Preparation and biocompatibility study of in situ forming polymer implants in rat brains.

PubMed

Nasongkla, Norased; Boongird, Atthaporn; Hongeng, Suradej; Manaspon, Chawan; Larbcharoensub, Noppadol

2012-02-01

We describe the development of polymer implants that were designed to solidify once injected into rat brains. These implants comprised of glycofurol and copolymers of D: ,L: -lactide (LA), ε-caprolactone and poly(ethylene glycol) (PLECs). Scanning electron microscopy (SEM) and gel permeation chromatography (GPC) showed that the extent of implant degradation was increased with LA: content in copolymers. SEM analysis revealed the formation of porosity on implant surface as the degradation proceeds. PLEC with 19.3% mole of LA: was chosen to inject in rat brains at the volume of 10, 25 and 40 μl. Body weights, hematological and histopathological data of rats treated with implants were evaluated on day 3, 6, 14, 30 and 45 after the injection. Polymer solution at the injection volume of 10 μl were tolerated relatively well compared to those of 25 and 40 μl as confirmed by higher body weight and healing action (fibrosis tissue) 30 days after treatment. The results from this study suggest a possible application as drug delivery systems that can bypass the blood brain barrier.

Comparison of peri-implant bone formation around injection-molded and machined surface zirconia implants in rabbit tibiae

PubMed Central

Kim, Hong-Kyun; Woo, Kyung mi; Shon, Won-Jun; Ahn, Jin-Soo; Cha, Seunghee; Park, Young-Seok

2017-01-01

The aim of this study was to compare osseointegration and surface characteristics of zirconia implants made by the powder injection molding (PIM) technique and made by the conventional milling procedure in rabbit tibiae. Surface characteristics of 2 types of implant were evaluated. Sixteeen rabbits received 2 types of external hex implants with similar geometry, machined zirconia implants and PIM zirconia implants, in the tibiae. Removal torque tests and histomorphometric analyses were performed. The roughness of PIM zirconia implants was higher than that of machined zirconia implants. The PIM zirconia implants exhibited significantly higher bone-implant contact and removal torque values than the machined zirconia implants (P < 0.001). The osseointegration of the PIM zirconia implant is promising, and PIM, using the roughened mold etching technique, can produce substantially rough surfaces on zirconia implants. PMID:26235717

A comparison of implantation methods for large PIT tags or injectable acoustic transmitters in juvenile Chinook salmon

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

Cook, Katrina V.; Brown, Richard S.; Deng, Zhiqun

The miniaturization of acoustic transmitters may allow greater flexibility in terms of the size and species of fish available to tag. New downsized injectable acoustic tags similar in shape to passive integrated transponder tags can be rapidly injected rather than surgically implanted through a sutured incision, as is current practice. Before wide-scale field use of these injectable transmitters, standard protocols to ensure the most effective and least damaging methods of implantation must be developed. Three implantation methods were tested in various sizes of juvenile Chinook salmon Oncorhynchus tschawytscha. Methods included a needle bevel-down injection, a needle bevel-up injection with amore » 90-degree rotation, and tag implantation through an unsutured incision. Tagged fish were compared to untagged control groups. Weight and wound area were measured at tagging and every week for 3 weeks; holding tanks were checked daily for mortalities and tag losses. No differences among treatments were found in growth, tag loss, or survival, but wound area was significantly reduced among incision-treated fish. The bevel-up injection had the worst results in terms of tag loss and wound area and also had high mortality. Implantation through an incision resulted in the lowest tag loss but the highest mortality. Fish from the bevel-down treatment group had the least mortality; wound areas also were smaller than the bevel-up treatment group. Cumulatively, the data suggest that the unsutured incision and bevel-down injection methods were the most effective; the drawbacks of both methods are described in detail. However, we further recommend larger and longer studies to find more robust thresholds for tagging size that include more sensitive measures.« less

Ion-implanted epitaxially grown ZnSe

NASA Technical Reports Server (NTRS)

Chernow, F.

1975-01-01

The use of ZnSe to obtain efficient, short wavelength injection luminescence was investigated. It was proposed that shorter wavelength emission and higher efficiency be achieved by employing a p-i-n diode structure rather than the normal p-n diode structure. The intervening i layer minimizes concentration quenching effects and the donor-acceptor pair states leading to long wavelength emission. The surface p layer was formed by ion implantation; implantation of the i layer rather than the n substrate permits higher, uncompensated p-type doping. An ion implanted p-n junction in ZnSe is efficiency-limited by high electron injection terminating in nonradiative recombination at the front surface, and by low hole injection resulting from the inability to obtain high conductivity p-type surface layers. While the injection ratio in p-n junctions was determined by the radio of majority carrier concentrations, the injection ratio in p-i-n structures was determined by the mobility ratios and/or space charge neutrality requirements in the i layer.

Evisceration With Injectable Hydrogel Implant in a Rabbit Model.

PubMed

Koreen, Irina V; McClintic, Elysa A; Mott, Ryan T; Stanton, Constance; Yeatts, R Patrick

To determine the safety, durability, and biocompatibility of 2.5% polyacrylamide hydrogel (Aquamid, Specialty European Pharma, Ltd., London, UK) as an injectable viscoelastic implant following evisceration in a rabbit model. The protocol was reviewed and approved by the Wake Forest Institutional Animal Care and Use Committee. Adult New Zealand rabbits underwent cornea-sparing evisceration of the right eye with injection of 2.5% polyacrylamide hydrogel implant. The rabbits were sacrificed after 2 weeks (n = 1), 5 weeks (n = 2), 12 weeks (n = 3), 25 weeks (n = 3), and 1 year (n = 3) to evaluate the implant volume and host reaction to the implant. Both eyes were enucleated and their diameters were measured. The eviscerated eyes were fixed in formalin and processed using routine histopathologic methods to assess inflammatory reaction and vascularization. The implant material was well tolerated with a moderate giant cell reaction seen at 6 weeks that improved over time. Extensive vascularization of the implant was noted starting at 6 weeks. There was excellent maintenance of globe volume that did not diminish over time. The relative diameters of the eviscerated eyes compared with control were 89 ± 6% (mean% ± SD) at 12 weeks (n = 3), 94 ± 2% at 25 weeks (n = 3), and 93 ± 4% at 1 year (n = 3). With further study, injectable 2.5% polyacrylamide hydrogel may provide an excellent alternative to solid orbital implants. The implant material was universally well tolerated and maintained appropriate volume in the orbit for the study period of 1 year. Extensive vascularization of the implant was noted indicating biointegration.

Intracameral air injection during Ahmed glaucoma valve implantation in neovascular glaucoma for the prevention of tube obstruction with blood clot: Case Report.

PubMed

Hwang, Sung Ha; Yoo, Chungkwon; Kim, Yong Yeon; Lee, Dae Young; Nam, Dong Heun; Lee, Jong Yeon

2017-12-01

Glaucoma drainage implant surgery is a treatment option for the management of neovascular glaucoma. However, tube obstruction by blood clot after Ahmed glaucoma valve (AGV) implantation is an unpredictable clinically challenging situation. We report 4 cases using intracameral air injection for the prevention of the tube obstruction of AGV by blood clot. The first case was a 57-year-old female suffering from ocular pain because of a tube obstruction with blood clot after AGV implantation in neovascular glaucoma. Surgical blood clot removal was performed. However, intractable bleeding was noted during the removal of the blood clot, and so intracameral air injection was performed to prevent a recurrent tube obstruction. After the procedure, although blood clots formed around the tube, the tube opening where air could touch remained patent. In 3 cases of neovascular glaucoma with preoperative severe intraocular hemorrhages, intracameral air injection and AGV implantation were performed simultaneously. In all 3 cases, tube openings were patent. It appears that air impeded the blood clots formation in front of the tube opening. Intracameral air injection could be a feasible option to prevent tube obstruction of AGV implant with a blood clot in neovascular glaucoma with high risk of tube obstruction. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Peri-implant bone formation and surface characteristics of rough surface zirconia implants manufactured by powder injection molding technique in rabbit tibiae.

PubMed

Park, Young-Seok; Chung, Shin-Hye; Shon, Won-Jun

2013-05-01

To evaluate osseointegration in rabbit tibiae and to investigate surface characteristics of novel zirconia implants made by powder injection molding (PIM) technique, using molds with and without roughened inner surfaces. A total of 20 rabbits received three types of external hex implants with identical geometry on the tibiae: machined titanium implants, PIM zirconia implants without mold etching, and PIM zirconia implants with mold etching. Surface characteristics of the three types of implant were evaluated. Removal torque tests and histomorphometric analyses were performed. The roughness of PIM zirconia implants was higher than that of machined titanium implants. The PIM zirconia implants exhibited significantly higher bone-implant contact and removal torque values than the machined titanium implants (P < 0.001). The PIM zirconia implants using roughened mold showed significantly higher removal torque values than PIM zirconia implants without using roughened mold (P < 0.001). It is concluded that the osseointegration of PIM zirconia implant is promising and PIM using roughened mold etching technique can produce substantially rough surfaces on zirconia implants. © 2012 John Wiley & Sons A/S.

Photoactivated Composite Biomaterial for Soft Tissue Restoration in Rodents and in Humans

PubMed Central

Nahas, Zayna; Reid, Branden; Coburn, Jeannine M.; Axelman, Joyce; Chae, Jemin J.; Guo, Qiongyu; Trow, Robert; Thomas, Andrew; Hou, Zhipeng; Lichtsteiner, Serge; Sutton, Damon; Matheson, Christine; Walker, Patricia; David, Nathaniel; Mori, Susumu; Taube, Janis M.; Elisseeff, Jennifer H.

2015-01-01

Soft tissue reconstruction often requires multiple surgical procedures that can result in scars and disfiguration. Facial soft tissue reconstruction represents a clinical challenge because even subtle deformities can severely affect an individual’s social and psychological function. We therefore developed a biosynthetic soft tissue replacement composed of poly(ethylene glycol) (PEG) and hyaluronic acid (HA) that can be injected and photocrosslinked in situ with transdermal light exposure. Modulating the ratio of synthetic to biological polymer allowed us to tune implant elasticity and volume persistence. In a small-animal model, implanted photocrosslinked PEG-HA showed a dose-dependent relationship between increasing PEG concentration and enhanced implant volume persistence. In direct comparison with commercial HA injections, the PEG-HA implants maintained significantly greater average volumes and heights. Reversibility of the implant volume was achieved with hyaluronidase injection. Pilot clinical testing in human patients confirmed the feasibility of the transdermal photocrosslinking approach for implantation in abdomen soft tissue, although an inflammatory response was observed surrounding some of the materials. PMID:21795587

Alveolar bone regeneration for immediate implant placement using an injectable bone substitute: an experimental study in dogs.

PubMed

Boix, Damien; Gauthier, Olivier; Guicheux, Jérôme; Pilet, Paul; Weiss, Pierre; Grimandi, Gaël; Daculsi, Guy

2004-05-01

The aim of the present study was to assess the efficacy of a ready-to-use injectable bone substitute for bone regeneration around dental implants placed into fresh extraction sockets. Third and fourth mandibular premolars were extracted from three beagle dogs and the interradicular septa were surgically reduced to induce a mesial bone defect. Thereafter, titanium implants were immediately placed. On the left side of the jaw, mesial bone defects were filled with an injectable bone substitute (IBS), obtained by combining a polymer and biphasic calcium phosphate ceramic granules. The right defects were left unfilled as controls. After 3 months of healing, specimens were prepared for histological and histomorphometric evaluations. No post-surgical complications were observed during the healing period. In all experimental conditions, histological observations revealed a lamellar bone formation in contact with the implant. Histomorphometric analysis showed that IBS triggers a significant (P<0.05) increase in terms of the number of threads in contact with bone, bone-to-implant contact, and peri-implant bone density of approximately 8.6%, 11.0%, and 14.7%, respectively. In addition, no significant difference was observed when number of threads, bone-to-implant contact, and bone density in the filled defects were compared to the no-defect sites. It is concluded that an injectable bone substitute composed of a polymeric carrier and calcium phosphate significantly increases bone regeneration around immediately placed implants.

The influence of systemically administered oxytocin on the implant-bone interface area: an experimental study in the rabbit

PubMed Central

Cho, Sung-Am; Park, Sang-Hun

2014-01-01

PURPOSE The purpose of this study was to assess the effect of systemically administered oxytocin (OT) on the implant-bone interface by using histomorphometric analysis and the removal torque test. MATERIALS AND METHODS A total of 10 adult, New Zealand white, female rabbits were used in this experiment. We placed 2 implants (CSM; CSM Implant, Daegu, South Korea) in each distal femoral metaphysis on both the right and left sides; the implants on both sides were placed 10 mm apart. In each rabbit, 1 implant was prepared for histomorphometric analysis and the other 3 were prepared for the removal torque test (RT). The animals received intramuscular injections of either saline (control group; 0.15 M NaCl) or OT (experimental group; 200 µg/rabbit). The injections were initiated on Day 3 following the implant surgery and were continued for 4 subsequent weeks; the injections were administered twice per day (at a 12-h interval), for 2 days per week. RESULTS While no statistically significant difference was observed between the two groups (P=.787), the control group had stronger removal torque values. The serum OT concentration (ELISA value) was higher in the OT-treated group, although no statistically significant difference was found. Further, the histomorphometric parameter (bone-toimplant contact [BIC], inter-thread bone, and peri-implant bone) values were higher in the experimental group, but the differences were not significant. CONCLUSION We postulate that OT supplementation via intramuscular injection weakly contributes to the bone response at the implant-bone interface in rabbits. Therefore, higher concentrations or more frequent administration of OT may be required for a greater bone response to the implant. Further studies analyzing these aspects are needed. PMID:25551011

Does intrauterine injection of low-molecular-weight heparin improve the clinical pregnancy rate in intracytoplasmic sperm injection?

PubMed Central

El-Faissal, Yahia; Aboulghar, Mona; Mansour, Ragaa; Serour, Gamal I; Aboulghar, Mohamed

2016-01-01

Objective Heparin can modulate proteins, and influence processes involved in implantation and trophoblastic development. This study aimed to assess the improvement of clinical pregnancy and implantation rates after local intrauterine injection of low-molecular-weight heparin (LMWH) in patients undergoing intracytoplasmic sperm injection (ICSI). Methods A randomised case/control design was followed in women scheduled for ICSI. The study arm was injected with intrauterine LMWH during mock embryo transfer immediately following the ovum pickup procedure, while the control arm was given an intrauterine injection with a similar volume of tissue culture media. Side effects, the clinical pregnancy rate, and the implantation rate were recorded. Results The pregnancy rate was acceptable (33.9%) in the LMWH arm with no significant reported side effects, confirming the safety of the intervention. No statistically significant differences were found in the clinical pregnancy and implantation rates between both groups (p=0.182 and p=0.096, respectively). The odds ratio of being pregnant after intrauterine injection with LMWH compared to the control group was 0.572 (95% confidence interval [CI], 0.27−1.22), while the risk ratio was 0.717 (95% CI, 0.46−1.13; p=0.146). No statistical significance was found between the two groups in other factors affecting implantation, such as day of transfer (p=0.726), number of embryos transferred (p=0.362), or embryo quality. Conclusion Intrauterine injection of LMWH is a safe intervention, but the dose used in this study failed to improve the outcome of ICSI. Based on its safety, further research involving modification of the dosage and/or the timing of administration could result in improved ICSI success rates. PMID:28090465

The effects of subcutaneous injection of nicotine on osseointegration of machined and anodized implants in rabbits.

PubMed

Linden, Maria Salete Sandini; Bittencourt, Marcos Eugênio de; Carli, João Paulo De; Miyagaki, Daniela Cristina; Santos, Pâmela Letícia Dos; Paranhos, Luiz Renato; Groppo, Francisco Carlos; Ramacciato, Juliana Cama

2018-01-01

To evaluate the influence of subcutaneous injection nicotine in osseointegration process on different implant surfaces. Twenty-two male rabbits were distributed into two groups according to the subcutaneous injections: (1) nicotine 3 mg/day/kg and (2) 0.9 % NaCI 3 mL/day/kg, three times a day; subgroups were then designated-machined and anodized implants were placed in the right and left tibia bones, respectively. The animals were submitted euthanasia after periods of eight weeks to determine nicotine and cotinine levels, alkaline phosphatase and biomechanical analysis. The plasmatic levels of nicotine and cotinine were 0.5 ± 0.28 ng/mL and 9.5 ± 6.51 ng/mL, respectively. The alkaline phosphatase analyses in blood levels in control group were observed 40.8 ± 11.88 UI/L and 40.75 ± 12.46 UI/L, for the surfaces machined and anodized, respectively. In the test group was observed levels 37.9 ± 4.84 UI/L, for both implant surfaces. No significant differences were observed between control and test groups and between the implant surfaces regarding alkaline phosphatase blood levels. For biomechanics, no significant differences were observed in control group between the machined (25±8.46 Ncm) or anodized (31.2 ± 6.76 Ncm) implants. However, the treatment with nicotine induced higher torque than control in both machined (38.3 ± 13.52 Ncm) and anodized (35.5 ± 14.17 Ncm) implants, with p = 0.0024 and p = 0.0121, respectively. Subcutaneous injection of nicotine following implant insertion didn't have effect on osseointegration, independently from the implant surface.

In vivo studies on insulin permeability of an immunoisolation device intended for islet transplantation using the microdialysis technique.

PubMed

Rafael, E; Wernerson, A; Arner, P; Tibell, A

1999-01-01

In this study, insulin was injected into Theracyte immunoisolation devices to analyze changes in the permeability of the device over time after implantation. The recovery of insulin was studied after subcutaneous implantation of the devices in rats, using the microdialysis technique. The area under the insulin concentration vs. time curves (AUC) after insulin injection in devices implanted 1 day previously did not differ significantly from the AUC after subcutaneous injection. At 1, 2 and 4 weeks after implantation, the recovery of insulin was significantly reduced, but at 3 months, the AUC was not significantly different from that in the control group. Histological examination showed that the number of vascular profiles within 15 microm of the device were significantly higher at 2, 4 weeks and 3 months after transplantation when compared to numbers at 1 week. The design of the device allows transplantation of cells at a chosen time point after its implantation. Delayed filling of the device would allow neovascularization of the device surface before graft implantation and we suggest that such a schedule might improve function of the encapsulated graft.

Perilymph pharmacokinetics of marker applied through a cochlear implant in guinea pigs

PubMed Central

Hartsock, Jared; Gill, Ruth; Smyth, Daniel; Kirk, Jonathon; Verhoeven, Kristien

2017-01-01

Patients undergoing cochlear implantation could benefit from a simultaneous application of drugs into the ear, helping preserve residual low-frequency hearing and afferent nerve fiber populations. One way to apply drugs is to incorporate a cannula into the implant, through which drug solution is driven. For such an approach, perilymph concentrations achieved and the distribution in the ear over time have not previously been documented. We used FITC-labeled dextran as a marker, delivering it into perilymph of guinea pigs at 10 or 100 nL/min though a cannula incorporated into a cochlear implant with the outlet in the mid basal turn. After injections of varying duration (2 hours, 1 day or 7 days) perilymph was collected from the cochlear apex using a sequential sampling technique, allowing dextran levels and gradients along scala tympani to be quantified. Data were interpreted quantitatively using computer simulations of the experiments. For injections of 2 hours duration, dextran levels were critically influenced by the presence or absence of fluid leakage at the cochleostomy site. When the cochleostomy was fluid-tight, substantially higher perilymph levels were achieved at the injection site, with concentration declining along scala tympani towards the apex. Contrary to expectations, large dextran gradients along scala tympani persisted after 24 hours of sustained injection and were still present in some animals after 7 days injection. Functional changes associated with implantation and dextran delivery, and the histological state of the implant and cannula were also documented. The persistent longitudinal gradients of dextan along the ear were not readily explained by computer simulations of the experiments based on prior pharmacokinetic data. One explanation is that inner ear pharmacokinetics are altered in the period after cochlear implantation, possibly by a permeabilization of the blood-labyrinth barrier as part of the immune response to the implant. PMID:28817653

Comparative Matched-Pair Analysis of the Injection Versus Implantation of Mesenchymal Stem Cells for Knee Osteoarthritis.

PubMed

Kim, Yong Sang; Kwon, Oh Ryong; Choi, Yun Jin; Suh, Dong Suk; Heo, Dong Beom; Koh, Yong Gon

2015-11-01

The mesenchymal stem cell (MSC)-based tissue engineering approach has been developed to address the problem of articular cartilage repair in knee osteoarthritis (OA). However, the most effective method of MSC application has not yet been established. To compare the injection and implantation of MSCs in patients with knee OA in terms of clinical and second-look arthroscopic outcomes. Cohort study; Level of evidence, 3. Among 182 patients treated with arthroscopic surgery using MSCs for knee OA from October 2010 to August 2012, patients treated with an injection of MSCs in combination with platelet-rich plasma (injection group; n = 20) were pair-matched with patients who underwent MSC implantation on a fibrin glue scaffold (implantation group; n = 20) based on sex, age, and lesion size. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) score and Tegner activity scale, and cartilage repair was assessed arthroscopically with the International Cartilage Repair Society (ICRS) grading system. The mean (±SD) IKDC and Tegner activity scores significantly improved from 38.5 ± 9.2 to 55.2 ± 15.0 and from 2.5 ± 1.2 to 3.5 ± 1.2, respectively, in the injection group and from 36.6 ± 4.9 to 62.7 ± 14.1 and from 2.3 ± 0.9 to 3.6 ± 1.1, respectively, in the implantation group at the time of second-look arthroscopic surgery (mean, 12.6 months postoperatively) (P < .001 in all cases). At final follow-up (mean, 28.6 months postoperatively), the mean IKDC and Tegner activity scores in the implantation group had improved further to 64.8 ± 13.4 and 3.9 ± 1.0, respectively (P < .001 and P = .035, respectively), while no significant improvements were found in the injection group (P = .130 and P = .655, respectively). At final follow-up, there was a significant difference in the mean IKDC score between groups (P = .049). Significant correlations between the number of administered MSCs and the postoperative clinical outcomes were found only in the injection group. Significant correlations between the clinical outcomes and the ICRS grades were found in both groups. The ICRS grades were significantly better in the implantation group (P = .041). In the injection group, 2 of the 20 lesions (10%) were grade I (normal), 5 (25%) were grade II (near normal), 8 (40%) were grade III (abnormal), and 5 (25%) were grade IV (severely abnormal). In the implantation group, 6 of the 20 lesions (30%) were grade I, 7 (35%) were grade II, 4 (20%) were grade III, and 3 (15%) were grade IV. Utilizing the described method, MSC implantation for knee OA resulted in better clinical and second-look arthroscopic outcomes than an MSC injection. © 2015 The Author(s).

Quantitative evaluation of hard exudates in diabetic macular edema after short-term intravitreal triamcinolone, dexamethasone implant or bevacizumab injections.

PubMed

Shin, Yong Un; Hong, Eun Hee; Lim, Han Woong; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon

2017-10-03

To quantitatively compare short-term hard exudates (HEs) alteration in patients with diabetic macular edema (DME) after intravitreal triamcinolone, dexamethasone implant or bevacizumab injections. This retrospective study enrolled DME eyes with HEs that underwent a single-dose intravitreal injection of triamcinolone (25 eyes), dexamethasone implant (20 eyes), or three monthly injections of bevacizumab (25 eyes) and completed at least three months of follow-up. All patients were examined before and after 1, 2 and 3 months of injections. Using color fundus photographs, the amount of HEs was quantified by two masked graders. The difference in HEs area between baseline and each follow-up visit was compared among the three groups. After three months, HEs area was reduced to 52.9 ± 4.21% (P < 0.001) in the triamcinolone group, 63.6 ± 6.08% (P = 0.002) in the dexamethasone implant group, and 85.2 ± 5.07% (P = 0.198) in the bevacizumab group. A significant reduction in HEs appeared at one month in the triamcinolone group (53.5 ± 4.91%, P < 0.001) and at two months in the dexamethasone implant group (70.1 ± 5.21%, P = 0.039). Our study suggests intravitreal steroids (triamcinolone, dexamethasone implants) significantly reduce HEs in DME patients on short-term follow-up, whereas intravitreal bevacizumab does not. Therefore, intravitreal steroids may be useful in DME with HEs in the fovea.

The effects of lauromacrogol injection into rat endometrial cysts: a preliminary experimental study.

PubMed

Liu, Wei; Wang, LongXia; Guo, Cui-Xia

2016-09-01

To determine the effectiveness of different concentrations of lauromacrogol injections for the treatment of endometriosis in an experimental animal model and to provide an experimental basis for a pre-clinical application of the drug. After autologous transplantation of endometrial tissue, 40 endometrial cysts were successfully established and randomly divided into three groups: a 1 % lauromacrogol injection group, a 0.5 % lauromacrogol injection group, and cysts without intervention (control group). We measured the changes in the volumes of the cysts in each group. We then compared the volumes of the endometrial implants before and after treatment and between the different groups and examined the histological findings. A significant difference in the spherical volume was found between the 1 % lauromacrogol injection group (P < 0.05). No significant difference was observed between the volume of the endometrial implants in the 0.5 % lauromacrogol injection group (P > 0.05). Regarding the histopathological observations, in the 1 % lauromacrogol injection group, the epithelia of the cystic implants had atrophied, and the glands had atrophied and were reduced in number. The surrounding stromal tissue had become loose and edematous. A 1 % lauromacrogol injection produced significant regression of the endometrial foci compared with a 0.5 % lauromacrogol injection or no treatment in a rat model of endometriosis.

76 FR 22610 - Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-22

.... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin AGENCY: Food... amending the animal drug regulations to reflect approval of a supplemental new animal drug application... INFORMATION: Bayer HealthCare LLC, Animal Health Division, P.O. Box 390, Shawnee Mission, KS 66201, filed a...

75 FR 13225 - Implantation or Injectable Dosage Form New Animal Drugs; Flunixin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-19

.... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Flunixin AGENCY: Food and... amending the animal drug regulations to reflect approval of an original abbreviated new animal drug... copy of BANAMINE-S, sponsored by Schering-Plough Animal Health Corp. under NADA 101-479. The ANADA is...

77 FR 4226 - Implantation or Injectable Dosage Form New Animal Drugs; Danofloxacin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

.... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Danofloxacin AGENCY: Food... amending the animal drug regulations to reflect approval of a supplemental new animal drug application.... 801-808. List of Subjects in 21 CFR Part 522 Animal drugs. Therefore, under the Federal Food, Drug...

In situ forming phase-inversion implants for sustained ocular delivery of triamcinolone acetonide.

PubMed

Sheshala, Ravi; Hong, Gan Chew; Yee, Wong Pui; Meka, Venkata Srikanth; Thakur, Raghu Raj Singh

2018-02-26

The objectives of this study were to develop biodegradable poly-lactic-co-glycolic acid (PLGA) based injectable phase inversion in situ forming system for sustained delivery of triamcinolone acetonide (TA) and to conduct physicochemical characterisation including in vitro drug release of the prepared formulations. TA (at 0.5%, 1% and 2.5% w/w loading) was dissolved in N-methyl-2-pyrrolidone (NMP) solvent and then incorporated 30% w/w PLGA (50/50 and 75/25) polymer to prepare homogenous injectable solution. The formulations were evaluated for rheological behaviour using rheometer, syringeability by texture analyser, water uptake and rate of implant formation by optical coherence tomography (OCT) microscope. Phase inversion in situ forming formulations were injected into PBS pH 7.3 to form an implant and release samples were collected and analysed for drug content using a HPLC method. All formulations exhibited good syringeability and rheological properties (viscosity: 0.19-3.06 Pa.s) by showing shear thinning behaviour which enable them to remain as free-flowing solution for ease administration. The results from OCT microscope demonstrated that thickness of the implants were increased with the increase in time and the rate of implant formation indicated the fast phase inversion. The drug release from implants was sustained over a period of 42 days. The research findings demonstrated that PLGA/NMP-based phase inversion in situ forming implants can improve compliance in patient's suffering from ocular diseases by sustaining the drug release for a prolonged period of time and thereby reducing the frequency of ocular injections.

A monoclonal antibody to an early pregnancy factor-induced suppressor factor (EPF-S1) disrupts implantation in mice.

PubMed

Athanasas-Platsis, S; Hoskin, M J; Rolfe, B E; Cavanagh, A C; Morton, H

1995-03-01

The importance of EPF during pregnancy has been established previously but the importance of the EPF-induced suppressor factor EPF-S1 in pregnancy has to date been unaddressed. Investigations were therefore conducted in order to study this. Monoclonal antibodies to EPF-S1 were produced, and one antibody, designated R2T gamma, was characterized. Mated mice were passively immunized with R2T gamma and the effect on implantation determined. Characterization of anti-EPF-S1 R2T gamma revealed that it cross-reacted with EPF-S1 of different MHC restriction but not with EPF or EPF-S2. When injected into mated mice on days 1 to 4, R2T gamma had no effect on pregnancy but when injections continued to day 5, pregnancy was affected; the number of embryos implanted on day 7 were significantly less than the number of corpora lutea counted, signifying embryonic loss. These studies show that anti-EPF-S1 R2T gamma disrupts implantation in mice when injected on days 1 to 5 of pregnancy but not when injected on days 1 to 4, demonstrating that EPF-S1 exerts its effects around the time of implantation.

Orbital volume augmentation using expandable hydrogel implants in acquired anophthalmia and phthisis bulbi.

PubMed

Kim, Esther Lee; Bernardino, Carlo Rob; Levin, Flora

2016-01-01

The purpose of this study is to describe our experience using expandable spherical hydrogel implants and injectable hydrogel pellets for orbital volume augmentation in cases of post-enucleation socket syndrome after acquired anophthalmia or phthisis bulbi. We retrospectively reviewed the clinical records of all adult patients who received an expandable hydrogel implant for orbital volume loss following enucleation or phthisis bulbi at the Emory Eye Center between 2004 and January 2007 and the Yale Eye Center between 2009 and 2011. The study included 9 women and 5 men with a mean age of 51.2 years old (range 35-76 years old). Follow-up spanned 6 to 71 months (median of 18.5 months). Four patients received spherical hydrogel implants and 10 patients received hydrogel pellet injections. On average, nine pellets (range 5-16) were placed in each patient over an average of 1.7 injections (range 1-3). Most commonly, five pellets were injected per session, as was the case for 13 of the 17 treatment sessions. Post-operative complications included 2 cases of pellet migration, one subcutaneously and one anteriorly due to insufficiently posterior implant placement, and 1 hospital admission for pain after injection of 10 pellets in one visit. All patients experienced an overall subjective improvement in cosmesis. Self-expandable hydrogel implants appear to offer several advantages over other existing options for orbital volume augmentation, as they are easy to place, generally well-tolerated, volume-titratable, and to the extent that our follow-up shows, may be a safe and durable means of treating orbital volume loss in patients with acquired anophthalmia and phthisis bulbi.

Why are US women not using long-acting contraceptives?

PubMed

Tanfer, K; Wierzbicki, S; Payn, B

2000-01-01

Given the level of unintended pregnancy in the United States, it is somewhat surprising that hormonal implants and injectables-methods that are long-acting, reversible, highly effective and convenient--have not attained the popularity enjoyed by other medical methods. Knowing the reasons why women have so far spurned these methods might lead to the design and implementation of interventions and targeted social marketing to promote their use. Data from the 1993 and 1995 rounds of the National Survey of Women are used to examine the reasons women gave for not having used the implant or injectables, whether they intended to use these methods and how their attitudes toward them may influence their decision to use such methods in the future. Logistic regression models were used to identify the social and demographic characteristics that influence women's decisions not to use these methods. Fewer than 2% of women who were at risk of an unintended pregnancy in 1995 were using the implant, and under 3% were using the injectable. Women gave three major reasons for not using either of these methods: lack of knowledge; fear of side effects or health hazards; and satisfaction with the method they were currently using. Age, education, marital status, parity and current contraceptive method strongly predicted fear of side effects, lack of knowledge and satisfaction with the current method as reasons for not using the implant or the injectable. For example, women aged 30 or older and those with a college education were half as likely as younger women and those with no college education to mention fear of side effects as their main reason for not using the implant. Likewise, single women, women with one or more children and those using a barrier method were 2-3 times as likely as married women, childless women and those using a medical method to attribute nonuse to the implant's side effects. Few women said they intended to use these methods in the next 12 months: 5% for the implant and 10% for the injectable. Single women, women with no college education, women with children, women wanting to have a child (or another child) and women with positive attitudes toward the effect of using an injectable were significantly more likely to say they intended to use the injectable. Nevertheless, substantial proportions of women reported quite negative attitudes about these methods. The low prevalence of use and the low level of use intention for the implant and for injectables raise questions about the promise for the future of these methods. Each method seems to appeal to certain subgroups of women, however. Thus, if proper interventions and social marketing are targeted to such groups, they may be disabused of misperceptions regarding these methods and possibly become more willing to try them.

A novel injectable in situ forming poly-DL-lactide and DL-lactide/glycolide implant containing lipospheres for controlled drug delivery.

PubMed

Yehia, Soad A; Elshafeey, Ahmed H; Elsayed, Ibrahim

2012-06-01

One of the greatest challenges in in situ forming implant (ISFI) systems by polymer precipitation is the large burst release during the first 1-24 hours after implant injection. The aim of this study was to decrease the burst-release effect of a water-soluble model drug, donepezil HCl, with a molecular weight of 415.96 Da, from in situ forming implants using a novel in situ implant containing lipospheres (ISILs). In situ implant suspensions were prepared by dispersing cetyl alcohol and glyceryl stearate lipospheres in a solution of poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG). Also, in situ implant solutions were prepared using different concentrations of PDL or PDLG solutions in N-methyl-2-pyrrolidone (NMP). Triacetin and Pluronic L121 were used to modify the release pattern of donepezil from the in situ implant solutions. In vitro release, rheological measurement, and injectability measurement were used to evaluate the prepared in situ implant formulae. It was found that ISIL decreased the burst effect as well as the rate and extent of drug release, compared to lipospheres, PDL, and PDLG in situ implant. The amount of drug released in the first day was 37.75, 34.99, 48.57, 76.3, and 84.82% for ISIL in 20% PDL (IL-1), ISIL in 20% PDLG (IL-2), lipospheres (L), 20% PDL ISFI (I5), and 20% PDLG ISFI (I8), respectively. The prepared systems showed Newtonian flow behavior. ISIL (IL-1 and IL-2) had a flow rate of 1.94 and 1.40 mL/min, respectively. This study shows the potential of using in situ implants containing lipospheres in controlling the burst effect of ISFI.

Complications of penile augmentation by use of nonmedical industrial silicone.

PubMed

Shamsodini, Ahmad; Al-Ansari, Abdulla A; Talib, Raidh A; Alkhafaji, Haidar M; Shokeir, Ahmed A; Toth, Csaba

2012-12-01

Penile augmentation has been reported in the literature by injecting various materials by nonmedical persons. This study aims to present our experience in management of penile augmentation complications associated with injection or implantation of industrial silicone by lay persons. Early surgical intervention can lead to faster recovery and better cosmetic and functional outcome. Two patients had injection of industrial silicone paste, and the other two had industrial silicone ring implantation. All the patients except one were presented after 13 months of the procedure. Patients with industrial silicone ring presented with multiple sinuses of penile skin in one, and abscess discharge pus from the site of implanted ring in the other. Both patients with injected silicone paste presented with swelling and deformity of the penis that interfered with their intercourse. Silicone ring patients underwent skin incision and drainage of the infected materials and extraction of the implants with delayed skin closure. The two patients with silicone paste injection underwent two-stage penile reconstructions using scrotal flap. Patients with extracted rings had smooth recovery with acceptable cosmetic outcome. One of them was not initially satisfied with the length of his penis that was overcome by short-term use of vacuum device. One of the patients with silicone paste injection had wound infection that was successfully treated with local wound care. Both had satisfactory penile length and acceptable cosmetic outcome. All patients had normal erectile function postoperatively. Complications of using industrial silicone injection can be drastic, and awareness of the public can avoid using of this material for penile augmentation. © 2011 International Society for Sexual Medicine.

Induction of estrus during the non-breeding season in Egyptian Baladi goats.

PubMed

Medan, Mohamed; Shalaby, Abdel-Hamid; Sharawy, Sayed; Watanabe, Gen; Taya, Kazuyoshi

2002-01-01

The induction of estrus during the non-breeding season was investigated in 100 Egyptian Baladi goats (Capra hircus). All animals assigned to treatments had low progesterone concentrations (<0.5 ng/ml) tested 2 times 10 days apart to confirm anestrous condition. Animals were assigned to three experimental groups. A group of animals received subcutaneous norgestomet ear implant for 11 days and a single i.m. injection of PGF2alpha 24 hr before implant removal (group I; n=40). Second group of animals received subcutaneous norgestomet ear implant for 11 days and a single i.m. injection of PGF2alpha 24 hr before implant removal and gonadotropin releasing hormone 24 hr after implant removal (group II; n=40). Third group of animals received no treatment (control group; n=20). The percentage of goats that showed estrous behavior during the first 72 hr after implant removal was 77.5, 85.0% and 10.0% in group I, group II and control group, respectively. The fertility rate was 57.5, 70.0% and 10.0% in group I, group II and control group, respectively. In conclusion, estrus can be induced in seasonally anestrous Egyptian Baladi goats using norgestomet and PGF2alpha and the injection of GnRH 24 hr after norgestomet implant removal synchronized ovulation in a higher percentage of goats.

First-in-human testing of a wirelessly controlled drug delivery microchip.

PubMed

Farra, Robert; Sheppard, Norman F; McCabe, Laura; Neer, Robert M; Anderson, James M; Santini, John T; Cima, Michael J; Langer, Robert

2012-02-22

The first clinical trial of an implantable microchip-based drug delivery device is discussed. Human parathyroid hormone fragment (1-34) [hPTH(1-34)] was delivered from the device in vivo. hPTH(1-34) is the only approved anabolic osteoporosis treatment, but requires daily injections, making patient compliance an obstacle to effective treatment. Furthermore, a net increase in bone mineral density requires intermittent or pulsatile hPTH(1-34) delivery, a challenge for implantable drug delivery products. The microchip-based devices, containing discrete doses of lyophilized hPTH(1-34), were implanted in eight osteoporotic postmenopausal women for 4 months and wirelessly programmed to release doses from the device once daily for up to 20 days. A computer-based programmer, operating in the Medical Implant Communications Service band, established a bidirectional wireless communication link with the implant to program the dosing schedule and receive implant status confirming proper operation. Each woman subsequently received hPTH(1-34) injections in escalating doses. The pharmacokinetics, safety, tolerability, and bioequivalence of hPTH(1-34) were assessed. Device dosing produced similar pharmacokinetics to multiple injections and had lower coefficients of variation. Bone marker evaluation indicated that daily release from the device increased bone formation. There were no toxic or adverse events due to the device or drug, and patients stated that the implant did not affect quality of life.

Implants and depot injections for treating opioid dependence: Qualitative study of people who use or have used heroin.

PubMed

Neale, Joanne; Tompkins, Charlotte N E; McDonald, Rebecca; Strang, John

2018-05-25

Long-acting opioid pharmacotherapy (OPT) is presumed to offer benefits over more conventional OPT formulations. This paper analyzes the views and experiences of people who use or have used heroin in order to explore two novel systems for delivering long-acting OPT: implants and depot injections. New materialism theorizing is used to interpret and frame the findings. Qualitative data were generated via seven focus groups conducted during 2017 in London, UK. Participants (n = 44; 28 men and 16 women; ages 33-66 years) had all received OPT. Focus group discussions covered real and potential OPT delivery systems. All participant data relating to implants and depot injections were coded using MAXQDA software and analysed inductively via Iterative Categorisation. Participants discussed implants and depot injections in terms of interacting physical, psychological and social factors: dose stability; OPT administration; stopping treatment; co-presence of an antagonist; breaking rituals and habits; reduced choice and control; feeling normal; information needs; getting on with everyday life; and social interaction. Participants identified both benefits and concerns, and variable needs and preferences, with respect to each delivery system. Implants and depot injections are not 'fixed' medications that can be administered to people to achieve pre-determined treatment aims. Rather, they are complex 'assemblages' with uncertain outcomes. Furthermore, they are themselves part of wider interactive 'assemblages'. Drug developers and treatment providers need to understand this complexity in order to target long-acting OPT at people most likely to benefit from it, and to reduce any unintended negative consequences. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of poly(2-hydroxyethyl methacrylate) and poly(vinyl-pyrrolidone) hydrogel implants on myopic and normal chick sclera

PubMed Central

Su, James; Iomdina, Elena; Tarutta, Elena; Ward, Brian; Song, Jie; Wildsoet, Christine F.

2008-01-01

There has been generally little attention paid to the utilization of biomaterials as an anti-myopia treatment. The purpose of this study was to investigate whether polymeric hydrogels, either implanted or injected adjacent to the outer scleral surface, slow ocular elongation. White Leghorn (gallus gallus domesticus) chicks were used at 2 weeks of age. Chicks had either (1) strip of poly(2-hydroxyethyl methacrylate) (pHEMA) implanted monocularly against the outer sclera at the posterior pole, or (2) an in situ polymerizing gel [main ingredient: poly(vinyl-pyrrolidone) (PVP)] injected monocularly at the same location. Some of the eyes injected with the polymer were fitted with a diffuser or a −10D lens. In each experiment, ocular lengths were measured at regular intervals by high frequency A-scan ultrasonography, and chicks were sacrificed for histology at staged intervals. No in vivo signs of either orbital or ocular inflammation were observed. The pHEMA implant significantly increased scleral thickness by the third week, and the implant became encapsulated with fibrous tissue. The PVP-injected eyes left otherwise untreated, showed a significant increase in scleral thickness, due to increased chondrocyte proliferation and extracellular matrix deposition. However, there was no effect of the PVP injection on ocular elongation. In eyes wearing optical devices, there was no effect on either scleral thickness or ocular elongation. These results represent “proof of principle” that scleral growth can be manipulated without adverse inflammatory responses. However, since neither approach slowed ocular elongation, additional factors must influence scleral surface area expansion in the avian eye. PMID:19109950

Evidence of low injection efficiency for implanted p-emitters in bipolar 4H-SiC high-voltage diodes

NASA Astrophysics Data System (ADS)

Matthus, Christian D.; Huerner, Andreas; Erlbacher, Tobias; Bauer, Anton J.; Frey, Lothar

2018-06-01

In this study, the influence of the emitter efficiency on the forward current-voltage characteristics, especially the conductivity modulation of bipolar SiC-diodes was analyzed. It was determined that the emitter efficiency of p-emitters formed by ion implantation is significantly lower compared to p-emitters formed by epitaxy. In contrast to comparable studies, experimental approach was arranged that the influence of the quality of the drift-layer or the thickness of the emitter on the conductivity modulation could be excluded for the fabricated bipolar SiC-diodes of this work. Thus, it can be established that the lower emitter injection efficiency is mainly caused by the reduced electron lifetime in p-emitters formed by ion implantation. Therefore, a significant enhancement of the electron lifetime in implanted p-emitters is mandatory for e.g. SiC-MPS-diodes where the functionality of the devices depends significantly on the injection efficiency.

[Local injection of exogenous nerve growth factor improves early bone maturation of implants].

PubMed

Yao, Yang; Du, Yu; Gu, Xia; Guang, Meng-Kai; Huang, Bo; Gong, Ping

2018-04-01

To investigate the effects of nerve growth factor (NGF) in the osteogenic action of implants and the maturation and reconstruction changes in bone tissues in the early stage of osseointegration. The mouse implant model was established by placing titanium in the femoral head of the mouse and locally injecting NGF in the implant zone. On 1, 2 and 4 weeks after operation, stain samples were collected from animals using hematoxylin-eosin (HE) staining and Masson staining. The effect of NGF on the bone maturation was compared at different time points of early stage osseointegration. The results of HE and Masson staining indicated that the local injection of external NGF can up-regulate bone mass, amount of bone trabecula, and bone maturity in the mouse model. The mature bone rate in treatment group of 1 week and 4 weeks after operation were significantly higher than those in the control group (P<0.05). NGF can shorten the period of bone maturation.

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

PubMed

Horozoğlu, Fatih; Sever, Özkan

2018-06-05

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

Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer’s disease

PubMed Central

Bastiat, Guillaume; Plourde, François; Motulsky, Aude; Furtos, Alexandra; Dumont, Yvan; Quirion, Rémi; Fuhrmann, Gregor; Leroux, Jean-Christophe

2015-01-01

Organogels can be prepared by immobilizing an organic phase into a three-dimensional network coming from the self-assembly of a low molecular weight gelator molecule. In this work, an injectable subcutaneous organogel system based on safflower oil and a modified-tyrosine organogelator was evaluated in vivo for the delivery of rivastigmine, an acetylcholinesterase (AChE) inhibitor used in the treatment of Alzheimer’s disease. Different implant formulations were injected and the plasmatic drug concentration was assayed for up to 35 days. In parallel, the inhibition of AChE in different brain sections and the biocompatibility of the implants were monitored. The pharmacokinetic profiles were found to be influenced by the gel composition, injected dose and volume of the implant. The sustained delivery of rivastigmine was accompanied by a significant prolonged inhibition of AChE in the hippocampus, a brain structure involved in memory. The implant induced only a minimal to mild chronic inflammation and fibrosis, which was comparable to poly(D,L-lactide-co-glycolide) in situ-forming implants. These findings suggest that tyrosine-based organogels could represent an alternative approach to current formulations for the sustained delivery of cholinesterase inhibitors. PMID:20472283

Injection of embryo culture supernatant to the endometrial cavity does not affect outcomes in IVF/ICSI or oocyte donation cycles: a randomized clinical trial.

PubMed

Prapas, Yannis; Petousis, Stamatios; Panagiotidis, Yannis; Gullo, Giuseppe; Kasapi, Lia; Papadeothodorou, Achilleas; Prapas, Nikos

2012-06-01

To evaluate whether intrauterine injection of embryo culture supernatant before embryo transfer has any impact on pregnancy and implantation rates. A total of 400 cycles, of which 200 IVF/ICSI and 200 oocyte donor (OD), were randomly assigned to have their uterine cavity injected (group I) or not (group II). Primary endpoints to be studied were pregnancy and implantation rates. Clinical pregnancy rate per transfer (47.87%, 90/188 versus 48.45%, 94/194) based on transvaginal scan findings at 7 weeks of gestation and implantation rate (25.6% versus 26.5%) were similar in the two groups. The day of embryo transfer, day 3 or day 5, did not affect the final outcome. Injection of embryo culture supernatant into the uterine cavity, 30 min before the embryo transfer on either day 3 or 5, neither improves nor adversely affects the pregnancy rate in IVF/ICSI or oocyte donation cycles. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

[Prolonged-release drug formulations for parenteral administration. Part II. Microspheres and implants for injection].

PubMed

Płaczek, Margin; Jacyna, Julia; Sznitowska, Małgorzata

2014-01-01

Microspheres and implants are injectable drug forms, which by special design and selection of appropriate excipients, provide for a long time constant release rate of an active substance in the body. Development of both would not be possible without advances in polymer technology and invention of safe and biocompatible polymers such as: polyesters, vinyl acetate derivatives or silicones. Polymeric matrices provide retardation of drug release--for some implants up to a few years. In addition, this paper presents examples of all commercially available medicinal products containing microspheres and implants, currently registered in Poland, together with their characteristics: composition, time course and frequency of administration. Comments are also enclosed on frequently occurring inconsistent terminology in pharmaceutical forms.

Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants.

PubMed

Cox, Sophie C; Jamshidi, Parastoo; Eisenstein, Neil M; Webber, Mark A; Hassanin, Hany; Attallah, Moataz M; Shepherd, Duncan E T; Addison, Owen; Grover, Liam M

2016-07-01

Additive manufacturing technologies have been utilised in healthcare to create patient-specific implants. This study demonstrates the potential to add new implant functionality by further exploiting the design flexibility of these technologies. Selective laser melting was used to manufacture titanium-based (Ti-6Al-4V) implants containing a reservoir. Pore channels, connecting the implant surface to the reservoir, were incorporated to facilitate antibiotic delivery. An injectable brushite, calcium phosphate cement, was formulated as a carrier vehicle for gentamicin. Incorporation of the antibiotic significantly (p=0.01) improved the compressive strength (5.8±0.7MPa) of the cement compared to non-antibiotic samples. The controlled release of gentamicin sulphate from the calcium phosphate cement injected into the implant reservoir was demonstrated in short term elution studies using ultraviolet-visible spectroscopy. Orientation of the implant pore channels were shown, using micro-computed tomography, to impact design reproducibility and the back-pressure generated during cement injection which ultimately altered porosity. The amount of antibiotic released from all implant designs over a 6hour period (<28% of the total amount) were found to exceed the minimum inhibitory concentrations of Staphylococcus aureus (16μg/mL) and Staphylococcus epidermidis (1μg/mL); two bacterial species commonly associated with periprosthetic infections. Antibacterial efficacy was confirmed against both bacterial cultures using an agar diffusion assay. Interestingly, pore channel orientation was shown to influence the directionality of inhibition zones. Promisingly, this work demonstrates the potential to additively manufacture a titanium-based antibiotic eluting implant, which is an attractive alternative to current treatment strategies of periprosthetic infections. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-05-01

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

Effect of an intravitreal cyclosporine implant on experimental uveitis in horses.

PubMed

Gilger, B C; Malok, E; Stewart, T; Horohov, D; Ashton, P; Smith, T; Jaffe, G J; Allen, J B

2000-10-31

The purpose of this study was to determine the effects of an intravitreal device releasing cyclosporine A (CsA) on recurrent inflammatory episodes in experimental uveitis. Nine normal horses were immunized peripherally with H37RA-mTB antigen twice, and then received 25 microg of H37RA-mTB antigen intravitreally in the right eye and an equal volume of balanced salt solution intravitreally in the left eye. Two weeks later, the animals randomly received either a CsA or a polymer implant (without CsA) in both eyes 1 week following implantation of the devices, 25 microg of H37RA-mTB antigen was reinjected into the right eye of each animal. Clinical signs of ophthalmic inflammation were graded following injections and implantation. The animals from each group were euthanized at 3, 14, and 28 days following the second injection. Aqueous and vitreous humor protein concentrations were measured. The presence, number, and type (CD4, 5 and 8) of infiltrating inflammatory cells and amount of tissue destruction were determined. Total RNA was isolated and quantitative reverse transcriptase-polymerase chain reaction was performed for equine specific interleukin (IL) 2 and 4, interferon-gamma (IFN gamma) and beta-actin. In addition, aqueous and vitreous humor and peripheral blood were collected at the termination of the experiments and analyzed for CsA concentration by HPLC. Within 4h of the first intravitreal H37RA-mTB antigen injection, each animal developed epiphora, blepharospasm, mild corneal edema, aqueous flare, myosis, and vitreous opacity. The severity of signs peaked 48 to 72 h after injection and subsequently decreased back to normal within 14 days. Following the second injection, clinical signs in the eyes with the CsA device were less severe and significantly shorter in duration than signs with the polymer only implant eyes. Aqueous and vitreous humor protein levels, infiltrating cell numbers, total number of T-lymphocytes, and levels of IL-2 and IFN gamma-mRNA were significantly less in eyes with the CsA implant compared to eyes with the polymer only. CsA implants did not completely eliminate the development of a second ('recurrent') experimental inflammatory episode in these horses. However, the duration and severity of inflammation, cellular infiltration, tissue destruction, and pro-inflammatory cytokines RNA transcript levels were significantly less in those eyes implanted with the CsA device.

Wound Dehiscence and Device Migration after Subconjunctival Bevacizumab Injection with Ahmed Glaucoma Valve Implantation.

PubMed

Miraftabi, Arezoo; Nilforushan, Naveed

2016-01-01

To report a complication pertaining to subconjunctival bevacizumab injection as an adjunct to Ahmed Glaucoma Valve (AGV) implantation. A 54-year-old woman with history of complicated cataract surgery was referred for advanced intractable glaucoma. AGV implantation with adjunctive subconjunctival bevacizumab (1.25 mg) was performed with satisfactory results during the first postoperative week. However, 10 days after surgery, she developed wound dehiscence and tube exposure. The second case was a 33-year-old man with history of congenital glaucoma and uncontrolled IOP who developed AGV exposure and wound dehiscence after surgery. In both cases, for prevention of endophthalmitis and corneal damage by the unstable tube, the shunt was removed and the conjunctiva was re-sutured. The potential adverse effect of subconjunctival bevacizumab injection on wound healing should be considered in AGV surgery.

Effect of intrauterine injection of human chorionic gonadotropin before embryo transfer on clinical pregnancy rates from in vitro fertilisation cycles: a prospective study.

PubMed

Santibañez, Alvaro; García, Jorge; Pashkova, Olga; Colín, Omar; Castellanos, Guillermo; Sánchez, Ana P; De la Jara, Julio F

2014-01-29

The implantation process after embryo transfer depends on the embryo quality and endometrial receptivity. It is estimated that fifty to seventy-five per cent of pregnancies are lost due to a failure of implantation. There is evidence that there is an early secretion of human chorionic gonadotrophin before embryo implantation, and this secretion has been linked to an important function in angiogenesis and the inflammatory response that promotes the implantation process. Our objective was to determine the effects of intrauterine injection of human chorionic gonadotropin (hCG) before the embryo transfer in an in vitro fertilisation cycle. A prospective randomised study was conducted in Reproductive Medicine Centre PROCREA in Mexico City. Infertile patients who had a medical indication for in vitro fertilisation were studied. Two groups were included (n 210); the intervention group received an intrauterine injection of 500 IU of hCG before the embryo transfer (n 101). The control group (n 109) did not receive hCG. Comparisons were performed using a chi-square test. The clinical pregnancy rate (CPR) was our principal outcome. The implantation rate was a secondary outcome. The implantation rate was significantly higher in the hCG group compared to the control group (52.4% vs 35.7%, p 0.014). The clinical pregnancy rate was also significantly higher (50.4 vs 33.0%, p 0.010). No adverse effects were observed. The intrauterine injection of hCG before embryo transfer showed a significant increase in the clinical pregnancy rate. More clinical trials are needed to reproduce these results on this promising intervention. The live birth rate must be included in subsequent studies.

[Clinical effect of ultrasound-guided injection of biodegradable poly(lactic-co-glycolic acid)-Fe3O4 in situ implant for magnetic thermal ablation in treatment of nude mice with human liver cancer SMMC-7721 cells].

PubMed

Liang, B; Zuo, G Q; Zheng, Y Y; He, S; Zuo, D Y

2016-12-20

Objective: To prepare the Fe 3 O 4 -loaded biodegradable liquid-solid phase inversion poly(lactic-co-glycolic acid) (PLGA) in situ implant for ultrasound-guided injection into nude mouse tumor model, and to investigate its clinical effect in thermomagnetic treatment of nude mice with human liver cancer SMMC-7721 cells in an alternating magnetic field. Methods: An in situ implant containing 10% Fe 3 O 4 was prepared, and 50 μl Fe 3 O 4 -PLGA-NMP gel was injected into the subcutaneous tissue of Kunming mice. The degradation of this material was observed for 2 consecutive months, and the changes in body weight were recorded. HE staining and Prussian blue staining were performed for the heart, liver, spleen, lung, and kidney of Kunming mice. Fresh ex vivo bovine liver was taken and cut into cubes with a dimension of 2 cm×2 cm×2 cm and then 50 μl Fe 3 O 4 -PLGA-NMP gel was injected; after phase inversion, the cubes of ex vivo bovine liver were heated for 1, 2, 3, 4, and 5 minutes, respectively, and then cut open for observing the range of ablation; HE staining was also performed. Micro-CT scan was performed after ultrasound-guided injection of 50 μl Fe 3 O 4 -PLGA gel into the tumors of the nude mice, and then the nude mice were divided into treatment group and control group. The mice in the treatment group were given thermomagnetic treatment for 3 minutes, and tumor growth was observed daily. Results: The biodegradation of Fe 3 O 4 -PLGA-NMP implant showed that the subcutaneously injected material was gradually metabolized at 2 weeks after injection and that the nude mice were in good condition. The bovine liver ablation experiment showed that the range of ablation of 50 μl Fe 3 O 4 -PLGA implant reached 1.46 ± 0.11 cm. HE staining showed that part of bovine liver had coagulative necrosis. The phase inversion experiment of Fe 3 O 4 -PLGA gel showed quick liquid-solid phase inversion of the material after injection into the tumor, and the process of liquid-solid phase inversion could be monitored by ultrasound and CT. The detachment and incrustation of the tumor started at 2 days after treatment, the wound started to heal 15 days later, and the tumor tissue disappeared completely. Conclusion: Ultrasound-guided injection of biodegradable Fe 3 O 4 -PLGA in situ implant combined with magnetic thermal ablation can effectively treat human liver cancer SMMC-7721 cells in nude mice.

Intravenous injections of soluble drag-reducing polymers reduce foreign body reaction to implants.

PubMed

Marascalco, Philip J; Blair, Harry C; Nieponice, Alejandro; Robinson, Lisa J; Kameneva, Marina V

2009-01-01

We tested whether soluble viscoelastic drag-reducing polymers (DRPs), which modify blood flow in the macro- and microcirculation, affect host response to implanted biomaterials and control biodegradation and tissue ingrowth processes. Porous poly(L-lactate) (PLLA) implants, which are naturally hydrolyzed by foreign body giant cells, were used to evaluate differences in host response. Intravenous DRPs, high-molecular weight poly(ethylene oxide) (PEO) or poly(mannose) (PMNN), were given biweekly at 0.3-0.4 nM in saline (equivalent volumes of saline in controls) to rats with subcutaneous PLLA implants. After 7 weeks, there was no difference in weight gain or behavior between control and DRP-injected groups. Implanted PLLA scaffolds in controls were almost totally degraded and replaced by giant cell granulomas. On the contrary, PEO- or PMNN-treated animals retained a significant part of the implanted scaffold (p < 0.0001 vs. controls). The foreign body reaction was markedly decreased, and there was an increase in well-oriented collagen deposition within the implanted scaffold area in the animals treated with DRPs. The DRP-mediated effects observed in this study potentially reflect alteration in inflammatory events in response to implanted bioengineered materials, and, thus, warrant further investigation.

Design and evaluation of wide-range and low-power analog front-end enabling body-implanted devices to monitor charge injection properties

NASA Astrophysics Data System (ADS)

Ito, Keita; Uno, Shoma; Goto, Tatsuya; Takezawa, Yoshiki; Harashima, Takuya; Morikawa, Takumi; Nishino, Satoru; Kino, Hisashi; Kiyoyama, Koji; Tanaka, Tetsu

2017-04-01

For safe electrical stimulation with body-implanted devices, the degradation of stimulus electrodes must be considered because it causes the unexpected electrolysis of water and the destruction of tissues. To monitor the charge injection property (CIP) of stimulus electrodes while these devices are implanted, we have proposed a charge injection monitoring system (CIMS). CIMS can safely read out voltages produced by a biphasic current pulse to a stimulus electrode and CIP is calculated from waveforms of the acquired voltages. In this paper, we describe a wide-range and low-power analog front-end (AFE) for CIMS that has variable gain-frequency characteristics and low-power analog-to-digital (A/D) conversion to adjust to the degradation of stimulus electrodes. The designed AFE was fabricated with 0.18 µm CMOS technology and achieved a valuable gain of 20-60 dB, an upper cutoff frequency of 0.2-10 kHz, and low-power interleaving A/D conversion. In addition, we successfully measured the CIP of stimulus electrodes for body-implanted devices using CIMS.

Wound Dehiscence and Device Migration after Subconjunctival Bevacizumab Injection with Ahmed Glaucoma Valve Implantation

PubMed Central

Miraftabi, Arezoo; Nilforushan, Naveed

2016-01-01

Purpose: To report a complication pertaining to subconjunctival bevacizumab injection as an adjunct to Ahmed Glaucoma Valve (AGV) implantation. Case Report: A 54-year-old woman with history of complicated cataract surgery was referred for advanced intractable glaucoma. AGV implantation with adjunctive subconjunctival bevacizumab (1.25 mg) was performed with satisfactory results during the first postoperative week. However, 10 days after surgery, she developed wound dehiscence and tube exposure. The second case was a 33-year-old man with history of congenital glaucoma and uncontrolled IOP who developed AGV exposure and wound dehiscence after surgery. In both cases, for prevention of endophthalmitis and corneal damage by the unstable tube, the shunt was removed and the conjunctiva was re-sutured. Conclusion: The potential adverse effect of subconjunctival bevacizumab injection on wound healing should be considered in AGV surgery. PMID:27195095

Injectable fillers: review of material and properties.

PubMed

Attenello, Natalie Huang; Maas, Corey S

2015-02-01

With an increasing understanding of the aging process and the rapidly growing interest in minimally invasive treatments, injectable facial fillers have changed the perspective for the treatment and rejuvenation of the aging face. Other than autologous fat and certain preformed implants, the collagen family products were the only Food and Drug Administration approved soft tissue fillers. But the overwhelming interest in soft tissue fillers had led to the increase in research and development of other products including bioengineered nonpermanent implants and permanent alloplastic implants. As multiple injectable soft tissue fillers and biostimulators are continuously becoming available, it is important to understand the biophysical properties inherent in each, as these constitute the clinical characteristics of the product. This article will review the materials and properties of the currently available soft tissue fillers: hyaluronic acid, calcium hydroxylapatite, poly-l-lactic acid, polymethylmethacrylate, and autologous fat (and aspirated tissue including stem cells). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Comparison of 180-degree and 90-degree needle rotation to reduce wound size in PIT-injected juvenile Chinook salmon

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

Bryson, Amanda J.; Woodley, Christa M.; Karls, Rhonda K.

2013-04-30

Animal telemetry, which requires the implantation of passive transponders or active transmitters, is used to monitor and assess fish stock and conservation to gain an understanding of fish movement and behavior. As new telemetry technologies become available, studies of their effects on species of interest are imperative as is development of implantation techniques. In this study, we investigated the effects of bevel rotation (0-, 90-, 180-degree axis rotation) on wound extent, tag loss, and wound healing rates in juvenile Chinook salmon injected with an 8-gauge needle, which is required for implantation of the novel injectable Juvenile Salmon Acoustic Telemetry Systemsmore » (JSATS) acoustic transmitter or large passive integrated transponder (PIT) tags. Although the injection sites were not closed after injection (e.g., with sutures or glue), there were no mortalities, dropped tags, or indications of fungus, ulceration, and/or redness around the wound. On Day 0 and post-implantation Day 7, the 90-degree bevel rotation produced smaller wound extent than the 180-degree bevel rotation. No axis rotation (0-degrees) resulted in the PIT tag frequently misleading or falling out upon injection. The results of this study indicated the 90-degree bevel rotation was the more efficient technique, produced less wound extent. Given the wound extent compared to size of fish, we recommend researchers should consider a 90-degree rotation over the 180-degree rotation in telemetry studies. Highlights •Three degrees of needle rotation were examined for effects in Chinook salmon. •Mortality, tag loss, wound extent, healing, and infection indicators were measured. •There were no mortalities, tag loss, or indications of infection. •The 90-degree needle rotation through Day 7 produced the smallest wound extent.« less

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

PubMed

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

2017-08-01

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

Evaluation of injectable strontium-containing borate bioactive glass cement with enhanced osteogenic capacity in a critical-sized rabbit femoral condyle defect model.

PubMed

Zhang, Yadong; Cui, Xu; Zhao, Shichang; Wang, Hui; Rahaman, Mohamed N; Liu, Zhongtang; Huang, Wenhai; Zhang, Changqing

2015-02-04

The development of a new generation of injectable bone cements that are bioactive and have enhanced osteogenic capacity for rapid osseointegration is receiving considerable interest. In this study, a novel injectable cement (designated Sr-BBG) composed of strontium-doped borate bioactive glass particles and a chitosan-based bonding phase was prepared and evaluated in vitro and in vivo. The bioactive glass provided the benefits of bioactivity, conversion to hydroxyapatite, and the ability to stimulate osteogenesis, while the chitosan provided a cohesive biocompatible and biodegradable bonding phase. The Sr-BBG cement showed the ability to set in situ (initial setting time = 11.6 ± 1.2 min) and a compressive strength of 19 ± 1 MPa. The Sr-BBG cement enhanced the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells in vitro when compared to a similar cement (BBG) composed of chitosan-bonded borate bioactive glass particles without Sr. Microcomputed tomography and histology of critical-sized rabbit femoral condyle defects implanted with the cements showed the osteogenic capacity of the Sr-BBG cement. New bone was observed at different distances from the Sr-BBG implants within eight weeks. The bone-implant contact index was significantly higher for the Sr-BBG implant than it was for the BBG implant. Together, the results indicate that this Sr-BBG cement is a promising implant for healing irregularly shaped bone defects using minimally invasive surgery.

