Activation of the central melanocortin system chronically reduces body mass without the necessity of long-term caloric restriction.

Melanotan II (MTII) is a potent appetite suppressor that rapidly reduces body mass. Given the rapid loss of anorexic response upon chronic MTII treatment, most investigations have focused on the initial physiological adaptations. However, other evidence supports MTII as a long-term modulator of energy balance that remains to be established. Therefore, we examined the chronic effects of MTII on energy homeostasis. MTII (high or low dose) or artificial cerebrospinal fluid (aCSF) was infused into the lateral ventricle of the brain of 6-month-old F344BN rats (6-7/group) over 40 days. MTII suppressed appetite in a dose-dependent manner (P < 0.05). Although food intake promptly rose back to control level, body mass was persistently reduced in both MTII groups (P < 0.01). At day 40, both MTII groups displayed lower adiposity than the aCSF animals (P < 0.01). These results show that MTII chronically reduces body mass without the requirement of long-term caloric restriction. Our study proposes that food restriction helps initiate mass loss; however, combined with a secondary pharmacological approach preserving a negative energy balance state over time may help combat obesity.

[ROLE OF SLC2A9 AND ABCG2 GENE POLYMORPHISMS IN ORIGIN OF HYPERURICEMIA AND GOUT].

The polymorphisms V253I, Q126X, Q141K of SLC2A9 and ABCG2 genes were characterized. GCA и GTC haplotypes of Q126X and Q141K variants can be predictors of gout. The relationship of these polymorphisms with hyperuricaemia according to gender, metabolic syndrome components, with the response to allopurinol was analyzed. It has been established that Q141K polymorphism can directly modulate BCRP-mediated allopurinol and oxypurinol efflux, the K allele is associated with a lower reduction in serum uric acid in response to allopurinol treatment.

[The use of a "buffet" style meals in the system of health-resort treatment].

The authors summarized literature sources, concerning modern ideas about the role of nutritional therapy in the system of health-resort treatment. The authors also made a research on the basis of literature, concerning health-resort nutrition divided into two systems-- buffet system and special-order system. On the basis of sanatorium establishments of the Ministry of Defense authors summarized an experience of clinical nutrition in different age groups and categories of patients. On the basis of current regulatory acts were defined forms and methods of meal catering in the Russian Federation. The results of the study are a scientific supposition for substantiation of management decision-making process, which allows to increase an efficiency of health-resort treatment via nutrition therapy.

[Hemostasiological, lipidemic, and hemodynamic indicators associated with the risk of cardiovascular death in high- and very high-risk patients according to the SCORE scale].

AIM: To identify lipidemic, hemostasiological, and hemodynamic indicators associated with the risk of cardiovascular death in high- and very high-risk patients. SUBJECTS AND METHODS: One hundred and forty-eight patients whose mean age was 50.8 +/- 4.4 years were examined. All the patients were divided into high (1 group) and very high (2 group) cardiovascular death risk groups according to the SCORE scale. Lipid metabolism, hemostatic system parameters (fibrinogen, time of ADP-induced platelet aggregation initiation, D-dimer), endothelial dysfunction markers (von Willebrand factor), and echocardiographic findings were studied. RESULTS: Multivariate regression analysis showed that the odds ratio for a cardiovascular death risk was 1.8 (95% confidence interval (CI), 1.1 to 4.2; p = 0.04) in patients with a D-dimer level of greater than 1 mg/ml, 0.77 (95% CI, 0.6 to 0.97; p = 0.03) in those with an ADP-induced platelet aggregation initiation time of 13.5 sec, 1.04 (95% CI, 1.01 to 1.07; p = 0.02) in those with an end-diastolic volume of more than 123 ml, 1.1 (95% CI, 1.04 to 1.2; p = 0.003) in those with an end-diastolic dimension of more than 51 mm, 1.5 (95% CI, 1.1 to 2.0; p = 0.009) in those with a ventricular septal thickness of more than 11.5 mm, and 2.1 (95% CI, 1.03 to 3.2; p = 0.0032) in those with avon Willebrand factor level of more than 140%. CONCLUSION: The high levels of von Willebrand factor, D-dimer, ADP-induced platelet aggregation, triglycerides, end-diastolic volume, end-diastolic dimension, and ventricular septal thickness are independent predictors of cardiovascular death in very high-risk patients. These indicators bear out a close relationship between lipid metabolic and hemostatic disturbances and between endothelial dysfunction and intracardiac hemodynamic worsening in these patients.

State of integral remodeling parameters of target organs in patients with essential hypertension and obesity.

