality of studies meeting the selection criteria will be evaluated using the Cochrane Collaboration tool for assessing risk of bias. The PRISMA reporting standards will be used to write the review. A narrative analysis of the findings will be done, but if pooling is possible, meta-analysis will be considered. Burns may have a long-lasting impact on both psychological and physical functioning and thus it is important to identify and evaluate the effects of current and past aerobic and strength exercises on patients with burns. By identifying the characteristics of effective exercise programmes, guidelines can be suggested for developing intervention programmes aimed at improving the function of patients with burns. The safety and precautions of exercise regimes and the optimal frequency, duration, time and intensity will also be examined to inform further intervention. PROSPERO CDR42016048370 .