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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. The effect of BMA-1321 was more manifest (53%; p

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 N1-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. Their pharmacophoric features were elucidated with neural network modeling. Several compounds combine NHE-1 inhibition with antiplatelet activity. Compound 6b reduces intraocular pressure in rats and effectively inhibits the formation of glycated proteins. Compounds 3e and 3i inhibit pro-inflammatory activation of murine macrophages, LPS-induced interleukin-6 secretion and also exhibit antidepressant activity similar to amiloride. Hence, novel compounds represent an interesting starting point for the development of agents against cardiovascular diseases, thrombotic events, excessive inflammation, long-term diabetic complications and glaucoma.

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

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. The effect of BMA-1321 was more manifest (53%; p0.05) in comparison with zoniporide (35%; p0.05).

Heating of substituted benzimidazole-2-sulfonic acids in the presence of excess quantities of secondary amines was used to synthesize dialkylaminobenzimidazoles. Experimental studies of potential antiarrhythmic, antiaggregation, hemorheological, AT1 angiotensin- and NHE-1-inhibiting, and antiserotonin activity identified active compounds. 1[-2-(5-Methyl)benzimidazole]pyrrolidine had greater NHE-inhibiting activity than zoniporide. 1-{[2-(5-Methoxy)benzimidazole]-4-N-methyl}piperazine dihydrochloride had greater antiaggregatory activity than acetylsalicylic acid, while 1-[2-(5-methyl)benzimidazole]piperidine was as active as cyproheptadine in terms of 5-HT2A antagonistic activity. 1-(2-Benzimidazole)pyrrolidine and 1-[2-(5-chloro) benzimadazole pyrrolidine dihydrochlorides had 5-HT3 antagonist activity equal to that of tropisetron..

Diverticulosis of distal parts of a small intestine is a rare and difficultly diagnosed disease. This pathology usually is asymptomatic, and the first clinical manifestations oftenly testify the development of complications. The leading seat in the diagnosis of diverticulosis is borrowed with beam investigative techniques: ultrasonography, barium enterography, CT or MRI. In this article a brief review of clinics and possibilities of instrumental diagnosis of diverticulosis of small intestine is presented and illustrated by clinical case of a patient with large jejunoileal diverticulosis.

Condensation of 1-substituted 2-aminobenzimidazoles with aromatic aldehydes produced the corresponding azomethines, reduction of which by sodium borohydride afforded 1-substituted 2-benzylaminobenzimidazoles. The Microcosm information technology (IT) tool was used to assess in silico the potential for antiarrhythmic, antiaggregant, antioxidant, hemorheologic, and antiglycating activity in this series of compounds. Pharmacological screening identified which of the synthesized compounds were active. It was shown that the computer predictions correlated with the experimental data.

The article analyzes the causes of recurrent abdominal pain and dyspeptic phenomena in 657 patients after cholecystectomy. The authors found out that after gall bladder resection 48% of patients complain of pain and dyspepsia. Postcholecystectomy syndrome (dysfunction of Oddi’s sphincter) is diagnosed in 15.2% of the patients. The proportion of diseases of the esophagus and organs of the gastroduodenal zone is 36.4%, of the hepato-pancreato-biliary one is 38.3 per cent. Diagnostic errors at the preoperative stage and/or tactical ones during cholecystectomy amounted to 7.8%.

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 (2.3 times) the size of the necrotic zone, and reduced by 59% (p0.05) the degree of cerebral edema According to the results of morphometric, immunoassay, and neurological assessments of brain damage, compound RU-1355 is superior on ave- rage by 43.5% (p0.05) in comparison to selective NHE1 inhibitor zoniporide.

Ecological and entomological observations of some key areas in the Norilsk industrial district, which are subject to technogenic impact of varying intensity, have been performed in the field seasons of 2008–2009. The composition and biodiversity of entomological complexes, as well as the activity of main indicator groups of arthropods, have been estimated depending on the distance from the sources of pollution. Flexible reactions of phyllophages to technogenic emissions have been observed. The necessity of monitoring of the impact zone’s marginal areas is emphasized.

Opening of the oxirane ring in 1-oxiranylmethylindoles yielded new indole derivatives containing 1,2-amino alcohol residues at the nitrogen atom. Compounds were studied in vitro in relation to various types of pharmacological activity typical of this class of compounds, including receptor (5-HT2, 5-HT3, P2Y1-ergic, κ-opioid), antiaggregant, hemorheological, antiarrhythmic, and antioxidant activities.

