Aim： To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods： Forty-eight male Sprague-Dawley rats were randomly divided into four groups： group A, normal rats...Aim： To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods： Forty-eight male Sprague-Dawley rats were randomly divided into four groups： group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone （T） undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T （FT） and dihydrotestosterone （DHT） were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score （VESS） was computed. Results： Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups （P 〈 0.01）; DHT concentrations of group D rats were significantly decreased （P 〈 0.01 ） when compared with those of groups A and C. Rats in groups B and D rats （with low androgen levels） had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion： These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.展开更多
5α-reductase inhibitors （5α-RIs）, including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia （BPH）. Many studies reported that preoperative 5α-RI had impact on i...5α-reductase inhibitors （5α-RIs）, including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia （BPH）. Many studies reported that preoperative 5α-RI had impact on intraoperative haemorrhage during surgery for BPH, but it was still in controversial. So, we conducted a systematic review of the effects and mechanisms of 5α-RIs on intraoperative bleeding for BPH. MEDLINE, EMBASE, the Cochrane Controlled Trail Register of Controlled Trials and the reference lists of retrieved studies were searched in the analysis. Sixteen publications involving 15 different randomized controlled trials （RCTs） and a total of 1156 patients were used in the analysis, including 10 RCTs for finasteride and five RCTs for dutasteride. We found that preoperative finasteride treatment decreases microvessel density （MVD） in resected prostate specimens. Total blood loss, blood loss per gram of resected prostate tissue and decreases in haemoglobin were all greatly reduced in the finasteride group as compared to controls. Dutasteride appeared to have no effect on bleeding. This meta-analysis shows that preoperative finasteride treatment could decrease intraoperative haemorrhage during surgery for BPH. Preoperative dutasteride had no effect on intraoperative haemorrhage, but further high-qualitv prospective studies are still needed to confirm this observation.展开更多
Benign prostatic hyperplasia(BPH)is a common disease in men,and is known to be related to 5α-reductase,which can affect steroid metabolism.Under the promotion of 5α-reductase,testosterone can be converted into dihyd...Benign prostatic hyperplasia(BPH)is a common disease in men,and is known to be related to 5α-reductase,which can affect steroid metabolism.Under the promotion of 5α-reductase,testosterone can be converted into dihydrotestosterone(DHT),and excessive DHT will cause related diseases.Since BPH seriously affects the quality of life of patients,it is essential to discover effective 5α-reductase inhibitors.In this study,the simple analytical method of high performance thin layer chromatography(HPTLC)was used to screen active compounds,and seven compounds with strong activity were screened out.This research will provide a reference for studying the material basis of drugs for the treatment of BPH.展开更多
Postfinasteride syndrome(PFS)is a term coined to characterize a constellation of reported undesirable sexual,physical,and neuropsychiatric side effects.In the present study,we conducted the meta-analysis to demonstrat...Postfinasteride syndrome(PFS)is a term coined to characterize a constellation of reported undesirable sexual,physical,and neuropsychiatric side effects.In the present study,we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors(5ARIs)increases the risk of PFS-like adverse effects.A search of studies published until May 10,2020,was performed using PubMed,EMBASE,and the Cochrane Library.We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia(BPH)or androgenetic alopecia(AGA),and identified 34 studies from 28 articles that met our eligibility criteria.In the random-effects model,the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial(95%confidence interval[CI]:1.64-2.14).Regarding specific types of adverse effects,the use of 5ARIs had a 1.89-fold risk of sexual adverse effects(95%CI:1.74-2.05)and was associated with an increased risk of physical adverse effects(relative risk[RR]:1.31,95%CI:0.80-2.15),albeit without statistical significance.This meta-analysis helped to better define the adverse effects caused by 5ARIs.We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment.Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.展开更多
Aim To synthesize dutasteride. Methods The target compound was synthesized from pregnenolol via eight steps, including esterification, oxidation, hydrolysis, then oxidative ring-opening, cyclization, reduction, oxidiz...Aim To synthesize dutasteride. Methods The target compound was synthesized from pregnenolol via eight steps, including esterification, oxidation, hydrolysis, then oxidative ring-opening, cyclization, reduction, oxidization and finally acylation. Results The structure of the target molecule was identified by ^1H NMR, ^13C NMR and element analysis. The overall yield was 31.5%. Conclusion The effects of different reaction conditions on the yield of product in each step have been investigated and the optimal reaction conditions have been established.展开更多
基金Acknowledgment This study was support by Natural Science Foundation of Shanghai, China （No. 06ZR14137）.
