[Effect of the energy metabolism regulator Yantar-Antitox on the system of energy production in rat liver during experimental pathology of beta-oxidation].

Effects of the Yantar-Aantitox (succinic acid preparation) preparation on bioenergetic processes in mitochondria of rat liver during the experimental disorders of beta oxidation process evoked by 4-pentenoic acid have been studied. It is established that the course administration of Yantar-Antitox leads to normalization of disturbed bioenergetic processes in rat liver, which is due to stimulation of the rapid metabolic cluster of mitochondria.

[Functional state of a sphingomyeline cycle and free radical lipid oxidation activity of a rat's liver during different phases of starvation].

The functional state of a sphingomyeline cycle and character of its mutual relations with the processes of free radical lipid oxidation during starvation of animals without any restriction of access to drinking water at 1, 2, 3 day (I phase) and 6 day (II phase of starvation) were studied at the liver of rats. The maximal values of the ceramide/sphingomyeline ratio and activity neutral sphingomyelinase and executive caspase-3 were reached in a liver of animals at the 3rd day of starvation. From the 3rd day of starvation the concentration of the tumour necrosis factor-alpha which is one of activators neutral sphingomyelinase was increase in rats blood serum. During the extent of large part of the I phase of starvation the intensity of free radical lipid peroxidation in a liver had almost the same level as in control group--that was a result of the high-grade functioning of antioxidant defense system. After transition the I phase of starvation into the II phase (6 day of experiment) the oxidative stress was developed as result of an exhaustion of system antioxidant defense potential in a liver. The results of this data can testify that during I phase of starvation in a liver the conditions was raised for display of the ceramide-mediated proapoptotic signalling. We assume that ceramide-mediated apoptosis is one of mechanisms of optimization of liver cellular population at the frames of metabolic adaptation. The I phase of starvation in a liver proves by the ceramide-mediated proapoptotic signaling developing. During the II phase of starvation the oxidative stress process were prevailed.

[The parameters of collagen proteolytic and metabolic systems in chronic liver diseases of viral and toxic etiologies].

AIM: To study a relationship of the plasma activity of elastase-like and collagenase-like proteinases and their inhibitors to hepatic collagen metabolism and to detect the serum markers of fibrosis severity. SUBJECTS AND METHODS: Three hundred and fifty-nine patients with chronic liver diseases (CLD), including 118 patients with chronic viral hepatitis (CVH), 113 with CVH concurrent with alcoholic liver disease (ALD), 109 with ALD, and 19 with CLD in the presence of opiomania were examined. The activities of alpha1-proteinase inhibitor and alpha2-macroglobulin (alpha2-MG) were determined by the unified spectrophometric assay from the inhibition of N-benzoyl-arginine ethyl ester hydrolysis. The activity of elastase-like proteinases was determined by enzymatic assay from the hydrolysis of the synthetic substrate N-butyloxycarbonyl-L-alanine-para-nitrophenyl ester. That of collagenase-like proteinases was determined, by using a collagen type 1 substrate and expressed in terms of micromoles of the resultant hydroxyproline. The content of hydroxyproline was determined by a color reaction with demethylbenzaldehyde, a free, peptide- and protein-bound hydroxyproline; their fraction was obtained under various conditions of plasma protein isolation and hydrolysis. Plasma fibronectin levels were measured by solid-phase immunoassay. Liver biopsy specimens were morphologically studied in the majority of patients to determine the histological hepatitis activity index and the stage of fibrosis. RESULTS: Fibrois formation in the liver in its chronic diseases was attended by a significant reduction in the activity of collagenase-like proteinases hydrolyzing collagen and by the lower activity of alpha2-MG, an inhibitor limiting collagen formation. CONCLUSION: The identified changes make themselves evident just in early fibrosis, which suggests the rapid onset of imbalance in the mechanisms responsible for regulation of connective tissue synthesis and promotes intensified fibrosis formation.

[Activity of the sphingomyelin cycle enzymes and concentration of products of sphingomyelin degradation in the rat liver in the course of acute toxic hepatitis].

Activity of key enzymes of a sphingomyelin cycle and the maintenance of its components (sphingomyelin, ceramide and sphingosine-1-phosphate) have been studied in livers of rats in dynamics of the acute toxic hepatitis caused by hypodermic introduction of an oil solution of CCl4. Sphingomyelinase activity significally increased already on early terms and remained increased over the whole period of observation. Activity of ceramidase insignificantly differed from the control level. The levels of sphingomyelin and sphingosine-1-phosphate did not undergo marked changes while ceramide content significally increased. Thus, balance between liver content of ceramide (proapoptotic) and the sphingosine-1-phosphate, being the antiapoptotic factor, was shifted towards ceramide. In sphingomyelin molecules there was a significant decrease in the content of fatty acids C18: and C22:2, while in ceramide molecules and sphingosine-1-phosphate only fatty acid C22:2 changed. In spite of significant decrease in content of some unsaturated fatty acids, calculated unsaturation coefficients of the fatty acid component of the sphingomyelin cycle metabolites. Thus, our results together with literature data suggests involvement of ceramide-mediated apoptosis in the pathogenesis of acute toxic hepatitis. Elimination of damaged hepatocytes facilitates realization of repair processes and optimization of cellular community of a liver.

