Search Results

1 - 6 of 6 items

  • Author: P. Mokrý x
Clear All Modify Search

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.

Changes in Several Inflammatory and Oxidation Markers after Ovalbumin-Sensitization in a Guinea Pig Model of Allergic Asthma - A Pilot Study

Ovalbumin (OVA)-sensitization is a common way to evoke changes similar to changes in allergic asthma in humans. Activated cells produce various pro-inflammatory and vasoactive substances including reactive oxygen species. The goal of this pilot study was to evaluate mobilization of leukocytes into the lungs and oxidation processes induced by OVA-sensitization in a guinea-pig model of allergic asthma. Guinea-pigs were divided into OVA-sensitized and naïve animals. After sacrificing animals, blood samples were taken and total and differential leukocyte counts were calculated, and eosinophil cationic protein (ECP) and total antioxidant status (TAS) in the plasma were determined. Left lungs were saline-lavaged and total number of cells and differential leukocyte count in the bronchoalveolar lavage fluid (BAL) were calculated. Right lung tissue was homogenized, ECP, TAS and products of lipid and protein oxidation (thiobarbituric acid-reactive substances and lysine-lipoperoxidation end-products) were determined in the lung homogenate. OVA-sensitization increased a total number of cells and percentages of eosinophils and neutrophils and slightly increased ECP in the blood and in the BAL fluid. In addition, increased lipid and protein oxidation in the lung homogenate, and decreased TAS in the plasma was found in OVA-sensitized compared to naïve animals. In conclusion, OVA-sensitization increased mobilization of leukocytes into the lungs and elevated production of reactive oxygen spesies (ROS), accompanied by a decrease in plasma TAS.

Abstract

Tuberculosis, a disease caused by Mycobacterium tuberculosis, represents one of the deadliest infections worldwide. The incidence of resistant forms is increasing year by year; therefore, it is necessary to involve new methods for rapid diagnostics and treatment. One of the possible solutions is the use of whole-genome sequencing (WGS).

The WGS provides an identification of complete genome of the microorganism, including all genes responsible for resistance, in comparison with other genotypic methods (eg. Xpert MTB / RIF or Hain line-probes) that are capable to detect only basic genes. WGS data are available in 1-9 days and several online software tools (TBProfiler, CASTB, Mykrobe PredictorTB) are used for their interpretation and analysis, compared to 3-8 weeks in the case of classic phenotypic evaluation.

Furthermore, WGS predicts resistance to the first-line antituberculotics with a sensitivity of 85-100% and a specificity of 85-100%.

This review elucidates the importance and summarizes the current knowledge about the possible use of WGS in diagnosis and treatment of resistant forms of tuberculosis elucidates.

WGS of M. tuberculosis brings new possibilities for rapid and accurate diagnostics of resistant forms of tuberculosis. Introducing WGS into routine practice can help to reduce the spread of resistant forms of tuberculosis as well as to increase the success rate of the treatment, especially through an appropriate combination of antituberculotics ATs. Introduction of WGS into routine diagnostics can, in spite of the financial difficulty, significantly improve patient care.

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

Introduction: With an increasing prevalence of major depressive disorder (MDD) in population there is a particular interest in finding a suitable biomarker for diagnosis and prognosis of the disease. Many studies have shown that MDD is linked to a systemic inflammatory process, so blood elements counts and ratios have been suggested to be promising indicators in the management and effectiveness of the disease therapy. The aim of this retrospective study was to compare absolute and relative white blood cells counts and to search for any changes in their ratios before and after the therapy of the patients.

Methods: Our study included 36 patients who were admitted to hospital with either a new diagnosis or a recurrent episode of MDD and who were treated by a standard protocol. The peripheral blood samples were collected both at admission and at hospital discharge. Absolute white blood cell count and counts of neutrophils, lymphocytes, monocytes, platelets, as well as mean platelet volume, red blood cell distribution width, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and monocyte/lymphocyte ratio before and after hospitalization (14–29 days) were evaluated and compared. The test of normality was performed and, accordingly, single t-test or Mann-Whitney U-test was used for data analysis.

Results: There were no significant differences between any blood cell ratios in blood samples before and after stay in hospital and appropriate treatment. Monocyte count was significantly higher in MDD patients after hospital discharge (p=0.007), there was a significantly higher difference in discharged patients suffering from MDD recurrent episode (F.33) compared to newly diagnosed MDD (F.32) patients (p=0.010). In patients treated with venlafaxine (N=23) there was a significant increase in monocyte/lymphocyte ratio observed at the end of hospitalization (p=0.018).

Conclusions: The pharmacotherapy and additive treatment of the patients suffering from MDD led only to mild changes in blood cells counts. As our study included only a small number of patients, and blood cell parameters and ratios were compared after a relatively short duration of treatment, further and more detailed research is needed for final conclusions.

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.