Heredity mode of genetic polymorphism in aldehyde oxidase activity in Donryu strain rats

Donryu strain rats show genetic polymorphisms in the aldehyde oxidase gene, resulting in the phenotypic expression of ultrarapid metabolizers with homozygous nucleotide sequences (337G, 2604C), extensive metabolizers with heterozygous nucleotide sequences (377G/A, 2604C/T), and poor metabolizers with homozygous nucleotide sequences (377A, 2604T). In the mating experiments the ratio of the number of ultrarapid metabolizers, extensive metabolizers, and poor metabolizers rats in the F1 generation from the heterozygous F0 extensive metabolizers male and female rats was roughly 0.6 : 1.5 : 1, and the ratio converged to approximately 1 : 2 : 1 in the F2 generation from the heterozygous F1 extensive metabolizers male and female rats. On the contrary, all the F2 generation from homozygous F1 ultrarapid metabolizers male and female rats or from homozygous F1 poor metabolizers male and female rats had the ultrarapid metabolizers or the poor metabolizers genotypes and phenotypes. The genotypes completely agreed with the phenotypes in all individuals of F0, F1, and F2 generations. The results indicate that the genetic polymorphism of aldehyde oxidase in Donryu strain rats obeys Mendelian heredity. The reason for a low ratio of the ultrarapid metabolizers rats in the commercially available Donryu strain rats?—?not more than several per cent?—?compared with the ratio expected from the Mendelian rule is unknown.     

Short‐term intravenous insulin infusion is associated with reduced expression of NADPH oxidase p47phox subunit in monocytes from type 2 diabetes patients

Hyperglycemia is a well‐known inducing factor of oxidative stress through activation of NADPH oxidase. In addition to its plasma glucose lowering effect, insulin may also have antioxidant activity and was shown to downregulate NADPH oxidase expression in vitro. In this study, we show that a short‐term (3‐day) intravenous insulin infusion in patients with type 2 diabetes induces normalization of both glycemia and mRNA expression of circulating monocyte p47^phox subunit.     

Spatial memory extinction differentially affects dorsal and ventral hippocampal metabolic activity and associated functional brain networks

Previous studies showed the involvement of brain regions associated with both spatial learning and associative learning in spatial memory extinction, although the specific role of the dorsal and ventral hippocampus and the extended hippocampal system including the mammillary body in the process is still controversial. The present study aimed to identify the involvement of the dorsal and ventral hippocampus, together with cortical regions, the amygdaloid nuclei, and the mammillary bodies in the extinction of a spatial memory task. To address these issues, quantitative cytochrome c oxidase histochemistry was applied as a metabolic brain mapping method. Rats were trained in a reference memory task using the Morris water maze, followed by an extinction procedure of the previously acquired memory task. Results show that rats learned successfully the spatial memory task as shown by the progressive decrease in measured latencies to reach the escape platform and the results obtained in the probe test. Spatial memory was subsequently extinguished as shown by the descending preference for the previously reinforced location. A control naïve group was added to ensure that brain metabolic changes were specifically related with performance in the spatial memory extinction task. Extinction of the original spatial learning task significantly modified the metabolic activity in the dorsal and ventral hippocampus, the amygdala and the mammillary bodies. Moreover, the ventral hippocampus, the lateral mammillary body and the retrosplenial cortex were differentially recruited in the spatial memory extinction task, as shown by group differences in brain metabolic networks. These findings provide new insights on the brain regions and functional brain networks underlying spatial memory, and specifically spatial memory extinction. © 2016 Wiley Periodicals, Inc.     

Expression dynamics of NADPH oxidases during early zebrafish development

Nicotinamide dinucleotide phosphate oxidases (NOX) control various cellular signaling cascades. In the nervous system, there is recent evidence that NOX‐derived reactive oxygen species (ROS) regulate neurite outgrowth, regeneration, and stem cell proliferation; however, a comprehensive NOX gene expression analysis is missing for all major model systems. Zebrafish embryos provide an excellent model system to study neurodevelopment and regeneration because they develop quickly and are well suited for in vivo imaging and molecular approaches. Although the sequences of five NOX genes (nox1, nox2/cybb, nox4, nox5, and duox) have been identified in the zebrafish genome, nothing is known about their expression pattern. Here, we used quantitative polymerase chain reaction combined with in situ hybridization to develop a catalog of nox1, nox2/cybb, nox5, and duox expression in zebrafish during early nervous system development from 12 to 48 hours post fertilization. We found that expression levels of nox1, nox5, and duox are dynamic during the first 2 days of development, whereas nox2/cybb levels remain remarkably stable. By sectioning in situ hybridized embryos, we found a pattern of broad and overlapping NOX isoform expression at 1 and 1.5 days post fertilization. After 2 days of development, a few brain regions displayed increased NOX expression levels. Collectively, these results represent the first comprehensive analysis of NOX gene expression in the zebrafish and will provide a basis for future studies aimed at determining the functions of NOX enzymes in neurodevelopment and regeneration. J. Comp. Neurol. 524:2130–2141, 2016. © 2015 Wiley Periodicals, Inc.     