Flexible-Device Injector with a Microflap Array for Subcutaneously Implanting Flexible Medical Electronics.

PubMed

Song, Kwangsun; Kim, Juho; Cho, Sungbum; Kim, Namyun; Jung, Dongwuk; Choo, Hyuck; Lee, Jongho

2018-06-25

Implantable electronics in soft and flexible forms can reduce undesired outcomes such as irritations and chronic damages to surrounding biological tissues due to the improved mechanical compatibility with soft tissues. However, the same mechanical flexibility also makes it difficult to insert such implants through the skin because of reduced stiffness. In this paper, a flexible-device injector that enables the subcutaneous implantation of flexible medical electronics is reported. The injector consists of a customized blade at the tip and a microflap array which holds the flexible implant while the injector penetrates through soft tissues. The microflap array eliminates the need of additional materials such as adhesives that require an extended period to release a flexible medical electronic implant from an injector inside the skin. The mechanical properties of the injection system during the insertion process are experimentally characterized, and the injection of a flexible optical pulse sensor and electrocardiogram sensor is successfully demonstrated in vivo in live pig animal models to establish the practical feasibility of the concept. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Monte Carlo simulation of radiation transport and dose deposition from locally released gold nanoparticles labeled with 111In, 177Lu or 90Y incorporated into tissue implantable depots

NASA Astrophysics Data System (ADS)

Lai, Priscilla; Cai, Zhongli; Pignol, Jean-Philippe; Lechtman, Eli; Mashouf, Shahram; Lu, Yijie; Winnik, Mitchell A.; Jaffray, David A.; Reilly, Raymond M.

2017-11-01

Permanent seed implantation (PSI) brachytherapy is a highly conformal form of radiation therapy but is challenged with dose inhomogeneity due to its utilization of low energy radiation sources. Gold nanoparticles (AuNP) conjugated with electron emitting radionuclides have recently been developed as a novel form of brachytherapy and can aid in homogenizing dose through physical distribution of radiolabeled AuNP when injected intratumorally (IT) in suspension. However, the distribution is unpredictable and precise placement of many injections would be difficult. Previously, we reported the design of a nanoparticle depot (NPD) that can be implanted using PSI techniques and which facilitates controlled release of AuNP. We report here the 3D dose distribution resulting from a NPD incorporating AuNP labeled with electron emitters (90Y, 177Lu, 111In) of different energies using Monte Carlo based voxel level dosimetry. The MCNP5 Monte Carlo radiation transport code was used to assess differences in dose distribution from simulated NPD and conventional brachytherapy sources, positioned in breast tissue simulating material. We further compare these dose distributions in mice bearing subcutaneous human breast cancer xenografts implanted with 177Lu-AuNP NPD, or injected IT with 177Lu-AuNP in suspension. The radioactivity distributions were derived from registered SPECT/CT images and time-dependent dose was estimated. Results demonstrated that the dose distribution from NPD reduced the maximum dose 3-fold when compared to conventional seeds. For simulated NPD, as well as NPD implanted in vivo, 90Y delivered the most homogeneous dose distribution. The tumor radioactivity in mice IT injected with 177Lu-AuNP redistributed while radioactivity in the NPD remained confined to the implant site. The dose distribution from radiolabeled AuNP NPD were predictable and concentric in contrast to IT injected radiolabeled AuNP, which provided irregular and temporally variant dose distributions. The use of NPD may serve as an intermediate between PSI and radiation delivered by radiolabeled AuNP by providing a controlled method to improve delivery of prescribed doses as well as homogenize dose from low penetrating electron sources.

Forehead augmentation with a methyl methacrylate onlay implant using an injection-molding technique.

PubMed

Park, Dong Kwon; Song, Ingook; Lee, Jin Hyo; You, Young June

2013-09-01

The forehead, which occupies about one third of the face, is one of the major determinants of a feminine or masculine look. Various methods have been used for the augmentation of the forehead using autologous fat grafts or alloplastic materials. Methylmethacrylate (MMA) is the most appropriate material for augmentation of the forehead, and we have used an injection-molding technique with MMA to achieve satisfactory results. Under local anesthesia with intravenous (IV) sedation, an incision was made on the scalp and a meticulous and delicate subperiosteal dissection was then performed. MMA monomers and polymers were mixed, the dough was injected into the space created, and manual molding was performed along with direct inspection. This surgery was indicated for patients who wanted to correct an unattractive appearance by forehead augmentation. Every patient in this study visited our clinics 3 months after surgery to evaluate the results. We judged the postoperative results in terms of re-operation rates caused by the dissatisfaction of the patients and complications. During a 13-year period, 516 patients underwent forehead augmentation with MMA. With the injection-molding technique, the inner surface of the MMA implant is positioned close to the underlying frontal bone, which minimizes the gap between the implant and bone. The borders of the implant should be tapered sufficiently until no longer palpable or visible. Only 28 patients (5.4%) underwent a re-operation due to an undesirable postoperative appearance. The injection-molding technique using MMA is a simple, safe, and ideal method for the augmentation of the forehead.

Forehead Augmentation with a Methyl Methacrylate Onlay Implant Using an Injection-Molding Technique

PubMed Central

Park, Dong Kwon; Song, Ingook; Lee, Jin Hyo

2013-01-01

Background The forehead, which occupies about one third of the face, is one of the major determinants of a feminine or masculine look. Various methods have been used for the augmentation of the forehead using autologous fat grafts or alloplastic materials. Methylmethacrylate (MMA) is the most appropriate material for augmentation of the forehead, and we have used an injection-molding technique with MMA to achieve satisfactory results. Methods Under local anesthesia with intravenous (IV) sedation, an incision was made on the scalp and a meticulous and delicate subperiosteal dissection was then performed. MMA monomers and polymers were mixed, the dough was injected into the space created, and manual molding was performed along with direct inspection. This surgery was indicated for patients who wanted to correct an unattractive appearance by forehead augmentation. Every patient in this study visited our clinics 3 months after surgery to evaluate the results. We judged the postoperative results in terms of re-operation rates caused by the dissatisfaction of the patients and complications. Results During a 13-year period, 516 patients underwent forehead augmentation with MMA. With the injection-molding technique, the inner surface of the MMA implant is positioned close to the underlying frontal bone, which minimizes the gap between the implant and bone. The borders of the implant should be tapered sufficiently until no longer palpable or visible. Only 28 patients (5.4%) underwent a re-operation due to an undesirable postoperative appearance. Conclusions The injection-molding technique using MMA is a simple, safe, and ideal method for the augmentation of the forehead. PMID:24086816

A review of biocompatible metal injection moulding process parameters for biomedical applications.

PubMed

Hamidi, M F F A; Harun, W S W; Samykano, M; Ghani, S A C; Ghazalli, Z; Ahmad, F; Sulong, A B

2017-09-01

Biocompatible metals have been revolutionizing the biomedical field, predominantly in human implant applications, where these metals widely used as a substitute to or as function restoration of degenerated tissues or organs. Powder metallurgy techniques, in specific the metal injection moulding (MIM) process, have been employed for the fabrication of controlled porous structures used for dental and orthopaedic surgical implants. The porous metal implant allows bony tissue ingrowth on the implant surface, thereby enhancing fixation and recovery. This paper elaborates a systematic classification of various biocompatible metals from the aspect of MIM process as used in medical industries. In this study, three biocompatible metals are reviewed-stainless steels, cobalt alloys, and titanium alloys. The applications of MIM technology in biomedicine focusing primarily on the MIM process setting parameters discussed thoroughly. This paper should be of value to investigators who are interested in state of the art of metal powder metallurgy, particularly the MIM technology for biocompatible metal implant design and development. Copyright © 2017 Elsevier B.V. All rights reserved.

Continuous PECS II block for postoperative analgesia in patients undergoing transapical transcatheter aortic valve implantation.

PubMed

Shakuo, Tomoharu; Kakumoto, Shinichi; Kuribayashi, Junya; Oe, Katsunori; Seo, Katsuhiro

2017-01-01

It has been reported that PECS II block can alleviate postoperative pain following transapical transcatheter aortic valve implantation (TA-TAVI). However, the effectiveness of continuous PECS II block with catheterization has not yet been reported on the postoperative pain in patients undergoing TA-TAVI. We experienced two cases of TA-TAVI who received PECS II block with catheterization to manage postoperative pain. In the first case, a bolus injection for intraoperative pain and subsequent catheterization were performed before the implantation. However, the patient developed severe pain postoperatively in spite of the continuous block due to displacement of the catheter. In the second case, a bolus injection and the catheterization for the continuous block were performed before and after the implantation, respectively, which provided high-quality pain control. Continuous PECS II block may be useful to control perioperative pain associated with TA-TAVI. The insertion of the catheter after the implantation could be useful to avoid its displacement during the surgery.

The effect of montelukast and antiadhesion barrier solution on the capsule formation after insertion of silicone implants in a white rat model.

PubMed

Yang, J-D; Kwon, O-H; Lee, J-W; Chung, H-Y; Cho, B-C; Park, H-Y; Kim, T-G

2013-01-01

Capsular contracture is one of the most severe complications that can occur in breast surgery following silicone implant insertion. The purpose of this study was to investigate the effect of montelukast and antiadhesion barrier solution (AABS) on reducing capsular formation and their possible synergism. This study was approved by the Animal Ethics Committee (Reference No. KNU 2012-33) and was conducted in accordance with the Kyungpook National University - Institutional Animal Care and Use Committee, Animal Ethics Committee. The experiments in this study were conducted in vivo in 4 groups of 24 rats. Following silicone implant insertion, the pocket was injected with different agents. Group I (control group) was given normal saline injections into the pocket and fed with pure water. Group II was given injections of AABS and fed with pure water. Group III was given injections of normal saline and the medication montelukast during the experimental period. Group IV was given injections of AABS and montelukast as postoperative medication. Peri-implant capsules were excised after 8 weeks and were evaluated for transparency, inflammatory cell content, capsule thickness, collagen pattern and TGF-β expression. The capsules in the experimental groups (i.e., groups II-IV) were significantly more transparent than those in group I (controls; p < 0.05, Student's t test). The mean capsule thickness of the experimental groups II (296 ± 14.76 μm), III (280 ± 14.77 μm) and IV (276 ± 39.28 μm) was smaller than that of the control group I (361 ± 35.43 μm). Compared to the control group, the histologic findings in the experimental groups suggested a decreased inflammatory response occurring in the peri-implant capsules as they exhibited minor vascularization and a reduced number of mast cells and macrophages. The collagen patterns in the experimental groups were of a lower density than in the control group with the former showing a loose, tidy collagen pattern. The amounts of TGF-β and collagen I were higher in the control group than in the experimental groups. Group IV (the synergic effect group) had a more pronounced effect on all the parameters examined than that in groups II and III with separate drug administration. Montelukast and AABS reduced the thickness, the inflammatory cell infiltrate and the myofibroblast content of the peri-implant capsules around silicone implants in this white rat model. They lowered the expression of the fibrotic mediator, TGF-β, and inhibited the peri-implant capsular fibrosis. Therefore, montelukast and AABS are effective in the reduction of silicone-induced peri-implant capsular formation.

21 CFR 522.850 - Estradiol valerate and norgestomet in combination.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... (c) Conditions of use—(1) Amount. One implant and 2 milliliters of injection at time of implantation. (2) Indications for use. For synchronization of estrus/ovulation in cycling beef cattle and non...

21 CFR 522.850 - Estradiol valerate and norgestomet in combination.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... (c) Conditions of use—(1) Amount. One implant and 2 milliliters of injection at time of implantation. (2) Indications for use. For synchronization of estrus/ovulation in cycling beef cattle and non...

21 CFR 522.850 - Estradiol valerate and norgestomet in combination.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... (c) Conditions of use—(1) Amount. One implant and 2 milliliters of injection at time of implantation. (2) Indications for use. For synchronization of estrus/ovulation in cycling beef cattle and non...

21 CFR 522.850 - Estradiol valerate and norgestomet in combination.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... (c) Conditions of use—(1) Amount. One implant and 2 milliliters of injection at time of implantation. (2) Indications for use. For synchronization of estrus/ovulation in cycling beef cattle and non...

21 CFR 522.850 - Estradiol valerate and norgestomet in combination.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... (c) Conditions of use—(1) Amount. One implant and 2 milliliters of injection at time of implantation. (2) Indications for use. For synchronization of estrus/ovulation in cycling beef cattle and non...

Nanofibrous hollow microspheres self-assembled from star-shaped polymers as injectable cell carriers for knee repair.

PubMed

Liu, Xiaohua; Jin, Xiaobing; Ma, Peter X

2011-05-01

To repair complexly shaped tissue defects, an injectable cell carrier is desirable to achieve an accurate fit and to minimize surgical intervention. However, the injectable carriers available at present have limitations, and are not used clinically for cartilage regeneration. Here, we report nanofibrous hollow microspheres self-assembled from star-shaped biodegradable polymers as an injectable cell carrier. The nanofibrous hollow microspheres, integrating the extracellular-matrix-mimicking architecture with a highly porous injectable form, were shown to efficiently accommodate cells and enhance cartilage regeneration, compared with control microspheres. The nanofibrous hollow microspheres also supported a significantly larger amount of, and higher-quality, cartilage regeneration than the chondrocytes-alone group in an ectopic implantation model. In a critical-size rabbit osteochondral defect-repair model, the nanofibrous hollow microspheres/chondrocytes group achieved substantially better cartilage repair than the chondrocytes-alone group that simulates the clinically available autologous chondrocyte implantation procedure. These results indicate that the nanofibrous hollow microspheres are an excellent injectable cell carrier for cartilage regeneration.

[Early efficacy of dexamethasone implant (OZURDEX®) in diabetic macular edema: Real life study].

PubMed

Sarda, V; Fajnkuchen, F; Nghiem-Buffet, S; Grenet, T; Chaine, G; Giocanti-Auregan, A

2017-05-01

To assess early efficacy of dexamethasone intravitreal implant 0.7mg (OZURDEX ® ) at the time of peak efficacy (2 months after injection) in patients with decreased visual acuity secondary to diabetic macular edema (DME). Retrospective monocentric study. Inclusion criteria were best-corrected visual acuity (BCVA)≤70 letters (20/40) due to DME and central retinal thickness (CRT)≥300 microns (Cirrus 2, Carl Zeiss Meditec, Inc, Dublin). Enrolled patients could be treatment naive or not (after failure of laser photocoagulation and/or anti-VEGF therapy). Follow-up was at least 6 months. Our primary endpoint was BCVA gain at M2 after injection. Secondary endpoints were best-corrected visual acuity at 2 and 4 months, central retinal thickness at 2 and 4 months, mean interval between 2 injections, and adverse events. Nineteen eyes of 19 patients were included in this study. The mean age was 67.45 years, sex ratio was 2.17 men/women, and the patients were all type 2 diabetics. Three of 19 patients were treatment naive for anti-VEGF intravitreal injection, and 52.3% were pseudophakic (10/19 patients). The mean gain of BCVA at M2 was +7.7 letters. The mean BCVA was 51.1 ETDRS letters at baseline and 58.8 at M2. Mean CRT was 568.9μm at baseline and 291.2μm at M2. Treatment with dexamethasone implant was mainly a second-line treatment after failure of other treatments (macular laser photocoagulation and/or intravitreal injection of anti-VEGF). Three patients were naive of anti-VEGF treatment. Intraocular pressure≥25mmHg was found in 2 patients, and controlled medically. No glaucoma surgery was performed. The dexamethasone implant (OZURDEX ® ) allows an anatomical and functional improvement in patients suffering from vision loss due to DME. In this series, the implant was well tolerated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Metabolic Biofouling of Glucose Sensors in Vivo: Role of Tissue Microhemorrhages

PubMed Central

Klueh, Ulrike; Liu, Zenghe; Feldman, Ben; Henning, Timothy P; Cho, Brian; Ouyang, Tianmei; Kreutzer, Don

2011-01-01

Objective: Based on our in vitro study that demonstrated the adverse effects of blood clots on glucose sensor function, we hypothesized that in vivo local tissue hemorrhages, induced as a consequence of sensor implantation or sensor movement post-implantation, are responsible for unreliable readings or an unexplained loss of functionality shortly after implantation. Research Design and Methods: To investigate this issue, we utilized real-time continuous monitoring of blood glucose levels in a mouse model. Direct injection of blood at the tissue site of sensor implantation was utilized to mimic sensor-induced local tissue hemorrhages. Results: It was found that blood injections, proximal to the sensor, consistently caused lowered sensor glucose readings, designated temporary signal reduction, in vivo in our mouse model, while injections of plasma or saline did not have this effect. Conclusion: These results support our hypothesis that tissue hemorrhage and resulting blood clots near the sensor can result in lowered local blood glucose concentrations due to metabolism of glucose by the clot. The lowered local blood glucose concentration led to low glucose readings from the still functioning sensor that did not reflect the systemic glucose level. PMID:21722574

Optimization of Glioblastoma Mouse Orthotopic Xenograft Models for Translational Research.

PubMed

Irtenkauf, Susan M; Sobiechowski, Susan; Hasselbach, Laura A; Nelson, Kevin K; Transou, Andrea D; Carlton, Enoch T; Mikkelsen, Tom; deCarvalho, Ana C

2017-08-01

Glioblastoma is an aggressive primary brain tumor predominantly localized to the cerebral cortex. We developed a panel of patient-derived mouse orthotopic xenografts (PDOX) for preclinical drug studies by implanting cancer stem cells (CSC) cultured from fresh surgical specimens intracranially into 8-wk-old female athymic nude mice. Here we optimize the glioblastoma PDOX model by assessing the effect of implantation location on tumor growth, survival, and histologic characteristics. To trace the distribution of intracranial injections, toluidine blue dye was injected at 4 locations with defined mediolateral, anterioposterior, and dorsoventral coordinates within the cerebral cortex. Glioblastoma CSC from 4 patients and a glioblastoma nonstem-cell line were then implanted by using the same coordinates for evaluation of tumor location, growth rate, and morphologic and histologic features. Dye injections into one of the defined locations resulted in dye dissemination throughout the ventricles, whereas tumor cell implantation at the same location resulted in a much higher percentage of small multifocal ventricular tumors than did the other 3 locations tested. Ventricular tumors were associated with a lower tumor growth rate, as measured by in vivo bioluminescence imaging, and decreased survival in 4 of 5 cell lines. In addition, tissue oxygenation, vasculature, and the expression of astrocytic markers were altered in ventricular tumors compared with nonventricular tumors. Based on this information, we identified an optimal implantation location that avoided the ventricles and favored cortical tumor growth. To assess the effects of stress from oral drug administration, mice that underwent daily gavage were compared with stress-positive and -negative control groups. Oral gavage procedures did not significantly affect the survival of the implanted mice or physiologic measurements of stress. Our findings document the importance of optimization of the implantation site for preclinical mouse models of glioblastoma.

Optimization of Glioblastoma Mouse Orthotopic Xenograft Models for Translational Research

PubMed Central

Irtenkauf, Susan M; Sobiechowski, Susan; Hasselbach, Laura A; Nelson, Kevin K; Transou, Andrea D; Carlton, Enoch T; Mikkelsen, Tom; deCarvalho, Ana C

2017-01-01

Glioblastoma is an aggressive primary brain tumor predominantly localized to the cerebral cortex. We developed a panel of patient-derived mouse orthotopic xenografts (PDOX) for preclinical drug studies by implanting cancer stem cells (CSC) cultured from fresh surgical specimens intracranially into 8-wk-old female athymic nude mice. Here we optimize the glioblastoma PDOX model by assessing the effect of implantation location on tumor growth, survival, and histologic characteristics. To trace the distribution of intracranial injections, toluidine blue dye was injected at 4 locations with defined mediolateral, anterioposterior, and dorsoventral coordinates within the cerebral cortex. Glioblastoma CSC from 4 patients and a glioblastoma nonstem-cell line were then implanted by using the same coordinates for evaluation of tumor location, growth rate, and morphologic and histologic features. Dye injections into one of the defined locations resulted in dye dissemination throughout the ventricles, whereas tumor cell implantation at the same location resulted in a much higher percentage of small multifocal ventricular tumors than did the other 3 locations tested. Ventricular tumors were associated with a lower tumor growth rate, as measured by in vivo bioluminescence imaging, and decreased survival in 4 of 5 cell lines. In addition, tissue oxygenation, vasculature, and the expression of astrocytic markers were altered in ventricular tumors compared with nonventricular tumors. Based on this information, we identified an optimal implantation location that avoided the ventricles and favored cortical tumor growth. To assess the effects of stress from oral drug administration, mice that underwent daily gavage were compared with stress-positive and ‑negative control groups. Oral gavage procedures did not significantly affect the survival of the implanted mice or physiologic measurements of stress. Our findings document the importance of optimization of the implantation site for preclinical mouse models of glioblastoma. PMID:28830577

BMP7 Induces Dormancy of Prostatic Tumor Stem Cell in Bone

DTIC Science & Technology

2012-10-01

the upper back of nude mice. Recombinant human BMP7 was peritumorally injected daily after implantation. Tumor growth was monitored weekly by...of BMP7 was administrated daily through i.v. after intracardiac injection of CSCs from PC3mm or C4-2B cells to the mice. As shown in Figure 5A...mice, and then BMP7 was administrated daily . BLI of representative mice in each group six weeks after implantation (A). Normalized BLI signals

21 CFR 522.2220 - Sulfadimethoxine injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sulfadimethoxine injection. 522.2220 Section 522.2220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522...

21 CFR 522.2615 - Tripelennamine hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Tripelennamine hydrochloride injection. 522.2615 Section 522.2615 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS...

21 CFR 522.2220 - Sulfadimethoxine injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfadimethoxine injection. 522.2220 Section 522.2220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522...

Evaluation of best corrected visual acuity and central macular thickness after intravitreal dexamethasone implant injections in patients with Irvine-Gass syndrome: A retrospective study of six cases.

PubMed

Keilani, Chafik; Halalchi, Aziz; Wakpi Djeugue, Désiré; Regis, Anne; Abada, Samir

2016-10-01

Irvine-Gass syndrome is a macular edema (ME) that specifically occurs after cataract surgery. Its incidence varies from 0.2-2%. The purpose of this study is to evaluate the effectiveness of intravitreal dexamethasone implant injections in patients with Irvine-Gass syndrome. Patients with ME secondary to cataract surgery who underwent intravitreal injections of dexamethasone implant between December 2011 to October 2014 at François-Quesnay hospital (Mantes-la-Jolie, France) were retrospectively reviewed. The patients were followed for at least 10 months. All the patients were handled by intravitreal injection of dexamethasone in the eye of study among which some resisted to a preliminary treatment by non-steroidal anti-inflammatory drug (NSAID) and acetazolamide. The patients were examined each month. The patients were again handled by intravitreal injection of dexamethasone if they presented a recurrence. The primary endpoint of the study was determined on best corrected visual acuity (BCVA) using early diabetic retinopathy study (ETDRS) scale and central macular thickness (CMT) [μm] using optical coherence tomography (OCT) 3 and 6 months after the first injection. Secondary endpoints were the number of recurrences, the number of injections, the duration average before the first recurrence, the BCVA 10 months after the first injection and the tolerance. Six eyes of six patients were studied. At baseline, the mean (standard deviation [SD]) of the BCVA was 59.8±11. Three months after the first injection, the mean (SD) of the BCVA showed a statistically significant increase to 72.2±8.6 (P=0.03). Six months after the first injection, the mean (SD) of the BCVA showed a statistically significant increase to 72±11.8 (P=0.03). Concerning the CMT, the mean (SD) was 495.6±135.2 before treatment. Three months after the first injection, the mean (SD) of the CMT showed a statistically significant decrease to 268.6±57.8 (P=0.03). Six months after the first injection, the mean (SD) of the CMT showed a significant decrease to 350.1±56.3 (P=0.09). In this study, both mean BCVA and mean CMT had significantly improved from baseline after treatment with dexamethasone implant in patients with Irvine-Gass syndrome. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Suspected bacterial endophthalmitis following sustained-release dexamethasone intravitreal implant: a case report.

PubMed

Arıkan Yorgun, Mücella; Mutlu, Melek; Toklu, Yasin; Cakmak, Hasan Basri; Cağıl, Nurullah

2014-06-01

A 58-year-old man admitted to our opthalmology department with the complaint of branch retinal vein occlusion. He was treated with intravitreal Ozurdex in the right eye. Two days after the injection, the patient presented with ocular pain and the visual acuity was hand movement. A diagnosis of endophthalmitis was made. We performed emergent pars plana vitrectomy (PPV) and the implant was removed from the vitreous cavity using a retinal forceps. A combination of vancomycin 1.0 mg and amikacin 0.4 mg was injected intravitreally. However, because of the blurring in the vitreus one week after the procedure, phacoemulsification and a repeat PPV was performed. Five days after the last procedure the signs and symptoms of endophthalmitis were resolved. Our case demonstrated that endophthalmitis could develop after intravitreal implantation of Ozurdex. Surgical removal of the implant and immediate vitrectomy seems to be a useful treatment option in these cases.

Neural stem cell implantation extends life in Niemann-Pick C1 mice.

PubMed

Ahmad, Iram; Hunter, Robert E; Flax, Jonathan D; Snyder, Evan Y; Erickson, Robert P

2007-01-01

In order to evaluate the phenotypic effects of implanted neural stem cells (NSCs) in the mouse model of Niemann-Pick C (NPC) disease, we injected a well-characterized clone of murine NSCs into the cerebella of neonatal Npc1(-/-) and control mice. The implanted cells survived and were abundant in some regions of the cerebellum. Life span was lengthened in NPC mice with the implanted NSCs. However, the rate of weight gain and subsequent weight loss, resulting from neurodegeneration, was not significantly different from un-injected controls. Ataxia was measured by Rota-Rod performance. The overall rate of decline in time on the Rota-Rod was not significantly slowed down. Thus, in this small group of NPC mice, a single administration in the neonatal period of the NSCs (which were not engineered to over-express the missing gene and not directed into the parenchyma) was only partially therapeutic.

Intravitreal dexamethasone implants for the treatment of refractory scleritis combined with uveitis in adult-onset Still's disease: a case report.

PubMed

Ahn, Seong Joon; Hwang, Sun Jin; Lee, Byung Ro

2016-11-08

Adult-onset Still's disease is a systemic inflammatory disease which presents with uveitis and scleritis in the eye. Intravitreal dexamethasone implants are used for the treatment of refractory uveitis. A 19-year-old woman diagnosed to have adult-onset Still's disease for fevers, joint pain, and a salmon-colored bumpy rash presented with scleritis and uveitis in the left eye. Topical and systemic steroids with oral methotrexate failed to control the inflammation. We performed intravitreal injections of dexamethasone implants for side effects of steroid and refractory ocular inflammation. The therapy resulted in improvements in the patient's uveitis with reductions in scleral vessel engorgement and redness. There was no recurrence of uveitis or scleritis during 4 months following treatment. Intravitreal injections of dexamethasone implants may result in clinical improvements of refractory scleritis combined with uveitis.

21 CFR 522.2063 - Pyrilamine maleate injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522... treating horses in conditions in which antihistaminic therapy may be expected to lead to alleviation of...

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-07-01

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

Fracture resistance of inter-joined zirconia abutment of dental implant system with injection molding technique.

PubMed

Yang, Jianjun; Wang, Ke; Liu, Guangyuan; Wang, Dashan

2013-11-01

Zirconia powder in nanometers can be fabricated into inter-joined abutment of dental implant system with the injection shaping technique. This study was to detect the resistance of inter-joined zirconia abutment with different angle loading for clinical applications. The inter-joined abutments were shaped with the technique of injection of zirconia powder in nanometers. Sixty Osstem GSII 5 × 10 mm implants were used with 30 zirconia abutments and 30 Osstem GSII titanium abutments for fixation using 40 N torque force. The loading applications included 90°, 30°, and 0° formed by the long axis of abutments and pressure head of universal test machine. The fracture resistances of zirconia and titanium abutments were documented and analyzed. The inter-joined zirconia abutments were assembled to the Osstem GSII implants successfully. In the 90° loading mode, the fracture resistance of zirconia abutment group and titanium abutment group were 301.5 ± 15.4 N and 736.4 ± 120.1 N, respectively. And those in the 30° groups were 434.7 ± 36.1 N and 1073.1 ± 74 N, correspondingly. Significant difference in the two groups was found using t-test and Wilcoxon test. No damage on the abutments of the two groups but S-shaped bending on the implants was found when the 0° loading was 1300-2000 N. Through the assembly of Zirconia abutments and implants, all the components presented sufficient resistance acquired for the clinical application under loadings with different angle. © 2012 John Wiley & Sons A/S.

Effects of a Novel Acoustic Transmitter on Swimming Performance and Predator Avoidance of Juvenile Chinook Salmon: Determination of a Size Threshold

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

Walker, Ricardo W.; Ashton, Neil K.; Brown, Richard S.

Abstract Telemetry studies are used worldwide to investigate the behavior and migration of fishes. The miniaturization of acoustic transmitters enables researchers to tag smaller fish, such as the juvenile life stages of salmon, thus representing a greater proportion of the population of interest. The development of an injectable acoustic transmitter has led to research determining the least invasive and quickest method of tag implantation. Swimming performance and predator avoidance were examined. To quantify critical swimming speed (Ucrit; an index of prolonged swimming performance) and predator avoidance for juvenile Chinook salmon (Oncorhynchus tshawytscha), fish were split into three groups: (1) fishmore » implanted with a dummy injectable acoustic transmitter (IAT treatment), (2) fish implanted with a dummy injectable acoustic transmitter and passive integrated transponder (PIT) tag (IAT+PIT treatment), and (3) an untagged control group. The Ucrits and predator avoidance capability of tagged fish were compared with untagged fish to determine if carrying an IAT adversely affected swimming performance or predator avoidance. Fish implanted with only an IAT had lower Ucrit values than untagged fish and a size threshold at 79 mm fork length was found. Conversely, Ucrit values for fish implanted with an IAT+PIT were not significantly different from untagged controls and no size threshold was found. Predator avoidance testing showed no significant difference for fish implanted with an IAT compared to untagged individuals, nor was there a significant difference for IAT+PIT fish compared to untagged fish.« less

Broad gap junction blocker carbenoxolone disrupts uterine preparation for embryo implantation in mice.

PubMed

Diao, Honglu; Xiao, Shuo; Howerth, Elizabeth W; Zhao, Fei; Li, Rong; Ard, Mary B; Ye, Xiaoqin

2013-08-01

Gap junctions have an important role in cell-to-cell communication, a process obviously required for embryo implantation. Uterine luminal epithelium (LE) is the first contact for an implanting embryo and is critical for the establishment of uterine receptivity. Microarray analysis of the LE from peri-implantation mouse uterus showed low-level expression of 19 gap junction proteins in preimplantation LE and upregulation of gap junction protein, beta 2 (GJB2, connexin 26, Cx26) in postimplantation LE. Time course study using in situ hybridization and immunofluorescence revealed upregulation of GJB2 in the LE surrounding the implantation site before decidualization. Similar dynamic expression of GJB2 was observed in the LE of artificially decidualized mice but not pseudopregnant mice. To determine the potential function of uterine gap junctions in embryo implantation, carbenoxolone (CBX), a broad gap junction blocker, was injected i.p. (100 mg/kg) or via local uterine fat pad (10 mg/kg) into pregnant mice on Gestation Day 3 at 1800 h, a few hours before embryo attachment to the LE. These CBX treatments disrupted embryo implantation, suggesting local effects of CBX in the uterus. However, i.p. injection of glycyrrhizic acid (100 mg/kg), which shares similar structure and multiple properties with CBX but is ineffective in blocking gap junctions, did not affect embryo implantation. Carbenoxolone also inhibited oil-induced artificial decidualization, concomitant with suppressed molecular changes and ultrastructural transformations associated with uterine preparation for embryo implantation, underscoring the adverse effect of CBX on uterine preparation for embryo implantation. These data demonstrate that uterine gap junctions are important for embryo implantation.

21 CFR 522.90b - Ampicillin trihydrate powder for injection.

Code of Federal Regulations, 2014 CFR

2014-04-01

....90b Section 522.90b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.90b Ampicillin trihydrate powder for injection. (a) Specifications. Each milliliter of...

75 FR 54018 - Implantation or Injectable Dosage Form New Animal Drugs; Florfenicol and Flunixin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

... respiratory disease (BRD) pathogens for which use of an injectable solution containing florfenicol and.... For treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella...

Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel.

PubMed

Fukui, Takaaki; Kitamura, Nobuto; Kurokawa, Takayuki; Yokota, Masashi; Kondo, Eiji; Gong, Jian Ping; Yasuda, Kazunori

2014-04-01

Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.

Destiny of autologous bone marrow-derived stromal cells implanted in the vocal fold.

PubMed

Kanemaru, Shin-ichi; Nakamura, Tatsuo; Yamashita, Masaru; Magrufov, Akhmar; Kita, Tomoko; Tamaki, Hisanobu; Tamura, Yoshihiro; Iguchi, Fuku-ichiro; Kim, Tae Soo; Kishimoto, Masanao; Omori, Koichi; Ito, Juichi

2005-12-01

The aim of this study was to investigate the destiny of implanted autologous bone marrow-derived stromal cells (BSCs) containing mesenchymal stem cells. We previously reported the successful regeneration of an injured vocal fold through implantation of BSCs in a canine model. However, the fate of the implanted BSCs was not examined. In this study, implanted BSCs were traced in order to determine the type of tissues resulting at the injected site of the vocal fold. After harvest of bone marrow from the femurs of green fluorescent transgenic mice, adherent cells were cultured and selectively amplified. By means of a fluorescence-activated cell sorter, it was confirmed that some cells were strongly positive for mesenchymal stem cell markers, including CD29, CD44, CD49e, and Sca-1. These cells were then injected into the injured vocal fold of a nude rat. Immunohistologic examination of the resected vocal folds was performed 8 weeks after treatment. The implanted cells were alive in the host tissues and showed positive expression for keratin and desmin, markers for epithelial tissue and muscle, respectively. The implanted BSCs differentiated into more than one tissue type in vivo. Cell-based tissue engineering using BSCs may improve the quality of the healing process in vocal fold injuries.

Modulating Phonation Through Alteration of Vocal Fold Medial Surface Contour

PubMed Central

Mau, Ted; Muhlestein, Joseph; Callahan, Sean; Chan, Roger W.

2012-01-01

Objectives 1. To test whether alteration of the vocal fold medial surface contour can improve phonation. 2. To demonstrate that implant material properties affect vibration even when implant is deep to the vocal fold lamina propria. Study Design Induced phonation of excised human larynges. Methods Thirteen larynges were harvested within 24 hours post-mortem. Phonation threshold pressure (PTP) and flow (PTF) were measured before and after vocal fold injections using either calcium hydroxylapatite (CaHA) or hyaluronic acid (HA). Small-volume injections (median 0.0625 mL) were targeted to the infero-medial aspect of the thyroarytenoid (TA) muscle. Implant locations were assessed histologically. Results The effect of implantation on PTP was material-dependent. CaHA tended to increase PTP, whereas HA tended to decrease PTP (Wilcoxon test P = 0.00013 for onset). In contrast, the effect of implantation on PTF was similar, with both materials tending to decrease PTF (P = 0.16 for onset). Histology confirmed implant presence in the inferior half of the vocal fold vertical thickness. Conclusions Taken together, these data suggested the implants may have altered the vocal fold medial surface contour, potentially resulting in a less convergent or more rectangular glottal geometry as a means to improve phonation. An implant with a closer viscoelastic match to vocal fold cover is desirable for this purpose, as material properties can affect vibration even when the implant is not placed within the lamina propria. This result is consistent with theoretical predictions and implies greater need for surgical precision in implant placement and care in material selection. PMID:22865592

77 FR 39390 - Implantation or Injectable Dosage Form New Animal Drugs; Maropitant; Tildipirosin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-03

...., Summit, Injectable the treatment NJ 07901. Solution. of bovine respiratory disease (BRD) in beef and non-lactating dairy cattle; and for the control of respiratory disease in beef and non- lactating dairy cattle... subcutaneous injection in the neck. (ii) Indications for use. For the treatment of bovine respiratory disease...

Self-expandable CoreValve implantation without contrast media.

PubMed

Bruschi, Giuseppe; Colombo, Paola; De Marco, Federico; Barosi, Alberto; Mauri, Silvia; Klugmann, Silvio

2016-09-01

Transcatheter aortic valve implantation has been designed to treat high-risk surgical patients affected by severe aortic stenosis, many of whom are affected by chronic kidney disease. To perform transcatheter self-expandable valve implantation, multiple contrast injections are required to monitor the procedure, so these patients are at increased risk of acute kidney injury. We described self-expandable transcatheter aortic valve implantation without contrast media in an 80-year-old man affected by severe aortic stenosis and endstage chronic kidney disease. © The Author(s) 2015.

75 FR 62468 - Implantation and Injectable Dosage Form New Animal Drugs; Ceftiofur Crystalline Free Acid

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

... swine, by intramuscular injection, for the control of swine respiratory disease (SRD) in groups of pigs... treatment of lower respiratory tract infections in horses caused by susceptible strains of Streptococcus...

Epidural catheterization with a subcutaneous injection port for the long-term administration of opioids and local anesthetics to treat zoster-associated pain -a report of two cases-

PubMed Central

Min, Bo Mi

2013-01-01

Continuous epidural analgesia has been used for decades to treat acute herpes zoster pain and to prevent postherpetic neuralgia. However, many technical problems can arise during chronic treatment with epidural medications. These complications include catheter dislodgement, infection, injection pain, leakage, and occlusion. Epidural catheter placement utilizing subcutaneous injection port implantation has gained widespread acceptance as a method to overcome such complications. The technique reduces the risk of infection, the most feared complication, compared to the use of a percutaneous epidural catheter. Herein, we present 2 cases in which the continuous thoracic epidural administration of opioids and local anesthetics through an implantable subcutaneous injection port for over 2 months successfully treated zoster-associated pain without any technique- or medication-related complications in patients with risk factors for epidural abscess. PMID:24363852

Glans Penis Augmentation Using Hyaluronic Acid Gel as an Injectable Filler

PubMed Central

Kwak, Tae Il; Kim, Je Jong

2015-01-01

Glans penis augmentation (GPA) has received little attention from experts despite the existence of a subset of patients who may be dissatisfied with a small glans or poor tumescence of the glans during erection. Recently, GPA using an injectable filler or implantation of a graft or filler has been developed. Despite a demanding injection technique and inevitable uneven undulation of the glandular surface, GPA using injectable hyaluronic acid (HA) gel is a novel and useful therapy and an effective and safe procedure for soft tissue enhancement. For long-term presence of implants, timed supplementation can be used similar to that for fascial plasty. In complications such as mucosal necrosis of the glans penis, most cases occur from the use of non-HA gel or an unpurified form and misunderstanding of the management protocol for immediate side effects. Currently, GPA using injectable HA gel is not recommended in the International Society for Sexual Medicine guideline due to possible sensory loss. In a 5-year long-term follow-up of GPA by subcutaneous injection of HA gel, the residual volume of implants decreased by 15% of the maximal glandular circumference, but was still effective for alleviating the hypersensitivity of the glans penis in premature ejaculation patients. For efficacy in premature ejaculation, selection of appropriate candidates is the most important factor for success. GPA does not harm erectile function and is less invasive and irreversible compared to dorsal neurectomy. To refine the procedure, more interest and well-designed studies are required for the establishment of the procedure. PMID:26331121

Glans Penis Augmentation Using Hyaluronic Acid Gel as an Injectable Filler.

PubMed

Moon, Du Geon; Kwak, Tae Il; Kim, Je Jong

2015-08-01

Glans penis augmentation (GPA) has received little attention from experts despite the existence of a subset of patients who may be dissatisfied with a small glans or poor tumescence of the glans during erection. Recently, GPA using an injectable filler or implantation of a graft or filler has been developed. Despite a demanding injection technique and inevitable uneven undulation of the glandular surface, GPA using injectable hyaluronic acid (HA) gel is a novel and useful therapy and an effective and safe procedure for soft tissue enhancement. For long-term presence of implants, timed supplementation can be used similar to that for fascial plasty. In complications such as mucosal necrosis of the glans penis, most cases occur from the use of non-HA gel or an unpurified form and misunderstanding of the management protocol for immediate side effects. Currently, GPA using injectable HA gel is not recommended in the International Society for Sexual Medicine guideline due to possible sensory loss. In a 5-year long-term follow-up of GPA by subcutaneous injection of HA gel, the residual volume of implants decreased by 15% of the maximal glandular circumference, but was still effective for alleviating the hypersensitivity of the glans penis in premature ejaculation patients. For efficacy in premature ejaculation, selection of appropriate candidates is the most important factor for success. GPA does not harm erectile function and is less invasive and irreversible compared to dorsal neurectomy. To refine the procedure, more interest and well-designed studies are required for the establishment of the procedure.

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

Carlson, Thomas J.; Myjak, Mitchell J.

At the request of the U.S. Army Corps of Engineers, Portland District, researchers from Pacific Northwest National Laboratory investigated the use of an application-specific integrated circuit (ASIC) to reduce the weight and volume of Juvenile Salmon Acoustic Telemetry System (JSATS) transmitters while retaining current functionality. Review of the design of current JSATS transmitters identified components that could be replaced by an ASIC while retaining the function of the current transmitter and offering opportunities to extend function if desired. ASIC design alternatives were identified that could meet transmitter weight and volume targets of 200 mg and 100 mm3. If alternatives tomore » the cylindrical batteries used in current JSATS transmitters can be identified, it could be possible to implant ASIC-based JSATS transmitters by injection rather than surgery. Using criteria for the size of fish suitable for surgical implantation of current JSATS transmitters, it was concluded that fish as small as 70 mm in length could be implanted with an ASIC-based transmitter, particularly if implantation by injection became feasible.« less

75 FR 1274 - Implantation or Injectable Dosage Form New Animal Drugs; Hyaluronate Sodium

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... safety warning for use of hyaluronate sodium injectable solution in horses. DATES: This rule is effective... human food safety warning on product labeling. The supplemental NADA is approved as of December 11, 2009...

Implantable Drug Dispenser

NASA Technical Reports Server (NTRS)

Collins, E. R. J.

1983-01-01

Drugs such as insulin are injected as needed directly into bloodstream by compact implantable dispensing unit. Two vapor cavities produce opposing forces on drug-chamber diaphragm. Heaters in cavities allow control of direction and rate of motion of bellows. Dispensing capsule fitted with coil so batteries can be recharged by induction.

75 FR 69591 - Medicaid Program; Withdrawal of Determination of Average Manufacturer Price, Multiple Source Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-15

... issue a proposed regulation addressing the Affordable Care Act provisions. Inhalation, Infusion..., infusion, instilled, implanted and injectable drugs that are not generally dispensed through retail... publish a list of drugs that meet the statutory definition of inhalation, infusion, instilled, implanted...

Impact of the shape of the implantable ports on their efficiency of flow (injection and flushing)

PubMed Central

Guiffant, Gérard; Flaud, Patrice; Durussel, Jean Jacques; Merckx, Jacques

2014-01-01

Now widely used, totally implantable venous access devices allow mid- and long-term, frequent, repeated, or continuous injection of therapeutic products by vascular, cavitary, or perineural access. The effective flushing of these devices is a key factor that ensures their long-lasting use. We present experimental results and a numerical simulation to demonstrate that the implementation of rounded edge wall cavities improves flushing efficiency. We use the same approaches to suggest that the deposit amount may be reduced by the use of rounded edge wall cavities. PMID:25258561

Prospective unmasked randomized evaluation of the iStent inject® versus two ocular hypotensive agents in patients with primary open-angle glaucoma

PubMed Central

Fea, Antonio M; Belda, Jose I; Rękas, Marek; Jünemann, Anselm; Chang, Lydia; Pablo, Luis; Voskanyan, Lilit; Katz, L Jay

2014-01-01

Purpose The purpose of this study was to compare outcomes of subjects with open-angle glaucoma (OAG) not controlled on one medication who underwent either implantation of two iStent inject® trabecular micro-bypass devices or received medical therapy consisting of a fixed combination of latanoprost/timolol. Patients and methods Of 192 subjects who qualified for the study and were enrolled, 94 were randomized to surgery with implantation of two iStent inject® devices in the treated eye and 98 to receive medical therapy. Results At the month 12 visit, 94.7% of eyes (89/94) in the stent group reported an unmedicated intraocular pressure (IOP) reduction of ≥20% versus baseline unmedicated IOP, and 91.8% of eyes (88/98) in the medical therapy group reported an IOP reduction ≥20% versus baseline unmedicated IOP. A 17.5% between-group treatment difference in favor of the iStent inject group was statistically significant (P=0.02) at the ≥50% level of IOP reduction. An IOP ≤18 mmHg was reported in 92.6% of eyes (87/94) in the iStent inject group and 89.8% of eyes (88/98) in the medical therapy group. Mean (standard deviation) IOP decreases from screening of 8.1 (2.6) mmHg and 7.3 (2.2) mmHg were reported in the iStent inject and medical therapy groups, respectively. A high safety profile was also noted in this study in both the iStent inject and medical therapy groups, as measured by stable best corrected visual acuity, cup-to-disc ratio, and adverse events. Conclusion These data show that the use of iStent inject is at least as effective as two medications, with the clinical benefit of reducing medication burden and assuring continuous treatment with full compliance to implant therapy as well as having a highly favorable safety profile. PMID:24855336

Preferences for Long-Acting Pre-Exposure Prophylaxis (PrEP), Daily Oral PrEP, or Condoms for HIV Prevention among U.S. Men Who Have Sex with Men

PubMed Central

Greene, George J.; Swann, Greg; Fought, Angela J.; Carballo-Diéguez, Alex; Hope, Thomas J.; Kiser, Patrick F.; Mustanski, Brian; D’Aquila, Richard T.

2016-01-01

HIV prevention method preferences were evaluated among 512 U.S. men who have sex with men (MSM; median age: 22 years). Approximately 90% consistently preferred one option across pairwise comparisons of condoms, daily oral pre-exposure prophylaxis (PrEP), and long-acting PrEP delivered via either an injectable or one of two types of PrEP implants differing in visibility. Condoms were most frequently preferred (33.8%), followed by non-visible implants (21.5%), and oral PrEP (17.0%); HIV risk was reported by more choosing implants. In a follow-up question comparing the four PrEP options only, daily oral pills and non-visible implants were most frequently preferred (35.5% and 34.3%, respectively), followed by injections (25.2%) and visible implants (4.3%). An inductive, open-coding approach determined that convenience, duration of protection, and privacy were the most commonly cited reasons for a PrEP method choice, and associated with self-report of HIV risk. Tailoring PrEP product development to privacy and other concerns important to those at highest HIV risk may improve HIV prevention. PMID:27770215

(68)Ga-DOTA-Siglec-9 PET/CT imaging of peri-implant tissue responses and staphylococcal infections.

PubMed

Ahtinen, Helena; Kulkova, Julia; Lindholm, Laura; Eerola, Erkki; Hakanen, Antti J; Moritz, Niko; Söderström, Mirva; Saanijoki, Tiina; Jalkanen, Sirpa; Roivainen, Anne; Aro, Hannu T

2014-01-01

Staphylococcus epidermidis (S. epidermidis) has emerged as one of the leading pathogens of biomaterial-related infections. Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial molecule controlling extravasation of leukocytes. Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand of VAP-1. We hypothesized that (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated Siglec-9 motif containing peptide ((68)Ga-DOTA-Siglec-9) could detect inflammatory response due to S. epidermidis peri-implant infection by positron emission tomography (PET). Thirty Sprague-Dawley rats were randomized into three groups. A sterile catheter was implanted into the medullary canal of the left tibia. In groups 1 and 2, the implantation was followed by peri-implant injection of S. epidermidis or Staphylococcus aureus (S. aureus) with adjunct injections of aqueous sodium morrhuate. In group 3, sterile saline was injected instead of bacteria and no aqueous sodium morrhuate was used. At 2 weeks after operation, (68)Ga-DOTA-Siglec-9 PET coupled with computed tomography (CT) was performed with the measurement of the standardized uptake value (SUV). The presence of the implant-related infection was verified by microbiological analysis, imaging with fluorescence microscope, and histology. The in vivo PET results were verified by ex vivo measurements by gamma counter. In group 3, the tibias with implanted sterile catheters showed an increased local uptake of (68)Ga-DOTA-Siglec-9 compared with the intact contralateral bones (SUVratio +29.5%). (68)Ga-DOTA-Siglec-9 PET detected inflammation induced by S. epidermidis and S. aureus catheter-related bone infections (SUVratio +58.1% and +41.7%, respectively). The tracer uptake was significantly higher in the S. epidermidis group than in group 3 without bacterial inoculation, but the difference between S. epidermidis and S. aureus groups was not statistically significant. The difference between the S. aureus group and group 3 was neither statistically significant. PET/CT imaging with novel (68)Ga-DOTA-Siglec-9 tracer was able to detect inflammatory tissue response induced by catheter implantation and staphylococcal infections.

68Ga-DOTA-Siglec-9 PET/CT imaging of peri-implant tissue responses and staphylococcal infections

PubMed Central

2014-01-01

Background Staphylococcus epidermidis (S. epidermidis) has emerged as one of the leading pathogens of biomaterial-related infections. Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial molecule controlling extravasation of leukocytes. Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand of VAP-1. We hypothesized that 68Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated Siglec-9 motif containing peptide (68Ga-DOTA-Siglec-9) could detect inflammatory response due to S. epidermidis peri-implant infection by positron emission tomography (PET). Methods Thirty Sprague-Dawley rats were randomized into three groups. A sterile catheter was implanted into the medullary canal of the left tibia. In groups 1 and 2, the implantation was followed by peri-implant injection of S. epidermidis or Staphylococcus aureus (S. aureus) with adjunct injections of aqueous sodium morrhuate. In group 3, sterile saline was injected instead of bacteria and no aqueous sodium morrhuate was used. At 2 weeks after operation, 68Ga-DOTA-Siglec-9 PET coupled with computed tomography (CT) was performed with the measurement of the standardized uptake value (SUV). The presence of the implant-related infection was verified by microbiological analysis, imaging with fluorescence microscope, and histology. The in vivo PET results were verified by ex vivo measurements by gamma counter. Results In group 3, the tibias with implanted sterile catheters showed an increased local uptake of 68Ga-DOTA-Siglec-9 compared with the intact contralateral bones (SUVratio +29.5%). 68Ga-DOTA-Siglec-9 PET detected inflammation induced by S. epidermidis and S. aureus catheter-related bone infections (SUVratio +58.1% and +41.7%, respectively). The tracer uptake was significantly higher in the S. epidermidis group than in group 3 without bacterial inoculation, but the difference between S. epidermidis and S. aureus groups was not statistically significant. The difference between the S. aureus group and group 3 was neither statistically significant. Conclusion PET/CT imaging with novel 68Ga-DOTA-Siglec-9 tracer was able to detect inflammatory tissue response induced by catheter implantation and staphylococcal infections. PMID:25520903

Transdermal Photopolymerization for Minimally Invasive Implantation

NASA Astrophysics Data System (ADS)

Elisseeff, J.; Anseth, K.; Sims, D.; McIntosh, W.; Randolph, M.; Langer, R.

1999-03-01

Photopolymerizations are widely used in medicine to create polymer networks for use in applications such as bone restorations and coatings for artificial implants. These photopolymerizations occur by directly exposing materials to light in "open" environments such as the oral cavity or during invasive procedures such as surgery. We hypothesized that light, which penetrates tissue including skin, could cause a photopolymerization indirectly. Liquid materials then could be injected s.c. and solidified by exposing the exterior surface of the skin to light. To test this hypothesis, the penetration of UVA and visible light through skin was studied. Modeling predicted the feasibility of transdermal polymerization with only 2 min of light exposure required to photopolymerize an implant underneath human skin. To establish the validity of these modeling studies, transdermal photopolymerization first was applied to tissue engineering by using "injectable" cartilage as a model system. Polymer/chondrocyte constructs were injected s.c. and transdermally photopolymerized. Implants harvested at 2, 4, and 7 weeks demonstrated collagen and proteoglycan production and histology with tissue structure comparable to native neocartilage. To further examine this phenomenon and test the applicability of transdermal photopolymerization for drug release devices, albumin, a model protein, was released for 1 week from photopolymerized hydrogels. With further study, transdermal photpolymerization potentially could be used to create a variety of new, minimally invasive surgical procedures in applications ranging from plastic and orthopedic surgery to tissue engineering and drug delivery.

Applying data mining techniques for increasing implantation rate by selecting best sperms for intra-cytoplasmic sperm injection treatment.

PubMed

Mirroshandel, Seyed Abolghasem; Ghasemian, Fatemeh; Monji-Azad, Sara

2016-12-01

Aspiration of a good-quality sperm during intracytoplasmic sperm injection (ICSI) is one of the main concerns. Understanding the influence of individual sperm morphology on fertilization, embryo quality, and pregnancy probability is one of the most important subjects in male factor infertility. Embryologists need to decide the best sperm for injection in real time during ICSI cycle. Our objective is to predict the quality of zygote, embryo, and implantation outcome before injection of each sperm in an ICSI cycle for male factor infertility with the aim of providing a decision support system on the sperm selection. The information was collected from 219 patients with male factor infertility at the infertility therapy center of Alzahra hospital in Rasht from 2012 through 2014. The prepared dataset included the quality of zygote, embryo, and implantation outcome of 1544 injected sperms into the related oocytes. In our study, embryo transfer was performed at day 3. Each sperm was represented with thirteen clinical features. Data preprocessing was the first step in the proposed data mining algorithm. After applying more than 30 classifiers, 9 successful classifiers were selected and evaluated by 10-fold cross validation technique using precision, recall, F1, and AUC measures. Another important experiment was measuring the effect of each feature in prediction process. In zygote and embryo quality prediction, IBK and RandomCommittee models provided 79.2% and 83.8% F1, respectively. In implantation outcome prediction, KStar model achieved 95.9% F1, which is even better than prediction of human experts. All these predictions can be done in real time. A machine learning-based decision support system would be helpful in sperm selection phase of ICSI cycle to improve the success rate of ICSI treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Neural progenitor cell implants modulate vascular endothelial growth factor and brain-derived neurotrophic factor expression in rat axotomized neurons.

PubMed

Talaverón, Rocío; Matarredona, Esperanza R; de la Cruz, Rosa R; Pastor, Angel M

2013-01-01

Axotomy of central neurons leads to functional and structural alterations which largely revert when neural progenitor cells (NPCs) are implanted in the lesion site. The new microenvironment created by NPCs in the host tissue might modulate in the damaged neurons the expression of a high variety of molecules with relevant roles in the repair mechanisms, including neurotrophic factors. In the present work, we aimed to analyze changes in neurotrophic factor expression in axotomized neurons induced by NPC implants. For this purpose, we performed immunofluorescence followed by confocal microscopy analysis for the detection of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF) on brainstem sections from rats with axotomy of abducens internuclear neurons that received NPC implants (implanted group) or vehicle injections (axotomized group) in the lesion site. Control abducens internuclear neurons were strongly immunoreactive to VEGF and BDNF but showed a weak staining for NT-3 and NGF. Comparisons between groups revealed that lesioned neurons from animals that received NPC implants showed a significant increase in VEGF content with respect to animals receiving vehicle injections. However, the immunoreactivity for BDNF, which was increased in the axotomized group as compared to control, was not modified in the implanted group. The modifications induced by NPC implants on VEGF and BDNF content were specific for the population of axotomized abducens internuclear neurons since the neighboring abducens motoneurons were not affected. Similar levels of NT-3 and NGF immunolabeling were obtained in injured neurons from axotomized and implanted animals. Among all the analyzed neurotrophic factors, only VEGF was expressed by the implanted cells in the lesion site. Our results point to a role of NPC implants in the modulation of neurotrophic factor expression by lesioned central neurons, which might contribute to the restorative effects of these implants.

Dexamethasone intravitreal implant (Ozurdex) for the treatment of pediatric uveitis.

PubMed

Bratton, Monica L; He, Yu-Guang; Weakley, David R

2014-04-01

To report our experience using Ozurdex (Allergan, Irvine, CA), a biodegradable intravitreal implant containing of 0.7 mg of dexamethasone approved for use in adults with noninfectious uveitis in adults, in the treatment of pediatric uveitis. The medical records of consecutive patients with noninfectious posterior uveitis who were unresponsive to standard treatment and subsequently received the Ozurdex implant from March 2011 to March 2013 were retrospectively reviewed. A total of 14 eyes of 11 patients (mean age, 10.1 years; range 4-12) received 22 Ozurdex implants during the study period. Of the 11 patients, 7 had idiopathic intermediate or posterior uveitis, 1 had sympathetic ophthalmia, 2 had juvenile idiopathic arthritis, and 1 had sarcoidosis. All patients were uncontrolled with standard treatment, including topical or sub-Tenon's or systemic corticosteriods and/or immune-modulation. Visual acuity improved after Ozurdex implant in 5 of 8 patients (63%). Intraocular inflammation was controlled or improved after 17 of 22 of implants (12 eyes [77%]). The frequency of topical corticosteroids was decreased and/or discontinued after 18 of 22 implants (12 eyes [82%]). Complications included implant migration into the anterior chamber (4 aphakic eyes), increased intraocular pressure (5 eyes), and progression of a preexisting cataract (1 eye). The uveitis reoccurred in 57% of eyes at 4.3 months (2-7 months) after injection. The Ozurdex implant in combination with systemic immunomodulatory therapy resulted in improved visual acuity, control of intraocular inflammation, and a decrease in corticosteroid use. In the majority of eyes the uveitis reoccurred around 4 months after injection. The adverse events in our study are similar to those identified in adult studies. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

A Comparison of Gene Expression of Decorin and MMP13 in Hypertrophic Scars Treated With Calcium Channel Blocker, Steroid, and Interferon: A Human-Scar-Carrying Animal Model Study.

PubMed

Yang, Shih-Yi; Yang, Jui-Yung; Hsiao, Yen-Chang; Chuang, Shiow-Shuh

2017-01-01

The formation of hypertrophic scaring (HSc) is an abnormal wound-healing response. In a previous study, an animal model with human scar tissue implanted into nude mice (BALB/c) has been successfully established. The effects of verapamil as well as combination therapy with verapamil and kenacort have been studied and compared. To treat persistent hypertrophic scars, local injection of drugs composed of steroids, calcium channel blockers (CCBs), and interferon might be a good method. What is the best dose of the regimen and what are the mechanisms are also a worthwhile study. Scar specimens were harvested from patients with HSc or Keloid resulting from burn injury, and then implanted to BALB/c-nu nude mice for 4 weeks. Before implantation, the specimen was either injected with or without drugs such as steroids (kenacort), CCBs (verapamil), and interferons (INFα2b), respectively. After the removal of implants, quantitative gene expressions of decorin and collagenase (MMP13) were measured using a real-time polymerase chain reaction to detect their mRNAs. Two way-ANOVA and Post Hoc were used for statistical analysis using the software SPSS 15.0. All drug-treated groups increased the expressions of decorin and MMP13 in comparison with those in noninjected group (p < .001) in a dose-dependent manner. Comparing equal amounts of individual drugs, gene expression of decorin was increased with increasing injection amount, and the best result in low amount of injection (0.02 mL of each) was shown in the group injected with INFα2b followed by kenacort and verapamil. However, the results were changed while injection amount was up to 0.04 mL and the strongest decorin gene expression was found in kenacort injection. Regarding MMP-13 expression, low-amount injection (0.02 mL) of INFα2b has strongest gene expression followed by kenacort and verapamil, but in the large-amount regimes (0.04 mL), verapamil had strongest gene expression followed by INFα2b and kenacort. This study showed that the kenacort, verapamil, and INFα2b all inhibited HSc in a dose-dependent manner through the evidence of gene expression of decorin and MMP13. In comparison with the injections between small amounts of drugs, INFα2b potentiated the strongest decorin and MMP13 expression. On the contrary, among the large-amount injection regimes, kenacrot was more effective on decorin expression as verapamil to MMP13 expression. To decrease side effects from the drugs and produce promising results for the clinical practice, it is suggested to maintain the dose of INFα2b along with an increased dose of verapamil for HSc improvement.

21 CFR 522.1155 - Imidocarb powder for injection.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Staff, Veterinary Services, Animal and Plant Health Inspection Service, U.S. Department of Agriculture... 522.1155 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS...

21 CFR 522.1468 - Naproxen for injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1468.... Five milligrams per kilogram of body weight intravenously followed by maintenance oral therapy of 10...

75 FR 20268 - Implantation or Injectable Dosage Form New Animal Drugs; Change of Sponsor; Propofol

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-19

... use in dogs and cats--(1) Amount. The drug is administered by intravenous injection as follows: (i) Dogs. For induction of general anesthesia without the use of preanesthetics the dosage is 5.5 to 7.0 mg...

Intrauterine administration of recombinant human chorionic gonadotropin before embryo transfer on outcome of in vitro fertilization/ intracytoplasmic sperm injection: A randomized clinical trial

PubMed Central

Zarei, Afsoon; Parsanezhad, Mohammad Ebrahim; Younesi, Masoumeh; Alborzi, Saeed; Zolghadri, Jaleh; Samsami, Alamtaj; Amooee, Sedigheh; Aramesh, Shahintaj

2014-01-01

Background: The direct effect of hCG on the human endometrium was studied several times. Objective: The objectives of this study were to evaluate the effectiveness of intrauterine injection of recombinant human chorionic gonadotropin (rhCG) before embryo transfer (ET). Materials and Methods: In this randomized placebo-controlled clinical trial, a total number of 182 infertile patients undergoing their first in vitro fertilization/ intracytoplasmic sperm injection (IVF-ICSI) cycles were randomly assigned to receive 250μg intrauterine rhCG (n=84) or placebo (n=98) before ET. The implantation and pregnancy rates were compared between groups. Results: Patients who received intrauterine rhCG before ET had significantly higher implantation (36.9% vs. 22.4%; p=0.035), clinical pregnancy rates (34.5% vs. 20.4%; p=0.044) and ongoing pregnancy rate (32.1% vs. 18.4%; p=0.032) when compared to those who received placebo. The abortion (2.4% vs. 2.0%; p=0.929) and ectopic pregnancy rates (1.2% vs. 1.0%; p=0.976) were comparable between groups of rhCG and placebo, respectively. Conclusion: Intrauterine injection of 250μg of rhCG before ET significantly improves the implantation and pregnancy rates in IVF/ICSI cycles. Registration ID in IRCT: IRCT2012121711790N1 This article extracted from fellowship course thesis. (Masoumeh Younesi) PMID:24799855

“Finding a Voice”: Imaging Features after Phonosurgical Procedures for Vocal Fold Paralysis

PubMed Central

Vachha, B.A.; Ginat, D.T.; Mallur, P.; Cunnane, M.; Moonis, G.

2017-01-01

SUMMARY Altered communication (hoarseness, dysphonia, and breathy voice) that can result from vocal fold paralysis, secondary to numerous etiologies, may be amenable to surgical restoration. In this article, both traditional and cutting-edge phonosurgical procedures targeting the symptoms resulting from vocal fold paralysis are reviewed, with emphasis on the characteristic imaging appearances of various injectable materials, implants, and augmentation procedures used in the treatment of vocal fold paralysis. In addition, complications of injection laryngoplasty and medialization laryngoplasty are illustrated. Familiarity with the expected imaging changes following treatment of vocal fold paralysis may prevent the misinterpretation of posttreatment changes as pathology. Identifying common complications related to injection laryngoplasty and localization of displaced implants is crucial in determining specific management in patients who have undergone phonosurgical procedures for the management of vocal fold paralysis. PMID:27173367

Inflammasome components ASC and AIM2 modulate the acute phase of biomaterial implant-induced foreign body responses

PubMed Central

Christo, Susan N.; Diener, Kerrilyn R.; Manavis, Jim; Grimbaldeston, Michele A.; Bachhuka, Akash; Vasilev, Krasimir; Hayball, John D.

