线粒体脑肌病相关的线粒体DNA突变

<正>线粒体DNA(mtDNA)或核DNA突变可造成线粒体结构形态或(和)功能发生异常,由此导致的以神经肌肉系统(脑和肌肉组织)受累为主的多系统疾病,称为线粒体脑肌病。mtDNA突变是导致神经肌肉系统发生病变的重要原因之一。早在上世纪70年代,有研究者在患有脑肌病儿童的肌肉组织中首次发现了线粒体形态的畸变和呼吸链功能的缺陷,提示线粒体功能异常可能与该疾病有关[1]。1988年,Holt等[2]首先报     

弱精症患者精子线粒体的相关研究分析

选取2013年5月~2015年3月本院收治的30例弱精症患者,采用对照的临床试验设计方法,应用反转录-聚合酶链反应监测线粒体细胞色素氧化酶亚基I和线粒体细胞色素氧化酶亚基II的表达水平,采用流式细胞术检测两组精子的凋亡率、线粒体膜电位和钙离子含量。与正常精子相比,线粒体细胞色素氧化酶亚基I和线粒体细胞色素氧化酶亚基II在弱精症患者中的表达明显降低(P0.05),凋亡率在弱精症患者中显著增加(P0.05),线粒体膜电位显著降低(P0.05)。钙离子含量在两组中无显著差异(P0.05)。人精子线粒体细胞色素氧化酶亚基I和线粒体细胞色素氧化酶亚基II表达降低,凋亡率增加和线粒体膜电位降低是精子活力下降的重要原因。     

线粒体基因突变机制及其相关疾病的研究进展

线粒体是位于真核细胞浆中的一些小体(0.5～1um)，由内膜、外膜、基质和膜间隙构成。分子量1万以下的小分子物质可透过外膜，而内膜对许多物质具有选择性，内膜的这种相对的不通透性对于合成三磷酸腺苷(ATP)时所需维持的质子梯度很重要。线粒体间质、内膜、外膜、内外膜间空隙都储存多种酶或酶群。基质食线粒体DNA(mitochon     

药物性耳聋相关线粒体12S rRNA突变

  目的  探讨极重度非综合征性耳聋患者线粒体DNA(mitochondrial DNA, mtDNA)1555A > G和1494C > T突变情况。  方法  选取黑龙江省佳木斯地区聋哑学校学生和北京协和医院门诊散发的极重度感音神经性耳聋患者共208例作为研究对象, 使用基因芯片方法和限制性内切酶法对其mtDNA 1555和1494两个位点进行检测, 并用直接测序的方法进行验证。  结果  208例患者中共发现1555A > G突变者10例, 该突变的携带率为4.81%;未发现1494C > T突变。  结论  mtDNA 1555A > G突变在极重度非综合征性耳聋患者中阳性率较高, 而在汉族人群中1494C > T突变较为罕见。     

Bid蛋白在内质网和线粒体相关的凋亡过程中的作用

目的 研究Bid蛋白在内质网和线粒体相关的凋亡过程中的作用。方法 以高三尖杉酯碱（HHT）诱导人骨髓增生异常综合征（MDS）细胞系MUTZ-1细胞凋亡，用流式细胞术检测细胞凋亡率，RT—PCR及Westernblot法检测线粒体和内质网凋亡途径的相关基因及蛋白表达，激光共聚焦显微镜观察用药前后钙离子浓度和线粒体膜电位的改变以及凋亡相关蛋白Bid的转位。结果 0．05μg／ml HHT作用后4h胞质内Ca^2＋浓度增高，12h达高峰，其后开始下降。HHT作用后线粒体膜电位持续下降。内质网应激相关因子基因及蛋白表达增强，12h达到高峰，其后开始下降。激光共聚焦显微镜观察发现Bid蛋白用药前位于内质网，用药12h后转位至线粒体。结论 HHT可以诱导MDS细胞凋亡，内质网和线粒体相关的凋亡途径在其中发挥了重要的作用，Bid蛋白可能是两种凋亡途径的交叉点。     

高血压合并血管性痴呆的相关危险因素分析

目的 探讨高血压( primary hypertension,PH)合并血管性痴呆(vascular dementia,VD)发生的危险因素.方法 于我院就诊的PH患者388例,分为两组,PH合并VD患者96例为病例组,PH不合并VD患者292例为对照组.全部病例测量身高、体质量、收缩压、舒张压,检测甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL C)、空腹胰岛素(FINS)、空腹葡萄糖(FPG)等生化指标.结果 TG、TC、HDL-C、LDL-C、FINS、胰岛素抵抗指数(IRI)等因素在病例组与对照组之间的差异有统计学意义(均P＜0.05);Logistic回归分析显示:脑血管病史、TC≥6.17 mmol/L、IRI≥2.8 mU/L是预测PH合并VD的主要指标,OR值分别是4.284、3.459、7.471,OR值95％ CI分别为2.254～6.474、2.103～5.622、5.843～9.555,均P＜0.05.结论 脑血管病病史、TC≥6.17 mmol/L、IRI≥2.8 mU/L是PH合并VD的主要危险因素.     

