利福昔明治疗急性感染性腹泻的疗效观察

目的：利福昔明治疗急性感染性腹泻的疗效及安全性。方法：将50例急性感染性腹泻患者随机分成两组，每组各25例。治疗组给予口服利福昔明200mg3次／日，对照组给予环丙沙星200mg3／日口服，用药3天。观察药物的止泻天数，大便常规复常率及临床症状缓解，进行疗效评价。结果：利福昔明的止泻率、大便常规复常率及临床症状缓解与环丙沙星相比无显著性差异（P〉0．05）。结论：利福昔明治疗急性感染性腹泻具有明显疗效。未见不良反应。     

Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis

In addition to their well characterized role in allergic inflammation, recent data confirm that mast cells play a more extensive role in a variety of immune responses. However, their contribution to autoimmune and neurologic disease processes has not been investigated. Experimental allergic encephalomyelitis (EAE) and its human disease counterpart, multiple sclerosis, are considered to be CD4(+) T cell-mediated autoimmune diseases affecting the central nervous system. Several lines of indirect evidence suggest that mast cells could also play a role in the pathogenesis of both the human and murine disease. Using a myelin oligodendrocyte glycoprotein (MOG)-induced model of acute EAE, we show that mast cell-deficient W/W(v) mice exhibit significantly reduced disease incidence, delayed disease onset, and decreased mean clinical scores when compared with their wild-type congenic littermates. No differences were observed in MOG-specific T and B cell responses between the two groups, indicating that a global T or B cell defect is not present in W/W(v) animals. Reconstitution of the mast cell population in W/W(v) mice restores induction of early and severe disease to wild-type levels, suggesting that mast cells are critical for the full manifestation of disease. These data provide a new mechanism for immune destruction in EAE and indicate that mast cells play a broader role in neurologic inflammation.     

Virus inactivation of plasma-derived proteins by pasteurization in the presence of guanidine hydrochloride

BACKGROUND: Viruses, among them parvovirus B19 and other small, nonenveloped viruses, may be present in human blood and may contaminate plasma-derived therapeutics. Efficient inactivation or removal of such viruses, especially parvoviruses, represents a current problem and corresponding technologies are under investigation. In this report, such a technology is described. STUDY DESIGN AND METHODS: A recently developed pasteurization of human apolipoprotein A-I (apoA-I), which is performed at 60 degrees C for 10 hours in the presence of guanidine hydrochloride (GdnHCl), was validated by using a series of model viruses, including members of the families parvoviridae and picornaviridae. The model viruses were spiked into the apoA-I- and GdnHCl-containing solutions, and virus inactivation was evaluated by infectivity assays in cell cultures. The mechanism of virus inactivation was studied by virus sedimentation analysis using the picornavirus model. RESULTS: All viruses tested were inactivated to levels below the limit of detection, although different inactivation kinetics were obtained for the different viruses. The mechanism of virus inactivation by this pasteurization was disassembly of the virus particles into single proteins or small noninfectious viral subunits. CONCLUSION: The pasteurization validated in this report has the potential to inactivate a wide range of transfusion-relevant viruses including parvoviruses and picornaviruses.     

Silver nanoparticles at sublethal concentrations disrupt cytoskeleton and neurite dynamics in cultured adult neural stem cells

Silver nanoparticles (AgNPs) have potent antimicrobial properties at concentrations far below those that cause cytotoxic and genotoxic effects in eukaryotic cells. This property has resulted in the widespread use of AgNPs in consumer products, leading to environmental exposures at sub-lethal levels through ingestion and inhalation. Although the toxicity of AgNPs has been well characterized, effects of environmentally relevant exposures have not been extensively investigated in spite of studies that suggest accumulation of silver in tissues, including brain. To assess the sublethal effects of AgNPs on neural cell function, we used cultured SVZ-NSCs, a model of neurogenesis and neural cells. Throughout life, neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricles proliferate and migrate via the rostral migratory stream to the olfactory bulb. Once there, they complete differentiation into neurons and glia and integrate into existing circuits. This process of neurogenesis is tightly regulated, and is considered a part of healthy brain function. We found that 1.0 μg/mL AgNP exposure in cultured differentiating NSCs induced the formation of f-actin inclusions, indicating a disruption of actin function. These inclusions did not co-localize with AgNPs, and therefore do not represent sequestered nanoparticles. Further, AgNP exposure led to a reduction in neurite extension and branching in live cells, cytoskeleton-mediated processes vital to neurogenesis. We conclude that AgNPs at sublethal concentrations disrupt actin dynamics in SVZ-NSCs, and that an associated disruption in neurogenesis may contribute to documented deficits in brain function following AgNP exposure.     

