Role of Matrix Metalloproteinase-2 in the Development of Cyclophosphamide-Induced Cardiomyopathy.

Immunohistochemical assay was employed to determine localization of MMP-2 in cardiomyocytes of WAG rats and changes in MMP-2 expression during modeled cardiomyopathy induced by single intraperitoneal injection of cyclophosphamide (125 mg/kg) alone or in combination with preventive intraperitoneal administration of an equal dose of asparcam-L (potassium-magnesium asparaginate) 30 min prior to the cytostatic. In the myocardium of control and experimental rats, MMP-2 was mostly located in cardiomyocyte nuclei. During the development of cyclophosphamide-induced cardiomyopathy (in 3 days after injection), the index of MMP-2-positive cardiomyocyte nuclei increased by 76%. In contrast to control hearts, MMP-2 was also expressed in the cardiomyocyte sarcoplasm. Preventive injection of asparcam-L moderated the cardiotoxic effect of cyclophosphamide, which manifested in less pronounced increase in the volume density of cardiomyocytes with lytic changes (by 42%) and index of MMP-2+ cardiomyocyte nuclei (by 23%) in comparison with the rats exposed to cyclophosphamide alone.

[Biochemical changes in rats under the influence of cesium chloride].

Cesium is lately accumulated actively in the environment, but its influence on human and animal organism is the least studied among heavy metals. It is shown that the action of cesium chloride in rats caused significant changes in blood chemistry, which are characterized by a decrease of total protein content, pH, an increase in the level of urea, creatinine, glucose and total hemoglobin. The results showed that potassium content in all the studied organs and tissues of poisoned rats decreases under the action of cesium chloride. Histological examination of the heart tissue in rats poisoned with cesium chloride indicates the onset of pathology of cardiovascular system. It was found out that use of the drug "Asparkam" reduces the negative effect of cesium chloride on the body of rats.

[Comparison of neuroprotective properties of nootropes, calcium channel blockers, and panangin].

Neuroprotective properties of a series of drugs including nootropes, calcium channel antagonists, and panangin have been studied on a model of craniocerebral trauma. It is established that beglimin and nooglutil exhibit a moderate antiischemic, antihypoxic, and antiamnesic action in posttraumatic period; panangin possesses antiischemic, anticonvulsant, and antiamnesic properties; while nimodipin exhibit only antiamnesic action. It is concluded that beglimin, nooglutil and panangin are of importance in the pharmacological treatment of secondary traumatic brain injury.

Effect of panangin on activity of messengers systems in hypertrophied rat myocardium.

The balance between the two major second messenger systems in hypertrophied myocardium was studied in rats receiving panangin for 16 days. Panangin producing stimulating and polarizing effects on cardiomyocyte membrane improved electrophysiological characteristics of hypertrophied myocardium (electrical stability, duration of supernormal excitability period, and action potential), activated the phosphoinositide exchange, and inhibited the adenylate cyclase system. The panangin-induced change in membrane potentials was accompanied by a pronounced inositol response, i.e. a decrease in the content of membrane polyphosphoinositides (phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-biphosphate) in the brain. It was concluded that function of ion channels depends on activity of phosphoinositide- and adenylate cyclase second messengers systems.

Effect of acute potassium-magnesium aspartate supplementation on ammonia concentrations during and after resistance training.

This study examined the effects of aspartate supplementation (ASP) on plasma ammonia concentrations ([NH4+]) during and after a resistance training workout (RTW). Twelve male weight trainers were randomly administered ASP or vitamin C in a crossover, double blind protocol, each trial separated by 1 wk. ASP and vitamin C were given over a 2-hr period beginning 5 hr prior to the RTW. The RTW consisted of bench, incline, shoulder, and triceps presses, and biceps curls at 70% of one repetition maximum (1-RM). After the RTW a bench press test (BPT) to failure at 65% of 1-RM was used to assess performance. [NH4+] was determined preexercise, 20 and 40 min midworkout, immediately postexercise, and 15 min postexercise. Treatment-by-time ANOVAs, paired t tests, and contrast comparisons were used to identify mean differences. No significant differences were observed between treatments for [NH4+] or BPT. [NH4+] increased significantly from Pre to immediately postexercise for both the ASP and vitamin C trials. Acute ASP supplementation does not reduce [NH4+] during and after a high intensity RTW in weight trained subjects.

