Correction of Oxidant Stress
Correction of Oxidant Stress during Respiratory Pathologies
Tech Area / Field
- INF-SIG/Sensors and Signal Processing/Information and Communications
- MED-DID/Diagnostics & Devices/Medicine
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
3 Approved without Funding
Highest Medical School AIETI, Georgia, Tbilisi
- Henry Dunant Hospital, Greece, Athens\nGerman Heart Institute, Germany, Berlin\nUniversity of Missouri / School of Medicine, USA, MO, Columbia
Project summaryPathologies of respiratory system take the main place in the structure of children’s diseases, therefore in spite of conducted multiple investigations for the study of etiology, pathogenesis, clinical appearance and therapy of bronchopulmonary diseases it stays as the problem of present interest. Our preceding investigations established that appearance and realization of pathological process in broncho-pulmonary system is caused by structural and functional organization of cell membranes. Level of destruction of biomembranes depends on destabilizing processes’ activity in organism, including lipid peroxidation process, which is the basis of oxidant stress. Oxidant stress and peroxidation syndrome currently is considered as universal pathogenetical factor, which is important in developing practically all basic human disorders.
Basic system maintaining peroxidation in organism at the stationary level is antioxidant system. Antioxidants are substances destructing action of molecular oxygen via removing of oxygen active forms, lowering their production and destructing free radical oxidation products. In the presence of abundant oxygen active forms and insufficiency of antioxidant defense, NO transforms into high toxic peroxynitrit, which is characterized by cytotoxic, bronchoconstructive and surfactant inhibiting effects, these lead to disturbing of NO dependent compensatory mechanisms and complicates disease course. NO influences the effector systems, controlling proliferation, apoptosis and cell differentiation and also causes their stress intolerance.
Oxidant stress developed as the result of balance infringement between bio-oxidants production and lowered activity of key antioxidant protective forces causes “switching on” of apoptosis process. Investigation of apoptosis processes gives basis for working out new approaches to administration of immunopathologic processes over creation of new generation immune-modulating medications, which can regulate atypical or restore disturbed apoptosis. Working out new strategy of pharmacological treatment with abovementioned drugs, will give a chance for recover to the patients, who’s disease can’t be treated with the medications existing now. Coming out from the importance and scientific meaning of problem, the purpose of our work is: at the basis of studying lipid peroxidation processes’ activities and antioxidant defense system to prove their role in clinical-pathogenetic manifestations of respiratory system diseases and working out therapeutic recommendations for receiving medication, for their correction. To study immune status in the presence of indicated pathologies and to reveal correlation between oxidant stress and immune misbalance (cell, humoral immunity, quantity of neutrophiles expressing adhesive receptors, cytolyses and apoptosis). To work out NO registration methods with the help of original NO-sensitive microelectrode and inculcate it in the practice. These investigations certainly will allow clinicists to evaluate oxidant stress severity level and elaborate appropriate treatment.
Fulfillment of project is planned in 3 stages:
I stage - Definition of oxidant stress intensity in surgical and somatic patients with acute respiratory pathologies. About intensity of oxidant stress we’ll judge according to free radical processes intensification, antioxidant enzyme activity and lipid metabolism level. By intensity of electro-paramagnetic resonance signals (EPR) we’ll establish lipid peroxidation processes’ intensification termin LP final product level (malonic dialdehid), with biochemical method of investigation. With EPR method we’ll study ceruroplasmin, Fe-transferin, superoxiddismutase activity. We’ll determine intensity of oxygen active forms-xantinoxidaze, NO, Mn2+, methemoglobin. Investigate adrenoreceptor’s activity.
II stage - we’ll study immune status during abovementioned pathologies and reveal correlation between oxidant stress and immunology status misbalance (cell, humoral immunity, quantity of neutrophyles, expressing adhesion receptors, cytolysis, CD3 (T-lymphocytes), CD4 (T-helpers), CD8 (T-suppressors), LNK (T-killers), CD-19 (B-lymphocytes), A, M, G, E class immunoglobulins.
III stage - we’ll work out ways of NO registration with original NO-sensible microelectrode and inculcate in the practice. Study apoptosis’ mechanisms in neutrophile granulocytes and eusinophiles. Study experimentally and clinically influence of Myeloid, Leukinferon, and Betaleikin on the processes of apoptosis. Creation of special computer program will give opportunity to make minimal mistakes in diagnostics, to choose strategy and tactics of treatment, to prognoses before manifestation course of pathologic process, expelling in favorable issue at the basis of advanced biotechnologies, medical informational telemedicine.
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