Age-dependent MRI-detected lesions at early stages of transient global ischemia in rat brain

Although ischemic stroke has higher incidence and severity in aged than in young humans, the age factor is generally neglected in ischemia animal models. This study was aimed at comparing age-dependent effects at early stages of transient global cerebral ischemia (TGCI) in rats. TGCI was induced in two groups of rats (3–6 and 20–24 months old, respectively) by exposure to 15% oxygen and 15 min occlusion of the two common carotid arteries. Brains were analysed in vivo by MRI–apparent diffusion coefficient (ADC) and T₂ maps–at 1–3 h post-TGCI and in vitro by histochemical examination of triphenyltetrazolium chloride (TTC)-stained slices. At 1–3 h post-TGCI, a higher incidence of lesions was found in aged than in young rats especially in the hippocampus and cortex (occipital plus parietal) but not in the thalamus. The lesioned regions showed lower ADC values in aged than in younger rats. The most substantial ADC decreases were associated with enhanced spin-spin relaxation and lower TTC staining. The different responses of the two age groups support the use of aged animals for investigations on different ischemia models. Our model of brain ischemia appears appropriate for further studies including drug effects.     

新生牛肝活性肽的制备及其毒性检测

目的制备新生牛肝活性肽并评价其安全性。方法采用膜法分离制备新生牛肝活性肽。将3批制品于37～40℃,75%相对湿度条件下存放3个月,以多肽含量为指标观察其稳定性,并进行急性毒性试验、小鼠骨髓细胞微核试验、Ames试验、小鼠精子畸形试验和大鼠喂养试验。结果制备的3批新生牛肝活性肽存放3个月后,多肽含量无明显下降,质量稳定。小鼠和大鼠经口灌人大于20.0g/kg体重的新生牛肝活性肽,均无急性毒性。3种致突变试验均未显示出致突变性,大鼠喂养试验各项指标均未见明显毒性。结论新生牛肝活性肽未表现出明显毒性。     

Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial K_ATP (Sur1–Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.     

晚期产后出血的临床数据分析

目的根据产后子宫超声影像学数据建模,探讨产后出血情况的评测。方法通过经腹超声动态观测60例产妇的产后24h内及产后6周,测量采集子宫肌壁厚度、宫腔分离大小及子宫体长、宽、厚等数据,并记录产后24h内的出血量。结果经数据分析表明产后24h内的出血量与胎盘娩出后宫腔分离大小及产后6周的子宫复旧成正相关性(P<0.05),而与胎盘娩出后胎盘附着面宫壁厚度之间无明显的相关性(P>0.05)。结论监测产后的宫腔分离和子宫体复旧情况有助于动态分析产后出血的发展及转归,并为临床采取相应措施提供有力的依据。     

庆大霉素诱导急性肾损伤大鼠模型肾损伤分子-1的表达

目的探讨庆大霉素(Gentamycin,GM)诱导急性肾损伤大鼠模型肾损伤分子-1(Kidney injury molecule-1,KIM-1)的表达。方法建立GM诱导大鼠急性肾损伤模型;检测各组大鼠血、尿各项生化指标;取大鼠肾组织,进行病理组织学观察;ELISA法检测各组大鼠尿液中KIM-1的分泌;RT-PCR法检测各组大鼠肾组织KIM-1mRNA的表达;免疫组织化学SP法检测各组大鼠肾组织KIM-1、α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)的表达。结果与对照组比较,模型组大鼠血、尿各项生化指标及病理组织学观察均出现不同程度的病变;ELISA检测显示,大鼠尿液中KIM-1的含量显著增高(P<0.05);RT-PCR检测显示,肾组织KIM-1mRNA表达上调(P<0.05),且呈时间依赖性;免疫组化法检测显示,KIM-1表达量随肾损伤加重而显著升高,且呈时间依赖性。结论 KIM-1具有良好的敏感性和特异性,可作为GM所致肾小管损伤的早期诊断标志物。     

应用绵羊肝细胞生长因子治疗小鼠急性中毒性肝损伤的疗效

将小白鼠随机分组，用四氯化碳（CCl4）造成急性肝损伤模型，以sHGF进行治疗。结果sHGF治疗组的小鼠血清GPT水平比肝损伤组明显降低（P＜0．001）；肝细胞变性、坏死等病理损伤也比肝损伤组明显减轻，可见大量的新生肝细胞；肝细胞超微结构提示，治疗组肝细胞核及胞浆内各种细胞器的损伤程度，比肝损伤组明显减轻，尤以线粒体和粗面内质网更为明显。     

Cytotoxic activity to acute myeloid leukemia cells by Antp-TPR hybrid peptide targeting Hsp90

We previously reported that Antp-TPR hybrid peptide inhibited the interaction of Hsp90 with TPR2A and had selective cytotoxic activity discriminating between normal and cancer cells to induce cancer cell death. In this study, we investigated the cytotoxic activity of Antp-TPR peptide toward acute myeloid leukemia (AML) cells. It was demonstrated that Antp-TPR peptide induced AML cell death in cell lines such as U937, K562, THP-1, and HL-60 via activation of caspases 3 and 7, and disruption of mitochondrial membrane potential. Conversely, Antp-TPR peptide did not reduce the viability of normal cells including peripheral blood mononuclear cells (PBMCs), although both geldanamycin and 17-AAG, small-molecule inhibitors of Hsp90, mediated cytotoxicity to these normal cells at low concentrations. In addition, mutation analysis of TPR peptide demonstrated that the highly conserved amino acids Lys and Arg were critical to the cytotoxic activity. These results indicated that Antp-TPR hybrid peptide would provide potent and selective therapeutic options in the treatment of AML.     

心电图变化在急性胰腺炎患者诊断中的应用

目的评价急性胰腺炎患者的心电图变化对其预后及诊疗的价值。方法收集2001年1月—2006年1月在天津市南开医院确诊的新发急性胰腺炎患者(230例)的心电图,并进行回顾性分析,综合评价。结果230例急性胰腺炎患者,95例出现心电图异常(41.31%),其中:急性水肿性胰腺炎(MAP)174例,出现心电图异常为61例(35.06%);出血坏死性胰腺炎(SAP)56例,出现心电图异常为34例(60.71%)。结论心电图的变化对急性胰腺炎预后及诊疗均具有一定的临床意义。