2016-01-01

Detailing the inflammatory mechanisms of biomaterial-implant induced foreign body responses (FBR) has implications for revealing targetable pathways that may reduce leukocyte activation and fibrotic encapsulation of the implant. We have adapted a model of poly(methylmethacrylate) (PMMA) bead injection to perform an assessment of the mechanistic role of the ASC-dependent inflammasome in this process. We first demonstrate that ASC−/− mice subjected to PMMA bead injections had reduced cell infiltration and altered collagen deposition, suggesting a role for the inflammasome in the FBR. We next investigated the NLRP3 and AIM2 sensors because of their known contributions in recognising damaged and apoptotic cells. We found that NLRP3 was dispensable for the fibrotic encapsulation; however AIM2 expression influenced leukocyte infiltration and controlled collagen deposition, suggesting a previously unexplored link between AIM2 and biomaterial-induced FBR. PMID:26860464

Inflammasome components ASC and AIM2 modulate the acute phase of biomaterial implant-induced foreign body responses.

PubMed

Christo, Susan N; Diener, Kerrilyn R; Manavis, Jim; Grimbaldeston, Michele A; Bachhuka, Akash; Vasilev, Krasimir; Hayball, John D

2016-02-10

Detailing the inflammatory mechanisms of biomaterial-implant induced foreign body responses (FBR) has implications for revealing targetable pathways that may reduce leukocyte activation and fibrotic encapsulation of the implant. We have adapted a model of poly(methylmethacrylate) (PMMA) bead injection to perform an assessment of the mechanistic role of the ASC-dependent inflammasome in this process. We first demonstrate that ASC(-/-) mice subjected to PMMA bead injections had reduced cell infiltration and altered collagen deposition, suggesting a role for the inflammasome in the FBR. We next investigated the NLRP3 and AIM2 sensors because of their known contributions in recognising damaged and apoptotic cells. We found that NLRP3 was dispensable for the fibrotic encapsulation; however AIM2 expression influenced leukocyte infiltration and controlled collagen deposition, suggesting a previously unexplored link between AIM2 and biomaterial-induced FBR.

21 CFR 522.311 - Cefovecin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.311 Cefovecin. (a.... A second subcutaneous injection of 3.6 mg/lb (8 mg/kg) may be administered if response to therapy is...

Progestin-based contraceptive on the same day as medical abortion.

PubMed

Park, Jeanna; Robinson, Nuriya; Wessels, Ursula; Turner, James; Geller, Stacie

2016-05-01

To determine the success rate of medical abortion when a progestin-based contraceptive-either an etonogestrel implant or depot medroxyprogesterone acetate (DMPA) injection-is given on the same day as mifepristone for medical abortion. In a retrospective chart review, data were assessed for women aged 15-49years who underwent medical abortion (≤63days of pregnancy) at two hospitals in KwaZulu Natal, South Africa, between August 2013 and July 2014. The women were given oral mifepristone (200mg) and buccal misoprostol (800μg), and received an etonogestrel implant or DMPA injection on the same day as mifepristone. The primary outcome was the success rate of medical abortion. Comparative data were obtained through a PubMed search. A total of 89 women were included. Complete termination was achieved in 87 (98%, 95% confidence interval 95%-100%) women. This success rate is similar to that reported in a previous systematic review of the rate of medical abortion success without progestin contraceptive administration (94.8%). Administration of a progestin-based contraceptive such as an etonogestrel implant or DMPA injection on the same day as mifepristone for medical abortion did not alter the success rates. Published by Elsevier Ireland Ltd.

Single Dexamethasone Intravitreal Implant in the Treatment of Noninfectious Uveitis.

PubMed

Frère, Ariane; Caspers, Laure; Makhoul, Dorine; Judice, Lia; Postelmans, Laurence; Janssens, Xavier; Lefebvre, Pierre; Mélot, Christian; Willermain, François

2017-05-01

To investigate the effect of a single intravitreal dexamethasone implant (IVT-DI; Ozurdex; Allergan, Inc.) on visual acuity, macular thickness, and intraocular pressure (IOP) in active noninfectious uveitis. Medical records of patients with noninfectious active uveitis treated by IVT-DIs were retrospectively reviewed. Uveitis etiologies, treatment indications, best corrected visual acuity (BCVA), central retinal thickness measured by ocular coherence tomography, IOP, and systemic, local, and topical treatments were collected. Parameters were analyzed before the injection of the implant, after 1.5 ± 0.8 months and 4.4 ± 0.9 months for the BCVA, after 2 ± 1.3 months and 4.6 ± 1.3 months for the ocular coherence tomography, and after 1.3 ± 0.7 months and 4.4 ± 1 months for the IOP. We included 14 patients (20 eyes, 20 implant injections) with cystoid macular edema (78%), vasculitis (7%), choroiditis (7%), and vasculitis associated with choroiditis (7%). Before the injection, mean visual acuity was 0.4 ± 0.5 logMAR (logarithm of the minimum angle of resolution) that improved to 0.3 ± 0.5 logMAR (P = 0.0002) after 1.5 ± 0.8 months and to 0.3 ± 0.5 logMAR (P = 0.005) after 4.4 ± 0.9 months. A statistically significant decrease of macular thickness was observed both at 2 ± 1.3 months and at 4.6 ± 1.3 months after IVT-DI. Mean IOP was 16 ± 5 mmHg before injections, 18 ± 6 mmHg (P = 0.13) at 1.3 ± 0.7 months, and 15 ± 4 mmHg (P = 0.65) at 4.4 ± 1 months. By Kaplan-Meier analysis, we found that after 3.3 months, 17% of the eyes still present a BCVA amelioration ≥0.3 logMAR. In our patients with active noninfectious uveitis, injection of a first single dexamethasone implant was found to improve visual acuity and decrease macular thickness without significant increase of IOP, although the effect seems limited in time.

Kinetic study of bone ingrowth and ceramic resorption associated with the implantation of different injectable calcium-phosphate bone substitutes.

PubMed

Gauthier, O; Bouler, J M; Weiss, P; Bosco, J; Daculsi, G; Aguado, E

1999-10-01

This study investigated the in vivo performance of two composite injectable bone substitutes (IBS), each with different calcium-phosphate particles granulometries [40-80 (IBS 40-80) and 200-500 microm (IBS 200-500)]. These biomaterials were obtained by associating a biphasic calcium-phosphate (BCP) ceramic mineral phase with a 3% aqueous solution of a cellulosic polymer (hydroxy-propyl-methyl-cellulose). Both materials were injected for periods of 2, 3, 8, or 12 weeks into bone defects at the distal end of rabbit femurs. Quantitative results on new bone formation, BCP resorption, and staining for tartrate-resistant acid phosphatase (TRAP) activity were studied for statistical purposes. Measurements with scanning electron microscopy and image analysis showed that the final rates of newly formed bone were similar for both tested IBS after 12 weeks of implantation. Bone colonization occurred more extensively during early implantation times for IBS 40-80 than for IBS 200-500. For the latter, BCP degradation occurred regularly throughout the implantation period, whereas it was very intensive during the first 2 weeks for IBS 40-80. Positive TRAP-stained degradation cells were significantly more numerous for IBS 40-80 than for IBS 200-500 regardless of implantation time. With the granulometry of either mineral phase, both tested IBS supported extensive bone colonization, which was greater than that previously reported for an equivalent block of macroporous BCP. The resorption-bone substitution process seemed to occur earlier and faster for IBS 40-80 than for IBS 200-500. Both tested IBS expressed similar biological efficiency, with conserved in vivo bioactivity and bone-filling ability. Copyright 1999 John Wiley & Sons, Inc.

Short-term implantation effects of a DCPD-based calcium phosphate cement.

PubMed

Frayssinet, P; Gineste, L; Conte, P; Fages, J; Rouquet, N

1998-06-01

Calcium phosphate cements can be handled in paste form and set in a wet medium after precipitation of calcium phosphate crystals in the implantation site. Depending on the products entering into the chemical reaction leading to the precipitation of calcium phosphates, different phases can be obtained with different mechanical properties, setting times and injectability. We tested a cement composed of a powder, containing beta-tricalcium phosphate (beta-TCP) and sodium pyrophosphate mixed with a solution of phosphoric and sulphuric acids. The cement set under a dicalcium phosphate dihydrate (DCPD)-based matrix containing beta-TCP particles. This was injected with a syringe into a defect drilled in rabbit condyles, the control being an identical defect left empty in the opposite condyle. The condyles were analysed histologically 2, 6 and 18 weeks after implantation. After injection into the bone defect the cement set and formed a porous calcium phosphate structure. Two different calcium phosphate phases with different solubility rates could be identified by scanning electron microscopy (SEM) observation. The less-soluble fragments could be degraded by cell phagocytosis in cell compartments of low pH or integrated in the newly formed bone matrix. The degradation rate of the material was relatively high but compatible with the ingrowth of bone trabeculae within the resorbing material. The ossification process was different from the creeping substitution occurring at the ceramic contact. Bone did not form directly at the cement surface following the differentiation of osteoblasts at the material surface. The trabeculae came to the material surface from the edges of the implantation site. Bone formation in the implantation site was significantly higher than in the control region during the first week of implantation. In conclusion, this material set in situ was well tolerated, inducing a mild foreign-body reaction, which did not impair its replacement by newly formed bone within a few weeks.

Hypercalcemia in a bodybuilder with cosmetic silicone injections.

PubMed

Hamadeh, Majdi; Fares, Jawad; Maatouk, Khalil; Darwish, Mohamad

2018-04-13

Granulomatous hypercalcemia due to silicone injections is a rare disease with scarce literature. We present a case of a 35-year-old Caucasian male bodybuilder with multiple silicone injections in his upper extremities who developed hypercalcemia and urinary symptoms. He necessitated two sessions of dialysis. A biopsy of the upper arm showed granulomatous tissue. Corticosteroids were administered to relieve symptoms and reverse laboratory abnormalities. Silicone-induced hypercalcemia should be on high alert because of the increasing trend of body contour enhancements with injections, implants and fillers.

Preferences for Long-Acting Pre-exposure Prophylaxis (PrEP), Daily Oral PrEP, or Condoms for HIV Prevention Among U.S. Men Who Have Sex with Men.

PubMed

Greene, George J; Swann, Greg; Fought, Angela J; Carballo-Diéguez, Alex; Hope, Thomas J; Kiser, Patrick F; Mustanski, Brian; D'Aquila, Richard T

2017-05-01

HIV prevention method preferences were evaluated among 512 U.S. men who have sex with men (MSM; median age: 22 years). Approximately 90 % consistently preferred one option across pairwise comparisons of condoms, daily oral pre-exposure prophylaxis (PrEP), and long-acting PrEP delivered via either an injectable or one of two types of PrEP implants differing in visibility. Condoms were most frequently preferred (33.8 %), followed by non-visible implants (21.5 %), and oral PrEP (17.0 %); HIV risk was reported by more choosing implants. In a follow-up question comparing the four PrEP options only, daily oral pills and non-visible implants were most frequently preferred (35.5 and 34.3 %, respectively), followed by injections (25.2 %) and visible implants (4.3 %). An inductive, open-coding approach determined that convenience, duration of protection, and privacy were the most commonly cited reasons for a PrEP method choice, and associated with self-report of HIV risk. Tailoring PrEP product development to privacy and other concerns important to those at highest HIV risk may improve HIV prevention.

IN VIVO MEASUREMENT OF PHENYLGLUCUCURONIDE IN RAINBOW TROUT BY ON-LINE INJECTION MICRODIALYSIS

EPA Science Inventory

Phenylglucuronide (PG) was measured in vivo in arterial blood of rainbow trout using on-line injection microdialysis. A microdialysis probe was surgically implanted in the dorsal aorta of spinally-transected trout. The trout were dosed continuously with PG for 24 h using a ventra...

21 CFR 522.2470 - Tiletamine hydrochloride and zolazepam hydrochloride for injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Tiletamine hydrochloride and zolazepam hydrochloride for injection. 522.2470 Section 522.2470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR...

21 CFR 522.84 - Beta-aminopropionitrile fumarate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 522.84 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.... Do not use in horses with dermal irritation or open skin lesions in the injection area. Do not...

21 CFR 522.2474 - Tolazoline hydrochloride injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Section 522.2474 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... a general anesthetic. This drug is for use in horses only and not for use in food-producing animals...

21 CFR 522.2474 - Tolazoline hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 522.2474 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... a general anesthetic. This drug is for use in horses only and not for use in food-producing animals...

21 CFR 522.84 - Beta-aminopropionitrile fumarate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 522.84 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.... Do not use in horses with dermal irritation or open skin lesions in the injection area. Do not...

21 CFR 522.2474 - Tolazoline hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Section 522.2474 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... a general anesthetic. This drug is for use in horses only and not for use in food-producing animals...

21 CFR 522.84 - Beta-aminopropionitrile fumarate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 522.84 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.... Do not use in horses with dermal irritation or open skin lesions in the injection area. Do not...

21 CFR 522.2474 - Tolazoline hydrochloride injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Section 522.2474 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... a general anesthetic. This drug is for use in horses only and not for use in food-producing animals...

21 CFR 522.300 - Carfentanil citrate injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522... effect, use 7 milligrams of diprenorphine for each milligram of carefentanil citrate, given intravenously... animals intended for food. Do not use 30 days before or during hunting season. Do not use in animals that...

76 FR 57905 - Implantation or Injectable Dosage Form New Animal Drugs; Ivermectin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... solution for treatment and control of various internal and external parasites in cattle, swine, reindeer...: John K. Harshman, Center for Veterinary Medicine (HFV-170), Food and Drug Administration, 7500 Standish... of BIMECTIN (ivermectin) Injection for Cattle and Swine for treatment and control of various internal...

75 FR 4692 - Implantation or Injectable Dosage Form New Animal Drugs; Ceftiofur Crystalline Free Acid

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

... suspension for the treatment of lower respiratory tract infections in horses. DATES: This rule is effective... ceftiofur crystalline free acid injectable suspension for the treatment of lower respiratory tract... of lower respiratory tract infections in horses caused by susceptible strains of Streptococcus equi...

75 FR 22524 - Implantation or Injectable Dosage Form New Animal Drugs; Butorphanol

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 [Docket No... application (ANADA) filed by Modern Veterinary Therapeutics, LLC. The ANADA provides for use of an injectable..., 2010. FOR FURTHER INFORMATION CONTACT: John K. Harshman, Center for Veterinary Medicine (HFV-170), Food...

75 FR 59610 - Implantation and Injectable Dosage Form New Animal Drugs; Firocoxib

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 [Docket No...) filed by Merial Ltd. The NADA provides for the veterinary prescription use of firocoxib injectable... Veterinary Medicine (HFV-110), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-276...

21 CFR 522.650 - Dihydrostreptomycin sulfate injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... 055529 in § 510.600(c) of this chapter. (c) National Academy of Sciences/National Research Council (NAS... dihydrostreptomycin resistant organisms. Discontinue use 30 days before slaughter for food. Not for use in animals...

21 CFR 522.650 - Dihydrostreptomycin sulfate injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... 055529 in § 510.600(c) of this chapter. (c) National Academy of Sciences/National Research Council (NAS... dihydrostreptomycin resistant organisms. Discontinue use 30 days before slaughter for food. Not for use in animals...

21 CFR 522.480 - Repository corticotropin injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... refrigerated. With prolonged use supplement daily diet with potassium chloride at one gram for small animals and from 5 to 10 grams for large animals. (4) Conditions of use. (i) It is used as an intramuscular or...

21 CFR 522.480 - Repository corticotropin injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... refrigerated. With prolonged use supplement daily diet with potassium chloride at one gram for small animals and from 5 to 10 grams for large animals. (4) Conditions of use. (i) It is used as an intramuscular or...

Elimination of carbon vacancies in 4H-SiC epi-layers by near-surface ion implantation: Influence of the ion species

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

Ayedh, H. M.; Svensson, B. G.; Hallén, A.

The carbon vacancy (V{sub C}) is a prevailing point defect in high-purity 4H-SiC epitaxial layers, and it plays a decisive role in controlling the charge carrier lifetime. One concept of reducing the V{sub C}-concentration is based on carbon self-ion implantation in a near surface layer followed by thermal annealing. This leads to injection of carbon interstitials (C{sub i}'s) and annihilation of V{sub C}'s in the epi-layer “bulk”. Here, we show that the excess of C atoms introduced by the self-ion implantation plays a negligible role in the V{sub C} annihilation. Actually, employing normalized implantation conditions with respect to displaced Cmore » atoms, other heavier ions like Al and Si are found to be more efficient in annihilating V{sub C}'s. Concentrations of V{sub C} below ∼2 × 10{sup 11} cm{sup −3} can be reached already after annealing at 1400 °C, as monitored by deep-level transient spectroscopy. This corresponds to a reduction in the V{sub C}-concentration by about a factor of 40 relative to the as-grown state of the epi-layers studied. The negligible role of the implanted species itself can be understood from simulation results showing that the concentration of displaced C atoms exceeds the concentration of implanted species by two to three orders of magnitude. The higher efficiency for Al and Si ions is attributed to the generation of collision cascades with a sufficiently high energy density to promote C{sub i}-clustering and reduce dynamic defect annealing. These C{sub i}-related clusters will subsequently dissolve during the post-implant annealing giving rise to enhanced C{sub i} injection. However, at annealing temperatures above 1500 °C, thermodynamic equilibrium conditions start to apply for the V{sub C}-concentration, which limit the net effect of the C{sub i} injection, and a competition between the two processes occurs.« less

In-situ photopolymerization and monitoring device for controlled shaping of tissue fillers, replacements, or implants

NASA Astrophysics Data System (ADS)

Schmocker, Andreas M.; Khoushabi, Azadeh; Bourban, Pierre-Etienne; Schizas, Constantin; Pioletti, Dominique; Moser, Christophe

2015-03-01

Photopolymerization is a common tool to harden materials initially in a liquid state. A surgeon can directly trigger the solidification of a dental implant or a bone or tissue filler simply by illumination. Traditionally, photopolymerization has been used mainly in dentistry. Over the last decade advances in material development including a wide range of biocompatible gel- and cement-systems open up a new avenue for in-situ photopolymerization. However, at the device level, surgical endoscopic probes are required. We present a miniaturized light probe where a photoactive material can be 1) mixed, pressurized and injected 2) photopolymerized or photoactivated and 3) monitored during the chemical reaction. The device enables surgeries to be conducted through a hole smaller than 1 mm in diameter. Beside basic injection mechanics, the tool consists of an optical fiber guiding the light required for photopolymerization and for chemical analysis. Combining photorheology and fluorescence spectroscopy, the current state of the photopolymerization is inferred and monitored in real time. Biocompatible and highly tuneable Poly-Ethylene-Glycol (PEG) hydrogels were used as the injection material. The device was tested on a model for intervertebral disc replacement. Gels were successfully implanted into a bovine caudal model and mechanically tested in-vitro during two weeks. The photopolymerized gel was evaluated at the tissue level (adherence and mechanical properties of the implant), at the cellular level (biocompatibility and cytotoxicity) and ergonomic level (sterilization procedure and feasibility study). This paper covers the monitoring aspect of the device.

The clinical outcomes of surgical management of anterior chamber migration of a dexamethasone implant (Ozurdex®).

PubMed

Kang, Hyunseung; Lee, Min Woo; Byeon, Suk Ho; Koh, Hyoung Jun; Lee, Sung Chul; Kim, Min

2017-09-01

Our purpose was to describe the clinical course, and individualized management approaches, of patients with migration of a dexamethasone implant into the anterior chamber. This was a retrospective review of four patients with seven episodes of anterior chamber migration of a dexamethasone implant. After 924 intravitreal dexamethasone injections, anterior migration of the implant occurred in four eyes of four patients (0.43%). All four eyes were pseudophakic: one eye had a posterior chamber intraocular lens in the capsular bag but in a post-laser posterior capsulotomy state, two eyes had a sulcus intraocular lens (IOL), and one eye had an iris-fixated retropupillary IOL. All eyes had a prior vitrectomy and no lens capsule. The time interval from injection to detection of the implant migration ranged from 2 to 6 weeks. Of the four eyes with corneal edema, only one eye required a corneal transplantation, although it was unclear whether the implant migration was the direct cause of the corneal decompensation because the patient had a history of bullous keratopathy resulting from an extended history of uveitis. All patients underwent surgical intervention: two patients with a repositioning procedure, and the other two patients with removal due to repeated episodes, although surgical removal was not always necessary to reverse the corneal complications. In our study, not all patients required surgical removal of the implants. Repositioning the implant back into the vitreous cavity may be considered as an option in cases involving the first episode with no significant corneal endothelial decompensation. Considering potential anterior segment complications and the loss of drug effectiveness together, an individualized approach is recommended to obtain the best treatment outcomes and to minimize the risk of corneal complications.

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

NASA Astrophysics Data System (ADS)

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

2015-08-01

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

An injectable acoustic transmitter for juvenile salmon

DOE PAGES

Deng, Zhiqun; Carlson, Thomas J.; Li, Huidong; ...

2015-01-29

Salmon recovery, and the potential detrimental effects of dams on fish, has been attracting national attention in due to great environmental and economic implications. Acoustic Telemetry has been the primary method for studying salmon passage. However, the size of the existing transmitters limits the minimum size of fish that can be studied, introducing bias to the study results. We developed the first acoustic fish transmitter that can be implanted by injection instead of surgery. The new injectable transmitter offers improved performance and 30% weight reduction. Because the new transmitter costs significantly less to use, substantially reduces adverse effects of implantation,more » and provides additional biological benefits for tagged fish, it will become the enabling technology for studying migration behavior and survival of species and sizes of fish that have never been studied before. This will lead to critical information for salmon recovery and the development of fish-friendly hydroelectric systems.« less

An injectable acoustic transmitter for juvenile salmon

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

Deng, Zhiqun; Carlson, Thomas J.; Li, Huidong

Salmon recovery, and the potential detrimental effects of dams on fish, has been attracting national attention in due to great environmental and economic implications. Acoustic Telemetry has been the primary method for studying salmon passage. However, the size of the existing transmitters limits the minimum size of fish that can be studied, introducing bias to the study results. We developed the first acoustic fish transmitter that can be implanted by injection instead of surgery. The new injectable transmitter offers improved performance and 30% weight reduction. Because the new transmitter costs significantly less to use, substantially reduces adverse effects of implantation,more » and provides additional biological benefits for tagged fish, it will become the enabling technology for studying migration behavior and survival of species and sizes of fish that have never been studied before. This will lead to critical information for salmon recovery and the development of fish-friendly hydroelectric systems.« less

An injectable acoustic transmitter for juvenile salmon

NASA Astrophysics Data System (ADS)

Deng, Z. D.; Carlson, T. J.; Li, H.; Xiao, J.; Myjak, M. J.; Lu, J.; Martinez, J. J.; Woodley, C. M.; Weiland, M. A.; Eppard, M. B.

2015-01-01

Salmon recovery and the potential detrimental effects of dams on fish have been attracting national attention due to the environmental and economic implications. In recent years acoustic telemetry has been the primary method for studying salmon passage. However, the size of the existing transmitters limits the minimum size of fish that can be studied, introducing a bias to the study results. We developed the first acoustic fish transmitter that can be implanted by injection instead of surgery. The new injectable transmitter lasts four times longer and weighs 30% less than other transmitters. Because the new transmitter costs significantly less to use and may substantially reduce adverse effects of implantation and tag burden, it will allow for study of migration behavior and survival of species and sizes of fish that have never been studied before. The new technology will lead to critical information needed for salmon recovery and the development of fish-friendly hydroelectric systems.

An injectable acoustic transmitter for juvenile salmon

PubMed Central

Deng, Z. D.; Carlson, T. J.; Li, H.; Xiao, J.; Myjak, M. J.; Lu, J.; Martinez, J. J.; Woodley, C. M.; Weiland, M. A.; Eppard, M. B.

2015-01-01

Salmon recovery and the potential detrimental effects of dams on fish have been attracting national attention due to the environmental and economic implications. In recent years acoustic telemetry has been the primary method for studying salmon passage. However, the size of the existing transmitters limits the minimum size of fish that can be studied, introducing a bias to the study results. We developed the first acoustic fish transmitter that can be implanted by injection instead of surgery. The new injectable transmitter lasts four times longer and weighs 30% less than other transmitters. Because the new transmitter costs significantly less to use and may substantially reduce adverse effects of implantation and tag burden, it will allow for study of migration behavior and survival of species and sizes of fish that have never been studied before. The new technology will lead to critical information needed for salmon recovery and the development of fish-friendly hydroelectric systems. PMID:25630763

Biocompatibility of Advanced Manufactured Titanium Implants-A Review.

PubMed

Sidambe, Alfred T

2014-12-19

Titanium (Ti) and its alloys may be processed via advanced powder manufacturing routes such as additive layer manufacturing (or 3D printing) or metal injection moulding. This field is receiving increased attention from various manufacturing sectors including the medical devices sector. It is possible that advanced manufacturing techniques could replace the machining or casting of metal alloys in the manufacture of devices because of associated advantages that include design flexibility, reduced processing costs, reduced waste, and the opportunity to more easily manufacture complex or custom-shaped implants. The emerging advanced manufacturing approaches of metal injection moulding and additive layer manufacturing are receiving particular attention from the implant fabrication industry because they could overcome some of the difficulties associated with traditional implant fabrication techniques such as titanium casting. Using advanced manufacturing, it is also possible to produce more complex porous structures with improved mechanical performance, potentially matching the modulus of elasticity of local bone. While the economic and engineering potential of advanced manufacturing for the manufacture of musculo-skeletal implants is therefore clear, the impact on the biocompatibility of the materials has been less investigated. In this review, the capabilities of advanced powder manufacturing routes in producing components that are suitable for biomedical implant applications are assessed with emphasis placed on surface finishes and porous structures. Given that biocompatibility and host bone response are critical determinants of clinical performance, published studies of in vitro and in vivo research have been considered carefully. The review concludes with a future outlook on advanced Ti production for biomedical implants using powder metallurgy.

The effect of intravitreal bevacizumab injection before Ahmed valve implantation in patients with neovascular glaucoma.

PubMed

Kang, Jung Youb; Nam, Ki Yup; Lee, Sang Joon; Lee, Seung Uk

2014-08-01

To evaluate the effect of intravitreal bevacizumab (IVB) before Ahmed valve implantation for treatment of neovascular glaucoma (NVG). This study is a retrospective, comparative, consecutive case series. The study group consisted of 27 eyes of 26 patients with NVG who underwent an Ahmed valve implantation. Thirteen eyes were treated with Ahmed valve implantation alone (control group), and 14 eyes were treated with a combination of preoperative IVB injection and Ahmed valve implantation (IVB group). Visual acuity, intraocular pressure (IOP), number of anti-glaucoma medications, surgical complications, and success rate were compared between the two groups. There were no significant differences in preoperative characteristics between the two groups. Visual acuity at 1, 2 weeks, and 1 month after surgery were significantly better in the IVB group (p = 0.038, 0.034, and 0.032, respectively). Hyphema associated with Ahmed valve implantation occurred significantly less in the IVB group (p = 0.016). On the other hand, the mean IOP and number of anti-glaucoma medications at all follow-up periods were similar between the two groups. Kaplan-Meier survival analysis showed the probability of success 6 months after surgery as 71.4 % in the IVB group and 84.6 % in the control group. No significant difference in success rate was found between the groups (p = 0.422). IVB before Ahmed valve implantation for treatment of NVG reduced the incidence of hyphema. In this retrospective study, IVB provided better visual outcome in the early postoperative periods but did not significantly improve mean IOP, number of anti-glaucoma medications, or success rate.

Current status of grafts and implants in rhinoplasty: Part II. Homologous grafts and allogenic implants.

PubMed

Sajjadian, Ali; Naghshineh, Nima; Rubinstein, Roee

2010-03-01

After reading this article, the participant should be able to: 1. Understand the challenges in restoring volume and structural integrity in rhinoplasty. 2. Identify the appropriate uses of various homologous grafts and allogenic implants in reconstruction, including: (a) freeze-dried acellular allogenic cadaveric dermis grafts, (b) irradiated cartilage grafts, (c) hydroxyapatite mineral matrix, (d) silicone implants, (e) high-density polyethylene implants, (f) polytetrafluoroethylene implants, and (g) injectable filler materials. 3. Identify the advantages and disadvantages of each of these biomaterials. 4. Understand the specific techniques that may aid in the use these grafts or implants. This review specifically addresses the use of homologous grafts and allogenic implants in rhinoplasty. It is important to stress that autologous materials remain the preferred graft material for use in rhinoplasty, owing to their high biocompatibility and low risk of infection and extrusion. However, concerns of donor-site morbidity, graft availability, and graft resorption have motivated the development and use of homologous and allogenic implants.

Radiesse: Advanced Techniques and Applications for a Unique and Versatile Implant.

PubMed

Eviatar, Joseph; Lo, Christopher; Kirszrot, James

2015-11-01

Radiesse is a well-tolerated facial injectable with unique filling and lifting capabilities. Although initially approved for facial volumizing in HIV-related lipodystrophy patients, it quickly gained wide acceptance for aesthetic facial rejuvenation. In the USA, the Food and Drug Administration has approved several new indications for its use. This synopsis presents the experience and injection techniques currently favored by the primary author after many years of use in thousands of patients. The anecdotal practice of an experienced injector is presented along with the current Food and Drug Administration-approved standards of Radiesse injection. Radiesse has many on- and off-label applications that can be thoughtfully incorporated into clinical practice. Its unique chemical composition allows for immediate lifting and filling with long-term collagen stimulation. The product can be reconstituted to increase its versatility and minimize adverse events. Injections can be performed in the supraperiosteal space and the subcutaneous layer and are best administered in small, calculated doses to prevent nodules or vascular occlusion. Various techniques for Radiesse injection in specific areas are discussed in detail. Radiesse is a versatile injectable implant and a valuable tool for short- and long-term cosmetic and reconstructive treatments. In addition to various off-label uses, this injectable is often used in conjunction with botox, other injectables, collagen stimulators and tightening devices. A customized reconstitution of product increases its versatility for natural appearing and long lasting results that are both economical and effective for full facial rejuvenation.

Evaluation of a new soft tipped injector for the implantation of foldable intraocular lenses.

PubMed

Kleinmann, Guy; Apple, David J

2007-08-01

To evaluate the R-INJ-04 soft-tipped injector, a new injector with an integral round nozzle manufactured by Rayner Intraocular Lenses, England. 16 Rayner C-flex intraocular lenses (IOLs; Rayner Intraocular lenses, England) ranging between +10 and +30 D (2 for each power) were tested. An ophthalmic viscoelastic device (Healon, AMO, Santa Ana, California, USA) was applied to the injectors. The IOLs were loaded according to the company injector's instructions for use and were injected into a Petri dish. After the injection, all the IOLs and nozzles were evaluated by gross (macroscopic) and microscopic analyses and photographed under a light microscope. One lens of each power and the cartridge used for the implantation were then sent for further analysis by scanning electron microscopy (SEM). The rest of the IOLs were tested for power and modulation transfer function (MTF). All the injections were successful. No damage to the IOLs or to the injectors was found by gross examination, light microscopy and SEM. No deposits were found on the IOL optical surfaces or haptics. Power and MTF analysis showed a close match with the original measurements. Our results suggest that the R-INJ-04 soft-tipped injector is safe for the implantation of the C-flex IOL with power range from 10 to 30 D. No structural damage to the IOLs or to the injectors was found, and the lens power and light transmission properties were not damaged in any way by the injection process.

Transcatheter aortic-valve implantation with one single minimal contrast media injection.

PubMed

Arrigo, Mattia; Maisano, Francesco; Haueis, Sabine; Binder, Ronald K; Taramasso, Maurizio; Nietlispach, Fabian

2015-06-01

Performing transcatheter aortic valve implantation (TAVI) with the use of minimal contrast in patients at high-risk for acute kidney injury (AKI). Contrast-induced nephropathy (CIN) is a major cause of AKI following TAVI and is associated with increased morbidity and mortality. The amount of contrast media used increases the risk for CIN. Computed tomography was omitted during the screening process. For the procedure transfemoral access was default. The self-expanding CoreValve prosthesis was chosen in all patients to minimize the risk of annular rupture in case of oversizing. Valve sizing was based on echocardiography, aortography, calcification on fluoroscopy, as well as weight and height of the patient. A single contrast injection was performed to confirm correct position of the pigtail catheter at the level of the annulus. The pigtail then served as the marker for the device landing zone. Intraprocedural assessment of the implantation result relied on echocardiography and hemodynamics. Five patients with severe aortic stenosis and at high risk for developing CIN were included. Device success was achieved in all patients and no major complications occurred. The median dose of injected contrast media was 8 ml (4-9). All but one patient had improved renal function after the intervention compared to baseline. Our study shows feasibility of performing TAVI with a single minimal contrast media injection, using a self-expandable valve. This technique has the potential to reduce the incidence of CIN. © 2015 Wiley Periodicals, Inc.

21 CFR 522.300 - Carfentanil citrate injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... recommend use in pregnant animals. Avoid use during breeding season. Federal law restricts this drug to use...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522... animals intended for food. Do not use 30 days before or during hunting season. Do not use in animals that...

75 FR 76260 - Implantation or Injectable Dosage Form New Animal Drugs; Flunixin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

... meglumine solution by intravenous injection in lactating dairy cows for control of pyrexia associated with... cows for control of pyrexia associated with acute bovine mastitis. The supplemental application is... for 36 hours after the last treatment must not be used for food. Do not use in dry dairy cows. A...

124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results

PubMed Central

2010-01-01

Background 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of 18F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized CH2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaCH2), radiolabeled with iodine-124 (124I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging. Methods HuCC49deltaCH2 was radiolabeled with 124I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of 124I-HuCC49deltaCH2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of 18F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection. Results At approximately 1 hour after i.v. injection, 124I-HuCC49deltaCH2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, 124I-HuCC49deltaCH2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, 124I-HuCC49deltaCH2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, 18F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands of the bony orbits of the eyes, brown fat of the posterior neck, kidneys, and bladder. Conclusions On microPET imaging, 124I-HuCC49deltaCH2 demonstrates an increased level of specific localization to tumor implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on delayed imaging, while 18F-FDG failed to demonstrate this. The antigen-directed and cancer-specific 124I-radiolabled anti-TAG-72 monoclonal antibody conjugate, 124I-HuCC49deltaCH2, holds future potential for use in human clinical trials for preoperative, intraoperative, and postoperative PET-based imaging strategies, including fused-modality PET-based imaging platforms. PMID:20691066

Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increases in TNF-stimulated gene 6.

PubMed

Maruyama, Takashi; Fukuda, Noboru; Matsumoto, Taro; Kano, Koichiro; Endo, Morito; Kazama, Minako; Kazama, Tomohiko; Ikeda, Jin; Matsuda, Hiroyuki; Ueno, Takahiro; Abe, Masanori; Okada, Kazuyoshi; Soma, Masayoshi; Matsumoto, Koichi; Kawachi, Hiroshi

2015-04-16

Implantation of mesenchymal stem cells (MSCs) has recently been reported to repair tissue injuries through anti-inflammatory and immunosuppressive effects. We established dedifferentiated fat (DFAT) cells that show identical characteristics to MSCs. We examined the effects of 10(6) of DFAT cells infused through renal artery or tail vein on monoclonal antibody (mAb) 1-22-3-induced glomerulonephritis (as an immunological type of renal injury) and adriamycin-induced nephropathy (as a non-immunological type of renal injury) in rats. The mAb 1-22-3-injected rats were also implanted with 10(6) of DFAT cells transfected with TSG-6 siRNA through tail vein. Although DFAT cells transfused into blood circulation through the tail vein were trapped mainly in lungs without reaching the kidneys, implantation of DFAT cells reduced proteinuria and improved glomerulosclerosis and interstitial fibrosis. Implantation of DFAT cells through the tail vein significantly decreased expression of kidney injury molecule-1, collagen IV and fibronectin mRNAs, whereas nephrin mRNA expression was increased. Implantation of DFAT cells did not improve adriamycin-induced nephropathy, but significantly decreased the glomerular influx of macrophages, common leukocytes and pan T cells. However, the glomerular influx of helper T cells, was increased. Implantation of DFAT cells decreased expression of interleukin (IL)-6 and IL-12β mRNAs and increased expression of TNF-stimulated gene (TSG)-6 mRNA in renal cortex from mAb 1-22-3-injected rats. The basal level of TSG-6 protein was significantly higher in DFAT cells than in fibroblasts. Expression of TSG-6 mRNA in MCs cocultured with DFAT cells was significantly higher than in mesangial cells or DFAT cells alone. Systematic implantation of DFAT cells with TSG-6 siRNA through tail vein did not improve proteinuria, renal dysfunction and renal degeneration in the mAb 1-22-3-injected rats. Systematic implantation of DFAT cells effectively ameliorated mAb 1-22-3-induced glomerulonephritis through immunosuppressive effects accompanied by the suppression of macrophage infiltration and expression of IL-6, IL-10 and IL-12β, and increased production of serum and renal TSG-6 that improved the mAb 1-22-3-induced renal degeneration by the immunosuppressive effects of TSG-6. Thus DFAT cells will be suitable cell source for the treatment of immunological progressive renal diseases.

A preliminary report on the usage of an intracorporal antibiotic cast with synthetic high purity CaSO4 for the treatment of infected penile implant.

PubMed

Swords, Kelly; Martinez, Daniel R; Lockhart, Jorge L; Carrion, Rafael

2013-04-01

Currently, the surgical treatment of infected penile prostheses is complete removal and either immediate salvage procedure, which carries a significant infection risk, or delayed implantation. With delayed implantation the risk of infection is lower, but the patient loses penile length and width due to corporal fibrosis. We present our experience with the use of a novel temporary synthetic high purity calcium sulfate (SHPCaSO4) component that acts as a "spacer" at the time of removal of an infected prosthesis while providing constant delivery of local antibiotic elution to the infected area. Demonstrate that the use of a novel material, SHPCaSO4, can be an innovative way to bridge the gap between removal of an infected penile implant and delayed reimplantation. Two patients (Patient A and B) presented with pain and erythema and were found to have infected malleable penile prosthesis. Both underwent removal of all infected components, and sent for tissue culture. The SHPCaSO4 was mixed with vancomycin and tobramycin, allowed to set up for 5 minutes, and then injected into the corporal space followed by closure with 2-0 Vicryl sutures. The injected SHPCaSO4 was palpable in the penile shaft both proximally and distally, as an "intracorporal casts." Patients denied pain postoperatively. Delayed implantation occurred at 6 weeks for patient A. This went uneventful and a new three-piece inflatable implant was inserted. Patient B underwent salvage placement of right malleable implant at 15 weeks, and here significant corporal fibrosis was encountered. Patients have had no infection since their delayed implantation (mean follow-up 4 months). Data in reference to SHPCaSO4 shows that this product dissolves in approximately 4-6 weeks. This may account for the difference in the ease of delayed implantation between the two patients. Further investigation is warranted. © 2013 International Society for Sexual Medicine.

A novel injectable borate bioactive glass cement for local delivery of vancomycin to cure osteomyelitis and regenerate bone.

PubMed

Cui, Xu; Zhao, Cunju; Gu, Yifei; Li, Le; Wang, Hui; Huang, Wenhai; Zhou, Nai; Wang, Deping; Zhu, Yi; Xu, Jun; Luo, Shihua; Zhang, Changqing; Rahaman, Mohamed N

2014-03-01

Osteomyelitis (bone infection) is often difficult to cure. The commonly-used treatment of surgical debridement to remove the infected bone combined with prolonged systemic and local antibiotic treatment has limitations. In the present study, an injectable borate bioactive glass cement was developed as a carrier for the antibiotic vancomycin, characterized in vitro, and evaluated for its capacity to cure osteomyelitis in a rabbit tibial model. The cement (initial setting time = 5.8 ± 0.6 min; compressive strength = 25.6 ± 0.3 MPa) released vancomycin over ~25 days in phosphate-buffered saline, during which time the borate glass converted to hydroxyapatite (HA). When implanted in rabbit tibial defects infected with methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis, the vancomycin-loaded cement converted to HA and supported new bone formation in the defects within 8 weeks. Osteomyelitis was cured in 87 % of the defects implanted with the vancomycin-loaded borate glass cement, compared to 71 % for the defects implanted with vancomycin-loaded calcium sulfate cement. The injectable borate bioactive glass cement developed in this study is a promising treatment for curing osteomyelitis and for regenerating bone in the defects following cure of the infection.

Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs.

PubMed

Guarnieri, Michael; Tyler, Betty M; Detolla, Louis; Zhao, Ming; Kobrin, Barry

2014-01-01

Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Drug implants can retain significant and unintended reservoirs of drugs.

Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

PubMed Central

Guarnieri, Michael; Tyler, Betty M.; DeTolla, Louis; Zhao, Ming; Kobrin, Barry

2014-01-01

Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs. PMID:24459402

[The penis prolongation and augmentation combined with autologous granular fat injection and silicone implantation].

PubMed

Xie, Yang-chun; Zhang, Yang; Fan, Jin-cai; Liu, Yuan-bo; Liu, Li-qiang; Wang, Qian

2007-07-01

To prevent the retraction of the penis after prolongation and augmentation. After all the superficial and part of the deep suspensory ligament amputation, we implanted the silicon sheet (the length 2.3-3.6 cm, the width 1.5-2.5 cm, the thickness 2-3 mm) and injected autologous granular fat (30-48 ml) into penis. 16 patients (age 22-63 years, averagely 38 years) underwent this kind operation, the prolongation length is 1.8-5.1 cm, the average was 2.91 cm, the increased diameter of penis was 0.6-1 cm, the average is 0.85 cm, the following period is 3 months to 2 years. The results are satisfactory with the penis retraction less than 8%, and less than 10% decrease in diameter. This method is an ideal way of the penis prolongation and augmentation, the implantation of the silicon sheet is effective way to prevent the retraction of the penis.

The treatment of vesicoureteral reflux in children by endoscopic sub-mucosal intra-ureteral injection of dextranomer/hyaluronic acid: A case-series, multi-centre study.

PubMed

Bawazir, Osama

2017-04-01

Vesicoureteral reflux is a risk factor for progressive renal damage. In addition to long-term antibiotic prophylaxis and open surgical re-implantation, endoscopic sub-mucosal intra-ureteral injection of implant material is a therapeutic alternative that gained a world-wide preference. The aim of this study was to determine the effectiveness and safety of the implant material, dextranomer/hyaluronic acid, in a cohort of Saudi children with vesicoureteral reflux. In this case-series study, 61 patients with vesicoureteral reflux, who were 7 months to 10 years old (mean age 2.6 years), underwent sub-mucosal intra-ureteral injection of dextranomer/hyaluronic acid at our institutions in the period from October 2003 to October 2013. The operative protocol was the same in all institutions. Dextranomer/hyaluronic acid was injected submucosally within the intramural ureter (modified STING). Renal ultrasonography was performed to detect the presence of hydronephrosis. At 6 weeks' fluoroscopic voiding cystourethrograms were used to evaluate the success of the technique. Data were analysed by SPSS version 19 using Pearson Chi square, Fisher's Exact and Cramér's V test. Reflux was corrected in 44 patients out of 61 (72.13%) and in 60 (75.00%) out of 80 ureteric units. Statistically, there was no significant difference (p>0.05) in success rate of the technique according to gender, age group and unilateral vs. bilateral cases. The success rate was significantly (p=0.025) higher in the lower grades (I-III) (87.50%) compared to grade IV (73.53%) and grade V (50.00%). No complications related to the technique were reported. The technique had failed in 17 patients (27.87%) or 20 ureters (25.00%). These cases underwent open surgery. Sub-mucosal intra-ureteral implantation with dextranomer/hyaluronic acid by the modified STING technique is a simple, safe and effective outpatient procedure for vesicoureteral reflux.

Micro-CT based modelling for characterising injection-moulded porous titanium implants.

PubMed

Chen, Junning; Chen, Liangjian; Chang, Che-Cheng; Zhang, Zhongpu; Li, Wei; Swain, Michael V; Li, Qing

2017-01-01

Design of prosthetic implants to ensure rapid and stable osseointegration remains a significant challenge, and continuous efforts have been directed to new implant materials, structures and morphology. This paper aims to develop and characterise a porous titanium dental implant fabricated by metallic powder injection-moulding. The surface morphology of the specimens was first examined with a scanning electron microscope (SEM), followed by microscopic computerised tomography (μ-CT) scanning to capture its 3D microscopic features non-destructively. The nature of porosity and pore sizes were determined statistically. A homogenisation technique based on the Hills-energy theorem was adopted to evaluate its directional elastic moduli, and the conservation of mass theorem was employed to quantify the oxygen diffusivity for bio-transportation feature. This porous medium was found to have pore sizes varying from 50 to 400 µm and the average porosity of 46.90 ± 1.83%. The anisotropic principal elastic moduli were found fairly close to the upper range of cortical bone, and the directional diffusivities could potentially enable radial osseous tissue ingrowth and vascularisation. This porous titanium successfully reduces the elastic modulus mismatch between implant and bone for dental and orthopaedic applications, and provides improved capacity for transporting oxygen, nutrient and waste for pre-vascular network formation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Resveratrol inhibits development of experimental endometriosis in vivo and reduces endometrial stromal cell invasiveness in vitro.

PubMed

Bruner-Tran, Kaylon L; Osteen, Kevin G; Taylor, Hugh S; Sokalska, Anna; Haines, Kaitlin; Duleba, Antoni J

2011-01-01

Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10-12 and 18-20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10-30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis.

INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

PubMed

Barikian, Anita; Salti, Haytham; Safar, Ammar; Mahfoud, Ziyad R; Bashshur, Ziad F

2017-07-01

To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 μm to 236.2 μm, occurred 1 month after dexamethasone implant (P < 0.0001). By Month 6, mean central retinal thickness was 287.3 μm (P = 0.16). Eyes with only intraretinal fluid (13 eyes) achieved a fluid-free macula. Eyes with predominantly subretinal fluid (6 eyes) did not improve central retinal thickness and continued monthly ranibizumab. Mean baseline intraocular pressure was 13.2 mmHg, which peaked at 15.6 mmHg by Month 2 (P = 0.004). Intravitreal dexamethasone implant improved only macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

Local strategies to prevent and treat osteoporosis.

PubMed

Torstrick, F Brennan; Guldberg, Robert E

2014-03-01

Despite advances in systemic osteoporosis therapeutic outcomes, management of fragility fractures and implant fixation in osteoporotic bone remain difficult clinical challenges. Low initial bone density and a prolonged healing response can lead to fracture nonunion and aseptic implant loosening. Local treatment strategies could be used to prevent fracture, accelerate healing, and increase implant fixation by locally stimulating anabolic pathways or inhibiting catabolic pathways. Local strategies under investigation include direct drug release from injectable materials or implant surface coatings. Common locally delivered drugs include bisphosphonates, parathyroid hormone, and bone morphogenetic proteins, yet additional compounds targeting novel pathways in bone biology are also being actively explored. Mechanical stimulation via low intensity pulsed ultrasound, alone or in combination with drug therapy, may also prove effective to promote local bone healing and implant fixation within osteoporotic bone.

Practical evolution and application of direct intracytoplasmic sperm injection for male factor and idiopathic fertilization failure infertilities.

PubMed

Tucker, M J; Wright, G; Morton, P C; Mayer, M P; Ingargiola, P E; Jones, A E

1995-04-01

To analyze the introduction of a new assisted fertilization technique for the treatment of severe male factor and idiopathic fertilization failure infertilities. Retrospective analysis of 16-month clinical application of IVF-ET where insemination was performed solely by direct intracytoplasmic sperm injection. Clinical IVF-ET program. Ninety-two couples undergoing 105 cycles of sperm injection. One hundred embryo transfers yielded 28 viable pregnancies (28%) from which eight normal deliveries have occurred to date. Complete cleavage arrest or fertilization failure occurred in four cycles, and one couple had all embryos cryopreserved. One thousand one hundred forty-three eggs were injected of which 173 (15%) degenerated. Four hundred seventy-nine of the surviving 970 eggs became normally fertilized (49%), and 381 of these zygotes (79.5%) developed suitably for cryopreservation or for transfer. Thirty-four of 310 embryos transferred implanted, yielding an implantation rate of 11%. Both testicular and epididymal sperm were used successfully to achieve fertilization and pregnancies, as was sperm retrieved by electroejaculation. Older women and couples suffering from prior idiopathic fertilization failure had a markedly poorer outcome. These results confirm that the intracytoplasmic sperm injection technique is a successful form of assisted fertilization that can be applied to a wide range of couples at significant risk from fertilization failure.

Anabolic actions of PTH (1-34): use of a novel tissue engineering model to investigate temporal effects on bone.

PubMed

Pettway, Glenda J; Schneider, Abraham; Koh, Amy J; Widjaja, Effendi; Morris, Michael D; Meganck, Jeffrey A; Goldstein, Steven A; McCauley, Laurie K

2005-06-01

PTH is in clinical use for the treatment of osteoporosis and is under intensive investigation for its potential in applications of tissue engineering, fracture healing, and implant integration. However, the mechanisms of its action to stimulate bone formation are still unclear. A novel bone tissue engineering model was used to elucidate basic mechanisms of PTH anabolic actions. Ectopic ossicles containing cortical bone, trabecular bone, and a hematopoietic marrow were generated from implanted bone marrow stromal cells (BMSC). One week after implantation, nude mice were administered PTH or vehicle for 1 week (group 1), 3 weeks (group 2), or 7 weeks (group 3). Another group was also treated for 3 weeks, initiated 12 weeks after implantation (group 4). Micro-radiography and histomorphometry revealed increased marrow cellularity in group 1 PTH-treated ossicles, increased bone in group 2 PTH-treated ossicles, and similar amounts of bone in both group 3 and 4 ossicles regardless of treatment. Incidence of phosphate mineral and phosphate mineral to hydroxyproline ratio via Raman spectroscopy were significantly higher after 3 weeks versus 1 week of PTH treatment, but there was no difference between PTH- and vehicle-treated ossicles. Early events of PTH action in group 1 ossicles and the effects of a single injection of PTH on 1- and 2-week-old ossicles were evaluated by Northern blot analysis. Osteocalcin (OC) mRNA was increased after 1 week of intermittent PTH treatment in ossicles and calvaria but an acute injection did not alter OC mRNA. In contrast, a single injection of PTH increased matrix gamma-carboxyglutamic acid protein (MGP) mRNA in 2-week-old ossicles. Differential and temporal-dependent effects of PTH on OC and MGP suggest at the molecular level, that PTH acts to inhibit osteoblast mineralization. However, this does not translate into tissue level alterations. These data indicate that anabolic actions of PTH in ectopic ossicles are temporally dependent on the BMSC implanted and suggest that cell implantation strategies are particularly responsive to PTH.

Validation of a cage implant system for assessing in vivo performance of long-acting release microspheres.

PubMed

Doty, Amy C; Hirota, Keiji; Olsen, Karl F; Sakamoto, Naoya; Ackermann, Rose; Feng, Meihua R; Wang, Yan; Choi, Stephanie; Qu, Wen; Schwendeman, Anna; Schwendeman, Steven P

2016-12-01

Here we describe development of a silicone rubber/stainless steel mesh cage implant system, much like that used to assess biocompatibility of biomaterials [1], for easy removal of injectable polymer microspheres in vivo. The sterile cage has a type 316 stainless steel mesh size (38 μm) large enough for cell penetration and free fluid flow in vivo but small enough for microsphere retention, and a silicone rubber shell for injection of the microspheres. Two model drugs, the poorly soluble steroid, triamcinolone acetonide, and the highly water-soluble luteinizing hormone-releasing hormone (LHRH) peptide superagonist, leuprolide, were encapsulated in PLGA microspheres large enough (63-90 μm) to be restrained by the cage implant in vivo. The in vitro release from both formulations was followed by ultra-performance liquid chromatography (UPLC) with and without the cage in a standard release media, PBS pH 7.4 + 0.02% Tween 80 + 0.05% sodium azide, at 37 °C. Pharmacokinetics (PK) in rats was assessed after SC injection or SC in-cage implantation of microspheres with plasma analysis by LC-MS/MS or EIA. Tr-A and leuprolide in vitro release was largely unaffected after the initial burst irrespective of the cage or test tube incubation vessel and release was much slower than observed in vivo for both drugs. Moreover, Tr-A and leuprolide pharmacokinetics with and without the cage were highly similar during the 2-3 week release duration before a significant inflammatory response was caused by the cage implant. Hence, the PK-validated cage implant provides a simple means to recover and evaluate the microsphere drug carriers in vivo during a time window of at least a few weeks in order to characterize the polymer microsphere release and erosion behavior in vivo. This approach may facilitate development of mechanism-based in vitro/in vivo correlations and enable development of more accurate and useful in vitro release tests. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biocompatibility of Advanced Manufactured Titanium Implants—A Review

PubMed Central

Sidambe, Alfred T.

2014-01-01

Titanium (Ti) and its alloys may be processed via advanced powder manufacturing routes such as additive layer manufacturing (or 3D printing) or metal injection moulding. This field is receiving increased attention from various manufacturing sectors including the medical devices sector. It is possible that advanced manufacturing techniques could replace the machining or casting of metal alloys in the manufacture of devices because of associated advantages that include design flexibility, reduced processing costs, reduced waste, and the opportunity to more easily manufacture complex or custom-shaped implants. The emerging advanced manufacturing approaches of metal injection moulding and additive layer manufacturing are receiving particular attention from the implant fabrication industry because they could overcome some of the difficulties associated with traditional implant fabrication techniques such as titanium casting. Using advanced manufacturing, it is also possible to produce more complex porous structures with improved mechanical performance, potentially matching the modulus of elasticity of local bone. While the economic and engineering potential of advanced manufacturing for the manufacture of musculo-skeletal implants is therefore clear, the impact on the biocompatibility of the materials has been less investigated. In this review, the capabilities of advanced powder manufacturing routes in producing components that are suitable for biomedical implant applications are assessed with emphasis placed on surface finishes and porous structures. Given that biocompatibility and host bone response are critical determinants of clinical performance, published studies of in vitro and in vivo research have been considered carefully. The review concludes with a future outlook on advanced Ti production for biomedical implants using powder metallurgy. PMID:28788296

Exposure to Zearalenone During Early Pregnancy Causes Estrogenic Multitoxic Effects in Mice.

PubMed

Kunishige, Kohji; Kawate, Noritoshi; Inaba, Toshio; Tamada, Hiromichi

2017-03-01

Although zearalenone (ZEN; Sigma Chemicals, St Louis, Missouri) is a well-known mycotoxin with estrogenic activity, the toxic effects of ZEN during pregnancy are unknown. This study compared the effects of daily subcutaneous injections of ZEN (2, 4, or 8 mg/kg) with those of 17β-estradiol (E2; [Sigma Chemicals] 0.8, 1.6, or 3.2 μg/kg) in mice. Injections were administered on gestational days (GDs) 1 to 5, the period including implantation which is sensitive to hormonal balance. The effects of ZEN or E2 were evaluated by comparing the number of live fetuses, their weight, and absorbed conceptuses on GD 18, with those in vehicle-treated controls. In addition, implantation, embryos in the oviducts and those in uteri without implantation sites were investigated on GD 5. In mice treated with the highest dose of ZEN or E2, decidual responses and plasma progesterone concentrations were measured on GDs 5 and 6, respectively, and delayed implantation was investigated on GDs 9 and 14. The results showed that treatment with ZEN, in a manner similar to that seen for E2, led to obstruction of essential processes for establishing and maintaining pregnancy, such as embryo migration from oviducts to uteri, the decidual response, and activation of luteal function. Zearalenone also induced delayed implantation and loss of conceptuses and at low doses caused a retarded growth of the fetuses after normal implantation. It was therefore concluded that ZEN causes multiple estrogenic toxic actions when administered during early pregnancy in mice.

Safety assessment of a new single-use small-incision injector for intraocular lens implantation.

PubMed

Satanovsky, Alexandra; Ben-Eliahu, Shmuel; Apple, David J; Kleinmann, Guy

2011-07-01

To evaluate the safety of a new injector, the Raysert R-INJ-04/18, for implantation of the C-flex intraocular lens (IOL). Ophthalmology Department, Kaplan Medical Center, Rehovot, Israel. Experimental study. Sixty IOLs were subdivided into 2 equally sized groups. Group A IOLs were injected using the established R-INJ-04 injector, and those in Group B were injected with the new injector. The IOLs were injected into a Petri dish. Subsequently, all IOLs and injectors were evaluated macroscopically and microscopically and then photographed under light microscopy (LM). Two IOLs in each group were randomly chosen and sent for evaluation by scanning electron microscopy (SEM) and energy dispersive analysis of x-ray. All remaining IOLs were sent for power and modulation transfer function (MTF) analysis. All Group B IOLs were successfully injected without evident signs of scratching, cracks, or deposits on LM and SEM examination. In Group A, findings were confined to a singular incidence of a small deposit detected on the periphery of the posterior optical surface of the IOL, with corresponding findings detected on the injector nozzle. No signs of scratching, cracks, or deposits were found in the rest of the IOLs or injectors. The power and MTF analyses were within the normal range for all IOLs. The new 1.8 mm external diameter soft-tipped injector for 2.4 to 2.2 mm incisions was shown to be safe for the implantation of the C-flex 21.0 diopter IOL. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas.

PubMed

Ruban, Angela; Berkutzki, Tamara; Cooper, Itzik; Mohar, Boaz; Teichberg, Vivian I

2012-12-01

L-Glutamate (Glu) plays a crucial role in the growth of malignant gliomas. We have established the feasibility of accelerating a naturally occurring brain to-blood Glu efflux by decreasing blood Glu levels with intravenous oxaloacetate, the respective Glu co-substrate of the blood resident enzyme humane glutamate–oxaloacetate transaminase(hGOT). We wished to demonstrate that blood Glu scavenging provides neuroprotection in the case of glioma.We now describe the neuroprotective effects of blood Glu scavenging in a fatal condition such as brain-implanted C6 glioma in rats and brain-implanted human U87 MG glioma in nude mice. Rat (C-6) or human (U87) glioma cells were grafted stereotactically in the brain of rats or mice. After development of tumors, the animals were drinking oxaloacetate with or without injections of hGOT. In addition, mice were treated with combination treatment, which included drinking oxaloacetate with intracutaneous injections of hGOT and intraperitoneal injection of Temozolomide. Animals drinking oxaloacetate with or without injections of hGOT displayed a smaller tumor volume, reduced invasiveness and prolonged survival than control animals drinking saline. These effects were significantly enhanced by Temozolomide in mice, which increased survival by 237%. This is the first demonstration of blood Glu scavenging in brain cancer, and because of its safety, is likely to be of clinical significance for the future treatment of human gliomas. As we demonstrated, the blood glutamate scavenging treatment in combination with TMZ could be a good candidate or as an alternative treatment to the patients that do not respond to TMZ.

Image-guided tissue engineering of anatomically shaped implants via MRI and micro-CT using injection molding.

PubMed

Ballyns, Jeffery J; Gleghorn, Jason P; Niebrzydowski, Vicki; Rawlinson, Jeremy J; Potter, Hollis G; Maher, Suzanne A; Wright, Timothy M; Bonassar, Lawrence J

2008-07-01

This study demonstrates for the first time the development of engineered tissues based on anatomic geometries derived from widely used medical imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Computer-aided design and tissue injection molding techniques have demonstrated the ability to generate living implants of complex geometry. Due to its complex geometry, the meniscus of the knee was used as an example of this technique's capabilities. MRI and microcomputed tomography (microCT) were used to design custom-printed molds that enabled the generation of anatomically shaped constructs that retained shape throughout 8 weeks of culture. Engineered constructs showed progressive tissue formation indicated by increases in extracellular matrix content and mechanical properties. The paradigm of interfacing tissue injection molding technology can be applied to other medical imaging techniques that render 3D models of anatomy, demonstrating the potential to apply the current technique to engineering of many tissues and organs.

77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

... for Injection, administered as two doses 4 weeks apart to intact male pigs for the reduction of boar... pigs and barrows. Do not use in intact male pigs intended for breeding because of the disruption of.... Pigs should be slaughtered no earlier than 3 weeks and no later than 10 weeks after the second dose...

76 FR 27888 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor-Diphtheria...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... taint in intact male pigs intended for slaughter. DATES: This rule is effective May 13, 2011. FOR... function) and reduction of boar taint in intact male pigs intended for slaughter. The application is... of use in swine--(1) Amount. Administer 0.4 mg per intact male pig (2 mL) by subcutaneous injection...

Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results.

PubMed

Haller, Julia A; Bandello, Francesco; Belfort, Rubens; Blumenkranz, Mark S; Gillies, Mark; Heier, Jeffrey; Loewenstein, Anat; Yoon, Young Hee; Jiao, Jenny; Li, Xiao-Yan; Whitcup, Scott M; Li, Joanne

2011-12-01

To evaluate the safety and efficacy of 1 or 2 treatments with dexamethasone intravitreal implant (DEX implant) over 12 months in eyes with macular edema owing to branch or central retinal vein occlusion (BRVO or CRVO). Two identical, multicenter, prospective studies included a randomized, 6-month, double-masked, sham-controlled phase followed by a 6-month open-label extension. We included 1256 patients with vision loss owing to macular edema associated with BRVO or CRVO. At baseline, patients received DEX implant 0.7 mg (n = 421), DEX implant 0.35 mg (n = 412), or sham (n = 423) in the study eye. At day 180, patients could receive DEX implant 0.7 mg if best-corrected visual acuity (BCVA) was <84 letters or retinal thickness was >250 μm. The primary outcome for the open-label extension was safety; BCVA was also evaluated. At day 180, 997 patients received open-label DEX implant. Except for cataract, the incidence of ocular adverse events was similar in patients who received their first or second DEX implant. Over 12 months, cataract progression occurred in 90 of 302 phakic eyes (29.8%) that received 2 DEX implant 0.7 mg injections versus 5 of 88 sham-treated phakic eyes (5.7%); cataract surgery was performed in 4 of 302 (1.3%) and 1 of 88 (1.1%) eyes, respectively. In the group receiving two 0.7-mg DEX implants (n = 341), a ≥ 10-mmHg intraocular pressure (IOP) increase from baseline was observed in (12.6% after the first treatment, and 15.4% after the second). The IOP increases were usually transient and controlled with medication or observation; an additional 10.3% of patients initiated IOP-lowering medications after the second treatment. A ≥ 15-letter improvement in BCVA from baseline was achieved by 30% and 32% of patients 60 days after the first and second DEX implant, respectively. Among patients with macular edema owing to BRVO or CRVO, single and repeated treatment with DEX implant had a favorable safety profile over 12 months. In patients who qualified for and received 2 DEX implant injections, the efficacy and safety of the 2 implants were similar with the exception of cataract progression. Proprietary or commercial disclosure may be found after the references. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Recovery of Donor Hematopoiesis after Graft Failure and Second Hematopoietic Stem Cell Transplantation with Intraosseous Administration of Mesenchymal Stromal Cells

PubMed Central

Sats, Natalia; Risinskaya, Natalya; Sudarikov, Andrey; Dubniak, Daria; Kraizman, Alina

2018-01-01

Multipotent mesenchymal stromal cells (MSCs) participate in the formation of bone marrow niches for hematopoietic stem cells. Donor MSCs can serve as a source of recovery for niches in patients with graft failure (GF) after allogeneic bone marrow (BM) transplantation. Since only few MSCs reach the BM after intravenous injection, MSCs were implanted into the iliac spine. For 8 patients with GF after allo-BMT, another hematopoietic stem cell transplantation with simultaneous implantation of MSCs from their respective donors into cancellous bone was performed. BM was aspirated from the iliac crest of these patients at 1-2, 4-5, and 9 months after the intraosseous injection of donor MSCs. Patients' MSCs were cultivated, and chimerism was determined. In 6 out of 8 patients, donor hematopoiesis was restored. Donor cells (9.4 ± 3.3%) were detected among MSCs. Thus, implanted MSCs remain localized at the site of administration and do not lose the ability to proliferate. These results suggest that MSCs could participate in the restoration of niches for donor hematopoietic cells or have an immunomodulatory effect, preventing repeated rejection of the graft. Perhaps, intraosseous implantation of MSCs contributes to the success of the second transplantation of hematopoietic stem cells and patient survival. PMID:29760731

Recovery of Donor Hematopoiesis after Graft Failure and Second Hematopoietic Stem Cell Transplantation with Intraosseous Administration of Mesenchymal Stromal Cells.