[Paticipation of cannabinoid receptors in the regulation of cardiac rhythm and cardiac contractility].

It has been found that i. v. administration of cannabinoid receptor (CB) agonists (HU-210, ACPA, anandamide, methanandamide) induced a decrease in the heart rate (HR) in anesthetized rats. Pretreatment with CB1 receptor antagonist SR141716A completely abolished a negative chronotropic effect of CB receptor agonist HU-210. The CB2 receptor antagonist SRI 44528 did not prevent a HU-210-induced decrease in the HR. Pretreatment with the ganglion blocker hexamethonium had no effect on the negative chronotropic action of HU-210. Addition of HU-210 (100 nM) to perfusion solution induced a decrease in the HR, left ventricular development pressure, rate of contractility and relaxation of isolated perfused rate heart without change in end diastolic pressure. These data suggest that cardiac CBI receptor activation induces a decrease in the HR both in vivo and in vitro. An occupancy of the same receptors mediates a negative inotropic effects of cannabinoids.

[The effect of K(ATP)-channel activation on the electrical stability of myocardium in rats with postinfarction cardiosclerosis]. / Vliianie aktivatsii K(ATP)-kanalov na élektricheskuiu stabil'nost' miokarda pri postinfarktnom kardioskleroze.

Opening of the ATP-dependent K-channels (K(ATP) channels) upon intravenous administration of the cardioselective activator BMS 180448 (3 mg/kg) decreased the ventricular fibrillation threshold (VFT) in rats with postinfarction cardiosclerosis (PIC). Preliminary injection of the selective K(ATP) channel blocker glibenclamide (0.3 mg/kg, i.v.) completely abolished the profibrillatory effect of BMS 180448. At the same time, the mitochondrial K(ATP) channel blocker 5-hydroxydecanoic acid (5 mg/kg) did not influence the proarrhythmogen activity of BMS 180448. Simultaneous administration of the sarcoK(ATP) channel inhibitor HMR 1098 (3 mg/kg) and BMS 180448 increased the VFT up to a level in intact animals. Administration of the mitoK(ATP) channel activator diazoxide (5 mg/kg) after preliminary treatment with guanethidine (50 mg/kg) increased the VFT in rats with PIC. It is concluded that opening of the mitoK(ATP) channels increases the cardiac electrical stability in rats with PIC.

[Lipid spectrum of lymphocyte plasma membranes in abstinent syndrome in patients with opioid dependence]. / Spektr lipidov plazmaticheskikh membran pri abstinentnom sindrome u bol'nykh opioidnoi narkomaniei.

The lipid composition of the lymphocyte plasmatic membranes was studied in the withdrawal syndrome as observed in patients with opioid addiction. The method of thin-layer chromatography was used to identify the lipid fractions. Higher cholesterol content, a bigger trans-membrane asymmetry index and a higher ratio between cholesterol and total phospholipids were detected. The contents of the lysophospholipid fraction and of the total fraction of phosphatidylcholine and serine were increasing. The contents of cholesterol ethers as well as of the fractions of sphingomyelin and phosphatidyl ethanolamine were found to be lower.

[The activity of superoxide dismutase and glutathione peroxidase and the level of malonic dialdehyde in prematures with hypoxic disorders of the central nervous system]. / Aktivnost'superoksiddismutazy,glutationperoksidazy i uroven; malonovogo dial'degida u nedonoshennykh novorozhdennykh s gipoksicheskim porazheniem tsentral'noi nervnoi sistemy.

The activity of superoxide dismutase and glutathione peroxidase and the level of malonic dialdehyde were studied 53 prematures with hypoxia of the central nervous system. A low activity of superoxide dismutase and glutathione peroxidase, which depended on a prematurity degree and on a content of malonic dialdehyde in the erythrocyte cell membranes, was found. A higher level of malonic dialdehyde in erythrocyte membranes was shown to be an unfavorable prognostication factor for the development of intraventricular hemorrhages in prematures.

[The ratio of components of sphingomyelin cycle and lipid composition in patients with viral hepatitis]. / Sootnoshenie komponentov sfingomielinovogo tsikla i sostav lipidov u bol'nykh virusnym gepatitom.

The aim of the study is the investigation of the content of the lipids and the sphingomyelin cycle components in the liver of the patients suffered from viral hepatitis. The methods used were thin layer chromatography for the detection of the lipid pattern and gas liquid chromatography for evaluation of the sphingomyelin fatty acid's and spectrum and ceramides. In the patients suffered from viral hepatitis HCV with moderate activity of the process cholesterin and triglycerides level were less and lysophospholipids content was two-fold and sphingomyelin level was insignificantly higher comparingly than in patients with low activity of the process. In the group of patients suffered from mixt infection (HCV + HBV) there is decreased cholesterin and both phosphatidylcholin and the sphingomyelin content along with lysophospholipids level elevation. In the fatty acid spectrum the palmitate acid (16:0) and the long chain acids (C22-C24) content were higher comparingly with ceramides. Significant difference is observed in oleic acid (18:1) content being as small as 9.3-9.9% in the liver damaged by viral hepatitis.

