Structural and Functional State of Erythrocyte Membranes in Mice at Different Stages of Experimental Parkinson's Disease Induced by Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP).

We studied some structural and functional parameters of erythrocyte membranes in mice at the late presymptomatic and early symptomatic stages of experimental Parkinson's disease induced by administration of MPTP (hemolysis, microviscosity of different regions of the lipid bilayer, LPO intensity, activity of antioxidant enzymes, and kinetic properties of acetylcholinesterase). At the presymptomatic stage, significant deviations of the studied parameters from the normal were observed; they were similar in direction and magnitude to those in humans with Parkinson's disease. At the early symptomatic stage, most parameters tended to normal. Microviscosity of bulk lipids increased at the presymptomatic stage and decreased after appearance of clinical symptoms. This dynamics probably reflects activation of compensatory mechanisms aimed at inhibition of oxidative stress triggered by the development of the pathological process.

[The Effect of NT-1505 on a Membrane Structure of Endoplasmic Reticulum in vivo].

The effect of neuroprotector NT-1505 on endoplasmic reticulum membranes was studied. It was shown that the dynamics of changes in lipid and near-protein areas microviscosity of endoplasmic reticulum membranes at drug administration is of an antibate nature. This points to the absence of pathological disturbances in the membrane structure. Membrane microviscosity was measured by electron paramagnetic resonance spin labeling of 2,2,6,6-tetramethyl-4-capryloyl-oxylpiperidine-1-oxyl (lipid probe) and 5,6-benzo-2,2,6,6-tetramethyl-1,2,3,4-tetrahydro-γ-carboline-3-oxyl (near protein probe). To obtain more complete information about changes in membrane structure under the action of neuroprotector NT-1505 the temperature dependence of rotational diffusion correlation time was measured in the temperature range of 283-317 K (10-44 degrees C). The two structural transitions were characterized for both areas of .membranes of control group in temperature intervals 16-20 degrees C and 32-38 degrees C which were still present after NT-1505 introduction. Therefore, NT-1505 has no significant effect on membrane structure of the endoplasmic reticulum.

[Effects of low doses of essential oil on the antioxidant state of the erythrocytes, liver, and the brains of mice].

We studied the effects of essential oil from oregano and clove and a mixture of lemon essential oil and a ginger extract on the antioxidant state of organs in intact and three experimental groups of Bulb mice. We found that the essential oil was an efficient in vivo bioantioxidant when mice were treated with it for 6 months even at very low doses, such as 300 ng/day. All essential oil studied inhibited lipid peroxidation (LPO) in the membranes of erythrocytes that resulted in increased membrane resistance to spontaneous hemolysis, decreased membrane microviscosity, maintenance of their structural integrity, and functional activity. The essential oil substantially decreased the LPO intensity in the liver and the brains of mice and increased the resistance of liver and brain lipids to oxidation and the activity of antioxidant enzymes in the liver. The most expressed bioantioxidant effect on erythrocytes was observed after clove oil treatment, whereas on the liver and brain, after treatment with a mixture of lemon essential oil and a ginger extract.

[Studying the effect of Dimebon and NT-1505 on microviscosity of mice brain synaptosomal membranes in vivo by EPR spin labeling method].

In this work membrane fluidity alterations in synaptosomes, isolated from mice brain tissue, at chronic administration of neuroprotectors Dimebon and NT-1505 in vivo were studied. Membrane microviscosity was measured by electron paramagnetic resonance spin labeling of 2,2,6,6-tetramet-hyl-4-capryloyl-oxylpiperidine-l-oxyl (lipid probe) and 5,6-benzo-2,2,6,6-tetramethyl-1,2,3,4-tetrahydro-gamma-carboline-3-oxyl (near protein probe). It was shown that the neuroprotectors Dimebon and NT-1505 affect a membrane structure. Despite the difference in membrane structures, fluidity of the lipid bilayer in time returned to control values.