PubMed

Petinati, Nataliya; Drize, Nina; Sats, Natalia; Risinskaya, Natalya; Sudarikov, Andrey; Drokov, Michail; Dubniak, Daria; Kraizman, Alina; Nareyko, Maria; Popova, Natalia; Firsova, Maya; Kuzmina, Larisa; Parovichnikova, Elena; Savchenko, Valeriy

2018-01-01

Multipotent mesenchymal stromal cells (MSCs) participate in the formation of bone marrow niches for hematopoietic stem cells. Donor MSCs can serve as a source of recovery for niches in patients with graft failure (GF) after allogeneic bone marrow (BM) transplantation. Since only few MSCs reach the BM after intravenous injection, MSCs were implanted into the iliac spine. For 8 patients with GF after allo-BMT, another hematopoietic stem cell transplantation with simultaneous implantation of MSCs from their respective donors into cancellous bone was performed. BM was aspirated from the iliac crest of these patients at 1-2, 4-5, and 9 months after the intraosseous injection of donor MSCs. Patients' MSCs were cultivated, and chimerism was determined. In 6 out of 8 patients, donor hematopoiesis was restored. Donor cells (9.4 ± 3.3%) were detected among MSCs. Thus, implanted MSCs remain localized at the site of administration and do not lose the ability to proliferate. These results suggest that MSCs could participate in the restoration of niches for donor hematopoietic cells or have an immunomodulatory effect, preventing repeated rejection of the graft. Perhaps, intraosseous implantation of MSCs contributes to the success of the second transplantation of hematopoietic stem cells and patient survival.

Nanocarrier mediated retinal drug delivery: overcoming ocular barriers to treat posterior eye diseases.

PubMed

Bisht, Rohit; Mandal, Abhirup; Jaiswal, Jagdish K; Rupenthal, Ilva D

2018-03-01

Effective drug delivery to the retina still remains a challenge due to ocular elimination mechanisms and complex barriers that selectively limit the entry of drugs into the eye. To overcome these barriers, frequent intravitreal injections are currently used to achieve high drug concentrations in vitreous and retina. However, these repetitive injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery could overcome some of these unmet needs and various preclinical studies conducted to date have demonstrated promising results of nanotherapies in the treatment of retinal diseases. Compared to the majority of commercially available ocular implants, the biodegradable nature of most nanoparticles (NPs) avoids the need for surgical implantation and removal after the release of the payload. In addition, the sustained drug release from NPs over an extended period of time reduces the need for frequent intravitreal injections and the risk of associated side effects. The nanometer size and highly modifiable surface properties make NPs excellent candidates for targeted ocular drug delivery. Studies have shown that nanocarriers enhance the intravitreal half-life and thus bioavailability of a number of drugs including proteins and peptides. In addition, they have shown promising results in delivering genetic material to the retinal tissues by protecting it from possible intravitreal degradation. This review covers the various challenges associated with drug delivery to the posterior segment of the eye, particularly the retina, and highlights the application of nanocarriers to overcome these challenges in context with recent advances in preclinical studies. WIREs Nanomed Nanobiotechnol 2018, 10:e1473. doi: 10.1002/wnan.1473 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants. © 2017 Wiley Periodicals, Inc.

Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain.

PubMed

Liu, Cui-Cui; Zhang, Xin-Sheng; Ruan, Yu-Ting; Huang, Zhu-Xi; Zhang, Su-Bo; Liu, Meng; Luo, Hai-Jie; Wu, Shao-Ling; Ma, Chao

2017-08-01

Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons (<30 μm in diameter). Intrathecal injection of MG also induced mechanical allodynia, and its application to DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus generation of AGEs from MG may represent a target for treatment of LDH-induced pain. NEW & NOTEWORTHY Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain. Copyright © 2017 the American Physiological Society.

Resveratrol Inhibits Development of Experimental Endometriosis In Vivo and Reduces Endometrial Stromal Cell Invasiveness In Vitro1

PubMed Central

Bruner-Tran, Kaylon L.; Osteen, Kevin G.; Taylor, Hugh S.; Sokalska, Anna; Haines, Kaitlin; Duleba, Antoni J.

2010-01-01

Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10–12 and 18–20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10–30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis. PMID:20844278

Birth control - slow release methods

MedlinePlus

Contraception - slow-release hormonal methods; Progestin implants; Progestin injections; Skin patch; Vaginal ring ... might want to consider a different birth control method. SKIN PATCH The skin patch is placed on ...

Viral retinitis following intraocular or periocular corticosteroid administration: a case series and comprehensive review of the literature.

PubMed

Takakura, Ako; Tessler, Howard H; Goldstein, Debra A; Guex-Crosier, Yan; Chan, Chi-Chao; Brown, Diane M; Thorne, Jennifer E; Wang, Robert; Cunningham, Emmett T

2014-06-01

To describe viral retinitis following intravitreal and periocular corticosteroid administration. Retrospective case series and comprehensive literature review. We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25-13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%). Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy.

Viral Retinitis following Intraocular or Periocular Corticosteroid Administration: A Case Series and Comprehensive Review of the Literature

PubMed Central

Takakura, Ako; Tessler, Howard H.; Goldstein, Debra A.; Guex-Crosier, Yan; Chan, Chi-Chao; Brown, Diane M.; Thorne, Jennifer E.; Wang, Robert; Cunningham, Emmett T.

2014-01-01

Purpose To describe viral retinitis following intravitreal and periocular corticosteroid administration. Methods Retrospective case series and comprehensive literature review. Results We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25–13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%). Conclusions Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy. PMID:24655372

Antidiuretic effect of morphine in the rat: tolerance and physical dependence.

PubMed Central

Huidobro, F

1978-01-01

1 Injection of rats with morphine or methadone, before they received a water load equivalent to 5% of their body weight, produced a dose-dependent antidiuretic effect. Following the antidiuresis, urine was eliminated with kinetics similar to control untreated rats. 2 The antidiuretic effect of morphine or methadone was blocked by naloxone administered before the opiate, or reversed when given after the opiate. 3 Rats implanted with morphine pellets developed a marked degree of tolerance to the antidiuretic effect of morphine. Tolerance was also obtained on injection of three daily doses of morphine or methadone over two days. 4 Withdrawal symptoms were precipitated by naloxone in rats implanted with pellets of morphine; under these conditions the animals showed a marked reduction in urine production as compared to naive rats. PMID:568501

Mesenchymal stem cells display hepato-protective activity in lymphoma bearing xenografts.

PubMed

Secchiero, Paola; Corallini, Federica; Zavan, Barbara; Tripodo, Claudio; Vindigni, Vincenzo; Zauli, Giorgio

2012-04-01

A disseminated model of non-Hodgkin's lymphoma with prevalent liver metastasis was generated by intraperitoneal (i.p.) injection of EBV(+) B lymphoblastoid SKW6.4 in nude-SCID mice. The survival of SKW6.4 xenografts (median survival = 27 days) was significantly improved when hyaluronan scaffolds embedded with mesenchimal stem cells (MSC) were implanted in the abdominal area 4 days after SKW6.4 injection (median survival = 39.5 days). Mice implanted with MSC showed a significant improvement of hepatic functionality in lymphoma xenografts, as demonstrated by measurement of serum ALT/AST levels. Co-culture of MSC with lymphoma cells enhanced the release of hepatocyte growth factor (HGF) by MSC. These data suggest that hyaluronan-embedded MSC exert anti-lymphoma activity by ameliorating hepatic functionality.

Impact of transforming growth factor-beta1 on atrioventricular node conduction modification by injected autologous fibroblasts in the canine heart.

PubMed

Bunch, T Jared; Mahapatra, Srijoy; Bruce, G Keith; Johnson, Susan B; Miller, Dylan V; Horne, Benjamin D; Wang, Xiao-Li; Lee, Hon-Chi; Caplice, Noel M; Packer, Douglas L

2006-05-30

Atrioventricular (AV) nodal ablation for management of atrial fibrillation (AF) is irreversible and requires permanent pacemaker implantation. We hypothesized that as an alternative, implantation of autologous fibroblasts in the perinodal region would focally modify AV nodal conduction and that this modulation would be enhanced by pretreatment with transforming growth factor-beta1 (TGF-beta1), a stimulant of fibroblasts. Skin biopsies were taken from 12 mongrel dogs, and derived fibroblasts were dissociated and grown in culture for 2 weeks. Multiple injections (0.25 mL) were made through an 8F NOGA catheter along the fast/slow AV nodal pathways as guided by an electroanatomic mapping system. Seven dogs received fibroblasts alone (1x10(6) cells/mL), 7 dogs received TGF-beta1 (5 microg), 4 dogs received fibroblasts and TGF-beta1 (1x10(6) cells/mL+5 microg), and 4 dogs received saline only. AV node function was assessed at baseline and after 4 weeks. Saline (80 mL) with assigned therapy (0.25 mL per injection) was injected into the peri-AV nodal region in each dog. At baseline, the AH interval (66+/-3 ms) and the average RR interval (331+/-17 ms) in pacing-induced AF were similar in each cohort. The increase in AH interval in normal sinus rhythm was longer after fibroblast (23+/-4 versus 5+/-5 ms; P=0.05) and fibroblast plus TGF-beta1 (50+/-5 versus 5+/-5 ms; P<0.001) injections than with saline alone, with similar findings during high right atrium and distal coronary sinus pacing. The AH interval was not significantly increased after TGF-beta1 injections. The AH interval was significantly longer after fibroblast plus TGF-beta1 injections than with either therapy (TGF-beta1 or fibroblasts) alone. The RR interval during AF was increased in dogs that received fibroblasts alone (110+/-36 versus -41+/-34 ms) and to a greater extent with the addition of TGF-beta1 (294+/-108 versus -41+/-34 ms). No AV block was seen in any cohort at 4 weeks. Labeled fibroblasts that expressed vimentin were identified in all dogs that received cell injections at 4 weeks. AV nodal modification can be achieved with injected fibroblasts without the creation of AV block. The effect on AV node conduction is substantially enhanced by pretreatment of fibroblasts with TGF-beta1. These data have therapeutic potential for the management of rapid ventricular rate during AF without pacemaker implantation.

Strategies to improve electrode positioning and safety in cochlear implants.

PubMed

Rebscher, S J; Heilmann, M; Bruszewski, W; Talbot, N H; Snyder, R L; Merzenich, M M

1999-03-01

An injection-molded internal supporting rib has been produced to control the flexibility of silicone rubber encapsulated electrodes designed to electrically stimulate the auditory nerve in human subjects with severe to profound hearing loss. The rib molding dies, and molds for silicone rubber encapsulation of the electrode, were designed and machined using AutoCad and MasterCam software packages in a PC environment. After molding, the prototype plastic ribs were iteratively modified based on observations of the performance of the rib/silicone composite insert in a clear plastic model of the human scala tympani cavity. The rib-based electrodes were reliably inserted farther into these models, required less insertion force and were positioned closer to the target auditory neural elements than currently available cochlear implant electrodes. With further design improvements the injection-molded rib may also function to accurately support metal stimulating contacts and wire leads during assembly to significantly increase the manufacturing efficiency of these devices. This method to reliably control the mechanical properties of miniature implantable devices with multiple electrical leads may be valuable in other areas of biomedical device design.

Chronic intracortical microstimulation (ICMS) of cat sensory cortex using the Utah Intracortical Electrode Array.

PubMed

Rousche, P J; Normann, R A

1999-03-01

In an effort to assess the safety and efficacy of focal intracortical microstimulation (ICMS) of cerebral cortex with an array of penetrating electrodes as might be applied to a neuroprosthetic device to aid the deaf or blind, we have chronically implanted three trained cats in primary auditory cortex with the 100-electrode Utah Intracortical Electrode Array (UIEA). Eleven of the 100 electrodes were hard-wired to a percutaneous connector for chronic access. Prior to implant, cats were trained to "lever-press" in response to pure tone auditory stimulation. After implant, this behavior was transferred to "lever-presses" in response to current injections via single electrodes of the implanted arrays. Psychometric function curves relating injected charge level to the probability of response were obtained for stimulation of 22 separate electrodes in the three implanted cats. The average threshold charge/phase required for electrical stimulus detection in each cat was, 8.5, 8.6, and 11.6 nC/phase respectively, with a maximum charge/phase of 26 nC/phase and a minimum of 1.5 nC/phase thresholds were tracked for varying time intervals, and seven electrodes from two cats were tracked for up to 100 days. Electrodes were stimulated for no more than a few minutes each day. Neural recordings taken from the same electrodes before and after multiple electrical stimulation sessions were very similar in signal/noise ratio and in the number of recordable units, suggesting that the range of electrical stimulation levels used did not damage neurons in the vicinity of the electrodes. Although a few early implants failed, we conclude that ICMS of cerebral cortex to evoke a behavioral response can be achieved with the penetrating UIEA. Further experiments in support of a sensory cortical prosthesis based on ICMS are warranted.

Protective coatings for intraocular wirelessly controlled microrobots for implantation: Corrosion, cell culture, and in vivo animal tests.

PubMed

Pokki, Juho; Ergeneman, Olgaç; Chatzipirpiridis, George; Lühmann, Tessa; Sort, Jordi; Pellicer, Eva; Pot, Simon A; Spiess, Bernhard M; Pané, Salvador; Nelson, Bradley J

2017-05-01

Diseases in the ocular posterior segment are a leading cause of blindness. The surgical skills required to treat them are at the limits of human manipulation ability, and involve the risk of permanent retinal damage. Instrument tethering and design limit accessibility within the eye. Wireless microrobots suturelessly injected into the posterior segment, steered using magnetic manipulation are proposed for procedures involving implantation. Biocompatibility is a prerequisite for these procedures. This article investigates the use of polypyrrole- and gold-coated cobalt-nickel microrobots. While gold has been used in ocular implants, no ocular implantation involving polypyrrole is reported, despite its well-established biocompatibility properties. Coated and uncoated microrobots were investigated for their corrosion properties, and solutions that had contained coated and uncoated microrobots for one week were tested for cytotoxicity by monitoring NIH3T3 cell viability. None of the microrobots showed significant corrosion currents and corrosion potentials were as expected in relation to the intrinsic nobility of the materials. NIH3T3 cell viability was not affected by the release medium, in which coated/uncoated microrobots were stored. In vivo tests inside rabbit eyes were performed using coated microrobots. There were no significant inflammatory responses during the first week after injection. An inflammatory response detected after 2 weeks was likely due to a lack of longer-duration biocompatibility. The results provide valuable information for those who work on implant technology and biocompatibility. Coated microrobots have the potential to facilitate a new generation of surgical treatments, diagnostics and drug-delivery techniques, when implantation in the ocular posterior segment will be possible. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 836-845, 2017. © 2016 Wiley Periodicals, Inc.

A novel ropivacaine-loaded in situ forming implant prolongs the effect of local analgesia in rats

PubMed Central

Lu, Lei; Zhang, Wei; Wu, Xin; Wang, Xiaoyu; Zhang, Min; Zhu, Quangang; Ding, Xueying; Xu, Zhiyun

2012-01-01

Introduction Prolonged postoperative analgesia cannot be achieved by a single injection of local anesthetic solution. The objective of this study was to optimize the formulation of a ropivacaine hydrochloride (Ropi-HCl) loaded in situ forming implant (ISI) by addition of different co-solvents, and evaluate the in vitro release of Ropi-HCl, and the analgesic effect and toxicity of the optimized formulation in rats. Material and methods Triacetin (TA), benzyl benzoate (BB) and polyethylene glycol 400 (PEG 400) were used as additives and added to the solvent of N-methyl-2-pyrrolidone (NMP). Drug release to the surface and inner structural properties of the formed implant were evaluated by scanning electron microscopy (SEM). The analgesic effect was determined by injection near the rat sciatic nerve. Results The solvent system added with TA or BB significantly decreased the burst release, whereas PEG 400 increased the Ropi-HCl burst release from the formulation. Over 70% of the incorporated Ropi-HCl was released from all formulations in 14 days in the in vitro assay. The SEM showed that the surface of NMP-BB formulation was less porous and more homogeneous, compared with the other formulations. Compared with Ropi-HCl injection, the optimized formulation (NMP-BB) significantly prolonged the analgesic effect in 48 h (p < 0.05), with a mild degree of motor block from 3 h to 12 h. Histological evaluation of the injection site revealed only mild inflammatory infiltration without obvious pathological nerve alterations. Conclusions The biodegradable Ropi-HCl-loaded ISI system with NMP-BB may prove to be an attractive and safe alternative for the delivery of parenteral local anesthetics to prolong pain relief. PMID:24049519

Prevention of arterial graft spasm in rats using a vasodilator-eluting biodegradable nano-scaled fibre†

PubMed Central

Yagami, Kei; Yamawaki-Ogata, Aika; Satake, Makoto; Kaneko, Hiroaki; Oshima, Hideki; Usui, Akihiko; Ueda, Yuichi; Narita, Yuji

2013-01-01

OBJECTIVES Arterial graft spasm occasionally causes circulatory collapse immediately following coronary artery bypass graft. The aim of this study is to evaluate the efficacy of our developed materials, which were composed of milrinone (phosphodiesterase III inhibitor) or diltiazem (calcium-channel blocker), with nano-scaled fibre made of biodegradable polymer to prevent arterial spasm. METHODS Milrinone- or diltiazem-releasing biodegradable nano-scaled fibres were fabricated by an electrospinning procedure. In vivo milrinone- or diltiazem-releasing tests were performed to confirm the sustained release of the drugs. An in vivo arterial spasm model was established by subcutaneous injection of noradrenalin around the rat femoral artery. Rats were randomly divided into four groups as follows: those that received 5 mg of milrinone-releasing biodegradable nano-scaled fibre (group M, n = 14); 5 mg of diltiazem-releasing biodegradable nano-scaled fibre (group D, n = 12); or those that received fibre without drugs (as a control; group C, n = 14) implanted into the rat femoral artery. In the fourth group, sham operation was performed (group S, n = 10). One day after the implantation, noradrenalin was injected in all groups. The femoral arterial blood flow was measured continuously before and after noradrenalin injection. The maximum blood flow before noradrenalin injection and minimum blood flow after noradrenalin injection were measured. RESULTS In vivo drug-releasing test revealed that milrinone-releasing biodegradable nano-scaled fibre released 78% of milrinone and diltiazem-releasing biodegradable nano-scaled fibre released 50% diltiazem on the first day. The ratios of rat femoral artery blood flow after/before noradrenalin injection in groups M (0.74 ± 0.16) and D (0.72 ± 0.05) were significantly higher than those of groups C (0.54 ± 0.09) and S (0.55 ± 0.16) (P < 0.05). CONCLUSION Noradrenalin-induced rat femoral artery spasm was inhibited by the implantation of milrinone-releasing biodegradable nano-scaled fibre or diltiazem-releasing biodegradable nano-scaled fibre. These results suggested that our materials might be effective for the prevention of arterial graft spasm after coronary artery bypass graft. PMID:23513005

Effects of prosthetic materials on the host immune response: evaluation of polymethyl-methacrylate (PMMA), polyethylene (PE), and polystyrene (PS) particles.

PubMed

Frick, Chris; Dietz, Andrew C; Merritt, Katharine; Umbreit, Thomas H; Tomazic-Jezic, Vesna J

2006-01-01

The main causes for the long-term prosthetic implants' failure are the body's reaction to the implanted material or mechanical stress on the device resulting in the formation of wear particles. Particulate wear debris attracts macrophages, and depending on the chemical composition of the material and particle size, various levels of inflammatory response may occur. While transient inflammation is common, development of chronic inflammation may have serious consequences, leading to implant failure. Such a process may also cause systemic changes to immune functions and long-term effects on the host immune responses. In this study, we evaluated the effects of polystyrene (PS), polyethylene (PE), and polymethylmethacrylate (PMMA) particles on macrophage function and the generation of T-cell responses. Particles of various diameters were injected intraperitoneally into Balb/c mice, and immune functions were examined at 3, 10, and 21 days after the injection. The intensity of phagocytosis by peritoneal exudate cells (PECs) and the proliferative response of spleen cells from treated mice were evaluated. Enumeration of PECs revealed an increase in the total number of cells. Mice injected with PS or PE particles had a higher percentage of cells containing particles than PMMA-injected mice. Macrophages with PS or PE particles tended to adhere to and/or infiltrate peritoneal fibro-fatty tissues surrounding the spleen and pancreas, while the PMMA-carrying macrophages infiltrated the spleen, resulting in an increase of spleen size and "weight. The spleen cell proliferation assay revealed only mild and transient effects on the mitogen response in both PE and PS particle-injected mice. However, in the PMMA-injected mice we observed a lasting increase of the Con A response and a decrease of the LPS response. In vitro exposure of PECs from untreated mice showed a dose-response pattern in nitric oxide (NO) and TNFalpha production. While exposure to either PMMA or PE induced comparable levels of NO, exposure to PMMA induced a markedly higher production of TNFalpha than exposure to PE. The results indicate that particulate biomaterials may, in addition to the initial activation of phagocytes, significantly affect immune functions and compromise the host response to other antigenic stimuli.

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

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

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

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

Physiological Monitoring in Diving Mammals

DTIC Science & Technology

2015-09-30

obtain the required 70 MHz sine wave, we instead created a 10 MHz rectangle pulse wave and used a 70 MHz band pass filter (KR electronics 2657 sma) to...animals (Table 1) were sedated on the beach and transported to Long Marine Laboratory where the data logger was attached and the oximeter sensor...implanted under injectable sedation. In addition, the implantation procedure of the oximeter was assessed and we carefully noted any indications of trauma

Evaluation of injection augmentation treatment of hyaluronic acid based materials on rabbit vocal folds viscoelasticity.

PubMed

Borzacchiello, A; Mayol, L; Gärskog, O; Dahlqvist, A; Ambrosio, L

2005-06-01

The viscoelastic properties of vocal folds after injection of hyaluronic acid (hyaluronan, HA) based materials have been studied in an animal model (rabbit) six months after injection. The results indicate that the viscoelastic properties of the vocal folds injected with the HA based materials are similar to the healthy vocal folds (non-injected samples) used as control. Histological analysis has been also performed to investigate on the fate of the injected materials after six months from the implant. The HA based materials remain up to six months and they recruited fibroblasts that induce the ingrowth of new connective tissue resulting in an endogenous soft tissue augmentation. The HA based compounds are good candidate for further studies aimed at restoring/preserving the vibratory capacity of the vocal folds with injection treatment in glottal insufficiency.

Surgical insertions of transmitters and telemetry methods in fisheries research

USGS Publications Warehouse

Wargo Rub, A. Michelle; Jepsen, Niels; Liedtke, Theresa L.; Moser, L; Weber III, E. P. Scott

2015-01-01

Use of electronic transmitter and monitoring systems to track movements of aquatic animals has increased continuously since the inception of these systems in the mid-1950s. The purpose of the present report is to provide information about veterinary principles and their incorporation into surgical implantation procedures for fish. We also intend to provide insight into the unique challenges of field-based aquatic surgical studies. Within this context, 4 aspects of the process for surgical implantation of transmitters in fish (ie, handling, aseptic technique, anesthesia, and implantation) will be described. Effects of surgical insertion of transmitters (ie, tagging) and aspects of the surgical implantation process where collaboration and professional exchanges among nonveterinarian researchers and veterinarians may be most fruitful will be discussed. Although this report focuses on surgical implantation, the principles and protocols described here (other than incision and suture placement) are also applicable to studies that involve injection of transmitters into fish.

Microfabricated injectable drug delivery system

DOEpatents

Krulevitch, Peter A.; Wang, Amy W.

2002-01-01

A microfabricated, fully integrated drug delivery system capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.

BCA-kMC Hybrid Simulation for Hydrogen and Helium Implantation in Material under Plasma Irradiation

NASA Astrophysics Data System (ADS)

Kato, Shuichi; Ito, Atsushi; Sasao, Mamiko; Nakamura, Hiroaki; Wada, Motoi

2015-09-01

Ion implantation by plasma irradiation into materials achieves the very high concentration of impurity. The high concentration of impurity causes the deformation and the destruction of the material. This is the peculiar phenomena in the plasma-material interaction (PMI). The injection process of plasma particles are generally simulated by using the binary collision approximation (BCA) and the molecular dynamics (MD), while the diffusion of implanted atoms have been traditionally solved by the diffusion equation, in which the implanted atoms is replaced by the continuous concentration field. However, the diffusion equation has insufficient accuracy in the case of low concentration, and in the case of local high concentration such as the hydrogen blistering and the helium bubble. The above problem is overcome by kinetic Monte Carlo (kMC) which represents the diffusion of the implanted atoms as jumps on interstitial sites in a material. In this paper, we propose the new approach ``BCA-kMC hybrid simulation'' for the hydrogen and helium implantation under the plasma irradiation.

Laser sclerectomy and 5-FU controlled-drug-release biodegradable implant for glaucoma therapy

NASA Astrophysics Data System (ADS)

Villain, Franck L.; Parel, Jean-Marie A.; Kiss, Katalin; Parrish, Richard K.; Kuhne, Francois; Takesue, Yoshiko; Hostyn, Patrick

1993-06-01

Laser sclerectomy, a simple filtering procedure performed to alleviate high intraocular pressure in glaucoma patients, was taught to offer longer lasting effect and therefore improve the patient's outcome when compared with the standard trabeculectomy procedure. Recent clinical trials have shown that this was not the case and pharmacologic wound healing modulation is also required with this new procedure. Five-Fluorouracil (5-FU) is useful as an adjunct treatment for glaucoma filtering surgery. However, efficacy depends upon maintaining sustained drug levels, currently achieved by repeated daily injection of the drug for several weeks. To overcome this limitation, we designed a biodegradable implant for the sustained release of 5-FU. After laser sclerectomy, the implant is inserted through the same 1 mm wide conjunctival snip incision and positioned below the open channel. Implantation takes less than a minute. The implant releases the drug for over 15 days and totally biodegrades in less than 100 days. The combined laser surgery and implantation procedure show great potentials for the treatment of glaucoma.

Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy

PubMed Central

Jabs, Douglas A.; Ahuja, Alka; Van Natta, Mark; Dunn, JP; Yeh, Steven

2012-01-01

Purpose To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). Design Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. Participants 250 patients with CMV retinitis and CD4+ T cells <100 cells/µL (n=221) at enrollment or incident retinitis (n=29) during cohort follow-up. Methods The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. Main Outcome Measures Mortality, CMV dissemination, retinitis progression, treatment side effects. Results Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR]=0.5; 95% confidence interval [CI] = 0.3, 0.7; P=0.006), 90% reduction in new visceral CMV disease (adjusted HR=0.1; 95% CI = 0.04, 0.4;P=0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR=0.2; 95% CI= 0.1, 0.5; P=0.0005) when compared to those using only intraocular therapy (implants or injections). Compared to systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR=3.4, P=0.004) and greater visual field loss (for loss of ½ of the normal field, adjusted HR=5.5, P<0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression =0.5, P=0.26, and for loss ½ visual field =0.5, P=0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis among those treated with intravitreal injections was 0.017/EY (95% CI =0.006, 0.05) and among those treated with an implant 0.01/EY (95% CI =0.002, 0.04). Conclusions In the HAART era, systemic anti-CMV therapy, while there is immune compromise, appears to provide benefits in terms of longer survival and decreased CMV dissemination. PMID:23419804

Outcomes of intrathecal baclofen therapy in patients with cerebral palsy and acquired brain injury

PubMed Central

Yoon, Young Kwon; Lee, Kil Chan; Cho, Han Eol; Chae, Minji; Chang, Jin Woo; Chang, Won Seok; Cho, Sung-Rae

2017-01-01

Abstract Intrathecal baclofen (ITB) has been known to reduce spasticity which did not respond to oral medications and botulinum toxin treatment. However, few results have been reported comparing the effects of ITB therapy in patients with cerebral palsy (CP) and acquired brain injury. This study aimed to investigate beneficial and adverse effects of ITB bolus injection and pump therapy in patients with CP and to compare outcomes to patients with acquired brain injury such as traumatic brain injury and hypoxic brain injury. ITB test trials were performed in 37 patients (19 CP and 18 acquired brain injury). Based on ambulatory function, CP patients were divided into 2 groups: 11 patients with nonambulatory CP and 8 patients with ambulatory CP. Change of spasticity was evaluated using the Modified Ashworth Scale. Additional positive or negative effects were also evaluated after ITB bolus injection. In patients who received ITB pump implantation, outcomes of spasticity, subjective satisfaction and adverse events were evaluated until 12 months post-treatment. After ITB bolus injection, 32 patients (86.5%) (CP 84.2% versus acquired brain injury 88.9%) showed a positive response of reducing spasticity. However, 8 patients with CP had negative adverse effects. Particularly, 3 ambulatory CP patients showed standing impairment and 1 ambulatory CP patient showed impaired gait pattern such as foot drop because of excessive reduction of lower extremity muscle tone. Ambulatory CP patients received ITB pump implantation less than patients with acquired brain injury after ITB test trials (P = .003 by a chi-squared test). After the pump implantation, spasticity was significantly reduced within 1 month and the effect maintained for 12 months. Seventeen patients or their caregivers (73.9%) were very satisfied, whereas 5 patients (21.7%) suffered from adverse events showed no subjective satisfaction. In conclusion, ITB therapy was effective in reducing spasticity in patients with CP and acquired brain injury. Before ITB pump implantation, it seems necessary to perform the ITB bolus injection to verify beneficial effects and adverse effects especially in ambulatory CP. PMID:28834868

A meta-analysis of the effect of a dexamethasone intravitreal implant versus intravitreal anti-vascular endothelial growth factor treatment for diabetic macular edema.

PubMed

He, Ye; Ren, Xin-Jun; Hu, Bo-Jie; Lam, Wai-Ching; Li, Xiao-Rong

2018-05-21

This meta-analysis evaluated the effectiveness and safety of dexamethasone (DEX) implant and intravitreal anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). The PubMed, Embase, clinicaltrials.gov website and Cochrane Library databases were comprehensively searched for studies comparing DEX implant with anti-VEGF in patients with DME. Best-corrected visual acuity (BCVA), central subfield thickness (CST) and adverse events were extracted from the final eligible studies. Review Manager (RevMan) 5.3 for Mac was used to analyze the data and GRADE profiler were used to access the quality of outcomes. Based on four randomized clinical trials assessing a total of 521 eyes, the DEX implant can achieve visual acuity improvement for DME at rates similar to those achieved via anti-VEGF treatment (mean difference [MD] = - 0.43, P = 0.35), with superior anatomic outcomes at 6 months (MD = - 86.71 μm, P = 0.02), while requiring fewer injections, in comparison to anti-VEGF treatment. Although the mean reduction in CST did not showed significant difference at 12 months (MD = - 33.77 μm, P = 0.21), the significant in BCVA from baseline to 12 months supported the anti-VEGF treatment (MD = - 3.26, P < 0.00001). No statistically significant differences in terms of the serious adverse events. However, use of the DEX implant has higher risk of intraocular pressure elevation and cataract than anti-VEGF treatment. Compared with anti-VEGF, DEX implant improved anatomical outcomes significantly. However, this did not translate to improved visual acuity, which may be due to the progression of cataract. Therefore, the DEX implant may be recommended as a first chioce for select cases, such as for pseudophakic eyes, anti-VEGF-resistant eyes, or patients reluctant to receive intravitreal injections frequently.

Use of subconjunctival injections of 5-fluorouracil to rescue and prolong intraocular pressure reduction for a failing Ahmed glaucoma implant.

PubMed

Kaplowitz, Kevin; Khodadadeh, Sarah; Wang, Samantha; Lee, Daniel; Tsai, James C

2017-06-01

5-Fluorouracil (5-FU) has been well described for a failing trabeculectomy bleb, but not for aqueous shunts. We sought to determine whether subconjunctival 5-FU prolongs the intraocular pressure (IOP) efficacy of Ahmed shunts. We included all patients with Ahmed FP-7 implantation by one surgeon at Yale University. Patients with <3 months follow-up were excluded. Injections were done on a case-by-case basis, usually for IOP > 21 on >2 medications. Five-milligram (0.1 cc) injections were made over the plate. The control group consisted of Ahmed FP-7 patients without injections. The main outcome measure was IOP. Secondary outcome was success (IOP <21 mmHg, 20% decrease from preoperative IOP, and no reoperation). The average age of controls was 72.5 ± 16.6 years, and 63.7 ± 18.8 with 5-FU (p = 0.02). Forty-four patients received 5-FU and 45 did not. Mean preoperative IOP in controls was 31.5 ± 11 mmHg on 3.1 ± 1 medications, and 31.9 ± 9.0 mmHg (p = 0.86) on 3.3 ± 0.9 medications with 5-FU (p = 0.18). At a mean 137 days after surgery, mean pre-injection IOP was 25.3 ± 7.7 mmHg on 2.0 ± 1.3 medications. Five years following implantation, control IOPs averaged 12.9 ± 7.1 mmHg (53% decrease from preoperative IOP, p < 0.001) on 1.4 ± 1.1 medications versus 17.2 ± 4.9 mmHg (46% decrease from preoperative, 32% decrease from pre-5FU IOP, p < 0.001) on 2.7 ± 0.8 medications with 5-FU. The IOP at 5 years was statistically similar in both groups (p = 0.23). Five-year success rates trended higher with 5-FU (77 vs. 67%, p = 0.38). Subconjunctival injection of 5-FU sustained a significant long-term decline in intraocular pressures in eyes with failing Ahmed shunts. Outcomes between eyes receiving injections and controls were statistically similar.

Flushing ports of totally implantable venous access devices, and impact of the Huber point needle bevel orientation: experimental tests and numerical computation.

PubMed

Guiffant, Gérard; Durussel, Jean Jacques; Flaud, Patrice; Vigier, Jean Pierre; Merckx, Jacques

2012-01-01

The use of totally implantable venous access devices developed as a medical device allowing mid- and long-term, frequent, repeated, or continuous injection of therapeutic products, by vascular, cavitary, or perineural access. The effective flushing of these devices is a central element to assure long-lasting use. Our experimental work demonstrates that directing the Huber point needle opening in the diametrically opposite direction of the implantable port exit channel increases the flushing efficiency. These results are consolidated by numerical computations, which support recommendations not only for their maintenance, but also for their use.

Flushing ports of totally implantable venous access devices, and impact of the Huber point needle bevel orientation: experimental tests and numerical computation

PubMed Central

Guiffant, Gérard; Durussel, Jean Jacques; Flaud, Patrice; Vigier, Jean Pierre; Merckx, Jacques

2012-01-01

The use of totally implantable venous access devices developed as a medical device allowing mid- and long-term, frequent, repeated, or continuous injection of therapeutic products, by vascular, cavitary, or perineural access. The effective flushing of these devices is a central element to assure long-lasting use. Our experimental work demonstrates that directing the Huber point needle opening in the diametrically opposite direction of the implantable port exit channel increases the flushing efficiency. These results are consolidated by numerical computations, which support recommendations not only for their maintenance, but also for their use. PMID:23166455

Magnesium Powder Injection Molding (MIM) of Orthopedic Implants for Biomedical Applications

NASA Astrophysics Data System (ADS)

Wolff, M.; Schaper, J. G.; Suckert, M. R.; Dahms, M.; Ebel, T.; Willumeit-Römer, R.; Klassen, T.

2016-04-01

Metal injection molding (MIM) has a high potential for the economic near-net-shape mass production of small-sized and complex-shaped parts. The motivation for launching Mg into the MIM processing chain for manufacturing biodegradable medical implants is related to its compatibility with human bone and its degradation in a non-toxic matter. It has been recognized that the load-bearing capacity of MIM Mg parts is superior to that of biodegradable polymeric components. However, the choice of appropriate polymeric binder components and alloying elements enabling defect-free injection molding and sintering is a major challenge for the use of MIM Mg parts. This study considered the full processing chain for MIM of Mg-Ca alloys to achieve ultimate tensile strength of up to 141 MPa with tensile yield strength of 73 MPa, elongation at fracture Af of 7% and a Young's modulus of 38 GPa. To achieve these mechanical properties, a thermal debinding study was performed to determine optimal furnace and atmosphere conditions, sintering temperature, heating rates, sintering time and pressure.

Biomaterial-based regional chemotherapy: Local anticancer drug delivery to enhance chemotherapy and minimize its side-effects.

PubMed

Krukiewicz, Katarzyna; Zak, Jerzy K

2016-05-01

Since the majority of anticancer pharmacological agents affect not only cancer tissue but also normal cells, chemotherapy is usually accompanied with severe side effects. Regional chemotherapy, as the alternative version of conventional treatment, leads to the enhancement of the therapeutic efficiency of anticancer drugs and, simultaneously, reduction of toxic effects to healthy tissues. This paper provides an insight into different approaches of local delivery of chemotherapeutics, such as the injection of anticancer agents directly into tumor tissue, the use of injectable in situ forming drug carriers or injectable platforms in a form of implants. The wide range of biomaterials used as reservoirs of anticancer drugs is described, i.e. poly(ethylene glycol) and its copolymers, polyurethanes, poly(lactic acid) and its copolymers, poly(ɛ-caprolactone), polyanhydrides, chitosan, cellulose, cyclodextrins, silk, conducting polymers, modified titanium surfaces, calcium phosphate based biomaterials, silicone and silica implants, as well as carbon nanotubes and graphene. To emphasize the applicability of regional chemotherapy in cancer treatment, the commercially available products approved by the relevant health agencies are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

Effectiveness of computer-assisted anesthetic delivery system (sta™) in dental implant surgery: a prospective study

PubMed Central

GRASSI, F.R.; RAPONE, B.; SCARANO CATANZARO, F.; CORSALINI, M.; KALEMAJ, Z.

2017-01-01

SUMMARY Objectives. This prospective cohort study aimed to investigate effectiveness of Computerized Local Anesthesia (CLA) on oral implantology through estimation of pain and discomfort and total quantity of injected anesthetic. Methods. Forty-five consecutive patients whose treatment plan included immediate or late dental implants were included in this study. The main inclusion criteria comprised: previous implant intervention under conventional anesthesia (CA) during the past 3 years and no previous treatment of pain relief. All patients reported on a 0–10 scale on previous experience with CA, and new experience with CLA. The same CLA system, namely Single Tooth Anesthesia (STA) was used for all patients with half of the quantity normally used for CA. Data on quantity of anesthetic and reported ratings were collected and described. Potential associations and determinant variables were analysed through correlation analysis and regression models. Results. Out of 45 patients, 27 received post-extractive implant surgery whereas the rest 18 implant surgery on healed sites. The reported pain from STA (mean 1.6, SD 0.7) showed important difference as compared to CA (7.9, SD 1.2; z=5.873; p<0.0001). The comfort perceived during the STA ranged from 7 to 10 (mean 9.5, SD 0.79). A second injection with half of the initial dose was necessary in three cases only. Conclusions. STA system proved to be effective during interventions of dental implantology, by markedly reducing patients’ pain and discomfort and the total quantity of necessary anesthetic. PMID:29682255

Oxygen-related vacancy-type defects in ion-implanted silicon

NASA Astrophysics Data System (ADS)

Pi, X. D.; Burrows, C. P.; Coleman, P. G.; Gwilliam, R. M.; Sealy, B. J.

2003-10-01

Czochralski silicon samples implanted to a dose of 5 × 1015 cm-2 with 0.5 MeV O and to a dose of 1016 cm-2 with 1 MeV Si, respectively, have been studied by positron annihilation spectroscopy. The evolution of divacancies to vacancy (V)-O complexes is out-competed by V-interstitial (I) recombination at 400 and 500 °C in the Si- and O-implanted samples; the higher oxygen concentration makes the latter temperature higher. The defective region shrinks as the annealing temperature increases as interstitials are injected from the end of the implantation range (Rp). VmOn (m> n) are formed in the shallow region most effectively at 700 °C for both Si and O implantation. VxOy (x< y) are produced near Rp by the annealing. At 800 °C, implanted Si ions diffuse and reduce m and implanted O ions diffuse and increase n in VmOn. All oxygen-related vacancy-type defects appear to begin to dissociate at 950 °C, with the probable formation of oxygen clusters. At 1100 °C, oxygen precipitates appear to form just before Rp in O-implanted silicon.

The effects of the concentration of high-density polyethylene particles on the bone-implant interface.

PubMed

Brooks, R A; Sharpe, J R; Wimhurst, J A; Myer, B J; Dawes, E N; Rushton, N

2000-05-01

We used a rat model in vivo to study the effects of the concentration of polyethylene particles on the bone-implant interface around stable implants in the proximal tibia. Intra-articular injections of 10(4), 10(6) or 10(8) high-density polyethylene (HDPE) particles per joint were given 8, 10 and 12 weeks after surgery. The animals were killed after 14 and 26 weeks and the response at the interface determined. Fibrous tissue was seen at the bone-implant interface when the head of the implant was flush with the top of the tibia but not when it was sunk below the tibial plateau. In the latter case the implant was completely surrounded by a shell of bone. The area of fibrous tissue and that of the gap between the implant and bone was related to the concentration of particles in the 14-week group (p < 0.05). Foreign-body granulomas containing HDPE particles were seen at the bone-implant interface in animals given 10(8) particles. The pathology resembles that seen around prostheses with aseptic loosening and we suggest that this is a useful model by which to study this process.

Fillers: from the past to the future.

PubMed

Glogau, Richard G

2012-06-01

Modern medical use of injectable soft-tissue augmentation fillers has evolved from the introduction of bovine collage implants to an array of synthesized materials in the current domestic and foreign markets. The concept of augmentation has moved from simple lines, scars, and wrinkles to revolumizing the aging face. A brief overview of the past, present, and future injectable fillers is presented. Copyright © 2012 Elsevier Inc. All rights reserved.

Sex and Sexuality and HIV

MedlinePlus

... Education Home HIV Meds Updates Online Courses (CME) Case Studies Journal Articles Glossary Quick References Quick References Home ... against HIV: oral contraceptive ("the pill") injectable contraceptive (shot) contraceptive implant IUD (intrauterine device) emergency contraception ("morning- ...

Photovoltaic Retinal Prosthesis for Restoring Sight to Patients Blinded by Retinal Injury or Degeneration

DTIC Science & Technology

2016-02-01

are rapidly expanding [1][2]. Cochlear implants [3] have seen the most remarkable success in sensory neuroprosthetics, while retinal implants [4][5...intensities: Imax (bright pixels) and Imin (dark pixels). In the common return configurations (connected and monopolar), the current flowing through the...array forces the injected current to flow to the back side, which results in a potential build-up in front of the device. Near each pixel (within

Synthetic matrix of polyether-polyurethane as a biological platform for pancreatic regeneration.

PubMed

Pereira, Luciana Xavier; Viana, Celso Tarso Rodrigues; Orellano, Laura Alejandra Ariza; Almeida, Simone Aparecida; Vasconcelos, Anilton Cesar; Goes, Alfredo de Miranda; Birbrair, Alexander; Andrade, Silvia Passos; Campos, Paula Peixoto

2017-05-01

Several alternative cellular approaches using biomaterials to host insulin-producing cells derived from stem cells have been developed to overcome the limitations of type 1 diabetes treatment (exogenous insulin injection). However, none seem to fulfill all requirements needed to induce pancreatic cells successful colonization of the scaffolds. Here, we report a polymeric platform adherent to the native mice pancreas filled with human adipose stem cells (hASCs) that was able to induce growth of pancreatic parenchyma. Synthetic polyether-polyurethane discs were placed adjacent to pancreas of normoglycemic and streptozotocin-induced diabetic mice. At day 4 post implantation, 1×10 6 hASCs were injected intra-implant in groups of normoglycemic and diabetic mice. Immunohistochemistry analysis of the implants was performed to identify insulin positive cells in the newly formed tissue. In addition, metabolic, inflammatory and angiogenic parameters were carried out in those mice. This study provides evidence of the ability of a biohybrid device to induce the growth of differentiated pancreas parenchyma in both normoglycemic and streptozotocin-induced diabetic mice as detected by histological analysis. Glucose metabolism and body weight of hyperglycemic mice bearing hASCs implants improved. The synthetic porous scaffold bearing hASC cells placed adjacent to the native animal pancreas exhibits the potential to be exploited in future cell-based type 1 diabetes therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

A multicentre study investigating subcutaneous etonogestrel implants with injectable testosterone decanoate as a potential long-acting male contraceptive.

PubMed

Brady, B M; Amory, J K; Perheentupa, A; Zitzmann, M; Hay, C J; Apter, D; Anderson, R A; Bremner, W J; Pollanen, P; Nieschlag, E; Wu, F C W; Kersemaekers, W M

2006-01-01

The combination of etonogestrel implants with injectable testosterone decanoate was investigated as a potential male contraceptive. One hundred and thirty subjects were randomly assigned to three treatment groups, all receiving two etonogestrel rods (204 mg etonogestrel) and 400 mg testosterone decanoate either every 4 weeks (group I, n = 42), or every 6 weeks (group II, n = 51) or 600 mg testosterone decanoate every 6 weeks (group III, n = 37) for a treatment period of 48 weeks. One hundred and ten men completed 48 weeks of treatment. Sperm concentrations of <1 x 10(6)/ml were achieved in 90% (group I), 82% (group II) and 89% (group III) of subjects by week 24. Suppression was slower in group II, which also demonstrated more frequent escape from gonadotrophin suppression than groups I and III. Peak testosterone concentrations remained in the normal range throughout in all groups. Mean trough testosterone concentrations were initially subphysiological but increased into the normal range during treatment. Mean haemoglobin levels increased in group I, and a non-significant increase in weight and decline in high-density lipoprotein cholesterol was observed in all groups. Fourteen subjects discontinued treatment due to adverse events. Subcutaneous etonogestrel implants in combination with injectable testosterone decanoate resulted in profound suppression of spermatogenesis that could be maintained for up to 1 year. Efficacy of suppression was less in group II, probably due to inadequate testosterone dosage. This combination has potential as a long-acting male hormonal contraceptive.

Design and properties of novel gallium-doped injectable apatitic cements.

PubMed

Mellier, Charlotte; Fayon, Franck; Boukhechba, Florian; Verron, Elise; LeFerrec, Myriam; Montavon, Gilles; Lesoeur, Julie; Schnitzler, Verena; Massiot, Dominique; Janvier, Pascal; Gauthier, Olivier; Bouler, Jean-Michel; Bujoli, Bruno

2015-09-01

Different possible options were investigated to combine an apatitic calcium phosphate cement with gallium ions, known as bone resorption inhibitors. Gallium can be either chemisorbed onto calcium-deficient apatite or inserted in the structure of β-tricalcium phosphate, and addition of these gallium-doped components into the cement formulation did not significantly affect the main properties of the biomaterial, in terms of injectability and setting time. Under in vitro conditions, the amount of gallium released from the resulting cement pellets was found to be low, but increased in the presence of osteoclastic cells. When implanted in rabbit bone critical defects, a remodeling process of the gallium-doped implant started and an excellent bone interface was observed. The integration of drugs and materials is a growing force in the medical industry. The incorporation of pharmaceutical products not only promises to expand the therapeutic scope of biomaterials technology but to design a new generation of true combination products whose therapeutic value stem equally from both the structural attributes of the material and the intrinsic therapy of the drug. In this context, for the first time an injectable calcium phosphate cement containing gallium was designed with properties suitable for practical application as a local delivery system, implantable by minimally invasive surgery. This important and original paper reports the design and in-depth chemical and physical characterization of this groundbreaking technology. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Preservation of viscoelastic properties of rabbit vocal folds after implantation of hyaluronic Acid-based biomaterials.

PubMed

Choi, Jeong-Seok; Kim, Nahn Ju; Klemuk, Sarah; Jang, Yun Ho; Park, In Suh; Ahn, Kyung Hyun; Lim, Jae-Yol; Kim, Young-Mo

2012-09-01

To compare the rheological characteristics of structurally different hyaluronic acid (HA)-based biomaterials that are presently used for phonosurgery and to investigate their influence on the viscoelastic properties of vocal folds after implantation in an in vivo rabbit model. In vitro and in vivo rheometric investigation. Experimental laboratory, Inha and Seoul National Universities. Viscoelastic shear properties of 3 HA-based biomaterials (Rofilan, Restylane, and Reviderm) were measured with a strain-controlled rheometer. These biomaterials were injected into the deep layers of rabbit vocal folds, and viscoelastic moduli of the injected vocal folds were determined 2 months after the injection. The vocal fold specimens were observed using a light microscope and a transmission electron microscope. All HA-based biomaterials showed similar levels of shear viscosity, which were slightly higher than that of human vocal folds reported in previous studies. Compared with noninjected control vocal folds, there were no significant differences in the magnitudes of both elastic shear modulus (G') and viscous modulus (G") of injected vocal folds among all of the materials. Light microscopic images showed that all materials were observed in the deep layers of vocal folds and electron scanning images revealed that injected HA particles were homogeneously distributed in regions of collagenous fibers. HA-based biomaterials could preserve the viscoelastic properties of the vocal folds, when they were injected into vocal folds in an in vivo rabbit model. However, further studies on the influence of the biomaterials on the viscoelasticity of human vocal folds in ECM surroundings are still needed.

Comparison of mechanical and biological properties of zirconia and titanium alloy orthodontic micro-implants.

PubMed

Choi, Hae Won; Park, Young Seok; Chung, Shin Hye; Jung, Min Ho; Moon, Won; Rhee, Sang Hoon

2017-07-01

The aim of this study was to compare the initial stability as insertion and removal torque and the clinical applicability of novel orthodontic zirconia micro-implants made using a powder injection molding (PIM) technique with those parameters in conventional titanium micro-implants. Sixty zirconia and 60 titanium micro-implants of similar design (diameter, 1.6 mm; length, 8.0 mm) were inserted perpendicularly in solid polyurethane foam with varying densities of 20 pounds per cubic foot (pcf), 30 pcf, and 40 pcf. Primary stability was measured as maximum insertion torque (MIT) and maximum removal torque (MRT). To investigate clinical applicability, compressive and tensile forces were recorded at 0.01, 0.02, and 0.03 mm displacement of the implants at angles of 0°, 10°, 20°, 30°, and 40°. The biocompatibility of zirconia micro-implants was assessed via an experimental animal study. There were no statistically significant differences between zirconia micro-implants and titanium alloy implants with regard to MIT, MRT, or the amount of movement in the angulated lateral displacement test. As angulation increased, the mean compressive and tensile forces required to displace both types of micro-implants increased substantially at all distances. The average bone-to-implant contact ratio of prototype zirconia micro-implants was 56.88 ± 6.72%. Zirconia micro-implants showed initial stability and clinical applicability for diverse orthodontic treatments comparable to that of titanium micro-implants under compressive and tensile forces.

Osseointegration is improved by coating titanium implants with a nanostructured thin film with titanium carbide and titanium oxides clustered around graphitic carbon.

PubMed

Veronesi, Francesca; Giavaresi, Gianluca; Fini, Milena; Longo, Giovanni; Ioannidu, Caterina Alexandra; Scotto d'Abusco, Anna; Superti, Fabiana; Panzini, Gianluca; Misiano, Carlo; Palattella, Alberto; Selleri, Paolo; Di Girolamo, Nicola; Garbarino, Viola; Politi, Laura; Scandurra, Roberto

2017-01-01

Titanium implants coated with a 500nm nanostructured layer, deposited by the Ion Plating Plasma Assisted (IPPA) technology, composed of 60% graphitic carbon, 25% titanium oxides and 15% titanium carbide were implanted into rabbit femurs whilst into the controlateral femurs uncoated titanium implants were inserted as control. At four time points the animals were injected with calcein green, xylenol orange, oxytetracycline and alizarin. After 2, 4 and 8weeks femurs were removed and processed for histology and static and dynamic histomorphometry for undecalcified bone processing into methylmethacrylate, sectioned, thinned, polished and stained with Toluidine blue and Fast green. The overall bone-implant contacts rate (percentage of bone-implant contacts/weeks) of the TiC coated implant was 1.6 fold than that of the uncoated titanium implant. The histomorphometric analyses confirmed the histological evaluations. More precisely, higher Mineral Apposition Rate (MAR, μm/day) (p<0.005) and Bone Formation Rate (BFR, μm 2 /μm/day) (p<0.0005) as well as Bone Implant Contact (Bic) and Bone Ingrowth values (p<0.0005) were observed for the TiC coated implants compared to uncoated implants. In conclusion the hard nanostructured TiC layer protects the bulk titanium implant against the harsh conditions of biological tissues and in the same time, stimulating adhesion, proliferation and activity of osteoblasts, induces a better bone-implant contacts of the implant compared to the uncoated titanium implant. Copyright © 2016. Published by Elsevier B.V.

Hormonal Contraception, Pregnancy, Breastfeeding, and Risk of HIV Disease Progression Among Zambian Women.

PubMed

Wall, Kristin M; Kilembe, William; Haddad, Lisa; Vwalika, Bellington; Lakhi, Shabir; Khu, Naw Htee; Brill, Ilene; Chomba, Elwyn; Mulenga, Joseph; Tichacek, Amanda; Allen, Susan

2016-03-01

Some studies suggest that hormonal contraception, pregnancy, and/or breastfeeding may influence rates of HIV disease progression. From 1994 to 2012, HIV discordant couples recruited at couples' voluntary HIV counseling and testing centers in Lusaka were followed 3-monthly. Multivariate survival analyses explored associations between time-varying contraception, pregnancy, and breastfeeding and 2 outcomes among HIV-positive women: (1) time to death and (2) time to antiretroviral treatment (ART) initiation. Among 1656 female seropositive, male seronegative couples followed for 3359 person-years (PY), 224 women died [6.7/100 PY; 95% confidence interval (CI): 5.8 to 7.6]. After 2003, 290 women initiated ART (14.5/100 PY; 95% CI: 12.9 to 16.2). In a multivariate model of time to death, hormonal implant [adjusted hazard ratio (aHR) = 0.30; 95% CI: 0.10 to 0.98] and injectable (aHR = 0.59; 95% CI: 0.36 to 0.97) were significantly protective relative to nonhormonal method use, whereas oral contraceptive pill (OCP) use was not (aHR = 1.08; 95% CI: 0.74 to 1.57) controlling for baseline HIV disease stage, time-varying pregnancy, time-varying breastfeeding, and year of enrollment. In a multivariate model of time-to-ART initiation, implant was significantly protective (aHR = 0.54; 95% CI: 0.31 to 0.95), whereas OCP (aHR = 0.70; 95% CI: 0.44 to 1.10) and injectable (aHR = 0.85; 95% CI: 0.55 to 1.32) were not relative to nonhormonal method use controlling for variables above, woman's age, and literacy. Pregnancy was not significantly associated with death (aHR = 1.07; 95% CI: 0.68 to 1.66) or ART initiation (aHR = 1.24; 95% CI: 0.83 to 1.86), whereas breastfeeding was protective for death (aHR = 0.34; 95% CI: 0.19 to 0.62) and ART initiation (aHR = 0.49; 95% CI: 0.29 to 0.85). Hormonal implants and injectables significantly predicted lower mortality; implants were protective for ART initiation. OCPs and pregnancy were not associated with death or ART initiation, whereas breastfeeding was protective for both. Findings from this 18-year cohort study suggest that (1) HIV-positive women desiring pregnancy can be counseled to do so and breastfeed and (2) all effective contraceptive methods, including injectables and implants, should be promoted to prevent unintended pregnancy.

Darunavir

MedlinePlus

... HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex ... while taking darunavir, call your doctor. Do not breast-feed if you are ... rings, injections, or implants). Talk to your doctor about other ways to ...

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration.

PubMed

Eap, Sandy; Keller, Laetitia; Schiavi, Jessica; Huck, Olivier; Jacomine, Leandro; Fioretti, Florence; Gauthier, Christian; Sebastian, Victor; Schwinté, Pascale; Benkirane-Jessel, Nadia

2015-01-01

New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 μm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days' implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days' implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration.

Extended defects and hydrogen interactions in ion implanted silicon

NASA Astrophysics Data System (ADS)

Rangan, Sanjay

The structural and electrical properties of extended defects generated because of ion implantation and the interaction of hydrogen with these defects have been studied in this work. Two distinct themes have been studied, the first where defects are a detrimental and the second where they are useful. In the first scenario, transient enhanced diffusion of boron has been studied and correlated with defect evolution studies due to silicon and argon ion implants. Spreading resistance profiles (SRP) correlated with deep level transient spectroscopy (DLTS) measurements, reveal that a low anneal temperatures (<650°C) defect dissolution and defect injection dominates, resulting in increased junction depths. At higher anneal temperatures, however, repair dominates over defect injection resulting in shallower junctions. Hydrogenation experiments shows that hydrogen enhances dopant activation and reduces TED at low anneal temperatures (<550°C). At anneal temperatures >550°C, the effect of hydrogen is lost, due to its out-diffusion. Moreover, due to catastrophic out-diffusion of hydrogen, additional damage is created resulting in deeper junctions in hydrogenated samples, compared to the non-hydrogenated ones. Comparing defect evolution due to Si and Ar ion implants at different anneal temperatures, while the type of defects is the same in the two cases, their (defect) dissolution occurs at lower anneal temperatures (˜850°C) for Si implants. Dissolution for Ar implants seems to occur at higher anneal temperatures. The difference has been attributed to the increased number of vacancies created by Ar to that of silicon implant. In second aspect, nano-cavity formation due to vacancy agglomeration has been studied by helium ion implantation and furnace anneal, where the effect of He dose, implant energy and anneal time have been processing parameters that have been varied. Cavities are formed only when the localized concentration of He is greater than 3 x 1020 cm-3. While at high implant doses, a continuous cavity layer is formed, at low implant doses a discontinuous layer is observed. The formation of cavities at low doses has been observed for the first time. Variation of anneal times reveal that cavities are initially facetted (for short anneal times) and tend to become spherical when annealed for along time (300min). Also presented is the recipe for formation of multiple cavity layers and the electrical and optical properties of these cavities. Electrically, these cavities are metastable, with two strong minority carrier peaks formed by multiple defect levels. Photoluminescence measurements reveal a strong 0.8eV photon peak.

Search and Neutralize Factors (CSPGs) that Induce Decline in Transmission to Motoneurons from Spared Fibers after Chronic Spinal Cord Injury

DTIC Science & Technology

2013-10-01

animals received a subcutaneous injection of Buprenorphine (0.01mg/kg) to reduce post-operative pain. Contusion injury was performed at T10 spinal...HX SCI is attached). A downside of administration of NG2-antibody vial mini- pump in clinics is that it requires intrathecal implantation of the...principle, some recent clinical studies (Novartis clinical trials) showed that similar delivery of therapeutic agents using catheter implantation may

Persistence of bacterial DNA in orthopedic infections.

PubMed

Kaplan, Heidi B; Miranda, Justin A; Gogola, Gloria R; Gomez, Karen; Ambrose, Catherine G

2018-06-01

Polymerase chain reaction (PCR) has been proposed as a method to identify bacteria in clinical samples because it is more sensitive than culture techniques and can produce results rapidly. However, PCR can detect DNA from dead cells and thus cannot distinguish between live and dead cells in a tissue sample. Killed Staphylococcus aureus cells were implanted into the femurs and knee joints of rats to determine the length of time that DNA from dead cells is detectable in a living animal under conditions similar to common orthopedic infections. In the joint infection model studied here, the DNA from the dead planktonic bacteria was detected using PCR immediately after injection or 24 h later, but was undetectable 48 and 72 h after injection. In the biofilm implanted-device model studied, the DNA from these dead biofilm cells was detected by PCR immediately after implantation and at 24 h, but not at 48 or 72 h. Thus, our results indicate that DNA from dead cells does not persist in these animal model systems for more than 2 days, which should reduce concerns about possible false positive results using molecular DNA-based techniques for the detection of pathogens. Copyright © 2018. Published by Elsevier Inc.

Influence of serotonin and melatonin on some parameters of gastrointestinal activity.

PubMed

Bubenik, G A; Dhanvantari, S

1989-01-01

In vitro melatonin (M) reduced the tone of gut muscles and counteracted the tonic effect of serotonin (5-HT). In vivo 0.1 to 4 mg of 5-HT (contained in beeswax implants) decreased the food transit time (FTT) in a dose-dependent manner, but higher doses (5 and 6 mg) increased the FTT. Melatonin injected intraperitoneally into mice bearing 5-HT implants (2 mg per animal) blocked partly the serotonin effect and increased FTT by 50%; however, no dose-dependent effect was observed when doses between 0.01 and 1 mg were used. Surprisingly, M injected into intact mice decreased FTT to levels comparable to those observed in 5-HT implanted, M-treated mice. Again, this significant decrease was not dose-dependent between 0.02 and 1 mg. Although in vitro the maximal inhibition of serotonin-induced spasm was achieved when the M:5-HT ratio was 50-100:1, in vivo the effective ratio was about 1:1. This may indicate that part of M action on the gut movement is mediated by extraintestinal mechanisms. A hypothetical, counterbalancing system of M and 5-HT regulation of gut activity (similar to adrenaline-acetylcholine system) is proposed.

Percutaneously injectable fetal pacemaker: electrodes, mechanical design and implantation.

PubMed

Zhou, Li; Chmait, Ramen; Bar-Cohen, Yaniv; Peck, Raymond A; Loeb, Gerald E

2012-01-01

We are developing a self-contained cardiac pacemaker with a small, cylindrical shape (~3 × 20 mm) that permits it to be implanted percutaneously into a fetus to treat complete heart block and consequent hydrops fetalis, which is otherwise fatal. The device uses off-the-shelf components including a rechargeable lithium cell and a highly efficient relaxation oscillator encapsulated in epoxy and glass. A corkscrew electrode made from activated iridium can be screwed into the myocardium, followed by release of the pacemaker and a short, flexible lead entirely within the chest of the fetus to avoid dislodgement from fetal movement. The feasibility of implanting the device percutaneously under ultrasonic imaging guidance was demonstrated in acute adult rabbit experiments.

Disseminated Pleural Siliconoma Mimicking Malignant Pleural Mesothelioma.

PubMed

Tanaka, Toshiki; Tao, Hiroyuki; Hayashi, Tatsuro; Yoshiyama, Koichi; Furukawa, Masashi; Yoshida, Kumiko; Okabe, Kazunori

2015-12-01

A 48-year-old woman with a 3-month history of back pain was admitted for further examination of multiple left pleural nodules. She had undergone bilateral breast augmentation with silicone implants 10 years previously. Nine years after the operation, both ruptured implants were removed, and autologous fat was injected. Computed tomography revealed multiple pleural nodules suggestive of malignant pleural mesothelioma. Thoracoscopic exploration revealed multiple pleural nodules with massive pleural adhesions. The nodules were filled with viscous liquid and were histologically determined to be siliconomas. Disseminated pleural siliconoma should be recognized as a late adverse event of silicone breast implantation. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

GAVeCeLT* consensus statement on the correct use of totally implantable venous access devices for diagnostic radiology procedures.

PubMed

Bonciarelli, Giorgio; Batacchi, Stefano; Biffi, Roberto; Buononato, Massimo; Damascelli, Bruno; Ghibaudo, Flavio; Orsi, Franco; Pittiruti, Mauro; Scoppettuolo, Giancarlo; Verzè, Alessia; Borasi, Guido; De Cicco, Marcello; Dosio, Roberto; Gazzo, Paolo; Maso, Renzo; Roman, Alessandro; Ticha, Vladimira; Venier, Giacomo; Blackburn, Paul; Goossens, Godelieve A; Bowen Santolucito, Jamie; Stas, Marguerite; Van Boxtel, Ton; Vesely, Thomas M; de Lutio, Enrico

2011-01-01

The use of totally implantable venous access devices in radiology may be associated with complications such as occlusion of the system (because of the high density of some contrast), infection (if the port is not handled in aseptic conditions, using proper barrier protections), and mechanical complications due to the high-pressure administration of contrast by automatic injectors (so-called power injector), including extravasation of contrast media into the soft tissues, subintimal venous or myocardial injection, or serious damage to the device itself (breakage of the external connections, dislocation of the non-coring needle, or breakage of the catheter). The last problem - i.e., the damage of the device from a power injection - is not an unjustified fear, but a reality. A warning by the US Food and Drug Administration of July 2004 reports around 250 complications of this kind, referring to both port and central venous catheters and peripherally inserted central catheter systems, which occurred over a period of several years; in all cases, the damage occurred during the injection of contrast material by means of power injectors for computed tomography or magnetic resonance imaging procedures. Though the risk associated with the use of ports in radiodiagnostics is thus clear, it has been suggested that administration of the contrast material via the port may have some advantage in terms of image quality, increased comfort for the patient, and maybe more accurate reproducibility of the patient's own follow-up exams. This contention needs to be supported by evidence. Also, since many cancer patients who need frequent computed tomography studies already have totally implantable systems, it would seem reasonable to try to define how and when such systems may safely be used. The purpose of this consensus statement is to define recommendations based on the best available evidence, for the safe use of implantable ports in radiodiagnostics.

Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema.

PubMed

Busch, Catharina; Zur, Dinah; Fraser-Bell, Samantha; Laíns, Inês; Santos, Ana Rita; Lupidi, Marco; Cagini, Carlo; Gabrielle, Pierre-Henry; Couturier, Aude; Mané-Tauty, Valérie; Giancipoli, Ermete; Ricci, Giuseppe D'Amico; Cebeci, Zafer; Rodríguez-Valdés, Patricio J; Chaikitmongkol, Voraporn; Amphornphruet, Atchara; Hindi, Isaac; Agrawal, Kushal; Chhablani, Jay; Loewenstein, Anat; Iglicki, Matias; Rehak, Matus

2018-05-05

To compare functional and anatomical outcomes of continued anti-vascular endothelial growth factor (VEGF) therapy versus dexamethasone (DEX) implant in eyes with refractory diabetic macular edema (DME) after three initial anti-VEGF injections in a real-world setting. To be included in this retrospective multicenter, case-control study, eyes were required: (1) to present with early refractory DME, as defined by visual acuity (VA) gain ≤ 5 letters or reduction in central subfield thickness (CST) ≤ 20%, after a loading phase of anti-VEGF therapy (three monthly injections) and (2) to treat further with (a) anti-VEGF therapy or (b) DEX implant. Main outcome measures were change in visual acuity (VA) and central subfield thickness (CST) at 12 months. Due to imbalanced baseline characteristics, a matched anti-VEGF group was formed by only keeping eyes with similar baseline characteristics as those in the DEX group. A total of 110 eyes from 105 patients were included (anti-VEGF group: 72 eyes, DEX group: 38 eyes). Mean change in VA at 12 months was - 0.4 ± 10.8 letters (anti-VEGF group), and + 6.1 ± 10.6 letters (DEX group) (P = 0.004). Over the same period, mean change in CST was + 18.3 ± 145.9 µm (anti-VEGF group) and - 92.8 ± 173.6 µm (DEX group) (P < 0.001). Eyes in the DEX group were more likely to gain ≥ 10 letters (OR 3.71, 95% CI 1.19-11.61, P = 0.024) at month 12. In a real-world setting, eyes with DME considered refractory to anti-VEGF therapy after three monthly injections which were switched to DEX implant and had better visual and anatomical outcomes at 12 months than those that continued treatment with anti-VEGF therapy.

Alginate microencapsulation technology for the percutaneous delivery of adipose-derived stem cells.

PubMed

Moyer, Hunter R; Kinney, Ramsey C; Singh, Kimberly A; Williams, Joseph K; Schwartz, Zvi; Boyan, Barbara D

2010-11-01

Autologous fat is the ideal soft-tissue filler; however, its widespread application is limited because of variable clinical results and poor survival. Engineered fillers have the potential to maximize survival. Alginate is a hydrogel copolymer that can be engineered into spheres of <200 μm, thus facilitating mass transfer, allowing for subcutaneous injection, and protecting cells from shearing forces. Alginate powder was dissolved in saline, and adipose-derived stem cells (ADSCs) were encapsulated (1 million cells/mL) in alginate using an electrostatic bead generator. To assess effects of injection on cell viability, microspheres containing ADSCs were separated into 2 groups: the control group was decanted into culture wells and the injection group was mixed with basal media and injected through a 21-gauge needle into culture wells. Microbeads were cultured for 3 weeks, and cell number and viability were measured weekly using electron and confocal microscopy. To assess effects of percutaneous injection in vivo, twenty-four male nude mice were randomly separated into 2 groups and injected with either empty microcapsules or ADSC-laden microcapsules. Mice were harvested at 1 and 3 months, and the implants were examined microscopically to assess bead and cell viability. A flow rate of 5 mL/h and an electrostatic potential of 7 kV produced viable ADSC-laden microbeads of <200 μm. There were no differences in bead morphology and ADSC viability between microcapsules placed versus injected into tissue culture plates for up to 3 weeks. Microspheres implanted in a nude mouse model show durability up to 3 months with a host response around each individual sphere. ADSCs remained viable and showed signs of mitosis. ADSCs can be readily cultured, encapsulated, and injected in alginate microspheres. Stem cells suspended in alginate microspheres survive in vivo and are seen to replicate in vitro.

Evidence of increased endometrial vascular permeability at the time of implantation in the short-nosed fruit bat, Cyanopterus sphinx.

PubMed

Pakrasi, Pranab Lal; Tiwari, Anjana

2007-09-01

Early embryonic development and implantation were studied in tropical short-nosed fruit bat Cyanopterus sphinx. We report preimplantation development and embryo implantation. Different stages of cleavage were observed in embryo by direct microscopic examination of fresh embryos after retrieving them either from the oviduct or the uterus at different days, up to the day of implantation. Generally, the embryos enter the uterus at the 8-cell stage. Embryonic development continued without any delay and blastocyst were formed showing attachment to the uterine epithelium at the mesometrial side of the uterus. A distinct blue band was formed in the uterus. The site of blastocyst attachment was visualized as a blue band following intravenous injection of pontamine blue. Implantation occurred 9+/-0.7 days after mating. This study reports that bat embryonic development can be studied like other laboratory animals and that this bat shows blue dye reaction, indicating the site and exact time of implantation. This blue dye reaction can be used to accurately find post-implantational delay. We prove conclusively that this species of tropical bat does not have any type of embryonic diapause.

Peri-implant and systemic effects of high-/low-affinity bisphosphonate-hydroxyapatite composite coatings in a rabbit model with peri-implant high bone turnover

PubMed Central

2012-01-01

Background Hydroxyapatite (HA) coatings composed with bisphosphonates (BPs) which have high mineral-binding affinities have been confirmed to successfully enhance implant stability. However, few previous studies focused on HA coatings composed with low-affinity BPs or on systemic effects of locally released BPs. Methods In this long-term study, we developed two kinds of BP-HA composite coatings using either high-affinity BP (alendronate, ALN) or low-affinity BP (risedronate, RIS). Thirty-six rabbits were divided into three groups according to different coating applications (group I: HA, group II: ALN-HA, and group III: RIS-HA). Implants were inserted into the proximal region of the medullary cavity of the left tibiay. At insertion, 2 × 108 wear particles were injected around implants to induce a peri-implant high bone turnover environment. Both local (left tibias) and systemic (right tibias and lumbar vertebrae) inhibitory effect on bone resorption were compared, including bone-implant integration, bone architecture, bone mineral density (BMD), implant stability, and serum levels of bone turnover markers. Results The results indicated that ALN-HA composite coating, which could induce higher bone-implant contact (BIC) ratio, bone mass augmentation, BMD, and implant stability in the peri-implant region, was more potent on peri-implant bone, while RIS-HA composite coating, which had significant systemic effect, was more potent on non-peri-implant bone, especially lumbar vertebrae. Conclusions It is instructive and meaningful to further clinical studies that we could choose different BP-HA composite coatings according to the patient’s condition. PMID:22686414

Anti-infection activity of nanostructured titanium percutaneous implants with a postoperative infection model

NASA Astrophysics Data System (ADS)

Tan, Jing; Li, Yiting; Liu, Zhiyuan; Qu, Shuxin; Lu, Xiong; Wang, Jianxin; Duan, Ke; Weng, Jie; Feng, Bo

2015-07-01

The titanium percutaneous implants were widely used in clinic; however, they have an increased risk of infection since they breach the skin barrier. Lack of complete skin integration with the implants can cause infection and implant removal. In this work, three titania nanotubes (TNT) with different diameters, 50 nm (TNT-50), 100 nm (TNT-100) and 150 nm (TNT-150) arrays were prepared on titanium surfaces by anodization, pure titanium (pTi) was used as control. Samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and contact angle analysis. The antibacterial efficiency of TNT was evaluated in vitro against Staphylococcus aureus under the visible light. The results indicated that TNT-100 had the highest antibacterial efficiency under the visible light. Subsequently, TNT implants and pTi implants were placed subcutaneously to the dorsum of New Zealand White rabbits, 108 CFU S. aureus was inoculated into the implant sites 4 h after surgery. The TNF-alpha and IL-1alpha were determined using enzyme linked immunoassay (ELISA). TNT implants revealed less inflammatory factor release than pTi implants with or without injected S. aureus liquid. According to the histological results, the TNT implants displayed excellent tissue integration. Whereas, pTi implants were surrounded with fibrotic capsule, and the skin tissue was almost separated from the implant surface. Therefore, the TNT significantly inhibited the infection risk and enhanced tissue integration of the percutaneous implants compared to pTi. The immersion test in the culture medium suggested that one of causes be probably more proteins adsorbed on TNT than on pTi.

[Differential expression genes of bone tissues surrounding implants in diabetic rats by gene chip].

PubMed

Wang, Xin-xin; Ma, Yue; Li, Qing; Jiang, Bao-qi; Lan, Jing

2012-10-01

To compare mRNA expression profiles of bone tissues surrounding implants between normal rats and rats with diabetes using microarray technology. Six Wistar rats were randomly selected and divided into normal model group and diabetic group. Diabetic model condition was established by injecting Streptozotocin into peritoneal space. Titanium implants were implanted into the epiphyseal end of the rats' tibia. Bone tissues surrounding implant were harvested and sampled after 3 months to perform comprehensive RNA gene expression profiling, including 17983 for genome-wide association study.GO analysis was used to compare different gene expression and real-time PCR was used to confirm the results on core samples. The results indicated that there were 1084 differential gene expression. In the diabetic model, there were 352 enhanced expression genes, 732 suppressed expression genes. GO analysis involved 1154 different functional type. Osteoblast related gene expressions in bone tissue samples of diabetic rats were decreased, and lipid metabolism pathway related gene expression was increased.

Ranibizumab versus dexamethasone implant for central retinal vein occlusion: the RANIDEX study.

PubMed

Chatziralli, Irini; Theodossiadis, George; Kabanarou, Stamatina A; Parikakis, Efstratios; Xirou, Tina; Mitropoulos, Panagiotis; Theodossiadis, Panagiotis

2017-10-01

To compare intravitreal ranibizumab and dexamethasone implant in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). Participants were 42 treatment naive patients with ME due to CRVO, who received either intravitreal 0.5 mg ranibizumab (n = 25) or intravitreal 0.7 mg dexamethasone implant (n = 17). The main outcomes included the mean change in best corrected visual acuity (BCVA) and central subfield thickness (CST) at month 12 compared to baseline in the two groups. At month 12, there was no statistically significant difference in BCVA and CST change between the two groups. However, there was recurrence in ME at month 5 in the dexamethasone group. Both ranibizumab and dexamethasone implant were found to be safe and effective at the 12-month follow-up in patients with ME secondary to CRVO. Since there was a recurrence in ME at month 5 in the dexamethasone group, we suggested that intravitreal injection of dexamethasone implant should be potentially administered sooner than 6 months.

Vascularization of repaired limb bone defects using chitosan-β-tricalcium phosphate composite as a tissue engineering bone scaffold.

PubMed

Yang, Le; Wang, Qinghua; Peng, Lihua; Yue, Hong; Zhang, Zhendong

2015-08-01

Ensuring histocompatibility in the tissue engineering of bones is a complex issue. The aim of this study was to observe the feasibility of chitosan-β-tricalcium phosphate composite in repairing limb bone defects, and to evaluate the therapeutic effects on osteogenesis. Beagle mesenchymal stem cells (MSCs) were divided into an experimental group that was cultured with an injectable form of chitosan-β-tricalcium phosphate composite and a control group. The effect of the composite on bone tissue growth was evaluated by MTT assay. In addition, 12-month-old beagles were subjected to 15-mm femur defects and subsequently implanted with scaffolds to observe the effects on osteogenesis and vascularization. The dogs were subdivided into two groups of five animals: Group A, which was implanted with scaffold-MSC compounds, and Group B, which was implanted with scaffolds alone. The dogs were observed on the 2nd, 4th, 8th and 12th weeks post-implantation. Scanning electron microscopy analysis revealed that the composite was compatible with MSCs, with similar outcomes in the control and experimental groups. MTT analysis additionally showed that the MSCs in the experimental group grew in a similar manner to those in the control group. The composite did not significantly affect the MSC growth or proliferation. In combination with MSCs, the scaffold materials were effective in the promotion of osteogenesis and vascularization. In conclusion, the chitosan-β-tricalcium phosphate composite was compatible with the MSCs and did not affect cellular growth or proliferation, therefore proving to be an effective injectable composite for tissue engineered bone. Simultaneous implantation of stem cells with a carrier composite proved to function effectively in the repair of bone defects.

Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium.

PubMed Central

Dalton, T; Fu, K; Enders, G C; Palmiter, R D; Andrews, G K

1996-01-01

Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. Transgenic and control males were injected with cadmium, and the histology of the testes was examined. An injection of 7.5 mumol Cd/kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 mumol Cd/kg caused rapid changes in the histology of the testes and resulted in pronounced testicular necrosis in both control and transgenic mice. Female transgenic and control mice were mated and then injected with cadmium (30-45 mumol Cd/kg) on the day of blastocyst implantation (day 4). In both of these groups, injection of cadmium reduced pregnancy rate, and no dramatic protection was afforded by maternal and/or embryonic overexpression of MT. Thus, overexpression of MT-I does not significantly protect against either of these cadmium-induced effects on fertility. Images Figure 1. A Figure 1. B Figure 2. A Figure 2. B Figure 2. C Figure 3. Figure 4. A Figure 4. A Figure 4. B Figure 4. B Figure 4. B Figure 4. B Figure 4. D4 Figure 4. D4 Figure 4. D6 Figure 4. D6 Figure 4. D8 Figure 5. A Figure 5. B Figure 5. C Figure 5. D Figure 5. E Figure 6. A Figure 6. B Figure 6. C Figure 6. D Figure 6. E Figure 6. F PMID:8834864

Biomedical Imaging in Implantable Drug Delivery Systems

PubMed Central

Zhou, Haoyan; Hernandez, Christopher; Goss, Monika; Gawlik, Anna; Exner, Agata A.

2015-01-01

Implantable drug delivery systems (DDS) provide a platform for sustained release of therapeutic agents over a period of weeks to months and sometimes years. Such strategies are typically used clinically to increase patient compliance by replacing frequent administration of drugs such as contraceptives and hormones to maintain plasma concentration within the therapeutic window. Implantable or injectable systems have also been investigated as a means of local drug administration which favors high drug concentration at a site of interest, such as a tumor, while reducing systemic drug exposure to minimize unwanted side effects. Significant advances in the field of local DDS have led to increasingly sophisticated technology with new challenges including quantification of local and systemic pharmacokinetics and implant-body interactions. Because many of these sought-after parameters are highly dependent on the tissue properties at the implantation site, and rarely represented adequately with in vitro models, new nondestructive techniques that can be used to study implants in situ are highly desirable. Versatile imaging tools can meet this need and provide quantitative data on morphological and functional aspects of implantable systems. The focus of this review article is an overview of current biomedical imaging techniques, including magnetic resonance imaging (MRI), ultrasound imaging, optical imaging, X-ray and computed tomography (CT), and their application in evaluation of implantable DDS. PMID:25418857

A simple and effective approach to prepare injectable macroporous calcium phosphate cement for bone repair: Syringe-foaming using a viscous hydrophilic polymeric solution.

PubMed

Zhang, Jingtao; Liu, Weizhen; Gauthier, Olivier; Sourice, Sophie; Pilet, Paul; Rethore, Gildas; Khairoun, Khalid; Bouler, Jean-Michel; Tancret, Franck; Weiss, Pierre

2016-02-01

In this study, we propose a simple and effective strategy to prepare injectable macroporous calcium phosphate cements (CPCs) by syringe-foaming via hydrophilic viscous polymeric solution, such as using silanized-hydroxypropyl methylcellulose (Si-HPMC) as a foaming agent. The Si-HPMC foamed CPCs demonstrate excellent handling properties such as injectability and cohesion. After hardening the foamed CPCs possess hierarchical macropores and their mechanical properties (Young's modulus and compressive strength) are comparable to those of cancellous bone. Moreover, a preliminary in vivo study in the distal femoral sites of rabbits was conducted to evaluate the biofunctionality of this injectable macroporous CPC. The evidence of newly formed bone in the central zone of implantation site indicates the feasibility and effectiveness of this foaming strategy that will have to be optimized by further extensive animal experiments. A major challenge in the design of biomaterial-based injectable bone substitutes is the development of cohesive, macroporous and self-setting calcium phosphate cement (CPC) that enables rapid cell invasion with adequate initial mechanical properties without the use of complex processing and additives. Thus, we propose a simple and effective strategy to prepare injectable macroporous CPCs through syringe-foaming using a hydrophilic viscous polymeric solution (silanized-hydroxypropyl methylcellulose, Si-HPMC) as a foaming agent, that simultaneously meets all the aforementioned aims. Evidence from our in vivo studies shows the existence of newly formed bone within the implantation site, indicating the feasibility and effectiveness of this foaming strategy, which could be used in various CPC systems using other hydrophilic viscous polymeric solutions. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Evaluation of the poly(lactic-co-glycolic acid)/pluronic F127 for injection laryngoplasty in rabbits.

PubMed

Lee, Jin Ho; Kim, Dong Wook; Kim, Eun Na; Park, Seok-Won; Kim, Hee-Bok; Oh, Se Heang; Kwon, Seong Keun

2014-11-01

Poly(lactic-co-glycolic acid) (PLGA) is an aliphatic polyester and one of the most commonly used synthetic biodegradable polymers for tissue engineering. The objectives of this study were to evaluate the biocompatibility of PLGA/Pluronic F127 in the vocal fold. A randomized, prospective, controlled animal study. University laboratory. We used 18 New Zealand white rabbits, which were divided into 5% PLGA solution (n = 9) and 10% PLGA solution (n = 9) groups. The PLGA/Pluronic F127 solutions were injected into the rabbit vocal fold. Laryngoscopic exams were performed at 1, 4, and 8 weeks after implantation; then larynx specimens were sampled. High-speed video camera examination was performed for functional analysis of vocal mucosa vibration at 8 weeks after implantation. Also, we evaluated the amplitude of the mucosal wave from the laryngeal midline on high-speed recording. Histologic study of larynx specimen was performed at 4 and 8 weeks. All animals survived until the scheduled period. Laryngoscopic analysis showed that both 5% and 10% PLGA/Pluronic F127 maintained after 8 weeks after injection without significant inflammatory response. On functional analysis, high-speed camera examination revealed regular and symmetric contact of vocal fold mucosa without a distorted movement by injected PLGA/Pluronic F127. Histologically, no significant inflammation was observed in the injected vocal fold. As a vocal fold injection material, PLGA/Pluronic F127 showed a good bio-compatibility without significant inflammatory response. Further experiment will follow to elucidate its role for drug or gene delivery into the vocal fold. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2014.

Clinical significance of intercellular contact at the four-cell stage of human embryos, and the use of abnormal cleavage patterns to identify embryos with low implantation potential: a time-lapse study.

PubMed

Liu, Yanhe; Chapple, Vincent; Feenan, Katie; Roberts, Peter; Matson, Phillip

2015-06-01

To investigate the clinical significance of intercellular contact point (ICCP) in four-cell stage human embryos and the effectiveness of morphology and abnormal cleavage patterns in identifying embryos with low implantation potential. Retrospective cohort study. Private IVF center. A total of 223 consecutive IVF and intracytoplasmic sperm injection treatment cycles, with all resulting embryos cultured in the Embryoscope, and a subset of 207 cycles analyzed for ICCP number where good-quality four-cell embryos were available on day 2 (n = 373 IVF and n = 392 intracytoplasmic sperm injection embryos). None. Morphologic score on day 3, embryo morphokinetic parameters, incidence of abnormal biological events, and known implantation results. Of 765 good-quality four-cell embryos, 89 (11.6%) failed to achieve six ICCPs; 166 of 765 (21.7%) initially had fewer than six ICCPs but were able to establish six ICCPs before subsequent division. Embryos with fewer than six ICCPs at the end of four-cell stage had a lower implantation rate (5.0% vs. 38.5%), with lower embryology performance in both conventional and morphokinetic assessments, compared with embryos achieving six ICCPs by the end of four-cell stage. Deselecting embryos with poor morphology, direct cleavage, reverse cleavage, and fewer than six ICCPs at the four-cell stage led to a significantly improved implantation rate (33.6% vs. 22.4%). Embryos with fewer than six ICCPs at the end of the four-cell stage show compromised subsequent development and reduced implantation potential. Deselection of embryos with poor morphology and abnormal cleavage revealed via time-lapse imaging could provide the basis of a qualitative algorithm for embryo selection. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

PubMed

Manna, Soumyarwit; Donnell, Anna M; Kaval, Necati; Al-Rjoub, Marwan F; Augsburger, James J; Banerjee, Rupak K

2018-05-29

Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. In the current study, different combinations of Poly(lactic-co-glycolic) acid (PLGA)/PLA coatings were used for lipophilic surface modification of the CS-MTX micro-implant, such as PLGA 5050, PLGA 6535 and PLGA 7525 (PLA: PGA - 50:50, 65:35, 75:25, respectively; M.W: 54,400 - 103,000) and different PLA, such as PLA 100 and PLA 250 (MW: 102,000 and 257,000, respectively). This improved the duration of total MTX release from the coated CS-MTX micro-implants to ∼3-5 months. With an increase in PLA content in PLGA and molecular weight of PLA, a) the initial burst of MTX and the mean release rate of MTX can be reduced; and b) the swelling and biodegradation of the micro-implants can be delayed. The controlled drug release mechanism is caused by a combination of diffusion process and hydrolysis of the polymer coating, which can be modulated by a) PLA content in PLGA and b) molecular weight of PLA, as inferred from Korsmeyer Peppas model, Zero order, First order and Higuchi model fits. This improved micro-implant formulation has the potential to serve as a platform for controlled release of hydrophilic drugs to treat selected VR diseases. Copyright © 2018. Published by Elsevier B.V.

Outcomes of Fat-Augmented Latissimus Dorsi (FALD) Flap Versus Implant-Based Latissimus Dorsi Flap for Delayed Post-radiation Breast Reconstruction.

PubMed

Demiri, Efterpi C; Dionyssiou, Dimitrios D; Tsimponis, Antonios; Goula, Christina-Olga; Pavlidis, Leonidas C; Spyropoulou, Georgia-Alexandra

2018-06-01

Although free abdominal flaps constitute the gold standard in post-radiation delayed breast reconstruction, latissimus dorsi-based methods offer alternative reconstructive options. This retrospective study aims to compare outcomes of delayed breast reconstruction using the fat-augmented latissimus dorsi (FALD) autologous reconstruction and the latissimus dorsi-plus-implant reconstruction in irradiated women. We reviewed the files of 47 post-mastectomy irradiated patients (aged 29-73 years), who underwent delayed latissimus dorsi-based breast reconstruction between 2010 and 2016. Twenty-three patients (Group A) had an extended FALD flap and twenty-four patients (Group B) an implant-based latissimus dorsi reconstruction. Patients' age, BMI, pregnancies, volume of injected fat, implant size, postoperative complications, and secondary surgical procedures were recorded and analyzed. Age, BMI, pregnancies, and donor-site complications were similar in both groups (p > 0.05). Mean fat volume injected initially was 254 cc (ranged 130-380 cc/session); mean implant volume was 323 cc (ranged 225-420 cc). Breast complications were significantly fewer in Group A (one wound dehiscence, two oily cysts) compared to Group B (three cases with wound dehiscence, two extrusions, thirteen severe capsular contractions). Non-statistically significant difference was documented for secondary procedures between groups; although the mean number of additional surgeries/patient was higher in Group A, they referred to secondary lipofilling, whereas in Group B they were revision surgeries for complications. The FALD flap constitutes an alternative method for delayed autologous reconstruction after post-mastectomy irradiation, avoiding implant-related complications. Although additional fat graft sessions might be required, it provides an ideal autogenous reconstructive option for thin nulliparous women, with a small opposite breast and adequate fat donor sites. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Contraceptive method switching in the United States.

PubMed

Grady, William R; Billy, John O G; Klepinger, Daniel H

2002-01-01

Switching among contraceptive method types is the primary determinant of the prevalence of use of specific contraceptive methods, and it has direct implications for women's ability to avoid unintended pregnancies. Yet, method switching among U.S. women has received little attention from researchers. Data from the 1995 National Survey of Family Growth were used to construct multiple-decrement life tables to explore the gross switching rates of married and unmarried women. Within each group, discrete-time hazard models were estimated to determine how women's characteristics affect their switching behavior. Overall rates of method switching are high among both married and unmarried women (40% and 61%, respectively). Married women's two-year switching rates vary from 30% among women who use the implant, injectable, IUD or other reversible methods to 43% among nonusers, while unmarried women's rates vary from 33% among women who use the implant, injectable or IUD to 70% among nonusers. Multivariate analyses of method switching according to women's characteristics indicate that among married women, women without children are less likely than other women to adopt sterilization or a long-term reversible contraceptive (the implant, injectable or IUD). Older married women have a higher rate than their younger counterparts of switching to sterilization, but are also more likely to continue using no method. Among unmarried women, younger and more highly educated women have high rates of switching to the condom and to dual methods. Women's method switching decisions may be driven primarily by concerns related to level and duration of contraceptive effectiveness, health risks associated with contraceptive use and, among single women, sexually transmitted disease prevention.

Cannula Implantation into the Cisterna Magna of Rodents.

PubMed

Xavier, Anna L R; Hauglund, Natalie Linea; von Holstein-Rathlou, Stephanie; Li, Qianliang; Sanggaard, Simon; Lou, Nanhong; Lundgaard, Iben; Nedergaard, Maiken

2018-05-23

Cisterna magna cannulation (CMc) is a straightforward procedure that enables direct access to the cerebrospinal fluid (CSF) without operative damage to the skull or the brain parenchyma. In anesthetized rodents, the exposure of the dura mater by blunt dissection of the neck muscles allows the insertion of a cannula into the cisterna magna (CM). The cannula, composed either by a fine beveled needle or borosilicate capillary, is attached via a polyethylene (PE) tube to a syringe. Using a syringe pump, molecules can then be injected at controlled rates directly into the CM, which is continuous with the subarachnoid space. From the subarachnoid space, we can trace CSF fluxes by convective flow into the perivascular space around penetrating arterioles, where solute exchange with the interstitial fluid (ISF) occurs. CMc can be performed for acute injections immediately following the surgery, or for chronic implantation, with later injection in anesthetized or awake, freely moving rodents. Quantitation of tracer distribution in the brain parenchyma can be performed by epifluorescence, 2-photon microscopy, and magnetic resonance imaging (MRI), depending on the physico-chemical properties of the injected molecules. Thus, CMc in conjunction with various imaging techniques offers a powerful tool for assessment of the glymphatic system and CSF dynamics and function. Furthermore, CMc can be utilized as a conduit for fast, brain-wide delivery of signaling molecules and metabolic substrates that could not otherwise cross the blood brain barrier (BBB).

New injectable elastomeric biomaterials for hernia repair and their biocompatibility.

PubMed

Skrobot, J; Zair, L; Ostrowski, M; El Fray, M

2016-01-01

Complications associated with implantation of polymeric hernia meshes remain a difficult surgical challenge. We report here on our work, developing for the first time, an injectable viscous material that can be converted to a solid and elastic implant in vivo, thus successfully closing herniated tissue. In this study, long-chain fatty acids were used for the preparation of telechelic macromonomers end-capped with methacrylic functionalities to provide UV curable systems possessing high biocompatibility, good mechanical strength and flexibility. Two different systems, comprising urethane and ester bonds, were synthesized from non-toxic raw materials and then subjected to UV curing after injection of viscous material into the cavity at the abdominal wall during hernioplasty in a rabbit hernia model. No additional fixation or sutures were required. The control group of animals was treated with commercially available polypropylene hernia mesh. The observation period lasted for 28 days. We show here that artificially fabricated defect was healed and no reherniation was observed in the case of the fatty acid derived materials. Importantly, the number of inflammatory cells found in the surrounding tissue was comparable to these found around the standard polypropylene mesh. No inflammatory cells were detected in connective tissues and no sign of necrosis has been observed. Collectively, our results demonstrated that new injectable and photocurable systems can be used for minimally invasive surgical protocols in repair of small hernia defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Experiences with power-injectable port systems: complications, patient satisfaction and clinical benefit].

PubMed

Chang, D-H; Kabbasch, C; Bovenschulte, H; Libicher, M; Maintz, D; Bangard, C

2013-05-01

Evaluation of complications, patient satisfaction and clinical benefit of port systems with authorization for high pressure injection of contrast agent during CT/MR examinations. Ultrasound-guided insertions of central venous port catheters were performed through the lateral subclavian vein at a university teaching hospital. The radiological information system (HIS/RIS) was used to evaluate technical success and complication rates. Assessment of patient satisfaction and clinical benefit was carried out by a questionnaire during a telephone call 6 months after implantation of the port system. A total of 195 port systems in 193 patients were implanted. The catheter remained in place for a mean duration of 169 days (overall 29,210 catheter days). The technical success rate was 99.5 % and the overall complication rate was 17.4 % (24/138; 0.82 per 1000 catheter days). Follow-up revealed 13 early port explantations (9 %). Most of the patients reported high satisfaction in general (satisfied/very satisfied: 94 %). 34/209 contrast-enhanced CT/MRT scans (16 %) were performed using the port for contrast media injection. There were no complications during or after administration of contrast agent via the port system. The Powerport system is a safe alternative for peripheral i. v. contrast media injection during CT/MR scans, but has been infrequently used. Most patients reported high overall satisfaction with the port system. © Georg Thieme Verlag KG Stuttgart · New York.

Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy.

PubMed

Jabs, Douglas A; Ahuja, Alka; Van Natta, Mark; Dunn, J P; Yeh, Steven

2013-06-01

To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. A total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/μl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up. The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. Mortality, CMV dissemination, retinitis progression, and treatment side effects. Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04-0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1-0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006-0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002-0.04) among those treated with an implant. In the HAART era, systemic anti-CMV therapy, while there is immune compromise, seems to provide benefits in terms of longer survival and decreased CMV dissemination. Proprietary or commercial disclosure may be found after the references. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Selective etching of injection molded zirconia-toughened alumina: Towards osseointegrated and antibacterial ceramic implants.

PubMed

Flamant, Quentin; Caravaca, Carlos; Meille, Sylvain; Gremillard, Laurent; Chevalier, Jérôme; Biotteau-Deheuvels, Katia; Kuntz, Meinhard; Chandrawati, Rona; Herrmann, Inge K; Spicer, Christopher D; Stevens, Molly M; Anglada, Marc

2016-12-01

Due to their outstanding mechanical properties and excellent biocompatibility, zirconia-toughened alumina (ZTA) ceramics have become the gold standard in orthopedics for the fabrication of ceramic bearing components over the last decade. However, ZTA is bioinert, which hampers its implantation in direct contact with bone. Furthermore, periprosthetic joint infections are now the leading cause of failure for joint arthroplasty prostheses. To address both issues, an improved surface design is required: a controlled micro- and nano-roughness can promote osseointegration and limit bacterial adhesion whereas surface porosity allows loading and delivery of antibacterial compounds. In this work, we developed an integrated strategy aiming to provide both osseointegrative and antibacterial properties to ZTA surfaces. The micro-topography was controlled by injection molding. Meanwhile a novel process involving the selective dissolution of zirconia (selective etching) was used to produce nano-roughness and interconnected nanoporosity. Potential utilization of the porosity for loading and delivery of antibiotic molecules was demonstrated, and the impact of selective etching on mechanical properties and hydrothermal stability was shown to be limited. The combination of injection molding and selective etching thus appears promising for fabricating a new generation of ZTA components implantable in direct contact with bone. Zirconia-toughened alumina (ZTA) is the current gold standard for the fabrication of orthopedic ceramic components. In the present work, we propose an innovative strategy to provide both osseointegrative and antibacterial properties to ZTA surfaces: we demonstrate that injection molding allows a flexible design of surface micro-topography and can be combined with selective etching, a novel process that induces nano-roughness and surface interconnected porosity without the need for coating, avoiding reliability issues. These surface modifications have the potential to improve osseointegration. Furthermore, our results show that the porosity can be used for drug delivery and suggest that the etched surface could reduce bacterial adhesion. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Tissue Engineering in Osteoarthritis: Current Status and Prospect of Mesenchymal Stem Cell Therapy.

PubMed

Im, Gun-Il

2018-04-27

Osteoarthritis (OA) is the most common form of arthritis. Over the last 20 years, attempts have been made to regenerate articular cartilage to overcome the limitations of conventional treatments. As OA is generally associated with larger and diffuse involvement of articular surfaces and alteration of joint homeostasis, a tissue engineering approach for cartilage regeneration is more difficult than in simple chondral defects. Autologous and allogeneic mesenchymal stem cells (MSCs) have rapidly emerged as investigational products for cartilage regeneration. This review outlines points to consider in MSC-based approaches for OA treatment, including allogeneic MSCs, sources of MSCs, dosages, feasibility of multiple injections, indication according to severity of OA lesion and patient age, and issues regarding implantation versus injection. We introduce possible mechanisms of action of implanted or injected MSCs as well as the immunological aspects of MSC therapy and provide a summary of clinical trials of MSCs in the treatment of OA. Given current knowledge, it is too early to draw conclusions on the ultimate effectiveness of intra-articular application of MSCs in terms of regenerative effects. Further radiological and histological data will be needed, with a larger pool of patients, before this question can be answered.

Comparison of mechanical properties for polyamide 12 composite-based biomaterials fabricated by fused filament fabrication and injection molding

NASA Astrophysics Data System (ADS)

Rahim, Tuan Noraihan Azila Tuan; Abdullah, Abdul Manaf; Akil, Hazizan Md; Mohamad, Dasmawati

2016-12-01

The emergence of 3D printing technology known as fused filament fabrication (FFF) has offered the possibility of producing an anatomically accurate, patient specific implant with more affordable prices. The only weakness of this technology is related to incompatibility and lack of properties of current material to be applied in biomedical. Therefore, this study aims to develop a new, polymer composite-based biomaterial that exhibits a high processability using FFF technique, strong enough and shows acceptable biocompatibility, and safe for biomedical use. Polyamide 12 (PA12), which meets all these requirements was incorporated with two bioceramic fillers, zirconia and hydroxyapatite in order to improve the mechanical and bioactivity properties. The obtained mechanical properties were compared with injection-molded specimens and also a commercial biomedical product, HAPEXTM which is composed of hydroxyapatite and polyethylene. The yield strength and modulus of the PA12 composites increased steadily with increasing filler loading. Although the strength of printed PA12 composites were reduced compared with injection molded specimen, but still higher than HAPEXTM material. The higher surface roughness obtained by printed PA12 was expected to enhance the cell adhesion and provide better implant fixation.

Long acting systemic HIV pre-exposure prophylaxis: an examination of the field.

PubMed

Lykins, William R; Luecke, Ellen; Johengen, Daniel; van der Straten, Ariane; Desai, Tejal A

2017-12-01

Oral pre-exposure prophylaxis for the prevention of HIV-1 transmission (HIV PrEP) has been widely successful as demonstrated by a number of clinical trials. However, studies have also demonstrated the need for patients to tightly adhere to oral dosing regimens in order to maintain protective plasma and tissue concentrations. This is especially true for women, who experience less forgiveness from dose skipping than men in clinical trials of HIV PrEP. There is increasing interest in long-acting (LA), user-independent forms of HIV PrEP that could overcome this adherence challenge. These technologies have taken multiple forms including LA injectables and implantables. Phase III efficacy trials are ongoing for a LA injectable candidate for HIV PrEP. This review will focus on the design considerations for both LA injectable and implantable platforms for HIV PrEP. Additionally, we have summarized the existing LA technologies currently in clinical and pre-clinical studies for HIV PrEP as well as other technologies that have been applied to HIV PrEP and contraceptives. Our discussion will focus on the potential application of these technologies in low resource areas, and their use in global women's health.

An in vitro and in vivo investigation of the biological behavior of a ferrimagnetic cement for highly focalized thermotherapy.

PubMed

Portela, Ana; Vasconcelos, Mário; Branco, Rogério; Gartner, Fátima; Faria, Miguel; Cavalheiro, José

2010-08-01

The cancer treatment by local hyperthermia, using a high frequency electromagnetic field is an extensively studied subject. For this propose it was developed a ferrimagnetic cement (FC) to be injected directly into the tumor. In this study it was determined the FC injectability, its capability to generate heat when placed within a magnetic field and its interaction with a modified simulated body fluid using SEM/EDS and XRD. The FC biological response was assessed by the intramuscular implantation in rats and histological analysis of the surrounding tissues. The results suggest that FC can be injected directly into the tumor, its temperature can be increased when exposed to a magnetic field and the surface of the immersed samples quickly becomes coated with precipitate denoting its ionic change with the surrounding medium. The histological analysis revealed a transient local inflammatory reaction, similar to the control material, only slightly more abundant during the first weeks, with a gradual decrease over the implantation time. Based on these results, we concluded that FC might be useful for highly focalized thermotherapy, with a good potential for clinical use.

Interspecies chimera between primate embryonic stem cells and mouse embryos: Monkey ESCs engraft into mouse embryos, but not post-implantation fetuses

PubMed Central

Simerly, Calvin; McFarland, Dave; Castro, Carlos; Lin, Chih-Cheng; Redinger, Carrie; Jacoby, Ethan; Mich-Basso, Jocelyn; Orwig, Kyle; Mills, Parker; Ahrens, Eric; Navara, Chris; Schatten, Gerald

2016-01-01

Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst injection. Aggregation chimera produced mouse blastocysts with GFP-nhpESCs at the inner cell mass (ICM), and embryo transfers (ETs) generated dimly-fluorescencing abnormal fetuses. Direct injection of GFP-nhpESCs into blastocysts produced normal non-GFP-fluorescencing fetuses. Injected chimera showed >70% loss of GFP-nhpESCs after 21 h culture. Outgrowths of all chimeric blastocysts established distinct but separate mouse- and NHP-ESC colonies. Extensive endogenous autofluorescence compromised anti-GFP detection and PCR analysis did not detect nhpESCs in fetuses. NhpESCs localize to the ICM in chimera and generate pregnancies. Because primate ESCs do not engraft post-implantation, and also because endogenous autofluorescence results in misleading positive signals, interspecific chimera assays for pluripotency with primate stem cells is unreliable with the currently available ESCs. Testing primate ESCs reprogrammed into even more naïve states in these inter-specific chimera assays will be an important future endeavor. PMID:21543277

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

PubMed Central

Eap, Sandy; Keller, Laetitia; Schiavi, Jessica; Huck, Olivier; Jacomine, Leandro; Fioretti, Florence; Gauthier, Christian; Sebastian, Victor; Schwinté, Pascale; Benkirane-Jessel, Nadia

2015-01-01

New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 μm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days’ implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days’ implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration. PMID:25709432

Implantable batteryless device for on-demand and pulsatile insulin administration

NASA Astrophysics Data System (ADS)

Lee, Seung Ho; Lee, Young Bin; Kim, Byung Hwi; Lee, Cheol; Cho, Young Min; Kim, Se-Na; Park, Chun Gwon; Cho, Yong-Chan; Choy, Young Bin

2017-04-01

Many implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.

Tag retention, growth, and survival of red swamp crayfish marked with a visible implant tag

USGS Publications Warehouse

Isely, J.J.; Stockett, P.E.

2001-01-01

Eighty juvenile (means: 42.4 mm total length, 1.6 g) red swamp crayfish Procambarus clarkii were implanted with sequentially numbered visible implant tags and held in the laboratory. Tags were injected transversely into the musculature just beneath the exoskeleton of the third abdominal segment from the cephalothorax; tags were visible upon inspection. An additional 20 crayfish were left untagged and served as controls. After 150 d, tag retention was 80% and all tags were readable. No tagged crayfish died during the study, and no differences in total length or weight were detected between tagged and control crayfish. All individuals molted at least three times during the 150-d study, and some individuals molted up to six times, suggesting that most tags would be permanently retained. The readability in the field without specialized equipment makes the visible implant tag ideal for studies of crayfish ecology, management, and culture.

Design and development of reactive injectable and settable polymeric biomaterials.

PubMed

Page, Jonathan M; Harmata, Andrew J; Guelcher, Scott A

2013-12-01

Injectable and settable biomaterials are a growing class of therapeutic technologies within the field of regenerative medicine. These materials offer advantages compared to prefabricated implants because of their ability to be utilized as part of noninvasive surgical procedures, fill complex defect shapes, cure in situ, and incorporate cells and other active biologics. However, there are significant technical barriers to clinical translation of injectable and settable biomaterials, such as achieving clinically relevant handling properties and benign reaction conditions. This review focuses on the engineering challenges associated with the design and development of injectable and chemically settable polymeric biomaterials. Additionally, specific examples of the diverse chemistries utilized to overcome these challenges are covered. The future translation of injectable and settable biomaterials is anticipated to improve patient outcomes for a number of clinical conditions. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

Digital data acquisition for a CAD/CAM-fabricated titanium framework and zirconium oxide restorations for an implant-supported fixed complete dental prosthesis.

PubMed

Lin, Wei-Shao; Metz, Michael J; Pollini, Adrien; Ntounis, Athanasios; Morton, Dean

2014-12-01

This dental technique report describes a digital workflow with digital data acquisition at the implant level, computer-aided design and computer-aided manufacturing fabricated, tissue-colored, anodized titanium framework, individually luted zirconium oxide restorations, and autopolymerizing injection-molded acrylic resin to fabricate an implant-supported, metal-ceramic-resin fixed complete dental prosthesis in an edentulous mandible. The 1-step computer-aided design and computer-aided manufacturing fabrication of titanium framework and zirconium oxide restorations can provide a cost-effective alternative to the conventional metal-resin fixed complete dental prosthesis. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Percutaneously Inject able Fetal Pacemaker: Electrodes, Mechanical Design and Implantation*

PubMed Central

Zhou, Li; Chmait, Ramen; Bar-Cohen, Yaniv; Peck, Raymond A.; Loeb, Gerald E.

2015-01-01

We are developing a self-contained cardiac pacemaker with a small, cylindrical shape (~3×20mm) that permits it to be implanted percutaneously into a fetus to treat complete heart block and consequent hydrops fetalis, which is otherwise fatal. The device uses off-the-shelf components including a rechargeable lithium cell and a highly efficient relaxation oscillator encapsulated in epoxy and glass. A corkscrew electrode made from activated iridium can be screwed into the myocardium, followed by release of the pacemaker and a short, flexible lead entirely within the chest of the fetus to avoid dislodgement from fetal movement. The feasibility of implanting the device percutaneously under ultrasonic imaging guidance was demonstrated in acute adult rabbit experiments. PMID:23367442

21 CFR 522.311 - Cefovecin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.311 Cefovecin. (a... not complete. (ii) Indications for use. For the treatment of skin infections (secondary superficial...

21 CFR 522.311 - Cefovecin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.311 Cefovecin. (a... not complete. (ii) Indications for use. For the treatment of skin infections (secondary superficial...

21 CFR 522.311 - Cefovecin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.311 Cefovecin. (a... not complete. (ii) Indications for use. For the treatment of skin infections (secondary superficial...

21 CFR 522.311 - Cefovecin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.311 Cefovecin. (a... not complete. (ii) Indications for use. For the treatment of skin infections (secondary superficial...

21 CFR 522.147 - Atipamezole.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.147... for use. For reversal of the sedative and analgesic effects of dexmedetomidine hydrochloride or...

21 CFR 522.147 - Atipamezole.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.147... for use. For reversal of the sedative and analgesic effects of dexmedetomidine hydrochloride or...

Intrascleral outflow after deep sclerectomy with absorbable and non-absorbable implants in the rabbit eye.

PubMed

Kałużny, Jakub J; Grzanka, Dariusz; Wiśniewska, Halina; Niewińska, Alicja; Kałużny, Bartłomiej J; Grzanka, Alina

2012-10-01

The purpose of the study is an analysis of intrascleral drainage vessels formed in rabbits' eyes after non-penetrating deep sclerectomy (NPDS) with absorbable and non-absorbable implants, and comparison to eyes in which surgery was performed without implanted material. NPDS was carried out in 12 rabbits, with implantation of non-absorbable methacrylic hydrogel (N=10 eyes) or absorbable cross-linked sodium hyaluronate (N=6 eyes), or without any implant (N=8 eyes). All the animals were euthanized 1 year after surgery. Twenty-one eyeballs were prepared for light microscopy and 3 were prepared for transmission electron microscope (TEM) analysis. Aqueous humour pathways were stained with ferritin in 6 eyeballs. By light microscopy, small vessels adjacent to the areas of scarring were the most common abnormality. Vessel density was significantly higher in operated sclera compared to normal, healthy tissue, regardless of the type of implant used. The average vessel densities were 2.18±1.48 vessels/mm2 in non-implanted sclera, 2.34±1.69 vessels/mm2 in eyes with absorbable implants, and 3.64±1.78 vessels/mm2 in eyes with non-absorbable implants. Analysis of iron distribution in ferritin-injected eyes showed a positive reaction inside new aqueous draining vessels in all groups. TEM analysis showed that the ultrastructure of new vessels matched the features of the small veins. Aqueous outflow after NPDS can be achieved through the newly formed network of small intrascleral veins. Use of non-absorbable implants significantly increases vessel density in the sclera adjacent to implanted material compared to eyes in which absorbable implants or no implants were used.

Increased crown-to-implant ratio may not be a risk factor for dental implant failure under appropriate plaque control.

PubMed

Okada, Shinsuke; Koretake, Katsunori; Miyamoto, Yasunari; Oue, Hiroshi; Akagawa, Yasumasa

2013-01-01

The aim of this study was to evaluate whether increased crown-to-implant (C/I) ratio influences implant stability or not under proper healthy control of peri-implant mucosa. The hypothesis of this study is that implant stability can be maintained despite High C/I, under appropriate plaque control. Five male Beagle-Labrador hybrid dogs (2 years old) were used. Their bilateral mandibular premolar extraction was performed. After allowing 12 weeks for bone healing, 3 types of vertical marginal bone loss were simultaneously prepared randomly. Then, 30 titanium implants were placed in the edentulous areas and defined as High C/I, Mid C/I and Low C/I groups. This time point was designated as the baseline (0 Week). Twelve weeks after implant placement, metal superstructures were cemented to the implants and an occlusal plate was set at the opposite side. At the same time, Calcein green was injected for remodeling evaluation. Implants were loaded by feeding the dogs a hard pellet diet. Tooth brushing was performed 5 days per week during the study to maintain healthy peri-implant mucosa. Twenty-four weeks following implant placement, the interface structure was evaluated clinically, radiologically, and histologically. Implant stability quotient (ISQ) increased with time in all 3 groups, without any significant correlation with the C/I value (p >0.05). Moreover, mean marginal bone loss adjacent around implants in all 3 groups ranged between 0.11 and 0.19 mm, with no significant difference (p >0.05). Many fluorescence-labeled bones are shown in the High C/I group. It is considered that high remodeling activity prevent marginal bone loss in the High C/I group and this may provide favorable implant stability under proper plaque control. These findings suggest that increased C/I may not be a risk factor for implant failure if the peri-implant mucosa is kept healthy, as was the case in this animal model.

Optoelectronic retinal prosthesis: system design and performance

NASA Astrophysics Data System (ADS)

Loudin, J. D.; Simanovskii, D. M.; Vijayraghavan, K.; Sramek, C. K.; Butterwick, A. F.; Huie, P.; McLean, G. Y.; Palanker, D. V.

2007-03-01

The design of high-resolution retinal prostheses presents many unique engineering and biological challenges. Ever smaller electrodes must inject enough charge to stimulate nerve cells, within electrochemically safe voltage limits. Stimulation sites should be placed within an electrode diameter from the target cells to prevent 'blurring' and minimize current. Signals must be delivered wirelessly from an external source to a large number of electrodes, and visual information should, ideally, maintain its natural link to eye movements. Finally, a good system must have a wide range of stimulation currents, external control of image processing and the option of either anodic-first or cathodic-first pulses. This paper discusses these challenges and presents solutions to them for a system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a head-mounted near-to-eye projection system operating at near-infrared wavelengths. Photodiodes convert light into pulsed electric current, with charge injection maximized by applying a common biphasic bias waveform. The resulting prosthesis will provide stimulation with a frame rate of up to 50 Hz in a central 10° visual field, with a full 30° field accessible via eye movements. Pixel sizes are scalable from 100 to 25 µm, corresponding to 640-10 000 pixels on an implant 3 mm in diameter.

Migration of polyethylene debris along well-fixed cemented implants.

PubMed

Massin, P; Viguier, E; Flautre, B; Hardouin, P; Astoin, E; Duponchel, B

2004-02-15

Implants, consisting of smooth Inox cylinders, were cemented into the lower femur and upper tibia of nine sheep to study the distal migration of polyethylene particles. Some implants had a titanium-bead porous coat at the proximal end. These were of three types: In the first type, the porous coat was covered with hydroxyapatite to obtain a bony seal; the second type was prepared for a polymethylmethacrylate seal; in the third type, the porous zone was surrounded by a 2-mm-thick space to allow the formation of a fibrous seal. Small polyethylene particles were injected into the knees once a week during the third and fourth months after implantation. The animals were euthanized 2 months later. Major longitudinal sections of the implants and the surrounding bone were examined under a polarized light microscope. Birefringent particles were counted at the cement-bone and cement-implant interfaces. Osteolysis was not observed. None of the seals significantly decreased the migration of particles around the cemented part of the implants. Particles were observed in cement fissures and vacuoles. They migrated at both interfaces and in the bone itself. They were visible in marrow spaces between bone trabeculae. Copyright 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 68B: 140-148, 2004

21 CFR 522.56 - Amikacin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.56 Amikacin. (a... Escherichia coli and Proteus spp. and skin and soft tissue infections caused by susceptible strains of...

21 CFR 522.46 - Alfaprostol.

Code of Federal Regulations, 2012 CFR

2012-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.46 Alfaprostol. (a... the skin and can cause abortion and/or bronchial spasms. Women of childbearing age, asthmatics, and...

21 CFR 522.56 - Amikacin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.56 Amikacin. (a... of Escherichia coli and Proteus spp. and skin and soft tissue infections caused by susceptible...

21 CFR 522.90b - Ampicillin trihydrate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.90b..., gastrointestinal infections, skin infections, soft tissue infections, and postsurgical infections. (iii...

21 CFR 522.90b - Ampicillin trihydrate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.90b..., gastrointestinal infections, skin infections, soft tissue infections, and postsurgical infections. (iii...

21 CFR 522.56 - Amikacin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.56 Amikacin. (a... of Escherichia coli and Proteus spp. and skin and soft tissue infections caused by susceptible...

21 CFR 522.2240 - Sulfaethoxypyridazine.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2240... of respiratory infection (pneumonia, shipping fever), foot rot, calf scours; as adjunctive therapy in...

A Fully Coupled Simulation and Optimization Scheme for the Design of 3D Powder Injection Molding Processes

NASA Astrophysics Data System (ADS)

Ayad, G.; Song, J.; Barriere, T.; Liu, B.; Gelin, J. C.

2007-05-01

The paper is concerned with optimization and parametric identification of Powder Injection Molding process that consists first in injection of powder mixture with polymer binder and then to the sintering of the resulting powders parts by solid state diffusion. In the first part, one describes an original methodology to optimize the injection stage based on the combination of Design Of Experiments and an adaptive Response Surface Modeling. Then the second part of the paper describes the identification strategy that one proposes for the sintering stage, using the identification of sintering parameters from dilatometer curves followed by the optimization of the sintering process. The proposed approaches are applied to the optimization for manufacturing of a ceramic femoral implant. One demonstrates that the proposed approach give satisfactory results.

Biodegradable chitosan and polylactic acid-based intraocular micro-implant for sustained release of methotrexate into vitreous: analysis of pharmacokinetics and toxicity in rabbit eyes.

PubMed

Manna, Soumyarwit; Banerjee, Rupak K; Augsburger, James J; Al-Rjoub, Marwan F; Donnell, Anna; Correa, Zelia M

2015-08-01

The purpose of this study was to evaluate the pharmacokinetics and toxicity of a chitosan (CS) and polylactic acid (PLA) based methotrexate (MTX) intravitreal micro-implant in an animal model using rabbit eyes. CS- and PLA-based micro-implants containing 400 μg of MTX were fabricated using lyophilization and dip-coating techniques. The micro-implants were surgically implanted in the vitreous of eight New Zealand rabbits employing minimally invasive technique. The PLA-coated CS-MTX micro-implant was inserted in the right eye and the placebo micro-implant in the left eye of each rabbit. Two rabbits were euthanized at each pre-determined time point post-implantation (days 5, 12, 19, and 33) for pharmacokinetics and histopathology evaluation. A therapeutic concentration of MTX (0.1-1.0 μM) in the vitreous was detected in the rabbit eyes studied for 33 days. The MTX release from the coated micro-implants followed a first order kinetics (R (2) ~ 0.88), implying that MTX release depends on the concentration of MTX in the micro-implant. Histopathological analysis of the enucleated eyes failed to show any signs of infection or tissue toxicity in any of the specimens. The PLA-coated CS-MTX micro-implants were able to deliver therapeutic release of MTX for a period of more than 1 month without detectable toxicity in a rabbit model. The micro-implants can be further investigated as a prospective alternative to current treatment protocols of repeated intravitreal MTX injections in intraocular disorders such as primary intraocular lymphoma, and selected cases of non-microbial intraocular inflammation.

Estrus synchronization in sheep with synthetic progestagens.

PubMed

Awel, Hayatu; Eshetu, Lisanework; Tadesse, Gebrehiwot; Birhanu, Alemselam; Khar, S K

2009-10-01

Sixteen female sheep of Degua breed were assigned to receive either the full dose of norgestomet ear implant and injectable solution containing norgestomet and estradiol valerate (n = 8) or half the dose (n = 8). The ear implants were removed in both groups on day 12. All ewes received an intramuscular administration of 500 IU PMSG at implant withdrawal. Synchronized ewes were individually hand mated twice at 48 and 60 hours after implant removal. One ewe in each group however refused mating on both occasions. Pregnancy diagnosis was conducted by bimanual external palpation 90 to 100 days post mating. The conception rates (3/7, 42.85%) and (5/7, 71.42%) were recorded in the two treatment groups, respectively. All eight ewes lambed between 145 to 153 days post mating. In group I ewes carried only singletons (prolificity rate 1.0) whereas in group II two ewes delivered twins, producing 7 lambs with prolificity rate of 1.4 (N.S). From this preliminary investigation it appears that the lower dose of norgestomet ear implants offers better option for estrus synchronization accompanied by higher fertility.

In Vivo Validation of Custom-Designed Silicon-Based Microelectrode Arrays for Long-Term Neural Recording and Stimulation

PubMed Central

Manoonkitiwongsa, Panya S.; Wang, Cindy X.; McCreery, Douglas B.

2012-01-01

We developed and validated silicon-based neural probes for neural stimulating and recording in long-term implantation in the brain. The probes combine the deep reactive ion etching process and mechanical shaping of their tip region, yielding a mechanically sturdy shank with a sharpened tip to reduce insertion force into the brain and spinal cord, particularly, with multiple shanks in the same array. The arrays’ insertion forces have been quantified in vitro. Five consecutive chronically-implanted devices were fully functional from 3 to 18 months. The microelectrode sites were electroplated with iridium oxide, and the charge injection capacity measurements were performed both in vitro and after implantation in the adult feline brain. The functionality of the chronic array was validated by stimulating in the cochlear nucleus and recording the evoked neuronal activity in the central nucleus of the inferior colliculus. The arrays’ recording quality has also been quantified in vivo with neuronal spike activity recorded up to 566 days after implantation. Histopathology evaluation of neurons and astrocytes using immunohistochemical stains indicated minimal alterations of tissue architecture after chronic implantation. PMID:22020666

Dexamethasone intravitreal implant for the treatment of noninfectious uveitis

PubMed Central

Hunter, Rebecca S; Lobo, Ann-Marie

2011-01-01

Uveitis can be a sight-threatening eye disease with significant morbidity. Corticosteroids remain the mainstay of treatment of uveitis and provide an effective treatment against ocular inflammation. However, the various modes available for corticosteroid drug delivery can carry significant ocular and systemic side effects which can limit their use in the treatment of uveitis. In an effort to avoid the damage to ocular structures that can ensue with recurrent episodes of ocular inflammation, the side effects associated with systemic steroids, and the need for repeated administration of both topical and locally injected corticosteroids, sustained-release intraocular corticosteroid implants have been developed. The dexamethasone (DEX) drug delivery system (Ozurdex®; Allergan Inc, Irvine, CA), is a biodegradable intravitreal implant. This implant has been shown to be effective in the treatment of macular edema and noninfectious posterior uveitis and has been approved by the FDA for these entities. This review will highlight the current methods available for corticosteroid delivery to the eye with a particular emphasis on the DEX intravitreal implant and the evidence currently available for its use in noninfectious uveitis. PMID:22140307

Simultaneous sentinel lymph node computed tomography and locoregional chemotherapy for lymph node metastasis in rabbit using an iodine-docetaxel emulsion

PubMed Central

Kim, Honsoul; Jang, Eun-Ji; Kim, Sang Kyum; Hyung, Woo Jin; Choi, Dong Kyu; Lim, Soo-Jeong; Lim, Joon Seok

2017-01-01

Purpose A sentinel lymph node (SLN) tracer can gain multi-functionality by combining it with additional components. We developed a SLN tracer consisting of iodine and docetaxel and applied it as a theragnostic nanoparticle to simultaneously perform SLN computed tomography (CT) lymphography and locoregional chemotherapy of the draining lymphatic system. Results Docetaxel could be loaded in iodine emulsions at a drug-to-surfactant weight ratio as high as that in the drug formulation Taxotere®. The particle size and drug concentration were stable during storage for up to 3 months in optimized nanoemulsions. Popliteal LN enhancement on CT was observed in all healthy rabbits (n=3) and VX2 tumor-implanted rabbits (n=6) 12 hours after injection. The rate of SLN metastasis was significantly lower in the treatment group (29.4%, 5/17) than in the non-treatment group (70.6%, 12/17) (P=0.038). Material and Methods We prepared a nanoemulsion carrying both iodine and docetaxel in a single structure by optimizing the composition of surfactants surrounding the inner iodized oil core. CT was performed 12 hours after subcutaneous injection of the emulsion in healthy rabbits (n=3) and VX2 tumor-implanted rabbits (n=6) for SLN imaging. Next, we tested the effect of treatment by histopathologically assessing the popliteal LN metastasis rate in VX2 tumor-implanted rabbits 7 days after subcutaneous injection of the emulsion (treatment group, n=17) and comparing it with that of non-treatment group rabbits (n=17). Conclusions We developed an iodine-docetaxel emulsion and demonstrated that it can be applied to simultaneously achieve CT SLN imaging and local chemotherapy against nodal metastasis. PMID:28460444

Adjunctive triamcinolone acetonide for Ahmed glaucoma valve implantation: a randomized clinical trial.

PubMed

Yazdani, Shahin; Doozandeh, Azadeh; Pakravan, Mohammad; Ownagh, Vahid; Yaseri, Mehdi

2017-06-26

To evaluate the effect of intraoperative sub-Tenon injection of triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation. In this triple-blind randomized clinical trial, 104 eyes with refractory glaucoma were randomly assigned to conventional AGV (non-TA group) or AGV with adjunctive triamcinolone (TA group). In the TA group, 10 mg TA was injected in the sub-Tenon space around the AGV plate intraoperatively. Patients were followed for 1 year. The main outcome measure was intraocular pressure (IOP). Other outcome measures included best-corrected visual acuity (BCVA), occurrence of hypertensive phase (HP), peak IOP, number of antiglaucoma medications, and complications. A total of 90 patients were included in the final analysis. Mean IOP was lower in the TA group at most follow-up visits; however, the difference was statistically significant only at the first month (p = 0.004). Linear mixed model showed that mean IOP was 1.5 mm Hg lower in the TA group throughout the study period (p = 0.006). Peak postoperative IOP was significantly lower in the TA group (19.3 ± 4.8 mm Hg versus 29 ± 9.2 mm Hg, p = 0.032). Rates of success (defined as 6 < IOP <21 mm Hg) were similar in both groups at 12 months. There was no difference in the occurrence of the HP between the 2 groups (p = 0.123). Loss of BCVA >2 lines was more common in the non-TA group (p = 0.032). Adjunctive intraoperative TA injection during AGV implantation can blunt peak IOP levels and reduce mean IOP up to 1 year. Visual outcomes also seem to be superior to standard surgery.

Minimally Invasive Monitoring of Chronic Central Venous Catheter Patency in Mice Using Digital Subtraction Angiography (DSA)

PubMed Central

Figueiredo, Giovanna; Fiebig, Teresa; Kirschner, Stefanie; Nikoubashman, Omid; Kabelitz, Lisa; Othman, Ahmed; Nonn, Andrea; Kramer, Martin; Brockmann, Marc A.

2015-01-01

Background Repetitive administration of medication or contrast agents is frequently performed in mice. The introduction of vascular access mini-ports (VAMP) for mice allows long-term vascular catheterization, hereby eliminating the need for repeated vessel puncture. With catheter occlusion being the most commonly reported complication of chronic jugular vein catheterization, we tested whether digital subtraction angiography (DSA) can be utilized to evaluate VAMP patency in mice. Methods Twenty-three mice underwent catheterization of the jugular vein and subcutaneous implantation of a VAMP. The VAMP was flushed every second day with 50 μL of heparinized saline solution (25 IU/ml). DSA was performed during injection of 100 μL of an iodine based contrast agent using an industrial X-ray inspection system intraoperatively, as well as 7±2 and 14±2 days post implantation. Results DSA allowed localization of catheter tip position, to rule out dislocation, kinking or occlusion of a microcatheter, and to evaluate parent vessel patency. In addition, we observed different ante- and retrograde collateral flow patterns in case of jugular vein occlusion. More exactly, 30% of animals showed parent vessel occlusion after 7±2 days in our setting. At this time point, nevertheless, all VAMPs verified intravascular contrast administration. After 14±2 days, intravascular contrast injection was verified in 70% of the implanted VAMPs, whereas at this point of time 5 animals had died or were sacrificed and in 2 mice parent vessel occlusion hampered intravascular contrast injection. Notably, no occlusion of the catheter itself was observed. Conclusion From our observations we conclude DSA to be a fast and valuable minimally invasive tool for investigation of catheter and parent vessel patency and for anatomical studies of collateral blood flow in animals as small as mice. PMID:26098622

Pre-exposure prophylaxis for HIV-1 prevention does not diminish the pregnancy prevention effectiveness of hormonal contraception.

PubMed

Murnane, Pamela M; Heffron, Renee; Ronald, Allan; Bukusi, Elizabeth A; Donnell, Deborah; Mugo, Nelly R; Were, Edwin; Mujugira, Andrew; Kiarie, James; Celum, Connie; Baeten, Jared M

2014-07-31

For women at risk of HIV-1, effective contraception and effective HIV-1 prevention are global priorities. In a clinical trial of pre-exposure prophylaxis (PrEP) for HIV-1 prevention in HIV-1-serodiscordant couples, we estimated the effectiveness of hormonal contraceptives (oral contraceptive pills, injectable depot medroxyprogesterone acetate, and hormonal implants) for pregnancy prevention relative to no contraception among 1785 HIV-1-uninfected women followed up to 36 months. We compared the effectiveness of each method among women assigned PrEP versus placebo. Contraception was not required for participation, but was offered on-site and was recorded monthly; incident pregnancy was determined by monthly urine testing. For women using no contraception, overall pregnancy incidence was 15.4% per year. Women reporting oral contraceptive use had comparable pregnancy incidence to women using no contraception, and this lack of contraceptive effectiveness was similar for those assigned PrEP and placebo (17.7 and 10.0% incidence per year, respectively; P-value for difference in effect by PrEP use = 0.24). Women reporting injectable contraception had reduced pregnancy incidence compared to those reporting no contraception, which did not differ by arm (PrEP 5.1%, placebo 5.3% per year; P-value for difference = 0.47). Contraceptive effectiveness was highest among women using implants (pregnancy incidence <1% per year in both arms). PrEP had no adverse impact on hormonal contraceptive effectiveness for pregnancy prevention. As seen previously in similar populations, women reporting contraceptive pill use had little protection from pregnancy, possibly due to poor adherence. Injectable or implantable hormonal contraception and PrEP provide effective prevention for pregnancy and HIV-1.

