The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone （T） and dihydrotestosterone （DHT）. T is converted to DHT by 5-alpha reductase （5-AR） i...The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone （T） and dihydrotestosterone （DHT）. T is converted to DHT by 5-alpha reductase （5-AR） isozymes. Differential expression of 5-AR isozymes is observed in both human benign and malignant prostatic tissues. 5-AR inhibitors （5-ARI） are commonly used for the treatment of benign prostatic hyperplasia （BPH） and were once promoted as chemopreventive agents for prostate cancer （PCa）. This review discusses the role of the differential expression of 5-AR in the normal development of the human prostate and in the pathogenesis and progression of BPH and PCa.展开更多
Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase defici...Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase deficiency patients in China's Mainland diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis.A high proportion of atypical 3-oxo-4-bile acids in the urine indicated a deficiency in 4-3-oxosteroid 5β-reductase.All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient's parents.One patient exhibited compound heterozygous mutations:c.396C>A and c.722A>T,while the other was heterozygous for the mutation c.797G>A.Based on these mutations,a diagnosis of primary 4-3-oxosteroid 5β-reductase deficiency could be confirmed.With ursodeoxycholic acid treatment and fat-soluble vitamin supplements,liver function tests normalized rapidly,and the degree of hepatomegaly was markedly reduced in both patients.展开更多
Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead ...Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead to complications including acute urinary retention(AUR)and the need for BPH-related surgery.Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone(DHT),which is formed from testosterone under the influence of 5-alpha reductase.Thus,5-alpha reductase inhibitors(5-ARIs)effectively reduce the serum and intraprostatic concentration of DHT,causing an involution of prostate tissue.Two 5-ARIs are currently available for the treatment of BPHdfinasteride and dutasteride.Both have been demonstrated to decrease prostate volume,improve LUTS and urinary flow rates,which ultimately reduces the risk of AUR and BPH-related surgery.Therefore,either alone or in combination with other BPH medications,5-ARIs are a mainstay of BPH management.展开更多
Objective. To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level.Methods. The plasma Hcy level was measured by capillary electrophoresis- ultravio...Objective. To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level.Methods. The plasma Hcy level was measured by capillary electrophoresis- ultraviolet detection and the gene polymorphism of N5, N10 - methylenetetrahydrofolate reductase (MTHFR) was studied with PCR - RFLP assay in 43 patients with cortical cerebral infarction and 42 healthy controls.Results. The plasma Hcy level of the patients ( 19. 3 + 6. 0 μ mol/L) was markedly higher than that of the controls (13.7 + 5.4 μ mol/L) ( t = 4. 16, P ＜ 0. 001). There are 3 genotypes, C/C, C/T and T/T, about base - variation of MTHFR gene at locus 677. The plasma Hcy level of the subjects with T/T genotype was higher than that of subjects with other genotypes. However, the frequencies of each genotype and allele were not significantly different between the patients and the controls.Conclusions. The elevated plasma Hcy level is a risk factor for atherothrombotic cerebral infarction, and is related to the C→T mutation at locus 677 of MTHFR gene.展开更多
Objectives To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organsMethods The expression level of 5α-reductase type 2 gene inhuman testis, epididymis and vas deferens tissues wa...Objectives To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organsMethods The expression level of 5α-reductase type 2 gene inhuman testis, epididymis and vas deferens tissues was determined by in situ hybridization using Digoxin labeled 5α-reductase type 2 cRNA probe.Results The brown granules of hybridizing signals distributed in the cytoplasm of Sertoli and Leydig cells of the testis, the principle cells of epididymis and the epithelial cells of vas deferens, but there was no positive signal in the nuclei of above-mentioned cells. No positive signal was observed in germ cells, basement of the testis, interstium of epididymis and basement, as well as smooth muscle of vas deferens. Conclusion This study confirmed that the 5α-reductase type 2 gene expressed in Sertoli , Leydig cells of the testis, and the principle cells of epididymis. The expression pattern of the gene in these cells in human was similar to that of rat and monkey. The presence of 5α-reductase type 2 gene in epithelial cells of the vas deferens suggested it might possess an important physiological role in human reproduction.展开更多
Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigat...Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigated on human leu-kemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to inves-tigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.展开更多
BACKGROUND Disorders of primary bile acid synthesis may be life-threatening if undiagnosed,or not treated with primary bile acid replacement therapy. To date, there are few reports on the management and follow-up of p...BACKGROUND Disorders of primary bile acid synthesis may be life-threatening if undiagnosed,or not treated with primary bile acid replacement therapy. To date, there are few reports on the management and follow-up of patients with Δ4-3-oxosteroid 5β-reductase(AKR1 D1) deficiency. We hypothesized that a retrospective analysis of the responses to oral bile acid replacement therapy with chenodeoxycholic acid(CDCA) in patients with this bile acid synthesis disorder will increase our understanding of the disease progression and permit evaluation of this treatment regimen as an alternative to the Food and Drug Administration(FDA) approved drug cholic acid, which is currently unavailable in China.AIM To evaluate the therapeutic responses of patients with AKR1 D1 deficiency to oral bile acid therapy, specifically CDCA.METHODS Twelve patients with AKR1 D1 deficiency, confirmed by fast atom bombardment ionization-mass spectrometry analysis of urine and by gene sequencing for mutations in AKR1 D1, were treated with differing doses of CDCA or ursodeoxycholic acid(UDCA). The clinical and biochemical responses to therapy were monitored over a period ranging 0.5-6.4 years. Dose adjustment, to optimize the therapeutic dose, was based on changes in serum biochemistry parameters,notably liver function tests, and suppression of the urinary levels of atypical hepatotoxic 3-oxo-Δ4-bile acids measured by mass spectrometry.RESULTS Physical examination, serum biochemistry parameters, and sonographic findings improved in all 12 patients during bile acid therapy, except one who underwent liver transplantation. Urine bile acid analysis confirmed a significant reduction in atypical hepatotoxic 3-oxo-Δ4 bile acids concomitant with clinical and biochemical improvements in those patients treated with CDCA. UDCA was ineffective in down-regulating endogenous bile acid synthesis as evidenced from the inability to suppress the urinary excretion of atypical 3-oxo-Δ4-bile acids. The dose of CDCA required for optimal clinical and biochemical responses varied from 5.5-10 mg/kg per day among patients based on maximum suppression of the atypical bile acids and improvement in serum biochemistry parameters, and careful titration of the dose was necessary to avoid side effects from CDCA.CONCLUSION The primary bile acid CDCA is effective in treating AKR1 D1 deficiency but the therapeutic dose requires individualized optimization. UDCA is not recommended for long-term management.展开更多
To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organs. Methods: The expression level of 5ct-reductase type 2 gene in human testis, epididymis and vas deferens tissues was deter...To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organs. Methods: The expression level of 5ct-reductase type 2 gene in human testis, epididymis and vas deferens tissues was determined by in situ hybridization using a digoxin-labeled 5α-reductase type 2 cRNA probe. Results: The brown granules of hybridizing signals distributed in the cytoplasm of the Sertoli and Leydig cells of the testis, the principle cells of epididymis and the epithelial cells of vas deferens, but there was no positive signal in the nuclei of these cells. No positive signal was observed in the germ cells, basement of the testis, interstium of the epididymis and basement and the smooth muscle cells of vas deferens. Conclusion: This study confirmed that the 5a-reductase type 2 gene expressed in the Sertoli and Leydig cells of the testis and the principle cells of the epididymis. The expression pattem of the gene in these cells in the human was similar to that in the rat and monkey. The presence of 5α-reductase type 2 gene in the epithelial cells of the vas deferens suggests that it may play a physiological role in human reproduction. [Reprod Contracep (in English) 2002; 13: 67]展开更多
