[Pharmacokinetic properties of an innovative nootropic agent based on a derivative of 3,7-diazabicyclo[3.3.1]nonane]. / Farmakokineticheskie svoistva veshchestva na osnove proizvodnogo 3,7-diazabitsiklo[3.3.1]nonana.

The pharmacokinetics and bioavailability of a derivative of 3,7-diazabicyclo[3.3.1]nonane exhibiting a nootropic effect, were studied after a single dose to rats. The pharmacokinetics of the compound was studied after oral and intravenous administration to 270 male rats Sprague Dawley at doses of 2.5 mg/kg, 13 mg/kg and 25 mg/kg. Its distribution in organs and tissues (brain, thymus, heart, lungs, liver, kidneys, and spleen) was also investigated. It was found that after a single intravenous administration, the investigated substance was determined in the blood of animals for 24 h; the half-life was 4.69 h. The relative bioavailability of the 3,7-diazabicyclo[3.3.1]nonane derivative after oral administration was 42.3%, thus suggesting the prospect of creating dosage forms for oral administration. After a single oral administration, the dose dependence of AUC0-t was exponential. The substance is characterized by heterogeneous distribution in the body with preferential accumulation mainly in well-vascularized tissues.

[Clinicomorphological aspects of adrenal pheochromocytoma diagnostics].

The removed pheochromocytomas of 25 patients aged from 25 to 72 years have been studied. Among them 5 tumors have had bilateral character, 8 pheochromocytomas have been diagnosed as malignant, 4 patients have had metastases. The average size of benign pheochromocytomas has been 4.0 cm, malignant - 4.5 cm. The majority of malignant tumors have had areas with diffusing growth patterns. The results of immunohistochemical study of benign and malignant pheochromocytomas have had small differences. The study of tumor ultrastructure hasn't found out their biological potential.

[Effect of perfluorane on the time course of changes in endogenous intoxication in victims with severe thermal injury].

The investigation was undertaken to study the effects of perfluorane on the degree of endogenous intoxication in the severely burnt. Sixty-five victims aged 20 to 55 years who had burns of the skin, involving more than 30% of the body surface area, without comorbidity (less than 9 SAPS scores), were examined. All the examinees were divided into 2 groups. They were comparable in age and burn injury degree. Perfluorane was administered in a dose of 4 ml/kg body weight within the first 24 hours after the moment of injury (a study group; n = 30). During the investigation, the authors estimated blood gas composition and acid-base balance, the level of lactate in mixed venous blood, the content of low and medium molecular-weight substances (LMMWS) in venous and arterial plasmas, on red blood cells and urine; erythrocytic deformity index; the level of reduced glutathione; total plasma antioxidative activity, and the plasma concentration of malonic dialdehyde. Blood was sampled on admission, an hour after administration of perfluorane, and onwards--on days 1, 3, 5, 7, 10, and 15. Perfluorane used in acute burn disease leads to normalization of oxygen balance, a reduction in the rate of free radical oxidation and lipid peroxidation, and a considerable decrease in LMMWS levels on the red blood cell membranes and plasma. Positive changes were recorded just an hour after administration of perfluorane and retained throughout the observation. In the study group victims, mortality was 15% less than that in the controls.

[Clinical and immunological criteria of burn sepsis].

A hundred and twenty-nine victims aged 16 to 60 years who had skin burns in the area of 15 to 60% of the body surface without severe concomitant somatic disease (SAPS less than 9 scores). The clinical symptoms of a systemic inflammatory response (SIR) and the signs of wound infection were recorded in all the examinees. The victims underwent a comprehensive clinical and laboratory examination, 55 of them were immunologically studied over time (on admission, on days 3 and 10). To reveal the predictive clinical and immunological criteria for sepsis, the examinees were divided into 3 groups. Group 1 comprised 33 burnt persons who were observed to have the symptoms of SIR and the signs of burn wound infections without impaired function of organs and systems. Group 2 included 46 victims with severe sepsis and a good outcome of burn disease. Group 3 consisted of 50 patients who had died from severe sepsis. Analysis of the results of the study has indicated that the count of formed blood elements by calculating the leukocytic intoxication index, the estimation of the level of lysosomal cation proteins in the neutrophilic granulocytes, the detection of populations of T helper cells, cytotoxic lymphocytes, as well as histomorphological and bacteriological findings are early and valid criteria for the development of infectious complications. Their use for the diagnosis and prediction of sepsis permits initiation of its treatment at early stages, without awaiting the appearance of the signs of a septic process.

