Reactivations of Latent Viral Infections Are Associated with an Increased Thr389 p70S6k Phosphorylation in Peripheral Lymphocytes of Renal Transplant Recipients

Reactivations of BK polyoma virus (BKPyV) and human cytomegalovirus (HCMV) frequently cause life- and graft-threatening complications after renal transplantation. Both viruses are dependent on the mTOR pathway for replication. In this study we investigated the association of viral replication with mTOR activity in peripheral lymphocytes of renal transplant recipients. A flow-cytometry based assay for the measurement of Thr389 p70S6k phosphorylation, a surrogate marker of the mTOR pathway was established. Forty-eight adult renal transplant recipients were recruited to measure p70S6k activity in their peripheral blood mononuclear cells. This data set in conjunction with information concerning previous replication of BKPyV and HCMV was examined for correlations. Episodes of BKPyV replication were significantly associated with increased p70S6k phosphorylation in CD4⁺ T lymphocytes (p = 0.0002) and CD19⁺ B lymphocytes (p = 0.0073). HCMV infection of patients with a high-risk HCMV constellation of donor and recipient (D+/R−) was associated with increased p70S6k phosphorylation in CD19⁺ B lymphocytes (p = 0.0325). These associations were found to be independent of the trough levels of the immunosuppressive drugs. Conclusion: P70S6k phosphorylation in peripheral lymphocytes is associated with BKPyV reactivations and to a lesser extent with HCMV infections in renal transplant recipients.     

Caspase-cleaved tau accumulation in neurodegenerative diseases associated with tau and α-synuclein pathology

Alzheimers disease (AD), Picks disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (DLB) are diseases associated with the accumulation of tau or -synuclein. In AD, -amyloid (A)-associated caspase activation and cleavage of tau at Asp⁴²¹ (Tau) may be an early step in neurofibrillary tangle (NFT) formation. To examine whether Tau accumulates in other diseases not characterized by extracellular A accumulation, we examined PiD, PSP, and CBD cases in comparison to those without extensive tau accumulation including frontotemporal lobar degeneration without Pick bodies (FTLD) and control cases. Additionally, we studied Tau accumulation in DLB cases associated with intracellular -synuclein. Tau was observed in all disease cases except non-PiD FTLD and controls. These results demonstrate that the accumulation of Tau may represent a common pathway associated with abnormal accumulation of intracellular tau or -synuclein and may be relatively less dependent on the extracellular accumulation of A in non-AD dementias.     

Randomised primary health center based interventions to improve the diagnosis and treatment of undifferentiated fever and dengue in Vietnam

Background  

Fever is a common reason for attending primary health facilities in Vietnam. Response of health care providers to patients with fever commonly consists of making a presumptive diagnosis and proposing corresponding treatment. In Vietnam, where malaria was brought under control, viral infections, notably dengue, are the main causes of undifferentiated fever but they are often misdiagnosed and inappropriately treated with antibiotics.     

白细胞介素1及白细胞介素8在心肌缺血再灌注损伤中的动态演变及药物干预效果

目的:在心肌缺血再灌注损伤中,炎症细胞因子参与其过程的多个环节。实验拟验证白细胞介素1、白细胞介素8因子在此过程中的动态变化,并分析其与药物干预的关系。方法:实验于2005-10/2006-11在新乡医学院形态学实验室完成。①实验分组:选择健康Wistar成年大鼠70只,按随机数字表法分为3组:对照组(n=10)、模型组(n=30)和药物组(n=30)。后两组又分为缺血0.5h,再灌注2,4,8,12,24h6个时相点,每个时相点5只。对照组只设12h一个时相点作为总体对照。②实验方法:大鼠麻醉后,药物组在右股静脉注入甲泼尼龙(30mg/kg),对照组及模型组注入生理盐水(0.75mg/kg)。采用夹闭左冠状动脉前降支建立大鼠心肌缺血再灌注损伤模型。对照组只开胸不夹闭。③实验评估:在各时相点观察各组大鼠缺血再灌注后的心肌细胞改变;血清学检测白细胞介素1、白细胞介素8因子的动态表达。结果:①模型组缺血再灌注12h炎细胞浸润最显著,药物组炎细胞呈散在浸润。②模型组和药物组白细胞介素1、白细胞介素8因子质量浓度明显高于对照组[缺血再灌注8h为例,白细胞介素1分别为(99.21±14.37),(85.77±11.31),(21.87±10.32)ng/L;白细胞介素8分别为(794.85±24.07),(536.95±19.72),(103.94±11.59)ng/L,P<0.05],峰值分别在缺血再灌注4,8h;同时相点药物组白细胞介素1、白细胞介素8因子质量浓度明显低于模型组(P<0.05)。结论:白细胞介素1和白细胞介素8因子在心肌缺血再灌注损伤的炎症反应中发挥着重要作用;甲泼尼龙对缺血再灌注损伤心肌有保护作用。     

