Pregnant women with MS experience fewer relapses, especially during the third trimester. In this study, we explore the cellular and molecular events that bring about the protective effect of late ...pregnancy on the course of de/remyelination in rats. Using cellular, molecular, and ultrastructural methods, we explored remyelination in response to a focal demyelination in the corpus callosum of late pregnant, virgin, and postpartum rats. We further explored the role of GABA
receptor (GABA
R) in the promyelinating effect observed during late pregnancy. Remyelination in response to a gliotoxin-induced demyelination in the corpus callosum was enhanced in late pregnant rats when compared to that seen in virgin and postpartum rats. This pregnancy-associated promyelinating effect was lost when either the GABA
R was blocked or when 5α-reductase, the rate limiting enzyme for the endogenous GABA
R activator allopregnanolone, was inhibited. Taken together, these data suggest that the pregnancy-associated pro-myelination operates, at least in part, through a GABAergic activated system.
The purpose of this study was to determine the efficacy and safety of dutasteride compared with finasteride, used for the treatment of benign prostatic hyperplasia (BPH). Pertinent studies were ...identified by searching of PubMed and Web of Science. The random effect model was used to combine the results. Both direct comparison using traditional meta-analysis method and indirect comparison using network meta-analysis method were performed. Twenty-one articles involving a total of 29,094 patients were included in this network meta-analysis. Pooled data demonstrated a significantly reduction in International Prostate Symptom Score in the dutasteride group compared with finasteride group weighted mean difference (WMD) = -1.80, 95% confidence interval (CI), -2.90 to -0.11. The treatment effects of dutasteride compared with finasteride were not significant in peak urinary flow (Qmax) (WMD = 0.76, 95% CI, -0.67 to 2.00) and total prostate volume (WMD = -7.6, 95% CI, -21 to 6.6). Also, there is no significant association between dutasteride and finasteride of the safety for the treatment of BPH. Our results suggested that there were no statistically significant differences in the treatment of symptomatic BPH among dutasteride compared with finasteride except that dutasteride can improve BPH symptoms measured by International Prostate Symptom Score.
BACKGROUND
Androgen deprivation therapy (ADT) improves outcomes in unfavorable‐risk prostate cancer (PCa) treated with radiation therapy (RT). It was hypothesized that replacing luteinizing ...hormone‐releasing hormone (LHRH) agonists with a 5‐α‐reductase inhibitor (5‐ARI) would improve hormonal health‐related quality of life (HRQOL) without differentially suppressing androgen‐responsive (AR) gene expression.
METHODS
Patients with localized unfavorable‐risk PCa, aged ≥70 years or Charlson Comorbidity Index score ≥2 were treated with oral ADT (oADT), consisting of 4 months of bicalutamide, a 5‐ARI, and RT at 78 Gy. The primary end point was Expanded Prostate Cancer Index Composite HRQOL at 6 months ≤30%, and improvement compared with a synchronous standard of care (SOC) cohort receiving 4 months of bicalutamide and long‐term LHRH agonist with RT. RNA sequencing was performed from matched pre‐/post‐ADT prostate tumor biopsies in a subset of men. Differential gene and pathway expressional changes were examined using gene set enrichment.
RESULTS
Between 2011 and 2018, 40 and 30 men were enrolled in the oADT and SOC cohorts, respectively. Median follow‐up was 40 months. Those with ≤30% decline in hormonal HRQOL at 6 months was 97% (oADT) and 93% (SOC). The average 6‐month hormonal decline was 1% (oADT) versus 12% (SOC; P = .04). The 4‐year freedom from biochemical failure was 88% (oADT) versus 81% (SOC; P = .48). RNA sequencing (n = 9) showed similar numbers of downregulated and upregulated genes between the treatment groups (fold‐change = 2; false‐discovery rate‐adjusted P ≤ .05). Both treatments comparably decreased the expression of 20 genes in canonical androgen receptor signaling.
CONCLUSIONS
For men with PCa undergoing RT, oral versus standard ADT may improve 6‐month QOL and appears to have a similar impact on androgen‐responsive gene expression.
For men with localized prostate cancer undergoing radiation therapy, oral versus standard androgen deprivation therapy may improve 6‐month quality of life and appears to have a similar effect on androgen‐responsive gene expression.
Summary
Background Hair loss is an unwelcome event at any age, but it can be particularly distressing for adolescents and their families. While androgenetic alopecia (AGA) is the most common form of ...hair loss in adults, little is known about its prevalence, clinical features and response to treatments in the paediatric population.
Objectives To better characterize the causes of alopecia in a paediatric population.
Methods We performed a retrospective chart review to identify all patients with hair loss seen in an academic paediatric dermatology practice at New York University over a 12‐year period to better characterize the causes of alopecia in this population. We review the clinical and histological features, natural progression and associated laboratory abnormalities of AGA in 57 paediatric patients.
