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  • Author: M. Stankovičová x
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Effects of lipid A analogues of the strains of E. coli on complement and myeloperoxidase activation in myocardial reperfusion following ischaemia in rats

The aim of the study was to evaluate the ability of lipid A analogues obtained from the native strain (LAS) or strains of E. coli resistant to either an amine oxide (modLANO) or to a quaternary ammonium salt (modLBr) to reduce myocardial ischaemia and reperfusion injury in rats. The 0.5, 2, 4, 24 h pretreatment of rats with lipid A from a strain of E. coli resistant to an amine oxide (modLANO 0.5 mg/kg i.v.) in an in vitro model of myocardial ischemia lasting 10 min followed by 10 min reperfusion did not reduce the myeloperoxidase (MPO) and complement activities. In an in vivo study, the 24 h pretreatment of rats with modLANO in a dose of 0.5 mg/kg i.v. only significantly decreased both the MPO and complement activities in serum (p<0.01). The analogues of lipid A indicate abilities to influence the myocardial ischaemia-reperfusion injury in times-dependent and structures-dependent ways.

Abstract

The substance BK 129 - 1-[2-(2-pentyloxyphenylcarbamoyloxy)-(2-methoxymethyl)-ethyl]-perhydroazepinium chloride was prepared in terms of influence of the connecting chain between the carbamate functional group and the basic part of molecule on biological activity. Such a structural feature is important with regard to its stability. In this work we determined the rate constants of alkaline hydrolysis of this compound at increased temperature under isothermal and non-isothermal conditions. The hydrolysis was also performed in buffer solutions with the purpose of evaluating its stability. Non-isothermal tests of stability enable to reduce the number of analyses. The necessary data for stability of compound are in this way achieved in a short time.

Abstract

The aim of our work was to investigate the effect of amitriptyline, citalopram and venlafaxine on the heart during ischemic- reperfusion (l-R) injury. Amitriptyline prolonged both QRS complex and QTc interval duration; citalopram and venlafaxine prolonged only QTc interval duration. Amitriptyline worked most proarrhythmogenic, citalopram least; venlafaxine increased the heart rate during ischemia; however, prolonged QTc interval at the beginning of reperfusion was followed by serious dysrhythmias.

Study of stability of potential betaadrenolytics, derivatives of the [(arylcarbonyl)oxy]aminopropanol by kinetics of alkaline hydrolysis

This work deals with the study of the stability of six derivatives of the [(arylcarbonyl)oxy]amino propanol with carbamate substitution on the benzene ring. The studied compounds are different in the substitution on the amine group in the side chain as well as in the substitution on the carbamate functional group. The hydrolysis of compounds was measured in the aqueous-ethanol sodium hydroxide solution (0.1 mol.l-1) at 25, 37, 45 and 60°C spectrophotometrically in the ultraviolet and visual regions. The studied compounds possess two functional groups, which undergo hydrolysis. The pseudo-first order rate constants of hydrolysis for individual reaction steps were determined. The ester functional group of compounds hydrolyses very quickly in this medium. The compounds possessing the tertiary substitution on the amino group are less stable toward alkaline hydrolysis. The course of hydrolysis of compounds was also investigated by thin layer chromatography (TLC).

Abstract

The aim of this paper is the study of physico-chemical properties of the chosen compounds, derivatives of 2-hydroxy-3-[2-(4-methoxyphenyl) ethylamino]propyl-4-[(alkoxycarbonyl)amino]benzoates and 2-hydroxy-3-[2-(2-methoxyphenyl)ethylamino]propyl-4-[(alkoxycarbonyl) amino]benzoates with potential ultra-short beta-adrenolytic activity. The studied compounds are different in the position of the substituent on the benzene ring in the side chain as well as in the aromatic ring in position 4 with alkyl- (methylto butyl-) carbamate. The physico-chemical characteristics, for example, lipophilicity, surface activity, adsorbability, acidobasic properties etc., are very important for the explanation of the relationship between structure and biological activity of the drug. These parameters serve as the base of quantitative structure-activity study. The goal of this work is to establish the spectral characteristics of studied compounds in UV-area, pKa values, the parameters of lipophilicity (the values of Rf and RM from thin layer chromatography, retention time t´R and capacity factor k´ from liquid chromatography and experimental partition coefficients log P´ values), surface tension, critical micelle concentrations, the adsorbability of compounds expressed by percent of adsorbed compound on active charcoal β% as well as by Freundlich adsorption isotherms. The obtained values are correlated with the parameters characterising the size of molecule, for example, the number of carbon atoms on carbamate functional group.

Abstract

In present work, we have studied kinetics of alkaline hydrolysis of 14 compounds, which are phenylcarbamic acid derivatives with integrated N-phenylpiperazine moiety in the structure. The compounds possessed moderate antiarrhythmic and antimycobacterial activity. Their hydrolysis was carried out in an aqueous medium ethanol sodium hydroxide solution. The course of the hydrolysis was observed spectrophotometrically in visible as well as in ultraviolet regions. The pseudo-first order rate constants were calculated at several temperatures. The values of the activation energy EA were determined by the Arrhenius equation. The rate of hydrolysis of the compounds under the study increase with the increase in temperature and it has been differentiated according to the substitution of N-phenylpiperazine as well as to the alkoxy substitution on phenyl ring.

