[Taurine in the treatment of non-alcoholic fatty liver disease].

Non-alcoholic fatty liver disease (NAFLD) has several phases of flow: from simple steatosis, steatohepatitis, and ending with fibrosis and cirrhosis. NAFLD characterized by elevated liver enzymes in blood serum, the morphological changes in biopsies of the liver often associated with metabolic disorders. Metabolic syndrome represents a complex of many linked to pathobiochemical and pathophysiological factors levels influencing the extremely high risk of developing coronary heart disease (CHD), diabetes mellitus type 2 and other diseases associated with atherosclerosis. NAFLD proceeds favorably without significant morphological changes in most of the patients. In connection with this treatment is given only to patients with high risk of progression of this disease or the presence of marked changes in biochemical liver tests. Therefore, prevention and treatment of these conditions should be conducted before the complications and lead to improvement of the liver.

Plasmin-independent gelatinase B (matrix metalloproteinase-9) release by monocytes under the influence of urokinase.

It is shown that the release of matrix metalloproteinase-9 (gelatinase B) by THP-1 and U937 cells into conditioned media is increased under the action of recombinant single-chain urokinase. This effect is not accompanied by proteolytic activation of gelatinase B and is related to release of a pro-form of the enzyme. The action of urokinase on monocytes is time-dependent and becomes significant 12-24 h after the beginning of cell incubation. The dependence of the effect on the concentration of urokinase is characterized by half-maximum at about 20 nM and saturation at about 200 nM. The urokinase-induced gelatinase B release is not dependent on the action of plasmin because plasmin inhibitors aprotinin and alpha2-antiplasmin do not abolish this action. Additionally, tissue type plasminogen activator does not induce gelatinase B release by monocytes as observed under the action of urokinase. Nevertheless, the catalytic activity of urokinase participates in the development of the observed effect because it is significantly depressed by the natural urokinase inhibitor PAI-1. The effect of urokinase is completely abolished by actinomycin D and cycloheximide, indicating the participation of transcription and translation processes in its development.

[The clinical efficacy of taufon in the combined treatment of patients with chronic circulatory failure]. / Klinicheskaia éffektivnost' taufona v kombinirovannom lechenii bol'nykh s khronicheskoi nedostatochnost'iu krovoobrashcheniia.

Monotherapeutic treatment of patients with chronic cardiac insufficiency of I and II functional class and patients of III FC with Russian drug taufon against the background of traditional therapy leads to improvement of objective and subjective indications of the disease. Taufon does not significantly affect central hemodynamics, but normalizes contractile myocardial function and increases tolerance to physical load. Taufon potentiates therapeutic efficacy of some drugs that makes it possible to reduce their doses. Pharmacokinetics is given. The efficacy and the absence of any toxic effects allow the authors to recommend the drug for treatment of patients with chronic cardiovascular as an drug additional to basic background therapy.

Effects on heart membranes after taurine treatment in rabbits with congestive heart failure.

Oral treatment with taurine (CAS 107-35-7) of rabbits with congestive heart failure (CHF) caused by impairment of aortic valve dose-dependently improved hemodynamic and contractile indices of the heart and prolonged the animals' life. Analysis of heart membrane fraction of CHF animals, using a paramagnetic probe 4-tempo-stearamide, demonstrated a loss of negative charge of the membranes. In vitro addition of taurine had no effect on the charge of phospholipid heads. The use of a 5-doxyl-stearate probe revealed that membrane fluidity decreased with the development of CHF as compared with normal membranes. Taurine increased membrane fluidity in animals with CHF, but did not affect membranes isolated from animals with CHF which had undergone taurine treatment and elevated membrane rigidity in the control group.

Modulation of receptor-dependent increase of calcium ions in human platelets by taurine.

Taurine (2-aminoethanesulfonic acid, CAS 107-35-7) is present in high concentrations in platelets. It suppresses bronchial responses to platelet-activating factor (PAF) and inhibits aggregation induced by ADP. In the present experiments human platelet calcium responses to PAF were measured by a fluorescent label "Quin-2" method. Preincubation with 0.01 mol/l of taurine decreased effects of PAF by 250 nmol/l if the initial Ca intracellular response (delta Ca2+) to inductor was more than 400 nmol/l. If the initial response to inductor was less than 150 nmol/l, taurine did not affect the response to inductor if PAF effect was in delta Ca2+ range of 150-400 nmol/l. Hence, some effects of taurine may be ascribed to its modulating influence on secondary Ca2+ messenger.