[Stress-limiting properties of a new tetrahydropyrrolopyrazine derivative].

The effect of compound PV-174, selected from a series of tetrahydropyrrolopyrazine derivatives was studied on a model of immobilization stress in rats. Pretreatment with PV-174 decreases the stress-induced involution of thymus and spleen, hypertrophy of cpinephrosis, and gastric ulceration. The drug also blocks the stress-enhanced lipid peroxidation in lungs and myocardium, while not influencing the effect of kenalog (an exogenous glucocorticoid). It is suggested that one of the possible mechanisms of the antistressor effect of PV-174 is related to the drug action upon CNS.

[Antiarrhythmic properties of 2-(2'-hydroxy-2')-substituted ethyl-1,2,3,4-octahydropyrrolo[1,2-a]pyrazines]. / Antiaritmicheskie svoistva 2-(2'-gidroksi-2'-zameshchennykh)-étil-oktagidropirrolo[1,2-a]pirazinov.

The antiarrhythmic activity and acute toxicity of a series of 2-(2'-hydroxy-2')-substituted ethyloctahydropyrrolo[1,2-a]pyrazines were studied. Two most promising compound (PV-238) is characterized by high antiarrhythmic activity, broad spectrum of action, and low toxicity.

[2-(2'-hydroxy 2'-substituted) ethyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines--a novel group of substances with anti-arrhythmia activity]. / 2-(2'-Gidroksi-2'-zameshchennye) étil-1,2,3,4-tetragidropirrolo[1,2-a]piraziny--novaia gruppa veshchestv, obladaiushchikh antiaritmicheskoi aktivnost'iu.

The antiarrhythmic activity and acute toxicity of a series of 2-(2'-hydroxy-2'-substituted) ethyl-1,2,3,4-tetrahydropyrrolo[1,2- a]pyrazines were studied. Two most promising compounds (PV-168 PV-174) are characterized by a high antiarrhythmic activity, a broad spectrum of action, and low toxicity.

[Use of thymogen in the treatment of various forms of acute abdominal disorders in an experiment]. / Primenenie timogena v lechenii nekotorykh vidov ostroi abdominal'noi patologii v éksperimente.

The authors have carried out experimental studies of thymogen action on the course of acute pancreatitis and acute peritonitis in white albino rat males. The preparation was introduced into the abdominal cavity early after the modeling and every 24 hours for 5 days. The results of the trial demonstrate that the degree of autoenzyme aggression (the data of blood serum alpha-amylolytic activity control) and the content of lipid peroxidation products (assessment of malonic dialdehyde quantity in tissue homogenate) were low in the experimental group as compared to the untreated animals. In the experimental group less pronounced depression of antiradical activity (superoxide dismutase and catalase activity control) was found, leukocytosis and leukocyte intoxication index were diminished. Thus, the efficiency of thymogen in acute inflammatory and destructive abdominal diseases has been proved.

[The effect of thymogen on the heart in ischemia and reperfusion]. / Vliianie timogena na sostoianie serdtsa pri ishemii i reperfuzii.

The anti-ischemic properties of thymogen were studied on an isolated heart model. Its cardioprotective effect was higher than that of dalargin and verapamil. The mechanism of the thymogen anti-ischemic action is realized without the participation of the opiate receptors and blockade of calcium entrance into the cardiomyocytes.

[Effect of the structure of polymeric materials on the properties of immobilized enzymes]. / Vliianie struktury polimernykh materialov na svoistva immobilizovannykh v nikh fermentov.

The relationship between the structure of triacetate cellulose fibres and films and properties of enzymes entrapped in these materials was investigated. Trypsin and penicillin amidase were entrapped in triacetate cellulose films and fibres during their formation. The effect of permeability of the films on the catalytic properties of entrapped trypsin was studied. The porous structure of triacetate cellulose fibres with entrapped penicillin amidase was studied, the fibres being produced by different methods. An increase of porosity and the specific surface of the fibre-biocatalyst reduced the Km value and the energy of activation of the hydrolytic decomposing of benzyl penicillin but increased the Vmax value.