Voprosy meditsinskoi khimii最新文献

Cholesterol of high density lipoprotein (HDL) subfractions (HDL2 and HDL3), activity of cholesterol ester transport protein (CETP), and standard lipoprotein parameters (cholesterol, triglycerides, HDL cholesterol) were measured in plasma of 192 patients with various psoriasis forms, which included simple "distributed psoriasis", erythrodermic and arthropathic psoriasis. Among psoriatic patients unusually high percent of persons with both hypo- and hyper-cholesterolemia was observed. The same situation was observed with frequency of cases with both low and high plasma HDL cholesterol levels, the distribution being depending from disease severity. In contrast to norm, psoriasis patients had big range not only in HDL2 cholesterol level, but also in HDL3 cholesterol. They also had decreased CETP activity. Data obtained suggest the existence of changes in reverse cholesterol transport system in psoriasis, which may influence skin cell proliferation (via control of cell supply with cholesterol).

The modification of a method of determination gelatinolytic activity in protein fractions obtained by one and two-dimensional polyacrylamide gel electrophoresis is presented. The presence of a fraction 115-125 kD among human proteins of cortex matter and glomerulus of kidney and also in myocardium having gelatinolytic activity is demonstrated.

The effect of administration of 3-acetylpyridine (antivitamin B3), on rat brain serotoninergic and NAD receptor systems was investigated. The injection of 3-acetylpyridine to rats caused a decrease of NAD and serotonin content in the brain and changes in [U-14C]NAD binding to synaptic membranes, serotonin uptake by nerve endings, as well as sensitivity of this process to NAD (10-5 M). Pretreatment of animals with nicotinamide restored modulating effect of NAD.

Nitric oxide production by the human peripheral blood platelets in normal condition and after thoracic and abdominal wounds was investigated. The platelets were obtained from blood by differential centrifuging. The nitric oxide production by platelets (0.5 x 10(8)) was studied in RPMI 1640 medium containing bovine fetal serum, glutamine, and antibiotics, during incubation at 37 degrees C for 15 hours. Nitric oxide level was determined by Griss reaction. A large-scale absolute production of nitric oxide by platelets was revealed both in normal condition (7.70 +/- 0.55 mumol/l), and after thoracic and abdominal wounds (11.45 +/- 0.84 mumol/l). Severe trauma course is associated with hyperproduction of nitric oxide possessing multiple damaging effects, including the anti-thrombogenic one, which should be taken into account in clinical practice.

The applicability of molecular docking method for finding of ligand binding site in a target protein was tested. The basic principle of tested approach consists in generation of hypotheses of protein-ligand complexes by molecular docking of small ligand to all surface of protein. The subsequent scoring of these hypotheses utilizes the values of contact surfaces and complex formation energy. The docking procedure was executed using the original software DockSearch running on PC Pentium or SGI computers. A set of hypotheses of probable ligand positions on the protein surface was created and evaluated with the help of DockSearch. Energy minimization of molecular complexes was done using Sybyl 6.5 (Tripos Inc.) running on SGI server Origin 200. The final set of the best hypotheses of complexes were selected by the values of contact surfaces and complex formation energy. The applicability and the limits of this approach was tested using known 3D structures of different proteins in free state and in complexes with ligands. For most target proteins the method allows to find the ligand binding site correctly. The accuracy of description of ligand binding site is adequate for subsequent searching of lead compounds by database mining. The reasons of some negative results obtained in testing of this approach are also discussed.

The action of extract from Aronia melanocarpa leaves to blood glucose level was investigated. It was shown that incorporated into drinking water and administrated intraperitoneally, the extract significantly reduce the blood glucose level of streptozotocin (STZ)-diabetic and normal rats.

The activity of neitrophil myeloperoxidase and content of blood etyrhrocyte cathecholamines in the blood of women in early postpartum period in dependence on distance of their living area from Semipalatinsk nuclear testing were studied. It was found that women who live closer to Semipalatinsk were characterised by significantly lower neitrophil myeloperoxidase activity and content of cathecholamines in erythrocytes than in control.

