血管性认知障碍的分子机制和遗传学

随着对血管性认知障碍概念认识的加深以及对其发病机制的深入研究,近年来有关血管性认知障碍的研究报道日益增多。文章就血管性认知障碍的分子机制和遗传学等方面做了综述。     

化学发光分析法研究珍珠卟啉类化合物抗自由基的作用

本文采用黄嘌呤-黄嘌呤氧化酶体系,研究了珍珠总卟啉成分(PFC)及其分离后产物对超氧阴离子(O(1/2))的作用。半数抑制发光率(IC_(50))分别是:PFC为170μg/ml、PFC-A为145μg/ml,PFC-B为124μg/ml、PFC-C为151μg/ml、PFC-D为706μg/ml和PCM-1为64μg/ml。实验结果提示PFC及其分离后产物为珍珠抗衰老作用的有效成分,其作用机理可能是抑制机体的自由基反应。     

氧自由基与家兔心肌缺血—再灌注后发生心律失常的关系

目的探讨再灌注性心律失常的发生机制.方法用家兔制成缺血-再灌注模型,测定缺血-再灌注心肌的丙二醛含量,同时在实验过程中监测心电图.再灌注性心律失常的严重程度用心律失常评分判定.结果缺血-再灌注心肌的丙二醛明显高于对照组(76.25±42.92vs 30.55±10.65,P＜0.05),且与心律失常评分明显正相关(r=0.808,P＜0.01).结论心肌缺血-再灌注后大量氧自由基产生,可能是导致再灌注性心律失常的原因之一.     

高氧液对家兔心肌缺血再灌注损伤的保护作用

目的 :观察高氧液对家兔心肌缺血再灌注损伤的保护作用。方法 :结扎兔冠状动脉左室支中段 ,40 min后解除结扎行再灌注 ,制成心肌急性缺血再灌注模型。于缺血前 10 min、再灌注前 10 m in,分别静滴平衡盐液、高氧平衡盐液 ,观察在急性缺血及再灌注状态下心电图、血浆肌酸磷酸激酶 （CK）、丙二醛 （MDA）和超氧化物岐化酶 （SOD）的变化。结果 :高氧平衡盐液能使抬高的心电图 S- T段明显下降 ,缺血再灌注心肌 CK活性明显降低 ;并能保护SOD的活性 ,降低脂质过氧化反应代谢产物 MDA的含量。结论 :高氧平衡盐液对家兔在体心肌缺血再灌注损伤具有明显的保护作用。     

儿茶素对拟衰老大鼠耳蜗氧自由基生成的影响

【目的】观察儿茶素对衰老大鼠动物模型耳蜗氧自由基生成的影响,初步探讨儿茶素对听觉老化的保护效应及其机制。【方法】通过腹腔注射D-半乳糖（D-gal）建立大鼠衰老动物模型,以腹腔注射生理盐水为阴性对照组,检测其听觉脑干诱发电位（ABR）明确衰老动物听力减退情况,检测大鼠耳蜗组织丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性;并观察胃内灌注儿茶素后衰老动物模型上述指标的变化。【结果】衰老模型组大鼠与对照组大鼠相比较,ABR阈值增高,耳蜗组织中MDA含量明显增高,SOD活性明显降低（P〈0.05）;儿茶素保护组大鼠耳蜗组织中MDA含量和SOD活性水平较对照组无变化（P〉0.05）,而与衰老模型组相比却逆转上述指标变化,并能提高听力（P〈0.05）。【结论】氧自由基及其引发的脂质过氧化反应参与了听觉老化过程,儿茶素可能通过提高SOD活性、减少MDA生成发挥清除自由基抗氧化作用,从而改善听觉功能。     

Hormones and health outcomes in aging men

Increasing age is a predictor of ill-health and mortality related to cardiovascular disease and to frailty, a syndrome characterized by deterioration of multiple organ systems leading to loss of physiological reserve, diminished capacity to cope with stressors, and increased risk of disability and death. As men grow older, their levels of testosterone decline while the prevalence of ill-health increases. Observational studies have linked lower testosterone levels with cardiovascular disease and mortality in middle-aged and older men. More recently, lower testosterone has been shown to predict reduced sexual activity and frailty in aging men. Additional studies are needed to determine whether lower testosterone is a biomarker or a potentially treatable risk factor for poorer health outcomes in older men. During aging, the response of the pituitary–thyroid axis alters to manifest higher thyrotropin levels. The presences of subclinical hypo- and hyper-thyroidism predict adverse cardiovascular outcomes. Newer results indicate that in euthyroid older men, differences in free thyroxine levels within the normal range predict specific health outcomes including frailty. Clarification of the roles of endogenous testosterone and thyroxine in the genesis of ill-health during male aging offers the prospect of future intervention to preserve health and well-being in this growing population.     

Comparison of direct sequencing and Invader assay for Y93H mutation and response to interferon‐free therapy in hepatitis C virus genotype 1b

Background and Aim

Virologic failure of interferon‐free therapy has been associated with Y93H mutation in the non‐structure 5A region in hepatitis C virus (HCV) genotype 1b, and screening is recommended. A simple assay based on Q‐Invader technology was developed for Y93H mutant screening to reduce cost and effort. The present study sought to compare two methods of detection of Y93H mutation and to evaluate the effect of Y93H mutation on response to interferon‐free therapy.

Methods

Y93H mutation was examined in 258 patients with HCV genotype 1b using both direct sequencing analysis and the polymerase chain reaction (PCR)‐Invader assay. Daclatasvir and asunaprevir or ledipasvir and sofosbuvir therapy was administered to 205 patients whose sustained virological responses (SVR) were checked.

Results

Hepatitis C virus was detected in 232 of 258 patients by direct sequencing and in 236 of 258 patients by the PCR‐Invader assay. Forty of 231 cases were defined as Y93 mutation by direct sequencing, and 46 of 236 cases were defined as Y93 mutation by the PCR‐Invader assay. SVR of patients who were Y93H by direct sequencing, Y93H by the PCR‐Invader assay, and Y93H by both methods was 62.5%, 82.4%, and 50%, respectively.

Conclusions

The sensitivity of the PCR‐Invader assay was similar to that of direct sequencing analysis; however, the PCR‐Invader assay had a better ability to detect minor strains. Combination of the two assays would improve prediction of the response to daclatasvir and asunaprevir, but Y93H mutation had little effect on SVR in ledipasvir and sofosbuvir therapy.