女性压力性尿失禁盆底赖氨酰氧化酶表达的研究

目的分析压力性尿失禁(SUI)女性盆底组织中赖氨酰氧化酶(LOX)的表达及血清Cu2 水平,探讨LOX在女性SUI发病中的作用。方法选取因SUI而行尿控手术治疗的患者25例,以同期因妇科良性疾病行全子宫切除术的患者25例作为对照。术前抽取空腹血采用原子吸收法测定Cu2 水平,术中取患者子宫主骶韧带,行HE染色及VG染色观察韧带中胶原纤维形态,免疫组化法观察LOX在组织中的分布,Western blotting免疫印迹法检测LOX在组织中的表达。结果SUI患者主骶韧带中胶原纤维排列松散,LOX主要在成纤维细胞胞质中表达,其表达水平明显低于对照组(P<0.01);血清Cu2 水平两组比较无显著性差异(P>0.05)。结论SUI患者盆底组织中LOX含量减少可能是SUI发病过程中的重要环节。     

Changes in muscle morphology in dialysis patients after 6 months of aerobic exercise training.

BACKGROUND: In the present study we investigated the effect of a 6-month aerobic exercise programme on the morphology of the gastrocnemius muscle of end-stage renal disease (ESRD) patients. METHODS: Twenty-four ESRD patients volunteered to participate in the training programme and underwent muscle biopsy before training. Eighteen patients completed the training programme of whom nine agreed to a post-training biopsy (one woman and eight men, mean age 56 +/- 15 years). Data are presented for the nine subjects who were biopsied before (PRE) and after training (POST) and separately for the 15 subjects for whom we only have a biopsy before training (cross-sectional group). RESULTS: There were no significant differences (P > 0.05) in fibre type distribution or myosin heavy chain (MyHC) expression between the cross-sectional and PRE/POST groups. The mean cross-section fibre area after training (POST) increased by 46% compared with the PRE training status (P < 0.01). The proportion of atrophic fibres decreased significantly after training in type I, IIa and IIx fibre populations (from 51 to 15%, 58 to 21% and 62 to 32%, respectively). Significant differences were also found in capillary contact per fibre (CC/F), with the muscle having 24% (P < 0.05) more CC/F compared with the PRE training status. No significant differences in cytochrome c oxidase concentration were found between the groups. CONCLUSIONS: In conclusion, exercise appeared to be beneficial in renal rehabilitation by correcting the fibre atrophy, increasing the cross-section fibre area and improving the capillarization in the skeletal muscle of renal failure patients.     

生长激素应用于全身炎症反应综合征时二胺氧化酶及内毒素变化的临床意义

目的 探讨生长激素应用于全身炎症反应综合征时二胺氧化酶(DAO)和内毒索(ET)水平的变化及其与肠粘膜屏障损伤的关系。方法 将146例严重感染性疾病合并全身炎症反应综合征思考分为非手术组和手术组两组，再分别将此两组随机分为治疗组及对照组，于治疗前及治疗后1周监测血浆DA0和ET水平。结果 治疗组血浆DA0及ET水平在治疗后较治疗前下降，且差异有显著性意义(P＜0．05，P＜0．01)。结论 生长激素对严重感染性疾病合并全身炎症反应综合征患者的肠粘膜屏障具有一定的保护作用。     

过氧化氢导致肠上皮细胞线粒体DNA损伤及其编码蛋白活性变化

目的：探讨过氧化氢（H2O2）对肠上皮细胞线粒体DNA（mtDNA）结构与功能的损伤作用。方法：肠上皮细胞株（SW－480），采用4mmol/L H2O2处理细胞后进行线粒体DNA的提取，对细胞色素C氧化酶（COXⅠ、COXⅡ、COXⅢ）基因进行聚合酶链反应（PCR）扩增，并将PCR产物进行直接测序；同时于该时相点测定酶活性。结果：细胞色素C氧化酶COXⅠ从6803－6848出现大范围的点突变及7027出现点突变（TC），在7329（CG）、7341（TG）、7352（GA）出现点突变，在7337出现缺失突变（缺T）；COXⅡ序列在8219－8260段出现大范围的点突变；H2O2可导致mtDNA突变基因所编码的细胞色素C氧化酶活性明显下降，结论：H2O2可明显损伤mtDNA编码的细胞色素C氧化酶基因，这种损伤作用最终导致其编码的酶蛋白活性明显下降。