Proteomic characterization of HIV-modulated membrane receptors, kinases and signaling proteins involved in novel angiogenic pathways

Background  

Kaposi's sarcoma (KS), hemangioma, and other angioproliferative diseases are highly prevalent in HIV-infected individuals. While KS is etiologically linked to the human herpesvirus-8 (HHV8) infection, HIV-patients without HHV-8 and those infected with unrelated viruses also develop angiopathies. Further, HIV-Tat can activate protein-tyrosine-kinase (PTK-activity) of the vascular endothelial growth factor receptor involved in stimulating angiogenic processes. However, Tat by itself or HHV8-genes alone cannot induce angiogenesis in vivo unless specific proteins/enzymes are produced synchronously by different cell-types. We therefore tested a hypothesis that chronic HIV-replication in non-endothelial cells may produce novel factors that provoke angiogenic pathways.     

Attenuation of pulmonary hypertension secondary to left ventricular dysfunction in the rat by Rho‐kinase inhibitor fasudil

Pulmonary hypertension (PH) in left ventricular dysfunction is attributable not only to backward failure of the left ventricle, but also to increased pulmonary vascular resistance (PVR) in some patients. Recently, Rho‐kinase has been known as a potent growth stimulator and mediator of vasoconstriction, and Rho‐kinase inhibitors could ameliorate PVR, little is known about the role of Rho‐kinase in left ventricular dysfunction‐induced PH. We utilized the ascending aortic‐banded rat and assessed the effect of Rho‐kinase inhibitor fasudil on the development of PH secondary to left ventricular dysfunction. Subsequently, in rats subjected to aortic banding for 6 weeks, there were increases in mean pulmonary arterial pressure, pulmonary arteriolar medial thickness, active RhoA, Rho‐kinase II, Rho‐kinase activity, endothelial nitric oxide synthase (eNOS) and endothelin‐1(ET‐1) concomitant with decreased levels in NO and cGMP in the lung. Treatment with fasudil at a dose of 30 mg/kg/day from days 1 to 28 or from days 29 to 42 decreased the mean pulmonary arterial pressure by 57% and 56%, right ventricular hypertrophy by 31% and 30%, pulmonary arteriolar medial thickness by 50% and 50%, and pulmonary expression of Rho‐kinase II by 41% and 28%, respectively, as well as augmented pulmonary expression of eNOS by 16% and 31% and NO by 50% and 76%, respectively, when compared with the vehicle controls. In conclusion, these results suggest that inhibition of Rho‐kinase may provide therapeutic potential for preventing and attenuating the development of PH in left ventricular dysfunction. Further translational study in human is needed to substantiate the findings. Pediatr Pulmonol. 2011; 46:45–59. © 2010 Wiley‐Liss, Inc.     

Effect of hyperthermia and anoxia on glucocorticoid and mineralocorticoid receptor expression in neonatal rat hippocampus

Brief periods of neonatal asphyxia are frequently observed. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia. The hippocampus contains the highest concentration of both mineralocorticoid (MR) and glucocorticoid (GR) receptors and the balance between MR/GR activation influences cell birth and death. MR occupation appears to promote prosurvival actions, while GR overactivation favours neurodegeneration. It has been widely recognized that core body temperature is a critical determinant of the severity of hypoxic–ischemic brain injury; indeed, hyperthermia exacerbates the degree of damage. Therefore, the aim of the present investigation was to study the effect of elevated body temperature in newborn rats under control conditions or during neonatal exposure to a critical anoxia, on changes of MR and GR mRNA expression in the rat hippocampus. 2-day-old rats were exposed to anoxia in 100% nitrogen atmosphere. Rectal temperature was kept at 33 °C (typical for the rat neonates), or elevated to a level typical for febrile (39 °C) adults. Control rats were exposed to atmospheric air under the respective thermal conditions. The changes in MR and GR mRNA expression in hippocampus were examined 24 h after exposure. Our data show that hyperthermia with or without added anoxia, causes induction of MR mRNA expression in neonatal rat hippocampus without any effect on GR mRNA expression. We suggest this elevation of MR plays an important role in modulating the survival of neurons in the injured hippocampus.     

Drug delivery into the skin by degradable particles

Recently, it was demonstrated that particles could be utilized as carrier systems for drugs into the hair follicles. In the present study, a two-component drug delivery system is presented consisting of degradable particles loaded with fluorescein isothiocyanate and a separate protease formulation for degradation. The particles were applied alone, 30 min previous to the protease application and simultaneously with the protease onto porcine skin. Subsequently, biopsies were removed, and the penetration depths of the particles were analyzed using laser scanning microscopy.The obtained results demonstrate that the particles alone achieved a penetration depth of around 900 μm. Similar results were obtained for the successive application of particles and protease, whereas a release of the fluorescent dye was only observed in the upper 250 μm corresponding to the penetration depth of the protease. In the case of the simultaneous application, the particles were partly dissolved before application, leading to a reduced particle size and diminished penetration depth.The results revealed that degradable particles are a promising tool for drug delivery into the skin.     

内镜治疗与药物治疗黏附血凝块的消化性溃疡出血的疗效对比

目的:探讨内镜治疗与药物治疗黏附血凝块的消化性溃疡出血的疗效.方法:将黏附血凝块的消化性溃疡出血患者88例随机分为两组,对照组44例实施药物治疗,观察组44例实施内镜治疗,比较两组治疗效果.结果:治疗后,两组Blatchford评分、Rockall评分降低(P0.05),日常生活能力评分、生活质量评分增加(P0.05).观察组Blatchford评分、Rockall评分、治疗后再出血率、转外科手术率低于对照组(P0.05),日常生活能力评分、生活质量评分、治疗总有效率高于对照组(P0.05),止血时间早于对照组(P0.05),住院时间少于对照组(P0.05),住院费用多于对照组(P0.05).结论:与药物治疗相比,内镜治疗黏附血凝块的消化性溃疡出血的疗效更佳,值得临床推广使用.     

南昌市新建建设项目二次供水系统预防性卫生学评价分析

目的对江西省南昌市28家新建建设项目二次供水系统预防性卫生学评价结果进行分析,找出新建二次供水系统在设计中存在的问题,为保障二次供水安全提供技术依据。方法依据国家二次供水系统相关卫生法规和卫生标准,通过检查表法对28家新建建设项目的设计方案、可行性研究报告和卫生专篇等设计文件进行分析评价,找出可能存在的健康危害因素。结果全市28个新建二次供水系统中,选址、水源水质、水箱容积、水箱材质的合格率为100%;所有生活水箱均未与消防水箱共用且生活水箱内部无死水区;67.86%的设施管道未与非饮用水管道连接;53.57%的生活水箱的位置、入孔、爬梯、管道设计合理;89.29%的排气管、溢水管、排水管设有防虫网罩;64.29%的系统设置有防止水污染的设备;7.14%的系统设置有消毒器或预留安装消毒器的位置;所有输配水设备均无法提供具有省级以上卫生行政部门颁发的"产品卫生安全评价报告"。结论目前南昌市新建建设项目的二次供水系统在设计阶段均存在一些问题,卫生行政部门应该严格把关,要求业主严格按照相关卫生规范对设计进行修改,以免对今后二次供水系统的运行管理留下安全隐患。