Widening and Elaboration of Consecutive Research into Therapeutic Antioxidant Enzyme Derivatives

Undiminishing actuality of enzyme modification for therapeutic purposes has been confirmed by application of modified enzymes in clinical practice and numerous research data on them. Intravenous injection of the superoxide dismutase-chondroitin sulfate-catalase (SOD-CHS-CAT) conjugate in preventive and medicative regimes in rats with endotoxin shock induced with a lipopolysaccharide bolus has demonstrated that antioxidant agents not only effectively prevent damage caused by oxidative stress (as believed previously) but also can be used for antioxidative stress therapy. The results obtained emphasize the importance of investigation into the pathogenesis of vascular damage and the role of oxidative stress in it. The effects of intravenous medicative injection of SOD-CHS-CAT in a rat model of endotoxin shock have demonstrated a variety in the activity of this conjugate in addition to prevention of NO conversion in peroxynitrite upon interaction with O2∙- superoxide radical. Together with the literature data, these findings offer a prospect for the study of NO-independent therapeutic effects of SOD-CHS-CAT, implying the importance of a better insight into the mechanisms of the conjugate activity in modeled cardiovascular damage involving vasoactive agents other than NO

Supramolecular bioenzyme ensemble: Widening of antioxidant protective potential

The antioxidant enzymes (as superoxide dismutase /SOD/ and catalase /CAT/) are significant potential agents for therapeutic aim but they demanded the improvement of their biopharmaceutical properties. For this goal the bienzyme covalent conjugate was obtained by binding SOD with CAT via endothelial glycocalyx glycosaminoglycan – chondroitin sulfate (SOD-CHS-CAT). The SOD-CHS-CAT conjugate had preventive actions after intravenous administration of hydrogen peroxide in rabbits and rats. It should be noted the oxidative stress accompanies for development of endotoxin shock. There is the model of septic shock of animals due to administration of bacterial lypopolysaccharide (LPS, from Salmonella enterica serotype Typhimurium) them as provoking infectious agent. The therapeutic effect of bienzyme SOD-CHS-CAT conjugate has special research interest associated with activity of conjugate after preventive and medicative administration (i.e. before and after LPS administration, respectively). The effect of bienzyme conjugate administered in medicative regime had increased the survival of rats for endotoxin shock. It was the expressive efficacy of medicinal employment of SOD-CHS-CAT conjugate. The obtained results have been grounded the need of experimental evaluation in respect to efficacy of per oral prophylaxis administration of SOD-CHS-CAT conjugate on the endotoxin model injury in rats induced by LPS bolus. The intravenous bolus administration of LPS in rats has been induced the endotoxin shock development with arterial pressure (AP) decrease, heart rate (HR) increase, impairment of condition even before the lethal termination. The AP decrease was restored faster in experimental group; the alterations of HR were similar in both groups. The survival index (73 % in experimental and 63 % in control groups) for twenty-four hours was similar. Higher survival index (95 % in experimental and 75 % in control groups, for five hours) was marked in experimental group emphasizing the action celerity of SOD-CHS-CAT conjugate in vivo. The SOD-CHS-CAT conjugate was active during cytokine phase of endotoxin injury and distant damage stages. Moreover, the level of NO in lever, lung, kidney, heart was enhanced during endotoxin shock progress and there were not significant alterations of NO level after bienzyme conjugate administration intravenously. The changes of urea and creatinine in blood samples have been evidenced the protective action of bienzyme conjugate in respect to kidney function. Diversity of other index alterations have been hampered the forming agreed conclusions about state of other organs. Taken together these date indicated (on the base of survival increase of rats with SOD-CHS-CAT conjugate for endotoxin shock) the other protective effects of this conjugate (besides NO preservation) and importance of its action mechanism investigation on animal model with continuous development of injury and involvement of other vasoactive agents (NO-independent progress of therapeutic effect). This research was supported in part by RFBR grant 15-04-03584 and Ministry of Health Care of Russian Federation

Statistical models of economic burden : a case study in medicine

Purpose: The main aim of this article is to use statistical methods for the estimation of the economic burden and the survival rate of deeply premature babies. Design/Methodology/Approach: The results of a survey of 2.222 children with a birth weight of 501-1500 grams and a gestational age of 23-37 weeks were used as input data. Cox’s proportional hazards model was used as a survival tool. Findings: The results of Cox survival regression model showed a series of statistically significant predictors of survivability (p<0.05) for three age cohorts: neonatal, postnatal and pediatric (until 2 years). One of the statistically significantly predictors of survivability of premature infants with very low birth weight (VLBW) and extremely low birth weight (ELBW) in every age cohort is the volume of primary resuscitation measure and the length of stay in the neonatal pathology unit (NPU). Practical Implications: The results permitted to assess the amount of nursing care measures, the duration of care in a neonatal pathology unit, the rehabilitation of children with VLBW and ELBW in the long run. The assessment will ultimately help to estimate the overall economic burden associated with maintaining health and quality of life of premature babies. Originality/Value: The scientific contribution of the study consists in the use of an integrated approach to the problem of estimating the economic burden of nursing very premature babies, taking into account their survival and subsequent disability risks in the neonatal, postnatal, and pediatric periods.peer-reviewe

Antioxidant enzymes as potential targets in cardioprotection and treatment of cardiovascular diseases. Enzyme antioxidants: the next stage of pharmacological counterwork to the oxidative stress

The focus in antioxidant research is on enzyme derivative investigations. Extracellular superoxide dismutase (EC-SOD) is of particular interest, as it demonstrates in vivo the protective action against development of atherosclerosis, hypertension, heart failure, diabetes mellitus. The reliable association of coronary artery disease with decreased level of heparin-released EC-SOD was established in clinical research. To create a base for and to develop antioxidant therapy, various SOD isozymes, catalase (CAT), methods of gene therapy, and combined applications of enzymes are used. Covalent bienzyme SOD-CHS-CAT conjugate (CHS, chondroitin sulphate) showed high efficacy and safety as the drug candidate. There is an evident trend to use the components of glycocalyx and extra-cellular matrix for target delivery of medical substances. Development of new enzyme antioxidants for therapeutic application is closely connected with progress in medical biotechnology, the pharmaceutical industry, and the bioeconomy

Pedagogical methods of formation of the employees of internal affairs bodies and the ability to interact with persons with disabilities (hearing)

The article deals with pedagogical methods of formation of communicative competences of employees of internal organs when communicating with persons with disabilitiesРассматриваются педагогические приемы формирования коммуникативных компетенций сотрудников органов внутренних при общении с лицами с ограниченными возможностям

No-Reflow Phenomenon and Endothelial Glycocalyx of Microcirculation

The progress in reperfusion therapy dictated the necessity for developing new tools and procedures for adjacent/additional therapy of acute cardiovascular disorders. The adjacent therapy is targeted on the damage of the microcirculation, leading to the unfavorable prognosis for the patients. The no-reflow phenomenon holds special place in the multifactorial etiology of the microcirculation disorders, offering a new challenge in treating the patients associated with ST-segment elevation on ECG at myocardial infarction. One of the numerous causes of no-reflow, the influence of the endothelial glycocalyx of the microcirculation, is analyzed. The results obtained in the studies of the endothelial glycocalyx ultrastructure are generalized, the effect that the fragments of the glycocalyx glycosaminoglycans have on the function of the vascular wall is demonstrated. The trends in searching for correlations between the thickness of the capillary glycocalyx and the cardiovascular disease risk are noted