[A clinical case of three times treatment of hepatitis C with repeated infection in HIV-positive patient. Case Report].

The article presents a clinical case of hepatitis C treatment with repeated reinfection in an HIV-positive patient. Despite the possibility of hepatitis C cure with modern antiviral drugs and long-term duration and quality of patients' life, remains the risk of reinfection. It is necessary to intensify prevention and regular laboratory screening for viral hepatitis among all population in order to start treatment in time and prevent new cases of hepatitis.

Radiomics in Determining Tumor-to-Normal Brain SUV Ratio Based on 11C-Methionine PET/CT in Glioblastoma.

Modern methodology of PET/CT quantitative analysis in patients with glioblastomas is not strictly standardized in clinic settings and does not exclude the influence of the human factor. Methods of radiomics may facilitate unification, and improve objectivity and efficiency of the medical image analysis. The aim of the study is to evaluate the potential of radiomics in the analysis of PET/CT glioblastoma images identifying the relationship between the radiomic features and the 11С-methionine tumor-to-normal brain uptake ratio (TNR) determined by an expert in routine. Materials and Methods: PET/CT data (2018-2020) from 40 patients (average age was 55±12 years; 77.5% were males) with a histologically confirmed diagnosis of "glioblastoma" were included in the analysis. TNR was calculated as a ratio of the standardized uptake value of 11C-methionine measured in the tumor and intact tissue. Calculation of radiomic features for each PET was performed in the specified volumetric region of interest, capturing the tumor with the surrounding tissues. The relationship between TNR and the radiomic features was determined using the linear regression model. Predictors were included in the model following correlation analysis and LASSO regularization. The experiment with machine learning was repeated 300 times, splitting the training (70%) and test (30%) subsets randomly. The model quality metrics and predictor significance obtained in 300 tests were summarized. Results: Of 412 PET/CT radiomic parameters significantly correlated with TNR (p<0.05), the regularization procedure left no more than 30 in each model (the median number of predictors was 9 [7; 13]). The experiment has demonstrated a non-random linear correlation (the Spearman correlation coefficient was 0.58 [0.43; 0.74]) between TNR and separate radiomic features, primarily fractal dimensions, characterizing the geometrical properties of the image. Conclusion: Radiomics enabled an objective determination of PET/CT image texture features reflecting the biological activity of glioblastomas. Despite the existing limitations in the application, the first results provide a good perspective of these methods in neurooncology.

[Anthra-cycline-Induced Cardiotoxicity: the Role of Genetic Predictors].

Aim      To evaluate the predictive significance of gene polymorphism in endothelin-1 type 2A receptor, NADPH oxidase, p53 protein, endothelial nitric oxide synthase, caspase 8, interleukin-1ß, tumor necrosis factor-α, superoxide dismutase-2, glutathione peroxidase-1, ß1-adrenoceptor, angiotensin-converting enzyme, and matrix metalloproteinase-3 (MMP-3) genes in evaluating the risk of anthracycline-induced cardiotoxicity (AIC) in women without concurrent cardiovascular diseases (CVD).Material and methods  This study included 176 women aged 45.0 [42.0; 50.0] years with breast cancer without concurrent CVD who were scheduled for polychemotherapy (PCT) with anthracycline antibiotics. Echocardiography was performed for all patients at baseline and at 12 months after the end of PCT course. Genetic polymorphism was determined with the polymerase chain reaction.Results At 12 months, all patients were in remission of the underlying disease. They were retrospectively included into 2 groups: 1st group, 52 patients with AIC and 2nd group, 124 women without AIC symptoms. The development of AIC was associated with the presence of the p53 protein gene Arg / Arg genotype (odds ratio (OR), 2.972; p=0.001), NOS3 gene T / T genotype (OR, 3.059; p=0.018), NADPH oxidase gene T / T genotype (OR, 2.753; p=0.008), GPX1 gene C / C genotype (OR, 2.345; p=0.007), MMP-3 gene 5A / 5A genotype (OR, 2.753; p=0.008), and ADRB1 gene G / G genotype (OR, 3.271; p=0.043).Conclusion      Evaluation of genetic polymorphism in p53 protein (rs1042522), NOS3 (rs1799983), NADPH-oxidase (rs4673), GPX1 (rs1050450), ADRB1 (Arg389Gly, rs1801253), and MMP-3 (rs3025058) genes can be recommended for use prior to starting chemotherapy in women with breast cancer without CVD for assessing the risk of AIC. A maximum risk of cardiotoxicity is associated with the presence of the p53 protein gene Arg / Arg genotype and NOS3 gene T / T genotype.

