Derivatives of 2-aminobenzimidazole potentiate ASIC open state with slow kinetics of activation and desensitization.

The pharmacology of acid-sensitive ion channels (ASICs) is diverse, but potent and selective modulators, for instance for ASIC2a, are still lacking. In the present work we studied the effect of five 2-aminobenzimidazole derivatives on native ASICs in rat brain neurons and recombinant receptors expressed in CHO cells using the whole-cell patch clamp method. 2-aminobenzimidazole selectively potentiated ASIC3.

Guanidine Derivatives of Quinazoline-2,4(1,3)-Dione as NHE-1 Inhibitors and Anti-Inflammatory Agents.

Quinazolines are a rich source of bioactive compounds. Previously, we showed NHE-1 inhibitory, anti-inflammatory, antiplatelet, intraocular pressure lowering, and antiglycating activity for a series of quinazoline-2,4(1,3)-diones and quinazoline-4(3)-one guanidine derivatives. In the present work, novel N1,N3-bis-substituted quinazoline-2,4(1,3)-dione derivatives bearing two guanidine moieties were synthesized and pharmacologically profiled.

Antithrombotic Activity of the Antiplatelet Agent Angipur on the Model of Arterial Thrombosis in Rats with Isoproterenol-Induced Myocardial Infarction.

We studied the effect of Angipur on the process of experimental thrombosis induced by damage to the carotid artery wall by surface application of 50% ferric chloride (III) solution in rats without comorbidities and with isoproterenol-induced myocardial infarction. In animals without comorbidities, Angipur administered intravenously was 1.2 times less effective, in terms of ED, than the well-known inhibitor of GPIIb/IIIa platelet receptors tirofiban.

Synthesis and multifaceted pharmacological activity of novel quinazoline NHE-1 inhibitors.

The Na/H exchanger isoform 1 (NHE-1) attracts ongoing attention as a validated drug target for the management of cardiovascular and ocular diseases owing to cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. Herein we report novel NHE-1 inhibitors realized via functionalization of N-alkyl quinazoline-2,4(1H,3H)-dione and quinazoline-4(3H)-one with N-acylguanidine or 3-acyl(5-amino-1,2,4-triazole) side chain. Lead compounds show activity in a nanomolar range.

Effects of Zoniporide and BMA-1321 Compound on the Rate of Oxygen Absorption by Cardiomyocyte Mitochondria in Rats with Experimental Chronic Heart Failure.

Uncoupling of respiration and ATP production by myocardial mitochondria was observed in rats with chronic isoproterenol intoxication (L-isoproterenol subcutaneously, 1 mg/kg, for 10 days) in comparison with controls (injected with the solvent). Inhibitors of NHE-1 zoniporide (1 mg/kg intraperitoneally, 13 days) and BMA-1321 compound (0.92 mg/kg intraperitoneally, 13 days) improved the mitochondrial function in rats with isoproterenol-induced cardiac failure: respiratory control coefficients increased, more so for the respiratory chain complex II, the main source of ROS in heart failure.

NEUROPROTECTIVE PROPERTIES OF A NEW INHIBITOR OF NA+/H+ EXCHANGER (COMPOUND RU-1355) ON THE MODEL OF FOCAL ISCHEMIA IN RATS.

Primary neuroprotective properties of new inhibitor of Na⁺/⁺ exchanger (compound RU-1355) were established on the model of 60-min focal ischemia of the left middle cerebral artery followed by 24-h reperfusion in rats. Compound RU-1355 significantly (by 34%) decreased neurological symptoms, reduced (1.67 times) the growth of neuron-specific enolase level in serum, decreased (2.

[Cardioprotective properties of zoniporide studied on experimental ischemia and reperfusion models in rat myocardium].

Using the experimental model of rat heart ischemia/reperfusion, it is established that zoniporide (inhibitor of Na+/H+ exchanger) produces a significant (1.4-fold) decrease in the area of myocardial necrosis, 2.1-fold decrease in the serum troponin I level, and 2-fold decrease in the severity of post-reperfusion arrhythmias.

[Structure and physiological role of NHE1 and pharmacological regulation of its activity].

This article summarizes results of preclinical and clinical trials concerning the effects of NHE1 inhibitors and prospects for their clinical application. NHE1 has been identified as the most abundant isoform of Na+/H+ exchanger in the heart of mammals. NHE1 regulates pH homeostasis, cell proliferation, migration, adhesion, and apoptosis.

[Biliary sludge: diagnosis and treatment at an outpatient's clinic].

The purpose of the study--to develop a diagnostic and management tactics for patients with biliary sludge (BS) in an outpatient setting. The study included 115 patients who, according to the ultrasound revealed a BS. Own methodological approach used by ultrasound scan of the gall bladder and the interpretation of ultrasonographic BS types: Type 1 (suspension echo-positive particles) was set at 59.

[Functional reserves of the heart under conditions of alimentary magnesium deficit].

Aim of the study was to assess functional reserves of myocardium in animals with deficit of magnesium during stress tests. Magnesium deficit was modeled by 10 week long magnesium deficient diet. After 54% lowering of magnesium level in erythrocytes we registered left ventricular pressure, myocardial contraction and relaxation rates, heart rate, systolic and diastolic arterial pressure, intensity of structures functioning.

Arrhythmogenic threshold of the myocardium under conditions of magnesium deficiency.

