-
Pflugers Archiv : European Journal of... Sep 2021The second messengers, cGMP and Ca, have both been implicated in retinal degeneration; however, it is still unclear which of the two is most relevant for photoreceptor... (Review)
Review
The second messengers, cGMP and Ca, have both been implicated in retinal degeneration; however, it is still unclear which of the two is most relevant for photoreceptor cell death. This problem is exacerbated by the close connections and crosstalk between cGMP-signalling and calcium (Ca)-signalling in photoreceptors. In this review, we summarize key aspects of cGMP-signalling and Ca-signalling relevant for hereditary photoreceptor degeneration. The topics covered include cGMP-signalling targets, the role of Ca permeable channels, relation to energy metabolism, calpain-type proteases, and how the related metabolic processes may trigger and execute photoreceptor cell death. A focus is then put on cGMP-dependent mechanisms and how exceedingly high photoreceptor cGMP levels set in motion cascades of Ca-dependent and independent processes that eventually bring about photoreceptor cell death. Finally, an outlook is given into mutation-independent therapeutic approaches that exploit specific features of cGMP-signalling. Such approaches might be combined with suitable drug delivery systems for translation into clinical applications.
Topics: Animals; Calcium Signaling; Cell Death; Cyclic GMP; Drug Delivery Systems; Drug Implants; Humans; Nanoparticles; Photoreceptor Cells; Retinal Degeneration
PubMed: 33864120
DOI: 10.1007/s00424-021-02556-9 -
BioMed Research International 2015Growth factors are a class of cytokines that stimulate cell growth and are widely used in clinical practice, such as wound healing, revascularization, bone repair, and... (Review)
Review
Growth factors are a class of cytokines that stimulate cell growth and are widely used in clinical practice, such as wound healing, revascularization, bone repair, and nervous system disease. However, free growth factors have a short half-life and are instable in vivo. Therefore, the search of excellent carriers to enhance sustained release of growth factors in vivo has become an area of intense research interest. The development of controlled-release systems that protect the recombinant growth factors from enzymatic degradation and provide sustained delivery at the injury site during healing should enhance the growth factor's application in tissue regeneration. Thus, this study reviews current research on commonly used carriers for sustained release of growth factors and their sustained release effects for preservation of their bioactivity and their accomplishment in tissue engineering approaches.
Topics: Animals; Delayed-Action Preparations; Drug Implants; Humans; Intercellular Signaling Peptides and Proteins; Regeneration; Regenerative Medicine; Tissue Engineering
PubMed: 26347885
DOI: 10.1155/2015/808202 -
Reproductive Biology and Endocrinology... Mar 2021Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress...
BACKGROUND
Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. The overall objective was to develop and validate a rodent model of implanted etonogestrel (ENG) LARC, at body size equivalent doses to the average dose received by women during each of the first 3 years of ENG subdermal rod LARC use.
METHODS
Intact, virgin, female Sprague-Dawley rats (16-wk-old) were randomized to 1 of 4 groups (n = 8/group) of ENG LARC (high-0.30μg/d, medium-0.17μg/d, low-0.09μg/d, placebo-0.00μg/d) via a slow-release pellet implanted subcutaneously. Animals were monitored for 21 days before and 29 days following pellet implantation using vaginal smears, ultrasound biomicroscopy (UBM), saphenous blood draws, food consumption, and body weights. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA.
RESULTS
Prior to pellet implantation there was no difference in time spent in estrus cycle phases among the treatment groups (p > 0.30). Following pellet implantation there was a dose-dependent impact on the time spent in diestrus and estrus (p < 0.05), with the high dose group spending more days in diestrus and fewer days in estrus. Prior to pellet insertion there was not an association between treatment group and estrus cycle classification (p = 0.57) but following pellet implantation there was a dose-dependent association with cycle classification (p < 0.02). Measurements from the UBM (ovarian volume, follicle count, corpora lutea count) indicate an alteration of ovarian function following pellet implantation.
CONCLUSION
Assessment of estrus cyclicity indicated a dose-response relationship in the shift to a larger number of acyclic rats and longer in duration spent in the diestrus phase. Therefore, each dose in this model mimics some of the changes observed in the ovaries of women using ENG LARC and provides an opportunity for investigating the impacts on non-reproductive tissues in the future.