Latissimus dorsi flap for total autologous immediate breast reconstruction without implants.

PubMed

Santanelli di Pompeo, Fabio; Laporta, Rosaria; Sorotos, Michail; Pagnoni, Marco; Falesiedi, Federica; Longo, Benedetto

2014-12-01

The latissimus dorsi flap provides suitable recipient tissue for fat transfer, with a good blood supply and a reasonable volume of host tissue to inject into. The authors present their experience with use of the pedicled latissimus dorsi flap for fat grafting in total autologous immediate breast reconstruction without implants. From 2010 to 2013, 23 patients underwent breast reconstruction with primary fat augmented latissimus dorsi flaps (21 unilateral procedures and two bilateral procedures). Mean patient age was 52.3 years (range, 39 to 68 years); mean body mass index was 24.77 kg/m2 (range, 21.5 to 28.7 kg/m2). Fat was harvested using the Coleman technique with 10-ml syringes and injected into the adipose layer and muscle fascia of the latissimus dorsi flap skin paddle with 1-ml syringes. The mean size of the harvested skin paddle was 19.7 × 11.04 cm (range, 18 × 10 cm to 21 × 12 cm). Mean operative time was 2.62 hours (range, 2.10 to 3.20 hours) and 4.12 hours (range, 4.10 to 4.15 hours) for unilateral and bilateral reconstructions, respectively. Mean harvested fat volume was 126 ml (range, 90 to 180 ml), and mean injected fat volume was 101 ml (range, 60 to 150 ml). All flaps healed uneventfully, no seroma occurred at the flap donor-site, and no fat grafting-related complications were observed. To the best of the authors' knowledge, this is the first report in which fat transfer was used to achieve immediate latissimus dorsi flap volume augmentation as an alternative for total autologous reconstruction, avoiding implant-related complications.

A low dose of subperiosteal anaesthesia injection versus a high dose of infiltration anaesthesia to minimise the risk of nerve damage at implant placement: A randomised controlled trial.

PubMed

Sánchez-Siles, Mariano; Camacho-Alonso, Fabio; Salazar-Sánchez, Noemi; Aguinaga-Ontoso, Enrique; Muñoz, Javier Guardia; Calvo-Guirado, Jose Luis

2016-01-01

To evaluate whether a low-dose subperiosteal anaesthesia is effective in minimising risks of inferior alveolar nerve damage at implant placement when compared to high-dose infiltration anaesthesia. One hundred and twenty patients requiring the placement of a single implant in order to replace a missing first mandibular were randomly allocated to two groups: group A (awake hemilip) subperiosteal crestal injection equal to 0.9 ml of articaine with 0.5% epinephrine and group B (numb hemilip) infiltration equal to 7.2 ml of articaine with 0.5% epinephrine in the vestibular fundus. Intraoperative sensory control using sensory tests was carried out in all patients. Outcome measures were neurological complications, intraoperative and postoperative visual analogue scale (VAS) scores for pain and swelling, and a questionnaire evaluating patient satisfaction. Patients were followed for 1 week postoperatively. There were no cases of nerve injury. Seven days after surgery the postoperative VAS score for pain and swelling was lower in group A in a statistically significant manner (difference = -3.41%; 95% CI: -5.57, -1.26; P = 0.002 and difference = -3.33%; 95% CI: -5.41, -1.25; P = 0.002, respectively). No nerve damage occurred using either anaesthesia types, therefore the choice of type of anaesthesia is a subjective clinical decision, however it may be preferable to use a low dose (0.9 ml) of subperiosteal anaesthesia, since it is unnecessary to deliver 7.2 ml of articaine to anaesthetise a single mandibular molar implant site.

Simvastatin protects against the development of endometriosis in a nude mouse model.

PubMed

Bruner-Tran, Kaylon L; Osteen, Kevin G; Duleba, Antoni J

2009-07-01

Endometriosis is a common condition associated with infertility and pelvic pain in women. Recent in vitro studies have shown that statins decrease proliferation of endometrial stroma (ES) and inhibit angiogenesis. The aim was to evaluate effects of simvastatin on development of endometriosis in a nude mouse model. Proliferative phase human endometrial biopsies were obtained from healthy donors and established as organ cultures or used to isolate ES cells. To establish endometriosis in the nude mouse, endometrial tissues were maintained in 1 nm estradiol (E) for 24 h and subsequently injected into ovariectomized nude mice. Mice (n = 37) were treated with E (8 mg, SILASTIC capsule implants; made in author laboratory) alone or with E plus simvastatin (5 or 25 mg/kg x d) for 10 d beginning 1 d after tissue injection (from three donors). Mice were killed and examined for disease. Effects of simvastatin on matrix metalloproteinase-3 (MMP-3) were evaluated in cultures of ES cells. The number and size of endometriotic implants were measured. Simvastatin induced a dose-dependent decrease of the number and size of endometrial implants in mice. At the highest dose of simvastatin, the number of endometrial implants decreased by 87%, and the volume by 98%. Simvastatin also induced a concentration-dependent decrease in MMP-3 in the absence and presence of inflammatory challenge (using IL-1alpha). Simvastatin exerted a potent inhibitory effect on the development of endometriosis in the nude mouse. Mechanisms of action of simvastatin may include inhibition of MMP-3. The present findings may lead to the development of novel treatments of endometriosis involving statins.

Intracerebral Cell Implantation: Preparation and Characterization of Cell Suspensions.

PubMed

Rossetti, Tiziana; Nicholls, Francesca; Modo, Michel

2016-01-01

Intracerebral cell transplantation is increasingly finding a clinical translation. However, the number of cells surviving after implantation is low (5-10%) compared to the number of cells injected. Although significant efforts have been made with regard to the investigation of apoptosis of cells after implantation, very little optimization of cell preparation and administration has been undertaken. Moreover, there is a general neglect of the biophysical aspects of cell injection. Cell transplantation can only be an efficient therapeutic approach if an optimal transfer of cells from the dish to the brain can be ensured. We therefore focused on the in vitro aspects of cell preparation of a clinical-grade human neural stem cell (NSC) line for intracerebral cell implantation. NSCs were suspended in five different vehicles: phosphate-buffered saline (PBS), Dulbecco's modified Eagle medium (DMEM), artificial cerebral spinal fluid (aCSF), HypoThermosol, and Pluronic. Suspension accuracy, consistency, and cell settling were determined for different cell volume fractions in addition to cell viability, cell membrane damage, and clumping. Maintenance of cells in suspension was evaluated while being stored for 8 h on ice, at room temperature, or physiological normothermia. Significant differences between suspension vehicles and cellular volume fractions were evident. HypoThermosol and Pluronic performed best, with PBS, aCSF, and DMEM exhibiting less consistency, especially in maintaining a suspension and preserving viability under different storage conditions. These results provide the basis to further investigate these preparation parameters during the intracerebral delivery of NSCs to provide an optimized delivery process that can ensure an efficient clinical translation.

Penile Girth Enhancement With Polymethylmethacrylate-Based Soft Tissue Fillers.

PubMed

Casavantes, Luis; Lemperle, Gottfried; Morales, Palmira

2016-09-01

An unknown percentage of men will take every risk to develop a larger penis. Thus far, most injectables have caused serious problems. Polymethylmethacrylate (PMMA) microspheres have been injected as a wrinkle filler and volumizer with increasing safety since 1989. To report on a safe and permanently effective method to enhance penile girth and length with an approved dermal filler (ie, PMMA). Since 2007, the senior author has performed penile augmentation in 752 men mainly with Metacrill, a suspension of PMMA microspheres in carboxymethyl-cellulose. The data of 729 patients and 203 completed questionnaires were evaluated statistically. The overall satisfaction rate was 8.7 on a scale of 1 to 10. After one to three injection sessions, average girth increased by 3.5 cm, or 134% (10.2 to 13.7 cm = 134.31%). Penile length also increased by weight and stretching force of the implant from an average of 9.8 to 10.5 cm. Approximately half the patients perceived some irregularities of the implant, which caused no problems. Complications occurred in 0.4%, when PMMA nodules had to be surgically removed in three of the 24% of patients who had a non-circumcised penis. After 5 years of development, penile augmentation with PMMA microspheres appears to be a natural, safe, and permanently effective method. The only complication of nodule formation and other irregularities can be overcome by an improved injection technique and better postimplantation care. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Antinociceptive effect of intrathecal microencapsulated human pheochromocytoma cell in a rat model of bone cancer pain.

PubMed

Li, Xiao; Li, Guoqi; Wu, Shaoling; Zhang, Baiyu; Wan, Qing; Yu, Ding; Zhou, Ruijun; Ma, Chao

2014-07-08

Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

21 CFR 522.1081 - Chorionic gonadotropin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... if the animal's behavior or examination of the ovaries per rectum indicates retreatment. (A) 10,000... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

DISTRIBUTION OF FITC IMPLANTED SUBCUTANEOUSLY IN CONTROLLED RELEASE MATRICES IN CUNNER (TAUTOGOLABRUS ADSPERSUS)

EPA Science Inventory

Peritoneal injection is a major route for chemical introduction into fish for toxicological studies. This procedure, however, causes rapid exposure to toxicants at levels which aren't environmentally realistic. Long-term studies to determine effects of estrogenic chemicals on fis...

21 CFR 522.535 - Desoxycorticosterone pivalate.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522... variable and must be individualized on the basis of the response of the patient to therapy. Initial dose of... as replacement therapy for the mineralocorticoid deficit in dogs with primary adrenocortical...

Application of Coaxial Ion Gun for Film Generation and Ion Implantation

NASA Astrophysics Data System (ADS)

Takatsu, Mikio; Asai, Tomohiko; Kurumi, Satoshi; Suzuki, Kaoru; Hirose, Hideharu; Masutani, Shigeyuki

A magnetized coaxial plasma gun (MCPG) is here utilized for deposition on high-melting-point metals. MCPGs have hitherto been studied mostly in the context of nuclear fusion research, for particle and magnetic helicity injection and spheromak formation. During spheromak formation, the electrode materials are ionized and mixed into the plasmoid. In this study, this ablation process by gun-current sputtering is enhanced for metallic thin-film generation. In the proposed system geometry, only ionized materials are electromagnetically accelerated by the self-Lorentz force, with ionized operating gas as a magnetized thermal plasmoid, contributing to the thin-film deposition. This reduces the impurity and non-uniformity of the deposited thin-film. Furthermore, as the ions are accelerated in a parallel direction to the injection axis, vertical implantation of the ions into the substrate surface is achieved. To test a potential application of the developed system, experiments were conducted involving the formation of a buffer layer on hard ceramics, for use in dental materials.

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

PubMed Central

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

2014-01-01

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

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats.

PubMed

Guarnieri, M; Brayton, C; Sarabia-Estrada, R; Tyler, B; McKnight, P; DeTolla, L

2017-01-01

A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy.

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats

PubMed Central

Brayton, C.; Sarabia-Estrada, R.; McKnight, P.; DeTolla, L.

2017-01-01

A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy. PMID:28492060

Juvenile X-linked retinoschisis responsive to intravitreal corticosteroids.

PubMed

Ansari, Waseem H; Browne, Andrew W; Singh, Rishi P

2017-04-01

To report the case of an adult male with X-linked retinoschisis (XLRS) who presented with cystoid macular edema (CME) that responded consistently to treatment with intravitreal steroids. A 39 year old male with unilateral presentation of CME after repair of a retinal detachment secondary to XLRS responded initially to an injection of intravitreal triamcinolone acetonide (IVTA). Central subfield thickness on OCT was reduced. Three months later, the CME recurred and he was unresponsive to topical treatment so repeat IVTA was given, and the CME once again was reduced dramatically. After the next recurrence, intravitreal dexamethasone implant treatment was initiated and successful at treating recurrences in 3 month intervals for 5 additional injections. Finally, an intravitreal fluocinolone acetonide implant was surgically placed with control of CME. Corticosteroids have never been reported to be effective in CME related to XLRS. Here, we document a case of a man who successfully had decrease of intraretinal fluid and schisis with treatment of intravitreal corticosteroids as demonstrated by spectral domain optical coherence tomography.

Differential effects of acute and chronic estrogen treatment on thermogenic and metabolic pathways in ovariectomized sheep.

PubMed

Clarke, Scott D; Clarke, Iain J; Rao, Alexandra; Evans, Roger G; Henry, Belinda A

2013-01-01

Estrogen is protective against weight gain, but the underlying mechanisms are not fully elucidated. We sought to characterize the effects of estrogen on energy expenditure in skeletal muscle and adipose tissue in ovariectomized sheep. Temperature probes were implanted into sc (gluteal) and visceral (retroperitoneal) fat depots and skeletal muscle of the hind limb (vastus lateralis). Food was available from 1100-1600 h to entrain postprandial thermogenesis. We characterized the effects of single (50 μg estradiol benzoate, im) and repeated (25 μg estradiol-17β, iv) injections as well as chronic (3 × 3 cm estradiol-17β implants for 7 d) treatment on heat production. A single injection of estrogen increased heat production in visceral fat and skeletal muscle, without an effect on food intake. Increased heat production in skeletal muscle was sustained by repeated estradiol-17β injections. On the other hand, continuous treatment reduced food intake but had no effect on thermogenesis. To determine possible mechanisms that underpin estradiol-17β-induced heat production, we measured femoral artery blood flow, the expression of uncoupling protein (UCP) mRNA and the phosphorylation of AMP-activated protein kinase and Akt in fat and muscle. There was little effect of either single or repeated injections of estradiol-17β on the expression of UCP1, -2, or -3 mRNA in visceral fat or skeletal muscle. Acute injection of estradiol-17β increased the phosphorylation of AMP-activated protein kinase and Akt in muscle only. Estradiol-17β treatment did not alter femoral artery blood flow. Thus, the stimulatory effect of estradiol-17β on thermogenesis in female sheep is dependent upon a pulsatile pattern of treatment and not constant continuous exposure.

The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs.

PubMed

Tan, Naiwen; Liu, Xiangwei; Cai, Yanhui; Zhang, Sijia; Jian, Bo; Zhou, Yuchao; Xu, Xiaoru; Ren, Shuai; Wei, Hongbo; Song, Yingliang

2017-01-01

High failure rates of oral implants have been reported in diabetic patients due to the disruption of osseointegration. The aim of this study was to investigate whether direct laser metal sintering (DLMS) could improve osseointegration in diabetic animal models. Surface characterizations were carried out on two types of implants. Cell morphology and the osteogenic-related gene expression of MG63 cells were observed under conditions of DLMS and microarc oxidation (MAO). A diabetes model in mini-pigs was established by intravenous injection of streptozotocin (150 mg/kg), and a total of 36 implants were inserted into the mandibular region. Micro-computed tomography (micro-CT) and histologic evaluations were performed 3 and 6 months after implantation. The Ra (the average of the absolute height of all points) of MAO surface was 2.3±0.3 µm while the DLMS surface showed the Ra of 27.4±1.1 µm. The cells on DLMS implants spread out more podia than those on MAO implants through cell morphology analysis. Osteogenic-related gene expression was also dramatically increased in the DLMS group. Obvious improvement was observed in the micro-CT and Van Gieson staining analyses of DLMS implants compared with MAO at 3 months, although this difference disappeared by 6 months. DLMS implants showed a higher bone-implant contact percentage (33.2%±11.2%) at 3 months compared with MAO group (18.9%±7.3%) while similar results were showed at 6 months between DLMS group (42.8%±10.1%) and MAO group (38.3%±10.8%). The three-dimensional environment of implant surfaces with highly porous and fully interconnected channel and pore architectures can improve cell spreading and accelerate the progress of osseointegration in diabetic mini-pigs.

A tetracycline expression system in combination with Sox9 for cartilage tissue engineering.

PubMed

Yao, Yi; He, Yu; Guan, Qian; Wu, Qiong

2014-02-01

Cartilage tissue engineering using controllable transcriptional therapy together with synthetic biopolymer scaffolds shows higher potential for overcoming chondrocyte degradation and constructing artificial cartilages both in vivo and in vitro. Here, the potential regulating tetracycline expression (Tet-on) system was used to express Sox9 both in vivo and in vitro. Chondrocyte degradation was measured in vitro and overcome by Soxf9 expression. Experiments confirmed the feasibility of the combined use of Sox9 and Tet-on system in cartilage tissue engineering. Engineered poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) scaffolds were seeded with recombinant chondrocytes which were transfected with Tet-induced Sox9 expression; the scaffolds were implanted under the skin of 8-week-old rats. The experimental group was injected with Dox in the abdomen, while the control group was injected with normal saline. After 4 or 8 days of implantation in vivo, the newly formed pieces of articular chondrocytes were taken out and measured. Dox injection in vivo showed positive effect on recombinant chondrocytes, in which Sox9 expression was up-regulated by an inducible system with specific matrix proteins. The results demonstrate this controllable transcriptional therapy is a potential approach for tissue engineering. Copyright © 2013 Elsevier Ltd. All rights reserved.

A study of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer after two or more implantation failures.

PubMed

Huang, Pinxiu; Wei, Lihong; Li, Xinlin

2017-01-01

To investigate the effect of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer (FET) after two or more implantation failures (TIFs). The study was a prospective randomized single-blind study of 161 cycles in patients undergoing FET who had TIFs. The intervention group received an intrauterine injection of 1000 IU of hCG before embryo transfer (ET) (n = 62). A placebo group (n = 49) received an intrauterine injection of physiological saline before ET. A control group (n = 50) did not receive an intrauterine injection. Clinical pregnancy rates, abortion rates, and ongoing pregnancy rates were compared between the three groups. The clinical pregnancy rates were 59.68%, 53.06%, and 32.00% in the hCG group, placebo group, and control group, respectively. The clinical pregnancy rates were significantly higher in the hCG and placebo groups than in the control group. There were no significant differences in the abortion rates among the three groups. An intrauterine administration of hCG before FET significantly improved the pregnancy rates after TIFs. But local injury caused by the operation of intrauterine perfusion may play an important role in improving clinical pregnancy rates.

Short-term effects of mineral particle sizes on cellular degradation activity after implantation of injectable calcium phosphate biomaterials and the consequences for bone substitution.

PubMed

Gauthier, O; Bouler, J M; Weiss, P; Bosco, J; Aguado, E; Daculsi, G

1999-08-01

This in vivo study investigated the influence of two calcium phosphate particle sizes (40-80 microm and 200-500 microm) on the cellular degradation activity associated with the bone substitution process of two injectable bone substitutes (IBS). The tested biomaterials were obtained by associating a biphasic calcium phosphate (BCP) ceramic mineral phase and a 3% aqueous solution of a cellulosic polymer (hydroxypropylmethylcellulose). Both were injected into osseous defects at the distal end of rabbit femurs for 2- and 3-week periods. Quantitative results for tartrate-resistant acid phosphatase (TRAP) cellular activity, new bone formation, and ceramic resorption were studied for statistical purposes. Positive TRAP-stained degradation cells were significantly more numerous for IBS 40-80 than IBS 200-500, regardless of implantation time. BCP degradation was quite marked during the first 2 weeks for IBS 40-80, and bone colonization occurred more extensively for IBS 40-80 than for IBS 200-500. The resorption-bone substitution process occurred earlier and faster for IBS 40-80 than IBS 200-500. Both tested IBS displayed similar biological efficiency, with conserved in vivo bioactivity and bone-filling ability. Differences in calcium phosphate particle sizes influenced cellular degradation activity and ceramic resorption but were compatible with efficient bone substitution.

Tracing Fasting Glucose Fluxes with Unstressed Catheter Approach in Streptozotocin Induced Diabetic Rats

PubMed Central

Wu, Hui; Xu, Xiao; Meng, Ying; Xia, Fangzhen; Zhai, Hualing; Lu, Yingli

2014-01-01

Objective. Blood glucose concentrations of type 1 diabetic rats are vulnerable, especially to stress and trauma. The present study aimed to investigate the fasting endogenous glucose production and skeletal muscle glucose uptake of Streptozotocin induced type 1 diabetic rats using an unstressed vein and artery implantation of catheters at the tails of the rats as a platform. Research Design and Methods. Streptozotocin (65 mg·kg−1) was administered to induce type 1 diabetic state. The unstressed approach of catheters of vein and artery at the tails of the rats was established before the isotope tracer injection. Dynamic measurement of fasting endogenous glucose production was assessed by continuously infusing stable isotope [6, 6-2H2] glucose, while skeletal muscle glucose uptake by bolus injecting radioactively labeled [1-14C]-2-deoxy-glucose. Results. Streptozotocin induced type 1 diabetic rats displayed polydipsia, polyphagia, and polyuria along with overt hyperglycemia and hypoinsulinemia. They also had enhanced fasting endogenous glucose production and reduced glucose uptake in skeletal muscle compared to nondiabetic rats. Conclusions. The dual catheters implantation at the tails of the rats together with isotope tracers injection is a save time, unstressed, and feasible approach to explore the glucose metabolism in animal models in vivo. PMID:24772449

Interspecies chimera between primate embryonic stem cells and mouse embryos: monkey ESCs engraft into mouse embryos, but not post-implantation fetuses.

PubMed

Simerly, Calvin; McFarland, Dave; Castro, Carlos; Lin, Chih-Cheng; Redinger, Carrie; Jacoby, Ethan; Mich-Basso, Jocelyn; Orwig, Kyle; Mills, Parker; Ahrens, Eric; Navara, Chris; Schatten, Gerald

2011-07-01

Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst injection. Aggregation chimera produced mouse blastocysts with GFP-nhpESCs at the inner cell mass (ICM), and embryo transfers (ETs) generated dimly-fluorescencing abnormal fetuses. Direct injection of GFP-nhpESCs into blastocysts produced normal non-GFP-fluorescencing fetuses. Injected chimera showed >70% loss of GFP-nhpESCs after 21 h culture. Outgrowths of all chimeric blastocysts established distinct but separate mouse- and NHP-ESC colonies. Extensive endogenous autofluorescence compromised anti-GFP detection and PCR analysis did not detect nhpESCs in fetuses. NhpESCs localize to the ICM in chimera and generate pregnancies. Because primate ESCs do not engraft post-implantation, and also because endogenous autofluorescence results in misleading positive signals, interspecific chimera assays for pluripotency with primate stem cells is unreliable with the currently available ESCs. Testing primate ESCs reprogrammed into even more naïve states in these inter-specific chimera assays will be an important future endeavor. Copyright © 2011 Elsevier B.V. All rights reserved.

[A CASE OF DEXTRANOMER-HYALURONIC ACID COPOLYMER (Deflux®) IMPLANTS CALCIFICATION MIMICKING DISTAL URETERAL CALCULI].

PubMed

Matsumoto, Fumi; Matsui, Futoshi; Yazawa, Koji; Shimada, Kenji

2017-01-01

Since 2011, endoscopic correction of vesicoureteral reflux using dextranomer-hyaluronic acid copolymer (Deflux ® ) has been widely accepted in Japan due to its safety and minimally invasive nature. However, long-term complications are unknown. We present a case of Deflux ® implants calcification mimicking distal ureteral calculi in a 12-year-old boy with a history of Deflux ® injection performed at three years of age for primary VUR. We should be aware of this complication to avoid misdiagnosis and unnecessary invasive examination such as radiological imaging or endoscopy.

[Fluocinolone acetonide (ILUVIEN®) micro-implant for chronic diabetic macular edema].

PubMed

Soubrane, G; Behar-Cohen, F

2015-02-01

Diabetic macular edema (DME) is a frequent complication of diabetic retinopathy and may cause severe visual loss. In this article, we examine the pathophysiology of DME and review various treatment options, such as laser photocoagulation, anti-vascular endothelial growth factor (VEGF) receptor antibodies, and steroids including ILUVIEN(®), which is a new sustained-release, non biodegradable, injectable, intravitreal micro-implant containing fluocinolone acetonide. The results of the FAME (Fluocinolone Acetonide in Diabetic Macular Edema) studies, conducted to evaluate the efficacy and safety of ILUVIEN(®) in DME, are discussed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Some engineering aspects of insulin delivery systems.

PubMed

Spencer, W J; Bair, R E; Carlson, G A; Love, J T; Urenda, R S; Eaton, R P; Schade, D S

1980-01-01

The characteristics of electronically controlled insulin delivery systems are presented. Early experiments with an external system have shown promise in providing improved glycemic control over conventional methods of single or multiple subcutaneous insulin injections. The encouraging results with external insulin delivery systems have led to the development and early testing in dogs of an implantable system with remote controls to permit variable insulin flow rates. A number of questions remain to be answered before widespread experimentation with external and implanted insulin delivery systems is possible. There appears to be no major development problems with the engineering aspects of such systems.

Studying tumor growth in Drosophila using the tissue allograft method.

PubMed

Rossi, Fabrizio; Gonzalez, Cayetano

2015-10-01

This protocol describes a method to allograft Drosophila larval tissue into adult fly hosts that can be used to assay the tumorigenic potential of mutant tissues. The tissue of interest is dissected, loaded into a fine glass needle and implanted into a host. Upon implantation, nontransformed tissues do not overgrow beyond their normal size, but malignant tumors grow without limit, are invasive and kill the host. By using this method, Drosophila malignant tumors can be transplanted repeatedly, for years, and therefore they can be aged beyond the short life span of flies. Because several hosts can be implanted using different pieces from a single tumor, the method also allows the tumor mass to be increased to facilitate further studies that may require large amounts of tissue (i.e., genomics, proteomics and so on). This method also provides an operational definition of hyperplastic, benign and malignant growth. The injection procedure itself requires only ∼1 d. Tumor development can then be monitored until the death of the implanted hosts.

Production, characterisation, and cytocompatibility of porous titanium-based particulate scaffolds.

PubMed

Luthringer, B J C; Ali, F; Akaichi, H; Feyerabend, F; Ebel, T; Willumeit, R

2013-10-01

Despite its non-matching mechanical properties titanium remains the preferred metal implant material in orthopaedics. As a consequence in some cases stress shielding effect occurs, leading to implant loosening, osteopenia, and finally revision surgery. Porous metal scaffolds to allow easier specialised cells ingrowth with mechanical properties closer to the ones of bone can overcome this problem. This should improve healing processes, implant integration, and dynamic strength of implants retaining. Three Ti-6Al-4V materials were metal injection moulded and tailored porosities were effectively achieved. After microstructural and mechanical characterisation, two different primary cells of mesenchymal origin (human umbilical cord perivascular cells and human bone derived cells which revealed to be two pertinent models) as well as one cell line originated from primary osteogenic sarcoma, Saos-2, were bestowed to investigate cell-material interaction on genomic and proteome levels. Biological examinations disclosed that no material has negative impact on early adhesion, proliferation or cell viability. An efficient cell ingrowth into material with an average porosity of 25-50 μm was proved.

A 3D Printed Implantable Device for Voiding the Bladder Using Shape Memory Alloy (SMA) Actuators.

PubMed

Hassani, Faezeh Arab; Peh, Wendy Yen Xian; Gammad, Gil Gerald Lasam; Mogan, Roshini Priya; Ng, Tze Kiat; Kuo, Tricia Li Chuen; Ng, Lay Guat; Luu, Percy; Yen, Shih-Cheng; Lee, Chengkuo

2017-11-01

Underactive bladder or detrusor underactivity (DU) is defined as a reduction of contraction strength or duration of the bladder wall. Despite the serious healthcare implications of DU, there are limited solutions for affected individuals. A flexible 3D printed implantable device driven by shape memory alloys (SMA) actuators is presented here for the first time to physically contract the bladder to restore voluntary control of the bladder for individuals suffering from DU. This approach is used initially in benchtop experiments with a rubber balloon acting as a model for the rat bladder to verify its potential for voiding, and that the operating temperatures are safe for the eventual implantation of the device in a rat. The device is then implanted and tested on an anesthetized rat, and a voiding volume of more than 8% is successfully achieved for the SMA-based device without any surgical intervention or drug injection to relax the external sphincter.

21 CFR 522.810 - Embutramide, chloroquine, and lidocaine solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... euthanasia. (3) Limitations. Not for use in animals intended for food. Federal law restricts this drug to use... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.810 Embutramide, chloroquine, and lidocaine solution. (a) Specifications. Each...

21 CFR 522.810 - Embutramide, chloroquine, and lidocaine solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... euthanasia. (3) Limitations. Not for use in animals intended for food. Federal law restricts this drug to use... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.810 Embutramide, chloroquine, and lidocaine solution. (a) Specifications. Each...

21 CFR 522.810 - Embutramide, chloroquine, and lidocaine solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... euthanasia. (3) Limitations. Not for use in animals intended for food. Federal law restricts this drug to use... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.810 Embutramide, chloroquine, and lidocaine solution. (a) Specifications. Each...

21 CFR 522.810 - Embutramide, chloroquine, and lidocaine solution.

Code of Federal Regulations, 2014 CFR

2014-04-01

... euthanasia. (3) Limitations. Not for use in animals intended for food. Federal law restricts this drug to use... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.810 Embutramide, chloroquine, and lidocaine solution. (a) Specifications. Each...

21 CFR 522.1222 - Ketamine.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ketamine. 522.1222 Section 522.1222 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222 Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg) ketamine base...

21 CFR 522.1081 - Chorionic gonadotropin.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... Dosage may be repeated in 14 days if the animal's behavior or examination of the ovaries per rectum... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

21 CFR 522.1081 - Chorionic gonadotropin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... repeated in 14 days if the animal's behavior or examination of the ovaries per rectum indicates retreatment... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

21 CFR 522.1081 - Chorionic gonadotropin.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... Dosage may be repeated in 14 days if the animal's behavior or examination of the ovaries per rectum... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

21 CFR 522.1081 - Chorionic gonadotropin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... repeated in 14 days if the animal's behavior or examination of the ovaries per rectum indicates retreatment... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

DISTRIBUTION OF FITC AFTER SUBCUTANEOUS IMPLANTATION OF CONTROLLED RELEASE MATRICES IN CUNNER, TAUTOGOLABRUS ADSPERSUS

EPA Science Inventory

Peritoneal injection is a major route for chemical introduction into fish for toxicological studies. This procedure, however, causes rapid exposure to toxicants at levels which aren't environmentally realistic. Long-term studies to determine effects of estrogenic chemicals on fis...

75 FR 60307 - Implantation or Injectable Dosage Form New Animal Drugs; Dexmedetomidine

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 [Docket No... (NADA) filed by Orion Corp. The supplemental NADA provides for veterinary prescription use of... Veterinary Medicine (HFV-110), Food and Drug Administration, 7500 Standish Pl., [[Page 60308

21 CFR 522.1885 - Prednisolone tertiary butylacetate suspension.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Prednisolone tertiary butylacetate suspension. 522.1885 Section 522.1885 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW...

21 CFR 522.1890 - Sterile prednisone suspension.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sterile prednisone suspension. 522.1890 Section 522.1890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS...

Survival of rats bearing advanced intracerebral F 98 tumors after glutathione depletion and microbeam radiation therapy: conclusions from a pilot project.

PubMed

Schültke, E; Bräuer-Krisch, E; Blattmann, H; Requardt, H; Laissue, J A; Hildebrandt, G

2018-05-10

Resistance to radiotherapy is frequently encountered in patients with glioblastoma multiforme. It is caused at least partially by the high glutathione content in the tumour tissue. Therefore, the administration of the glutathione synthesis inhibitor Buthionine-SR-Sulfoximine (BSO) should increase survival time. BSO was tested in combination with an experimental synchrotron-based treatment, microbeam radiation therapy (MRT), characterized by spatially and periodically alternating microscopic dose distribution. One hundred thousand F98 glioma cells were injected into the right cerebral hemisphere of adult male Fischer rats to generate an orthotopic small animal model of a highly malignant brain tumour in a very advanced stage. Therapy was scheduled for day 13 after tumour cell implantation. At this time, 12.5% of the animals had already died from their disease. The surviving 24 tumour-bearing animals were randomly distributed in three experimental groups: subjected to MRT alone (Group A), to MRT plus BSO (Group B) and tumour-bearing untreated controls (Group C). Thus, half of the irradiated animals received an injection of 100 μM BSO into the tumour two hours before radiotherapy. Additional tumour-free animals, mirroring the treatment of the tumour-bearing animals, were included in the experiment. MRT was administered in bi-directional mode with arrays of quasi-parallel beams crossing at the tumour location. The width of the microbeams was ≈28 μm with a center-to-center distance of ≈400 μm, a peak dose of 350 Gy, and a valley dose of 9 Gy in the normal tissue and 18 Gy at the tumour location; thus, the peak to valley dose ratio (PVDR) was 31. After tumour-cell implantation, otherwise untreated rats had a mean survival time of 15 days. Twenty days after implantation, 62.5% of the animals receiving MRT alone (group A) and 75% of the rats given MRT + BSO (group B) were still alive. Thirty days after implantation, survival was 12.5% in Group A and 62.5% in Group B. There were no survivors on or beyond day 35 in Group A, but 25% were still alive in Group B. Thus, rats which underwent MRT with adjuvant BSO injection experienced the largest survival gain. In this pilot project using an orthotopic small animal model of advanced malignant brain tumour, the injection of the glutathione inhibitor BSO with MRT significantly increased mean survival time.

Optimal Design of Material and Process Parameters in Powder Injection Molding

NASA Astrophysics Data System (ADS)

Ayad, G.; Barriere, T.; Gelin, J. C.; Song, J.; Liu, B.

2007-04-01

The paper is concerned with optimization and parametric identification for the different stages in Powder Injection Molding process that consists first in injection of powder mixture with polymer binder and then to the sintering of the resulting powders part by solid state diffusion. In the first part, one describes an original methodology to optimize the process and geometry parameters in injection stage based on the combination of design of experiments and an adaptive Response Surface Modeling. Then the second part of the paper describes the identification strategy that one proposes for the sintering stage, using the identification of sintering parameters from dilatometeric curves followed by the optimization of the sintering process. The proposed approaches are applied to the optimization of material and process parameters for manufacturing a ceramic femoral implant. One demonstrates that the proposed approach give satisfactory results.

Hypertensive phase and early complications after Ahmed glaucoma valve implantation with intraoperative subtenon triamcinolone acetonide.

PubMed

Turalba, Angela V; Pasquale, Louis R

2014-01-01

To evaluate intraoperative subtenon triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation. Retrospective comparative case series. Forty-two consecutive cases of uncontrolled glaucoma undergoing AGV implantation: 19 eyes receiving intraoperative subtenon TA and 23 eyes that did not receive TA. A retrospective chart review was performed on consecutive pseudophakic adult patients with uncontrolled glaucoma undergoing AGV with and without intraoperative subtenon TA injection by a single surgeon. Clinical data were collected from 42 eyes and analyzed for the first 6 months after surgery. Primary outcomes included intraocular pressure (IOP) and number of glaucoma medications prior to and after AGV implantation. The hypertensive phase (HP) was defined as an IOP measurement of greater than 21 mmHg (with or without medications) during the 6-month postoperative period that was not a result of tube obstruction, retraction, or malfunction. Postoperative complications and visual acuity were analyzed as secondary outcome measures. Five out of 19 (26%) TA cases and 12 out of 23 (52%) non-TA cases developed the HP (P=0.027). Mean IOP (14.2±4.6 in TA cases versus [vs] 14.7±5.0 mmHg in non-TA cases; P=0.78), and number of glaucoma medications needed (1.8±1.3 in TA cases vs 1.6±1.1 in the comparison group; P=0.65) were similar between both groups at 6 months. Although rates of serious complications did not differ between the groups (13% in the TA group vs 16% in the non-TA group), early tube erosion (n=1) and bacterial endophthalmitis (n=1) were noted with TA but not in the non-TA group. Subtenon TA injection during AGV implantation may decrease the occurrence of the HP but does not alter the ultimate IOP outcome and may pose increased risk of serious complications within the first 6 months of surgery.

Hypertensive phase and early complications after Ahmed glaucoma valve implantation with intraoperative subtenon triamcinolone acetonide

PubMed Central

Turalba, Angela V; Pasquale, Louis R

2014-01-01

Objective To evaluate intraoperative subtenon triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation. Design Retrospective comparative case series. Participants Forty-two consecutive cases of uncontrolled glaucoma undergoing AGV implantation: 19 eyes receiving intraoperative subtenon TA and 23 eyes that did not receive TA. Methods A retrospective chart review was performed on consecutive pseudophakic adult patients with uncontrolled glaucoma undergoing AGV with and without intraoperative subtenon TA injection by a single surgeon. Clinical data were collected from 42 eyes and analyzed for the first 6 months after surgery. Main outcome measures Primary outcomes included intraocular pressure (IOP) and number of glaucoma medications prior to and after AGV implantation. The hypertensive phase (HP) was defined as an IOP measurement of greater than 21 mmHg (with or without medications) during the 6-month postoperative period that was not a result of tube obstruction, retraction, or malfunction. Postoperative complications and visual acuity were analyzed as secondary outcome measures. Results Five out of 19 (26%) TA cases and 12 out of 23 (52%) non-TA cases developed the HP (P=0.027). Mean IOP (14.2±4.6 in TA cases versus [vs] 14.7±5.0 mmHg in non-TA cases; P=0.78), and number of glaucoma medications needed (1.8±1.3 in TA cases vs 1.6±1.1 in the comparison group; P=0.65) were similar between both groups at 6 months. Although rates of serious complications did not differ between the groups (13% in the TA group vs 16% in the non-TA group), early tube erosion (n=1) and bacterial endophthalmitis (n=1) were noted with TA but not in the non-TA group. Conclusions Subtenon TA injection during AGV implantation may decrease the occurrence of the HP but does not alter the ultimate IOP outcome and may pose increased risk of serious complications within the first 6 months of surgery. PMID:25050061

Efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma.

PubMed

Tang, Min; Fu, Yang; Wang, Ying; Zheng, Zhi; Fan, Ying; Sun, Xiaodong; Xu, Xun

2016-01-09

Neovascular glaucoma is a refractive glaucoma. Recently, anti-VEGF factors have been used alone or in combination for the treatment of neovascular glaucoma. However, the medium- and long-term efficacy of such drugs remains to be evaluated. This study was to determine the efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma. In this prospective non-randomized study, 43 neovascular glaucoma patients (43 eyes) were assigned to receive either 0.5 mg intravitreal ranibizumab for three to 14 days before Ahmed glaucoma valve implantation (injection group, n = 21) or Ahmed glaucoma valve implantation alone (control group, n = 22). The patients were followed up for six to 12 months. Differences in surgical success rate, intraocular pressure, best corrected visual acuity, anti-glaucoma medications and postoperative complications were compared between the two groups. Surgical success was defined as IOP > = 6 mm Hg and < = 21 mm Hg, with or without the use of anti-glaucoma medications, and without severe complications or reoperation. Of the 43 patients, 40 completed the 6-month follow-up and 37 completed the 1-year follow-up. Success rate was 73.7% vs. 71.4% at six months and 72.2% vs. 68.4% at 12 months in the injection group and the control group respectively. No significant difference was noted between the two groups (six months: P = 0.87, 12 months: P = 1.00). There were no significant differences in the two groups with respect to intraocular pressure, best corrected visual acuity, anti-glaucoma medications or postoperative complications at six months or 12 months. Single intravitreal ranibizumab (0.5 mg) before surgery has no significant effect on the medium- or long-term outcomes of neovascular glaucoma treated with Ahmed glaucoma valve implantation. Chinese Clinical Trial Registry ( ChiCTR-OOC-14005709, Trial registration date: 2014-12-01).

Tumor-targeting Salmonella typhimurium A1-R Inhibits Osteosarcoma Angiogenesis in the In Vivo Gelfoam® Assay Visualized by Color-coded Imaging.

PubMed

Kiyuna, Tasuku; Tome, Yasunori; Uehara, Fuminari; Murakami, Takashi; Zhang, Yong; Zhao, Ming; Kanaya, Fuminori; Hoffman, Robert M

2018-01-01

We previously developed a color-coded imaging model that can quantify the length of nascent blood vessels using Gelfoam® implanted in nestin-driven green fluorescent protein (ND-GFP) nude mice. In this model, nascent blood vessels selectively express GFP. We also previously showed that osteosarcoma cells promote angiogenesis in this assay. We have also previously demonstrated the tumor-targeting bacteria Salmonella typhimurium A1-R (S. typhimurium A1-R) can inhibit or regress all tested tumor types in mouse models. The aim of the present study was to determine if S. typhimurium A1-R could inhibit osteosarcoma angiogenesis in the in vivo Gelfoam® color-coded imaging assay. Gelfoam® was implanted subcutaneously in ND-GFP nude mice. Skin flaps were made 7 days after implantation and 143B-RFP human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the implanted Gelfoam. After establishment of tumors in the Gelfoam®, control-group mice were treated with phosphate buffered saline via tail-vein injection (iv) and the experimental group was treated with S. typhimurium A1-R iv Skin flaps were made at day 7, 14, 21, and 28 after implantation of the Gelfoam® to allow imaging of vascularization in the Gelfoam® using a variable-magnification small-animal imaging system and confocal fluorescence microscopy. Nascent blood vessels expressing ND-GFP extended into the Gelfoam® over time in both groups. However, the extent of nascent blood-vessel growth was significantly inhibited by S. typhimurium A1-R treatment by day 28. The present results indicate S. typhimurium A1-R has potential for anti-angiogenic targeted therapy of osteosarcoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

PubMed

Firl, Kevin C; Montezuma, Sandra R

2016-11-09

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

Numerical Simulation of Sintering Process in Ceramic Powder Injection Moulded Components

NASA Astrophysics Data System (ADS)

Song, J.; Barriere, T.; Liu, B.; Gelin, J. C.

2007-05-01

A phenomenological model based on viscoplastic constitutive law is presented to describe the sintering process of ceramic components obtained by powder injection moulding. The parameters entering in the model are identified through sintering experiments in dilatometer with the proposed optimization method. The finite element simulations are carried out to predict the density variations and dimensional changes of the components during sintering. A simulation example on the sintering process of hip implant in alumina has been conducted. The simulation results have been compared with the experimental ones. A good agreement is obtained.

A comparison of the double hydrodistention implantation technique (HIT) and the HIT with a polyacrylate/polyalcohol copolymer (PPC) for the endoscopic treatment of primary vesicoureteral reflux.

PubMed

Akin, Melih; Erginel, Basak; Karadag, Cetin Ali; Yildiz, Abdullah; Ozçelik, Gül Sumru; Sever, Nihat; Genc, Nimetullah Mete; Dokucu, Ali Ihsan

2014-11-01

We aimed to compare the success rates of the double hydrodistention implantation technique (HIT) and the HIT with a polyacrylate/polyalcohol copolymer (PPC) for the treatment of primary vesicoureteral reflux (VUR) with a new nonbiodegradable tissue-augmenting substance (Vantris, Promedon, Cordoba, Argentina). Between January 2011 and December 2012, fifty-two children who underwent subureteric injection for primary VUR are included. The children were randomly separated into two groups, the HIT and the double HIT groups, according to the type of injection. Success was defined as no reflux on a follow-up voiding cystourethrogram (VCUG) after 6 months. The patients were evaluated according to sex, age, grade of reflux, number of injections, and injected volume, and the radiological success rates were compared. Fifty-two patients underwent an endoscopic injection for primary grade III-V VUR. The HIT group consisted of 26 patients with 33 ureters, and the double HIT group consisted of 26 patients with 35 ureters. There were no significant differences in terms of the sex, ages, VUR grades, bilaterality between the two groups. The mean injected volumes were ml 1.12 (1.02-1.22) in the HIT group and 1.24 ml (95 % CI 1.10-1.38) in the double HIT group. The reflux was resolved in 21/33 (63.6 %) ureters in the HIT group and in 30/35 (85.7 %) ureters in the double HIT group, (p < 0.05). We had only one complication. This patient in the double HIT group, developed bilateral hydronephrosis and oliguric renal failure requiring open reimplantation at the sixth month. We observed successful results double HIT method with PPC in Grade III-V reflux, but the long-term follow-up of patients is needed for hydronephrosis. As the double HIT treatment leads to a higher success rate, its use is preferable.

Fibrin(ogen) mediates acute inflammatory responses to biomaterials

PubMed Central

1993-01-01

Although "biocompatible" polymeric elastomers are generally nontoxic, nonimmunogenic, and chemically inert, implants made of these materials may trigger acute and chronic inflammatory responses. Early interactions between implants and inflammatory cells are probably mediated by a layer of host proteins on the material surface. To evaluate the importance of this protein layer, we studied acute inflammatory responses of mice to samples of polyester terephthalate film (PET) that were implanted intraperitoneally for short periods. Material preincubated with albumin is "passivated," accumulating very few adherent neutrophils or macrophages, whereas uncoated or plasma- coated PET attracts large numbers of phagocytes. Neither IgG adsorption nor surface complement activation is necessary for this acute inflammation; phagocyte accumulation on uncoated implants is normal in hypogammaglobulinemic mice and in severely hypocomplementemic mice. Rather, spontaneous adsorption of fibrinogen appears to be critical: (a) PET coated with serum or hypofibrinogenemic plasma attracts as few phagocytes as does albumin-coated material; (b) in contrast, PET preincubated with serum or hypofibrinogenemic plasma containing physiologic amounts of fibrinogen elicits "normal" phagocyte recruitment; (c) most importantly, hypofibrinogenemic mice do not mount an inflammatory response to implanted PET unless the material is coated with fibrinogen or the animals are injected with fibrinogen before implantation. Thus, spontaneous adsorption of fibrinogen appears to initiate the acute inflammatory response to an implanted polymer, suggesting an interesting nexus between two major iatrogenic effects of biomaterials: clotting and inflammation. PMID:8245787

Phase separation of in situ forming poly (lactide-co-glycolide acid) implants investigated using a hydrogel-based subcutaneous tissue surrogate and UV-vis imaging.

PubMed

Sun, Yu; Jensen, Henrik; Petersen, Nickolaj J; Larsen, Susan W; Østergaard, Jesper

2017-10-25

Phase separation of in situ forming poly (lactide-co-glycolide acid) (PLGA) implants with agarose hydrogels as the provider of nonsolvent (water) mimicking subcutaneous tissue was investigated using a novel UV-vis imaging-based analytical platform. In situ forming implants of PLGA-1-methyl-2-pyrrolidinone and PLGA-triacetin representing fast and slow phase separating systems, respectively, were evaluated using this platform. Upon contact with the agarose hydrogel, the phase separation of the systems was followed by the study of changes in light transmission and absorbance as a function of time and position. For the PLGA-1-methyl-2-pyrrolidinone system, the rate of spatial phase separation was determined and found to decrease with increasing the PLGA concentration from 20% to 40% (w/w). Hydrogels with different agarose concentrations (1% and 10% (w/v)) were prepared for providing the nonsolvent, water, to the in situ forming PLGA implants simulating the injection site environment. The resulting implant morphology depended on the stiffness of hydrogel matrix, indicating that the matrix in which implants are formed is of importance. Overall, the work showed that the UV-vis imaging-based platform with an agarose hydrogel mimicking the subcutaneous tissue holds potential in providing bio-relevant and mechanistic information on the phase separation processes of in situ forming implants. Copyright © 2017 Elsevier B.V. All rights reserved.

Orthotopic Implantation of Intact Tumor Tissue Leads to Metastasis of OCUM-2MD3 Human Gastric Cancer in Nude Mice Visualized in Real Time by Intravital Fluorescence Imaging.

PubMed

Murakami, Takashi; Zhang, Yong; Wang, Xiaoen; Hiroshima, Yukihiko; Kasashima, Hiroaki; Yashiro, Masakazu; Hirakawa, Kosei; Miwa, Atsushi; Kiyuna, Tasuku; Matsuyama, Ryusei; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

2016-05-01

Orthotopic (literally "correct place") implantation of cancer in nude mice has long been known to be superior to subcutaneous transplantation because the orthotopic tumor can metastasize. We reported previously on surgical orthotopic implantation (SOI) of gastric cancer tissue in nude mice resulting in the formation of metastases in 100% of the mice with extensive primary growth to the regional lymph nodes, liver, and lung. In contrast, when cell suspensions were used to inject gastric cancer cells orthotopically, metastases occurred in only 6.7% of the mice with local tumor formation, emphasizing the importance of orthotopically implanting intact tissue to allow full expression of metastatic potential. However, the different behavior of tumors implanted orthotopically by the two methods has not been visualized in real time. OCUM-2MD3 human gastric cancer cells labeled with the fluorescent protein Azami-Green were implanted orthotopically as cells or tissue in nude mice. Orthotopic implantation of cells resulted in local spread on the stomach. In contrast, SOI of tumor tissue of OCUM-2MD3 resulted in vessel spread of the Azami-Green-expressing cancer cells. Metastasis was also observed in the left lobe of the liver after SOI. These results demonstrate the physiological importance of intact cancer tissue for orthotopic implantation in order for tumors to properly grow and express their metastatic potential. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Implanted neural progenitor cells regulate glial reaction to brain injury and establish gap junctions with host glial cells.

PubMed

Talaverón, Rocío; Matarredona, Esperanza R; de la Cruz, Rosa R; Macías, David; Gálvez, Victoria; Pastor, Angel M

2014-04-01

Transplantation of neural stem/progenitor cells (NPCs) in the lesioned brain is able to restore morphological and physiological alterations induced by different injuries. The local microenvironment created at the site of grafting and the communication between grafted and host cells are crucial in the beneficial effects attributed to the NPC implants. We have previously described that NPC transplantation in an animal model of central axotomy restores firing properties and synaptic coverage of lesioned neurons and modulates their trophic factor content. In this study, we aim to explore anatomical relationships between implanted NPCs and host glia that might account for the implant-induced neuroprotective effects. Postnatal rat subventricular zone NPCs were isolated and grafted in adult rats after transection of the medial longitudinal fascicle. Brains were removed and analyzed eight weeks later. Immunohistochemistry for different glial markers revealed that NPC-grafted animals displayed significantly greater microglial activation than animals that received only vehicle injections. Implanted NPCs were located in close apposition to activated microglia and reactive astrocytes. The gap junction protein connexin43 was present in NPCs and glial cells at the lesion site and was often found interposed within adjacent implanted and glial cells. Gap junctions were identified between implanted NPCs and host astrocytes and less frequently between NPCs and microglia. Our results show that implanted NPCs modulate the glial reaction to lesion and establish the possibility of communication through gap junctions between grafted and host glial cells which might be involved in the restorative effects of NPC implants. Copyright © 2014 Wiley Periodicals, Inc.

Analgesia Induced by Isolated Bovine Chromaffin Cells Implanted in Rat Spinal Cord

NASA Astrophysics Data System (ADS)

Sagen, Jacqueline; Pappas, George D.; Pollard, Harvey B.

1986-10-01

Chromaffin cells synthesize and secrete several neuroactive substances, including catecholamines and opioid peptides, that, when injected into the spinal cord, induce analgesia. Moreover, the release of these substances from the cells can be stimulated by nicotine. Since chromaffin cells from one species have been shown to survive when transplanted to the central nervous system of another species, these cells are ideal candidates for transplantation to alter pain sensitivity. Bovine chromaffin cells were implanted into the subarachnoid space of the lumbar spinal region in adult rats. Pain sensitivity and response to nicotine stimulation was determined at various intervals following cell implantation. Low doses of nicotine were able to induce potent analgesia in implanted animals as early as one day following their introduction into the host spinal cord. This response could be elicited at least through the 4 months the animals were tested. The induction of analgesia by nicotine in implanted animals was dose related. This analgesia was blocked by the opiate antagonist naloxone and partially attenuated by the adrenergic antagonist phentolamine. These results suggest that the analgesia is due to the stimulated release of opioid peptides and catecholamines from the implanted bovine chromaffin cells and may provide a new therapeutic approach for the relief of pain.

Treatment of refractory uveitic macular edema: results of a first and second implant of long-acting intravitreal dexamethasone

PubMed Central

Zola, Marta; Briamonte, Cristina; Lorenzi, Umberto; Machetta, Federica; Grignolo, Federico M; Fea, Antonio M

2017-01-01

Purpose The purpose of this study was to report the functional and anatomical outcomes of a prospective study resulting from repeated dexamethasone intravitreal implants in patients with uveitic refractory macular edema. Methods Twelve eyes of 9 patients with intermediate and posterior noninfectious inflammatory uveitis complicated with refractory macular edema were regularly reviewed after a dexamethasone intravitreal implant. Patients were examined at baseline, 30, 90, 135, and 180 days with best-corrected visual acuity (BCVA), complete slit-lamp examination, intraocular pressure (IOP), optical coherence tomography, and fluorescein angiography. After 6 months of follow-up, eyes were reassessed to receive a second implant. Results BCVA significantly improved when comparing the baseline values after the first and second implant (16.2 and 25.8 letters, respectively, 9.6 letters improvements, p<0.05). BCVA was better after the second implant compared to the first one throughout the follow-up, but without statistical significance. Mean central macular thickness (CMT) was 446.3±129.9 μm at baseline and was significantly reduced until day 135 (p<0.05). CMT reductions after the second injection showed a similar pattern, though differences were not statistically significant. Cataract progression was observed in 4 of 8 phakic eyes (50%) after the first implant, and in 2 of 3 phakic eyes following the second implant, with 1 eye requiring cataract surgery. One eye developed an IOP >30 mmHg 30 days after the second implant, treated topically. Conclusion Repeated dexamethasone intravitreal implants in uveitic patients with refractory macular edema can be used effectively in a clinical setting with an acceptable safety profile. PMID:29184384

In vivo contaminant partitioning to silicone implants: Implications for use in biomonitoring and body burden.

PubMed

O'Connell, Steven G; Kerkvliet, Nancy I; Carozza, Susan; Rohlman, Diana; Pennington, Jamie; Anderson, Kim A

2015-12-01

Silicone polymers are used for a wide array of applications from passive samplers in environmental studies, to implants used in human augmentation and reconstruction. If silicone sequesters toxicants throughout implantation, it may represent a history of exposure and potentially reduce the body burden of toxicants influencing the risk of adverse health outcomes such as breast cancer. Objectives of this research included identifying a wide variety of toxicants in human silicone implants, and measuring the in vivo absorption of contaminants into silicone and surrounding tissue in an animal model. In the first study, eight human breast implants were analyzed for over 1400 organic contaminants including consumer products, chemicals in commerce, and pesticides. A total of 14 compounds including pesticides such as trans-nonachlor (1.2-5.9ng/g) and p,p'-DDE (1.2-34ng/g) were identified in human implants, 13 of which have not been previously reported in silicone prostheses. In the second project, female ICR mice were implanted with silicone and dosed with p,p'-DDE and PCB118 by intraperitoneal injection. After nine days, silicone and adipose samples were collected, and all implants in dosed mice had p,p'-DDE and PCB118 present. Distribution ratios from silicone and surrounding tissue in mice compare well with similar studies, and were used to predict adipose concentrations in human tissue. Similarities between predicted and measured chemical concentrations in mice and humans suggest that silicone may be a reliable surrogate measure of persistent toxicants. More research is needed to identify the potential of silicone implants to refine the predictive quality of chemicals found in silicone implants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer

PubMed Central

Belz, Jodi E.; Kumar, Rajiv; Baldwin, Paige; Ojo, Noelle Castilla; Leal, Ana S.; Royce, Darlene B.; Zhang, Di; van de Ven, Anne L.; Liby, Karen T.; Sridhar, Srinivas

2017-01-01

Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1-deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1-deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1Co/Co;MMTV-Cre;p53+/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro. Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors. PMID:29158830

Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer.

PubMed

Belz, Jodi E; Kumar, Rajiv; Baldwin, Paige; Ojo, Noelle Castilla; Leal, Ana S; Royce, Darlene B; Zhang, Di; van de Ven, Anne L; Liby, Karen T; Sridhar, Srinivas

2017-01-01

Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1 -deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1 -deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1 Co/Co ;MMTV-Cre;p53 +/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro . Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors.

21 CFR 522.1160 - Insulin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Insulin. 522.1160 Section 522.1160 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units (IU...

21 CFR 522.1160 - Insulin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Insulin. 522.1160 Section 522.1160 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units (IU...

21 CFR 522.1160 - Insulin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Insulin. 522.1160 Section 522.1160 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units (IU...

Applications of FM-CW laser radar to antenna contour mapping

NASA Technical Reports Server (NTRS)

Slotwinski, A. R.

1989-01-01

The FM-CW coherent laser radar concept, based on the FM radar principle which makes use of the coherence and lunability of injection laser diodes, is discussed. Laser radar precision/time tradeoffs, block diagrams, system performance, fiber optic system implantation, and receiver improvements are briefly described.

21 CFR 522.1222a - Ketamine.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

21 CFR 522.1222a - Ketamine.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

21 CFR 522.1222a - Ketamine.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

21 CFR 522.204 - Boldenone.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Boldenone. 522.204 Section 522.204 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.204 Boldenone. (a) Specifications. Each milliliter of solution contains 25 or 50 milligrams (mg) boldenone undecylenate. (b) Sponsor...

21 CFR 522.204 - Boldenone.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Boldenone. 522.204 Section 522.204 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.204 Boldenone. (a) Specifications. Each milliliter of solution contains 25 or 50 milligrams (mg) boldenone undecylenate. (b) Sponsor...

21 CFR 522.204 - Boldenone.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Boldenone. 522.204 Section 522.204 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.204 Boldenone. (a) Specifications. Each milliliter of solution contains 25 or 50 milligrams (mg) boldenone undecylenate. (b) Sponsor...

21 CFR 522.204 - Boldenone.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Boldenone. 522.204 Section 522.204 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.204 Boldenone. (a) Specifications. Each milliliter of solution contains 25 or 50 milligrams (mg) boldenone undecylenate. (b) Sponsor...

21 CFR 522.204 - Boldenone.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Boldenone. 522.204 Section 522.204 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.204 Boldenone. (a) Specifications. Each milliliter of solution contains 25 or 50 milligrams (mg) boldenone undecylenate. (b) Sponsor...

21 CFR 522.1222a - Ketamine.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

21 CFR 522.1160 - Insulin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Insulin. 522.1160 Section 522.1160 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units (IU...

21 CFR 522.1160 - Insulin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Insulin. 522.1160 Section 522.1160 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units (IU...

21 CFR 522.304 - Carprofen.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Carprofen. 522.304 Section 522.304 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.304 Carprofen. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) carprofen. (b) Sponsor. See No. 000069 in...

21 CFR 522.304 - Carprofen.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Carprofen. 522.304 Section 522.304 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.304 Carprofen. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) carprofen. (b) Sponsor. See No. 000069 in...

21 CFR 522.304 - Carprofen.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Carprofen. 522.304 Section 522.304 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.304 Carprofen. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) carprofen. (b) Sponsor. See No. 054771 in...

21 CFR 522.304 - Carprofen.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Carprofen. 522.304 Section 522.304 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.304 Carprofen. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) carprofen. (b) Sponsor. See No. 000069 in...

75 FR 38699 - Implantation or Injectable Dosage Form New Animal Drugs; Propofol

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-06

...The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a new animal drug application (NADA) filed by Fort Dodge Animal Health, Division of Wyeth. The NADA provides for veterinary prescription use of propofol as an anesthetic in dogs and cats.

21 CFR 522.46 - Alfaprostol.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Alfaprostol. 522.46 Section 522.46 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.46 Alfaprostol. (a...

21 CFR 522.1680 - Oxytocin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Oxytocin. 522.1680 Section 522.1680 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1680 Oxytocin. (a) Specifications. Each milliliter (mL) of solution contains 20 USP units oxytocin. (b) Sponsors. See Nos. , 000859...

21 CFR 522.2690 - Zinc gluconate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter of solution contains 13.1 milligrams zinc as zinc gluconate...

21 CFR 522.2690 - Zinc gluconate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter of solution contains 13.1 milligrams zinc as zinc gluconate...

21 CFR 522.304 - Carprofen.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Carprofen. 522.304 Section 522.304 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.304 Carprofen. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) carprofen. (b) Sponsor. See No. 000069 in...

75 FR 26647 - Implantation or Injectable Dosage Form New Animal Drugs; Ivermectin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-12

... solution in cattle and swine for treatment and control of various internal and external parasites. DATES... Veterinary Medicine (HFV-170), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-276... and swine for treatment and control of various internal and external parasites. Sparhawk Laboratories...

21 CFR 522.88 - Sterile amoxicillin trihydrate for suspension.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.88 Sterile amoxicillin trihydrate for suspension. (a)(1) Specifications. Each vial... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sterile amoxicillin trihydrate for suspension. 522...

21 CFR 522.88 - Sterile amoxicillin trihydrate for suspension.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.88 Sterile amoxicillin trihydrate for suspension. (a)(1) Specifications. Each vial... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sterile amoxicillin trihydrate for suspension. 522...

21 CFR 522.88 - Sterile amoxicillin trihydrate for suspension.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.88 Sterile amoxicillin trihydrate for suspension. (a)(1) Specifications. Each vial... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sterile amoxicillin trihydrate for suspension. 522...

21 CFR 522.88 - Sterile amoxicillin trihydrate for suspension.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.88 Sterile amoxicillin trihydrate for suspension. (a)(1) Specifications. Each vial... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sterile amoxicillin trihydrate for suspension. 522...

21 CFR 522.1155 - Imidocarb dipropionate sterile powder.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Imidocarb dipropionate sterile powder. 522.1155 Section 522.1155 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS...

Does flushing the endometrial cavity with follicular fluid after oocyte retrieval affect pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection? A randomized controlled trial.

PubMed

Hashish, N M; Badway, H S; Abdelmoty, H I; Mowafy, A; Youssef, M A F M

2014-05-01

Follicular fluid of mature oocytes is rich in growth factors and cytokines that may exert paracrine and autocrine effects on implantation. The aim of this study was to investigate if flushing the endometrial cavity with follicular fluid after oocyte retrieval improved pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection (ICSI). One hundred subfertile women undergoing ICSI between April 2012 and September 2012 at the centre for reproductive medicine, Cairo University, Egypt were enrolled in this open label, parallel randomized controlled study. Patients were randomized into two groups at the start of treatment using a computer-generated programme and sealed opaque envelopes: the follicular fluid group (n=50) and the control group (n=50). Inclusion criteria were: age 20-38 years; basal follicle-stimulating hormone <10mIU/ml; body mass index <35kg/m(2); and ostradiol >1000pg/ml and <4000pg/ml on the day of human chorionic gonadotrophin administration. Exclusion criteria were: evidence of endometriosis; uterine myoma; hydrosalpinges; endocrinological disorders; history of implantation failure in previous in-vitro fertilization/ICSI cycles; and severe male factor infertility. Clinical pregnancy and implantation rates were higher in the follicular fluid group compared with the control group [354% (17/48) vs 319% (15/47); p=0718] and (18.6% vs 11.3%; p=0.153), respectively. However, the difference was not statistically significant. Flushing the endometrial cavity with follicular fluid after oocyte retrieval neither improved nor adversely affected clinical pregnancy and implantation rates in subfertile women undergoing ICSI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Sustained secretion of anti-tumor necrosis factor α monoclonal antibody from ex vivo genetically engineered dermal tissue demonstrates therapeutic activity in mouse model of rheumatoid arthritis.