Arterial hypertension combined with obesity is a very common form of comorbid disease in most countries all over the world. The combination of these diseases is characterized by mutual burdening of remodelling processes in important target organs, what greatly increases the risk of cardiovascular complications and death. The mechanisms of injury progression to vital organs in essential hypertension (EH) and obesity have some common features. The most important risk factors of target organs damage are hemodynamic and neurohumoral: inflammatory, effectors of the renin- angiotensin-aldosterone system, insulin resistance and others. Polyethiologic remodelling, lack of knowledge concerning violations in structural and functional status of important target organs and mechanisms of the interactions of their progression with this comorbidity require further study of these issues. The objective of the study was the comparative study of the state of integral indicators of structural and functional state of the heart, blood vessels and liver in patients with EH second stage with normal body weight and with concomitant obesity I and II degrees. This study found that the presence of obesity I and II in patients with EH stage II is associated with the concentric type of left ventricular hypertrophy, saved by its ejection fraction and impaired diastolic filling processes. For the patients with EH in the early stages of obesity the following characteristics are quite typical: considerable increase of intima media thickness in the carotid arteries, increasing the stiffness in the main arteries and liver parenchyma, impaired of the functional state of endothelial.

[Clinical case. Chronic gastritis associated with Helicobacter pylori and Epstein-Barr virus].

The article describes a clinical case of chronic gastritis associated with Helicobacter pylori infection and Epstein-Barr virus. The authors draw attention to the peculiarities of dyspepsia syndrome, on the characteristics of this disease in the endoscopic and morphological study.

[Structural and functional changes of cell membranes in patients with renocardiac chronic syndrome].

The 53 patients with chronic renocardiac syndrome, with hypertension in chronic kidney disease, were investigated. In the presence of chronic renal failure there is a decrease of cholesterol in the membrane, which is the basis for the violation liquid characteristics of cell membranes. Changes in the exchange of phospholipids and an increase in the exchange rate reflect increasing phosphatidylcholine lipid peroxidation, increasing in chronic renal failure. The degradation of cell membranes reflects a compensatory accumulation in these fractions of phosphatidylcholine, a major component of the outer layer of biomembranes. Regardless of the degree of renal dysfunction and clinical manifestations of the disease in the membranes of platelets accumulate lizoform phospholipids, indicating a strengthening of the processes of lipid peroxidation and accumulation of biologically active substances, which have membrane-destructive activity.

High dietary fructose does not exacerbate the detrimental consequences of high fat diet on basilar artery function.

The objective of the study was to determine the effects of a high fat (HF) diet alone or with high fructose (HF/F) on functional and structural changes in the basilar arteries and cardiovascular health parameters in rats. Male Sprague Dawley rats were fed either a HF (30%) or HF/F (30/40%) diet for 12 weeks. The basilar artery was cannulated in a pressurized system (90 cm H2O) and vascular responses to KCl (30 - 120 mM), endothelin (10(-11) - 10(-7) M), acetylcholine (ACh) (10(-10) - 10(-4) M), diethylamine (DEA)-NONO-ate (10(-10) - 10(-4) M), and papaverine (10(-10) - 10(-4) M) were evaluated. Rats were also monitored for food intake, body weight, blood lipids, blood pressure, and heart rate. At death, asymmetrical dimethyl arginine level (ADMA) and leptin were assayed in serum. Although there was no significant difference in weight gain and food intake, HF and HF/F diets increased body fat composition and decreased the lean mass. HF/F diet accelerated the development of dyslipidemia. Although resting blood pressure remained unchanged, stress caused a significant elevation in blood pressure and a modest increase in heart rate in HF fed rats. Both HF and HF/F diet resulted in decreased response to endothelium-dependent and -independent relaxation, whereas increased basilar artery wall thickness was observed only in HF group. Serum leptin levels positively correlated with wall thickness. Moreover serum ADMA was increased and eNOS immunofluorescence was significantly decreased with both diets. These data suggest that the presence of high fructose in a HF diet does not exacerbate the detrimental consequences of a HF diet on basilar artery function.

[In vitro study of antiviral activity of Myramistin against subtypes H3N2 and H5N1 of influenza virus].

In vitro antiviral effect of myramistin on influenza virus (MDCK cell culture) was studied. The drug showed significant dose-dependent antiviral activity against the virus. When used prophylactically (1 hour before exposure to the virus) in subtoxic doses, myramistin was effective in inhibiting replication of the influenza virus [strains A/Aichi/2/68 (H3N2) and A/Chicken/Suzdalka/Nov-11/2005 (H5N1)]. In urgent prophylaxis (1 hour after exposure to the virus) the protective effect was less pronounced, especially when the contamination dose was high. When the drug was added 12 hours after exposure to the virus, it had no protective effect on the MDSK cell monolayer. The prospects of the myramistin use as a prophylactic agent in grippe are discussed.

[Isolation and characterization of genetic recombinants in protoplast fusion in Saccharopolyspora erythraea]. / Poluchenie i kharakteristika geneticheskikh rekombinantov pri sliianii protoplastov Saccharopolyspora erythraea.

