[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.

[Assessment of the role of matrix metalloproteinase-3 gene polymorphism in the development of chronic heart failure].

AIM: To study the impact of a polymorphic variant of the matrix metalloproteinase-3 (MMP-3) gene on the development and course of chronic heart failure (CHF) in patients with coronary heart disease. SUBJECTS AND METHODS: A total of 277 patients with New York Heart Association (NYHA) Functional Class (FC) II-IV CHF were examined. MMP-3 -1171 5A/6A genetic polymorphism was studied by polymerase chain reaction. A control group included 136 patients (mean age 53.6 ± 4.8 years) with no signs of cardiovascular diseases, as evidenced by the examination. RESULTS: The frequency of the 5A allele and the 5A/5A genotype of the 1171 5A/6A polymorphic locus in the MMP-3 gene proved to be higher in the patients with CHF than that in the control group. Thus, the variability of the 5A allele (odds ratio (OR), 1.39; 95% confidence interval (CI): 1.033 to 1.869; p = 0.03) and the 5A/5A genotype (OR, 2.15; 95% CI: 1.131 to 4.070; p = 0.02) was associated with increased risk for CHF. There were significant differences in the frequency of MMP-3 alleles and genotypes in relation to FC of CHF. The frequency of the 5A/5A genotype was substantially higher in the patients with NYHA FC IV CHF than that in those with NYHA FC II CHF (32.8% versus 15.2%; p = 0.039). The frequency of the 5A allele was significantly higher in the patients with NYHA FC IV CHF than that in those with NYHA FC II CHF (55.5% and 39.3%; respectively; p = 0.019). Thus, the carriage of the 5A allele and the 5A/5A genotype of the 1171 5A/6A polymorphic locus in the MMP-3 gene is a risk factor of severe CHF. CONCLUSION: The determination of MMP-3 -1171 5A/6A polymorphism may be recommended for the early prediction of a risk for the development and severe course of CHF.

Changes in lipid metabolism during Walker 256 tumor growth and the therapeutic effect of hyperthermia.

The dynamics of lipoprotein content during Walker 256 tumor growth in rats was studied. Moderate changes in HDL and LDL were paralleled by significant changes in VLDL level. A 2-fold increase of VLDL in comparison with the intact control was recorded on day 10 of tumor growth. Exposure to total hyperthermia additionally stimulated VLDL synthesis and this parameter increased by 4 times and more in rats with tumors in comparison with controls. This effect of hyperthermia correlated with significant subsequent decrease of rat mortality caused by the lethal effect of the tumor.

[The evaluation of metastatic damage of the liver of the Wistar rats under conditions of spontaneous development of the Walker 256 carcinosarcoma].

There was held micro- and ultrastructural study of the liver of the Wistar rats in the dynamics of development of transplantable Walker 256 carcinosarcoma. The regularities of the progression of the tumor process in the form of liver metastases with appearance of intralobular metastases. In the early stages of tumor development it was marked activation of cytotoxic function of the liver with necrosis of tumor lesions accompanied by a decrease of the structural density of metastases. In advanced stages of development of the Walker 256 carcinosarcoma an estimation of parameters of tumor invasion in the liver showed an intensification of these processes with increased severity of inflammatory reactions.

[Pharmacogenomic control of angiotensin converting enzyme gene I/D polymorphism predominant risk factor of development of chronic heart failure and target of enalapril treatment].

Aim of investigation - to study effect of angiotensin-converting enzyme (ACE) gene polymorphism as a dominant risk factor of development of chronic heart failure (CHF) and target for effective therapy with ACE inhibitor enalapril in patients with ischemic heart disease. We followed 226 patients with CHF on stable permanent basic therapy comprising -adrenoblocker, diuretic, aldosterone antagonist, digoxin, and ACE inhibitor. Seventy eight patients received enalapril (starting dose 2.5 mg twice daily with subsequent titration up to 10-20 mg twice daily). Control group comprised 136 patients without cardiovascular abnormalities. Allele D of polymorphic locus I/D of ACE gene in homozygous state was associated with high risk of development and severity of clinical manifestations of CHF. In patients with D/D genotype of ACE gene at the background of therapy with enelapril we noted more pronounced lowering of CHF functional class and augmentation of left ventricular ejection fraction compared with patients having I/I and I/D genotypes. We revealed associative interrelationships of ACE gene polymorphism (polymorphic locus I/D) with development and severity of CHF as well as effectiveness of therapy with an ACE inhibitor enalapril.

[Impact of angiotensionogen and angiotensin II receptor type 1 gene polymorphisms on the development and course of chronic heart failure].

AIM: To study the impact of angiotensinogen (AGT) and angiotensin II receptor type 1 (AGTR1) gene polymorphisms on the development and course of chronic heart failure (CHF) in patients with coronary heart disease (CHD). SUBJECTS AND METHODS: Two hundred and twenty-six patients (149 men and 77 women; mean age 55.9 +/- 5.8 years) with CHF were examined. Genotypes were identified by the restriction fragment length polymorphism analysis of polymerase chain reaction products. A control group comprised 136 subjects (63 men and 73 women; mean age 53.6 +/- 4.8 years) without signs of cardiovascular diseases, as evidenced by the examination. RESULTS: The T allele of the M235T polymorphism in the AGT gene was found to be associated with the development and unfavorable course of CHF in patients with CHD. At the same time, carriage of the M allele of the M235T polymorphism in the AGT gene reflected the favorable course of this disease. That of the C allele and A/C genotype of the A1166C polymorphism in the AGTR1 gene was associated with the development of CHF and the A allele and A/A genotype manifested themselves as protective factors. According to the severity of CHF and the nature of its course, the distribution of frequencies of the genotypes and alleles of the A1166C polymorphism in the AGTR1 gene showed no significant differences between the patient groups. CONCLUSION: There were associations of the polymorphisms of the AGT gene (the M235T polymorphic marker) and the AGTR1 gene (the A1166C polymorphic marker) with the development of CHF in patients with CHD.