PubMed

Zafir-Lavie, Inbal; Miari, Reem; Sherbo, Shay; Krispel, Simi; Tal, Osnat; Liran, Atar; Shatil, Tamar; Badinter, Felix; Goltsman, Haim; Shapir, Nir; Benhar, Itai; Neil, Garry A; Panet, Amos

2017-08-01

Rheumatoid arthritis (RA) is a symmetric inflammatory polyarthritis associated with high concentrations of pro-inflammatory, cytokines including tumor necrosis factor (TNF)-α. Adalimumab is a monoclonal antibody (mAb) that binds TNF-α, and is widely used to treat RA. Despite its proven clinical efficacy, adalimumab and other therapeutic mAbs have disadvantages, including the requirement for repeated bolus injections and the appearance of treatment limiting anti-drug antibodies. To address these issues, we have developed an innovative ex vivo gene therapy approach, termed transduced autologous restorative gene therapy (TARGT), to produce and secrete adalimumab for the treatment of RA. Helper-dependent (HD) adenovirus vector containing adalimumab light and heavy chain coding sequences was used to transduce microdermal tissues and cells of human and mouse origin ex vivo, rendering sustained secretion of active adalimumab. The genetically engineered tissues were subsequently implanted in a mouse model of RA. Transduced human microdermal tissues implanted in SCID mice demonstrated 49 days of secretion of active adalimumab in the blood, at levels of tens of microgram per milliliter. In addition, transduced autologous dermal cells were implanted in the RA mouse model and demonstrated statistically significant amelioration in RA symptoms compared to naïve cell implantation and were similar to recombinant adalimumab bolus injections. The results of the present study report microdermal tissues engineered to secrete active adalimumab as a proof of concept for sustained secretion of antibody from the novel ex vivo gene therapy TARGT platform. This technology may now be applied to a range of antibodies for the therapy of other diseases. Copyright © 2017 John Wiley & Sons, Ltd.

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

PubMed

Jung, Kyoung In; Park, Chan Kee

2016-01-01

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

Simvastatin Protects against the Development of Endometriosis in a Nude Mouse Model

PubMed Central

Bruner-Tran, Kaylon L.; Osteen, Kevin G.; Duleba, Antoni J.

2009-01-01

Context: Endometriosis is a common condition associated with infertility and pelvic pain in women. Recent in vitro studies have shown that statins decrease proliferation of endometrial stroma (ES) and inhibit angiogenesis. Objective: The aim was to evaluate effects of simvastatin on development of endometriosis in a nude mouse model. Methods: Proliferative phase human endometrial biopsies were obtained from healthy donors and established as organ cultures or used to isolate ES cells. To establish endometriosis in the nude mouse, endometrial tissues were maintained in 1 nm estradiol (E) for 24 h and subsequently injected into ovariectomized nude mice. Mice (n = 37) were treated with E (8 mg, SILASTIC capsule implants; made in author laboratory) alone or with E plus simvastatin (5 or 25 mg/kg · d) for 10 d beginning 1 d after tissue injection (from three donors). Mice were killed and examined for disease. Effects of simvastatin on matrix metalloproteinase-3 (MMP-3) were evaluated in cultures of ES cells. Primary Outcome: The number and size of endometriotic implants were measured. Results: Simvastatin induced a dose-dependent decrease of the number and size of endometrial implants in mice. At the highest dose of simvastatin, the number of endometrial implants decreased by 87%, and the volume by 98%. Simvastatin also induced a concentration-dependent decrease in MMP-3 in the absence and presence of inflammatory challenge (using IL-1α). Conclusions: Simvastatin exerted a potent inhibitory effect on the development of endometriosis in the nude mouse. Mechanisms of action of simvastatin may include inhibition of MMP-3. The present findings may lead to the development of novel treatments of endometriosis involving statins. PMID:19366846

Effects of hydrogen implantation into GaN

NASA Astrophysics Data System (ADS)

Pearton, S. J.; Abernathy, C. R.; Wilson, R. G.; Zavada, J. M.; Song, C. Y.; Weinstein, M. G.; Stavola, M.; Han, J.; Shul, R. J.

1999-01-01

Proton implantation in GaN is found to reduce the free carrier density through two mechanisms - first, by creating electron and hole traps at around EC - 0.8 eV and EV + 0.9 eV that lead to compensation in both n- and p-type material, and second, by leading to formation of (AH)° complexes, where A is any acceptor (Mg, Ca, Zn, Be, Cd). The former mechanism is useful in creating high resistivity regions for device isolation, whereas the latter produces unintentional acceptor passivation that is detrimental to device performance. The strong affinity of hydrogen for acceptors leads to markedly different redistribution behavior for implanted H + in n- and p-GaN due to the chemical reaction to form neutral complexes in the latter. The acceptors may be reactivated by simple annealing at ⩾600°C, or by electron injection at 25-150°C that produces debonding of the (AH)° centers. Implanted hydrogen is also strongly attracted to regions of strain in heterostructure samples during annealing, leading to pile-up at epi-epi and epi-substrate interfaces. IR spectroscopy shows that implanted hydrogen also decorates VGa defects in undoped and n-GaN.

Implantable photonic devices for improved medical treatments

NASA Astrophysics Data System (ADS)

Sheinman, Victor; Rudnitsky, Arkady; Toichuev, Rakhmanbek; Eshiev, Abdyrakhman; Abdullaeva, Svetlana; Egemkulov, Talantbek; Zalevsky, Zeev

2014-10-01

An evolving area of biomedical research is related to the creation of implantable units that provide various possibilities for imaging, measurement, and the monitoring of a wide range of diseases and intrabody phototherapy. The units can be autonomic or built-in in some kind of clinically applicable implants. Because of specific working conditions in the live body, such implants must have a number of features requiring further development. This topic can cause wide interest among developers of optical, mechanical, and electronic solutions in biomedicine. We introduce preliminary clinical trials obtained with an implantable pill and devices that we have developed. The pill and devices are capable of applying in-body phototherapy, low-level laser therapy, blue light (450 nm) for sterilization, and controlled injection of chemicals. The pill is also capable of communicating with an external control box, including the transmission of images from inside the patient's body. In this work, our pill was utilized for illumination of the sinus-carotid zone in dog and red light influence on arterial pressure and heart rate was demonstrated. Intrabody liver tissue laser ablation and nanoparticle-assisted laser ablation was investigated. Sterilization effect of intrabody blue light illumination was applied during a maxillofacial phlegmon treatment.

The influence of injection volume and capsular bag contraction on the refractive power of polymer refilled lenses - a finite element modelling simulation study.

PubMed

Martin, Heiner; Guthoff, Rudolf; Schmitz, Klaus-Peter

2011-09-01

Polymer injection into the capsular bag after phakoemulsification is an interesting and promising approach to lens surgery. Safe clinical application of this technique will require an appropriate estimate of the effect of implantation variables on the lens power. This article details the results of finite element investigations into the effects of the injected polymer volume and capsular bag contraction on the resultant lens power and accommodation amplitude. An axisymmetric finite element model was created from literature sources. Polymer injection and the capsular contraction were simulated, and their effect on the lens power was calculated. The simulations show that overfilling during polymer injection leads to a refractive power increase of the lens. Capsular bag contraction also results in a power increase. The calculated accommodative amplitude of the lens is minimally affected by capsular bag contraction but decreases significantly with increased capsular bag stiffness as a result of fibrosis. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

Recent progress in injectable bone repair materials research

NASA Astrophysics Data System (ADS)

Chen, Zonggang; Zhang, Xiuli; Kang, Lingzhi; Xu, Fei; Wang, Zhaoling; Cui, Fu-Zhai; Guo, Zhongwu

2015-12-01

Minimally invasive injectable self-setting materials are useful for bone repairs and for bone tissue regeneration in situ. Due to the potential advantages of these materials, such as causing minimal tissue injury, nearly no influence on blood supply, easy operation and negligible postoperative pain, they have shown great promises and successes in clinical applications. It has been proposed that an ideal injectable bone repair material should have features similar to that of natural bones, in terms of both the microstructure and the composition, so that it not only provides adequate stimulus to facilitate cell adhesion, proliferation and differentiation but also offers a satisfactory biological environment for new bone to grow at the implantation site. This article reviews the properties and applications of injectable bone repair materials, including those that are based on natural and synthetic polymers, calcium phosphate, calcium phosphate/polymer composites and calcium sulfate, to orthopedics and bone tissue repairs, as well as the progress made in biomimetic fabrication of injectable bone repair materials.

Acidification of uterine epithelium during embryo implantation in mice†

PubMed Central

Xiao, Shuo; Li, Rong; El Zowalaty, Ahmed E.; Diao, Honglu; Zhao, Fei; Choi, Yongwon; Ye, Xiaoqin

2017-01-01

Abstract Uterine luminal epithelium (LE) is essential for establishing uterine receptivity. Previous microarray analysis revealed upregulation of Atp6v0d2 in gestation day 4.5 (D4.5) LE in mice. Realtime PCR showed upregulation of uterine Atp6v0d2 starting right before embryo attachment ∼D4.0. In situ hybridization demonstrated specific uterine localization of Atp6v0d2 in LE upon embryo implantation. Atp6v0d2 encodes one subunit for vacuolar-type H+-ATPase (V-ATPase), which regulates acidity of intracellular organelles and extracellular environment. LysoSensor Green DND-189 detected acidic signals in LE and glandular epithelium upon embryo implantation, correlating with Atp6v0d2 upregulation in early pregnant uterus. Atp6v0d2−/− females had significantly reduced implantation rate and marginally reduced delivery rate from first mating only, but comparable number of implantation sites and litter size compared to control and comparable fertility to control from subsequent matings, suggesting a nonessential role of Atp6v0d2 subunit in embryo implantation. Successful implantation in both control and Atp6v0d2−/− females was associated with uterine epithelial acidification. No significant compensatory upregulation of Atp6v0d1 mRNA was detected in D4.5 Atp6v0d2−/− uteri. To determine the role of V-ATPase instead of a single subunit in embryo implantation, a specific V-ATPase inhibitor bafilomycin A1 (2.5 μg/kg) was injected via uterine fat pad on D3 18:00 h. This treatment resulted in reduced uterine epithelial acidification, delayed implantation, and reduced number of implantation sites. It also suppressed oil-induced artificial decidualization. These data demonstrate uterine epithelial acidification as a novel phenomenon during embryo implantation and V-ATPase is involved in uterine epithelial acidification and uterine preparation for embryo implantation. PMID:28395338

Botulinum Toxin Type A as Preoperative Treatment for Immediately Loaded Dental Implants Placed in Fresh Extraction Sockets for Full-Arch Restoration of Patients With Bruxism.

PubMed

Mijiritsky, Eitan; Mortellaro, Carmen; Rudberg, Omri; Fahn, Miri; Basegmez, Cansu; Levin, Liran

2016-05-01

The aim of the present report was to describe the use of Botulinum toxin type A as preoperative treatment for immediately loaded dental implants placed in fresh extraction sockets for full-arch restoration of patients with bruxism. Patients with bruxism who were scheduled to receive immediately loaded full-arch implant supported fixed restorations were included in this retrospective clinical report. To reduce the occlusal forces applied in patients with bruxism, Botulinum toxin type A was introduced prior to the implant placement procedure. Patients were followed and implant survival as well as peri-implant bone level was assessed in each periodic follow-up visit. Adverse effects were also recorded. A control group with no use of Botulinum toxin was evaluated as well. A total of 26 patients (13 test and 13 control), with bruxism, aged 59.15 ± 11.43 years on average were included in this retrospective report and received immediately loaded dental implants placed in fresh extraction sockets for full-arch restoration. The test group treatment preceded by Botulinum toxin type A injection. Maxillary arches were supported by 8 to 10 implants while the mandibular arch was supported by 6 implants. All surgeries went uneventfully and no adverse effects were observed. The average follow-up time was 32.5 ± 10.4 months (range, 18-51). In the test group, no implant failures were recorded. One patient presented with 1 to 2 mm bone loss around 4 of the implants; the other implants presented with stable bone level. In the control group 1 patient lost 2 implants and another demonstrated 2 mm bone loss around 3 of the implants. The preoperative use of Botulinum toxin in patients with bruxism undergoing full-arch rehabilitation using immediately loaded dental implants placed in fresh extraction sockets seems to be a technique that deserves attention. Further long-term, large-scale randomized clinical trials will help to determine the additional benefit of this suggested treatment modality.

Evaluation of new Deflux administration techniques: intraureteric HIT and Double HIT for the endoscopic correction of vesicoureteral reflux.

PubMed

Kirsch, Andrew J; Arlen, Angela M

2014-09-01

Vesicoureteral reflux (VUR) is one of the most common urologic diagnoses affecting children, and optimal treatment requires an individualized approach that considers potential risks. Management options include observation with or without continuous antibiotic prophylaxis and surgical correction via endoscopic, open or laparoscopic/robotic approaches. Endoscopic correction of VUR is an outpatient procedure associated with decreased morbidity compared with ureteral reimplantation. The concept of ureteral hydrodistention and intraluminal submucosal injection (Hydrodistention Implantation Technique [HIT]) has led to improved success rates in eliminating VUR compared with the subureteral transurethral injection technique. Further modifications now include use of proximal and distal intraluminal injections (Double HIT) that result in coaptation of both the ureteral tunnel and orifice. Endoscopic injection of dextranomer/hyaluronic acid copolymer, via the HIT and Double HIT, has emerged as a highly successful, minimally invasive alternative to open surgical correction, with minimal associated morbidity.

Characterization of sleep-pattern and neuro-immune-endocrine markers at 24 hour post-injection of a single low dose of lipopolysaccharide in male Wistar rats.

PubMed

Nachón-García, Francisco; Hurtado-Alvarado, Gabriela; Acosta-Hernández, Mario E; Peña-Escudero, Carolina; Priego-Fernández, Sergio; Alvarez-Herrera, Samantha; Becerril-Villanueva, Enrique; Pérez-Sánchez, Gilberto; Pavón, Lenin; García-García, Fabio

2018-07-15

The long-term effect of immune system activation by a low dose of lipopolysaccharide on neuro-immune-endocrine regulation is unclear. Sleep, neurotransmitter concentrations, TNF-α, and corticosterone levels were evaluated in male Wistar rats implanted with conventional sleep recordings. In this work, we found that REM sleep was reduced in the first 4 h post-injection, without affecting the total sleep time, while adrenaline concentration was reduced in the hippocampus at 24 h post-injection of LPS. Our results demonstrated that, although the acute immune response was not evident 24 h after the injection of LPS, it was able to promote the reduction of AD in the hippocampus, which may explain in part the depressive behavior reported in rodents following LPS administration. Copyright © 2018 Elsevier B.V. All rights reserved.

Injectable foams for regenerative medicine.

PubMed

Prieto, Edna M; Page, Jonathan M; Harmata, Andrew J; Guelcher, Scott A

2014-01-01

The design of injectable biomaterials has attracted considerable attention in recent years. Many injectable biomaterials, such as hydrogels and calcium phosphate cements (CPCs), have nanoscale pores that limit the rate of cellular migration and proliferation. While introduction of macroporosity has been suggested to increase cellular infiltration and tissue healing, many conventional methods for generating macropores often require harsh processing conditions that preclude their use in injectable foams. In recent years, processes such as porogen leaching, gas foaming, and emulsion-templating have been adapted to generate macroporosity in injectable CPCs, hydrogels, and hydrophobic polymers. While some of the more mature injectable foam technologies have been evaluated in clinical trials, there are challenges remaining to be addressed, such as the biocompatibility and ultimate fate of the sacrificial phase used to generate pores within the foam after it sets in situ. Furthermore, while implantable scaffolds can be washed extensively to remove undesirable impurities, all of the components required to synthesize injectable foams must be injected into the defect. Thus, every compound in the foam must be biocompatible and noncytotoxic at the concentrations utilized. As future research addresses these critical challenges, injectable macroporous foams are anticipated to have an increasingly significant impact on improving patient outcomes for a number of clinical procedures. © 2013 Wiley Periodicals, Inc.

Injectable Foams for Regenerative Medicine

PubMed Central

Prieto, Edna M.; Page, Jonathan M.; Harmata, Andrew J.

2013-01-01

The design of injectable biomaterials has attracted considerable attention in recent years. Many injectable biomaterials, such as hydrogels and calcium phosphate cements, have nanoscale pores that limit the rate of cellular migration and proliferation. While introduction of macroporosity has been suggested to increase cellular infiltration and tissue healing, many conventional methods for generating macropores often require harsh processing conditions that preclude their use in injectable foams. In recent years, processes such as porogen leaching, gas foaming, and emulsion-templating have been adapted to generate macroporosity in injectable calcium phosphate cements, hydrogels, and hydrophobic polymers. While some of the more mature injectable foam technologies have been evaluated in clinical trials, there are challenges remaining to be addressed, such as the biocompatibility and ultimate fate of the sacrificial phase used to generate pores within the foam after it sets in situ. Furthermore, while implantable scaffolds can be washed extensively to remove undesirable impurities, all of the components required to synthesize injectable foams must be injected into the defect. Thus, every compound in the foam must be biocompatible and non-cytotoxic at the concentrations utilized. As future research addresses these critical challenges, injectable macroporous foams are anticipated to have an increasingly significant impact on improving patient outcomes for a number of clinical procedures. PMID:24127230

Science to practice: Can we expand focal interventional oncologic ablation treatments into an effective systemic therapy?

PubMed

Goldberg, S Nahum

2013-05-01

Hamamoto et al (1) were able to demonstrate that combination therapy of a lung tumor by using radiofrequency ablation (RFA) with local injection of an immunostimulant, OK-432, resulted in improved survival when compared with other therapies tested in a VX2 rabbit model. In addition, not only was greater tumor regression seen in a second distant ear tumor implanted prior to the therapy, but also reduced tumor growth was seen when a second tumor implantation (ie, rechallenge) was attempted. These factors strongly suggest the successful activation of systemic antitumor immunity using this approach in this specific tumor model.

A sub-microwatt piezo-floating-gate sensor for long-term fatigue monitoring in biomechanical implants.

PubMed

Lajnef, Nizar; Chakrabartty, Shantanu; Elvin, Niell; Elvin, Alex

2006-01-01

In this paper we describe an implementation of a novel fatigue monitoring sensor based on integration of piezoelectric transduction with floating gate avalanche injection. The miniaturized sensor enables continuous battery-less monitoring and time-to-failure predictions of biomechanical implants. Measured results from a fabricated prototype in a 0.5 microm CMOS process indicate that the device can compute cumulative statistics of electrical signals generated by piezoelectric transducer, while consuming less that 1 microW of power. The ultra-low power operation makes the sensor attractive for integration with poly-vinylidene difluoride (PVDF) based transducers that have already proven to be biocompatible.

Proton redistribution and pseudoantiferroelectricity in H+ implanted Pb(Zr,Ti)O3 thin films

NASA Astrophysics Data System (ADS)

Zhang, X.; Jiang, A. Q.; Tang, T. A.

2009-05-01

Hydrogen ions were implanted into 500-nm-thick Pb(Zr,Ti)O3 ferroelectric thin films with different doses and energies. An antiferroelectric behavior was confirmed in the implanted thin films with proper H+ injection energies from independent measurements of polarization-electric hysteresis loops and capacitance-voltage curves. With the increase in the H+ doping concentration and implanting energy up to 25 keV, the characteristic pseudoantiferroelectric behavior becomes more evident in the films along with the concomitant reduction in the remnant polarization. However, the above antiferroelectricity is weakened for the restoration of a preferred ferroelectric state, once the implanting energy is higher than 35 eV. The consequent "Trim94" simulation of the H+ distribution as well as the induced oxygen vacancies (VOṡṡ) indicates the almost linear shift in the depth for the maximum charge density within the film with the enhanced implanting energy until the depth moves out of the film thickness above 40 keV. Beyond the antiferroelectric dependence on the implanting energy in thin films, the previous ferroelectric state can also be rejuvenated under a bipolar-field stressing through the redistribution of the H+ and VOṡṡ concentrations. The rejuvenation process is accelerated upon heating due to the increased charge mobility. The doping charges are immobile during short-time domain switching but movable under a long-time negative/positive field with the estimated activation energy of 0.23/0.29 eV. This study implies the potential application of high-density charge storage of the implanted ferroelectric capacitor with the property comparable to a genuine antiferroelectric capacitor.

Intrathecal transplantation of neuroblastoma cells decreases heat hyperalgesia and cold allodynia in a rat model of neuropathic pain.

PubMed

De la Calle, J L; Mena, M A; González-Escalada, J R; Paíno, C L

2002-11-30

Intrathecal grafting of cells as biological pumps to deliver monoamines, endorphins, and/or trophic factors, has been shown to be effective in treating chronic pain both in experimental animals and in clinical trials. We have tested whether intrathecal implantation of neuroblastoma cells reduces heat hyperalgesia and cold allodynia in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Behavioral tests and cerebrospinal fluid (CSF) collection were performed before CCI, 1 week later (after which, vehicle or NB69 cells were intrathecally injected) and at 4, 7, and 14 days post-injection. Both CSF sampling and injection of the cells were performed by direct lumbar puncture. Intrathecal grafting of 4 x 10(6) NB69 neuroblastoma cells reduced to basal levels the nociceptive response to heat in nerve-injured hindpaws, while the response of control limbs remained unchanged. Similarly, the allodynic response to cold elicited by acetone evaporation decreased in the animals implanted with NB69 cells. An increase in the concentrations of dopamine and serotonin metabolites of around 150% was observed in the CSF of animals that received grafts of NB69 cells. These data suggest that the monoamines released by NB69 cells in the intrathecal space produce analgesia to neuropathic pain in rats. Copyright 2002 Elsevier Science Inc.

Ultraminiaturized photovoltaic and radio frequency powered optoelectronic systems for wireless optogenetics.

PubMed

Park, Sung Il; Shin, Gunchul; Banks, Anthony; McCall, Jordan G; Siuda, Edward R; Schmidt, Martin J; Chung, Ha Uk; Noh, Kyung Nim; Mun, Jonathan Guo-Han; Rhodes, Justin; Bruchas, Michael R; Rogers, John A

2015-10-01

Wireless control and power harvesting systems that operate injectable, cellular-scale optoelectronic components provide important demonstrated capabilities in neuromodulatory techniques such as optogenetics. Here, we report a radio frequency (RF) control/harvesting device that offers dramatically reduced size, decreased weight and improved efficiency compared to previously reported technologies. Combined use of this platform with ultrathin, multijunction, high efficiency solar cells allows for hundred-fold reduction of transmitted RF power, which greatly enhances the wireless coverage. Fabrication involves separate construction of the harvester and the injectable µ-ILEDs. To test whether the presence of the implantable device alters behavior, we implanted one group of wild type mice and compared sociability behavior to unaltered controls. Social interaction experiments followed protocols defined by Silverman et al. with minor modifications. The results presented here demonstrate that miniaturized RF harvesters, and RF control strategies with photovoltaic harvesters can, when combined with injectable µ-ILEDs, offer versatile capabilities in optogenetics. Experimental and modeling studies establish a range of effective operating conditions for these two approaches. Optogenetics studies with social groups of mice demonstrate the utility of these systems. The addition of miniaturized, high performance photovoltaic cells significantly expands the operating range and reduces the required RF power. The platform can offer capabilities to modulate signaling path in the brain region of freely-behaving animals. These suggest its potential for widespread use in neuroscience.

Effect of Increased Endometrial Thickness and Implantation Rate by Granulocyte Colony-Stimulating Factor on Unresponsive Thin Endometrium in Fresh In Vitro Fertilization Cycles: A Randomized Clinical Trial

PubMed Central

Sarvi, Fatemeh; Arabahmadi, Marjan; Alleyassin, Ashraf; Aghahosseini, Marzieh

2017-01-01

Background The correlation between endometrial thickness and receptivity has been mentioned in various studies. This study investigated the effect of granulocyte colony-stimulating factor in treating thin endometrium of infertile women who were chosen for in vitro fertilization in our infertility clinic in 2014 and 2015. Methods In this randomized clinical trial, 28 women who were chosen for in vitro fertilization and had endometrial thickness of less than 6 mm on the day of human chorionic gonadotropin (hCG) injection were included in the study. They were randomly divided into two groups: investigation and control groups. In investigation group (n = 13) one granulocyte colony-stimulating factor vial (300 micrograms in 1 mL) was infused into the uterus within five minutes by embryo transfer catheter. In control group (n = 15) 1 mL of saline was injected into the uterus with the same catheter. Results There were significant differences between the two groups in terms of means of endometrial thickness on oocyte retrieval day (P = 0.001), embryo transfer day (P = 0.001), hCG injections (P = 0.001), and implantation rates (P = 0.001). Conclusion Granulocyte colony-stimulating factor can increase endometrial thickness in women treated with in vitro fertilization. RCT Code is 201406046063N2. PMID:28791050

Effect of sperm entry on blastocyst development after in vitro fertilization and intracytoplasmic sperm injection - mouse model.

PubMed

Piotrowska-Nitsche, Karolina; Chan, Anthony W S

2013-01-01

To investigate whether in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), influence the embryo's development and its quality using the mouse as a model. Assisted fertilization was performed using ICSI and IVF. Fluorescent beads were adhered to the fertilization cone or place of previous sperm injection in the natural mated (NM), IVF and ICSI embryos, respectively. Embryo examination was carried out at the two-cell and blastocyst stage to determine the position of fluorescent bead. Protein expression was detected by fluorescence immunocytochemical staining and confocal microscopic imaging of blastocysts. IVF and ICSI embryos developed at rates comparable to NM group. Embryos show similar expression patterns of two transcription factors, Oct4 and Cdx2. The most preferred place for spermatozoa attachment was the equatorial site of the egg, whether fertilization occurred in vitro or under natural conditions. We also link the sperm entry position (SEP) to embryo morphology and the number of cells at the blastocyst stage, with no influence of the method of fertilization. IVF and ICSI, do not compromise in vitro pre-implantation development. Additional data, related to sperm entry, could offer further criteria to predict embryos that will implant successfully. Based on embryo morphology, developmental rate and protein expression level of key transcription factors, our results support the view that ART techniques, such as IVF and ICSI, do not perturb embryonic development or quality.

Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction

PubMed Central

Khattab, Ahmad; Islam, Mohammad Ariful; Hweij, Khaled Abou; Zeitouny, Joya; Waters, Renae; Sayegh, Malek; Hossain, Md Monowar; Paul, Arghya

2015-01-01

Cardiac tissue damage due to myocardial infarction (MI) is one of the leading causes of mortality worldwide. The available treatments of MI include pharmaceutical therapy, medical device implants, and organ transplants, all of which have severe limitations including high invasiveness, scarcity of donor organs, thrombosis or stenosis of devices, immune rejection, and prolonged hospitalization time. Injectable hydrogels have emerged as a promising solution for in situ cardiac tissue repair in infarcted hearts after MI. In this review, an overview of various natural and synthetic hydrogels for potential application as injectable hydrogels in cardiac tissue repair and regeneration is presented. The review starts with brief discussions about the pathology of MI, its current clinical treatments and their limitations, and the emergence of injectable hydrogels as a potential solution for post MI cardiac regeneration. It then summarizes various hydrogels, their compositions, structures and properties for potential application in post MI cardiac repair, and recent advancements in the application of injectable hydrogels in treatment of MI. Finally, the current challenges associated with the clinical application of injectable hydrogels to MI and their potential solutions are discussed to help guide the future research on injectable hydrogels for translational therapeutic applications in regeneration of cardiac tissue after MI. PMID:27668147

21 CFR 522.2470 - Tiletamine hydrochloride and zolazepam hydrochloride for injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR... intramuscular dosage of 3 to 4.5 milligrams per pound of body weight for diagnostic purposes; 4.5 to 6 milligrams per pound of body weight for minor procedures of short duration such as repair of lacerations and...

21 CFR 522.2470 - Tiletamine hydrochloride and zolazepam hydrochloride for injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR... intramuscular dosage of 3 to 4.5 milligrams per pound of body weight for diagnostic purposes; 4.5 to 6 milligrams per pound of body weight for minor procedures of short duration such as repair of lacerations and...

TISSUE DISTRIBUTION AND HISTOLOGY OF FITC AND FITC-17B-ESTRADIOL IN CUNNER (TAUTOGOLABRUS ADSPERSUS) AFTER SUBCUTANEOUS IMPLANTATION IN A CONTROL RELEASE MATRIX

EPA Science Inventory

Peritoneal injection is a major route for chemical introduction into fish for toxicological studies. This procedure, however, causes rapid exposure to toxicants. Long-term studies to determine effects of estrogenic chemicals on fish reproduction require a methodology that allows ...

Development of an Injectable Salmon Fibrinogen-Thrombin Matrix to Enhance Healing of Compound Fractures of Extremities

DTIC Science & Technology

2011-10-01

of bone regeneration in animals treated with different implantable matrix. The material to be tested in this project is a salmon fibrin matrix... Buprenorphine and metacam (Meloxicam) are also administered at the time of surgery for short term pain relief. Fluoroscopy is performed before and after injury

21 CFR 522.2690 - Zinc gluconate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter...

21 CFR 522.2690 - Zinc gluconate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter...

21 CFR 522.2690 - Zinc gluconate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter...

75 FR 1274 - Implantation or Injectable Dosage Form New Animal Drugs; Florfenicol and Flunixin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 [Docket No... AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration... Veterinary Medicine (HFV-130), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-276...

GLUCOCORTICOIDS REGULATE THE SYNTHESIS OF GFAP IN INTACT AND ADRENALECTOMIZED RATS BUT DO NOT AFFECT ITS EXPRESSION FOLLOWING BRAIN INJURY

EPA Science Inventory

We examined the effects of corticosterone (CORT) on the amount of glial fibrillary acidic protein (GFAP) in INTACT, adrenalectomized (ADX) and brain-damaged rats. hort (5 days)- to long-term (4 months) CORT administration by injection, pellet implantation, or in the drinking wate...

BDNF gene delivery within and beyond templated agarose multi-channel guidance scaffolds enhances peripheral nerve regeneration

NASA Astrophysics Data System (ADS)

Gao, Mingyong; Lu, Paul; Lynam, Dan; Bednark, Bridget; Campana, W. Marie; Sakamoto, Jeff; Tuszynski, Mark

2016-12-01

Objective. We combined implantation of multi-channel templated agarose scaffolds with growth factor gene delivery to examine whether this combinatorial treatment can enhance peripheral axonal regeneration through long sciatic nerve gaps. Approach. 15 mm long scaffolds were templated into highly organized, strictly linear channels, mimicking the linear organization of natural nerves into fascicles of related function. Scaffolds were filled with syngeneic bone marrow stromal cells (MSCs) secreting the growth factor brain derived neurotrophic factor (BDNF), and lentiviral vectors expressing BDNF were injected into the sciatic nerve segment distal to the scaffold implantation site. Main results. Twelve weeks after injury, scaffolds supported highly linear regeneration of host axons across the 15 mm lesion gap. The incorporation of BDNF-secreting cells into scaffolds significantly increased axonal regeneration, and additional injection of viral vectors expressing BDNF into the distal segment of the transected nerve significantly enhanced axonal regeneration beyond the lesion. Significance. Combinatorial treatment with multichannel bioengineered scaffolds and distal growth factor delivery significantly improves peripheral nerve repair, rivaling the gold standard of autografts.

Preparation and characterization of injectable Mitoxantrone poly (lactic acid)/fullerene implants for in vivo chemo-photodynamic therapy.

PubMed

Li, Zhi; Zhang, Fei-long; Pan, Li-li; Zhu, Xia-li; Zhang, Zhen-zhong

2015-08-01

Fullerene (C60) L-phenylalanine derivative attached with poly (lactic acid) (C60-phe-PLA) was developed to prepare injectable Mitoxantrone (MTX) multifunctional implants. C60-phe-PLA was self-assembled to form microspheres consisting of a hydrophilic antitumor drug (MTX) and a hydrophobic block (C60) by dispersion-solvent diffusion method. The self-assembled microspheres showed sustained release pattern almost 15days in vitro release experiments. According to the tissue distribution of C57BL mice after intratumoral administration of the microspheres, the MTX mainly distributed in tumors, and rarely in heart, liver, spleen, lung, and kidney. Photodynamic antitumor efficacy of blank microsphere was realized. Microspheres afforded high antitumor efficacy without obvious toxic effects to normal organs, owing to its significantly increased MTX tumor retention time, low MTX levels in normal organs and strong photodynamic activity of PLA-phe-C60. These C60-phe-PLA microspheres may be promising for the efficacy with minimal side effects in future treatment of solid tumors. Copyright © 2015 Elsevier B.V. All rights reserved.

Injectable CMC/PEI gel as an in vivo scaffold for demineralized bone matrix.

PubMed

Kim, Kyung Sook; Kang, Yun Mi; Lee, Ju Young; Kim, E Sle; Kim, Chun Ho; Min, Byoung Hyun; Lee, Hai Bang; Kim, Jae Ho; Kim, Moon Suk

2009-01-01

A number of materials have been considered as sources of grafts to repair bone defects. Here, we examined the possibility of creating in situ-forming gels from sodium carboxymethylcellulose (CMC) and poly(ethyleneimine) (PEI) for use as an in vivo carrier of demineralized bone matrix (DBM). The interaction between anionic CMC and cationic PEI was examined by evaluating phase transition behavior and viscosity of CMC solutions containing 0-30 wt% PEI. CMC solutions containing 10 wt% PEI exhibited a sol-to-gel phase transition at temperatures greater than 35 degrees C. The phase transition is caused by electrostatic crosslinking of the CMC/PEI solution to form a gel with a three-dimensional network structure. In situ-formed gel implants were successfully fabricated in vivo by simple subcutaneous injection of the CMC/PEI (90/10) solution (with and without DBM) into Fisher rats. The resulting in situ-formed implant maintained its shape for 28 days in vitro and in vivo. Our results show that in situ-forming CMC/PEI gels can serve as a DBM carrier that can be delivered with a minimally invasive procedure.

An implantable bolus infusion pump for use in freely moving, nontethered rats

PubMed Central

HOLSCHNEIDER, D. P.; MAAREK, J.-M. I.; HARIMOTO, J.; YANG, J.; SCREMIN, O. U.

2014-01-01

One of the current constraints on functional neuroimaging in animals is that to avoid movement artifacts during data acquisition, subjects need to be immobilized, sedated, or anesthetized. Such measures limit the behaviors that can be examined, and introduce the additional variables of stress or anesthetic agents that may confound meaningful interpretation. This study provides a description of the design and characteristics of a self-contained, implantable microbolus infusion pump (MIP) that allows triggering of a bolus injection at a distance in conscious, behaving rats that are not restrained or tethered. The MIP is externally triggered by a pulse of infrared light and allows in vivo bolus drug delivery. We describe application of this technology to the intravenous bolus delivery of iodo[14C]antipyrine in a freely moving animal, followed immediately by lethal injection, rapid removal of the brain, and analysis of regional cerebral blood flow tissue radioactivity with the use of autoradiography. The ability to investigate changes in brain activation in nonrestrained animals makes the MIP a powerful tool for evaluation of complex behaviors. PMID:12234827

Degradation of oxalate in rats implanted with immobilized oxalate oxidase.

PubMed

Raghavan, K G; Tarachand, U

1986-01-20

Accumulation of oxalate leads to hyperoxaluria and calcium oxalate nephrolithiasis in man. Since oxalate is a metabolic end product in mammals, the feasibility of its enzymic degradation has been tested in vivo in rats by administering exogenous oxalate oxidase. Oxalate oxidase, isolated from banana fruit peels, in its native form was found to be non-active at the physiological pH of the recipient animal. However, its functional viability in the recipient animal was ensured by its prior binding with ethylenemaleic anhydride, thus shifting its pH activity curve towards the alkaline range. Rats implanted with dialysis membrane capsules containing such immobilized oxalate oxidase in their peritoneal cavities effectively metabolized intraperitoneally injected [14C]oxalate as well as its precursor [14C]glyoxalate. The implantation of capsules containing coentrapped multienzyme preparations of oxalate oxidase, catalase and peroxidase led to a further degradation of administered [14C]oxalate in rats.

The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs

PubMed Central

Tan, Naiwen; Liu, Xiangwei; Cai, Yanhui; Zhang, Sijia; Jian, Bo; Zhou, Yuchao; Xu, Xiaoru; Ren, Shuai; Wei, Hongbo; Song, Yingliang

2017-01-01

Background High failure rates of oral implants have been reported in diabetic patients due to the disruption of osseointegration. The aim of this study was to investigate whether direct laser metal sintering (DLMS) could improve osseointegration in diabetic animal models. Methods Surface characterizations were carried out on two types of implants. Cell morphology and the osteogenic-related gene expression of MG63 cells were observed under conditions of DLMS and microarc oxidation (MAO). A diabetes model in mini-pigs was established by intravenous injection of streptozotocin (150 mg/kg), and a total of 36 implants were inserted into the mandibular region. Micro-computed tomography (micro-CT) and histologic evaluations were performed 3 and 6 months after implantation. Results The Ra (the average of the absolute height of all points) of MAO surface was 2.3±0.3 µm while the DLMS surface showed the Ra of 27.4±1.1 µm. The cells on DLMS implants spread out more podia than those on MAO implants through cell morphology analysis. Osteogenic-related gene expression was also dramatically increased in the DLMS group. Obvious improvement was observed in the micro-CT and Van Gieson staining analyses of DLMS implants compared with MAO at 3 months, although this difference disappeared by 6 months. DLMS implants showed a higher bone–implant contact percentage (33.2%±11.2%) at 3 months compared with MAO group (18.9%±7.3%) while similar results were showed at 6 months between DLMS group (42.8%±10.1%) and MAO group (38.3%±10.8%). Conclusion The three-dimensional environment of implant surfaces with highly porous and fully interconnected channel and pore architectures can improve cell spreading and accelerate the progress of osseointegration in diabetic mini-pigs. PMID:28814861

Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode.

PubMed

MacEwan, Matthew R; Zellmer, Erik R; Wheeler, Jesse J; Burton, Harold; Moran, Daniel W

2016-01-01

Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm 2 surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline, or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation.

Development and experimental study of large size composite plasma immersion ion implantation device

NASA Astrophysics Data System (ADS)

Falun, SONG; Fei, LI; Mingdong, ZHU; Langping, WANG; Beizhen, ZHANG; Haitao, GONG; Yanqing, GAN; Xiao, JIN

2018-01-01

Plasma immersion ion implantation (PIII) overcomes the direct exposure limit of traditional beam-line ion implantation, and is suitable for the treatment of complex work-piece with large size. PIII technology is often used for surface modification of metal, plastics and ceramics. Based on the requirement of surface modification of large size insulating material, a composite full-directional PIII device based on RF plasma source and metal plasma source is developed in this paper. This device can not only realize gas ion implantation, but also can realize metal ion implantation, and can also realize gas ion mixing with metal ions injection. This device has two metal plasma sources and each metal source contains three cathodes. Under the condition of keeping the vacuum unchanged, the cathode can be switched freely. The volume of the vacuum chamber is about 0.94 m3, and maximum vacuum degree is about 5 × 10-4 Pa. The density of RF plasma in homogeneous region is about 109 cm-3, and plasma density in the ion implantation region is about 1010 cm-3. This device can be used for large-size sample material PIII treatment, the maximum size of the sample diameter up to 400 mm. The experimental results show that the plasma discharge in the device is stable and can run for a long time. It is suitable for surface treatment of insulating materials.

Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode

PubMed Central

MacEwan, Matthew R.; Zellmer, Erik R.; Wheeler, Jesse J.; Burton, Harold; Moran, Daniel W.

2016-01-01

Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm2 surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline, or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation. PMID:28008303

Juniper wood as a possible implant material.

PubMed

Gross, K A; Ezerietis, E

2003-03-15

Natural materials, such as wood and bone, possess structures fulfilling the requirements of support and transport of nutrients. Similarity in function and properties provides inspiration for investigating the possible use of wood as an implant material. Juniperus communis wood is dense, durable, and strong and has naturally impregnated essential oils that display antiseptic properties. This study investigated the toxicity of the oil, the effect of sterilization on the mechanical properties of the wood, and bone attachment with animal studies. The possible toxicity of the oil was determined orally and by intravenous injection. At low concentrations, the dose that would be released by the wood in the body could be tolerated without any detrimental effects. Sterilization of the wood in boiling water lowered the elastic modulus and modulus of rupture to a level at which the elastic modulus could be better matched to bone. Wood shaped into the form of femoral implants were implanted into rabbits and displayed good acceptance by the body up to a period of 3 years, indicating bone apposition, abutment into pores, and growth into drilled cavities. Copyright 2003 Wiley Periodicals, Inc.

Development of HEATHER for cochlear implant stimulation using a new modeling workflow.

PubMed

Tran, Phillip; Sue, Andrian; Wong, Paul; Li, Qing; Carter, Paul

2015-02-01

The current conduction pathways resulting from monopolar stimulation of the cochlear implant were studied by developing a human electroanatomical total head reconstruction (namely, HEATHER). HEATHER was created from serially sectioned images of the female Visible Human Project dataset to encompass a total of 12 different tissues, and included computer-aided design geometries of the cochlear implant. Since existing methods were unable to generate the required complexity for HEATHER, a new modeling workflow was proposed. The results of the finite-element analysis agree with the literature, showing that the injected current exits the cochlea via the modiolus (14%), the basal end of the cochlea (22%), and through the cochlear walls (64%). It was also found that, once leaving the cochlea, the current travels to the implant body via the cranial cavity or scalp. The modeling workflow proved to be robust and flexible, allowing for meshes to be generated with substantial user control. Furthermore, the workflow could easily be employed to create realistic anatomical models of the human head for different bioelectric applications, such as deep brain stimulation, electroencephalography, and other biophysical phenomena.

Successful transfemoral aortic Edwards(®) SAPIEN(®) bioprosthesis implantation without using iodinated contrast media in a woman with severe allergy to contrast agent.

PubMed

Leroux, Lionel; Dijos, Marina; Dos Santos, Pierre

2013-12-01

Severe anaphylactoid reaction after the use of iodinated contrast media are rare but can contraindicate the use of contrast agent. It was the case of a 53-year-old woman suffering from symptomatic severe aortic stenosis, recused for cardiac surgery because of deleterious effects of chest-wall irradiation, with porcelain aorta. We decided to implant a 23-mm Edwards(®) SAPIEN(®) transcatheter aortic valve via a femoral route without using any contrast media. The implantation was successful after surgical approach of the femoral artery, transesophageal echocardiography guiding, and localization of native leaflets and coronary trunk with catheters. Immediate and one month post-interventional follow-up was favorable and echocardiography showed a good functioning of the aortic bioprosthesis. Although conventional angiography is the best way to visualize the good positioning of the valve before deployment, our case suggests that, in special situations, transfemoral implantation of an Edwards(®) SAPIEN(®) aortic bioprosthesis is feasible without any contrast injection. Copyright © 2012 Wiley Periodicals, Inc.

Intracranial implantation with subsequent 3D in vivo bioluminescent imaging of murine gliomas.

PubMed

Abdelwahab, Mohammed G; Sankar, Tejas; Preul, Mark C; Scheck, Adrienne C

2011-11-06

The mouse glioma 261 (GL261) is recognized as an in vivo model system that recapitulates many of the features of human glioblastoma multiforme (GBM). The cell line was originally induced by intracranial injection of 3-methyl-cholantrene into a C57BL/6 syngeneic mouse strain (1); therefore, immunologically competent C57BL/6 mice can be used. While we use GL261, the following protocol can be used for the implantation and monitoring of any intracranial mouse tumor model. GL261 cells were engineered to stably express firefly luciferase (GL261-luc). We also created the brighter GL261-luc2 cell line by stable transfection of the luc2 gene expressed from the CMV promoter. C57BL/6-cBrd/cBrd/Cr mice (albino variant of C57BL/6) from the National Cancer Institute, Frederick, MD were used to eliminate the light attenuation caused by black skin and fur. With the use of albino C57BL/6 mice; in vivo imaging using the IVIS Spectrum in vivo imaging system is possible from the day of implantation (Caliper Life Sciences, Hopkinton, MA). The GL261-luc and GL261-luc2 cell lines showed the same in vivo behavior as the parental GL261 cells. Some of the shared histological features present in human GBMs and this mouse model include: tumor necrosis, pseudopalisades, neovascularization, invasion, hypercellularity, and inflammation (1). Prior to implantation animals were anesthetized by an intraperitoneal injection of ketamine (50 mg/kg), xylazine (5 mg/kg) and buprenorphine (0.05 mg/kg), placed in a stereotactic apparatus and an incision was made with a scalpel over the cranial midline. A burrhole was made 0.1 mm posterior to the bregma and 2.3mm to the right of the midline. A needle was inserted to a depth of 3mm and withdrawn 0.4 mm to a depth of 2.6 mm. Two μl of GL261-luc or GL261-luc2 cells (10(7) cells/ml) were infused over the course of 3 minutes. The burrhole was closed with bonewax and the incision was sutured. Following stereotactic implantation the bioluminescent cells are detectable from the day of implantation and the tumor can be analyzed using the 3D image reconstruction feature of the IVIS Spectrum instrument. Animals receive a subcutaneous injection of 150 μg luciferin /kg body weight 20 min prior to imaging. Tumor burden is quantified using mean tumor bioluminescence over time. Tumor-bearing mice were observed daily to assess morbidity and were euthanized when one or more of the following symptoms are present: lethargy, failure to ambulate, hunched posture, failure to groom, anorexia resulting in >10% loss of weight. Tumors were evident in all of the animals on necropsy.

Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model.

PubMed

Bi, Fanggang; Shi, Zhongli; Zhou, Chenhe; Liu, An; Shen, Yue; Yan, Shigui

2015-01-01

We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 μg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.

Rhein Induces Oxidative Stress and Apoptosis in Mouse Blastocysts and Has Immunotoxic Effects during Embryonic Development.

PubMed

Huang, Chien-Hsun; Chan, Wen-Hsiung

2017-09-20

Rhein, a glucoside chemical compound found in a traditional Chinese medicine derived from the roots of rhubarb, induces cell apoptosis and is considered to have high potential as an antitumor drug. Several previous studies showed that rhein can inhibit cell proliferation and trigger mitochondria-related or endoplasmic reticulum (ER) stress-dependent apoptotic processes. However, the side effects of rhein on pre- and post-implantation embryonic development remain unclear. Here, we show that rhein has cytotoxic effects on blastocyst-stage mouse embryos and induces oxidative stress and immunotoxicity in mouse fetuses. Blastocysts incubated with 5-20 μM rhein showed significant cell apoptosis, as well as decreases in their inner cell mass cell numbers and total cell numbers. An in vitro development assay showed that rhein affected the developmental potentials of both pre- and post-implantation embryos. Incubation of blastocysts with 5-20 μM rhein was associated with increased resorption of post-implantation embryos and decreased fetal weight in an embryo transfer assay. Importantly, in an in vivo model, intravenous injection of dams with rhein (1, 3, and 5 mg/kg body weight/day) for four days resulted in apoptosis of blastocyst-stage embryos, early embryonic developmental injury, and decreased fetal weight. Intravenous injection of dams with 5 mg/kg body weight/day rhein significantly increased the total reactive oxygen species (ROS) content of fetuses and the transcription levels of antioxidant proteins in fetal livers. Additional work showed that rhein induced apoptosis through ROS generation, and that prevention of apoptotic processes effectively rescued the rhein-induced injury effects on embryonic development. Finally, the transcription levels of the innate-immunity related genes, CXCL1 , IL-1 β and IL-8 , were down-regulated in the fetuses of dams that received intravenous injections of rhein. These results collectively show that rhein has the potential to induce embryonic cytotoxicity and induce oxidative stress and immunotoxicity during the development of mouse embryos.

Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema.

PubMed

Cicinelli, Maria Vittoria; Cavalleri, Michele; Querques, Lea; Rabiolo, Alessandro; Bandello, Francesco; Querques, Giuseppe

2017-12-01

To analyse the effects of intravitreal dexamethasone implant in patients suffering from diabetic macular oedema (DME) on the basis of their visual and functional response to antivascular endothelial growth factor (VEGF) loading dose, in order to early shift to corticosteroids in poorly responding patients. Retrospective monocentric study. Data of patients with diabetes shifted to 0.7 mg dexamethasone implant after three injections of ranibizumab (RNB) and followed-up to 12 months were reviewed. Main outcome was the evaluation of short-term changes after dexamethasone implant injection, stratifying patients on the basis of best-corrected visual acuity (BCVA) and central macular thickness (CMT) after RNB loading dose. Secondary outcome was to investigate clinical gain maintenance at long-term follow-up. Overall, 45 eyes of 45 patients (23 males, 51.1%), mean age 69.7±9 years, were included in the analysis. After 3 injections of RNB, 30 eyes (66.7%) had a poor visual response (-4.3±10.7 letters), while 15 eyes (33.3%) disclosed good visual outcome (+13.9±9.2 letters). Patients with poor visual response were associated with limited morphological improvement (p=0.04). After 1 month from dexamethasone, only poor responders showed relevant increase in BCVA (p=0.006) and reduction in CMT (p=0.002), in comparison to good visual response patients, featuring only minor clinical effects (p=0.3). The same trend was maintained up to 12 months, after a mean of 1.9±1.1 dexamethasone administrations. Visual and anatomical responses after RNB loading dose are significant predictors of both early term and long-term visual acuity improvement after switching to corticosteroids in patients with DME unresponsive to anti-VEGF. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Intracerebroventricular opiate infusion for refractory head and facial pain

PubMed Central

Lee, Darrin J; Gurkoff, Gene G; Goodarzi, Amir; Muizelaar, J Paul; Boggan, James E; Shahlaie, Kiarash

2014-01-01

AIM: To study the risks and benefits of intracerebroventricular (ICV) opiate pumps for the management of benign head and face pain. METHODS: SSix patients with refractory trigeminal neuralgia and/or cluster headaches were evaluated for implantation of an ICV opiate infusion pump using either ICV injections through an Ommaya reservoir or external ventricular drain. Four patients received morphine ICV pumps and two patientS received a hydromorphone pump. Of the Four patients with morphine ICV pumps, one patient had the medication changed to hydromorphone. Preoperative and post-operative visual analog scores (VAS) were obtained. Patients were evaluated post-operatively for a minimum of 3 mo and the pump dosage was adjusted at each outpatient clinic visit according to the patient’s pain level. RESULTS: All 6 patients had an intracerebroventricular opiate injection trial period, using either an Ommaya reservoir or an external ventricular drain. There was an average VAS improvement of 75.8%. During the trial period, no complications were observed. Pump implantation was performed an average of 3.7 wk (range 1-7) after the trial injections. After implantation, an average of 20.7 ± 8.3 dose adjustments were made over 3-56 mo after surgery to achieve maximal pain relief. At the most recent follow-up (26.2 mo, range 3-56), VAS scores significantly improved from an average of 7.8 ± 0.5 (range 6-10) to 2.8 ± 0.7 (range 0-5) at the final dose (mean improvement 5.0 ± 1.0, P < 0.001). All patients required a stepwise increase in opiate infusion rates to achieve maximal benefit. The most common complications were nausea and drowsiness, both of which resolved with pump adjustments. On average, infusion pumps were replaced every 4-5 years. CONCLUSION: These results suggest that ICV delivery of opiates may potentially be a viable treatment option for patients with intractable pain from trigeminal neuralgia or cluster headache. PMID:25133146

Simulation study of signal formation in position sensitive planar p-on-n silicon detectors after short range charge injection

NASA Astrophysics Data System (ADS)

Peltola, T.; Eremin, V.; Verbitskaya, E.; Härkönen, J.

2017-09-01

Segmented silicon detectors (micropixel and microstrip) are the main type of detectors used in the inner trackers of Large Hadron Collider (LHC) experiments at CERN. Due to the high luminosity and eventual high fluence of energetic particles, detectors with fast response to fit the short shaping time of 20-25 ns and sufficient radiation hardness are required. Charge collection measurements carried out at the Ioffe Institute have shown a reversal of the pulse polarity in the detector response to short-range charge injection. Since the measured negative signal is about 30-60% of the peak positive signal, the effect strongly reduces the CCE even in non-irradiated detectors. For further investigation of the phenomenon the measurements have been reproduced by TCAD simulations. As for the measurements, the simulation study was applied for the p-on-n strip detectors similar in geometry to those developed for the ATLAS experiment and for the Ioffe Institute designed p-on-n strip detectors with each strip having a window in the metallization covering the p+ implant, allowing the generation of electron-hole pairs under the strip implant. Red laser scans across the strips and the interstrip gap with varying laser diameters and Si-SiO2 interface charge densities (Qf) were carried out. The results verify the experimentally observed negative response along the scan in the interstrip gap. When the laser spot is positioned on the strip p+ implant the negative response vanishes and the collected charge at the active strip increases respectively. The simulation results offer a further insight and understanding of the influence of the oxide charge density in the signal formation. The main result of the study is that a threshold value of Qf, that enables negligible losses of collected charges, is defined. The observed effects and details of the detector response for different charge injection positions are discussed in the context of Ramo's theorem.

Glutamate microinjection in the medial septum of rats decreases paradoxical sleep and increases slow wave sleep.

PubMed

Mukherjee, Didhiti; Kaushik, Mahesh K; Jaryal, Ashok Kumar; Kumar, Velayudhan Mohan; Mallick, Hruda Nanda

2012-05-09

The role of the medial septum in suppressing paradoxical sleep and promoting slow wave sleep was suggested on the basis of neurotoxic lesion studies. However, these conclusions need to be substantiated with further experiments, including chemical stimulation studies. In this report, the medial septum was stimulated in adult male rats by microinjection of L-glutamate. Sleep-wakefulness was electrophysiologically recorded, through chronically implanted electrodes, for 2 h before the injection and 4 h after the injection. There was a decrease in paradoxical sleep during the first hour and an increase in slow wave sleep during the second hour after the injection. The present findings not only supported the lesion studies but also showed that the major role of the medial septum is to suppress paradoxical sleep.

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

PubMed

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

2018-06-19

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

Mechanical properties and biocompatibility of melt processed, self-reinforced ultrahigh molecular weight polyethylene.

PubMed

Huang, Yan-Fei; Xu, Jia-Zhuang; Li, Jian-Shu; He, Ben-Xiang; Xu, Ling; Li, Zhong-Ming

2014-08-01

The low efficiency of fabrication of ultrahigh molecular weight polyethylene (UHMWPE)-based artificial knee joint implants is a bottleneck problem because of its extremely high melt viscosity. We prepared melt processable UHMWPE (MP-UHMWPE) by addition of 9.8 wt% ultralow molecular weight polyethylene (ULMWPE) as a flow accelerator. More importantly, an intense shear flow was applied during injection molding of MP-UHMWPE, which on one hand, promoted the self-diffusion of UHMWPE chains, thus effectively reducing the structural defects; on the other hand, increased the overall crystallinity and induced the formation of self-reinforcing superstructure, i.e., interlocked shish-kebabs and oriented lamellae. Aside from the good biocompatibility, and the superior fatigue and wear resistance to the compression-molded UHMWPE, the injection-molded MP-UHMWPE exhibits a noteworthy enhancement in tensile properties and impact strength, where the yield strength increases to 46.3 ± 4.4 MPa with an increment of 128.0%, the ultimate tensile strength and Young's modulus rise remarkably up to 65.5 ± 5.0 MPa and 1248.7 ± 45.3 MPa, respectively, and the impact strength reaches 90.6 kJ/m(2). These results suggested such melt processed and self-reinforced UHMWPE parts hold a great application promise for use of knee joint implants, particularly for younger and more active patients. Our work sets up a new method to fabricate high-performance UHMWPE implants by tailoring the superstructure during thermoplastic processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Azoospermia in rabbits following an intravas injection of Vasalgel ™.

PubMed

Waller, Donald; Bolick, David; Lissner, Elaine; Premanandan, Christopher; Gamerman, Gary

2016-01-01

Vasectomy is currently the only long-acting contraceptive option available for men, despite increasing demand and potentially significant positive impacts on human health of additional male contraceptive options. Vasalgel ™ is a high molecular weight hydrogel polymer being developed as a non-hormonal long-acting reversible male contraceptive. Vasalgel consists of styrene-alt-maleic acid dissolved in dimethyl sulfoxide, which is distinct from styrene-alt-maleic anhydride materials previously studied. The goal of the study was to determine the contraceptive efficacy of two test articles with different levels of styrene maleic acid (100 %, and 80 % acid/20 % anhydride). The test articles were injected bilaterally in the vasa deferentia of mature male rabbits. Post-implantation analyses of semen parameters were completed over a 12 month period and compared to baseline measures of sperm concentration, motility and forward progression. Both test articles were effective in blocking the passage of spermatozoa through the vasa deferentia in the 12 subjects completing the study. A significant decrease in sperm concentration occurred following implantation of the test material, with no measurable sperm concentration except for a few samples in one animal that were markedly oligospermic. Vasalgel produced a rapid onset of azoospermia, with no sperm in semen samples collected as early as 29-36 days post-implantation, and was durable over a 12 month period. This study indicated that Vasalgel is an effective non-hormonal long-acting male contraceptive in a rabbit model.

Predicting and monitoring response to chemotherapy by 1,3-bis(2-chloroethyl)-1-nitrosourea in subcutaneously implanted 9L glioma using the apparent diffusion coefficient of water and 23Na MRI.

PubMed

Babsky, Andriy M; Hekmatyar, S K; Zhang, Hong; Solomon, James L; Bansal, Navin

2006-07-01

To examine the effects of the alkylating anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on (23)Na MRI and the water apparent diffusion coefficient (ADC) in subcutaneously- (sc-) implanted 9L glioma in rats. (23)Na MRI and (1)H water ADC measurements were performed on sham-treated control (N = 6) and BCNU-treated (N = 15) Fisher rats one day before BCNU injection and then one, three, and five days after BCNU injection. The BCNU-treated tumors were divided into BCNU-responsive (R(BCNU)) and BCNU-nonresponsive (NR(BCNU)) groups depending on the tumor volume changes that occurred after therapy. The pretreatment (23)Na MRI signal intensity (SI) and water ADC values were higher in R(BCNU) tumors compared to NR(BCNU) tumors. (23)Na MRI SI and water ADC increased with tumor growth in control and NR(BCNU) groups, but these changes were interrupted by BCNU therapy in R(BCNU) group. (23)Na MRI and water ADC measurements may be useful for predicting and monitoring response to chemotherapy in some tumors. However, the changes that occurred in (23)Na MRI SI and water ADC in sc-implanted 9L tumors are in contrast to previously published results for BCNU therapy of orthotopic 9L tumors. This may have important implications for monitoring therapy response in tumors. (c) 2006 Wiley-Liss, Inc.

INTRAVITREAL DEXAMETHASONE IMPLANTATION IN PATIENTS WITH DIFFERENT MORPHOLOGICAL DIABETIC MACULAR EDEMA HAVING INSUFFICIENT RESPONSE TO RANIBIZUMAB.

PubMed

Kaldırım, Havva; Yazgan, Serpil; Atalay, Kursat; Gurez, Ceren; Savur, Fatma

2018-05-01

To evaluate the effectiveness of a single intravitreal injection of dexamethasone implant in resistant diabetic macular edema that have different morphological types. In this retrospective study, 31 patients (35 eyes) with persistent diabetic macular edema, who underwent a single injection of dexamethasone implant, were evaluated. Diabetic macular edema was classified into three types: diffuse retinal thickening (n = 10), cystoid macular edema (n = 13), and serous retinal detachment (n = 12). Primary outcome measures were best corrected visual acuity, and central macular thickness. The three subgroups were similar in terms of age and gender (P > 0.05). Total duration of diabetes was significantly less in the serous retinal detachment subgroup (P = 0.01). There were no differences in the best corrected visual acuity between the three subgroups until the sixth month. However, the best corrected visual acuity was significantly better in the diffuse retinal thickness subgroup at the sixth month (P = 0.008). Regarding the central macular thickness values, it was statistically better in serous retinal detachment than in diffuse retinal thickening and cystoid macular edema subgroups till the sixth month (P = 0.001). However, at the sixth month, there was not any statistical difference between subgroups regarding central macular thickness values. Antiglaucomatous agents were required in 4 (11.4%) patients throughout the study. Treatment algorithms should differ according to the morphology of diabetic macular edema; however, more data is needed to give specific recommendations.

[Clinical efficacy and safety of uterine artery chemoembolization in abnormal placental implantation complicated with postpartum hemorrhage].

PubMed

Chen, Yao-ting; Xu, Lin-feng; Sun, Hong-liang; Li, Hui-qing; Hu, Ren-mei; Tan, Qi-yin

2010-04-01

To investigate the safety and clinical efficacy of uterime artery chemoembolization in postpartum hemorrhage (PPH) caused by abnormal placental implantation. Between December 2006 and September 2009, there were 23 cases of abnormal placental implantation with PPH in our hospital, among which 9 presented with continuous small amount of vaginal bleeding and 14 with acute excessive bleeding. The average bleeding time was (8+/-6) d and the mean blood loss was (980+/-660) ml. Abnormal placental implantation was confirmed by color Doppler ultrasound (CD-US) in all cases, the internal iliac artery angiography was performed to identify the uterine artery and bilateral uterine artery chemoembolization (UACE) with methotrexate (MTX) and gelfoam particles to the distal end of uterine artery was conducted after. CD-US rechecked all patients within 48 h after UACE and those patients with blurred margins between placenta and uterus and abnormal blood flow (>1 cmx1 cm) received ultrasonic-guided per vagina MTX multipoint injections. All cases were followed up for 3-26 months (average 12 months) to observe vaginal bleeding, placenta tissue discharge, serum human chorionic gonadotropin (hCG), uterine involution, menses, and side-effects or complications. (1) Curative effect: These 23 cases underwent 24 procedures of UACE successfully and vaginal bleeding ceased at an average of (3.5+/-1.3) min after UACE. Reduced blood flow in the placental implantation area was detected under CD-US after UACE. Among the 23 patients, wterine curettage was required in 16 cases due to retained placenta tissues with the mean blood loss of (40+/-28) ml during the operation, 2 underwent subtotal hysterectomy and confirmed to be placenta percreta by pathology examination, and placenta tissues were spontaneously discharged completely in 5 cases. Totally, 91% of the patients (21/23) reserved their uterus. (2) FOLLOW-UP: the serum hCG reduced to normal within 1-13 d after the placenta tissue were evacuated. Regular menstruation returned within 2-3 months in those patients who reserved uterus and normal size uterus was found under sonography at 3 months. No severe complication was reported except for some post embolization syndrome, such as pelvic pain or fever. UACE, combined with ultrasonic-guided transvaginal MTX injection, is a safe, minimal invasive and quick hemostatic procedure in treatment of abnormal placental implantation with PPH, and allows the preservation of uterus possible. CD-US is helpful in evaluation of the blood flow changes before and after UACE in abnormal placental implantation patients.

Additive manufacturing of hierarchical injectable scaffolds for tissue engineering.

PubMed

Béduer, A; Piacentini, N; Aeberli, L; Da Silva, A; Verheyen, C A; Bonini, F; Rochat, A; Filippova, A; Serex, L; Renaud, P; Braschler, T

2018-06-05

We present a 3D-printing technology allowing free-form fabrication of centimetre-scale injectable structures for minimally invasive delivery. They result from the combination of 3D printing onto a cryogenic substrate and optimisation of carboxymethylcellulose-based cryogel inks. The resulting highly porous and elastic cryogels are biocompatible, and allow for protection of cell viability during compression for injection. Implanted into the murine subcutaneous space, they are colonized with a loose fibrovascular tissue with minimal signs of inflammation and remain encapsulation-free at three months. Finally, we vary local pore size through control of the substrate temperature during cryogenic printing. This enables control over local cell seeding density in vitro and over vascularization density in cell-free scaffolds in vivo. In sum, we address the need for 3D-bioprinting of large, yet injectable and highly biocompatible scaffolds and show modulation of the local response through control over local pore size. This work combines the power of 3D additive manufacturing with clinically advantageous minimally invasive delivery. We obtain porous, highly compressible and mechanically rugged structures by optimizing a cryogenic 3D printing process. Only a basic commercial 3D printer and elementary control over reaction rate and freezing are required. The porous hydrogels obtained are capable of withstanding delivery through capillaries up to 50 times smaller than their largest linear dimension, an as yet unprecedented compression ratio. Cells seeded onto the hydrogels are protected during compression. The hydrogel structures further exhibit excellent biocompatibility 3 months after subcutaneous injection into mice. We finally demonstrate that local modulation of pore size grants control over vascularization density in vivo. This provides proof-of-principle that meaningful biological information can be encoded during the 3D printing process, deploying its effect after minimally invasive implantation. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

[Naringin reduced polymethylmethacrylate-induced osteolysis in the mouse air sacs model].

