Increasing procoagulant activity of circulating microparticles in patients living with HIV.

OBJECTIVES: HIV-infected individuals are at higher risk of non-AIDS diseases associated with procoagulant status. Microparticles are elevated in disorders associated with thrombosis (e.g., cardiovascular diseases). We investigated the association between microparticle levels in untreated and treated HIV-infected subjects, and determined the association with immune status, viral replication, and duration of antiretroviral therapy. PATIENTS AND METHODS: We included 144 HIV-infected subjects, including 123 on antiretroviral therapy (ART) and 21 before treatment initiation. A control group of 40 HIV-negative healthy adults matched for age and sex was used for comparison of microparticle levels. Treated subjects were divided into five groups depending on the period of antiretroviral exposure. Statistically significant differences were determined by Kruskal-Wallis test and Chi2 test. The relation between microparticles and other parameters was assessed using Spearman's coefficient of correlation. RESULTS: Microparticle levels were significantly higher in treated and untreated HIV-infected subjects than in non-HIV-infected controls (P<0.001). The microparticle level was similar between the groups on treatment (P=0.913). No association between the microparticle level and CD4+ count, CD4+/CD8+ ratio, number of HIV-1 RNA copies, or duration of exposure to antiretroviral treatment was observed. CONCLUSION: Increased levels of microparticles may be due to processes independent of viral replication and CD4+ cell count, and microparticle release might persist even during viral suppression by antiretroviral treatment. Elevated microparticle levels might occur in response to other triggers.

Progressive multifocal leukoencephalopathy - epidemiology, immune response, clinical differences, treatment.

Progressive multifocal leukoencephalopathy (PML) is a severe disease of the central nervous system with very high mortality. It is caused by the JC virus with high seroprevalence, at up to 80%. Development of PML is typically opportunistic, particularly in acquired immunodeficiency syndrome, and usually affects patients with profound immunodeficiency. Furthermore, as a result of highly efficient immunosuppressive and immunomodulatory treatments in recent years, the number of PML cases has increased in the general population. In this article, the authors mention virological and epidemiological relationships and characteristic manifestations of PML. Possible relationships of humoral and cellular immunity are discussed and limited treatment options including prophylaxis are mentioned.

Ascorbic acid: an old player with a broad impact on body physiology including oxidative stress suppression and immunomodulation: a review.

Ascorbic acid is a low molecular weight antioxidant well known as anti-scorbut acting vitamin C in humans, primates and guinea pigs. This review summarizes basic data about ascorbic acid in its physiological action point of view. It is divided into biochemistry of ascorbic acid synthesis, mechanism of antioxidant action and participation in anabolism, pharmacokinetics and excretion, exogenous ascorbic acid immunomodulatory effect and participation in infectious diseases, impact on irradiation and intoxication pathogenesis, and supplementary demands. The primary intention was to consider ascorbic acid not only as an antioxidant but also as a chemical compound affecting multiple pathways with a potential beneficial impact in many diseases and processes in human body.

Macrophage-assisted inflammation and pharmacological regulation of the cholinergic anti-inflammatory pathway.

Macrophages play an important role in the immune system. They also participate in multiple processes including angiogenesis and triggering of inflammation. The present study summarizes pieces of knowledge on the importance of macrophages in disease, especially the inflammation. Special attention is paid to the cholinergic anti-inflammatory pathway (CAP) associated with the nicotinic acetylcholine receptor (nAChR) and the parasympathetic nervous system. The current pharmacological effectiveness in suppressing the inflammation in general and the septic shock in particular, is limited. CAP was discovered recently and it seems to be a suitable target for the development of new drugs. Moreover, available drugs binding to either nAChR or acetylcholinesterase (AChE) are candidates for either an inhibition or enhancement of CAP. Though the current scientific databases do not include all necessary data on the association of CAP with body functions and the research is quite intensive, the objective of the present review is to introduce the current trends and to critically evaluate CAP and macrophage-associated pathways.