抗线粒体抗体与相关临床疾病

抗线粒体抗体（AMA）是针对线粒体两层生物膜蛋白的抗体。多种组织（肝、肾、胃、心脏）细胞内都含有线粒体膜蛋白，但该抗体主要在原发性胆汁性肝硬化（PBC）患者中特征性出现，另外它还可在其他一些自身免疫疾病患者体内检测到，抗体在这些疾病中作用尚不明确。本文拟对抗线粒体抗体与相关临床疾病的关系作一综述。[第一段]     

抗线粒体抗体与相关临床疾病

抗线粒体抗体(AMA)是针对线粒体两层生物膜蛋白的抗体.多种组织(肝、肾、胃、心脏)细胞内都含有线粒体膜蛋白,但该抗体主要在原发性胆汁性肝硬化(PBC)患者中特征性出现,另外它还可在其他一些自身免疫疾病患者体内检测到,抗体在这些疾病中作用尚不明确.……     

非酒精性脂肪性肝病线粒体相关的分子通路

近年来,以肥胖、糖尿病、脂代谢异常为代表的代谢性疾病在全球范围内不断增加,非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)的发病率也在逐年增加。NAFLD是一种肝脏病理生理变化的综合征,从肝脏脂质沉积到肝脏脂肪变性、纤维化、肝硬化,最终可发展为肝细胞癌。NAFLD疾病谱主要包括非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)及其相关的肝硬化和肝细胞癌。NAFLD的发病主要     

甲泼尼龙对脊髓损伤线粒体凋亡相关基因表达的影响

目的:探讨甲泼尼龙(MP)对脊髓损伤(SCI)早期线粒体凋亡相关基因表达的作用。方法:6只日本大耳兔随机分为两组:模型组和药物组(每组3只),行L4椎板切除后采用Allen法建立SCI模型。药物组于造模后2h按人-兔等效剂量给予MP冲击治疗。造模后8h处死分别获取损伤区长约8mm的脊髓组织Trizol法提取总RNA,经质检合格后采用Agilent兔子表达谱芯片进行检测。采用GeneSpring11.0软件,绘制箱线图和火山图;以P<0.05且FC≥2为差异表达基因的筛选条件,本文针对线粒体凋亡相关基因进行分析。结果:成功建立SCI的动物模型。抽提的6个RNA样品的2100 RIN>7.0并且28S/18S>0.7;重复探针点信号CV值<15%。在线粒体凋亡相关基因中VDAC5P、SLC25A5药物组和模型组比较呈现显著的差异性表达。VDAC5P和SLC25A5构成线粒体膜转化孔(PTP)的主要成分,二者构象的改变可引起线粒体转化孔的高通透状态。结论:MP能对线粒体凋亡相关基因的表达进行调节,可能是其发挥神经保护的机制之一。     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

Systematic Reviews Published in the January 2011 Issue of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The January 2011 issue (first quarterly DVD for 2011) contains 4515 complete reviews, 1985 protocols for reviews in production, and 13,521 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 641,000 randomized controlled trials, and 14,018 cited papers in the Cochrane methodology register. The health technology assessment database contains over 9300 citations. One hundred and seven new reviews have been published in the last 3 months, of which five have potential relevance for practitioners in pain and palliative medicine.     

Prospects for the control of neglected tropical diseases by mass drug administration

The prospects for the control of neglected tropical diseases, including soil-transmitted helminthiasis, shistosomiasis, lymphatic filariasis, onchocerciasis and trachoma, through mass drug administration, are exemplified by the elimination of the trachoma as a public-health problem in Morocco. In spite of this and other striking successes, mass drug administration programs are faced with major challenges resulting from suboptimal coverage and lack of efficacy. At current suboptimal coverage rates, programs may need prolongation for an extended period, increasing costs and undermining sustainability. Community participation through health education and information appears to be crucial to improve coverage and to achieve sustainability. Implementation of complementary measures, such as vector control, improved hygiene and environmental sanitation, are important to further control transmission and to prevent re-emergence of the infection and, again, may only be achieved effectively through community-based initiatives. To reduce costs and to relieve pressure on the health system, combining neglected tropical disease programs in areas where diseases coexist and integration with existing control programs for malaria, tuberculosis and HIV/AIDS is advocated. The risk of developing drug resistance is of particular concern in view of the lack of alternative drugs, and reduced treatment efficacy due to emerging resistance is evident for the soil-transmitted helminths and onchocerciasis. Given the risk for the development of drug resistance and the need for a high degree of participation, close attention should be paid to the monitoring of the coverage and efficacy of the different program components.     