[Use of taurine in the treatment of experimental congestive heart failure]. / Ispol'zovanie taurina dlia lecheniia zastoinoi serdechnoi nedostatochnosti v éksperimente.

The therapeutic effects of 2-aminoethanesulfonic acid (taurine) were tested in animals with congestive heart failure (HF) simulated by aortic valve damage. The drug given in a daily dose of 100 mg/kg for a month was shown to reduce mortality rates as compared to controls, to improve the animals' clinical condition, hemodynamic and myocardial contractility parameters. Taurine was found to exert a positive action on the heart response to stresses. The impaired response in the animals restored to heart rate stimulation, catecholamines and calcium loading. The mechanisms of the agent's action are discussed in the present paper. It is suggested that taurine-based taucard will be included into the arsenal of cardiotropic agents after its clinical trials are successfully completed.

[Taurine level in the blood and myocardium of rabbits with experimental heart failure]. / Soderzhanie taurina v krovi i miokarde krolikov s éksperimental'noi serdechnoi nedostatochnost'iu.

Experimental damage of the aortal heart valve in rabbits caused taurine accumulation in the heart. Taurine content in the heart increased for two months 2.7 times in the left ventricle and 1.8 times in the right one. Taurine concentration in the blood began rising 5-10 days after the operation, reached the maximal value of about 150% as compared with its initial level and then decreased to the level near the initial one. Animals with insignificant taurine accumulation in the heart died for the first two months after the operation. Results are discussed from consideration on the protective role of taurine for the myocardium under the heart failure.

[Pathomorphological and morphometric evaluation of a model of aortic insufficiency in rabbits treated with taurine]. / Patomorfologicheskaia i morfometricheskaia otsenka modeli aortal'noi nedostatochnosti u krolikov pri lechenii taurinom.

In 45 experimental rabbits, subjected to trans-carotid aorto-valvulotomy in a month developed a congestive heart failure. When this group of rabbits was compared to the control group of 20 animals, in the course of complete pathomorphologic, histochemical and stereomorphologic analysis the following results were obtained: potassium oroticum did not show any efficacy at all; the efficacy of taurine in a dose of 10 mg/kg was low. Its effect was both direct and indirect acting through the autonomic nervous system.

[Adenylate cyclase system of synaptosomes from the rat cerebral cortex during acute stress]. / Adenilattsiklaznaia sistema sinaptosom kory golovnogo mozga krys pri ostrom stressornom vozdeistvii.

Synaptosomes and synaptic membranes were studied in brain cortex of rats after 6 hrs emotional-painful stress. No alterations were observed in beta-adrenoreceptors, adenylate and guanylate cyclases to the end of the second day after the acute stress action.

[Effect of phosphate and acidosis on the calcium sensitivity of the cardiac myofibrils]. / Vliianie fosfata i atsidoza na kal'tsievuiu chuvstvitel'nost' miofibrill serdtsa.

The treatment of the bundles of rat myocardial fibers with ethyleneglycol-bis(beta-aminoethyl ether)-N,N-tetraacetate (EGTA) made the sarcolemma permeable for ions and small molecules. At the incubation medium pH 7.0 the EGTA-treated fibers developed a half-maximal tension at pCa 5.4, and the maximal tension at pCa 4.8. Inorganic phosphate (10 mM) reduced the maximal tension by 18 +/- 3% and decreased the calcium sensitivity of the myofibrils so that there was a shift of the pCa/tension curve by 0.3 unit to the right. Acidosis (pH 6.6) also decreased significantly the calcium sensitivity, while the presence of 10 mM phosphate produced additional depression of the calcium sensitivity. It is concluded that phosphate accumulation by the ischemic myocardium combined with acidosis may depress the contractility not only due to depletion of the free calcium concentration in the myoplasm but also as a result of the reduced calcium sensitivity of myofibrils.

[Effect of taurine on the properties of myocardial sarcoplasmic reticulum guanyl cyclase]. / Vliianie taurina na svoistva guanilattsiklazy sarkoplazmaticheskogo retikuluma serdtsa.

