Facts and Fallacies About Measuring Blood Pressure in Rats

Although blood pressure can easily be measured in anesthetized rats by simply connecting a catheter to a pressure transducer, repeated measurements taken over long periods of time in awake rats are much more difficult to make. For chronic experiments two methods are now commonly used: direct recording from chronically-implanted arterial catheters, or indirect measurement with the tail-cuff method. Direct recording of intraarterial pressure can be done continuously and is more accurate, but technically more demanding. On the other hand, although tail-cuff measurements are less accurate, they do not require surgery and can be repeated almost indefinitely. With most tail-cuff methods the rats are preheated to dilate the tail vessels and thereby facilitate pulse detection, but with the new IITC photoelectric sensor indirect measurements of systolic as well as of mean arterial pressure can be made without external preheating. Even with a properly validated tail-cuff method, however, errors can still occur particularly when it is used to quantify modest blood pressure changes like those during development of hypertension, or following administration of vasoactive drugs. To safeguard against such errors, each laboratory should always validate its own tail-cuff method under uniform experimental conditions similar to those existing when the method is actually used. Additionally, all blood pressure differences thereby detected should be verified by direct measurement of intraarterial pressure in the same rats.     

转录信号传导子和激活子3信号传导通路调控选择性环氧化酶2抑制剂抗结肠癌的机制

目的探究转录信号传导子和激活子3(Stat3)信号传导通路与选择性环氧化酶2(COX-2)抑制剂抗结肠癌细胞株HT-29机制的关系,明确COX-2抑制剂抗结肠癌细胞内信号传导机制。方法将选择性COX-2抑制剂NS-398,作用于结肠癌细胞系HT-29,运用MTT法检测细胞增殖状态;流式细胞仪观察NS-398对细胞凋亡的影响,进一步用RT-PCR检测药物作用前后HT-29中COX-2mRNA的表达;ELISA法测定体系前列腺素E2(PGE2)水平;Westernblot检测药物作用前后Stat3通路相关蛋白JAK2、Stat3的磷酸化活性和cyclinD1、Bcl-2的表达。结果结肠癌细胞系HT-29中COX-2mRNA呈高表达,NS-398呈时间、剂量依赖性方式抑制HT-29细胞增殖,促进其凋亡。NS-398使HT-29细胞COX-2mRNA和PGE2表达水平显著下降。同时p-JAK2、p-Stat3、cyclinD1、Bcl-2表达水平随作用时间延长而下降。结论癌基因Stat3信号传导通路调控了NS-398抗结肠癌的细胞内信号传导机制,最终通过其下游靶基因cyclinD1、Bcl-2影响结肠癌细胞系HT-29的增殖与凋亡。     

JAK／STAT信号通路与组织器官纤维化的相关性研究进展

Janus激酶／信号转导与转录激活子（JAK／STAT）是一条依靠多种细胞因子和生长因子共同介导的信号通路,广泛参与了细胞的增殖、分化、凋亡及免疫调节等病理生理过程。多项研究表明,JAK／sTAT信号通路对机体不同的组织及器官如肾脏、肝脏、肺、心脏等的纤维化形成过程具有重要的调控作用。该文就近年JAK／sTAT信号通路与机体组织器官纤维化形成的相关性研究作一综述。     

IL28B single nucleotide polymorphisms in the treatment of hepatitis C

Recent genome-wide association studies (GWAS) have identified genetic variations near the IL28B gene which are strongly associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. Protective IL28B variations are strongly associated with on-treatment viral kinetics and approximately 2-fold increased sustained virologic response (SVR) rates in HCV genotype 1 and 4 patients. In HCV genotype 1 patients, IL28B variations were shown to be the strongest pre-treatment predictor of virologic response. In the treatment of HCV genotype 2 and 3 infected patients, IL28B variations play only a minor role. Preliminary data indicate that IL28B variations are also associated with treatment outcome of regimens, including directly acting antiviral (DAA) agents, though their impact seems to be attenuated compared to standard treatment. Here, we review these important findings and discuss possible implications for clinical decision making in the treatment of HCV infection.     