Background: Patients with gross haematuria are sometimes found to have prostate cancer after clinical evaluation. The treatment of such haematuria could be very challenging. Use of a 5 alpha reductase inhibitor like d...Background: Patients with gross haematuria are sometimes found to have prostate cancer after clinical evaluation. The treatment of such haematuria could be very challenging. Use of a 5 alpha reductase inhibitor like dutasteride has been found helpful in bleeding prostate cancer patients if they have not undergone hormonal manipulation before they developed haematuria. Patients and Method: 26 patients with gross haematuria of prostatic origin who had histologic confirmation of adenocarcinoma of the prostate but who have not had chemical or surgical castration were randomized to receive daily dutasteride in addition to vigorous saline irrigation and antibiotics on one arm and vigorous saline irrigation and antibiotics only as control on the other arm. The time taken before haematuria resolved and the amount of irrigation fluid used were noted. Statistical analysis was done using SPSS. Student’s t-test and Kaplan Meier survival analysis were used to test various variables at 0.5 significant levels. Results: Of the 26 patients 12(46.2%) received 0.5 mg oral dutasteride in addition to saline irrigation while 14 (53.8%) received saline irrigation only. Haematuria stopped in all of 12 (100%) patients on dutasteride arm but on 12 (85.7%) of the 14 patients on the control arm. It took significantly shorter time and lesser volume of irrigation fluid before haematuria resolved in those treated with dutasteride than in those on the control arm. Conclusion: Dutasteride is effective in the control of acute haematuria in pre-androgen ablation prostate cancer patients.展开更多
The changes in 5α-reductase (type 2 ) gene expression in the epi-didymis of puberty diabetic rats were studied by the Northern blot and Dotblot method. Rats were divided into 3 groups: the control group (C), thediabe...The changes in 5α-reductase (type 2 ) gene expression in the epi-didymis of puberty diabetic rats were studied by the Northern blot and Dotblot method. Rats were divided into 3 groups: the control group (C), thediabetic group (D), and the diabetic group with insulin treatment (DI).Results: The Northern blot intensity of the caput epididymis in Group D is展开更多
基金This work was supported by the National Natural Science Foundation of China （No. 30973015） and the Beijing Natural Science Foundation （No. 7122074） at Beijing Chaoyang Hospital, Capital Medical University to YNN.
文摘The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone （T） and dihydrotestosterone （DHT）. T is converted to DHT by 5-alpha reductase （5-AR） isozymes. Differential expression of 5-AR isozymes is observed in both human benign and malignant prostatic tissues. 5-AR inhibitors （5-ARI） are commonly used for the treatment of benign prostatic hyperplasia （BPH） and were once promoted as chemopreventive agents for prostate cancer （PCa）. This review discusses the role of the differential expression of 5-AR in the normal development of the human prostate and in the pathogenesis and progression of BPH and PCa.
基金Supported by National Natural Science Foundation of China, No.81070281
文摘Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase deficiency patients in China's Mainland diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis.A high proportion of atypical 3-oxo-4-bile acids in the urine indicated a deficiency in 4-3-oxosteroid 5β-reductase.All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient's parents.One patient exhibited compound heterozygous mutations:c.396C>A and c.722A>T,while the other was heterozygous for the mutation c.797G>A.Based on these mutations,a diagnosis of primary 4-3-oxosteroid 5β-reductase deficiency could be confirmed.With ursodeoxycholic acid treatment and fat-soluble vitamin supplements,liver function tests normalized rapidly,and the degree of hepatomegaly was markedly reduced in both patients.
