APPLICATION OF QUERCETIN FOR CORRECTION OF THE IMPAIRMENT OF THE FUNCTIONAL STATE OF THE ENDOTHELIUS OF VESSELS (CLINICAL AND EXPERIMENTAL STUDY). / ZASTOSUVANNIa KVERTsETYNU DLIa KOREKTsIÏ PORUShEN' FUNKTsIONAL'NOGO STANU ENDOTELIIu SUDYN (KLINIKO-EKSPERYMENTAL'NE DOSLIDZhENNIa).

OBJECTIVE: in the experiment, to investigate the effect of Quercetin on the NO-dependent reactions of isolated vessels involving endothelium and perivascular adipose tissue (PVAT) after a single X-ray irradiation of rats at a sublethal dose. In a clinical study, to investigate the effect of long-term use of Quercetin on the functional state of themicrovascular endothelium in the elderly patients with metabolic syndrome (MS). MATERIAL AND METHODS: Experimental studies were performed on vascular fragments obtained from adult male rats(7-8 months) of the control group, in animals exposed to a single R-irradiation at a dose of 7 Gy and animals irradiated in the same dose, which received Quercetin orally for 14 days three times a week based on 10 mg/kg bodyweight. Fragments of the thoracic aorta (TA) and mesenteric artery (MA) were cleaned of perivascular adipose tissue (PVAT-) or left uncleaned (PVAT+), and then were cut into rings (up to 2 mm). The amplitude of the contractionof the rings TA and MA under the influence of phenylephrine (PE, 3 x 10-6 M), the amplitude of the contraction of therings TA and MA in the presence of a competitive blocker of NO-synthase methyl ester of N-nitro-L-arginine(L-NAME, 10-5 M), the amplitude of relaxation of the rings TA and MA in the presence of N-acetylcysteine (NAC, 10-4 M)were measured. The clinical study examined 110 patients with MS criteria in accordance with ATP III (2001).Patients in the main group for 3 months received Quercetin from the same manufacturer, 80 mg three times a day,patients in the control group received placebo. RESULTS: Single R-irradiation disrupts the regulation of the contractile function of TA and MA, which is evidenced bychanges in the contractile reactions of isolated fragments of these vessels as a response to the action of vasoactivecompounds. Course use of Quercetin in irradiated rats leads to the normalization of contractile and dilatory vascular responses due to partial correction of NO metabolism in the endothelium and PVAT. For the majority of patients(69 %) who received Quercetin, a post-occlusive hyperemia test showed a statistically significant increase of maximal volumetric velocity of the skin blood flow rate and duration of the recovery period to the baseline, which indicates about improvement of vasomotor vascular endothelial function. CONCLUSIONS: Course use of Quercetin improves the functional state of the microvascular endothelium among theelderly people with MS, normalizes contractile and dilatory vascular responses in irradiated rats due to partial correction of NO metabolism in the endothelium and PVAT.

SCIATIC NERVE REGENERATION AFTER AUTOGRAFTING AND APPLICATION OF THE BONE MARROW ASPIRATE CONCENTRATION.

The work aims at studying the effect of the autologous bone marrow aspirate concentrate on regeneration of the sciatic nerve and atrophy of m. tibialis cranialis. We have simulated autografting of the sciatic nerve in rabbits with application of bone marrow aspirate concentrate around the graft area. We obtained autologous aspirate (2mL) from the proximal part of the femur, added dextrosecitrate (1:8), centrifuged it, and added 0.1 of bovine thrombine to 1.0 mL of supraerythrocytic fraction to obtain gel. On days 30 and 90 we assessed the rate of the sciatic nervere generation and morphological changes of the m.tibialis cranialis as well as the content of products of oxidative modification of lipids and proteins (TBA-active products, diene conjugates and carbonyl groups, respectively) and activity of antioxidant enzymatic system (catalase, glutathion peroxidase, glutathione reductase) in this muscle. Evaluation of the nerve fibers regeneration through the sciatic nerve graft 1 cm long showed that 16.0% of them had regenerated into the graft by day 30 and 60.3% by day 90, with 34.7% having regenerated into the distal stump. Application of bone marrow aspirate concentrate had significantly increased regeneration by day 30, amounting to 31.9% in the graft and up to 8.7% in the distal stump and up to 68.0% and 60.1% by day 90 respectively. Prolonged nerve regeneration resulted in progressive muscle atrophy, with decrease of muscular fibers content up to 68.2% and 27.8%. In the group with aspirate concentrate hypothrophy was delayed (% of muscle fibers being 82.8% and57.2%). The content of peroxidation products has dramatically increased by day 30 and has decreased by day 90 with activation of glutathione peroxidase and glutathione reductase enzymes (with catalase activity being significantly high in all the terms).We have also observed decreased oxidative modification of lipids and proteins in the aspirate concentrate group, with additional increase of glutathione peroxidase activity demonstrating the supportive effect of the aspirate cells.

[THYMIC HORMONES, ANTIOXIDANT ENZYMES AND NEUROGENESIS OF BULBUS OLFACTORIUS IN RATS WITH PARKINSONISM: THE EFFECT OF MELATONIN].