IL-2诱导类风湿关节炎与骨关节炎T淋巴细胞STAT3 STAT5酪氨酸磷酸化状态的比较

目的观察白细胞介素(IL)-2作用于类风湿关节炎(RA)与骨关节炎(OA)外周血T淋巴细胞前后,T淋巴细胞中STAT3及STAT5的酪氨酸磷酸化活化状态,并进行比较.方法从RA与OA患者的外周血中分离培养单个核细胞,继而纯化得到T淋巴细胞,静息后,用重组人IL-2刺激,在各时相裂解细胞,收获提取蛋白,进行Western blot分析.结果在静息后,RA与OA的外周血T淋巴细胞中STAT3与STAT5均处于极低水平磷酸化的状态;在IL-2作用后,T淋巴细胞中STAT3和STAT5发生时相性的酪氨酸磷酸化,而RA的T淋巴细胞磷酸化程度较OA显著增高.结论IL-2对RA患者T淋巴细胞的STAT3和STAT5过度激活,引起T淋巴细胞中IL-2信号传导的异常放大效应,可能在RA的发病过程中发挥重要作用.     

An Implantable Microsystem for Tonometric Blood Pressure Measurement

This paper presents an implantable microsystem for tonometric blood pressure measurement in small animals. The microsystem consists of four major components: (1) a titanium base for supporting a pressure sensor and an interface chip, (2) a micromachined capacitive pressure sensor array, (3) a switched-capacitor interface chip, and (4) a titanium cap. A new micromachining fabrication process has been developed to create capacitive pressure transducers with a flat surface necessary for tonometric pressure measurement. An array of three capacitive sensors is used to increase signal output and improve stability. A custom-designed switched-capacitor CMOS interface circuit is used to measure changes in capacitance. In vitro calibration tests have been performed on the complete cuff using a silastic tube to mimic a pliable blood vessel. A sensitivity of 2 mV/mmHg @ 100 mmHg and a resolution of 0.5 mmHg (based on 1 mV RMS interface chip noise floor) has been obtained. The dimensions of the cuff system 10(L)×6.5(W)×3(H) mm³.     

Influenza A virus abrogates IFN-gamma response in respiratory epithelial cells by disruption of the Jak/Stat pathway

The innate immunity to viral infections induces a potent antiviral response mediated by interferons (IFN). Although IFN-gamma is detected during the acute stages of illness in the upper respiratory tract secretions and in the serum of influenza A virus-infected individuals, control of influenza A virus is not dependent upon IFN-gamma as evidenced by studies using anti-IFN-gamma Ab and IFN-gamma(-/-) mice. Thus, we hypothesized that IFN-gamma is not critical in host survival because influenza A virus has mechanisms to evade the antiviral activity of IFN-gamma. To test this, A549 cells, an epithelial cell line derived from lung adenocarcinoma, were infected with influenza virus strain A/Aichi/2/68 (H3N2) (Aichi) and/or stimulated with IFN-gamma to detect IFN-gamma-stimulated MHC class II expression. Influenza A virus infection inhibited IFN-gamma-induced up-regulation of HLA-DRalpha mRNA and the IFN-gamma induction of class II transactivator (CIITA), an obligate mediator of MHC class II expression. Nuclear translocation of Stat1alpha upon IFN-gamma stimulation was significantly inhibited in influenza A virus-infected cells and this was associated with a decrease in Tyr701 and Ser727 phosphorylation of Stat1alpha. Thus, influenza A virus subverts antiviral host defense mediated by IFN-gamma through effects on the intracellular signaling pathways.     

Transducers for foot pressure measurement: survey of recent developments

Recent advances in the development of transducers for the measurement of vertical and shear forces acting on the plantar surface of the foot are reviewed. Barefoot and in-shoe discrete and matrix transducers are reviewed in terms of structure, operation, performance and limitations. Examples of capacitive, piezoelectric, optical, conductive and resistive types of transducer are presented. Where available, the current clinical status is specified.     

RNAi沉默STAT3基因对结肠癌HCT116细胞侵袭的调控

目的:观察RNA干扰沉默STAT3基因对结肠癌细胞侵袭的影响,并探讨其可能机制。方法:应用STAT3小干扰RNA(small interfering RNA,siRNA)转染处理人结肠癌细胞系HCT116后,采用RT-PCR检测STAT3 mRNA表达,软琼脂集落培养试验检测锚着不依赖性增殖,Boyden小室模型试验检测癌细胞的侵袭性,琼脂糖凝胶电泳和TUNEL检测癌细胞失巢凋亡。结果:STAT3 siRNA可有效抑制结肠癌细胞集落生长和侵袭能力,且与浓度相关。琼脂糖凝胶电泳和TUNEL结果显示,STAT3 siRNA转染可诱导结肠癌细胞失巢凋亡,且与浓度相关。结论:STAT3 siRNA可抑制结肠癌细胞的恶性侵袭,其机制与诱导失巢凋亡有关。