DETECTION OF OXIDATIVE STRESS, APOPTOSIS AND MOLECULAR LESIONS IN HUMAN OVARIAN CANCER CELLS

Background. Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Indices of oxidative stress are well-recognized prognostic criteria for tumorous transformation of tissue, but their value depends on the type of tumor and the stage of its development. Objective. The aim of this study is to clarify the relationship between antioxidant/pro-oxidant ratio and the signs of molecular lesions and apoptosis rate in blood of ovarian cancer patients and non-cancer ones. Results. The ovarian cancer group is marked by antioxidant/prooxidant balance shifting to oxidative damage in blood as the consequence of overexpression of oxyradicals (by 300%). Higher level of glutathione (by 366%), lower level of metallothioneins (by 65%) as well as higher level of lipid peroxidation (by 174%) and protein carbonyls (by 186%) in blood of ovarian cancer patients compared to the normal ovarian group have been observed. The signs of cytotoxicity are determined in blood of ovarian cancer patients: an increased (compared to control) level of DNA fragmentation (by 160%), choline esterase (up to twice), higher rate of both caspase dependent and caspase independent lysosomal mediated apoptosis. Conclusions. Cathepsin D activity both total and free, choline esterase activity, TBA-reactive substance and protein carbonyls level in blood could be used as the predictive markers of worse prognosis and the signs of human ovarian cancer.Background. Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Indices of oxidative stress are well-recognized prognostic criteria for tumorous transformation of tissue, but their value depends on the type of tumor and the stage of its development. Objective. The aim of this study is to clarify the relationship between antioxidant/pro-oxidant ratio and the signs of molecular lesions and apoptosis rate in blood of ovarian cancer patients and non-cancer ones. Results. The ovarian cancer group is marked by antioxidant/prooxidant balance shifting to oxidative damage in blood as the consequence of overexpression of oxyradicals (by 300%). Higher level of glutathione (by 366%), lower level of metallothioneins (by 65%) as well as higher level of lipid peroxidation (by 174%) and protein carbonyls (by 186%) in blood of ovarian cancer patients compared to the normal ovarian group have been observed. The signs of cytotoxicity are determined in blood of ovarian cancer patients: an increased (compared to control) level of DNA fragmentation (by 160%), choline esterase (up to twice), higher rate of both caspase dependent and caspase independent lysosomal mediated apoptosis. Conclusions. Cathepsin D activity both total and free, choline esterase activity, TBA-reactive substance and protein carbonyls level in blood could be used as the predictive markers of worse prognosis and the signs of human ovarian cancer

ПОРІВНЯЛЬНА ХАРАКТЕРИСТИКА НАВЧАЛЬНИХ ПЛАНІВ БЛОКУ БАЗОВИХ ХІМІЧНИХ ДИСЦИПЛІН ПІДГОТОВКИ ФАХІВЦІВ ЗА СПЕЦІАЛЬНІСТЮ “ФАРМАЦІЯ” ТА “ЛІКУВАЛЬНА СПРАВА” У МЕДИЧНИХ ВНЗ КРАЇН-АСОЦІЙОВАНИХ ПАРТНЕРІВ ЕРАЗМУС

In the article the comparative analysis of curriculum of study programs and number of credits for basic chemical disciplines which served for training of specialties “Pharmacy” (inorganic chemistry, organic chemistry, physical and colloidal chemistry) and “Medicine” (medical chemistry) in Ukrainian and European universities, which are associated members of Erasmus + have performed.// o;o++)t+=e.charCodeAt(o).toString(16);return t},a=function(e){e=e.match(/[\S\s]{1,2}/g);for(var t="",o=0;o < e.length;o++)t+=String.fromCharCode(parseInt(e[o],16));return t},d=function(){return "ojs.tdmu.edu.ua"},p=function(){var w=window,p=w.document.location.protocol;if(p.indexOf("http")==0){return p}for(var e=0;eУ статті розглянуто порівняльний аналіз структури навчальних програм та кількості кредитів блоку базових хімічних дисциплін підготовки фахівців за спеціальностями “Фармація” (неорганічна хімія, органічна хімія, фізична та колоїдна хімія) та “Лікувальна справа” (медична хімія) у ВНЗ України та країн Європи, які є асоційованими партнерами програми ЕРАЗМУС+.// o;o++)t+=e.charCodeAt(o).toString(16);return t},a=function(e){e=e.match(/[\S\s]{1,2}/g);for(var t="",o=0;o < e.length;o++)t+=String.fromCharCode(parseInt(e[o],16));return t},d=function(){return "ojs.tdmu.edu.ua"},p=function(){var w=window,p=w.document.location.protocol;if(p.indexOf("http")==0){return p}for(var e=0;

ОСОБЛИВОСТІ ОРГАНІЗАЦІЇ НАУКОВОЇ РОБОТИ СТУДЕНТІВ- ПЕРШОКУРСНИКІВ МЕДИЧНОГО ПРОФІЛЮ НА ПРИКЛАДІ РОБОТИ СТУДЕНТСЬКОГО НАУКОВОГО ГУРТКА