Abstract

We evaluated the effect of the antipsychotic olanzapine on electrical activity of rat hearts under conditions of ischemic- reperfusion injury. We focused on the prolongation of the corrected QT interval as a risk factor for the incidence of different types of dysrhythmias. Pretreatment with olanzapine showed prolongation of the corrected QT interval as well as increased incidence of dysrhythmias in following order: ventricular premature beats > bigeminies > trigeminies > salvos. We also observed an increase in the frequency of episodes of ventricular tachycardia of about 64% and the average duration of ventricular tachycardia was more than doubled under the conditions of the ischemic-reperfusion injury.

Abstract

A number of pregnant women all over the world suffer from depression and are treated during gestation with antidepressants, mostly with selective serotonin reuptake inhibitors or selective serotonin and norepinephrine reuptake inhibitors. Exposure to prenatal stress is also a great risk factor for a developing fetus and could be responsible for altered fetal development or various neurobehavioral disturbances of a child. Administration of selective serotonin and norepinephrine reuptake inhibitor venlafaxine is associated with various cardiovascular adverse effects, such as tachycardia, increased blood pressure, arrhythmias and hypertensive crisis. The aim of this study was to focus on the effect of pre-gestational chronic mild unpredictable stress and/or administration of antidepressant venlafaxine (10 mg/kg/day, p. o.) on specific parameters, determining the function of the cardiovascular system of male and female rat offspring. Blood pressure and standard ECG were recorded in the offspring. Exposure to pre-gestational stress did not cause significant changes in the systolic, diastolic blood pressure and pulse frequency either in males or in females, compared to the unexposed control animals. Pre-gestational stress caused the shortening of QT interval and prolongation of QRS complex duration in males. On the other hand, in females, the effects of pre-gestational stress were potentiated by the administration of venlafaxine and resulted in elevated systolic and diastolic blood pressure, prolonged QT interval and shortened QRS complex duration, compared to the control. In conclusion, the female rat offspring are more sensitive to exposure to pre-gestational, to chronic mild unpredictable stress and venlafaxine.

Abstract

The aim of this work is the study of stability and kinetics of hydrolysis of the chosen compounds, derivatives of 2-hydroxy-3-[2-(4-methoxyphenyl)ethylamino]propyl-4- [(alkoxycarbonyl)amino]benzoates and 2-hydroxy-3-[2-(2-methoxyphenyl)ethylamino] propyl-4-[(alkoxycarbonyl)amino]benzoates with potential ultra-short beta-adrenolytic activity. The studied compounds are different in the position of the substituent on the benzene ring in the side chain as well as in the aromatic ring in position 4 with alkyl- (methyl- to butyl-) carbamate. Thin layer chromatography and UV-area spectrophotometry are used in order to establish the stability of these potential pharmaceuticals. The stability studies of the compounds were examined in acidic and alkaline media, in buffers and due oxidation at room and at elevated temperature chromatographically, and Rf values of incipient products and degradation products were detected. Kinetics of acid and base hydrolysis in various solutions at temperatures 80 °C and 100 °C were examined through UV-area spectrophotometry. Kinetic parameters such as rate constant k, half-life period t1/2 and usable life t90 were determined.

Abstract

The aim of our study was to evaluate the possibility of influencing the risk factors of metabolic syndrome (MetS) and metabolic cognitive syndrome. As a model of MetS, we used high-fat-fructose diet (HFFD) fed hypertriacylglycerolemic (HTG) rats. Control group included HTG rats fed with HFFD during 8 weeks (HFFD8). Furthermore, we tested the effect of pharmacological and non-pharmacological therapies. Non-pharmacological therapy, which we chose, was a change in diet from HFFD (5 weeks) to standard one (3 weeks) and thus caloric restriction (HFFD5+3). The drug we used was rosmarinic acid (RA; 100mg/kg), which we administered to rats after 5 weeks of HFFD once a day for consecutive 3 weeks with current change in diet to standard one (HFFD5+3+RA) or during lasting last 3 weeks of HFFD (HFFD8+RA). After 8 weeks of experiment, lipid peroxidation markers, lipid profile of blood serum, and neuronal transmission and synaptic plasticity (long-term potentiation [LTP]) in hippocampal sections were evaluated in vitro. We observed a significant effect of dietary change in lipid profile (decreased total cholesterol and low-density lipoprotein cholesterol [LDL-cholesterol] and increased high-density lipoprotein cholesterol [HDL-cholesterol]). The combination of pharmacological and non-pharmacological treatments caused a decrease in total cholesterol, LDL-cholesterol, and lipid peroxidation in blood serum. Change in HFFD to standard diet without treatment resulted in slight improvement in neuronal transmission in the hippocampus and caloric restriction alone also had positive effect on LTP maintenance. Our results suggest that combination of pharmacological and non-pharmacological approaches had better impact on the biochemical parameters of MetS in blood serum, but weak impact on neuronal functions in the hippocampus, where the expected positive effect was achieved only by caloric restriction.