[Enzymatic status of leukocytes and its correction in acute stenosing laryngotracheitis in children]. / Fermentnyi status lekotsitov krovi i ego korrektsiia pri ostrykh stenoziruiushchikh laringotrakheitakh u detei.

Virological and cytochemical parameters of blood leukocytes during acute stenosing laryngotracheitis in 53 children were measured, viz. succinate dehydrogenase, mitochondrial alpha-glycerophosphate dehydrogenase, acid and alkaline phosphatase, myeloperoxidase. The patients were subjected to a combined treatment which included metabolites and their cofactors. The treatment gave good results, shortening the duration and reducing the number of relapses of the disease.

The influence of rapid potassium administration on hemodynamics and endogenous catecholamine production during extracorporeal circulation.

In a prospective randomized double-blind study, the peripheral vascular effects of potassium chloride (KCl) and potassium-magnesium-aspartate (KMA) were compared. Twenty patients undergoing coronary artery bypass graft surgery received either 12 mmol of KCl (n = 10) or 12 mmol of KMA (n = 10) into the oxygenator of the heart-lung machine during extracorporeal circulation (ECC). The most striking difference between these two solutions was vasoconstriction following KCl administration and vasodilation after KMA injection. In the KMA group, decreases of perfusion pressure (MAP) and systemic vascular resistance (SVR), as well as changes in the oxygenator volume (dV), were significant (P less than 0.01) between the first and the fifth minutes. Maximal changes of MAP, from 72 +/- 13 to 59 +/- 12 mmHg (mean +/- SD), and SVR were recorded in the first and second minutes. Oxygenator volume changes reached their maximum (285 +/- 163 mL) in the tenth minute. In the KCl group, maximal increases in MAP, from 70 +/- 16 to 81 +/- 20 mmHg (mean +/- SD), and SVR were found in the fourth minute. Maximal changes in dV (300 +/- 315 mL) were measured in the tenth minute. Plasma epinephrine levels, which were already elevated during ECC, showed further increases in all cases in the KCl group and in most of the cases in the KMA group. The change in plasma epinephrine concentration following KCl injection was significant (P less than 0.01). No characteristic change in plasma norepinephrine was found in either of the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparative study on myocardial damage in irradiated for a long time and nonirradiated rats after administration of FCOL]. / Vergleichende Studie über Myokardschädigungen nach Applikation von FCOL an langzeitbestrahlten und unbestrahlten Ratten.

The trials were made to assess the effect of FCOL (9-alpha-fluorocortisol + Na2HPO4) and the effect of K and Mg asparaginates and their mixtures on the modifications of Ca2+, Na+, and K+ ions and of the K/Na ratio in the myocardium of rats not irradiated or submitted to permanent whole-body irradiation (gamma irradiation with 0.57 Gy per day during 25 days, total accumulated dose 14.25 Gy; the trials were performed 25 days after the irradiation). The totality of reversible and irreversible functional modifications of the myocardium, expressed by the quantitative assessment of the K/Na ratio and the concentration of Ca2+ ions, was evaluated in order to determine the cardiotoxicity or cardioprotection. It was demonstrated that irradiation alone causes a slight irreversible modification in the myocardium which is not found in non-irradiated rats. FCOL itself increases the rate of Ca2+ and Na+ ions in irradiated and non-irradiated rats, but does not influence the quantity of K+ ions. Severe irreversible myocardial damages are caused by FCOL, but these damages are considerably lower in irradiated rats. Neither in irradiated nor in non-irradiated rats, the isomers of Mg asparaginate show any protective action against the cardiotoxic effect of FCOL. The isomers of K asparaginate, also combined with Mg asparaginates, as well as the preparation Inzolen exert a demonstrable protective effect against myocardial ion modifications following to application of FCOL. The protection is more efficient in irradiated rats.

[Immunostimulant properties of aspartic acid]. / Immunostimuliruiushchee svoistvo asparaginovoi kisloty.

The experiments on mice have shown that aspartic acid and aspartic acid-containing functionally different agents (panangin, thymopentin, pentagastrin) promoted the in vitro differentiation of bone marrow T-precursors into T-lymphocytes and stimulated the in vivo immune response to SRBC. At the same time aspartic acid and panangin had no effect on the immune response to thymus-independent Vi-antigen.

Effects of potassium + magnesium aspartate on muscle metabolism and force development during short intensive static exercise.