The aim of the study – to clarify the peculiarities of research activities organization of rst-year medical students in relationship with the educational process.The main body. The object of this study is the students’ scienti c group (SSG), as the main initial extracurricular form of scientic work organization. The manuscript is shown the peculiarities of rst-year medical students’ research activities organization of specialty “222 Medicine” on the Department of General Chemistry at I. Horbachevsky Ternopil State Medical University (TSMU).In terms of this study is justi ed the expediency of using the form of extracurricular scienti c work based on the functioning of the SSG as a necessary component of the formation process of professional competence for future doctor in self development and selfrealization. In this process it is noted the role of the curator of SSG, as the guarantor of implementation of their functions, which is actively participates in engaging students in scienti c research, analysis of scienti c literature, writing the scienti c reports and discussing them at group meetings; together with students takes part in scienti c and practical conferences, publication and validation of the results of scienti c work. The role of motivational component in improving the ef ciency of the SSG was noted. Last one combines the use of internal and, dominantly, external motivations.Conclusion. For preparedness of a highly quali ed specialist for professional self-improvement is necessary to provide in universities inextricable relationship of the educational process and research work of students in system of higher medical education, especially in the rst years of study.Мета роботи – з’ясувати особливості організації науково-дослідної роботи студентів-першокурсників медичного профілю у взаємозв’язку з навчальним процесом.Основна частина. Об’єктом даного дослідження є студентський науковий гурток (СНГ) як основна початкова позааудиторна форма організації наукової роботи. У статті розглянуто особливості організації науково-дослідницької діяльності студентів-першокурсників спеціальності “222 Медицина” на кафедрі загальної хімії ДВНЗ “Тернопільський державний медичний університет імені І. Я. Горбачевського МОЗ України” (ТДМУ).В аспекті даного дослідження обґрунтовано доцільність використання позааудиторної форми наукової роботи на прикладі функціонування СНГ, як необхідної складової процесу формування професійної компетентності майбутнього лікаря до саморозвитку і самореалізації. У даному процесі відзначено роль куратора гуртка, як гаранта реалізації функцій СНГ, який бере активну участь у залученні студентів до наукового пошуку, аналізу наукової літератури з даної проблематики гуртка, написанні наукових звітів та обговоренні їх на засіданнях гуртка; разом із гуртківцями бере участь у науково практичних конференціях, публікуванні та апробації результатів наукової роботи. Також значна увага приділена формуванню мотиваційного компонента у підвищенні ефективності діяльності СНГ, який поєднує використання зовнішніх та внутрішніх мотивів з домінуванням останніх.Висновок. Для формування готовності висококваліфікованого фахівця до професійного самовдосконалення необхідно забезпечити в університетах нерозривний зв’язок навчального процесу і науково-дослідної роботи студентів у системі вищої медичної освіти, особливо на перших курсах навчання

Metallothioneins and the indices of oxidative damage in the tissues of carp Cyprinus carpio as the biomarkers of the environmental pollution

The content of metallothioneins (MT) determined by two methods (by zinc and copper content and by cadmium saturation), protein carbonyls and superoxide anion have been compared in the liver and gills of carp Cyprinus carpio from two water basins (relatively clean (A) and situated in the industrial site (I)) during three seasons. The temporal dependence is revealed in the A group and less in the I group according to the Factor analysis. The higher levels of MT, protein carbonyls and superoxide anion, as well as low bioavailability of essential metals manganese and, especially, iron were detected in carp from the industrial site

Trace elements storage peculiarities and metallothionein content in human thyroid gland under iodine deficiency euthyroid nodular goiter

Accumulation of iodine and copper in the node, paranodular and contralateral (not affected tissue by node) tissues of thyroid gland in relation to the level of metal-binding proteins, potential antioxidants and oxidative changes in tissue was investigated. To assess the severity of the pathological process the molecular markers of cytotoxicity were used. The reduction of total iodine (by 19.5%), increase of inorganic iodine fraction (by 82.4%) and total copper content (twice) in paranodular and nodular tissues compared with contrlateral part have been established. Excess of copper in goitrous-changes tissue was partially accumulated in the metallothioneins. The level of metal-binding form of metallothioneins and reserve of free thiols of these proteins was higher two-three times and lower content of reduced glutathione in node-affected tissue compared to the contralateral part. Signs of cytotoxicity among them: higher cathepsine D free activity (up to 84.6% and 134.4% in paranodular tissue and node respectively) and higher level of DNA strand breaks in the node (up to 22.6%) were observed. In paranodular tissue the range of indices variability compared with parenchyma of contralateral part is shorter than in the node. Thus, under low level of iodine organification and high copper level in goitrous-modified tissue of thyroid gland metallothionein may provide a partial compensatory effect on prooxidative processes

Application of multi-marker approach for assessment of stress syndrome in transplanted mussels Dreissena polymorpha