Topics: Animals; Contraceptive Agents, Female; Desogestrel; Dose-Response Relationship, Drug; Drug Implants; Estrus; Female; Humans; Models, Animal; Progestins; Rats; Rats, Sprague-Dawley; Rodentia
PubMed: 33752672
DOI: 10.1186/s12958-021-00729-w -
Indian Journal of Ophthalmology Aug 2018The management of uveitis is challenging for most treating ophthalmologists. The treatment of uveitis often requires the use of high dose of systemic corticosteroid and... (Review)
Review
The management of uveitis is challenging for most treating ophthalmologists. The treatment of uveitis often requires the use of high dose of systemic corticosteroid and immunosuppressive agents, which are almost always associated with potential side effects. Intravitreal medications have become a popular mode of drug administration in uveitis patients as they provide high volume of drug to the target tissues, eliminating the risk of systemic toxicity. There has been tremendous development in the intravitreal therapeutics over the last few years. With the advent of sustained-release technique, increasing patient compliance, biodegradable nature of the implant, and introduction of newer agents with better safety profile, the intravitreal medications have become more popular in recent years. This review presents evidence in the scientific literature supporting the use of intravitreal medications for the management of uveitis and its complications.
Topics: Drug Implants; Glucocorticoids; Humans; Immunosuppressive Agents; Intravitreal Injections; Macular Edema; Uveitis
PubMed: 30038143
DOI: 10.4103/ijo.IJO_35_18 -
Contraception Aug 2020To assess etonogestrel contraceptive implant location and outcomes among women referred for "difficult" removal to a specialist clinic in South Africa. (Review)
Review
OBJECTIVES
To assess etonogestrel contraceptive implant location and outcomes among women referred for "difficult" removal to a specialist clinic in South Africa.
STUDY DESIGN
We performed a retrospective review of cases referred to our clinic for removal of nonpalpable, deep, migrated, or damaged implants, or failed removals from March to August 2017.
RESULTS
Most (n = 68, 92%) of the 74 referrals were nonpalpable in our clinic. We used ultrasound for localization and successfully removed 72 implants (97%) in the outpatient clinic.
CONCLUSION
With proper protocols and equipment, localization and removal of nonpalpable implants can be safely and effectively achieved in an outpatient African setting.
IMPLICATIONS
Access to providers specially trained in ultrasound localization should be available in all settings where implants are offered. Providing timely access to safe and effective implant removals in routine and difficult cases is essential to ensuring that implant programs are in alignment with rights-based, client-centered family planning principles.
Topics: Contraceptive Agents, Female; Desogestrel; Device Removal; Drug Implants; Female; Humans; Referral and Consultation; Retrospective Studies; South Africa
PubMed: 32339484
DOI: 10.1016/j.contraception.2020.04.013 -
European Journal of Pharmaceutical... Dec 2023FDA's initiative Pharmaceutical CGMPs for the 21st century opened the door for introduction of several risk based approaches in pharmaceutical industry. One significant...
FDA's initiative Pharmaceutical CGMPs for the 21st century opened the door for introduction of several risk based approaches in pharmaceutical industry. One significant advancement that has emerged is the implementation of process analytical technology (PAT), which has opened doors for understanding and controlling complex technological processes. Two such processes, radial extrusion and pellet coating, offer a solid foundation for the application of PAT tools due to their numerous critical process parameters. The aim of the first part of the study was to optimize the neutral pellet production to produce the pellets with properties desired for successful film coating using design of experiments (DoE). In the second part the optimized pellets underwent film coating and the coating quantity was predicted in real or near real-time using in-line and at-line NIR probes and the performance of both probes was compared. The desired properties of the pellets, narrow particle size distribution, high sphericity and high process yield, were successfully achieved. Models for film coating quantity prediction using in-line and at-line NIR probe were successfully calibrated and tested by coating two additional batches. Despite the limited sample size for model calibration, at-line NIR exhibited excellent prediction performance and enabled accurate determination of process end-point. The coating quantity determined by UV/VIS spectroscopy in both test batches deviated by less than 2.0 % from the target value. However, the in-line NIR probe, primarily due to its inferior spectral resolution, displayed a slightly lower quality of the calibrated model and notable overprediction for the tested batches.
Topics: Spectroscopy, Near-Infrared; Technology, Pharmaceutical; Technology; Drug Implants; Drug Industry
PubMed: 37770005
DOI: 10.1016/j.ejps.2023.106595 -
Studies in Family Planning Mar 2019Contraceptive failure is a major contributor to unintended pregnancy worldwide. DHS retrospective calendars, which are the most widely used data source for estimating...
Contraceptive failure is a major contributor to unintended pregnancy worldwide. DHS retrospective calendars, which are the most widely used data source for estimating contraceptive failure in low-income countries, vary in quality across countries and surveys. We identified surveys with the most reliable calendar data and analyzed 105,322 episodes of contraceptive use from 15 DHSs conducted between 1992 and 2014. We estimate contraceptive method-specific 12-month failure rates. We also examined how failure rates vary by age, education, socioeconomic status, contraceptive intention, residence, and marital status using multilevel piecewise exponential hazard models. Our failure rate estimates are significantly lower than results from the United States and slightly higher than previous studies that included more DHS surveys, including some with lower-quality data. We estimate age-specific global contraceptive failure rates and find strong, consistent age patterns with the youngest users experiencing failure rates up to ten times higher than older women for certain methods. Failure also varies by socioeconomic status, with the poorest, and youngest, women at highest risk of experiencing unintended pregnancy due to failure.