[Evidence-based proposals for improving the Zemsky Doctor program].

Currently, more and more attention is paid to the shortage of medical staff in rural and remote areas. In order to ensure the staffing of medical institutions with workers in rural areas, in the regions one-time compensations are paid as part of an event called "Zemsky Doctor". However, "Zemsky Doctor" has shown a fading effect over the years of implementation, including due to the unwillingness of medical students to participate in this program. The purpose of the work is to identify the attitude of students of medical universities to participation in the "Zemsky Doctor" program and develop measures to increase the attractiveness of the program. To achieve the goal of the study, we conducted a survey of 250 medical students from all over Russia, interviews with medical students, with medical staff, including former and current participants. The novelty of the work lies in the study of the attitude of current and potential participants in the program in order to develop proposals for its improvement. To improve the program, it is necessary to choose the term for concluding the contract, differentiate payments depending on the distance from the regional center, create an information site, defer the army for the duration of the contract.

A Method for Recording the Bioelectrical Activity of Neural Axons upon Stimulation with Short Pulses of Infrared Laser Radiation.

The aim of the study was to develop a method for long-term non-invasive recording of the bioelectrical activity induced in isolated neuronal axons irradiated with short infrared (IR) pulses and to study the effect of radiation on the occurrence of action potentials in axons of a neuron culture in vitro. MATERIALS AND METHODS: Hippocampal cells of mouse embryos (E18) were cultured in microfluidic chips made of polydimethylsiloxane and containing microchannels for axonal growth at a distance of up to 800 µm. We studied the electrophysiological activity of a neuronal culture induced by pulses of focused laser radiation in the IR range (1907 and 2095 nm). The electrophysiological activity of the neuronal culture was recorded using a multichannel recording system (Multi Channel Systems, Germany). RESULTS: The developed microfluidic chip and the optical stimulation system combined with the multichannel registration system made it possible to non-invasively record the action potentials caused by pulsed IR radiation in isolated neuronal axons in vitro. The propagation of action potentials in axons was detected using extracellular microelectrodes when the cells were irradiated with a laser at a wavelength of 1907 nm with a radiation power of 0.2-0.5 W for pulses with a duration of 6 ms and 0.5 W for pulses with a duration of 10 ms. It was shown that the radiation power positively correlated with the occurrence rate of axonal response. Moreover, the probability of a response evoked by optical stimulation increased at short optical pulses. In addition, we found that more responses could be evoked by irradiating the neuronal cell culture itself rather than the axon-containing microchannels. CONCLUSION: The developed method makes it possible to isolate the axons growing from cultured neurons into a microfluidic chip, stimulate the neurons with infrared radiation, and non-invasively record the axonal spiking. The proposed approach allowed us to study the characteristics of neuronal responses in cell cultures over a long (weeks) period of time. The method can be used both in fundamental research into the brain signaling system and in the development of a non-invasive neuro-interface.

[Prevalence of human papillomavirus (Papillomaviridae; Human papillomavirus) of high carcinogenic risk based on the results of screening of three anatomical loci in men stratified by sexual behavior and HIV status].