亮度知觉效应与视觉加工方式研究

目的:利用微持续与微间隔时间技术,设计了两组相关的实验,对亮度知觉效应和视觉加工方式进行探讨。方法:实验于2006-06在中南民族大学物理楼脑认知实验室进行,所有受试者为年龄20～25岁的大学本科生,视力(含矫正视力)正常,均为右利手。①实验1:被试为10名(男5名,女5名),要求被试分别对n屏依次呈现的亮块的明度和n 1屏依次呈现的亮块的明度进行比较(n≤17)。②实验2:被试为28名(男13名,女15名),实验涉及两个刺激物,先呈现的刺激物由左右两个大小相同、亮度不同的亮块a和b组成,后呈现的刺激物把a和b的位置进行对调,当这两个刺激物依次显示时,要求被试报告左右两边的明度是否存在差异,存在何种差异。结果:①实验1∶1≤n≤3时,100%的被试报告,n 1屏的明度大于n屏的亮度,即n 1>n;4≤n≤10时,70%～90%的被试报告n 1>n;n>10时,50%～70%的被试报告n 1>n;随着n值的增加明度差异也在减小,大约在n=17时达到稳定,n屏和n 1屏的明度区别将很难被看出。②实验2:在L(a)b a,随着a和b的亮度差异减小,左右两边呈现的明度越相似;同样当L(a)相似文献   

Selected Nonpharmacological Therapies for Chronic Pain: The Therapeutic Use of the Placebo Effect

Chronic pain is a common problem requiring a multidisciplinary approach. Nursing can offer diverse therapies complementary to the medical-surgical approach. Guidelines for practice and challenges for research are outlined for selected nonpharmacological chronic pain therapies. This article discusses the placebo effect, which is common to all therapies. Placebos can therapeutically empower patients to stimulate their psychophysiologic self-regulation abilities. Effects, theories, ethics, and therapeutic methods of stimulating the placebo effect are explored.     

Engineering and characterization of the long‐acting glucagon‐like peptide‐1 analogue LY2189265, an Fc fusion protein

Background

Glucagon‐like peptide‐1 (GLP‐1) receptor agonists are novel agents for type 2 diabetes treatment, offering glucose‐dependent insulinotropic effects, reduced glucagonemia and a neutral bodyweight or weight‐reducing profile. However, a short half‐life (minutes), secondary to rapid inactivation by dipeptidyl peptidase‐IV (DPP‐IV) and excretion, limits the therapeutic potential of the native GLP‐1 hormone. Recently, the GLP‐1 receptor agonist exenatide injected subcutaneously twice daily established a novel therapy class. Developing long‐acting and efficacious GLP‐1 analogues represents a pivotal research goal. We developed a GLP‐1 immunoglobulin G (IgG4) Fc fusion protein (LY2189265) with extended pharmacokinetics and activity.

Methods

In vitro and in vivo activity of LY2189265 was characterized in rodent and primate cell systems and animal models.

Results

LY2189265 retained full receptor activity in vitro and elicited insulinotropic activity in islets similar to native peptide. Half‐life in rats and cynomolgus monkeys was 1.5–2 days, and serum immunoreactivity representing active compound persisted > 6 days. In rats, LY2189265 enhanced insulin responses during graded glucose infusion 24 h after one dose. LY2189265 increased glucose tolerance in diabetic mice after one dose and lowered weight and delayed hyperglycaemia when administered twice weekly for 4 weeks. In monkeys, LY2189265 significantly increased glucose‐dependent insulin secretion for up to a week after one dose, retained efficacy when administered subchronically (once weekly for 4 weeks) and was well tolerated.

Conclusions

LY2189265 retains the effects of GLP‐1 with increased half‐life and efficacy, supporting further evaluation as a once‐weekly treatment of type 2 diabetes. Copyright © 2010 John Wiley & Sons, Ltd.     

Cardiogenic shock in patient with posterior postinfarction septal rupture--successful treatment with extracorporeal membrane oxygenation (ECMO) as a ventricular assist device

Abstract   We present the case of a 62-year-old female patient admitted to our center for cardiogenic shock due to large inferior myocardial infarct. Echocardiography revealed dysfunction of left ventricle, dilation of right ventricle, mitral valve insufficiency, and a large posterior ventricular septal defect (VSD). Coronary angiography showed occlusion of the right coronary artery. An attempt of percutaneous coronary intervention (PCI) of right coronary and posterior descending artery was not successful due to old thrombi. Despite inotropes and intraaortic balloon pump (IABP) there was severe hemodynamic instability. Therefore, we commenced veno-arterial extracorporeal membrane oxygenation (ECMO) as a ventricular assist device (VAD). Immediately we obtained the stabilization of the patient and the improvement of the clinical conditions. The third day after implantation, the closure of the defect, mitral valve plasty, and bypass to posterior descending artery were performed. The patient was discharged from the hospital 59 days after the operation. Six months after the operation, the patient was in good condition.