Pharmacokinetic properties of benzimidazole derivatives drug possessing antipsychotic, actoprotector, antiarrhythmic, antiulcerogenic, antiallergic, uricosuric, anthelmintic activities have been summarized. Pharmacokinetics of benzimidazole derivatives used in veterinary practice as anthelmintic drugs is also considered. Benzimidazoles derivatives are characterised by multicompartment and ambiguous pharmacokinetic models. The derivatives of benzimidazoles are subjected to the first pass metabolism in the liver, and, therefore, they are converted to both active, and inactive metabolites. It is necessary to take into account for coadministration of benzimidazoles with other drugs. Hepatoduodenal circulation and repeated adsorption of unchanged drug and its metabolites in the gut is observed for benzimidazole. Many derivatives of benzimidazoles are characterised by rather low absolute bioavailability during peroral intake (from 2 up to 60%). Benzimidazsole derivative may bind to proteins and cell elements of blood. More often pharmacokinetic profile of benzimidazoles is linear for low doses, however, at high doses the linearity is lost. For animals and men pharmacokinetic models are always nearly identical.

Asthmatic (n = 100) and health (n = 104) children were compared for rates of homozygous deletions of the glutathione S-transferase class mu and theta genes (null genotypes, GSTM1"-" and GSTT1"-", respectively). The frequency of GSTM1"-" and GSTT1"-" genotypes in patients with bronchial asthma (BA) (52 [symbol: see text] 26%) were increased compared to healthy children (42 and 11%) (odds ratio (OR) for GSTM1"-" = 1.48; CI: 0.82-2.67; p = 0.16; OR for GSTT1"-" = 2.69; CI: 1.2-6.11; p = 0.0079). OR for GSTM1"-" and GSTT1"-"-combination was 5,12; CI: 0.55-119.5; p = 0.107. We conclude that null-genotypes are associated with susceptibility to BA in children. Passive smoking (PS) increased risk of BA for children with GSTM1"-" genotype, but not with GSTT1"-" genotype. The association of these genotypes was estimated with such clinical peculiarities of BA as polyvalent allergy, early development and heavy course. In the group of nonsmoking (NS) patients was found the statistically in significant association of individual null genotypes with any clinical peculiarities. Combination of null-genotypes in NS patients associated with early development of BA (OR = 6.5; CI: 0.78-64.95; p < 0.05), and combination of plus genotypes--with polyvalent allergy (OR = 7.35; CI: 1.07-63.44; p < 0.05). In the group of PS patients GSTM1"-" genotype was associated with early development of BA (OR = 9.0; CI: 1.02-203.3; p < 0.05) and GSTT1"-" genotype--with heavy course of disease (OR = 4.64; CI: 1.16-19.34; p < 0.05). Passive smoking was the risk factor for the unfavourable course of BA for the patients carrying GSTM1"-" genotype. Combination of plus genotypes protected PS patients from all unfavorable peculiarities of disease.

We determined the oxidative modification of proteins (spontaneous and metal-catalysing oxidation, MKO) and the level of corticosteroids in patients with the depersonalization and depression. For detecting oxidative modification of plasma proteins we measured the concentration of protein carbonyl groups formed with 2,4dinitrophenylhydrazine 2,4dinitrophenylhydrazone derivatives; the formation of dityrosine by fluorescence method; protein aggregation and fragmentation. Polyacrylamide gel electrophoresis with sodium dodecyl sulfate (SDS)-PAGE in the presence beta-mercaptoethanol was used to determine the aggregation or fragmentation of proteins by oxygen radicals (OH). Acid-soluble peptides were analised as products of the fragmentation oxidative modification proteins. The level of the corticosteroids was determined using HPLS. The increase of the concentration of protein carbonyl groups in blood plasma of patients with mental disorders. In patients with depersonalization we determined the increase of the bityrosyl cross-link, and different degrees of fragmentation compared with depressive patients. The cortisol level was decreased and corticosterone was increased in the blood plasma of patients with depersonalization. In depressive patients the cortisol level was increased and corticosterone was decreased is discussed. We discussed the role oxidative modification proteins in the disturbance of the corticosteroid and opioid receptors functions in the patients with mental disorders.