INTRODUCTION: Human papillomavirus (HPV) of high carcinogenic risk (HCR), in addition to being the etiological agent of cervical cancer, also contribute to development of cancer of the anus, vagina, penis, vulva and oropharyngeal cancer. In this connection, further study of the biological properties of this agent and its prevalence in different populations is an urgent task.The aim of the study was to examine the prevalence of HCR HPV in three anatomical loci in men stratified by HIV (human immunodeficiency virus) infection status (negative, HIV+/positive/HIV-) as well as by sexual behavior: men who have sex with men (MSM), heterosexual men (HM). MATERIAL AND METHODS: The study included 256 men from Moscow and Moscow region: 73 МSМ/HIV+, 66 МSМ/ HIV-, 58 HM/HIV+, and 59 HM/HIV-. All men were tested for 14 HCR genotypes of HPV (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). Smears were taken from three anatomical loci: urethra, anus, oropharynx. Testing was preformed using real-time polymerase chain reaction assay (PCR-RT). RESULTS: The highest prevalence of HCR HPV detection, regardless of the locus, was recorded for МSМ/HIV+ (82.2%), and the lowest for HM/HIV (20.3%). The highest detection of HCR HPV in scrapings of epithelial cells from anus was recorded for МSМ/HIV+ (79.5%). The highest incidence of this pathogen in oropharynx also was registered for МSМ/HIV+ (13.7%). The highest incidence of HCR HPV in scrapings of epithelial cells from urethra was recorded for HM/HIV+ (24%). The prevalence of HCR HPV among men was found to differ markedly depending on the anatomical locus, HIV status and sexual behavior. DISCUSSION: For the first time, there were obtained data on the prevalence of HCR HPV in men with different patterns of sexual behavior and HIV status in the Moscow region. CONCLUSION: Screening for HCR HPV in male population based on the identification of 14 genotypes of the virus in three anatomical loci (urethra, oropharynx, anus) by PCR-RT will provide the information necessary to improve the system of epidemiological monitoring and proper planning of preventive measures among men with any risk factors for HPV persistence (presence of HIV infection and/or belonging to the MSM group). HPV screening algorithm development is required for men considering their HIV status and sexual behavior. We recommend testing for 14 HCR HPV genotypes in three loci (urethra, anus, oropharynx).

Droplet microarrays for cell culture: effect of surface properties and nanoliter culture volume on global transcriptomic landscape.

The development of novel chemically developed and physically defined surfaces and environments for cell culture and screening is important for various biological applications. The Droplet microarray (DMA) platform based on hydrophilic-superhydrophobic patterning enables high-throughput cellular screening in nanoliter volumes and on various biocompatible surfaces. Here we performed phenotypic and transcriptomic analysis of HeLa-CCL2 cells cultured on DMA, with a goal to analyze cellular response on different surfaces and culture volumes down to 3 nL, compared with conventional cell culture platforms. Our results indicate that cells cultured on four tested substrates: nanostructured nonpolymer, rough and smooth variants of poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) polymer and poly(thioether) dendrimer are compatible with cells grown in Petri dish. Cells cultured on nanostructured nonpolymer coating exhibited the closet transcriptomic resemblance to that of cells grown in Petri dish. Analysis of cells cultured in 100, 9, and 3 nL media droplets on DMA indicated that all but cells grown in 3 nL volumes had unperturbed viability with minimal alterations in the transcriptome compared with 96-well plate. Our findings demonstrate the applicability of DMA for cell-based assays and highlight the possibility of establishing regular cell culture on various biomaterial-coated substrates and in nanoliter volumes, along with routinely used cell culture platforms.

[Prognostic role of p53 gene polymorphism in risk assessment of anthracycline-induced cardiotoxicity].