A series of amides of 2,3-dihydroimidazo- and 2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazolyl-N-acetic acids were synthesized. Their pharmacological activity was studied. It was established that the synthesized substances possessed antiaggregant properties and antiarrhythmic activity. Some of these amides exhibited antioxidant and hypoglycemic effects in addition to antagonist activity with respect to serotonin 5-HT2 and purine P2Y1 receptors.

Opening of the five-member ring of indolylmethyleneoxazolones with aliphatic amines was used to synthesize a series of amides of 2-amino-3-indolylacrylic acid. These compounds were studied in vitro in relation to the various types of pharmacological activity typical of this class, including receptor (5-HT2-, 5-HT3-, and P2Y1-ergic, K-opioid), antiaggregant, hemorheological, antiarrhythmic, and antioxidant activities.

A series of 3-(N,N-disubstituted)acetamide-1-R-2-aminobenzimidazolium chlorides were synthesized. Their pharmacological properties were studied. It was established that the synthesized substances decreased platelet aggregation and possessed antioxidant and antiarrhythmic activity. Some of the compounds produced a hypoglycemic action and exhibited antagonistic activity with respect to serotonin 5-HT2 receptors.

The synthesis of 10-chloroethyl-2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazole was described. The nucleophilic substitution of the chlorine atom by various amines was studied. As a result, 10-alkylaminoethyl-substituted derivatives of this tricycle containing alkylamines and 4-substituted piperazines were obtained. These compounds exhibited 5-HT2 antagonist activity; platelet antiaggregant properties; and moderate P2Y1-antagonist, antiarrhythmic, and hypoglycemic action.

Taking into account the structure—activity relationship established previously for imidazobenzimidazole derivatives with high hemorheological activity, several new 9-R-2-halogenophenyl-substituted imidazo[1,2-a]benzimidazoles with C2 fluoro-, chloro-, dichloro-, or bromo-phenyl radicals have been synthesized. All substances were tested in vitro for various types of pharmacological activity characteristic of this class of drugs including hemorheological, antiplatelet, antiarrhythmic, antioxidant; 5-HT2-, 5-HT3-, P2Y1-, and H1-antagonist; and κ-opioid-agonist.

In continuation of the investigation of 1-dialkylaminoethyl-2,3-dihydroimidazo[1,2-a]benzimidazoles demonstrating serotoninergic activity, several new substances of this class with 4-substituted piperazines and piperidines as amine moieties were synthesized and tested pharmacologically in vitro. All substances were investigated for antiserotoninergic, antiplatelet, haemorheological, antiarrhythmic, and antioxidant activity.

New water-soluble 3-acetyl-2-R-9-dialkylaminoethylimidazo[1,2-a]benzimidazoles were synthesized on the basis of previously described structure-effect relationships among imidazobenzimidazole derivatives with high levels of hypotensive activity. All these compounds were studied in vitro in terms of a variety of types of pharmacological activity characteristic for this class of compounds, including antiarrhythmic, antiaggregant, antioxidant, hemorheological, K-opioid agonistic, hypotensive, spasmolytic, and adrenoblocking activities; their effects on cAMP phosphodiesterdase activity and physical exercise tolerance were also studied.

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 59.1%, type 2 (low level of mobile like putty echo-positive bile)--23.5%, 3 type (like putty bile in the form of mobile and/or fixed clots)--17.4%. For the treatment of BS used drugs ursodeoxycholic acid. The daily dosage depends upon the type BS. For the treatment of type 1 requires a minimum of 1 month, 2 types--not less than 3 months. Sludge was the most resistant type 3, which is the duration of treatment was 6-12 months or more. Allocation of risk factors forming the BS is the basis for the formation of risk groups and prevention activities (including pharmacotherapeutic).

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.

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. Ischemic activation of the NHE1 in myocardium results in intracellular calcium overload, which aggravates ischemic/reperfusion injury. In accordance with results of preclinical experimental studies, selective inhibition of the sarcolemmal NHE1 can delay progression of injury during ischemia, thereby reducing myocardial necrosis and improving recovery of ventricular function upon reperfusion. Inhibitors of NHE1, which can provide beneficial effect in the clinical treatment of these conditions, are currently under preclinical and clinical tests. At present, there are 481 NHE inhibitors known according to the Thomson Reuters Integrity database.

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. Presence of combined pathologies in women of advanced age with chronic obstructive illness of lungs aggravates its clinical current. The accompanying ischemic heart trouble influences the clinical picture of COPD in a greater extent.

