Vol 67, No 5 (2012)
- Year: 2012
- Articles: 14
- URL: https://vestnikramn.spr-journal.ru/jour/issue/view/26
- DOI: https://doi.org/10.15690/vramn675
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Current methods of HIV treatment can contain a progression of the disease; however they do not lead to a cure. Lifelong antiretroviral therapy is therefore necessary, leading to problems of cost and toxicity of chemical drugs. The recent advances in science have allowed a new approach to the HIV-treatment — gene therapy. In the present publication we focus on one strategy of the gene therapy called «intracellular immunization». The strategy is based on the introducing of antiviral genes into the HIV-sensitive cells. We highlight the mechanisms of action of various antiviral genetic agents and discuss some issues concerning target cells and genes delivery. Finally we summarize the results of certain gene therapy clinical trials.
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Aim: to evaluate association between genetic polymorphism (SNPs) and myocardial infarction (identified in recent GWAS) as markers of high risk of myocardial infarction (MI) in Siberian population. Patients were divided into 2 groups — MI patients and control group (ratio 1:2) and presented the sapmle of population of Novosibirsk (9400 patients, 45–69 years) within international project HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe). 200 patients with MI (129 men, 71 women) were included. Control group — individuals without MI (420) matched for age and sex. Genomic DNA was extracted from venous blood by phenol-chloroform extraction. Gene polymorphism of genes tested by real-time PCR according to protocol (probes TaqMan, Applied Biosystems, USA) with the use of ABI 7900HT. The following SNPs were studied: rs28711149, rs499818, rs619203, rs10757278 and rs1333049 (hr. 9), rs1376251, rs2549513, rs4804611, rs17465637. The association of SNP and MI was confirmed for 4 of 9 studied SNPs: rs1333049 (hr. 9), rs10757278 (hr. 9), rs499818 (hr. 6), rs619203 gene ROS1. Heart rate was associated with rs1333049 and rs10757278. Glucose level was associated with rs619203, rs28711149 and rs1376251. Total cholesterol and atherogenic index was associated with rs28711149. For the first time in Russian population the associations of GWAS with myocardial infarction SNPs was detected for rs619203, rs499818, rs1333049 and rs10757278. These genetic markers can be used for assessing the risk of myocardial infarction in Russian population.
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In this article the authors discuss the issues related to assessment of activity and severity of sarcoidosis, course and radiographic manifestations of this disease. Problems in defining of different forms of sarcoidosis resulted in suggestion of new version of classification.
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At present the issues in regard to Chlamydia infection are not only limited by urogenital system. By the way optimal organization and non-urogenital chlamydiosis treatment strategy (with respiratory tract involvement in particular) have not been worked out yet and require immediate solutions. Due to new knowledge on respiratory chlamidiosis the authors discuss scientific background for future development of complex measures and main directions of health care support strategy for patients with upper respiratory associated with Chlamydia infection.
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Various aspects of protective and damaging influences of endotoxin-activated Kupffer cells on hepatocytes are discussed. Requests for protective subcellular mechanism activated by Kupffer cells mediators were formulated. Two possible mechanisms of activated Kupffer cells protective influence on hepatocytes which satisfy these requests are considered. One of them may operate via hepatocyte non-specific reaction to damage initiated by Kupffer cells mediators. Another one may work through activation of endotoxin-dependent tissue stress mechanism in hepatocytes. The data confirm the development of non-specific reaction to damage and the mechanism of tissue stress realized by means of tissue-specific effector in hepatocytes under endotoxin-activated Kupffer cells influence.
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The study has shown that activation of delta1-opioid receptors by a highly selective peptide agonist DPDPE (100 µg/kg) results in a significant increase of the immune response to antigen (SRBC, 5×108) in CBA mice. SCH-23390 (1 mg/kg), a selective antagonist of the postsynaptic dopamine D1-receptors, and selective D2-blocker haloperidol (1 mg/kg) prevented immunostimulating effect of DPDPE. Comparison of effects of the antagonists suggests that delta1-opioidergic immunostimulation has more significant impact due to involvement of dopamine D1-receptors.
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Molecular factors of pathogenesis of the eosinophilic blood reaction under pulmonary tuberculosis are analyzed in the article. It has been established that the key cytokine providing the development of hemic eosinophilia in patients with pulmonary tuberculosis is IL-5. IL-5 plasma concentration turned out to be increased only in patients with eosinophilia. Increase of eotaxin was determined in patients with tuberculosis despite of the presense of eosinophilia. One-directional nature of the defined changes in eotaxin concentration might be explained by dual properties of this chemokine: on the one hand, eotaxin mediates long-term presence of eosinophils in blood; on the other hand, it initiates the process of adhesion of eosinophilic leucocytes to vascular endothelium with their further migration to the focus of granulomatous inflammation. The established increase in number of IL-5R-positive eosinophils presents one more mechanism which explains the basis of long-term presence of eosinophils in peripheral blood in patients with pulmonary tuberculosis.
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An overview of the present status and prospects of gnotobiology along with a role of normal microflora studied using laboratory animals with controlled microflora (gnotobiotes) is presented. The principal elements of gnotobiotechnology as well as possibilities of its using in both experimental and clinical investigations are analyzed. A multifaceted role of normal microflora in the host physiology and pathology prejudge the increasing importance of gnotiological models in various fields of biology and medicine, such as the development of new generations probiotics. An assessment and characteristics of selected microbial strains, host-microbe interactions etc. An organization of further complex gnotobiotic research is of prospective value.
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