AIMS: To study the prognostic significance of polymorphism of the p53 gene (polymorphism Arg72Pro exon 4, rs1042522) on the development of cardiotoxic remodeling of the left ventricle and heart failure. MATERIAL AND METHODS: A total of 176 women with breast cancer who received anthracycline antibiotics as part of polychemotherapeutic treatment regimens were examined. Based on the results of the survey, 12 months after the end of polychemotherapy, patients in the remission of the underlying disease were divided into 2 groups: patients with cardiotoxic remodeling (52 patients) and women with preserved heart function (124 patients). All patients before the start of the course of chemotherapy, in the dynamics of treatment with anthracyclines and after therapy with such were carried out the study of echocardiographic parameters. All the patients were taken genetic material, followed by typing alleles of the gene for the protein p53 (rs1042522). RESULTS: Analysis of echocardiographic parameters in patients 12 months after the completion of polychemotherapy in comparison with those before treatment showed a significant difference in the final systolic (33 mm [31; 35] and 28 mm [26; 31], p<0.00001) and terminal diastolic dimensions (51 mm [49; 54.5] and 44 mm [42; 48.5], p=0.0003), as well as a significant decrease in the left ventricular ejection fraction (54.5% [51.5; 58] and 65.5% [62; 70], p<0.00001) in the group of women with developed anthracycline cardiotoxicity. The presence of the Arg/Arg genotype was associated with the development of cardiotoxic myocardial damage during polychemotherapy (OR=3.86, 95% C.I.=1.45-10.26, p=0.005). The Pro/Pro genotype has proved to be a protective factor (OR=0.26, 95% C.I.=0.09-0.69, p=0.015). The conclusion. Predicting the cardiotoxicity of chemotherapy using the polymorphism of the p53 gene is an effective measure of early pre-symptom diagnosis of an increased risk of anthracyclineinduced cardiotoxicity.

[The effect of bisphosphonate therapy on reducing the risk of cardiovascular complications associated with chronic heart failure, type 2 diabetes and osteoporosis in postmenopausal women].

AIM: To study the effectiveness of oral alendronate and ibandronate bisphosphonates for the prevention of cardiovascular complications in postmenopausal women with type 2 diabetes mellitus (DM) and osteoporosis during a 12-month prospective observation. MATERIALS AND METHODS: The study included 86 women with osteoporosis, chronic heart failure (CHF) and type 2 diabetes: the 1st group (n=52) included patients who received basic therapy for heart failure; the 2nd group (n=34) included patients who, in addition to the basic therapy of heart failure, were prescribed alendronic and ibandronic acid preparations for the treatment of osteoporosis. In order to identify the possibility of associating the studied factors with the nature of the course of heart failure, the patients were divided according to the results of a one - year follow - up into two subgroups: subgroup A (n=49) - patients with a favorable course of the disease and subgroup B (n=37) - patients with an unfavorable course of pathology. RESULTS AND DISCUSSION: After 12 months, a significant decrease in the levels of cerebral natriuretic peptide precursor (NT-proBNP), tumor necrosis factor-α, and interleukin-1ß was found in the group of women treated with bisphosphonates compared to baseline. Significant associations of NT-proBNP levels (p=0.02) and the studied cytokines (p=0.01) with an unfavorable course of heart failure were revealed. A significant association of bisphosphonate therapy with a favorable course of heart failure (p=0.01) was also revealed. The probability of developing adverse cardiovascular events during the year in the treatment of heart failure with basic therapy drugs with additional therapy of osteoporosis with bisphosphonates is significantly (p=0.0025) lower than the treatment of patients with heart failure with only basic therapy and not taking bisphosphonates for the treatment of osteoporosis. CONCLUSION: In postmenopausal women with associated cardiovascular pathology (CHF, type 2 diabetes and osteoporosis), prophylactic therapy with oral alendronate and ibandronate oral bisphosphonates is effective, reduces the risk of progression of heart failure, inhibits inflammatory mediators, positively affects the combined endpoints of comorbid cardiovascular pathology.

[Pathogenetic and Prognostic Role of Growth Factors in the Development of Chronic Heart Failure].