Improvement of muscle performance by 20%-50% in man at a submaximal work load after administration of potassium and magnesium salts of aspartic acid (K + Mg Asp) has been reported in the literature. Administration of K + Mg Asp has been reported to affect force production and energy metabolism in short-term activities of electrical stimulated animal muscles. The present study examined the possible effects of K + Mg Asp on: energy metabolism and force production of electrically stimulated rat quadriceps muscle and endurance time of a submaximal static force of voluntary contracting human muscles. In rat muscles metabolic parameters such as ATP, phosphocreatine, lactate, and L-aspartate were not influenced by oral administration of K + Mg Asp. Force parameters of rat quadriceps muscles were not enhanced after administration of K + Mg Asp. In human volunteers neither the exerted force nor the endurance time increased after oral administration of K + Mg Asp. An effect of K + Mg Asp on muscle metabolism by stimulation of the purine nucleotide cycle was not found. Improvement of muscle performance by 20%-50%, as reported for long-term activity, was not observed for short-term intensive activity.

Absence of effect of potassium-magnesium aspartate on physiologic responses to prolonged work in aerobically trained men.

The effects of oral administration of potassium and magnesium aspartate (K + Mg Asp) on physiologic responses to 90 min of treadmill walking at approximately 62% VO2 max were evaluated in seven healthy males (VO2 max = 59.5 ml X kg-1 X min-1). A total of 7.2 g of K + Mg Asp were administered to each subject during a 24 h period prior to work and compared to control and placebo trials. For control, placebo, and K + Mg Asp trials, no significant differences were observed in resting or exercise values for ventilation (VE), oxygen uptake (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RO), heart rate (HR), or blood pressure (BP). In addition, there were no differences between the three trials for exercise-induced decreases in body weight and increases in rectal temperature, or for pre- and post-exercise alterations in serum lactic acid, creatine kinase, lactic dehydrogenase, and percentage change in plasma volume. The findings from this study indicate that oral ingestion of K+ Mg Asp prior to exercise had no effect on cardiorespiratory, hematologic, and metabolic responses to 90 min of work conducted at approximately 62% VO2 max.

Effect of K and Mg salts of aspartic acid on haemopoiesis and recovery from radiation damage in mice.

Male mice of a non-inbred strain "H" were used to verify the effect of a 10-day peroral administration of K and Mg aspartates on haemopoietic functions. The salts were proved to stimulate the proliferation and differentiation processes in the thymus, bone marrow and spleen tissues. Mice exposed to a single whole-body X-irradiation after pretreatment with K, Mg aspartate exhibited a more conspicuous postirradiation regeneration of haemopoietic organs and an increased postirradiation survival. The results suggest the possibility of using K, Mg aspartate for radioprotective purposes.

[Effect of panangin on potassium level in patients with non-specific ulcerative colitis]. / Vliianie panangina na uroven' kaliia u bol'nykh nespetsificheskim iazvennym kolitom.

Daily injections of panangin to patients with non-specific ulcerative colitis results in the increased concentration of potassium in biological media of the organism.

The effect of magnesiumaspartate on preservation of the rat liver.

1. Isolated rat livers reperfused with an oxygenated isotonic Mg-aspartate or saline solution and stored 1 h at 36 degrees C, 4 h at 22 degrees C or 12 h at 6 degrees C were reperfused at 37 degrees C 150 min with a Krebs-Henseleit solution containing bovine albumin and erthrocytes gased with a 95% O2-5% CO2 gas mixture. 2. Light- and electronmicroscopic studies revealed minor changes after storage, whereas in the reperfused livers a focal distribution of well preserved and disintegrated hepatocytes was observed. 3. During storage the sum of adenine nucleotides in general decreased markedly paralleled by a significant rise of the lactate/pyruvate and hydroxybutyrate/acetoacetate ratios and pronounced breakdown of glycogen. Oxidative phosphorylation was resumed upon reperfusion resulting in de novo synthesis of ATP and ADP. The lactatelpyruvate and hydroxybutyrate/acetoacetate ratios normalized, whereas a resynthesis of glycogen was missing. 4. No conclusive evidence of a protective Mg-effect as observed in induced cardiac arrest has been obtained, probably due to structural and metabolic differences between the two organs and microcirculatory disorders as has been demonstrated by measurements of oxygen uptake using the multiwire electrode.