Bacterial meningitis: an update of new treatment options

The outcome of bacterial meningitis critically depends on the rapid initiation of bactericidal antibiotic therapy and adequate management of septic shock. In community-acquired meningitis, the choice of an optimum initial empirical antibiotic regimen depends on the regional resistance patterns. Pathogens resistant to antibacterials prevail in nosocomial bacterial meningitis. Dexamethasone is recommended as adjunctive therapy for community-acquired meningitis in developed countries. In comatose patients, aggressive measures to lower intracranial pressure <20 mmHg (in particular, external ventriculostomy, osmotherapy and temporary hyperventilation) were effective in a case–control study. Although many experimental approaches were protective in animal models, none of them has been proven effective in patients. Antibiotics, which are bactericidal but do not lyse bacteria, and inhibitors of matrix metalloproteinases or complement factor C5 appear the most promising therapeutic options. At present, vaccination is the most efficient method to reduce disease burden. Palmitoylethanolamide appears promising to enhance the resistance of the brain to infections.     

Prise en charge des entorses externes de cheville : étude clinique préliminaire sur l’efficacité du dispositif Myolux™

Ankle sprains are the most common injury of the musculoskeletal system and are associated with significant societal and economic impacts. It has been proven that classical therapeutic strategies may not be effective in preventing recurrent injuries: the recurrence rates reported in the literature can reach 73%. In order to provide an effective rehabilitation solution, a destabilizing orthosis was developed. This device is equipped with a mechanical articulator reproducing the subtalar mechanics and placed under the heel. In this paper, we present the main results of a preliminary clinical study conducted between 2004 and 2007. All subjects included in this study were treated with the abovementioned orthosis during 10 rehabilitation sessions of 30 minutes each. Data show a relatively low recurrence rate of 12% for the overall population. Moreover, it's of primary importance to note that this satisfactory ratio is largely reduced (3% of recurrence rate) for the 29 patients who performed one training session per month after the 10th initial rehabilitation sessions. Hence, the destabilizing orthosis appears to be an effective solution to prevent recurrent ankle sprains. However, joint protection requires long-term and regular training sessions. This result has motivated the development of a similar device allowing patients to perform training sessions at home. Finally, data obtained in this study are promising awaiting the final results of the comparative, multicentric and independent clinical trials currently managed by the Hospices Civils de Lyon.     

Imaging choices in occult hip fracture

Background: Hip fracture is a common injury, with an incidence rate of > 250,000 per year in the United States. Diagnosis is particularly important due to the high dependence on the integrity of the hip in the daily life of most people. Objectives: In this article we review the literature focused on hip fracture detection and discuss advantages and limitations of each major imaging modality. Discussion: Plain radiographs are usually sufficient for diagnosis as they are at least 90% sensitive for hip fracture. However, in the 3–4% of Emergency Department (ED) patients having hip X-ray studies who harbor an occult hip fracture, the Emergency Physician must choose among several methods, each with intrinsic limitations, for further evaluation. These methods include computed tomography, scintigraphy, and magnetic resonance imaging. Conclusion: We present an evidence-based algorithm for the evaluation of a patient suspected to have an occult hip fracture in the ED. Also outlined are future directions for research to distinguish more effective techniques for identifying occult hip fractures.     

Systematic Reviews Published in the April 2012 Issue of the Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD but monthly online. The April 2012 issue (second DVD for 2012) contains 5045 complete reviews, 2182 protocols for reviews in production, and 17,084 short summaries of systematic reviews published in the general medical literature. In addition, there are citations of 674,000 randomized controlled trials, and 15,400 cited papers in the Cochrane methodology register. The health technology assessment database contains just over 11,000 citations. One hundred and seventeen new reviews have been published in the last 3 months of which 12 have potential relevance for practitioners in pain and palliative medicine. The impact factor of the Cochrane Library stands at 6.186. Readers are encouraged to access the full report for any articles of interest as only a brief commentary is provided.     

Platelets,thrombosis, coagulation,and atherosclerosis

When I first got the invitation to join a medical delegation going to Moldova, I thought for a moment that our destination was the fictional country in the old Marx Brothers movie Duck Soup. On further checking, it turns out that entertaining place was called Freedonia. I now know that Moldova is indeed a real country, bordered on the west by Romania and on the other three sides by the Ukraine. It is a proud country, rich with traditions, and its people are warm, giving, eager to learn ways to improve their healthcare system, and deeply appreciative of our attempts to help them in the task.