AIM: To study the role of growth factors ((vascular endothelial growth factor (VEGF), platelet derived growth factor AB (PDGF-AB) and basic fibroblast growth factor (FGF-basic)) in the development and progression of chronic heart failure (CHF) in patients with ishcemic heart disease (IHD). MATERIALS AND METHODS: We included in this study 94 patients with CHF. The control group comprised 32 persons. Blood serum levels of growth factors were determined at baseline and after 12 months of observation by enzyme-linked immunosorbent assay. RESULTS: VEGF, PDGF-AB and FGF-basic play an important role in the pathogenesis and progression of heart failure in patients with IHD, determining the increased risk of adverse cardiovascular events in this pathology. Serum activity of growth factors characterizes the severity and course of CHF: with disease progression levels of VEGF and FGF-basic decrease and PDGF-AB concentration increases. Initial low level of VEGF expression regardless of the sex of the patient's sex, significantly low level of FGF-basic and significantly high PDGF-AB in men characterizes unfavorable course of CHF. CONCLUSION: A correlation has been established between blood serum levels of VEGF, PDGF-AB and FGF-basic and severity and course of CHF.

[Role of soluble Fas ligand in myocardial remodeling, severity and outcomes of chronic heart failure]. / Rol' rastvorimogo Fas-liganda v remodelirovanii miokarda, tyazhesti techeniya i iskhodakh khronicheskoi serdechnoi nedostatochnosti.

AIM: to reveal the specific features of Fas ligand-mediated ischemic myocardial remodeling and those of chronic heart failure (CHF) development during a 12-month prospective follow-up. SUBJECTS AND METHODS: A total of 94 patients with ischemic CHF were examined and divided into 3 groups according to NYHA Functional Class (FC): 1) FC II CHF in 35 patients; 2) FC III CHF in 31; 3) FC IV CHF in 28. According to the results of the 12-month follow-up, the patients were randomized into 2 groups: A) 49 patients with a favorable course of cardiovascular disease and B) 45 patients with its poor course. Serum soluble Fas ligand (sFas-L) levels were measured by enzyme immunoassay. RESULTS: In the patients with CHF, the baseline sFas-L levels substantially exceeded that in the control group by 3-6 times (p<0.01). In the men with the poor course of CHF, the baseline serum sFAS-L levels (85.94±4.14 pg/ml) were significantly higher than that in the favorable CHF group (107.33±5.13 pg/ml; р=0.0015). ROC analysis of the sensitivity and specificity of cardiovascular risk stratification according to sFAS-L levels revealed the high prognostic value of this marker - ROC-Area±S.E. was 0.75±0.05 (95% confidence interval, 0.60 to 0.81; p=0.0005). There was a statistically significant moderate correlation of left ventricular (LV) ejection fraction with sFAS-L concentrations and a moderate direct correlation between serum sFAS-L concentrations and LV remodeling parameters. CONCLUSION: The serum level of sFas-L determines the development of ischemic LV remodeling and the severity of CHF, by increasing in proportion to the degree of disease progression. The determination of serum sFas-L levels assists in objectively estimating the severity of apoptosis and may be an important prognostic test to assess the course of CHF in patients with coronary heart disease.

Neurotoxic Non-proteinogenic Amino Acid ß-N-Methylamino-L-alanine and Its Role in Biological Systems.

Secondary metabolites of photoautotrophic organisms have attracted considerable interest in recent years. In particular, molecules of non-proteinogenic amino acids participating in various physiological processes and capable of producing adverse ecological effects have been actively investigated. For example, the non-proteinogenic amino acid ß-N-methylamino-L-alanine (BMAA) is neurotoxic to animals including humans. It is known that BMAA accumulation via the food chain can lead to development of neurodegenerative diseases in humans such as Alzheimer's and Parkinson's diseases as well as amyotrophic lateral sclerosis. Moreover, BMAA can be mistakenly incorporated into a protein molecule instead of serine. Natural sources of BMAA and methods for its detection are discussed in this review, as well as the role of BMAA in metabolism of its producers and possible mechanisms of toxicity of this amino acid in different living organisms.

Biochemical and Molecular Phylogenetic Study of Agriculturally Useful Association of a Nitrogen-Fixing Cyanobacterium and Nodule Sinorhizobium with Medicago sativa L.