[Radiation-induced changes in structural state of membranes of human blood cells].

To evaluate radiation-induced changes in the structural state of the membranes, blood samples of healthy donors were subjected to gamma radiation in the range of small (1-10 cGy) and medium doses (50 cGy-2 Gy). After irradiation, the microviscosity of lipid membranes of red and white blood cells was measured by ESR spin probe method. At doses exceeding 1 cGy, statistically significant changes of the degree of spontaneous erythrocyte hemolysis and of the lymphocyte plasma membrane microviscosity were observed. Under identical irradiation conditions, the stability of lymphocyte membranes was less as compared to erythrocyte membranes.

[Effect of prolonged administration of low doses of essential oils on the immune response and sensitivity of mice to the action of ionizing radiation].

The effect of ionizing radiation (1 Gy) on the immunological characteristics of spleen in the mice that consumed essential oils of oregano, clove bud and the mixture of lemon oil with ginger extract at low doses with drinking water for 6 months was studied. It was found that the essential oils increased the content of antibody forming lymphocyte cells in the spleen. The maximal effect in comparison with control was found for essential oil of clove bud.

[Membrane structure markers and the acetylcholinesterase activity of erythrocytes in patients with mild cognitive impairment].

Patients with the syndrome of MCI (n=22) and a control group (31 people without signs of mental and neurological diseases) were tested for the degree of hemolysis of erythrocytes (RBC), (membrane structure markers, acetylcholinesterase (AChE) activity in RBC), the level of lipid peroxidation (LPO) (content of malondialdehyde - MDA), microviscosity of surface areas of the membrane using two spin probes localized in the bulk lipids (s1) and in adjacent to the proteins regions of lipid bilayer (s2). There was no difference between the level of spontaneous hemolysis in the group with MCI and the control group which indicated the absence of changes in the mechanical resistance of the RBC membrane. Significant between- group differences were identified for s2 (the increase by >40% in MCI). A trend toward the increase in MDA level in MCI was found as well. There was a decrease by approx. 30% in the Vmax and Km for AChE reaction that indicated the changes in properties or amount of this enzyme. The value of Vmax/Km that determined the real activity of AChE was similar in both groups. No correlations between parameters of membrane structural-functional state that are characteristic of normalcy were noted in the patients with MCI. This finding demonstrated the changes in structural-functional regulation in RBC membrane in elderly people with MCI. Membrane structure status of erythrocytes in MCI holds a special position and differs both from normal ageing and developed Alzheimer's disease. The s1/s2 ratio is recommended as a membrane "marker"for identification of MCI.

[Investigation of changes in fluidity of brain membranes in mice bearing experimental Alzheimer's disease using spin labeling electron paramagnetic resonance].

Changes in fluidity of membranes isolated from the microsomal and crude synaptosomal fractions which were obtained from forebrain tissue of mice bearing experimental Alzheimer's disease induced with olfactory bulbectomy were studied. Membrane microviscosity was measured by electron paramagnetic resonance with 2,2,6,6-tetramethyl-4-capryloyl-oxypiperidine-1-oxyl and 5,6-benzo-2,2,6,6-tetramethyl-1,2,3,4-tetrahydro-gamma-carboline-3-oxyl as spin labeling. Phasic alterations in relative fluidity were found during the development of experimental Alzheimer's disease pathology. These changes correlate with the stages of "clinical" features. Main abnormalities were related to structural changes in near-protein region of the lipid bilayer.

[Effect of oregano essential oil on the engraftment and development of Lewis carcinoma in F1 DBA C57 black hybrid mice].