Results AGA was identified as the most frequent cause of hair loss in adolescents and the second most common diagnosis overall. The male to female ratio was 2 : 1 and the average age at initial presentation with AGA was 14·8 years. Adolescent girls had diffuse thinning or thinning at the crown, and boys frequently presented with female pattern hair loss. When biopsies were performed, perifollicular inflammation was a common finding. A family history of AGA was reported in 83% of patients. Laboratory evaluation for androgens revealed polycystic ovarian syndrome in three girls and late‐onset congenital adrenal hyperplasia in one boy.
Conclusions AGA is the most common form of hair loss in adolescents, and can be the presenting sign of an underlying endocrine disorder. An accurate and timely diagnosis is essential for appropriate medical and psychosocial intervention when warranted.
The 5-α-reductase inhibitors finasteride and dutasteride are frequently used in the treatment of androgenetic alopecia and benign prostatichyperplasia. These drugs are effective at reducing levels of ...dihydrotestosterone, the primary androgen responsible for the pathogenesis of both these conditions. However, finasteride and dutasteride have also been shown to produce an increase in the incidence of sexual dysfunction, namely, impotence, decreased libido, and ejaculation disorder. The purpose of this study is to review the existing medical literature with regard to the sexual side effects of 5-α-reductase inhibitor therapy. This review is an extensive look at the sexual effects of 5-α-reductase inhibitors and compares outcomes for finasteride versus dutasteride in addition to comparing sexualside effects for each of the different dosages prescribed of finasteride and dutasteride.
Objective: The present paper describes the development and evaluation of a Novel Finasteride (FSD) nanogel topical delivery for the treatment of Androgenetic Alopecia. Nano-based topical formulation ...was chosen to enhance the solubility, permeability, biocompatibility of drug and to overcome the problems associated with the oral delivery of finasteride.
Methods: Various trails batches were prepared by using probe sonication method. Based on stability studies and particle size, NP4 trail was optimized which exhibited a spherical shape with a mean diameter of 113.80±0.72, the polydispersity of 0.28±0.01, zeta potential of-25.2 mV, drug entrapment efficiency of 92.67±0.47 %, and drug loading of 6.15±0.02 %. Storage stability studies demonstrated that the particle size and entrapment efficiency were not changed during 3 mo both at 4 °C and room temperature. Finasteride (FSD) NLCs were characterized for particle size by scanning electron microscope (SEM), chemical state by X-Ray diffraction (XRD), physical stability by centrifugation and thermodynamic stability by Freeze-thaw method. These prepared nanoparticles were transformed into topical nanogel and further evaluated.
Results: Among the different trails, C2 trail of NLC gel has shown excellent gelling capacity, clear appearance, good viscosity characteristics and was selected for further evaluation studies. Batches of topical nanogel were characterized through pH, homogeneity, spreadability, viscosity, drug content and in vitro drug release study. Based on pH (6.5-6.8), drug content (91.25±0.9%), spreadability (6.7 cm/sec), C2 batch was subjected to In vitro skin occlusivity study, in-vitro release study and In vitro heamolysis study.
Conclusion: The percent cumulative drug release for Finasteride (FSD) gel was found to be 758.52±1.49 µg at 24 h which is quite higher than plain gel and Finasteride (FSD) gel showed maximum occlusiveness and excellent spreadability and found to be stable. In conclusion, prepared Finasteride (FSD) Nanogel could be used with promising potential for the treatment of Androgenetic Alopecia.
Abstract
Objective: We sought to determine whether topical finasteride can enhance the efficacy of intense pulsed light hair removal. Materials and methods: An intense pulsed light (IPL) treatment ...with radiofrequency (RF) was performed every four weeks, resulting in up to three sessions, and again at the end of the study - 6 months after the start of the experiment. Each patient also applied either finasteride or placebo solution twice daily to each side of the chin in a double-blinded manner. Results: A total of 77 patients were included in the study. Mean hair density before treatment in finasteride side of the patient's chin was 19.7 ± 11.7 and in placebo side was 19.1 ± 11.3. After three sessions of IPL + RF treatment, combined with twice daily application of finasteride and placebo solutions, at the end of 6-month period mean hair density of 8 ± 6.3 and 9 ± 5.6 was achieved in finasteride and placebo side respectively. Statistically significant difference was found between finasteride and placebo solution. Conclusions: We have demonstrated that the addition of finasteride solution to IPL + RF hair removal may result in a more reduction of unwanted facial hair in women when the combination is used for up to 6 months.