Seed inoculation with bacterial consortium was found to increase legume yield, providing a higher growth than the standard nitrogen treatment methods. Alfalfa plants were inoculated by mono- and binary compositions of nitrogen-fixing microorganisms. Their physiological and biochemical properties were estimated. Inoculation by microbial consortium of Sinorhizobium meliloti T17 together with a new cyanobacterial isolate Nostoc PTV was more efficient than the single-rhizobium strain inoculation. This treatment provides an intensification of the processes of biological nitrogen fixation by rhizobia bacteria in the root nodules and an intensification of plant photosynthesis. Inoculation by bacterial consortium stimulates growth of plant mass and rhizogenesis and leads to increased productivity of alfalfa and to improving the amino acid composition of plant leaves. The full nucleotide sequence of the rRNA gene cluster and partial sequence of the dinitrogenase reductase (nifH) gene of Nostoc PTV were deposited to GenBank (JQ259185.1, JQ259186.1). Comparison of these gene sequences of Nostoc PTV with all sequences present at the GenBank shows that this cyanobacterial strain does not have 100% identity with any organisms investigated previously. Phylogenetic analysis showed that this cyanobacterium clustered with high credibility values with Nostoc muscorum.

[Quorum sensing regulation in bacteria of the family Enterobacteriaceae].

Bacteria are able to sense an increase in population density and can respond to it by coordinated regulation of the expression of certain sets of genes in the total population of bacteria. This specific mode of regulation is known as Quorum Sensing (QS). The QS systems include low-molecular-weight signaling molecules of different chemical natures and the regulatory proteins that interact with the signaling molecules. The QS systems are global regulators of bacterial gene expression. They play an important role in controlling metabolic processes in bacteria. This review describes QS systems in members of the bacterial family Enterobacteriaceae functioning with the involvement of various signaling molecules, including N-acyl-homoserine lactones, AI-2, AI-3, peptides, and indole. The differences of the QS system in these bacteria from those in other taxonomic groups of bacteria are discussed. Data on the role of different types of QS systems in the regulation of different cellular processes in bacteria, i.e., their virulence, the synthesis of enzymes and antibiotics, biofilm formation, apoptosis, etc. are presented.

[The duration of an HIV infection course and its influencing factors].

AIM: To study the duration of the natural course of HIV infection and to identify its influencing factors. SUBJECTS AND METHODS: 938 outpatient case histories of adult HIV-positive patients registered at the dispensary and the data of 3403 AIDS patients registered in the computer base, including those on 2588 dead people, were retrospectively analyzed. Kaplan-Meier survival analysis and Cox regression model were used. Gender, age, and route of infection were regarded as potential factors influencing the natural course of HIV infection. RESULTS: In Russia before the mass use of antiretroviral therapy (ART), the median survival from infection to death in the HIV-infected was 11.8 years; that from infection to establishment of AIDS was 11.6 years; the life expectancy following its diagnosis was 1.9 months. Patient age was a main factor influencing the course of HIV infection: in persons who had been infected with HIV at an age of over 35 years, lower CD4 lymphocyte counts and clinical progression occurred more rapidly than in those infected at a younger age. Less than 50% of the patients needed ART 5 years after HIV infection. CONCLUSION: An HIV-infected patient without ART survives almost twice less. It is necessary to detect HIV infection as early as possible and to regularly follow up patients regardless of the duration of infection in order to timely initiate its treatment.

[The efficacy and safety of a therapy regimen including raltegravir and a fixed dose combination of lamivudine and abacavir in previously rifabutin-treated patients with tuberculosis and HIV infection].