PubMed

Li, Nian-Hu; Xu, Zhan-wang

2015-04-01

To evaluate the influence of naringin on PMMA-induced osteoclastic bone resorption using the mouse air sacs model. Total 48 female Balb/c mices with the age of 8 to 10 weeks were chosen in the study. Air were injected into the back in 32 mices and formed the air sacs, 6 d later, the skulls (originated from other 16 mices) were implanted to the air sacs. Thirty-two animals were divided into naringin treatment group (with 2 concentrations of 150 mg/kg and 30 mg/ kg) , DMSO group and PBS blank group, 8 animals in each group. Polymethylmethacrylate (PMMA) particles were injected into the air sacs in naringin treatment groups and DMSO group so as to irritate inflammatory reaction. Naringin with 2 concentrations of 150 mg/kg and 30 mg/kg were dissolved in DMSO of 0.2 ml, and were injected into air sacs, respectively. In PBS black group, no stimulation with PMMA particles, only injected PBS, and in DMSO group, injected DMSO without naringin. Tartrate resistant acid phosphatase (TRAP), Ca2+ release, modified Masson stain and histological analysis were performed on the 7th day after stimulation. Compared with DMSO group, naringin treatment group's cellular infiltration decreased (P < 0.01); concentration of 150 mg/kg was better than that of concentrations of 30 mg/kg (8.90 ± 1.75 vs 15.23 ± 1.86). Naringin can decrease calcium release in the lavage of the air sacs bone resorption model, especially obvious in naringin with concentration of 150 mg/kg. Naringin can ameliorate the inflammatory reaction and the subsequent bone resorption (including bone collagen loss, TRAP positive cells amount and so on) in air sacs with bone implant and PMMA particles. Naringin with concentration of 150 mg/kg appeared to be an optimal dosage to deliver the therapeutic effects. Naringin inhibits PMMA-induced osteoclastogenesis and ameliorates the PMMA-associated inflammatory reaction and the subsequent bone resorption.

[Electroacupuncture Combined with Clomiphene Promotes Pregnancy and Blastocyst Implantation Possibly by Up-regulating Expression of Insulin Receptor and Insulin Receptor Substrate 1 Proteins in Endometrium in Rats with PCOS].

PubMed

Lai, Mao-Hua; Ma, Hong-Xia; Song, Xing-Hua

2016-10-25

To observe the effect of electroacupuncture (EA) intervention combined with clomiphene critate (CC) on the blastocyst implantation and pregnancy rate and expression of insulin receptor (INSR) and insulin receptor substrate 1 (IRS 1) proteins in the endometrium in rats with polycystic ovary syndrome (PCOS), so as to reveal its mechanisms underlying improvement of PCOS. One hundred and twenty-five female SD rats were randomly divided into normal control, PCOS model, medication (CC), EA and EA+CC groups ( n =25 in each group, 15 for checking blastocyst implantation, and 10 for Western blot). The PCOS model was established by subcutaneous injection of Dehydroepiandrosterone (DHEA) and fed with high-fat diet. Rats of the normal control group were treated by subcutaneous injection of sesame oil and fed with the normal forage. EA stimulation was applied to "Zhongwan" (CV 12), "Guanyuan" (CV 4) and bilateral "Tianshu" (ST 25) for 30 min, 3 times a week, 5 weeks altogether. Rats of the CC and EA+CC groups were fed with CC (100 mg·kg -1 ·d -1 ) for 2 days after regular restriction (30 min, 3 times a week, 5 weeks altogether). The pregnancy was determined by vaginal smear tests and the number of blastocyst implantation determined by examination of the uterus after execution. The expression of INSR and IRS 1 proteins in the endometrium was detected by Western blot. The pregnancy rate and the number of blastocyst implantation were significantly lower in the model group than in the normal control group ( P <0.05), and remarkably increased after EA and EA+CC interventions ( P <0.05). The effects of EA+CC were obviously superior to those of simple EA and simple medication in raising the pregnancy rate and the number of blastocyst implantation ( P <0.05). No significant differences were found between the EA and CC groups in the pregnancy rate and the number of blastocyst implantation ( P >0.05). The relative expression levels of both INSR and IRS 1 proteins were markedly lower in the model group than in the normal control group ( P <0.05), and significantly higher in both EA and EA+CC groups than in the model group ( P <0.05). No significant differences were found between the model and the CC groups and between the EA and EA+CC groups in the expression levels of INSR and IRS 1 proteins ( P >0.05). EA intervention can improve pregnancy rate and the number of blastocyst implantation in PCOS rats, which may be related to its effects in up-regulating the expression of INSR and IRS 1 proteins in the endometrium.

Superficial Enhanced Fluid Fat Injection (SEFFI) to Correct Volume Defects and Skin Aging of the Face and Periocular Region.

PubMed

Bernardini, Francesco P; Gennai, Alessandro; Izzo, Luigi; Zambelli, Alessandra; Repaci, Erica; Baldelli, Ilaria; Fraternali-Orcioni, G; Hartstein, Morris E; Santi, Pier Luigi; Quarto, Rodolfo

2015-07-01

Although recent research on micro fat has shown the potential advantages of superficial implantation and high stem cell content, clinical applications thus far have been limited. The authors report their experience with superficial enhanced fluid fat injection (SEFFI) for the correction of volume loss and skin aging of the face in general and in the periocular region. The finer SEFFI preparation (0.5 mL) was injected into the orbicularis in the periorbital and perioral areas, and the 0.8-mL preparation was injected subdermally elsewhere in the face. The records of 98 consecutive patients were reviewed. Average follow-up time was 6 months, and average volume of implanted fat was 20 mL and 51.4 mL for the 0.5-mL and 0.8-mL preparations, respectively. Good or excellent results were achieved for volume restoration and skin improvement in all patients. Complications were minor and included an oil cyst in 3 patients. The smaller SEFFI quantity (0.5 mL) was well suited to correct volume loss in the eyelids, especially the deep upper sulcus and tear trough, whereas the larger SEFFI content was effective for larger volume deficits in other areas of the face, including the brow, temporal fossa, zygomatic-malar region, nasolabial folds, marionette lines, chin, and lips. The fat administered by SEFFI is easily harvested via small side-port cannulae, yielding micro fat that is rich in viable adipocytes and stem cells. Both volumes of fat (0.5 mL and 0.8 mL) were effective for treating age-related lipoatrophy, reducing facial rhytids, and improving skin quality. 4 Therapeutic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Enhancement of Cell-Based Therapeutic Angiogenesis Using a Novel Type of Injectable Scaffolds of Hydroxyapatite-Polymer Nanocomposite Microspheres

PubMed Central

Koyama, Hidenori; Okada, Masahiro; Tanaka, Shinji; Shoji, Tetsuo; Emoto, Masanori; Furuzono, Tsutomu; Nishizawa, Yoshiki; Inaba, Masaaki

2012-01-01

Background Clinical trials demonstrate the effectiveness of cell-based therapeutic angiogenesis in patients with severe ischemic diseases; however, their success remains limited. Maintaining transplanted cells in place are expected to augment the cell-based therapeutic angiogenesis. We have reported that nano-hydroxyapatite (HAp) coating on medical devices shows marked cell adhesiveness. Using this nanotechnology, HAp-coated poly(l-lactic acid) (PLLA) microspheres, named nano-scaffold (NS), were generated as a non-biological, biodegradable and injectable cell scaffold. We investigate the effectiveness of NS on cell-based therapeutic angiogenesis. Methods and Results Bone marrow mononuclear cells (BMNC) and NS or control PLLA microspheres (LA) were intramuscularly co-implanted into mice ischemic hindlimbs. When BMNC derived from enhanced green fluorescent protein (EGFP)-transgenic mice were injected into ischemic muscle, the muscle GFP level in NS+BMNC group was approximate fivefold higher than that in BMNC or LA+BMNC groups seven days after operation. Kaplan-Meier analysis demonstrated that NS+BMNC markedly prevented hindlimb necrosis (P<0.05 vs. BMNC or LA+BMNC). NS+BMNC revealed much higher induction of angiogenesis in ischemic tissues and collateral blood flow confirmed by three-dimensional computed tomography angiography than those of BMNC or LA+BMNC groups. NS-enhanced therapeutic angiogenesis and arteriogenesis showed good correlations with increased intramuscular levels of vascular endothelial growth factor and fibroblast growth factor-2. NS co-implantation also prevented apoptotic cell death of transplanted cells, resulting in prolonged cell retention. Conclusion A novel and feasible injectable cell scaffold potentiates cell-based therapeutic angiogenesis, which could be extremely useful for the treatment of severe ischemic disorders. PMID:22529991

Absence of systemic toxicity in mouse model towards BaTiO3 nanoparticulate based eluate treatment.

PubMed

Dubey, Ashutosh Kumar; Thrivikraman, Greeshma; Basu, Bikramjit

2015-02-01

One of the existing issues in implant failure of orthopedic biomaterials is the toxicity induced by the fine particles released during long term use in vivo, leading to acute inflammatory response. In developing a new class of piezobiocomposite to mimic the integrated electrical and mechanical properties of bone, bone-mimicking physical properties as well as in vitro cytocompatibility properties have been achieved with spark plasma sintered hydroxyapatite (HA)-barium titanate (BaTiO3) composites. However, the presence of BaTiO3 remains a concern towards the potential toxicity effect. To address this issue, present work reports the first result to conclusively confirm the non-toxic effect of HA-BaTiO3 piezobiocomposite nanoparticulates, in vivo. Twenty BALB/c mice were intra-articularly injected at their right knee joints with different concentrations of HA-BaTiO3 composite of up to 25 mg/ml. The histopathological examination confirmed the absence of any trace of injected particles or any sign of inflammatory reaction in the vital organs, such as heart, spleen, kidney and liver at 7 days post-exposure period. Rather, the injected nanoparticulates were found to be agglomerated in the vicinity of the knee joint, surrounded by macrophages. Importantly, the absence of any systemic toxicity response in any of the vital organs in the treated mouse model, other than a mild local response at the site of delivery, was recorded. The serum biochemical analyses using proinflammatory cytokines (TNF-α and IL-1β) also complimented to the non-immunogenic response to injected particulates. Altogether, the absence of any inflammatory/adverse reaction will open up myriad of opportunities for BaTiO3 based piezoelectric implantable devices in biomedical applications.

Brachytherapy with Intratumoral Injections of Radiometal-Labeled Polymers That Thermoresponsively Self-Aggregate in Tumor Tissues.

PubMed

Sano, Kohei; Kanada, Yuko; Kanazaki, Kengo; Ding, Ning; Ono, Masahiro; Saji, Hideo

2017-09-01

Brachytherapy is a type of radiotherapy wherein titanium capsules containing therapeutic radioisotopes are implanted within tumor tissues, enabling high-dose radioirradiation to tumor tissues around the seeds. Although marked therapeutic effects have been demonstrated, brachytherapy needs a complicated implantation technique under general anesthesia and the seeds could migrate to other organs. The aim of this study was to establish a novel brachytherapy using biocompatible, injectable thermoresponsive polymers (polyoxazoline [POZ]) labeled with 90 Y, which can self-aggregate above a specific transition temperature (Tt), resulting in long-term intratumoral retention of radioactivity and therapeutic effect. Therefore, we evaluated the tumor retention of radiolabeled POZ derivatives and their therapeutic effects. Methods: Using oxazoline derivatives with ethyl (Et), isopropyl (Isp), and propyl (Pr) side chains, we synthesized EtPOZ, IspPOZ, Isp-PrPOZ (heteropolymer), and PrPOZ and measured their characteristic Tts. The intratumoral retention of 111 In-labeled POZ was evaluated until 7 d after injection in nude mice bearing PC-3 human prostate cancer. The intratumoral localization of 111 In-labeled POZ derivatives was investigated by an autoradiographic study. Furthermore, a therapeutic study using 90 Y-labeled Isp-PrPOZ was performed, and tumor growth and survival rate were evaluated. Results: The Tts of EtPOZ, IspPOZ, Isp-PrPOZ, and PrPOZ (∼20 kDa) were greater than 70°C, 34°C, 25°C, and 19°C, respectively. In the intratumoral injection study, Isp-PrPOZ and PrPOZ (2,000 μM) with Tts lower than tumor temperature (33.5°C under anesthesia) showed a significantly higher retention of radioactivity at 1 d after injection (73.6% and 73.9%, respectively) than EtPOZ (5.6%) and IspPOZ (15.8%). Even at low injected dose (100 μM), Isp-PrPOZ exhibited high retention (68.3% at 1 d). The high level of radioactivity of Isp-PrPOZ was retained in the tumor 7 d after injection (69.5%). The autoradiographic study demonstrated that the radioactivity of 111 In-labeled Isp-PrPOZ and PrPOZ was localized in a small area. In the therapeutic study using 90 Y-labeled Isp-PrPOZ, significant suppression of tumor growth and prolonged survival rate were achieved in an injection dose-dependent manner compared with that observed for the vehicle-injected group and nonradioactive Isp-PrPOZ-injected group. Conclusion: The injectable 90 Y-labeled Isp-PrPOZ was retained for a prolonged period within tumor tissues via self-aggregation and exhibited marked therapeutic effect, suggesting its usefulness for brachytherapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Open-label dose-finding trial of buprenorphine implants (Probuphine) for treatment of heroin dependence.

PubMed

White, Jason; Bell, James; Saunders, John B; Williamson, Paul; Makowska, Maria; Farquharson, Aaron; Beebe, Katherine L

2009-07-01

Buprenorphine, a mu-opioid receptor partial agonist, has been shown to be safe and effective for treatment of opioid dependence. A novel implantable formulation of buprenorphine (Probuphine), using a polymer matrix sustained-release technology, has been developed to offer treatment for opioid dependence while minimizing risks of patient noncompliance and illicit diversion. The goal of the current study was to conduct an initial, open-label, evaluation of the safety, pharmacokinetics, and efficacy of two doses of Probuphine in subjects with opioid dependence maintained on sublingual buprenorphine. Two doses of Probuphine were evaluated in 12 heroin-dependent volunteers switched from daily sublingual buprenorphine dosing to either two or four Probuphine implants based upon their buprenorphine daily maintenance dose of 8 mg or 16 mg respectively, and were monitored for 6 months. Probuphine implants provided continuous steady state delivery of buprenorphine until their removal at 6 months. Withdrawal symptoms and craving remained low throughout the 6 months. For the 12 subjects, an average of 59% of urines were opioid-negative across the 6 month treatment period. Injection site reactions were present in half of patients, but none were serious. No safety concerns were evident. These results suggest that Probuphine implants offer significant promise for enhancing delivery of effective opioid substitution treatment while minimizing risk for abuse of medication.

Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model.

PubMed

Uyama, Koh; Sakiyama, Shoji; Yoshida, Mitsuteru; Kenzaki, Koichiro; Toba, Hiroaki; Kawakami, Yukikiyo; Okumura, Kazumasa; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira

2016-01-01

The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.

In-situ photopolymerized and monitored implants: successful application to an intervertebral disc replacement

NASA Astrophysics Data System (ADS)

Schmocker, Andreas M.; Khoushabi, Azadeh; Bourban, Pierre-Etienne; Schizas, Constantin; Pioletti, Dominique; Moser, Christophe

2016-02-01

Photopolymerization is a common method to harden materials initially in a liquid state. A surgeon can directly trigger the solidification of a dental implant or a bone or tissue filler by using ultra-violet light. Traditionally, photopolymerization has been used mainly in dentistry. Over the last decade advances in material development including a wide range of biocompatible gel- and cement-systems open up a new avenue for in-situ photopolymerization. We designed a miniaturized light probe where a photoactive material can be 1) mixed, pressurized and injected 2) photopolymerized or photoactivated and 3) monitored during the chemical reaction. The device enables surgeries to be conducted through a hole smaller than 500 μm in diameter. Using a combination of Raman and fluorescence spectroscopy, the current state of the photopolymerization was inferred and monitored in real time within an in-vitro tissue model. It was also possible to determine roughly the position of the probe within the tissue cavity by analysing the fluorescence signal. Using the technique hydrogels were successfully implanted into a bovine intervertebral disc model. Mechanical tests could not obstruct the functionality of the implant. Finally, the device was also used for other application such as the implantation of a hydrogel into an aneurysm tissue cavity which will be presented at the conference.

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

PubMed

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

2017-01-01

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

Relative effectiveness of carp pituitary extract, luteinizing hormone releasing hormone analog LHRHa injections and LHRHa implants for producing hybrid catfish fry

USDA-ARS?s Scientific Manuscript database

Adoption of the hybrid catfish (channel catfish, Ictalruus punctatus, female x blue catfish, I. furcatus, male) is increasing in the catfish industry. The most effective way to produce fry is hormone induced spawning of females coupled with hand stripping and in vitro fertilization. The success of...

In vivo demonstration of injectable microstimulators based on charge-balanced rectification of epidermically applied currents

NASA Astrophysics Data System (ADS)

Ivorra, Antoni; Becerra-Fajardo, Laura; Castellví, Quim

2015-12-01

Objective. It is possible to develop implantable microstimulators whose actuation principle is based on rectification of high-frequency (HF) current bursts supplied through skin electrodes. This has been demonstrated previously by means of devices consisting of a single diode. However, previous single diode devices caused dc currents which made them impractical for clinical applications. Here flexible thread-like stimulation implants which perform charge balance are demonstrated in vivo. Approach. The implants weigh 40.5 mg and they consist of a 3 cm long tubular silicone body with a diameter of 1 mm, two electrodes at opposite ends, and, within the central section of the body, an electronic circuit made up of a diode, two capacitors, and a resistor. In the present study, each implant was percutaneously introduced through a 14 G catheter into either the gastrocnemius muscle or the cranial tibial muscle of a rabbit hindlimb. Then stimulation was performed by delivering HF bursts (amplitude <60 V, frequency 1 MHz, burst repetition frequency from 10 Hz to 200 Hz, duration = 200 μs) through a pair of textile electrodes strapped around the hindlimb and either isometric plantarflexion or dorsiflexion forces were recorded. Stimulation was also assayed 1, 2 and 4 weeks after implantation. Main results. The implants produced bursts of rectified current whose mean value was of a few mA and were capable of causing local neuromuscular stimulation. The implants were well-tolerated during the 4 weeks. Significance. Existing power supply methods, and, in particular inductive links, comprise stiff and bulky parts. This hinders the development of minimally invasive implantable devices for neuroprostheses based on electrical stimulation. The proposed methodology is intended to relieving such bottleneck. In terms of mass, thinness, and flexibility, the demonstrated implants appear to be unprecedented among the intramuscular stimulation implants ever assayed in vertebrates.

Origins of endothelial and osteogenic cells in the subcutaneous collagen gel implant.

PubMed

Bilic-Curcic, I; Kalajzic, Z; Wang, L; Rowe, D W

2005-11-01

The interdependent relationship between vascular endothelial cells and osteoblasts during bone formation and fracture healing has been long appreciated. This paper reports a heterotopic implant model using FGF-2-expanded bone marrow stromal cells (BMSC) derived from Tie2eGFP (endothelial marker) and pOBCol3.6GFPcyan or topaz (early osteoblast marker) transgenic mice to appreciate the host/donor relationships of cells participating in the process of heterotopic bone formation. The study included various combinations of Tie2eGFP and pOBCol3.6GFPcyan and topaz transgenics as BMSC or whole bone marrow (WBM) donors and also as recipients. Rat tail collagen was used as a carrier of donor cells and implantation was done in lethally irradiated mice rescued with WBM injection. Development of ossicles in the implants was followed weekly during the 4- to 5-week long post-implantation period. By 4-5 weeks after total body irradiation (TBI) and implantation, a well-formed bone spicule had developed that was invested with bone marrow. Experiments showed absolute dominance of donor-derived cells in the formation of endothelial-lined vessels inside the implants as well as the marrow stromal-derived osteogenic cells. Host-derived fibroblasts and osteogenic cells were confined to the fibrous capsule surrounding the implant. In addition, cells lining the endosteal surface of newly formed marrow space carrying a pOBCol3.6GFP marker were observed that were contributed by WBM donor cells and the host. Thus, FGF-2-expanded BMSC appear to be a source of endothelial and osteogenic progenitor cells capable of eliciting heterotopic bone formation independent of cells from the host. This model should be useful for understanding the interactions between these two cell types that control osteogenic differentiation in vivo.

Side effects of corticosteroid injections: what's new?

PubMed

Berthelot, Jean-Marie; Le Goff, Benoît; Maugars, Yves

2013-07-01

The risk of sepsis with a hip or knee implant does not seem to be increased by prior joint injections, as long as the injection and surgery are separated by at least two months. Calcifications have been reported after intradiscal injection in the coccygeal region for coccydynia. Complete rest for 24 hours after injection of triamcinolone hexacetonide into the knee had no effect on systemic diffusion of the product. Patients infected by HIV who are treated with ritonavir are at much greater risk for Cushing syndrome after epidural injection. Problems with menstruation after corticosteroid injection seem to be related to a transient decrease in estradiol levels, without alterations in FSH and LH levels. The risk of central serous chorioretinopathy and acute necrosis of the retina after injection is not known, even by ophthalmologists. Transient dysphonia occurs in 12% of patients receiving corticosteroid injections. The impressive Tachon's syndrome seems to be the venous counterpart to Nicolau's syndrome for arteries. Injections into C1-C2 should be abandoned because of the neurological risks. Since serious neurological events after foraminal injections could be the result of an overly fast injection into the arterialized radicular veins rather than in the arteries, only slow injections with products having a low risk of embolism or vascular complications should be allowed. Dexamethasone-based preparations seem to contain no particles or crystals, and have not induced any neurological accidents in various animal models, even after direct administration into vertebral or carotid arteries. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Plasmin-Cleaved β-2-Glycoprotein 1 Is an Inhibitor of Angiogenesis

PubMed Central

Sakai, Taro; Balasubramanian, Krishnakumar; Maiti, Sourindra; Halder, Jyotsna B.; Schroit, Alan J.

2007-01-01

β-2-Glycoprotein 1, an abundant plasma glycoprotein, binds anionic cell surfaces and functions as a regulator of thrombosis. Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis. In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells. The protein was without effect on preformed endothelial cell tubes. In vivo, the cleaved protein inhibited neovascularization into subcutaneously implanted Matrigel and Gelfoam sponge implants and the growth of orthotopically injected tumors. Collectively, these data indicate that plasmin-cleaved β-2-glycoprotein 1 is a potent antiangiogenic and antitumor molecule of potential therapeutic significance. PMID:17872974

Nondestructive evaluation of orthopaedic implant stability in THA using highly nonlinear solitary waves

NASA Astrophysics Data System (ADS)

Yang, Jinkyu; Silvestro, Claudio; Sangiorgio, Sophia N.; Borkowski, Sean L.; Ebramzadeh, Edward; De Nardo, Luigi; Daraio, Chiara

2012-01-01

We propose a new biomedical sensing technique based on highly nonlinear solitary waves to assess orthopaedic implant stability in a nondestructive and efficient manner. We assemble a granular crystal actuator consisting of a one-dimensional tightly packed array of spherical particles, to generate acoustic solitary waves. Via direct contact with the specimen, we inject acoustic solitary waves into a biomedical prosthesis, and we nondestructively evaluate the mechanical integrity of the bone-prosthesis interface, studying the properties of the waves reflected from the contact zone between the granular crystal and the implant. The granular crystal contains a piezoelectric sensor to measure the travelling solitary waves, which allows it to function also as a sensor. We perform a feasibility study using total hip arthroplasty (THA) samples made of metallic stems implanted in artificial composite femurs using polymethylmethacrylate for fixation. We first evaluate the sensitivity of the proposed granular crystal sensor to various levels of prosthesis insertion into the composite femur. Then, we impose a sequence of harsh mechanical loading on the THA samples to degrade the mechanical integrity at the stem-cement interfaces, using a femoral load simulator that simulates aggressive, accelerated physiological loading. We investigate the implant stability via the granular crystal sensor-actuator during testing. Preliminary results suggest that the reflected waves respond sensitively to the degree of implant fixation. In particular, the granular crystal sensor-actuator successfully detects implant loosening at the stem-cement interface following violent cyclic loading. This study suggests that the granular crystal sensor and actuator has the potential to detect metal-cement defects in a nondestructive manner for orthopaedic applications.

Development and Assessment of a 3D-Printed Scaffold with rhBMP-2 for an Implant Surgical Guide Stent and Bone Graft Material: A Pilot Animal Study.

PubMed

Bae, Ji Cheol; Lee, Jin-Ju; Shim, Jin-Hyung; Park, Keun-Ho; Lee, Jeong-Seok; Bae, Eun-Bin; Choi, Jae-Won; Huh, Jung-Bo

2017-12-16

In this study, a new concept of a 3D-printed scaffold was introduced for the accurate placement of an implant and the application of a recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded bone graft. This preliminary study was conducted using two adult beagles to evaluate the 3D-printed polycaprolactone (PCL)/ β -tricalcium phosphate ( β -TCP)/bone decellularized extracellular matrix (bdECM) scaffold conjugated with rhBMP-2 for the simultaneous use as an implant surgical guide stent and bone graft material that promotes new bone growth. Teeth were extracted from the mandible of the beagle model and scanned by computed tomography (CT) to fabricate a customized scaffold that would fit the bone defect. After positioning the implant guide scaffold, the implant was placed and rhBMP-2 was injected into the scaffold of the experimental group. The two beagles were sacrificed after three months. The specimen block was obtained and scanned by micro-CT. Histological analysis showed that the control and experimental groups had similar new bone volume (NBV, %) but the experimental group with BMP exhibited a significantly higher bone-to-implant contact ratio (BIC, %). Within the limitations of this preliminary study, a 3D-printed scaffold conjugated with rhBMP-2 can be used simultaneously as an implant surgical guide and a bone graft in a large bone defect site. Further large-scale studies will be needed to confirm these results.

Injectable Self-Healing Hydrogel with Antimicrobial and Antifouling Properties.

PubMed

Li, Lin; Yan, Bin; Yang, Jingqi; Huang, Weijuan; Chen, Lingyun; Zeng, Hongbo

2017-03-22

Microbial adhesion, biofilm formation and associated microbial infection are common challenges faced by implanted biomaterials (e.g., hydrogels) in bioengineering applications. In this work, an injectable self-healing hydrogel with antimicrobial and antifouling properties was prepared through self-assembly of an ABA triblock copolymer employing catechol functionalized polyethylene glycol (PEG) as A block and poly{[2-(methacryloyloxy)-ethyl] trimethylammonium iodide}(PMETA) as B block. This hydrogel exhibits excellent thermosensitivity, and can effectively inhibit the growth of E. coli (>99.8% killing efficiency) and prevent cell attachment. It can also heal autonomously from repeated damage, through mussel-inspired catechol-mediated hydrogen bonding and aromatic interactions, exhibiting great potential in bioengineering applications.

An injectable particle-hydrogel hybrid system for glucose-regulatory insulin delivery.

PubMed

Zhao, Fuli; Wu, Di; Yao, Dan; Guo, Ruiwei; Wang, Weiwei; Dong, Anjie; Kong, Deling; Zhang, Jianhua

2017-12-01

Long-term and daily subcutaneous injections of insulin for the treatment of insulin-dependent diabetic patients often lead to poor patient compliance and undesired complications. Phenylboronic acid (PBA)-based polymeric hydrogels have been widely considered as one of the most promising insulin delivery system to replace the frequent insulin injections. However, their applications are limited by clinically irrelevant glucose-responsive range, slow response rate, low tissue-adhesiveness and poor biodegradability, undesirable leakage at normoglycemic state. Herein, we report a novel implantable insulin hydrogel for glucose-regulated delivery of insulin based on a unique particle-hydrogel hybrid platform featuring fast glucose responsiveness at physiological pH, shear-thinning behavior for injection, tissue-adhesive function for long-lasting adherence, and full biodegradability for safe use. The system was thoroughly characterized both in vitro and in vivo and was demonstrated to hold these unique functions. Using streptozotocin-induced diabetic mice as a model, it was shown that a single subcutaneous injection of the insulin-loaded particle-hydrogel formulation led to quasi-steady-state blood glucose levels within the normal range for about two weeks. In addition, the preparation of the formulation only involved simple mixing and self-assembling processes, and thus it had great scalability and reproducibility for practical use. The highly feasible preparation, excellent performance, inherent biocompatibility and biodegradability make this novel composite hydrogel promising platform for diabetes therapy. Phenylboronic acid (PBA)-based polymeric hydrogels have been widely considered as one of the most promising insulin delivery system to replace the frequent insulin injections. However, these hydrogels, mostly based on a variety of PBA-containing acrylamide monomers, are still far from clinical reality. Building upon a unique particle-hydrogel hybrid platform, herein we report a novel implantable insulin storage and delivery system with multifunctionalities including fast glucose-sensitiveness at physiological pH, shear-thinning behavior for injection, tissue-adhesive function for long-lasting adherence, biodegradable materials for safe use and well-controlled insulin release. These unique functions were demonstrated through research both in vitro and in vivo. In addition, the preparation of the formulation was simple, and thus it had great scalability and reproducibility for practical use. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Sustained viral gene delivery from a micro-fibrous, elastomeric cardiac patch to the ischemic rat heart.

PubMed

Gu, Xinzhu; Matsumura, Yasumoto; Tang, Ying; Roy, Souvik; Hoff, Richard; Wang, Bing; Wagner, William R

2017-07-01

Biodegradable and elastomeric patches have been applied to the surface of infarcted hearts as temporary mechanical supports to effectively alter adverse left ventricular remodeling processes. In this report, recombinant adeno-associated virus (AAV), known for its persistent transgene expression and low pathogenicity, was incorporated into elastomeric polyester urethane urea (PEUU) and polyester ether urethane urea (PEEUU) and processed by electrospinning into two formats (solid fibers and core-sheath fibers) designed to influence the controlled release behavior. The extended release of AAV encoding green fluorescent protein (GFP) was assessed in vitro. Sustained and localized viral particle delivery was achieved over 2 months in vitro. The biodegradable cardiac patches with or without AAV-GFP were implanted over rat left ventricular lesions three days following myocardial infarction to evaluate the transduction effect of released viral vectors. AAV particles were directly injected into the infarcted hearts as a control. Cardiac function and remodeling were significantly improved for 12 weeks after patch implantation compared to AAV injection. More GFP genes was expressed in the AAV patch group than AAV injection group, with both α-SMA positive cells and cardiac troponin T positive cells transduced in the patch group. Overall, the extended release behavior, prolonged transgene expression, and elastomeric mechanical properties make the AAV-loaded scaffold an attractive option for cardiac tissue engineering where both gene delivery and appropriate mechanical support are desired. Copyright © 2017. Published by Elsevier Ltd.

Botulinum toxin therapy for limb dystonias.

PubMed

Yoshimura, D M; Aminoff, M J; Olney, R K

1992-03-01

We investigated the effectiveness of botulinum toxin in 17 patients with limb dystonias (10 with occupational cramps, three with idiopathic dystonia unrelated to activity, and two each with post-stroke and parkinsonian dystonia) in a placebo-controlled, blinded study. We identified affected muscles clinically and by recording the EMG from implanted wire electrodes at rest and during performance of tasks that precipitated abnormal postures. There were three injections given with graded doses of toxin (average doses, 5 to 10, 10 to 20, and 20 to 40 units per muscle) and one with placebo, in random order. Subjective improvement occurred after 53% of injections of botulinum toxin, and this was substantial in 24%. Only one patient (7%) improved after placebo injection. Subjective improvement occurred in 82% of patients with at least one dose of toxin, lasting for 1 to 4 months. Response rates were similar between clinical groups. Objective evaluation failed to demonstrate significant improvement following treatment with toxin compared with placebo. The major side effect was transient focal weakness after 53% of injections of toxin.

Effect of inhibitors of prostaglandin synthesis on gonadotropin release in the rat.

PubMed

Ojeda, S R; Harms, P G; McCann, S M

1975-10-01

To study the effect of blockade of prostaglandin (PG) synthesis on gonadotropin release in the rat, inhibitors of PG synthesis were injected by various routes in various experimental conditions. The injection of 5-, 8-, 11-, 14-eicosatetraynoic acid (TYA) into the third ventricle (3rd V) significantly decreased plasma LH of ovariectomized (OVX) rats 1, 2, and 4 h following its injection; however, TYA failed to alter plasma LH in OVX rats when administered as a single sc injection and also failed to prevent the post-castration rise in plasma LH when administered sc once daily for 4 days to short-term OVX rats. None of these treatments altered plasma FSH concentrations. Indomethacin (Id) injected into the 3rd V or implanted into the medial basal hypothalamus (MBH) of OVX rats depressed plasma LH 1--6 h later. This effect was no longer observed 24--72 h following its implantation in the MBH. When different doses of Id were administered as single sc injections to OVX rats, plasma LH titers were depressed 24--32 h later, whereas plasma FSH remained either unaltered or was slightly increased. Similarly, the post-castration rise of plasma LH but not that of FSH in male rats was suppressed by a single sc injection of Id given 6 h before orchidectomy. Id administered acutely iv failed to modify the pulsatile release of LH in OVX rats, but it effectively inhibited this release when injected sc 20--30 h before the initiation of blood collection. Moreover, Id blocked the progesterone-induced LH and FSH release in OVX estrogen-primed rats when given sc 24 h before progesterone, but not when it was injected either sc or iv shortly (2 h) before or shortly after (1--3 h) progesterone treatment. Rats treated with Id showed a decrease in BW 24--32 h afters its sc injection. However, the effects of Id on LH release could not be explained by lack of food intake since fasted controls showed LH titers similar to fed rats. Id did not significantly inhibit the LH release in response to synthetic LH-releasing hormone (LHRH) in OVX rats, but partially blocked the response in OVX estrogen, progesterone-treated (OEP) rats. Surprisingly, in OEP rats, Id appeared to potentiate the FSH release in response to LHRH. The results of this study indicate that inhibitors of PG synthesis administered at high doses can inhibit LH release in the rat and that this effect is mainly due to a direct effect of the drug or drugs on the central nervous systen. Consequently, the results of this study give further support to the hypothesis that PGs play a physiological role in the control of gonadotropin secretion.

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

PubMed

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

2017-03-01

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

Fructose Synthesis and Transport at the Uterine-Placental Interface of Pigs: Cell-Specific Localization of SLC2A5, SLC2A8, and Components of the Polyol Pathway.

PubMed

Steinhauser, Chelsie B; Landers, McKinsey; Myatt, Louise; Burghardt, Robert C; Vallet, Jeffrey L; Bazer, Fuller W; Johnson, Greg A

2016-11-01

The fetal fluids and uterine flushings of pigs contain higher concentrations of fructose than glucose, but fructose is not detected in maternal blood. Fructose can be synthesized from glucose via enzymes of the polyol pathway, aldose reductase (AKR1B1) and sorbitol dehydrogenase (SORD), transported across cell membranes by solute carriers SLC2A5 and SLC2A8, and converted to fructose-1-phosphate by ketohexokinase (KHK). SLC2A8, SLC2A5, AKR1B1, SORD, and KHK mRNAs and proteins were analyzed using quantitative PCR and immunohistochemistry or in situ hybridization in endometria and placentae of cyclic and pregnant gilts, cyclic gilts injected with estrogen, and ovariectomized gilts injected with progesterone. Progesterone up-regulated SLC2A8 protein in uterine luminal (LE) and glandular epithelia during the peri-implantation period, and expression became exclusively placental, chorion and blood vessels, after Day 30. P4 up-regulated SLC2A5 mRNA in uterine LE and glandular epithelia after implantation, and the chorion expressed SLC2A5 between Days 30 and 85. AKR1B1 and SORD proteins localized to uterine LE during the peri-implantation period, but expression switched to chorion by Day 20 and was maintained through Day 85. Uterine expression of AKR1B1 mRNA was down-regulated by estrogen. KHK protein localized to trophectoderm/chorion throughout gestation. These results provide evidence that components for the conversion of glucose to fructose and for fructose transport are present at the uterine-placental interface of pigs. The shift in expression from LE to chorion during pregnancy suggests free-floating conceptuses are supported by fructose synthesized by the uterus, but after implantation, the chorion becomes self-sufficient for fructose synthesis and transport. © 2016 by the Society for the Study of Reproduction, Inc.

Transapical aortic valve implantation without angiography: proof of concept.

PubMed

Ferrari, Enrico; Sulzer, Christopher; Marcucci, Carlo; Rizzo, Elena; Tozzi, Piergiorgio; von Segesser, Ludwig K

2010-06-01

Cardiac computed tomographic scans, coronary angiograms, and aortographies are routinely performed in transcatheter heart valve therapies. Consequently, all patients are exposed to multiple contrast injections with a following risk of nephrotoxicity and postoperative renal failure. The transapical aortic valve implantation without angiography can prevent contrast-related complications. Between November 2008 and November 2009, 30 consecutive high-risk patients (16 female, 53.3%) underwent transapical aortic valve implantation without angiography. The landmarks identification, the stent-valve positioning, and the postoperative control were routinely performed under transesophageal echocardiogram and fluoroscopic visualization without contrast injections. Mean age was 80.1 +/- 8.7 years. Mean valve gradient, aortic orifice area, and ejection fraction were 60.3 +/- 20.9 mm Hg, 0.7 +/- 0.16 cm(2), and 0.526 +/- 0.128, respectively. Risk factors were pulmonary hypertension (60%), peripheral vascular disease (70%), chronic pulmonary disease (50%), previous cardiac surgery (13.3%), and chronic renal insufficiency (40%) (mean blood creatinine and urea levels: 96.8 +/- 54 microg/dL and 8.45 +/- 5.15 mmol/L). Average European System for Cardiac Operative Risk Evaluation was 32.2 +/- 13.3%. Valve deployment in the ideal landing zone was 96.7% successful and valve embolization occurred once. Thirty-day mortality was 10% (3 patients). Causes of death were the following: intraoperative ventricular rupture (conversion to sternotomy), right ventricular failure, and bilateral pneumonia. Stroke occurred in one patient at postoperative day 9. Renal failure (postoperative mean blood creatinine and urea levels: 91.1 +/- 66.8 microg/dL and 7.27 +/- 3.45 mmol/L), myocardial infarction, and atrioventricular block were not detected. Transapical aortic valve implantation without angiography requires a short learning curve and can be performed routinely by experienced teams. Our report confirms that this procedure is feasible and safe, and provides good results with low incidence of postoperative renal disorders. 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

Jung, Kyoung In; Park, Chan Kee

2016-01-01

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

Longitudinal Study of Sustained-Release Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema.

PubMed

Aknin, Isabelle; Melki, Laurent

2016-01-01

Observational studies are needed to confirm the long-term efficacy and safety of Ozurdex® intravitreal implant in real life. Among 29 patients with persistent diabetic macular edema (DME), of whom 14 (48%) patients did not have any previous treatments and 22 (76%) any previous antivascular endothelial growth factor (anti-VEGF) injections, significant visual acuity (VA) improvement was observed with a mean gain of 13.8 letters at month 6 (p < 0.0001), 12.7 letters at month 12 (p = 0.0032) and 16.5 letters at month 18 (p = 0.0313). During the follow-up, a total of 17 (59%) patients had a VA improvement of ≥15 letters. Significant central macular thickness decrease was observed with a mean reduction of 159.07 μm at month 6 (p < 0.0001), 181.8 μm at month 12 (p < 0.0001) and 236.17 μm at month 18 (p = 0.0313). No serious adverse events were reported. With a good efficacy and safety, manageable adverse events and an injection rate much lower compared to that of anti-VEGF, this study confirms the use of Ozurdex® for the treatment of persistent DME. © 2016 S. Karger AG, Basel.

Intra-articular Implantation of Mesenchymal Stem Cells, Part 1

PubMed Central

Kraeutler, Matthew J.; Mitchell, Justin J.; Chahla, Jorge; McCarty, Eric C.; Pascual-Garrido, Cecilia

2017-01-01

Osteoarthritis (OA) after a partial or total meniscectomy procedure is a common pathology. Because of the high incidence of meniscectomy in the general population, as well as the significant burden of knee OA, there is increasing interest in determining methods for delaying postmeniscectomy OA. Biological therapies, including mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), have been proposed as possible therapies that could delay OA in this and other settings. Several studies in various animal models have evaluated the effect of injecting MSCs into the knee joints of animals with OA induced either by meniscal excision with or without anterior cruciate ligament transection. When compared with control groups receiving injections without progenitor cells, short-term benefits in the experimental groups have been reported. In human subjects, there are limited data to determine the effect of biological therapies for use in delaying or preventing the onset of OA after a meniscectomy procedure. The purpose of this review is to highlight the findings in the presently available literature on the use of intra-articular implantation of MSCs postmeniscectomy and to offer suggestions for future research with the goal of delaying or treating early OA postmeniscectomy with MSCs. PMID:28203597

A re-assessment of the effects of intracortical delivery of inosine on transmidline growth of corticospinal tract axons after unilateral lesions of the medullary pyramid

PubMed Central

Steward, Oswald; Sharp, Kelli; Yee, Kelly Matsudaira

2011-01-01

This study was undertaken as part of the NIH “Facilities of Research Excellence-Spinal Cord Injury”, which supports independent replication of published studies. Here, we repeat an experiment reporting that intracortical delivery of inosine promoted trans-midline growth of corticospinal tract (CST) axons in the spinal cord after unilateral injury to the medullary pyramid. Rats received unilateral transections of the medullary pyramid and 1 day later, a cannula assembly was implanted into the sensorimotor cortex contralateral to the pyramidotomy to deliver either inosine or vehicle. The cannula assembly was attached to an osmotic minipump that was implanted sub-cutaneously. Seventeen or 18 days post-injury, the CST was traced by making multiple injections of miniruby-BDA into the sensorimotor cortex. Rats were killed for tract tracing 14 days after the BDA injections. Sections through the cervical spinal cord were stained for BDA and immunostained for GAP43 and GFAP. Our results revealed no evidence for enhanced growth of CST axons across the midline of the dorsal column in rats that received intracortical infusion of inosine. Possible reasons for the failure to replicate are discussed. PMID:21946267

In vitro and in vivo acute response towards injectable thermosensitive chitosan/TEMPO-oxidized cellulose nanofiber hydrogel.

PubMed

Nguyen, Trang Ho Minh; Abueva, Celine; Ho, Hai Van; Lee, Sun-Young; Lee, Byong-Taek

2018-01-15

TEMPO-oxidized cellulose nanofiber (TOCNF) is a natural material with many promising properties, including biocompatibility and degradability. In this study, we integrated TOCNF at different concentrations (0.2, 0.4, 0.6, 0.8% w/v) with chitosan (CS) and created a thermosensitive injectable hydrogel intended for biomedical applications. These hydrogels can undergo sol-gel transition at body temperature through interactions between chitosan and β-glycerophosphate. The addition of TOCNF resulted in faster gelation time and increased porosity. These hydrogels with TOCNF showed improved biocompatibility both in vitro and in vivo compared to CS hydrogel. Both MC3T3-E1 pre-osteoblast cells and L929 fibroblast cells showed biocompatibility towards CS/TOCNF 0.4. After 7days of implantation, initial inflammatory response to CS/TOCNF 0.4 was found. Such response was significantly subsided within 14days. Cell infiltration within the hydrogel was also prominent, showing anti-inflammatory or wound healing (M2) macrophage at 14days after implantation. These results showed that the addition of TOCNF could significantly improve the biocompatibility of CS hydrogel as a biomaterial for biomedical application. Copyright © 2017 Elsevier Ltd. All rights reserved.

Management of vocal fold scar with autologous fat implantation: perceptual results.

PubMed

Neuenschwander, M C; Sataloff, R T; Abaza, M M; Hawkshaw, M J; Reiter, D; Spiegel, J R

2001-06-01

Vocal fold scar disrupts the mucosal wave and interferes with glottic closure. Treatment involves a multidisciplinary approach that includes voice therapy, medical management, and sometimes surgery. We reviewed the records of the first eight patients who underwent autologous fat implantation for vocal fold scar. Information on the etiology of scar, physical findings, and prior interventions were collected. Videotapes of videostroboscopic findings and perceptual voice ratings [Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS)] were randomized and analyzed independently by four blinded observers. Etiology of scar included mass excision (7), vocal fold stripping (3), congenital sulcus (2), and hemorrhage (1). Prior surgical procedures performed included thyroplasty (1), autologous fat injection (9), excision of scar (2), and lysis of adhesions (2). Strobovideolaryngoscopy: Statistically significant improvement was found in glottic closure, mucosal wave, and stiffness (P = 0.05). Perceptual ratings (GRBAS): Statistically significant improvement was found in all five parameters, including overall Grade, Roughness, Breathiness, Asthenia, and Strain (P = 0.05). Patients appear to have improved vocal fold function and quality of voice after autologous fat implantation in the vocal fold. Autologous fat implantation is an important adjunctive procedure in the management of vocal fold scar, and a useful addition to the armamentarium of the experienced phonomicrosurgeon.

Limited importance of pre-embryo pronuclear morphology (zygote score) in assisted reproduction outcome in the absence of embryo cryopreservation.

PubMed

Nicoli, Alessia; Valli, Barbara; Di Girolamo, Roberta; Di Tommaso, Barbara; Gallinelli, Andrea; La Sala, Giovanni B

2007-10-01

To investigate the hypothesis that Z-score criteria represent a reliable predictor of implantation rate and pregnancy outcome in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles, excluding the possibility of embryo selection before the embryo transfer. Retrospective clinical study. Centre of Reproductive Medicine, Department of Obstetrics and Gynecology, Arcispedale S. Maria Nuova (ASMN), Reggio Emilia, Italy. We analyzed 393 pregnancies obtained by IVF or ICSI cycles. Morphologic evaluations of Z-score in pre-embryos obtained from IVF or ICSI cycles. Evaluations of Z-scores, implantation rate, and clinical pregnancy outcome. We did not find any statistically significant correlation between the Z-score of 1032 embryos transferred in 393 embryo transfers and the implantation rate or the pregnancy outcome. In particular, the best Z-score identified (Z1, 7.2%) did not seem to correlate with embryo implantation rate or pregnancy outcomes any better than those with worse scores (Z2, 6.9% and Z3, 85.9%). Our results seem to confirm that Z-score alone cannot be considered a better tool than standard morphologic criteria for identifying, controlling, or selecting embryos with a better chance of successful ongoing pregnancy.

Protective effect of vitamin E in an animal model of LPS-induced inflammation.

PubMed

Mayorga, M; Iborra, A; Estany, S; Martínez, P

2004-12-01

Many sterility outcomes may be associated to the presence of an inflammatory response that would lead to an inability of the endometrium to support implantation and maintain viable embryos. We have established an animal model of inflammation in which the systemic administration of lipopolysaccharyde (LPS) results in a low embryo implantation rate. The purpose of this work was to investigate the effect of the inflammatory agent LPS on embryo viability and to verify the ability of vitamin E to modulate the inflammatory effect of LPS on embryo viability. For pre-implantation studies B6CBAF1 mice, which were intraperitoneally inoculated with LPS (4-10 mg/kg), were used. Mice were also treated with vitamin E (4-10 mg/kg) before or after LPS injection. Embryos were obtained from the oviduct after each treatment. The LPS produces a decrease in the number of pre-implantational embryos in a concentration dependent manner. The LPS effect can be partially reversed or prevented by vitamin E. Preliminary results show that inflammatory cytokines are secreted by intraperitoneal macrophages in LPS treated mice. Our results demonstrate the ability of vitamin E to avoid an inflammatory environment and to allow viability of embryos. (c) Blackwell Munksgaard, 2004

Effects of Local and Systemic Zoledronic Acid Application on Titanium Implant Osseointegration: An Experimental Study Conducted on Two Surface Types.

PubMed

Dundar, Serkan; Yaman, Ferhan; Gecor, Orhan; Cakmak, Omer; Kirtay, Mustafa; Yildirim, Tuba Talo; Karaman, Tahir; Benlidayi, Mehmet Emre

2017-06-01

The aim of this study was to evaluate the effects of local and systemic zoledronic acid (ZA) applications on titaniumoksit ceramic blasted (TiO-CB)- and sandblasted large acid-grit (SLA)-surfaced titanium implant osseointegration. Twelve New Zealand White rabbits were used in the study, divided into 6 groups: the TiO-CB (TiO-CB-CNT) (n = 2) and SLA (SLA-CNT) (n = 2) control groups in which TiO-CB- and SLA-surfaced titanium implants were surgically inserted into rabbit tibias but no treatment was applied; the TiO-CB (TiO-CB-LZA) (n = 2) and SLA (SLA-LZA) (n = 2) local ZA groups in which 1 mL of normal saline solution containing 2 mg of ZA was injected into sockets and after this the implants were integrated; and the TiO-CB (TiO-CB-SZA) (n = 2) and SLA (SLA-SZA) (n = 2) systemic ZA groups in which a single infusion of 0.1 mg/kg of ZA was administered during surgical implant insertion. Following a period of osseointegration, bone implant contact (BIC) was recorded as a proportion of the total implant surface length in direct contact with the bone. Results of this study indicate that BIC was greater in the systemic ZA application groups than in the local ZA application groups, and BIC was greater in the local ZA groups than in the controls. Statistically significant differences in BIC were not detected between the TiO-CB- and SLA-surfaced implants in all the groups. Furthermore, this study did not reveal significant differences between the 2 types of surfaces due to similar average roughness values. Overall, systemic ZA application was found to be more effective in increasing BIC than local ZA application based on the results obtained by testing 2 implant surfaces.

Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

NASA Technical Reports Server (NTRS)

Vandenburgh, H.; Del Tatto, M.; Shansky, J.; Goldstein, L.; Russell, K.; Genes, N.; Chromiak, J.; Yamada, S.

1998-01-01

Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( < 0.02). This atrophy was significantly attenuated 41 to 55% (p < 0.02) in animals that received C2-BAM implants, but not in animals receiving daily injections of purified rhGH (1 mg/kg/day). These data support the concept that delivery of rhGH from BAMs may be efficacious in treating muscle-wasting disorders.

Percutaneous window chamber method for chronic intravital microscopy of sensor-tissue interactions.

PubMed

Koschwanez, Heidi E; Klitzman, Bruce; Reichert, W Monty

2008-11-01

A dorsal, two-sided skin-fold window chamber model was employed previously by Gough in glucose sensor research to characterize poorly understood physiological factors affecting sensor performance. We have extended this work by developing a percutaneous one-sided window chamber model for the rodent dorsum that offers both a larger subcutaneous area and a less restrictive tissue space than previous animal models. A surgical procedure for implanting a sensor into the subcutis beneath an acrylic window (15 mm diameter) is presented. Methods to quantify changes in the microvascular network and red blood cell perfusion around the sensors using noninvasive intravital microscopy and laser Doppler flowmetry are described. The feasibility of combining interstitial glucose monitoring from an implanted sensor with intravital fluorescence microscopy was explored using a bolus injection of fluorescein and dextrose to observe real-time mass transport of a small molecule at the sensor-tissue interface. The percutaneous window chamber provides an excellent model for assessing the influence of different sensor modifications, such as surface morphologies, on neovascularization using real-time monitoring of the microvascular network and tissue perfusion. However, the tissue response to an implanted sensor was variable, and some sensors migrated entirely out of the field of view and could not be observed adequately. A percutaneous optical window provides direct, real-time images of the development and dynamics of microvascular networks, microvessel patency, and fibrotic encapsulation at the tissue-sensor interface. Additionally, observing microvessels following combined bolus injections of a fluorescent dye and glucose in the local sensor environment demonstrated a valuable technique to visualize mass transport at the sensor surface.

Multimodal microscopy of immune cells and melanoma for longitudinal studies

NASA Astrophysics Data System (ADS)

Entenberg, David; Aranda, Iana; Li, Yongbiao; Toledo-Crow, Ricardo; Schaer, David; Li, Yanyun

2006-02-01

Intravital microscopy of cancer is a well established tool that provides direct visualization of the tumor cycle. It traditionally involves one of several strategies: invasive subcutaneous (SC) implantation of tumors followed by surgical opening of skin flaps for imaging, techniques utilizing skin fold chambers and implanted optical windows or intradermal injections under 200μm from the skin surface. All of these techniques allow the use of fluorescent proteins as markers for biologically significant constituents. However, observation methods utilizing skin-flaps, skin-fold chambers and optical windows are invasive and tend to alter the immune environment of the tissue and/or limit the duration of studies that can be performed. If implanted correctly, intradermally injected tumors can be minimally invasive, will not require biopsies or surgical intervention to observe and are accessible for direct transdermal imaging with a number of in vivo modalities. We present our work in the development of a small animal intravital microscopy workstation that allows the acquisition of different contrast imaging modalities: reflectance confocal, wide field epifluorescence, multiphoton and second harmonic generation (SHG). The images are acquired pair-wise simultaneously and sequentially in time. The aim of our instrumentation is to gather all information generated by the single probing beam via the reflected or back-scattered signal, SHG signal and various fluorescence signals. Additionally, we also present our development of a microscopic tissue navigation technique to mark, label and track sites of interest. This technique enables us to revisit sites periodically and record, with different imaging contrasts, their biological changes over time.

Combined micro computed tomography and histology study of bone augmentation and distraction osteogenesis

NASA Astrophysics Data System (ADS)

Ilgenstein, Bernd; Deyhle, Hans; Jaquiery, Claude; Kunz, Christoph; Stalder, Anja; Stübinger, Stefan; Jundt, Gernot; Beckmann, Felix; Müller, Bert; Hieber, Simone E.

2012-10-01

Bone augmentation is a vital part of surgical interventions of the oral and maxillofacial area including dental implantology. Prior to implant placement, sufficient bone volume is needed to reduce the risk of peri-implantitis. While augmentation using harvested autologous bone is still considered as gold standard, many surgeons prefer bone substitutes to reduce operation time and to avoid donor site morbidity. To assess the osteogenic efficacy of commercially available augmentation materials we analyzed drill cores extracted before implant insertion. In younger patients, distraction osteogenesis is successfully applied to correct craniofacial deformities through targeted bone formation. To study the influence of mesenchymal stem cells on bone regeneration during distraction osteogenesis, human mesenchymal stem cells were injected into the distraction gap of nude rat mandibles immediately after osteotomy. The distraction was performed over eleven days to reach a distraction gap of 6 mm. Both the rat mandibles and the drill cores were scanned using synchrotron radiation-based micro computed tomography. The three-dimensional data were manually registered and compared with corresponding two-dimensional histological sections to assess bone regeneration and its morphology. The analysis of the rat mandibles indicates that bone formation is enhanced by mesenchymal stem cells injected before distraction. The bone substitutes yielded a wide range of bone volume and degree of resorption. The volume fraction of the newly formed bone was determined to 34.4% in the computed tomography dataset for the augmentation material Geistlich Bio-Oss®. The combination of computed tomography and histology allowed a complementary assessment for both bone augmentation and distraction osteogenesis.

Enzymatically cross-linked injectable alginate-g-pyrrole hydrogels for neovascularization.

PubMed

Devolder, Ross; Antoniadou, Eleni; Kong, Hyunjoon

2013-11-28

Microparticles capable of releasing protein drugs are often incorporated into injectable hydrogels to minimize their displacement at an implantation site, reduce initial drug burst, and further control drug release rates over a broader range. However, there is still a need to develop methods for releasing drug molecules over extended periods of time, in order to sustain the bioactivity of drug molecules at an implantation site. In this study, we hypothesized that a hydrogel formed through the cross-linking of pyrrole units linked to a hydrophilic polymer would release protein drugs in a more sustained manner, because of an enhanced association between cross-linked pyrrole groups and the drug molecules. To examine this hypothesis, we prepared hydrogels of alginate substituted with pyrrole groups, alginate-g-pyrrole, through a horse-radish peroxidase (HRP)-activated cross-linking of the pyrrole groups. The hydrogels were encapsulated with poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with vascular endothelial growth factor (VEGF). The resulting hydrogel system released VEGF in a more sustained manner than Ca(2+) alginate or Ca(2+) alginate-g-pyrrole gel systems. Finally, implantations of the VEGF-releasing HRP-activated alginate-g-pyrrole hydrogel system on chicken chorioallantoic membranes resulted in the formation of blood vessels in higher densities and with larger diameters, compared to other control conditions. Overall, the drug releasing system developed in this study will be broadly useful for regulating release rates of a wide array of protein drugs, and further enhance the quality of protein drug-based therapies. © 2013 Elsevier B.V. All rights reserved.

Injectable PLGA/Fe3O4 implants carrying cisplatin for synergistic magnetic hyperthermal ablation of rabbit VX2 tumor.

PubMed

Yang, Yang; Wang, Fengjuan; Zheng, Kaiyuan; Deng, Liming; Yang, Lu; Zhang, Nan; Xu, Chunyan; Ran, Haitao; Wang, Zhaoxia; Wang, Zhigang; Zheng, Yuanyi

2017-01-01

Magnetic hyperthermia ablation has attracted wide attention in tumor therapy for its minimal invasion. Although the chemo-hyperthermal synergism has been proven to be effective in subcutaneously xenografted tumors of nude mice in our previous experiment, the occurrence of residual tumors due to incomplete ablation is more common in relatively larger and deeper-seated tumors in anti-tumor therapy. Thus, a larger tumor and larger animal model are needed for further study of the therapeutic efficacy. In this study, we tested the efficiency of this newly developed technique using a rabbit tumor model. Furthermore, we chose cisplatin (DDP), which has been confirmed with high efficiency in enhancing hyperthermia therapy as the chemotherapeutic drug for the synergistic magnetic hyperthermal ablation therapy of tumors. In vitro studies demonstrated that developed DDP-loaded magnetic implants (DDP/PLGA-Fe3O4) have great heating efficacy and the drug release can be significantly boosted by an external alternating magnetic field (AMF). In vivo studies showed that the phase-transitional DDP/PLGA-Fe3O4 materials that are ultrasound (US) and computerized tomography (CT) visible can be well confined in the tumor tissues after injection. When exposed to AMF, efficient hyperthermia was induced, which led to the cancer cells' coagulative necrosis and accelerating release of the drug to kill residual tumors. Furthermore, an activated anti-tumor immune system can promote apoptosis of tumor cells. In conclusion, the DDP/PLGA-Fe3O4 implants can be used efficiently for the combined chemotherapy and magnetic-hyperthermia ablation of rabbit tumors.

Evaluation of the safety and efficiency of novel metallic implant scaler tips manufactured by the powder injection molding technique.

PubMed

Chun, Kyung A; Kum, Kee-Yeon; Lee, Woo-Cheol; Baek, Seung-Ho; Choi, Hae-Won; Shon, Won-Jun

2017-07-11

Although many studies have compared the properties of ultrasonic scaling instruments, it remains controversial as to which is most suitable for implant scaling. This study evaluated the safety and efficiency of novel metallic ultrasonic scaler tips made by the powder injection molding (PIM) technique on titanium surfaces. Mechanical instrumentation was carried out using four types of metal scaler tips consisting of copper (CU), bronze (BR), 316 L stainless steel (316 L), and conventional stainless steel (SS) tips. The instrumented surface alteration image of samples was viewed with scanning electron microscope (SEM) and surface profile of the each sample was investigated with confocal laser scanning microscopy (CLSM). Arithmetic mean roughness (Ra) and maximum height roughness (Rmax) of titanium samples were measured and dissipated power of the scaler tip was estimated for scaling efficiency. The average Ra values caused by the 316 L and SS tip were about two times higher than those of the CU and BR tips (p < 0.05). The Rmax value showed similar results. The efficiency of the SS tip was about 3 times higher than that of CU tip, the 316 L tip is about 2.7 times higher than that of CU tip, and the BR tip is about 1.2 times higher than that of CU tip. Novel metallic bronze alloy ultrasonic scaler tip minimally damages titanium surfaces, similar to copper alloy tip. Therefore, this bronze alloy scaler tip may be promising instrument for implant maintenance therapy.

[Contraception in the future].

PubMed

Hamzaoui, R; Boukhris, M

1994-02-01

In the last decade, global use of contraceptive methods has increased. About 50% of couples of childbearing age use a modern contraceptive method. This evolution and a positive change in attitude towards male contraception has encouraged research in fertility regulation to enlarge and to improve acceptance of the contraceptive mix. Current injectable contraceptives interfere with the menstrual cycle. Research is exploring ways to minimize such secondary effects by reducing the total hormone dose and by changing the way the active product is delivered (e.g., microspheres). An injectable prototype is an analogue of levonorgestrel (HRP 002). A new IUD is made of leather suspended by a nylon suture which has been inserted into the uterine muscle. RU-486, often used to interrupt early pregnancy, is being tested as an oral contraceptive (OC). It inhibits secretion of gonadotropins and ovulation. It holds promise as an OC with no estrogen component. Since it also inhibits endometrial development and thus prevents implantation, it may someday be used for emergency contraception (i.e., postcoital contraception). New contraceptive implants under study include Norplant RII (2 rods of levonorgestrel lasting for 3 years), Implanon (desogestrel), and Capranor (biodegradable implant lasting 2 years). The female condom consists of a flexible polyurethane sheath with a flexible ring at each end. It has the potential to protect against sexually transmitted diseases since it covers the labial lips and is impermeable to HIV. France and Switzerland have both approved its use. It will enter the UK market at the end of the year. Approval for marketing has been sought in the US.

Selective enrichment of hypericin in malignant glioma: pioneering in vivo results.

PubMed

Noell, Susan; Mayer, Daniel; Strauss, Wolfgang S L; Tatagiba, Marcos S; Ritz, Rainer

2011-05-01

Malignant gliomas are diffuse infiltrative growing tumors with a poor prognosis despite treatment with a combination of surgery, radiotherapy and chemotherapy. It has been shown recently that complete tumor resection improves the survival time significantly. Hypericin, a component of St. Johns Wort, is one of the most powerful photosensitizers in nature. The aim of the present study was to investigate accumulation of hypericin in intracerebral implanted malignant glioma in vivo. Rats underwent stereotactic implantation of C6 glioma cells. After intravenous administration of hypericin (5 mg per kg body weight), accumulation of the compound was studied in tumor, the infiltration zone surrounding the tumor and healthy brain (contralateral hemisphere) by fluorescence microscopy between 0 and 48 h after injection. Results were compared by one-way analysis of variance. For post hoc pair-wise comparison the Tukey-Kramer HSD test was used. Accumulation of hypericin was significantly higher in C6 glioma as compared to normal tissue. Maximum hypericin uptake was achieved at 24 h after injection. Ratios of fluorescence intensity between tumor and normal tissue as well as infiltration zone and normal tissue of about 6.1:1 and 1.4:1 were found. Considering tissue auto-fluorescence, fluorescence ratios of about 19.8:1 and 2.5:1 were calculated, respectively. Therefore, hypericin seems to be quite an effective fluorescence marker for the detection of glioma in vivo. To the best of our knowledge, the present study demonstrates for the first time that hypericin accumulates selectively in intracerebral implanted C6 glioma in vivo after systemic (intravenous) administration.

Laser patterning of platinum electrodes for safe neurostimulation

NASA Astrophysics Data System (ADS)

Green, R. A.; Matteucci, P. B.; Dodds, C. W. D.; Palmer, J.; Dueck, W. F.; Hassarati, R. T.; Byrnes-Preston, P. J.; Lovell, N. H.; Suaning, G. J.

2014-10-01

Objective. Laser surface modification of platinum (Pt) electrodes was investigated for use in neuroprosthetics. Surface modification was applied to increase the surface area of the electrode and improve its ability to transfer charge within safe electrochemical stimulation limits. Approach. Electrode arrays were laser micromachined to produce Pt electrodes with smooth surfaces, which were then modified with four laser patterning techniques to produce surface structures which were nanosecond patterned, square profile, triangular profile and roughened on the micron scale through structured laser interference patterning (SLIP). Improvements in charge transfer were shown through electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and biphasic stimulation at clinically relevant levels. A new method was investigated and validated which enabled the assessment of in vivo electrochemically safe charge injection limits. Main results. All of the modified surfaces provided electrical advantage over the smooth Pt. The SLIP surface provided the greatest benefit both in vitro and in vivo, and this surface was the only type which had injection limits above the threshold for neural stimulation, at a level shown to produce a response in the feline visual cortex when using an electrode array implanted in the suprachoroidal space of the eye. This surface was found to be stable when stimulated with more than 150 million clinically relevant pulses in physiological saline. Significance. Critical to the assessment of implant devices is accurate determination of safe usage limits in an in vivo environment. Laser patterning, in particular SLIP, is a superior technique for improving the performance of implant electrodes without altering the interfacial electrode chemistry through coating. Future work will require chronic in vivo assessment of these electrode patterns.