FSH and bFGF stimulate the production of glutathione in cultured rat Sertoli cells

Migration of developing germ cells from the basal to the adluminal compartment of the seminiferous epithelium requires extensive tissue restructuring, resulting in the production of reactive oxygen species. Sertoli cells are involved in this process. Glutathione (GSH), produced by Sertoli cells, has an essential role in cell protection against oxidative stress. Intracellular GSH content is maintained by de novo synthesis, involving glutamate-cysteine ligase catalytic (GCLC) and modulatory (GCLM) subunits, and by recycling from oxidized GSH, catalysed by glutathione reductase (GR). To assess whether follicle-stimulating hormone (FSH) and basic fibroblast growth factor (bFGF) modulate GSH production in Sertoli cells by regulating the expression of GCLC, GCLM and/or GR, we performed in vitro studies using rat Sertoli cells in primary culture. FSH and bFGF stimulation increased Sertoli cell GSH levels after 24 h incubation. The simultaneous addition of FSH and bFGF did not produce any further effect. GCLM expression was upregulated by FSH and bFGF 6 h. At 24 h, only the FSH-mediated effect was still observed. FSH and bFGF also upregulated GR expression. In conclusion, our results show that FSH and bFGF increase GSH levels in Sertoli cells through stimulation of the de novo synthesis and recycling by upregulating GCLM and GR expression respectively. Therefore, protection of germ cells against oxidative stress seems to be regulated by hormones and germ cell-released growth factors capable of influencing the production of Sertoli cell GSH.     

Association of the methylenetetrahydrofolate reductase gene C677T polymorphism with the risk of male infertility: a meta-analysis

Several molecular epidemiological studies have been conducted to examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and male infertility susceptibility, but the results remain inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. In this meta-analysis, a total of 26 case–control studies including 5659 infertility cases and 5528 controls were selected to evaluate the possible association. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of association of C677T polymorphism with male infertility in the additive model, dominant model, recessive model and allele-frequency genetic model. In the overall analysis, the frequency of the 677T allele was significantly associated with male infertility susceptibility (OR?=?2.32, 95%CI?=?2.04–2.65 for TT vs. CC genotype; OR?=?1.09, 95%CI?=?1.00–1.19 for CT vs. CC genotype; OR?=?1.19, 95%CI?=?1.10–1.29 for CT/TT vs. CC genotype; OR?=?1.54, 95%CI?=?1.36–1.74 for TT vs. CC/TT genotype; OR?=?1.22, 95%CI?=?1.15–1.30 for T vs. C allele). A subgroup analysis of the subjects showed that significantly strong association between MTHFR C677T polymorphism and male infertility was present only in Asians, but not in Caucasians. Additionally, MTHFR C677T was associated with a significant increase in the risk of azoospermia in all genetic models. Meanwhile, no significantly increased risks of oligoasthenotertozoospermia (OAT) were found in most of the genetic models. In conclusion, this meta-analysis is in favor that the MTHFR C677T polymorphism is capable of causing male infertility susceptibility, especially in Asians and the subgroup of azoospermia.     

Impact of single‐dose nandrolone decanoate on gonadotropins,blood lipids and HMG CoA reductase in healthy men

The aim was to study the effect and time profile of a single dose of nandrolone decanoate (ND) on gonadotropins, blood lipids and HMG CoA reductase [3‐hydroxy‐3‐methyl‐glutaryl‐CoA reductase (HMGCR)] in healthy men. Eleven healthy male participants aged 29–46 years were given a single dose of 150 mg ND as an intramuscular dose of Deca Durabol®, Organon. Blood samples for sex hormones, lipids and HMGCR mRNA analysis were collected prior to ND administration day 0, 4 and 14. A significant suppression of luteinising hormone (LH) and follicle‐stimulating hormone (FSH) was seen after 4 days. Total testosterone and bioavailable testosterone level decreased significantly throughout the observed study period. A small but significant decrease in sexual hormone‐binding globulin (SHBG) was seen after 4 days but not after 14 days. Total serum (S)‐cholesterol and plasma (P)‐apolipoprotein B (ApoB) increased significantly after 14 days. In 80% of the individuals, the HMGCR mRNA level was increased 4 days after the ND administration. Our results show that a single dose of 150 mg ND increases (1) HMGCR mRNA expression, (2) total S‐cholesterol and (3) P‐ApoB level. The long‐term consequences on cardiovascular risk that may appear in users remain to be elucidated.     

Treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: sexual function

Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), and sexual dysfunction, are common, highly bothersome conditions in older men, and the prevalence of both disorders increases with age. Sexual dysfunction manifests mainly as erectile dysfunction (ED), ejaculatory disorders, or decreased libido/hypoactive sexual desire (HSD). Whereas both reduced rigidity and reduced ejaculate volume are highly prevalent in ageing men, reduced rigidity and pain on ejaculation are considered to be most bothersome. Sexual dysfunction is much more prevalent in patients with LUTS/BPH than in men with no LUTS/BPH, even after controlling for confounding variables such as age or comorbidities. Hence LUTS/BPH is considered an independent risk factor for sexual dysfunction. Whether this is because of a common underlying pathology, or whether the considerable bother associated with LUTS/BPH leads to reduced sexual functioning, remains to be elucidated. Despite a decline in the frequency of sexual intercourse, as well as in overall sexual functioning, most ageing men report regular sexual activity and consider their sex life as an important dimension of their quality of life (QoL). However, most patients with LUTS/BPH experience a negative effect of their LUTS on their sex life. Hence, treatment of LUTS/BPH should aim to at least maintain or, if possible, improve sexual function. Current medical treatment of LUTS/BPH consists of monotherapy with alpha1-adrenoceptor (AR) antagonists, 5alpha-reductase inhibitors (RIs) or a combination of these. Whereas 5alpha-RIs increase the risk of ED, ejaculatory disorders and HSD, alpha1-AR antagonists can induce ejaculatory disorders, but do not provoke HSD or ED. Combined therapy carries the cumulative risk for sexual dysfunction associated with either type of drug. As already indicated, ED is generally perceived as more bothersome than ejaculatory disorders. In addition, alpha1-AR antagonists slightly improve overall sexual function, possibly by increasing blood flow in the penis through alpha1-AR blockade and/or to an increased overall QoL from the relief of LUTS. It can be concluded that alpha1-AR antagonists constitute a first-line therapy for LUTS/BPH because they combine good treatment efficacy with very few adverse effects on sexual function.     

急性淋巴细胞白血病患儿MTHFR C677T基因多态性与大剂量甲氨蝶呤治疗后肝功能异常的相关性

目的：探讨急性淋巴细胞白血病（ALL）患儿亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性与大剂量甲氨蝶呤（HD-MTX）治疗后肝功能异常的相关性。方法：收集2017年10月至2020年3月温州医科大学附属第二医院育英儿童医院66例ALL患儿HD-MTX治疗的临床资料,检测MTHFR C677T的基因多态性,根据基因型将患儿分为野生型（CC）和突变型（CT+TT）,比较2组患儿经HD-MTX治疗后不良反应的发生率、肝功能指标PA、ALT、AST、AST/ALT、TP、ALB、LDH、GGT、TBIL、CHE以及48 h、72 h血药浓度的差异。结果：MTHFR C677T突变型与野生型相比肝功能异常的发生率更高（P＜0.05）,其中血清AST、ALT、CHE含量异常的患儿比例显著升高（P＜0.05）,其他肝功能指标差异无统计学意义（P＞0.05）。进一步分析不同基因型患儿HD-MTX血药浓度的差异,结果显示与野生型相比,突变型48 h、72 h血药浓度均升高（P＜0.05）。结论：MTHFR C677T突变型患儿HD-MTX治疗后,血清AST、ALT、CHE含量异常的患儿比例较高,检测MTHFR C677T基因型对预测HD-MTX治疗后肝功能异常有一定的临床应用价值。     

杜氏盐藻硝酸盐还原酶基因5'上游序列的克隆与序列分析

目的:克隆杜氏盐藻硝酸盐还原酶(NR)基因5'上游序列,并对其进行测序和序列分析.方法:提取杜氏盐藻基因组DNA,经过BamH I、EcoR I、Hind Ⅲ、Pst I、Sal Ⅰ及Xbal Ⅰ限制性内切酶分别酶切后,再与相应接头连接,分别构建盐藻步行基因组文库BL、EL、HL、PL、SL和XL.采用巢式(LA)-PCR方法,从上述步行基因组文库中扩增杜氏盐藻NR基因5'上游序列,克隆至pMD18-T,对酶切鉴定正确的克隆进行测序.结果:从HL里扩出约1 200 bp特异性片断,回收此片段并进行T载体克隆,对阳性克隆测序.该序列的3'端与已知NR基因cDNA 5'端序列完全一致.该序列含有多个与转录调控有关的保守序列(如CAAT-box和GAGA-box),含有与EBP、EFII、NF-E1、LV 等转录因子以及广谱激活剂Oct-1结合位点相似的核苷酸序列.结论:采用LA-PCR基因组步行方法,从已知cDNA 周围未知启动子或其他调控区域中克隆得到的NR基因的5'上游区序列,可能是一种新的杜氏盐藻启动子区序列.     