Topics: Adolescent; Adult; Age Factors; Coitus Interruptus; Condoms; Contraceptive Agents; Contraceptive Effectiveness; Contraceptives, Oral; Developing Countries; Drug Implants; Educational Status; Female; Humans; Intention; Intrauterine Devices; Marital Status; Multilevel Analysis; Natural Family Planning Methods; Proportional Hazards Models; Residence Characteristics; Risk Factors; Social Class; Young Adult
PubMed: 30791104
DOI: 10.1111/sifp.12085 -
Molecules (Basel, Switzerland) Dec 2022This work aimed to develop a new one-pot and readily scaled-up formulation capable of retaining 5-fluorouracil and prolonging its release to obtain a site-specific...
This work aimed to develop a new one-pot and readily scaled-up formulation capable of retaining 5-fluorouracil and prolonging its release to obtain a site-specific medication delivery for the potential treatment of colorectal cancer. Six polymer-based formulations were successfully produced using a thermal bulk polymerization method and loaded with 5-fluorouracil, which is a chemotherapeutic agent used in the treatment of colorectal carcinoma. The pellets produced were characterized by measuring the glass transition temperature, tensile strength, Young's modulus, and tensile elongation at break. Studies on in vitro swelling and release were carried out in phosphate-buffered saline to evaluate the behaviour of the developed system. The Young's modulus, glass transition temperature, and tensile strength all increased significantly as the crosslinker concentration increased, but the fracture strain value reduced significantly. The in vitro swelling profile of the produced formulations was significantly reduced by increasing crosslinking density. Less than 27% cumulative drug release was achieved for all formulations after 5 h of starting the release study. The highest cumulative drug release reached after 24 h was 69%. The developed drug delivery system demonstrated the ability to delay the release of 5-fluorouracil in upper gastrointestinal tract-mimicking conditions, while permitting its release in a controlled way afterward, which makes it promising for the potential delivery of 5-fluorouracil to the colon.
Topics: Fluorouracil; Drug Delivery Systems; Drug Implants; Polymers; Colon
PubMed: 36615499
DOI: 10.3390/molecules28010306 -
BMJ Case Reports Nov 2021The etonogestrel implant is the most effective contraceptive available. We report a case of ectopic pregnancy in a woman who had an etonogestrel implant inserted 15...
The etonogestrel implant is the most effective contraceptive available. We report a case of ectopic pregnancy in a woman who had an etonogestrel implant inserted 15 months ago and the effective concentration of the implant was within normal limits.
Topics: Contraceptive Agents, Female; Desogestrel; Drug Implants; Female; Humans; Pregnancy; Pregnancy, Ectopic
PubMed: 34785516
DOI: 10.1136/bcr-2021-245175 -
A review of ten years of experience using dexamethasone intravitreal implants (Ozurdex) for uveitis.European Review For Medical and... Mar 2023Uveitis is a type of ocular inflammatory disease caused by various etiologies, for which corticosteroids are the main treatment. Dexamethasone Intravitreal implant... (Review)
Review
Uveitis is a type of ocular inflammatory disease caused by various etiologies, for which corticosteroids are the main treatment. Dexamethasone Intravitreal implant (DEX-I) has been widely used in the treatment of uveitis across the world. Then, new indications and complications appeared. This review aims to summarize the use of DEX-I in uveitis in the past 10 years. We summarized the clinical data (baseline characteristics, efficacy and safety) and discussed controversies by retrospectively analyzing the articles and cases published in PubMed and Web of Science using the terms "Ozurdex", OR "intravitreal dexamethasone implant", AND "uveitis" from 2010 to 2022. DEX-I is effective in reducing edema, improving inflammation and improving vision when treating various conditions of uveitis including infectious, no-infectious, pediatric uveitis, and surgery-related applications. The efficacy of DEX-I as a monotherapy is related to the following: etiology and course of disease, treatment of systemic diseases, patients' toleration after multiple injections, economic situation, etc. In addition, intravitreal corticosteroids implantation may replace systemic therapy in some patients. In terms of safety, the incidence of high intraocular pressure is about 20.52%, and the incidence of cataract is about 15.51%. DEX-I can effectively treat non-infectious uveitis and some infectious uveitis such as suspected tuberculosis, and its safety is controllable. Further studies are necessary to evaluate the effect of monotherapy and to expand more indications.
Topics: Humans; Child; Glucocorticoids; Retrospective Studies; Treatment Outcome; Macular Edema; Visual Acuity; Intravitreal Injections; Dexamethasone; Uveitis; Drug Implants
PubMed: 36930471
DOI: 10.26355/eurrev_202303_31535