Blood-brain barrier breakdown by cold injury. Polyamine signals mediate acute stimulation of endocytosis, vesicular transport, and microvillus formation in rat cerebral capillaries

Polyamines have been previously implicated in the mediation of blood-brain barrier breakdown induced by cryogenic injury (H Koenig, AD Goldstone, CY Lu, Biochem Biophys Res Commun 116:1039, 1983). We studied acute (less than 5 minute) changes in capillary ultrastructure, microvascular permeability, and the levels of polyamines and their rate regulating synthetic enzyme ornithine decarboxylase (ODC) in rat cerebral cortex after focal cold injury. Microvascular permeability was measured by relative transport of intravenously administered fluorescein. Capillary ultrastructure was studied by quantitative stereology and morphometry after intravenous administration of horseradish peroxidase. Focal cold injury induced a 2.5-, 3.8-, 1.7-, and 1.4-fold increase in the levels of ODC, putrescine, spermidine and spermine, and a 46-fold increase in fluorescein uptake in perilesional cortex. Few capillaries in control cortex contained endocytic pits or horseradish peroxidase-positive vesicles, whereas most capillaries near lesions showed these structures. Cryoinjury induced a 5-fold increase in the relative volume of microvilli and horseradish peroxidase vesicles, a 2.3-fold increase in area of luminal endocytic pits, and a 6.3-fold increase in area of abluminal exocytic pits. The ODC inhibitor alpha-difluoromethylornithine blocked the cryoinjury-induced changes in ODC, polyamines, fluorescein uptake, and capillary ultrastructure. Putrescine negated the effect of alpha-difluoromethylornithine or capillary ultrastructure, and was previously shown to nullify the alpha-difluoromethylornithine effects on polyamines and fluorescein permeability (cited above). These data link rapid changes in ODC and polyamines to blood-brain barrier breakdown, and suggest that the abnormal permeability is associated with an acute, polyamine-mediated stimulation of microvillus formation, endocytosis, and vesicular transport in capillary endothelium.     

Psychotropic drug utilization patterns in a metropolitan population

Summary Psychotropic drug intake by a random sample of citizens of the city of Munich aged 30–69 years has been assessed. A 1-week prevalence of 9.3% for all psychotropic drug users was found, benzodiazepines accounting for approximately two-thirds (6.6%) of the users. Two-thirds of drug users were women. Drug use in both sexes increased with age. The doses of benzodiazepines prescribed in most cases were less than 10 mg diazepam equivalent per day. Intake of benzodiazepines in combination with analgesics or alcohol (40 g/day) did not appear to represent a major problem. Multiple logistic regression analysis showed that the number of chronic diseases was the strongest predictor of benzodiazepine intake in men, whereas stress and age determined intake in women. Long-term use seemed to be relatively rare at 11% of all benzodiazepine users, so it was not considered to be a severe public health problem.     

Paradigm shift in gastrointestinal surgery − combating sarcopenia with prehabilitation: Multimodal review of clinical and scientific data

A growing body of evidence has demonstrated the prognostic significance of sarcopenia in surgical patients as an independent predictor of postoperative complications and outcomes. These included an increased risk of total complications, major complications, re-admissions, infections, severe infections, 30 d mortality, longer hospital stay and increased hospitalization expenditures. A program to enhance recovery after surgery was meant to address these complications; however, compliance to the program since its introduction has been less than ideal. Over the last decade, the concept of prehabilitation, or “pre-surgery rehabilitation”, has been discussed. The presurgical period represents a window of opportunity to boost and optimize the health of an individual, providing a compensatory “buffer” for the imminent reduction in physiological reserve post-surgery. Initial results have been promising. We review the literature to critically review the utility of prehabilitation, not just in the clinical realm, but also in the scientific realm, with a resource management point-of-view.     

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

胰腺切除术后出血的诊断与治疗：669例连续胰腺切除术分析

目的：分析胰腺切除术后出血（postpancreatectomy hemorrhage，PPH）的临床病程及预后。背景：PPH是最致命的胰腺术后并发症，但目前仍缺少其标准治疗规程。方法：1992年至2006年，对1524例施行胰腺手术的患者进行了前瞻性研究。根据以下指标进行PPH危险分级：PPH严重程度（轻度，即血红蛋白浓度下降〈3g／dL；重度，即血红蛋白浓度下降〉3g／dL），PPH出现时间（早期，即术后1～5天；晚期，术后第6天），合并胰瘘，肠道内或肠道外出血表现以及存在“复杂的”血管病理变化（腐蚀、假性动脉瘤）。     

Internet网上细胞凋亡研究的信息资源及其利用

0　引言　 Internet网上含有丰富的信息资源 ,科研人员可以通过 Internet网了解其所研究领域的最新发展动态 ,获取全面和系统的科研信息 ,有利于进行学术交流[1 ] .然而网上信息浩如烟海 ,当检索某一专门领域的资料时 ,有时无从下手 .我们在科研实践中对 Internet网上主要的细胞凋亡研究信息资源及其查找方法进行了归纳 .1　细胞凋亡专业网站1. 1　 The Cell death society (http:/ / www.celldeath-apoptosis.org)　为美国细胞死亡学会主办 ,概括了细胞凋亡和程序性细胞死亡研究的各个领域 ,包括与细胞凋亡有关的各种疾病 .可以免费注册…     

Comparison of active and cancer registry-based follow-up for breast cancer in a prospective cohort study

The authors compared the relative effectiveness of two distinct follow-up designs in prospective cohort studies--the active approach, based on direct contact with study subjects, and the passive approach, based on record linkages with population-based cancer registries--utilizing available information from the New York University Women's Health Study (WHS) and the New York State Cancer Registry (NYSCR). The analyses were limited to breast cancer cases identified during the period 1985-1992, for which follow-up was considered reasonably complete by both the WHS and the NYSCR. Among 12,947 cohort members who reported a New York State address, 303 pathologically confirmed cases were identified through active follow-up and 284 through record linkage. Sixty-three percent of cancers were identified by both sources, 21% by the WHS only, and 16% by the NYSCR only. The agreement was appreciably better for invasive cancers. The percentage of cases identified only by the NYSCR was increased among subjects whose active follow-up was incomplete, as well as among nonwhites, obese patients, and parous patients. This suggests that relying on either type of follow-up alone may introduce certain biases in evaluating risk factors for breast cancer. Combining both approaches appears to be a better strategy in prospective cohort studies.