Hypothalamic‐Pituitary‐Adrenal Axis Functioning in Huntington's Disease and its Association with Depressive Symptoms and Suicidality

Hyperactivity of the hypothalamic‐pituitary‐adrenal (HPA) axis has been reported in Huntington's disease (HD). In non‐HD populations, alterations in HPA axis activity have been associated with depression and suicidality. The present study aims to compare HPA axis activity between HD mutation carriers and controls, and examine its association with depressive symptoms and suicidality. To this end, salivary cortisol concentrations at seven time points, as well as depressive symptoms and suicidality, were assessed in 49 pre‐motor, 102 motor symptomatic mutation carriers and 55 controls, at baseline and follow‐up combined. Differences in parameters of HPA axis activity between these three groups, and their associations with depressive symptoms and suicidality in HD mutation carriers, were analysed using multilevel regression analyses. There were no differences in parameters of HPA axis activity between mutation carriers and controls, whereas pre‐motor symptomatic mutation carriers had a significantly higher area under the curve to the increase (AUC_i) compared to motor symptomatic mutation carriers. In the entire HD cohort, HPA axis activity was not associated with depressive symptoms or suicidality. After stratifying mutation carriers into pre‐motor, early and advanced disease stages, β values differed between these groups. Remarkably, a higher AUC_i was significantly associated with depressive symptoms in pre‐motor and early disease stage mutation carriers, with a reverse nonsignificant association in advanced disease stage mutation carriers. The lower AUC_i in motor symptomatic mutation carriers and the varying associations with depressive symptoms and suicidality in pre‐motor, early and advanced disease stages could possibly be explained by exhaustion of the HPA axis after prolonged stress‐induced HPA axis hyperactivity and deserves further longitudinal study.     

P2X7受体和肾脏疾病

P2X7受体是三磷酸腺苷(ATP)门控阳离子通道受体,是嘌呤受体P2X家族受体亚型之一。P2X7受体信号通路与IL-1β、IL-6、COX-2等多种炎症因子的生成和释放相关,在多种疾病的发病过程中起到了至关重要的作用。目前以此受体为治疗靶点的P2X7受体拮抗剂已进入临床试验阶段,表现出良好的安全性和疗效。最新研究表明P2X7受体与多种肾脏疾病有关,P2X7受体拮抗剂具有潜在的肾脏疾病治疗作用。本文综述P2X7受体在肾脏疾病中的作用及其可能的作用机制,以期为肾脏疾病治疗的新靶点和新策略提供理论依据。     

Kyasanur Forest Disease Outbreak and Vaccination Strategy,Shimoga District,India, 2013–2014

We investigated a Kyasanur Forest disease outbreak in Karnataka, India during December 2013–April 2014. Surveillance and retrospective study indicated low vaccine coverage, low vaccine effectiveness, and spread of disease to areas beyond those selected for vaccination and to age groups not targeted for vaccination. To control disease, vaccination strategies need to be reviewed.     

Social network and census tract-level influences on substance use among emerging adult males: An activity spaces approach

Social network and area level characteristics have been linked to substance use. We used snowball sampling to recruit 90 predominantly African American emerging adult men who provided typical locations visited (n=510). We used generalized estimating equations to examine social network and area level predictors of substance use. Lower social network quality was associated with days of marijuana use (B=−0.0037, p<0.0001) and problem alcohol use (B=−0.0050, p=0.0181). The influence of area characteristics on substance use differed between risky and non-risky spaces. Peer and area influences are important for substance use among men, and may differ for high and low risk places.