文摘Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead to complications including acute urinary retention(AUR)and the need for BPH-related surgery.Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone(DHT),which is formed from testosterone under the influence of 5-alpha reductase.Thus,5-alpha reductase inhibitors(5-ARIs)effectively reduce the serum and intraprostatic concentration of DHT,causing an involution of prostate tissue.Two 5-ARIs are currently available for the treatment of BPHdfinasteride and dutasteride.Both have been demonstrated to decrease prostate volume,improve LUTS and urinary flow rates,which ultimately reduces the risk of AUR and BPH-related surgery.Therefore,either alone or in combination with other BPH medications,5-ARIs are a mainstay of BPH management.
基金This study was supported by"333 Talent Project " funds of Jiangsu Province in 1999.
文摘Objective. To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level.Methods. The plasma Hcy level was measured by capillary electrophoresis- ultraviolet detection and the gene polymorphism of N5, N10 - methylenetetrahydrofolate reductase (MTHFR) was studied with PCR - RFLP assay in 43 patients with cortical cerebral infarction and 42 healthy controls.Results. The plasma Hcy level of the patients ( 19. 3 + 6. 0 μ mol/L) was markedly higher than that of the controls (13.7 + 5.4 μ mol/L) ( t = 4. 16, P ＜ 0. 001). There are 3 genotypes, C/C, C/T and T/T, about base - variation of MTHFR gene at locus 677. The plasma Hcy level of the subjects with T/T genotype was higher than that of subjects with other genotypes. However, the frequencies of each genotype and allele were not significantly different between the patients and the controls.Conclusions. The elevated plasma Hcy level is a risk factor for atherothrombotic cerebral infarction, and is related to the C→T mutation at locus 677 of MTHFR gene.
基金This study was supported by the State Family Planning Committee
文摘Objectives To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organsMethods The expression level of 5α-reductase type 2 gene inhuman testis, epididymis and vas deferens tissues was determined by in situ hybridization using Digoxin labeled 5α-reductase type 2 cRNA probe.Results The brown granules of hybridizing signals distributed in the cytoplasm of Sertoli and Leydig cells of the testis, the principle cells of epididymis and the epithelial cells of vas deferens, but there was no positive signal in the nuclei of above-mentioned cells. No positive signal was observed in germ cells, basement of the testis, interstium of epididymis and basement, as well as smooth muscle of vas deferens. Conclusion This study confirmed that the 5α-reductase type 2 gene expressed in Sertoli , Leydig cells of the testis, and the principle cells of epididymis. The expression pattern of the gene in these cells in human was similar to that of rat and monkey. The presence of 5α-reductase type 2 gene in epithelial cells of the vas deferens suggested it might possess an important physiological role in human reproduction.
基金Project (No.30472036) supported by the National Natural Science Foundation of China
文摘Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigated on human leu-kemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to inves-tigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.
基金Supported by the National Natural Science Foundation of China,No.81570468 and No.81741056Jinshan Science and Technology Commission,No.2014-3-07
文摘BACKGROUND Disorders of primary bile acid synthesis may be life-threatening if undiagnosed,or not treated with primary bile acid replacement therapy. To date, there are few reports on the management and follow-up of patients with Δ4-3-oxosteroid 5β-reductase(AKR1 D1) deficiency. We hypothesized that a retrospective analysis of the responses to oral bile acid replacement therapy with chenodeoxycholic acid(CDCA) in patients with this bile acid synthesis disorder will increase our understanding of the disease progression and permit evaluation of this treatment regimen as an alternative to the Food and Drug Administration(FDA) approved drug cholic acid, which is currently unavailable in China.AIM To evaluate the therapeutic responses of patients with AKR1 D1 deficiency to oral bile acid therapy, specifically CDCA.METHODS Twelve patients with AKR1 D1 deficiency, confirmed by fast atom bombardment ionization-mass spectrometry analysis of urine and by gene sequencing for mutations in AKR1 D1, were treated with differing doses of CDCA or ursodeoxycholic acid(UDCA). The clinical and biochemical responses to therapy were monitored over a period ranging 0.5-6.4 years. Dose adjustment, to optimize the therapeutic dose, was based on changes in serum biochemistry parameters,notably liver function tests, and suppression of the urinary levels of atypical hepatotoxic 3-oxo-Δ4-bile acids measured by mass spectrometry.RESULTS Physical examination, serum biochemistry parameters, and sonographic findings improved in all 12 patients during bile acid therapy, except one who underwent liver transplantation. Urine bile acid analysis confirmed a significant reduction in atypical hepatotoxic 3-oxo-Δ4 bile acids concomitant with clinical and biochemical improvements in those patients treated with CDCA. UDCA was ineffective in down-regulating endogenous bile acid synthesis as evidenced from the inability to suppress the urinary excretion of atypical 3-oxo-Δ4-bile acids. The dose of CDCA required for optimal clinical and biochemical responses varied from 5.5-10 mg/kg per day among patients based on maximum suppression of the atypical bile acids and improvement in serum biochemistry parameters, and careful titration of the dose was necessary to avoid side effects from CDCA.CONCLUSION The primary bile acid CDCA is effective in treating AKR1 D1 deficiency but the therapeutic dose requires individualized optimization. UDCA is not recommended for long-term management.
