RNAi targeting µ-calpain increases neuron survival and preserves hippocampal function after global brain ischemia

The calpain family of cysteine proteases has a well-established causal role in neuronal cell death following acute brain injury. However, the relative contribution of calpain isoforms has not been determined in in vivo models. Identification of the calpain isoform responsible for neuronal injury is particularly important given the differential role of calpain isoforms in normal physiology. This study evaluates the role of m-calpain and µ-calpain in an in vivo model of global brain ischemia. Adeno-associated viral vectors expressing short hairpin RNAs targeting the catalytic subunits of µ- or m-calpain were used to knockdown expression of the targeted isoforms in adult rat hippocampal CA1 pyramidal neurons. Knockdown of µ-calpain, but not m-calpain, prevented calpain activity 72 h after 6-min transient forebrain ischemia, increased long-term survival and protected hippocampal electrophysiological function. These findings represent the first in vivo evidence that reducing expression of an individual calpain isoform can decrease post-ischemic neuronal death and preserve hippocampal function.     

血压对Valsalva动作反应在肺动脉高压中的应用

Objective To use a simple bedside technique to verify the pathophysiological mechanism of pulmonary hypertension (PH) in different races. Method The Valsalva maneuver (VM) was performed in patients referred to a specialty PH clinic. The blood pressure response of patients to VM was in different fashions. The blood pressure (BP) was measured by using cuff and stethoscope. When the cuff was inflated to 15 mmHg above the systolic pressure, sound could be heard by auscultation during VM and when the cuff was deflated the sound disappeared over 3 heart beats which was considered as abnormal BP response, and less than 3 heart beats defined as normal BP response. The right heart catheterization in patients with PH as a part of the standard evaluation. Results This study included 84 patients with a mean age of (63 ± 16) years. Those with abnormal BP response to VM had higher pulmonary artery wedge pressure (PAWP) [(22.5±6.6) vs. (11.9±4.3) mmHg, P ＜0.0001] and lower pulmonary vascular resistance [(5.8 ± 4.0) vs. (8.1 ± 4.6 ) WU, P = 0.01]. Blood pressure response to VM did not correlate with mean pulmonary artery (PA) pressure [(46.2 ± 9.9) vs. (43.4 ±10.4) mmHg, P =0.20] or cardiac index (both 2.4 ± 0.6 L/min/m2). The abnormal BP response to VM had high sensitivity (89.4%), specificity (86.1%) and accuracy (86.9%) for determining PAWP＞ 15 mmHg.Conclusions BP response to Valsalva maneuver provides important information about left heart filling pressures in patients with PH.     

左卡尼汀改善非糖尿病维持性血液透析患者胰岛素抵抗

目的探讨左卡尼汀对非糖尿病维持性血液透析(HD)患者胰岛素抵抗的影响。方法41例非糖尿病HD患者为研究对象,20例应用左卡尼汀治疗,另21例作为对照组。治疗方法为静脉注射左卡尼汀(雷卡)1.0g、每次透析结束后静脉注射,观察时间6月。观察指标包括空腹血糖、胰岛素、胰岛素抵抗指数(HOMA-IR)和炎症标志物血C反应蛋白(CRP)。结果左卡尼汀治疗6月后,治疗组和对照组空腹血糖无变化,而在治疗组空腹胰岛素和HOMA-IR明显下降,下降差值分别为-10(-35,20)vs-1(-15,20),P=0.03;(-2.8±0.6)vs(-0.4±0.5),P0.01。血CRP在治疗组明显下降,下降差值为(-5.9±1.2)vs(-0.1±0.1)(对照组),P0.01。相关分析显示,血CRP与空腹胰岛素(r=0.56,P0.01)和HOMA-IR(r=0.46,P0.05)呈正相关。结论静脉注射左卡尼汀治疗有效改善非糖尿病HD患者胰岛素抵抗,改善的胰岛素抵抗与改善炎症状态有关,我们的结果对HD患者胰岛素抵抗的治疗提供新的治疗思路。     