Formation of genetic recombinants after conjugation and protoplast fusion in Saccharopolyspora erythraea, an organism producing erythromycin, was studied comparatively. After the protoplast fusion the frequency of all the classes of the haploid recombinants increased 10 to 460 times by comparison with the conjugation. The protoplast fusion was characterized by higher diversity of the recombinant classes, up to 45.5 per cent of the recombinants being formed at the account of multiple crossing overs. It was shown that unlike conjugation of the S. erythraea strains the protoplast fusion had no gradient of inheritance of the parent genetic markers by the recombinants. The results indicated that in S. erythraea protoplast fusion the recombination involved more genes of the parent strains. This makes promising the procedure for genetic analysis and design of erythromycin-producing strains.

[Isolation and characteristics of rifampicin-resistant mutants of Streptomyces erythraeus strain]. / Poluchenie i kharakteristika rifampitsinoustoichivykh mutantov u shtamma Streptomyces erythraeus.

Erythromycin-producing strains of S. erythraeus were characterized with respect to formation of spontaneous and induced rifampicin-resistant mutants. It was shown that the frequency of spontaneous rifampicin-resistant mutants formed by various strains amounted to 0.9.10(-8) = 9.1.10(-7). In some events the exposure to nitrosoguanidine increased the frequency of such mutants by 2 orders of magnitude. The rifampicin-resistant mutants differed in antibiotic resistance. It was found that a significant part of the rifampicin-resistant mutants became sensitive to heating (19.1 per cent) and lost the ability to form aeromycelium (21.8 per cent).

[Effect of non-steroid anti-inflammatory and glucocorticoid agents on development of gastrointestinal lesions in patients with rheumatic diseases]. / Vliianie nesteroidnykh protivovospalitel'nykh i gliukokortikoidnykh preparatov na razvitie porazhenii pishchevaritel'nogo kanala u bol'nykh s revmatologicheskimi zabolevaniiami.

A comparative evaluation was done of frequency and severity of upper gastrointestinal mucosal lesions in patients taking nonsteroid antiinflammatory drugs (NSAID) and glucocorticosteroids (GCS). A total of 65 rheumatic patients examined endoscopically entered the study. The patients were divided into three groups. Group I comprised 12 patients placed on GCS only, group II was 35 patients on NSAID, group III was 18 patients who received NSAID plus GCS. Gastropathies were diagnosed in 25%, 45.7%, 44.4% of patients in groups I, II, and III respectively. Group II patients had a higher incidence of serious afflictions. As far as the gastrointestinal mucosa is concerned, GCS have been shown to be superior to NSAID. A combined use of NSAID + GCS, unlike NSAID alone, has not been found to increase the risk of development of gastropathy.

Leptin overexpression in VTA trans-activates the hypothalamus whereas prolonged leptin action in either region cross-desensitizes.

High-fat feeding or CNS leptin overexpression in chow-fed rats results in a region-specific cellular leptin resistance in medial basal hypothalamic regions and the ventral tegmental area (VTA). The present investigation examined the effects of targeted chronic leptin overexpression in the VTA as compared with the medial basal hypothalamus on long-term body weight homeostasis. The study also examined if this targeted intervention conserves regional leptin sensitivity or results in localized leptin resistance. Cellular leptin resistance was assessed by leptin-stimulated phosphorylation of signal transducers and activators of transcription 3 (STAT3). Tyrosine hydroxylase was measured in hypothalamus and VTA along with brown adipose tissue uncoupling protein 1. Leptin overexpression in VTA tempered HF-induced obesity, but to a slightly lesser extent than that with leptin overexpression in the hypothalamus. Moreover, the overexpression of leptin in the VTA stimulated cellular STAT3 phosphorylation in several regions of the medial basal hypothalamus, whereas verexpression in the hypothalamus did not activate STAT3 signaling in the VTA. This unidirectional trans-stimulation did not appear to involve migration of either the vector or the gene product. Long-term leptin overexpression in either the medial basal hypothalamus or VTA caused desensitization of leptin signaling in the treated region and cross-desensitization of leptin signaling in the untreated region. These results demonstrate a role of leptin receptors in the VTA in long-term body weight regulation, but the trans-activation of the hypothalamus following VTA leptin stimulation suggests that an integrative response involving both brain regions may account for the observed physiological outcomes.

Self-organization of ascending-bubble ensembles.

Self-organization of hydrogen bubbles generated by laser-treated areas of an aluminum plate etched in a basic aqueous solution of ammonia is studied experimentally and theoretically. The dynamics of the establishment of a stationary pattern of gas bubbles is experimentally is shown. In the theoretical model, the velocity field of liquid flows around an ensemble of several bubbles is obtained. Modeling of the process of self-organization of gas bubbles is performed on the basis of a continuum model of a bubble jet. Under certain assumptions, the pressure of a diluted system of bubbles is described by an equation similar to that for nonideal gas, which follows the van der Waals equation of state. The model predicts an alignment of gas bubbles along bisectors of the laser-treated area limited by a square, which is in good agreement with experimental observations. Further development of the model leads to an equation with a negative diffusion coefficient that may be responsible for symmetry breakdown and pattern formation.