The 18 kDa translocator protein (TSPO) is a five transmembrane domain protein that plays a crucial role in neurosteroid (e.g., allopregnanolone) synthesis by promoting the transport of cholesterol to ...the inner mitochondrial membrane. This protein is predominantly expressed in steroid-synthesizing tissues, including the central and peripheral nervous system, affecting stress-related disorders such as anxiety and depression. Recent studies have focused on the hippocampal dentate gyrus, which is very important for involvement of anxiety and depression. However, the exact role that TSPO plays in the pathophysiology of anxiety and depression and the involvement of the hippocampal dentate gyrus in regulating these behavioural effects remain elusive. This study used the lentiviral vectors mediating TPSO overexpression to assess the effects of TPSO overexpression in the hippocampal dentate gyrus on anxiolytic and antidepressant-like behavioural effects in mice. The expression of TSPO and the concentration of allopregnanolone in hippocampus tissues (3 mm in diameter around the injection site on both sides) were measured by Western blot and ELISA, respectively. The results indicated that microinjection of the LV-TSPO resulted in a significant increase in TSPO expression and allopregnanolone concentration in the hippocampus. Moreover, TSPO overexpression of the mouse hippocampal dentate gyrus generated significant anxiolytic and antidepressant-like behavioural effects in a series of behavioural models. These effects were completely blocked by the TSPO antagonist PK11195 (3 mg/kg, intraperitoneally) and the 5α-reductase inhibitor finasteride (5 mg/kg,intraperitoneally). Meanwhile, the increased allopregnanolone was also reversed by PK11195 and finasteride. In addition, neither PK11195 nor finasteride had an effect on the expression of TSPO. Overall, our results are the first to suggest that the overexpression of TSPO in the hippocampal dentate gyrus produced anxiolytic and antidepressant-like behavioural effects that are partially mediated by downstream allopregnanolone biosynthesis. Our results suggest that TSPO would be a potential anxiolytic and antidepressant therapeutic target.
•Translocator protein 18 kDa (TSPO) is a therapeutic target for anxiety and neurologic disorders.•Microinjection of the dentate gyrus with lentiviral vectors, which resulted in a significant increase in TSPO expression.•TSPO overexpression of the mice hippocampal dentate gyrus generated anxiolytic and antidepressant-like behavioural effects.•The effects were completely blocked by the TSPO antagonist PK11195 and the 5α-reductase inhibitor finasteride.
Fibroblast growth factor 5 (FGF5) is a famous dominant inhibitor of anagen phase of hair cycle. Mutations of FGF5 gene result in a longer wool in mice, donkeys, dogs, cats, and even in human ...eyelashes. Sheep is an important source of wool production. How to improve the production of wool quickly and effectively is an urgent problem to be solved. In this study, we generated five FGF5-knockout Dorper sheep by the CRISPR/Cas9 system. The expression level of FGF5 mRNA in knockout (KO) sheep decreased significantly, and all FGF5 proteins were dysfunctional. The KO sheep displayed a significant increase in fine-wool and active hair-follicle density. The crosstalk between androgen and Wnt/β-catenin signaling downstream of FGF5 gene plays a key role. We established downstream signaling cascades for the first time, including FGF5, FGFR1, androgen, AR, Wnt/β-catenin, Shh/Gli2, c-MYC, and KRTs. These findings further improved the function of FGF5 gene, and provided therapeutic ideas for androgen alopecia.
Pharmaceutical use of finasteride (Dilaprost®) has been well documents in the peer-reviewed literature; however, the presence of trace amounts of related substances (impurities) in finasteride may ...influence the tharapeutic efficacy and safely. Due to limited information available, the objective of this study was to develop a quantification method for the three impurities of finasteride using high performance liquid chromatography (HPLC) with an ultraviolet (UV) detector. The compounds (impurities) of finasteride that are registered with the European Pharmacopeia, which we sought to validate are: -N-(1,1-dimethylethyl)-3-oxo-4-aza-5α-androstane-17β-carboxamide (impurity A), methyl 3-oxo-4-aza-5α-androst-1-ene-17β-carboxylate (impurity B), and -N-(1,1-dimehylethyl)-3-oxo-4-azaandrosta-1,5-diene-17β-carboxamide (impurity C). Analyses were performed using a Nova Pac C18 column for HPLC with isocratic elution. Detection was carried out at 210 nm, the concentration of the three impurities was in the range was 1.5–4.5 μg mL−1 at ambient temperature with a mobile phase of water + acetonitrile + tetrahydrofuran (80:10:10, v/v/v) and the flow rate was 2.0 mL min−1. The recoveries were: 101.35 ± 0.62% (impurity A), 101.60 ± 2.66% (impurity B) and 101.97 ± 2.05% (impurity C). Validation of the method yielded fairly good results as it relates to the precision and accuracy. It is, therefore, concluded that the method would be suitable for not only the separation and determination of processed impurities to monitor the reactions, but also for the quality assurance of finasteride and its related substances.