The effect of a low uptake dose of oregano essential oil with drinking water for three months (Origanum vulgare L.) on the degree of Lewis carcinoma engraftment and some parameters of oxidative stress has been studied in vivo using F1 DBA C57 Black hybrid mice. Oregano essential oil has been established to possess an anticancer activity. The degree of tumor engraftment decreased by 1.8 times, its size decreased by 1.5 times, and the development of tumor was significantly suppressed in sick mice under the effect of oregano essential oil. It was found that the uptake of essential oil did not affect the intensity of lipid peroxidation in the brain of mice and resulted in a significantly (by 36%) decreased content of secondary lipid oxidation products in the liver as shown in a reaction with thiobarbituric acid as compared to control subjects. The activity of antioxidant enzymes was found to increase after three months of essential oil uptake (by 1.5-3 times) as compared to the control group. This effect of essential oil supports the presence of bioantioxidant properties in this essential oil.

[Comparison of the antiradical activity of ionol, components of fresh ginger, and its extracts].

The antiradical properties of three samples of ginger (Zingiber officinale R.)-juice from fresh rhizome, essential oil, and extracts (oleoresin)-were studied and compared with the properties of synthetic antioxidant ionol (butylatedhydroxy-toluene, BHT). Reaction antioxidants with stable free 2,2-diphenyl-1-picrylhydrozyl radicals were used as model systems. DPPH equivalents per gram of ginger sample, EC50, and antiradical efficiency (AE) were determined. The EC50 and AE values for ginger oleoresin and BHT were similar. They were the same as those of highly active natural antioxidants, and the values for essential oil and ginger juice were lower by two orders of magnitude. On the base of kinetic parameters, the ginger samples may belong to antiradical compounds with prolonged action.

[Effects of smoking and tumor process on the contents of key proteins of apoptosis and activity of antioxidant enzymes in blood].

The effects of smoking on the contents of the apoptosis markers Bcl-2 and p53 proteins in blood plasma; the activity of the antioxidant (AO) enzymes Cu, Zn-superoxide dismutase (SOD), glutathione peroxidase (GP), glutathione reductase (GR), glutathione S-transferase (GST), and catalase; and the content of malondialdehyde (MDA) in erythrocytes from healthy donors and cancer patients were studied. Two groups of donors were revealed among healthy smokers: one with high SOD and GP activities and high Bcl-2 protein levels and the other with lower Bcl-2 levels compared with those found in nonsmokers. In the group of cancer patients (both smokers and nonsmokers), significantly increased p53 protein levels and increased activity of GST were found. A negative correlation between MDA and GST in the group of smoking healthy donors and a positive correlation between MDA and p53 in cancer patients were found. The results suggest a relationship between the components of enzymatic defence and lipid peroxidation and the content of apoptosis regulator proteins in healthy smokers and cancer patients.

[Influence of the composition of essential oils on their antioxidant and antiradical properties].

The antiradical and antioxidant properties of essential oil mixtures (EOMs) with various compositions were studied and compared in model systems of hexanal autooxidation, thermal oxidation of methyl linoleate and beta3-carotene, and in a reaction with the stable diphenylpicrylhydrazyl radical. It was found that all EOMs under investigation exhibited antiradical activity. The highest antiradical activity was observed for an EOM containing monoterpene hydrocarbons as the main components (the phenol content was low). The antioxidant activity of all EOMs was from 60 to 98% and depended on the model system composition and the method of assay. The mixture with the highest phenol content exhibits the highest antioxidant activity level in the hexanal autooxidation system. EOMs with a high content of phenols and alpha- and y-terpinenes were the most efficient antioxidants in the beta3-carotene model system. The study confirmed the possibility to vary the antioxidant and antiradical properties of essential oils by preparing their mixtures with a specific composition.

[Gerontological aspects of age-dependent mortality from malignant neoplasms of the population in the Russian Federation].

The demographic analysis of population-age mortality from malignant neoplasms of the population of RF in the years 1980-2008 enables to see the real presentation of the positive impact of medicine and the negative impact of the environment, but also to reveal fundamental biological processes that determine the health and life expectancy of Russian men and women. The authors allocate the leading role in the origin and development of malignant tumors for the aging process.