文摘Aim： To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods： Forty-eight male Sprague-Dawley rats were randomly divided into four groups： group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone （T） undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T （FT） and dihydrotestosterone （DHT） were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score （VESS） was computed. Results： Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups （P 〈 0.01）; DHT concentrations of group D rats were significantly decreased （P 〈 0.01 ） when compared with those of groups A and C. Rats in groups B and D rats （with low androgen levels） had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion： These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.
文摘5α-reductase inhibitors （5α-RIs）, including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia （BPH）. Many studies reported that preoperative 5α-RI had impact on intraoperative haemorrhage during surgery for BPH, but it was still in controversial. So, we conducted a systematic review of the effects and mechanisms of 5α-RIs on intraoperative bleeding for BPH. MEDLINE, EMBASE, the Cochrane Controlled Trail Register of Controlled Trials and the reference lists of retrieved studies were searched in the analysis. Sixteen publications involving 15 different randomized controlled trials （RCTs） and a total of 1156 patients were used in the analysis, including 10 RCTs for finasteride and five RCTs for dutasteride. We found that preoperative finasteride treatment decreases microvessel density （MVD） in resected prostate specimens. Total blood loss, blood loss per gram of resected prostate tissue and decreases in haemoglobin were all greatly reduced in the finasteride group as compared to controls. Dutasteride appeared to have no effect on bleeding. This meta-analysis shows that preoperative finasteride treatment could decrease intraoperative haemorrhage during surgery for BPH. Preoperative dutasteride had no effect on intraoperative haemorrhage, but further high-qualitv prospective studies are still needed to confirm this observation.
基金This study was financially supported by the Program of Shanghai Municipal Commission of Health and Family Planning(ZY(2018-2020)-CCCX-5002).
文摘Benign prostatic hyperplasia(BPH)is a common disease in men,and is known to be related to 5α-reductase,which can affect steroid metabolism.Under the promotion of 5α-reductase,testosterone can be converted into dihydrotestosterone(DHT),and excessive DHT will cause related diseases.Since BPH seriously affects the quality of life of patients,it is essential to discover effective 5α-reductase inhibitors.In this study,the simple analytical method of high performance thin layer chromatography(HPTLC)was used to screen active compounds,and seven compounds with strong activity were screened out.This research will provide a reference for studying the material basis of drugs for the treatment of BPH.
基金the National Natural Science Foundation of China for their support in generating this manuscript(No.81770758 to LW).
文摘Postfinasteride syndrome(PFS)is a term coined to characterize a constellation of reported undesirable sexual,physical,and neuropsychiatric side effects.In the present study,we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors(5ARIs)increases the risk of PFS-like adverse effects.A search of studies published until May 10,2020,was performed using PubMed,EMBASE,and the Cochrane Library.We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia(BPH)or androgenetic alopecia(AGA),and identified 34 studies from 28 articles that met our eligibility criteria.In the random-effects model,the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial(95%confidence interval[CI]:1.64-2.14).Regarding specific types of adverse effects,the use of 5ARIs had a 1.89-fold risk of sexual adverse effects(95%CI:1.74-2.05)and was associated with an increased risk of physical adverse effects(relative risk[RR]:1.31,95%CI:0.80-2.15),albeit without statistical significance.This meta-analysis helped to better define the adverse effects caused by 5ARIs.We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment.Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.
文摘Aim To synthesize dutasteride. Methods The target compound was synthesized from pregnenolol via eight steps, including esterification, oxidation, hydrolysis, then oxidative ring-opening, cyclization, reduction, oxidization and finally acylation. Results The structure of the target molecule was identified by ^1H NMR, ^13C NMR and element analysis. The overall yield was 31.5%. Conclusion The effects of different reaction conditions on the yield of product in each step have been investigated and the optimal reaction conditions have been established.