Proliferation of Walker 256 carcinosarcoma cells: effect of whole-body hyperthermia and antitumor agents.

We studied the main biological characteristics of spontaneous growth of Walker 256 carcinosarcoma and under conditions of antitumor therapy. A combination of whole-body hyperthermia and cytostatic treatment (cyclophosphamide and melatonin) produced maximum suppression of the tumor growth, inhibition of mitotic activity of tumor cells, and stimulation of their necrotic and apoptotic death. The maximum decrease in mitotic activity of tumor cells was observed after combined exposure to whole-body hyperthermia and both cytostatic preparations; enhancement of apoptotic cell death and the decrease in the tumor node weight were also most pronounced under these conditions and practically no body weight loss was recorded in this case.

[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.

[Effect of whole-body controlled hyperthermia on lipid peroxidation products and lysosomal enzyme levels in blood serum from Wistar rats with Walker-256 carcinosarcoma].

Whole-body controlled hyperthermia (up to 43.5 degrees C) of Wistar rats with Walker-256 carcinosarcoma was followed by symptoms of enhanced lipid peroxidation for 3-14 days and release of lysosomal enzymes into blood on day 14. Our data, in totality, point to a potential to stimulate tumor cell apoptosis.

Ultrastructural and stereological analysis of walker 256 carcinosarcoma cells at various stages of their differentiation.

Ultrastructural and stereological study of Walker 256 carcinosarcoma cells implanted into the femoral muscle of Wistar rats was performed. Two types of Walker 256 carcinosarcoma cells were distinguished and their ultrastructural analysis was carried out. Five differentiation stages were described for each of the two cell types. Differentiation of carcinosarcoma cells was associated with a decrease of the nucleus/cytoplasm ratio, enlargement of the cell, and hyperplasia of granular cytoplasmic reticulum elements, fixed ribosomes, and mitochondria. Differences in the ultrastructure of the two cell types at similar differentiation stages were detected.

Immunohistochemical study for the expression of Bcl-2 family proteins in Walker 256 carcinosarcoma cells under the influence of cytostatic drugs.

Immunohistochemical study was performed to evaluate the expression of Bcl-2 family proteins (Bcl-2, Bax, and Bad) in Walker 256 carcinosarcoma cells after implantation into the thigh muscle of male Wistar rats (10(6) cells). The experiment was conducted under conditions of spontaneous tumor development and individual or combined treatment with melatonin and cyclophosphamide. The use of melatonin as monotherapy or in combination with cyclophosphamide was followed by a significant decrease in Bcl-2 expression in carcinosarcoma cells. The Bcl-2/Bax and Bcl-2/Bad ratio was significantly reduced under these conditions (particularly after combined treatment with cytostatic drugs). These changes were accompanied by a significant (by 93.61%) decrease in the volume of transplantable tumor on day 14. Daily treatment with melatonin was accompanied by significant changes in the structure of Walker 256 carcinosarcoma. It was manifested in the formation of connective tissue septa and pseudofollicles.

[Characteristics of systemic inflammatory reaction in elderly patients of different age with the chronic heart failure].

The peculiarities of development systemic inflammatory reactions during the chronic heart failure were studied in the research. The patients with different severity of the chronic heart failure and different clinical course were examined at the beginning and in the dynamics of the clinical observation. The functional activity of neutrophils, pro- and antioxidant activity of serum were estimated in these patients. It was found that the functional activity of neutrophils in the course of systemic inflammatory reactions during the chronic heart failure decreased against the misbalances between pro- and antioxidative

Use of primary human fetal chondroblast culture for xenotransplantation into rat articular cartilage defect.

The possibility of xenotransplantation of human fetal chondroblasts was studied. Filling of the rat articular cartilage defect with a tissue-engineering construction based on primary culture of human fetal chondroblasts and chitosan gel caused no immune rejection over 60 days and provided the formation of organotypical regenerate due to proliferation and differentiation of donor fetal chondroblasts and their integration in the recipient cartilage tissue.

[Characteristics of the cytokines and secretory IgA balance in the oral liquid in lymphoma patients with periodontal diseases].

We studied a balance between pro- and anti-inflammatory cytokines and secretory IgA in the oral liquid in lymphoma patients with chronic generalized periodontal diseases (CGPD). A marked increase in the level of IL-1 beta and a decrease in the level of INF-gamma were seen in lymphoma patients compared to patients without somatic pathology. This necessitates addition of local immunocorrection to rehabilitation programs for lymphoma patients to activate a monocytic-macrophagal phase of the immune response with subsequent activation of specific immune response.

[Correction of endotoxicosis in alcoholic pancreatitis in elderly and senile patients using discrete plasmapheresis].

The majority of critical conditions in man occur in diseases accompanied with development of endogenic intoxication syndrome. The search for universal criterion and design of highly effective programs for correction of this condition are of great importance for internal medicine and surgical practice. Discrete plasmapheresis for endotoxicosis in elderly and gerontological patients has its specific features which should be taken into consideration because of low adaptation abilities of such group of patients.