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 0.7 mmol/liter in the plasma and to 1.5 mmol/liter in erythrocytes, Mg L-aspartate, MgCl2, their combination with vitamin B6, as well as Mg2+ deficiency led to a decrease in the dose of CaCl2 provoking heart rhythm disturbances in 50% animals and shortening of animal life span. Administration of the test magnesium salts increased the arrhythmogenic threshold; Mg2+ salts were comparable by their efficiency with Magne B6 and were far superior to MgSO4.

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.

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.

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. The highest beneficial effect was observed on bioelectrogenesis of the brain, rheoencephalographic parameters and clinical manifestation of muscular spasticity.

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). Widely used K- and Mg-Asp preparations (asparkam, panangin, pamaton) are synthesized from aspartic acid representing a racemic mixture of L- and D-stereoisomers. Differences in metabolism and utilization of D- and L-amino acids probably influence the pharmacological properties of K and Mg L- and D-aspartates. Moreover, the pharmacologically effective doses of Mg and K salts can induce toxicity, which depends on the nature of anions. The aim of this study was to compare of antiarrhythmic action of K and Mg L-, D-, and DL-Asp stereoisomers using calcium chloride (CaCl2) and aconitine induced arrhythmia models in rats and strophanthin-K induced arrhythmia model in guinea pigs. It was found that intravenously administered K- and Mg-L-Asp exhibited higher activity compared to K- and Mg-D- and DL-Asp on the strophanthin-K, CaCl2, and aconitine induced arrhythmia models. Indeed, K- and Mg-L-Asp more effectively decreased the incidence of arrhythmias, increased the time to onset of the first arrhythmia, decreased percentage loss of rats, and increased the survival life of animals after the first arrhythmia onset in rats with arrhythmias induced by strophanthin-K and CaCl2 as compared to K and Mg-D- and DL-Asp. At the same time K- and Mg-L-Asp was better than D- and DL-Asp with respect to acute toxicity (LD50), effective dose (ED50) and antiarrhythmic (therapeutic) ratio (LD50/ED50) in rats with aconitine-induced arrhythmia model.

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. DL-carnitine caused symptoms of myasthenia and cardiac arrhythmias, which disappeared after L-carnitine administration. Therefore, the purposes of this work were (1) to study the effect of L-carnitine vs. that of D- and DL-stereoisomers on carnitine restoration rate in blood plasma of carnitine-deficient rats and (2) to evaluate the effect of stereoisomers and racemate of carnitine on the cardio- and hemodynamics of rats on carnitine-deficient diet. To induce carnitine deficiency, 60 rats were placed on a carnitine-deficient diet containing 1 g of N-trimethyl-hydrazine-3-propionate (mildronate) per a kilogram of the diet. The controls, 15 rats, received a basal control diet of the same duration. After 80 days, L-, D-, and DL-carnitine were administered in a dose of 200 mg/kg per os for 30 days, together with the carnitine-deficiency diet. To investigate the effect of L-, D-, and DL-carnitine on the abnormalities of the myocardial function of the carnitine-deficiency rats, various hemodynamic variables including left ventricular pressure, indices of contractility and relaxation, heart rate, systolic and diastolic blood pressure in response to volume loading test, adrenoreactivity test, and maximal isometric loading test, were measured. In this study, the carnitine-deficient diet with mildronate caused a substantial loss of carnitine in blood plasma by 56.49% (19.70 +/- 4.97 vs. 45.27 +/- 6.97 micromol/ 1, p0.001), which was accompanied by myocardial malfunctioning. After 30 days of L-carnitine administration, the plasma level of carnitine was significantly higher by an average of 118.55% (p0.001) compared with carnitine-deficient controls, while after administration of D- and DL-stereoisomers the carnitine content did not change or increased insignificantly. L-carnitine administration to carnitine-deficient rats led to normalization in myocardial function including indices of contractility and relaxation, systolic and diastolic blood pressure in response to volume loading test, adrenoreactivity test, and maximal isometric loading test. Chronic administration of D- and DL-carnitine did not change an altered cardio- and hemodynamics of carnitine-deficient rats compared with L-carnitine.

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.

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. The appearance of the cardiodepressive properties of the agents depended on the rate of their injection. The results of the study testify to the possibility of prognosticating the arrhythmogenic and cardiodepressive effects in experimental investigation of new antiarrhythmic agents.

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. Decreased concentrations of the both hormones were followed by the suppression of a humoral immune response to sheep red blood cells, diminished cell-mediated immunity in the mixed culture of lymphocytes. The inhibition of immune responses was correlated with the changes in the level of triiodothyronine.

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.