The adult rats received both neurotoxin 6-hidroxidophamine and neurotoxin and melatonin. It was investigated a link between the disturbances of the brain antioxidant enzymes activity and thymic endocrine function, as possible pathogenic factors of parkinsonism, with changes in the number of neural stem cells (NSC) in the bulbus olfactorius. Rats with motor asymmetry in the apomorphine test and significant damage of the dopaminergic neurons in the-substantia nigra have decreased levels of superoxide dismutase, catalase and glutathione peroxidase activities in striatum (1.3-1.4 times) and blood thymulin content (8 times) compared to control group. On the contrary, examined indices were not changed in rats without motor asymmetry and correspondingly partly damaged neurons. The number of nestin(+)-cells in the bulbus olfactorius of rats without motor asymmetry increased from 91.2% to 99.3% and remained unchanged after melatonin administration course (10 mg/kg during 18 days). Melatonin administration resulted in the decrease in the number of nestin(+)-cells along with significant elevation of the decreased antioxidant enzymes activity and blood thymulin content in rats with circulatory movements. Possibilities of the enhancement of NSC differentiation in bulbus olfactorius into neuronal direction in such animals has been discussed. The conclusion about the potential use of melatonin as a neuroprotector in parkinsonism therapy has been made.

Orion: a glimpse of hope in life span extension?

Orion is a multicomponent drug based on derivatives of taurocholic acid and several other compounds. Application of Orion into the feeding medium of Drosophila melanogaster resulted in increased life span and survival at stressful conditions. Two paradoxical features of the drug should be stressed: The "age-threshold" (life span extension was observed only when the drug was applied starting from the second half of life) and induction of "centenarian" flies (older 100 days). Orion enhanced survival at heat shock (38 degrees C) and acidic (pH = 1.6) or alkaline (pH = 11.8) feeding mediums, but not at oxidative stresses modeled by 100% oxygen or application of hydrogen peroxide (H(2)O(2)).

[The activity of gas metabolism, thermoregulation, and antioxidant enzymes in aging C57Bl/6 mice].

The distribution type and correlative links between physiological and biochemical indices characterizing functional condition of the systems of gaseous exchange (V(O2) and V(CO2)), thermoregulation (body temperature and coefficient of thermoconductivity) and antioxidant defense have been studied in 62 young (3-5 mo.) and 58 old (23-26 mo.) male C57Bl/ 6 mice. The coefficients of variation differed significantly depending on the variable but not the age-group. Mean values of V(O2) and V(CO2), body temperature and thermoconductivity, but not activities of the antioxidant enzymes, declined in aging. Moreover, the activities of catalase, glutathione-peroxidase and glutathionereductase, i.e. enzymes involved in regulation of hydrogen peroxide level, increased in aging. The correlations between V(O2) and V(CO2), V(O2) and body temperature or V(O2) and the liver pH, as well as between the antioxidant enzyme activities exhibited little age-changes. However, three-dimensional non-linear models revealed significant age-changes in relations between the studied variables.

[Catalase and glutathione-peroxidase: qualitatively different correlations with the rate of oxygen consumption]. / Katalaza i glutationperokxidaza: kachestvenno razlichnaia korreliatsiia so skorost'iu potrebleniia kisloroda.

Correlative relations of the liver supernatant enzymatic activity of catalase (CAT) and glutathione-peroxidase (GP) with the velocities of oxygen consumption (VO2) and carbon dioxide exhalation (VCO2) were analyzed by the two- and three-dimensional linear and non-linear statistical methods in mice. It is shown that despite the close functions, CAT and GP, nevertheless, exhibit opposite correlative and regressive links with the gaseous exchange indices. As was found by the pairwise linear method, the activity correlation with VO2 was positive for CAT, but negative for GP. The opposite patterns of correlation were also apparent under the three-dimensional non-linear analysis.

[Correlative links between superoxide dismutase, catalase and glutathione peroxidase activities in mouse liver]. / Korreliativnye sviazi mezhdu aktivnost'iu superoksiddismutazy, katalazy i glutationperoksidazy pecheni myshei.

Qualitative and quantitative differences in correlative and regressive links between superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase were assessed in the mice liver by two- and three-dimensional statistical methods. Paired linear correlation analysis indicated SOD-CAT tandem as the correlatively acting enzymatic pair. Three-dimensional analysis revealed uniform response surfaces which exhibited higher activities at disproportional values of the other two and lower activities at proportional activities of the other two enzymes. The direct effect of the enzymes on each other was positive [table: see text] while the effect of their product was always negative.

[Correlation between gaseous exchange rate, body temperature, and mitochondrial protein content in the liver of mice]. / Koreliatsiina zalezhnist' mizh hazoobminom, temperaturoiu tila ta vmistom mitokhondrial'noho bilka pechinki myshei.

Correlative and regressive relations between the gaseous exchange, thermoregulation and mitochondrial protein content were analyzed by two- and three-dimensional statistics in mice. It has been shown that the pair wise linear methods of analysis did not reveal any significant correlation between the parameters under exploration. However, it became evident at three-dimensional and non-linear plotting for which the coefficients of multivariable correlation reached and even exceeded 0.7-0.8. The calculations based on partial differentiation of the multivariable regression equations allow to conclude that at certain values of VO2, VCO2 and body temperature negative relations between the systems of gaseous exchange and thermoregulation become dominating.