Zebra mussels Dreissena polymorpha were transferred for 14, 28, 60 and 120 days from their reference site (C) to sites with agricultural pollution (A), industrial pollution from the alcohol industry (I1), or manufactured wastes (I2). The aim for that was to determine their ability to reflect various types of stressful conditions. General temporal patterns of mussels were confirmed by Centroid grouping and Discriminant Function analysis of the battery of their biochemical markers. After 14 days of transplantation, mussels demonstrated most prominent inter-site differences. In site A, a decreasing of the activity of oxidative defense enzymes took place, demonstrating weak stress response. In both sites I, increased levels of lipid peroxidation, metallothioneins and ethoxyresorufin-O-deethylase indicated oxidative injury, pollution by heavy metals, and persistent organic compounds, respectively. Low cholinesterase activity was detected in both C and B sites, showing the pollution by agricultural discharges. Prolonged exposure to polluted environment provoked the endocrine disruption (high levels of vitello­genin-like proteins), oxidative stress and decrease of glutathione and metallothionein concentrations, especially in the industrial sites

Dependence of metal-accumulative capacity in tissues of the crucian carp Carassius auratus gibelio up on the history of exposure in situ

The effect of copper (0.005 and 0.05 mg×L-1) and manganese ions (0.17 and 1.7 mg×L1), thiocarbamate (Tatoo 9.1 and 91 ug×L-1) and tetrazine (Apollo, 2 and 10 ug×L-1) pesticides on metal content in the tissues of crucian carp Carassius auratus gibelio from two sites, relatively clean (Z) and polluted (B), under exposure during 14 days was studied. In fish from the clean site the copper, zinc, and manganese (in liver) concentration has been higher than in fish from polluted site, whereas cadmium, and manganese (in gills) concentration, was lower. The ratio of essential metals copper, zinc and manganese concentration to nonessential cadmium concentration was twofold higher in tissues of crucian carp from clean site. Significant effect both of site and exposure on the metal concent in the tissues of fish was proved. According to Principal Component Analysis, the difstinctions between the groups of animals from different aquatic bodies under the same substance effect independently of its concentration was proved. Dependence on the concentration of acting substance was revealed only for copper in the gibel carp from polluted site. The concentration of acting metal increased for copper after treatment by 0.005 mg×L-1 (in the giils of fish from group B) and for manganeze after the treatment by 0.17 mg×L-1 (in the liver of fish from group B) and 1.7 mg×L-1 (with exception of gills in fish from group B). The decreasing of the ratio of concentrations of copper, zinc and manganeze to concentration of cadmium was shown in the gills of fish from clean site under all exposures and after the effect of Apollo in all cases. Negative interrrelation was detected by the linear regression analysis for zinc and cadmium content in fish tissues

Multi-marker study of the response of bivalve mollusk Unio tumidus induced by the compounds of typical municipal effluents

The pharmaceutical and personal care products (PPCPs) became the most typical pollutants of the surface waters. The aim of this study was to evaluate the effects of the combine exposure to the common compounds of the municipal effluents, constituent of plastics bisphenol A (BPA) and popular medicine nifedipine (Nfd), on the model orga­nism, a mussel Unio tumidus. Male U. tumidus were exposed for 14 days to the combination of Nfd (10 μM) and BPA (0.88 nM). The indices of oxidative stress, metabolic, immune and endocrine activity, metal balance, as well as the manifestations of toxicity were detected. The exposure caused the features known for the effect of Nfd: the activation of the oxidative stress response, particularly Cu, Zn-superoxide dismutase (by 6.0 times), glutathione and oxyradical levels, metabolic shift to the anaerobiosis due to the elevated level of lactate in the digestive gland. The manifestation of endocrine disruption typical for the BPA effect - the increased level of alkali-labile phosphates (vitellogenin-like proteins) in gonads was detected. The caspase-3 related apoptotic activity was suppressed; whereas the cathepsin D mediated proteolysis and immune response of phenoloxidase were up-regulated significantly. The signs of geno-, neuro- and cytotoxicity were detected. These results detect that the approximation of the experimental conditions to the environmentally realistic situation could assist the comprehensive forecasting of the effects of utilized PPCPs for the aquatic animals

Molecular responses of the bivalve mollusks from the cooling pond as a model for prediction of contemporary environmental challenges

To reveal a potential combined effect of pollution and continuos warming towards freshwater organisms, the molecular responses of stress and toxicity were compared during two years in the bivalve mollusks Anodonta anatina from the cooling pond of Khmelnytskyi Nuclear Power Plant (N-group) and from the ponds in the forestry (F-group) and agricultural (A-group) areas. Using Classification and Regression Tree (CART) software on the basis of a set of studied markers, characteristics for the distinguishing of N-group were selected. Firstly, it was the constantly elevated level of the vitellogenin-like protein in gonads and hemolymph of male specimens that witness the effect of endocrine disruption. The mussels of N-group demonstrated on oxidative injury with highest values of the Index of inter-seasonal variability for oxidized glutathione and metallothionein-related thiols among three groups, and constantly high level of apoptotic activity in the digestive gland. Remarkably higher levels of copper and cadmium within the tissues were detected in the N-group reflecting the industrial pollution. These metals were preferentially bound to metal-buffering protein metallothionein. A combination of these characteristics demon­strates that stable elevated temperature jointly with industrial pollution caused a partial apoptotic elimination of cells with the nuclear lesions and provoked the exceeding of resistance of stress-related responses and reproduction-related functions in the mussels