Microbial translocation is a cause of systemic immune activation in chronic HIV infection

Chronic activation of the immune system is a hallmark of progressive HIV infection and better predicts disease outcome than plasma viral load, yet its etiology remains obscure. Here we show that circulating microbial products, probably derived from the gastrointestinal tract, are a cause of HIV-related systemic immune activation. Circulating lipopolysaccharide, which we used as an indicator of microbial translocation, was significantly increased in chronically HIV-infected individuals and in simian immunodeficiency virus (SIV)-infected rhesus macaques (P 相似文献   

Ivermectin as a systemic insecticide

Like many broad-spectrum drugs, the antiparasitic agent ivermectin is not equally effective in the treatment of all parasitic infestations. Predicting arthropod susceptibility relies not only on an understanding of insect and acarine biology, but also on an appreciation of the pharmacokinetic properties of the drug which can be profoundly influenced by host differences and pharmaceutical formulation. In this review, Helen Jackson attempts to explain the diverse number of ivermectin-induced effects observed among parasitic arthropods feeding on treated animals and aims to provide an overview of the current and future use of ivermectin in the systemic treatment and control of arthropod pests of livestock.     

Allergy as a systemic disease

The prevalence of allergic diseases has shown an increase in the last few years. Allergic diseases develop in persons with a genetic background, this genetic trait being known as atopy. The main pathophysiological characteristic of allergy is inflammation. The inflammatory process may explain the diversity of symptoms and signs of allergy. The early sensitization increases the risk of developing different symptomatic forms of allergy, and one person may present different symptoms and signs of allergy. But some persons can become allergic without atopy trait in conditions of a higher and longer exposure to allergens (e.g. occupational allergy). In the last years new allergens have induced symptoms, sometimes with a life-threatening evolution. The load of allergen in public areas is also increasing. In this context, allergy must be understood as a unique systemic disease with various forms of presentation.     

Patients with chronic viral hepatitis as sources of infection

Dynamic observation on 126 foci of infection formed by patients with manifest forms of chronic hepatitis B, 41 foci of chronic hepatitis of unknown etiology, and 37 foci formed by chronic "healthy" carriers was made. In the foci of type 1 the epidemic process developed intensively and was manifested mainly by HBsAg carriership in persons having had contacts with the patients. During the period of observation 43.0% of new cases of infection were detected. In the foci of types 2 and 3 the frequency of contacting infection was not different from that in the control group of the population.     

Abrogation of tolerance to a chronic viral infection

This study documents failure of peripheral tolerance mechanisms in a chronic viral infection and shows that T cell tolerance to a viral Ag seen as self from fetal life can be broken despite the presence of this Ag in extrathymic tissues. Congenital infection of mice with lymphocytic choriomeningitis virus (LCMV) results in T cell tolerance to the virus. Such mice become carriers for life harboring virus in many tissues including the thymus and exhibit no LCMV-specific CTL responses. Our previous studies have documented the curing of this congenitally acquired chronic infection after adoptive transfer of CD8+ T cells from LCMV-immune mice and the presence of host-derived, LCMV-specific CTL in these "cured" carriers. In this study we have examined the mechanism by which these carriers acquired T cell competence and show that these CTL differentiated from the bone marrow after elimination of viral Ag from the thymus. These results demonstrate that even when a chronic infection has been established in utero, the adult thymus retains the ability to restore immunocompetence to the host and to provide protection against reinfection. Surprisingly, these LCMV specific CTL were acquired at a time when infectious virus and intracellular viral Ag, although cleared from the thymus, were readily detectable in organs such as the kidney, testes, and brain. In fact, active viral replication in peripheral tissues was ongoing when these mice acquired new virus-specific T cells. These results show that clearance of virus form the thymus was sufficient to abrogate tolerance to a congenitally acquired chronic infection and that Ag in peripheral tissues did not tolerize newly developing T cells. These findings suggest that mechanisms that operate on immature cells within the thymus to silence self-reactive T cells are effective in induction of tolerance to viruses, but mechanisms of tolerizing mature T cells are likely to breakdown. This has implications for virus-induced autoimmunity and for treatment of chronic infections.     

Syphilis 2001 a palaeopathological reappraisal

The origin and subsequent spread of the treponematoses, especially that of venereal syphilis, has been the subject of considerable scientific attention. Various theories were put forth and palaeopathological specimens were used for their validation in recent times. One influential contribution was the paper by Baker & Armelagos in 1988. Numerous new findings and results on both sides of the Atlantic call for a new evaluation of the available osseous material. A review of the recent literature leads to the suggestion of a worldwide distribution of non-venereal treponemal disease since the emergence of Homo and to a first epidemic outbreak of venereal syphilis in Europe of the late 15th and the early 16th century, which was a time of change and enormous sexual liberty. Old World specimens with pathological alterations attributed to venereal syphilis and dated to precolumbian times seem to invalidate the Columbian theory and call for a more differentiated analysis of the phenomenon of syphilis than a theory based on a single factor can provide. With the help of molecular methods which now allow a positive identification of Treponema pallidum pallidum, causative agent of venereal syphilis, in palaeopathological material, it seems possible to elucidate the matter of origin and spread of syphilis further and to evaluate previous diagnoses of treponemal disease.     

耐甲氧西林金黄色葡萄球菌小鼠全身感染模型的建立与评价

目的建立稳定、可靠的MRSA全身感染小鼠模型,为MRSA疫苗的研发提供参考依据,并对系统研究MRSA感染的发病机制及其防治策略奠定实验基础。方法在采用国际标准株MRSA-252建立OD600-CFU标准曲线的基础上,经尾静脉注射途径感染BALB/c小鼠,从感染剂量的选择、小鼠的生存率和体重变化、血液及多脏器的细菌定植量以及主要组织器官病理学变化等多个层面进行时相性监测,对建立的小鼠模型进行系统评价。结果经此途径建立的小鼠模型,致死剂量为每只5.0×109CFU,亚致死剂量为每只1.0×109CFU（生存率为60%～70%）。感染后小鼠生存率下降;体重下降;血液及肝脏、脾脏和肾脏均有细菌定植,定植量在感染后第3天达到高峰;心、肝、肺和肾等主要脏器中有较明显的细胞坏死和炎性细胞浸润。结论小鼠模型的建立,将为进一步研究MRSA疫苗的有效性和安全性评价等提供可靠的技术手段。     

Hepatitis C virus (HCV) infection: a systemic disease

Hepatitis C virus (HCV) infection is a global health problem, being the second most common chronic viral infection in the world with a global prevalence of about 3% (about 180 million people). HCV is both an hepatotropic and a lymphotropic virus; and chronic infection could cause, on one hand, chronic hepatitis, cirrhosis and hepatocellular carcinoma and on the other hand several extrahepatic diseases including, first, mixed cryoglobulinemia and lymphoma. The association between hepatic (hepatocellular carcinoma) and extrahepatic (lymphoma, thyroid cancer) malignancies has justified the inclusion of HCV among human cancer viruses. The pathogenesis of HCV-related sequelae (hepatic or extrahepatic) is not fully understood representing a challenge of prime importance in light of the optimization of clinico-therapeutic management of these patients. Combined treatment with pegylated interferon plus ribavirin is presently the first-line, gold standard treatment of most HCV-related diseases. However, mainly in the case of extrahepatic manifestations, a cautious approach to the patient, with a case to case accurate tailoring of therapy is frequently requested. The present review will outline the principal aspects of such HCV-induced systemic disease focusing on extrahepatic manifestations.