亚甲基四氢叶酸还原酶基因多态性与脑血管疾病的研究

目的　探讨N 亚甲基四氢叶酸还原酶 (MTHFR)基因多态性与脑血管疾病的关系。方法　利用聚合酶链反应和限制性片段长度多态性 (PCR RFLP)方法 ,检测了 72名健康人和 71名脑血管疾病患者MTHFR基因的6 77碱基多态性突变C→T情况 ,并加以对照分析。结果　脑血管疾病患者MTHFR基因突变型V6 77基因的频率 ,与正常健康人对比差异无显著意义 (P >0 .0 5 )。结论　MTHFR基因突变型V6 77基因可能是脑血管疾病的又一个遗传风险因子 ,但本研究结果显示与脑血管疾病的发病无关 ,是否为脑血管病的遗传风险因素有待进一步研究。     

洛伐他汀增加受白细胞介素-1β刺激的平滑肌细胞一氧化氮合成

目的　研究洛伐他汀对大鼠血管平滑肌合成一氧化氮的影响及其机理。方法　血管平滑肌取自SpragueDawley大鼠 (2 0 0 - 2 5 0g)的胸主动脉。大鼠血管平滑肌细胞培养液中亚硝酸盐水平由比色法测定。结果　洛伐他汀 (10 5mol/L)明显增加白细胞介素 1β(IL 1β ,10ng/mL)诱导的一氧化氮合成 ,呈时间 (0 - 2 4小时 )依赖型。外源性甲羟戊酸 (10 4 mol/L)和芒牛儿芒牛儿焦磷酸 (GGPP ,10 μmol/L)可完全逆转洛伐他汀的上述作用。而且用C3外酶 (2 5 - 5 0 μg/mL)抑制Rho可引起类似上述洛伐他汀的作用。结论　洛伐他汀上调受IL 1β刺激的大鼠SMCs合成NO ,其机理可能与Rho蛋白活性抑制有关     

Clinical Study of Jinmaitong Composita(复方筋脉通) on Diabetic Peripheral Neuropathy

Ｄｉａｂｅｔｉｃｐｅｒｉｐｈｅｒａｌｎｅｕｒｏｐａｔｈｙ（ＤＮ）ｉｓｏｎｅｏｆｔｈｅｍｏｓｔｃｏｍｍｏｎｄｉａｂｅｔｉｃｃｏｍｐｌｉｃａ ｔｉｏｎｓ．Ｉｔｓｐａｔｈｏｇｅｎｅｓｉｓｉｓｓｔｉｌｌｕｎｃｌｅａｒ,ｓｏｎｏｄｅｆｉｎｉｔｅｌｙｅｆｆｅｃｔｉｖｅｍｅｄｉｃｉｎｅｈａｓｂｅｅｎｆｏｕｎｄ．ＣｌｉｎｉｃａｌｓｙｍｐｔｏｍｓｏｆＤＮｃｏｕｌｄｂｅｓｉｇｎｉｆｉｃａｎｔｌｙｒｅｌｉｅｖｅｄｂｙＪｉｎｍａｉｔｏｎｇｃｏｍｐｏｓｉｔａ（ＪＭＴＣ,复方筋脉通）,ａｔｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅ…     

MTHFR基因C677T多态性与缺血性脑卒中关系的研究

目的：了解亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态性与中国人群缺血性脑卒中发病之间的关系。方法：利用PCR和分子杂交技术对北京地区294例缺血性脑卒中患者及280例无脑血管病对照者进行MTHFR基因C667T多态性检测和分析。结果：C677T多态性位点在两组人群中的分布均符合Hardy-Weinberg遗传平衡定律,但该位点基因型频率及等位基因频率在两组中分布无差异。结论：MTHFR基因C677T多态性不是中国人群缺血性脑卒中发病的遗传学危险因素。