AIM: To evaluate the efficiency and safety of using raltegravir (RAL) twice daily in conjunction with a once-daily fixed dose combination of abacavir (ABC)/lamivudine (3TC) in patients with HIV infection and active tuberculosis who have not previously received antiretroviral therapy (ART) and have taken rifabutin as antituberculosis therapy (ATT). SUBJECTS AND METHODS: The efficiency of ART was evaluated in 28 patients from a change in HIV RNA levels and from an increase in CD4+ lymphocyte counts during 48-week treatment that had been completed by 15 (53.6%) patients. The main reason for therapy discontinuation was that the patients returned to the use psychoactive agents. RESULTS: After 24 and 48 weeks of ART, the level of HIV RNA reached the undetectable values (less than 50 copies/ml) in 81.25 and 75% of the patients, respectively (according to an analysis including the patients who had completed the study in conformity with the requirements of the protocol). In only 2 patients, the virological therapy proved to be ineffective, which was likely to be associated with noncompliance with drug therapy. Following 24- and 48-week therapy, the increase in median CD4+ lymphocyte counts was 70 and 208.5 per µl, respectively. The concurrent use of ART and ATT caused positive changes in the lung skiagraphic pattern in 92.9% of the patients and complete resolution of lung tissue infiltration in 71.4%. Mixed infection ended in a fatal outcome caused by a progressive tuberculous process in 3 (10.7%) patients, in 2 of them within the first 8 weeks of treatment. The concomitant use of ATT including rifabutin and an ART (RAL + ABC/3TC) regimen was safe since one patient was noted to have a RAL-related adverse event (AE) (an allergic reaction) and caused the patient to discontinue therapy. ATT was not discontinued because of AE in any case. CONCLUSION: The ART regimen containing RAL and a fixed dose combination of ABC/3TC for adult patients with tuberculosis concurrent with HIV infection who are on combined therapy using rifabutin for tuberculosis may be recommended for the treatment of this category of patients.

[The value of changes in CD8+CD28+ and CD4+CD28+ cells in patients with HIV infection concurrent with tuberculosis during treatment].

AIM: To study the proportion of CD8+CD28+ and CD4+CD28+ cells among the CD8+ and CD4+ lymphocytes and the changes in these indicators in patients with HIV infection/tuberculosis (HIV/TB) versus those with HIV infection and those with TB. SUBJECTS AND METHODS: One hundred and six persons were examined and included into 4 study groups: 1) 39 patients with concomitant HIV/TB; 2) 25 patients with HIV monoinfection without TB who had not previously received antiretroviral therapy; 3) 17 patients with TB without HIV infection; 4) 25 healthy individuals (a control group). RESULTS: CD28 expression was found to be much more reduced on the CD8 lymphocytes than that on the CD4 ones. This is likely to be due to earlier CD8 lymphocyte dysfunction in both the patients with HIV infection and those with HIV/TB although the CD4 cell is the basic virus target. CONCLUSION: The study of the proportion of CD8+CD28+ cells among the CD8 lymphocytes is of more informative value than the determination of that of CD4+CD28+ among the CD4 lymphocytes.

[Analysis of lethal outcomes in patients with newly-diagnosed tuberculosis of the respiratory organs in combination with HIV-infection].

AIM: To analyse lethal outcomes in patients with newly-diagnosed respiratory tuberculosis comorbid with HIV-infection depending on initial count of CD4+ lymphocytes. MATERIAL AND METHODS: Of 304 HIV patients with newly-diagnosed tuberculosis treated in Moscow Tubercusis Hospital N 7 in 2006-2010, 40 (13.2%) patients died. Tuberculosis diagnosis was made after detection of M. tuberculosis (MT) by different tests, MT DNA in different biological material, histological verification or by effectiveness of specific antituberculous therapy. Postmortem examinations were made according to the protocol. RESULTS: Significant differences were detected in patients with initial count of CD4+ lymphocytes less than 50 in 1 mcl. Specific CNS affection was found in patients with initial lymphocyte count CD4+ less than 100 in 1 mcl. Most of autopsy examinations registered generalized acutely progressive tuberculosis with multiple lesions of internal organs and lymph nodes (LN). Microscopy revealed obscure morphological picture of specific inflammation with prevalence of alternative-exudative tissue reactions in the absence of a productive inflammation component. Cases with submiliary dissemination which was invisible in macroscopic examination due to a bright picture of exudative tissue reaction (rare plethora of the lungs, alveolar and interstitial edema, perifocal inflammatory reaction of nonspecific reactive nature) and small size of the lesions. The comparison of clinical and autopsy diagnoses revealed that involvement of intrathoracic LN and miliary dissemination, according to autopsy, occurred much more frequently than shown by antemortem standard x-ray examination of the chest. CONCLUSION: It is strongly recommended to perform computed tomography of the chest in all HIV-infected patients with long-term fever but without visible alterations on chest x-ray.