[Stimulation of delta1-opioid receptors increases the ventricular fibrillation threshold in post-infarct cardiosclerosis: the role of K(ATP)-channels]. / Stimuliatsiia del'ta1 opioidnykh retseptorov povyshaet porog zheludochkovoi fibrilliatsii pri postinfarktnom kardioskleroze: rol' K(ATP)-kanalov.

Preliminary administration of the delta 1-opioid receptor (delta 1-OR) selective peptide agonist DPDPE (0.1 mg/kg, i.v.) increased the ventricular fibrillation threshold (VFT) in postinfarction cardiosclerosis in rats. Pretreatment with the selective delta 1-OR antagonists ICI 174,864 (not affecting VFT) in a dose of 0.5 mg/kg completely eliminated the DPDPE-induced increase in the VFT. Pretreatment with the KATP channel selective blocker glibenclamide (0.3 mg/kg, i.v.) completely eliminated the delta 1-OR mediated increase in the VFT protective effect of the delta 1-OR stimulation. The intravenous injection of the mitochondrial KATP channel blocker 5-hydroxydecanoate (5 mg/kg) simultaneously with DPDPE not only eliminated the delta 1-OR mediated increase on VFT, but additionally increased the VBFT drop caused by cardiosclerosis. Injected separately, neither glibenclamide nor hydroxydecanoate affected the VFT level. It is concluded that stimulation of the delta 1-OR increases VFT by activating mitochondrial KATP-channels.

[Change in lipid composition and lipid peroxidation rate in brain tissue under conditions of thymic hormone deficiency]. / Izmenenie sostava i skorosti perekisnogo okisleniia lipidov tkani golovnogo mozga v usloviiakh defitsita timusnykh gormonov.

Experiments on mature male rats have shown that 3 and 6 months after removal of the brain thymus, the level of total lipids in all cell centrifugate fractions (homogenate, supramitochondrial and mitochondrial fractions), which was followed by the higher rate of lipid peroxidation and the lower activity of cellular compartments, the spectrum imbalance of lipid fractions with predominant increases in the levels of phospholipids and free cholesterol. It is suggested that these changes make a contribution to the dysfunction of brain structures and participate in regulatory processes in thymectomy.

[Effect of immunization on functional state of thyroid gland and thyroxine binding in rat organs]. / Vliianie immunizatsii na funktsional'noe sostoianie shchitovidnoi zhelezy i pogloshchenie tiroksina organami krys.

A number of modern research methods were used in experiments on 220 white rats to examine thyroid function at varying times after single immunization with typhoid vaccine. It was found that on the 1st and 2nd days of the observation period, only cAMP level of the thyroid parenchyma decreases. Three, four and seven days following immunization, thyroid function is drastically reduced, which manifests by a decrease in 131I uptake by the thyroid gland. Also decreased were the conversion ratio, the levels of thyroxine and triiodothyronine in blood serum and incorporation of labeled thyroxin by the heart, liver and spleen. During the productive phase of the immunogenesis (days 10, 15, 20 and 25), all the test indicators considerably increase. The phases of the reaction obtained seem likely to be a consequence of reciprocal relationship between the thyroid and sympathoadrenal systems (the inductive period), as well as by the feedback effect (the productive period of antibody formation). The reaction of thyroid function to immunization is regarded as a component of non-specific adaptation response of the body to an extreme irritant, that provides for metabolic reconstruction necessary for the synthesis of antibodies and formation of immune lymphocyte populations.

[Effect of an industrial frequency alternating magnetic field on the functional state of the thyroid gland and thyroxine absorption by the organs of rats]. / Vliianie peremennogo magnitnogo polia promyshlennoi chastoty na funktsional'noe sostoianie shchitovidnoi zhelezy i pogloshchenie tiroksina organami krys.

A study was made of the 131I radioisotope absorption by the thyroid gland, thyroxin binding by a number of tissues, and also protein-bound iodine (PBI) content in the blood plasma of albino rats after the application of alternating magnetic field (AMF)--industrial frequency 200 Ersted voltage--of various duration and periodicity. Plasma PBI increased in response to the 15-minute AMF application. When the exposure was increased to 6.5 hours and especially to 24 hours there was a reduction of the PBI level and of the process of 131I-thyroxin binding by the tissues of the testes, heart, liver, and spleen. The AMF application for 6.5 hours a day for 5 days resulted in a significant elevation of 131I in the thyroid gland and of the PBI, but the 131I-thyroxin binding by the tissues decreased markedly. It is suggested that functional condition of the thyroid gland and the tissue reaction to thyroxin altered depending on the AMF duration and periodicity of action.