基金The study was supported by the Chinese State Family Planning Commission
文摘To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organs. Methods: The expression level of 5ct-reductase type 2 gene in human testis, epididymis and vas deferens tissues was determined by in situ hybridization using a digoxin-labeled 5α-reductase type 2 cRNA probe. Results: The brown granules of hybridizing signals distributed in the cytoplasm of the Sertoli and Leydig cells of the testis, the principle cells of epididymis and the epithelial cells of vas deferens, but there was no positive signal in the nuclei of these cells. No positive signal was observed in the germ cells, basement of the testis, interstium of the epididymis and basement and the smooth muscle cells of vas deferens. Conclusion: This study confirmed that the 5a-reductase type 2 gene expressed in the Sertoli and Leydig cells of the testis and the principle cells of the epididymis. The expression pattem of the gene in these cells in the human was similar to that in the rat and monkey. The presence of 5α-reductase type 2 gene in the epithelial cells of the vas deferens suggests that it may play a physiological role in human reproduction. [Reprod Contracep (in English) 2002; 13: 67]
文摘Background: Patients with gross haematuria are sometimes found to have prostate cancer after clinical evaluation. The treatment of such haematuria could be very challenging. Use of a 5 alpha reductase inhibitor like dutasteride has been found helpful in bleeding prostate cancer patients if they have not undergone hormonal manipulation before they developed haematuria. Patients and Method: 26 patients with gross haematuria of prostatic origin who had histologic confirmation of adenocarcinoma of the prostate but who have not had chemical or surgical castration were randomized to receive daily dutasteride in addition to vigorous saline irrigation and antibiotics on one arm and vigorous saline irrigation and antibiotics only as control on the other arm. The time taken before haematuria resolved and the amount of irrigation fluid used were noted. Statistical analysis was done using SPSS. Student’s t-test and Kaplan Meier survival analysis were used to test various variables at 0.5 significant levels. Results: Of the 26 patients 12(46.2%) received 0.5 mg oral dutasteride in addition to saline irrigation while 14 (53.8%) received saline irrigation only. Haematuria stopped in all of 12 (100%) patients on dutasteride arm but on 12 (85.7%) of the 14 patients on the control arm. It took significantly shorter time and lesser volume of irrigation fluid before haematuria resolved in those treated with dutasteride than in those on the control arm. Conclusion: Dutasteride is effective in the control of acute haematuria in pre-androgen ablation prostate cancer patients.
文摘The changes in 5α-reductase (type 2 ) gene expression in the epi-didymis of puberty diabetic rats were studied by the Northern blot and Dotblot method. Rats were divided into 3 groups: the control group (C), thediabetic group (D), and the diabetic group with insulin treatment (DI).Results: The Northern blot intensity of the caput epididymis in Group D is