Effect of taurine on the properties of guanylate cyclase (GC) of the guinea-pig cardiac sarcoplasmic reticulum was studied. The enzymatic activity increased in the presence of Mn+2 at a concentration of 0.05 mM, reaching the maximal level at a concentration of 7 mM. Mg2+ (0.25-1 mM) did not alter the activity of GC in the absence of Mn2+, but stimulated it in the presence of Mn2+ at a concentration ranging within 0.1 to 1 mM. Taurine activated GC in the presence of Mn2+ (10 mM) and produced no effect on its activity at 0.5-3 mM of Mn2+ without Mg+2. Taurine (0.4-10 mM) potentiated the activity of GC stimulated with Mg+2. The structural analog of taurine, beta-alanine, suppressed the activity of GC 2-2.5-fold both in the absence and presence of Mg+2. Ca2+ (10(-9)--10(-4) mM) stimulated GC. Effect of Mg+2 and taurine on GC activity rose proportionally to an increase in Ca+2 concentration in the incubation medium. The data obtained evidence in favour of potential monitoring of the activity of GC through changes in the intracellular content of Ca+2, Mg+2 and taurine in the presence of Mn+2 at concentrations close to the physiological ones. The effect of taurine on GC is mediated via Mg+2 and Ca+2.

[Taurine and the adenosine cyclic monophosphate levels in the heart]. / Taurin i soderzhanie TsAMF v serdtse.

The mechanism of the decrease in the heart of cAMP content under the effect of taurine was studied. It was shown on a preparation of cytoplasmic membranes isolated from the rat heart that under the effect of taurine (10(-6)--10(-3) M) the activity of phosphodiesterase and adenylate cyclase increases to the maximum by 2.4 and 1.4 times, respectively. Taurine weakens the activation of adenylate cyclase by adrenaline. The effect of taurine on adenylate cyclase activity diminishes under the action of phentolamine and obsidan and is practically not manifested in the simultaneous presence of both adrenoblocking agents. Taurine obviously changes the content of cAMP in the heart by altering the activity of adenylate cyclase and phosphodiesterase.

[Effect of taurine on cyclic AMP and GMP levels in the hearts of rats exposed to stress]. / Vliianie taurina na uroven' tsiklicheskikh AMF i GMF v serdtse krysy pri stresse.

Taurine produced no effect on the cyclic nucleotides level in the heart of intact rats but sharply inhibited the cAMP and cGMP level elevation in the rat heart occuring in stress. After atropine pretreatment of the animals no effect of taurine on the heart cGMP level was observed; its effect on the cAMP level was significantly inhibited against the background of partial beta-adrenoreceptors block. It is suggested that taurine is a nonspecific regulator of the myocardial cells sensitivity to the biologically active drugs.

[Effect of swimming on the uptake and content of taurine in the rat heart]. / Vliianie plavaniia na vkliuchenie i soderzhanie taurina v serdtse krysy.

14C-taurine uptake and total taurine content increase during a 15-min period of swimming. Prolongation of this period leads to more active taurine metabolism (ISA formation) but the total taurine content does not change. Active accumulation against its concentration gradient and maintenance of the taurine content at the same level during the entire period of swimming suggest that the taurine uptake and its metabolism are interdependent and very important for heart activity.

[Taurine transport in the heart]. / Transport taurina v serrdtse.

The rat heart accumulates taurine against the concentration gradient when perfused for 60 minutes with solutions containing taurine in concentrations of 0.01 to 0.5 mM. The uptake of taurine by the myocardium at 37 degrees C is characterized by kinetic constants Km equal to 3.3 micron and Vmax equal to 0.77 micron/min. Heart taurine uptake is inhibited by sodium azide and carbonylcyanide-m-chlorophenylhydrosone and reduced by 30-50% by ouabain. Partial or total replacement of Na+ or K+ by equimolar amounts of trihydrochloride reduces taurine uptake. Competitive inhibition of taurine transport by beta-alanine and GABA is noted. The presence of alpha-alanine in the external medium does not affect the passage of taurine from the perfusate into the myocardium. It is concluded that the uptake of taurine by the rat heart is accomplished by means of active transport through a transport system which possesses affinity to gamma- and beta-amino acids.