肝脏纤维化指数对原发性肝癌患者术后生存状况的影响

目的探讨肝脏纤维化指数对原发性肝癌患者外科治疗后生存状况的影响。方法对2009年7月至2011年10月行肝切除的76例肝癌患者资料进行回顾性分析,根据手术前肝纤维化指数的高低将患者分为高指数组(40例)及低指数组(36例)。采用SPSS 21.0统计软件进行统计分析。患者肿瘤复发情况,生存率用卡方检验;平均生存期用均数±标准差表示,使用t检验;生存分析和比较用log rank法进行单因素分析,以P0.05视为差异有统计学意义。结果两组患者分别在肿瘤数目、最大肿瘤直径、血管侵犯情况、静脉栓塞情况及切缘阳性情况上,低指数组均低于高指数组,差异有统计学意义(P0.05);低指数组患者复发率为16.7%显著低于高指数组67.5%;低指数组患者生存时间(44.2±12.3)个月长于高指数组(21.3±8.7)个月;低指数组患者1、3、5年的生存率分别为94.4%、52.8%及47.2%均显著高于高指数组的72.5%、42.5%及22.5%,差异均有统计学意义(P0.05);回归分析显示:肝纤维化指数、甲胎蛋白含量及术前肿瘤数是肝癌手术后复发的独立危险因素(P0.05)。结论肝纤维化指数对于行肝切除术的肝癌患者的预后具有一定预测意义,可以在临床推广使用。     

Sexual Transmission of Cyst-Forming Coccidian Parasites with Complex Life Cycles

Purpose of Review

Cyst-forming heteroxenous Apicomplexan parasites are important parasites of both humans and animals. Here, we discuss currently available evidence of possible sexual transmission of these parasites.

Recent Findings

Seven genera of Apicomplexans are known to have multi-mode, multi-host life cycles. Prior studies have examined the possibility of sexual transmission in three of these genera: Besnoitia, Neospora, and Toxoplasma. There is extensive evidence of sexual transmission of Toxoplasma in several nonhuman animals. However, evidence for the sexual transmission in humans remains equivocal. Sexual transmission of Besnoitia and Neospora has remained contentious given the small number of inconclusive reports.

Summary

It is important to determine if Toxoplasma is a sexually transmitted infection in humans, due to the clinical implications of Toxoplasma in immune-deficient humans and its potential effects on pregnancy. Additionally, this class of parasites can serve as useful perturbation systems to understand the development of virulence and breach of the blood-testes barrier.

     

Areca nut‐induced micronuclei and cytokinesis failure in Chinese hamster ovary cells is related to reactive oxygen species production and actin filament deregulation

Epidemiological studies have shown a strong association between environmental exposure to betel quid (BQ) and oral cancer. Areca nut (AN), an ingredient of BQ, contains genotoxic and mutagenic compounds. In this study, we found that AN extract (ANE) inhibited the growth of Chinese hamster ovary cells (CHO‐K1) in a dose‐ and time‐dependent manner. Intracellular reactive oxygen species (ROS) levels and micronuclei (MN) frequency were significantly increased following ANE treatment in CHO‐K1 cells. Addition of catalase markedly inhibited ANE‐induced MN formation, indicating that ANE‐induced genotoxicity was correlated with intracellular H₂O₂. Incubation of CHO‐K1 cells with ANE (400–800 μg/ml) for 24 hr caused G2/M arrest, and prolonged exposure to ANE (800 μg/ml) significantly induced cell death. Surprisingly, ANE itself caused cytokinesis failure and subsequent increase in binucleated cell formation. Coexposure to catalase (2,000 U/ml) and ANE (800 μg/ml) reduced the generation of binucleated cells, indicating that ANE‐induced cytokinesis failure was associated with oxidative stress. Following prolonged exposure to ANE, an accumulation of hyperploid/aneuploid cells concomitant with bi‐, micro‐ or multinucleated cells was found. In summary, our results demonstrate that ANE exposure to CHO‐K1 cells caused increased MN frequency, G2/M arrest, cytokinesis failure, and an accumulation of hyperploid/aneuploid cells. These events are associated with an increase in intracellular H₂O₂ level and actin filament disorganization. Environ. Mol. Mutagen., 2009. © 2009 Wiley‐Liss, Inc.     

心肌细胞凋亡不参与小鼠胚胎心脏流出道的缩短机制研究

目的探讨小鼠胚胎心脏流出道缩短的机制。方法用抗α-横纹肌肌动蛋白(α-SCA)抗体、抗活性Caspase-3(Cas-3)抗体对25只胎龄10～12 d(E10～12)小鼠胚胎心脏连续切片进行免疫组织化学过氧化物酶-抗过氧化物酶复合体(PAP)法染色。结果小鼠胚胎心脏流出道绝对长度于胎龄第12天8:00后开始缩短,至20:00流出道远端心肌界已退至半月瓣水平。在流出道缩短前及缩短过程中,流出道心肌细胞未见Cas-3阳性细胞。结论同鸡胚一样,心肌细胞凋亡不是小鼠胚胎心脏流出道缩短的主要机制。