[Polymorphism of eNOS and iNOS Genes and Chronic Heart Failure in Patients With Ischemic Heart Disease].

UNLABELLED: URGENCY: Despite substantial progress in the treatment of coronary heart disease (CHD) and chronic heart failure (CHF) prognosis in these conditions remains extremely serious. This warrants their timely prevention and early detection. Aim. To study influence of inducible NO synthase (iNOS) (CCTTT)n, Glu298Asp and diallel polymorphism in the fourth intron (4a/4b polymorphism) of endothelial NO synthase gene (eNOS gene) on the state of endothelial function and risk of development of CHF in patients with CHD. MATERIALS AND METHODS: 165 patients with CHD were studied (121 male and 44 female, mean age 56.7 + or - 5.3 years). Vasomotor endothelial function was evaluated using ultrasound method in the reactive hyperemia and trinitroglycerol tests. Genotypes were identified using RFLP analysis of PCR products. Control group consisted of 114 persons (54 male and 60 female, mean age 53.2 + or - 4.9 years). RESULTS: It was determined that the number of repeats of polymorphic locus (CCTTT)n of the iNOS gene and Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state were associated with the risk of development of CHD and class of severity of CHF clinical manifestation. In addition Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state was associated with the severity and unfavorable development of CHF. The endothelial-dependent dysfunction was more severe in homozygotes of Glu allele of the polymorphic locus Glu298Asp of eNOS gene than in carrier of allele 298Asp. Associations between polymorphic variant of VNTR intron 4 gene eNOS and CHF with the risk of development and endothelial dysfunction were not found. CONCLUSION: An association between polymorphism of iNOS gene (CCTTT)n, eNOS gene (Glu298Asp) with development of CHD and severity of CHF was shown. The polymorphism of eNOS gene (Glu298Asp) was associated with endothelial dysfunction.

[Impact of Gly389Arg beta1-adrenoceptor polymorphism on the risk of chronic heart failure, the nature of its course, and on the efficiency of its treatment with carvedilol].

AIM: To study beta1-adrenoceptor gene (ADRB1) polymorphism on the development and course of chronic heart failure (CHF) and on the efficiency of its treatment with the beta-adrenoblocker carvedilol in patients with coronary heart failure. SUBJECTS AND METHODS: Two hundred and twenty-six patients (149 males and 77 females; mean age 55.9 +/- 5.8 years) with CHF, who received continuous basic therapy: angiotensin-converting enzyme inhibitors, a diuretic, an aldosterone antagonist, digoxin, and a beta-adrenoblocker, were examined; 68 patients were given for 24 weeks carvedilol (its starting dose was 3.125 mg twice daily with its further adjustment until an individually tolerable dose was achieved). Genotypes were identified by the restriction fragment length polymorphism analysis of polymerase chain reaction products. A control group comprised 136 subjects (63 males and 73 females; mean age 55.9 +/- 5.8 years) without signs of cardiovascular disorders, as evidenced by the examination. RESULTS: In patients with CHF, the Gly allele of the Gly389Arg polymorphic locus of the ADRB1 gene in homozygous state was associated with the high individual risk for CHF, the severity of its clinical manifestations and the nature of its course while carriage of the Arg allele of the Gly39Arg polymorphic locus manifested itself as a protective factor. During long-term carvedilol therapy, CHF patients with the Arg/Arg genotype of the ADRB1 gene were observed to have a more pronounced decrease in the functional class of heart failure, a significant increase in left ventricular ejection, and a decrease in left ventricular end-systolic and end-diastolic sizes as compared with patients with the Gly/Arg genotype. CONCLUSION: There were associations of the polymorphism of ADRB1 gene (the Gly39Arg polymorphic locus) with the development and severity of CHF and with the efficacy of therapy with beta-adrenoblocker carvedilol.