We studied the arrhythmogenic threshold of the myocardium after injection of CaCl2 to magnesium-deficient rats receiving Mg2+ L-aspartate, MgCl2, their combination with vitamin B6, and reference preparations Magne B6 and MgSO4 until complete compensation of magnesium level in the plasma and erythrocytes. Magnesium-deficient diet and deionized water were used for inducing alimentary Mg2+ deficiency and modeling pathological changes in rats. After reducing Mg2+ level to 0.

[Clinical and functional characteristics of chronic obstructive pulmonary disease in association with pathology of the cardiovascular system in persons of advanced age].

The study was aimed at clinic-functional features of chronic obstructive pulmonary disease (COPD) in association with an arterial hypertension and an ischemic heart disease in persons of advanced age. 69 women and 82 men have been examined through clinic-laboratory, functional and tool methods of inspection. Distinctions in frequency of combined pathologies in the group of women of advanced age have been revealed in comparison with men.

Use of magnetophoresis of glutamic acid and magnesium sulfate in the rehabilitation of children with cerebral palsy.

We report here our studies on the clinical efficacy of courses of magnetophoresis of glutamic acid and magnesium sulfate in the complex rehabilitation treatment of preschool children with spastic types of cerebral palsy. Clinical-neurophysiological investigations were performed in 40 children aged 1-7 years. Treatment was significantly more effective when use of running pulsed magnetic fields was combined with medicinal agents as compared with magnetotherapy using the same regime.

[Magnetophoresis of glutaminic acid and magnesium sulfate in rehabilitation of children with cerebral palsy].

Clinical efficacy of magnetophoresis of glutaminic acid and magnesium sulfate used in the rehabilitative complex for preschool children with spastic forms of cerebral palsy has been studied. The clinical and neurophysiological examination has been conducted in 40 children aged from 1 to 7 years. The higher efficacy of treatment with combination of running pulsed magnetic field and drugs as compared to magnetotherapy using the same procedure has been found.

[Efficacy of dynamic magnetotherapy with modulation frequency 10Hz in the complex of spa rehabilitation of children with cerebral palsy].

Two groups of children with cerebral paralysis received combined therapy. Treatment of one of the groups included a course of magnetotherapy (AMO-ATOS unit, 10 Hz) according to the suboccipital-lumbar method, the other group was control (no magnetotherapy). The study of cliniconeurophysiological indices showed significantly higher efficacy of the therapeutic complex with a course of magnetotherapy.

[Comparative study of the antiarrhythmic activity of L-, D-and DL-stereoisomers of potassium magnesium aspartate].

Injection forms of potassium (K) and magnesium (Mg) aspartate (Asp) were compared in preventing cardiac disorders caused by electrolytic disturbances, primarily low K and Mg levels (e.g. caused by the treatment with cardiac glycosides and diuretic drugs).

[Comparative evaluation of the effects of carnitine stereoisomers and racemate on the cardio- and hemodynamics of rats on a carnitine-deficient diet].

L-carnitine (L-beta-hydroxy-gamma-N,N,N-trimethylaminobutyric acid) is conditionally necessary for mitochondrial transport and metabolism of long-chain fatty acids, and thus for myocardial energetic metabolism. D-carnitine is not biologically active and might interfere with proper utilization of the L isomer, and so there are claims that the racemic mixture (DL-carnitine) should be avoided. The pharmacological effects of carnitine are stereospecific: L-carnitine was effective in various animal and clinical studies, while D- and DL-carnitine was found to be ineffective or even toxic to some cells and tissues, such as muscle cells and the myocardium.

[The cardiotoxic properties of kordaron in acute myocardial ischemia and infarct].

Cardiodepressive and arrhythmogenic properties of cordarone were studied on cat in conditions of experimental acute ischemia and myocardial infarction upon intravenous infusion. The obtained results showed an increase cordarone cardiotoxicity and arrhythmogenic properties in conditions of myocardial infarction. No reliable difference was observed in dynamics of cordarone-induced changes in ECG parameters in animals with myocardial ischemia of various duration and intact animals.

[The cardiotoxic properties of anti-arrhythmia agents].

Experiments were conducted on cats to study the cardiotoxic and arrhythmogenic properties of some antiarrhythmic agents in continuous intravenous infusion in doses multiple of the dose which causes an antiarrhythmic effect on an acontic model of arrhythmia in rats in 50% of cases. Novocainamide, cordarone, bonnecor, and quinidine possessed the most marked cardiotoxicity. A less marked cardiodepressive activity was encountered in the case of ethmosine and ethacysin.

[Immunologic response of the body in thyroid gland involvement due to incorporation of varying doses of 131I].

The body's immunological responses were examined in thyroid damage caused by the incorporation of varying 131I doses. The in-take of 131I in doses of 37, 74, and 148 KBc/g body weight caused reductions in the murine blood concentrations of thyroxin following 30, 60, and 180 days. The blood levels of triiodothyronine decreased 180 days after administration of 131I in a dose of 74 KBc/g body weight and 30, 60, and 180 days after incorporation of the radioisotope in a dose of 148 KBk/g body weight.

[Effect of lyophilization on IgG aggregation processes in immunoglobulin preparations].

The conditions of the lyophilization of immunoglobulins as prescribed by the current technical regulations lead to the increased content of aggregated molecules in the preparation. The storage of the bulk preparation for two months after drying considerably decreases the content of aggregations. The authors believe it to be expedient to introduce the stage of storage after drying into the regulations for drying immunoglobulin preparations in the process of their production.