Correction of Alcohol-Induced Damage to Mitochondria in Cardiac and Cerebral Cells by Derivatives of Neuroactive Amino Acids.

We studied LPO intensity and respiration of mitochondria in brain and heart cells of rats receiving 5% ethanol for 20 weeks and treated with derivatives of neuroactive amino acids. Chronic semicompulsory alcohol intoxication increased the concentration of LPO products in cardiac and cerebral mitochondria by 46 and 45% (diene conjugates), by 97 and 8% (diketones), and by 28 and 81% (malondialdehyde), respectively, reduced activity of antioxidant enzymes in cardiac and cerebral mitochondria by 24 and 45% (glutathione peroxidase) and by 22 and 26% (superoxide dismutase), respectively, and uncoupled the process of respiration and ATP synthesis, which manifested in a decrease in respiratory control (V3/V4 ratio according to Chance). Glutamic acid derivative Neuroglutam (26 mg/kg) and GABA derivative succicard (44 mg/kg) administered intraperitoneally daily for 28 days after termination of alcoholization decreased the levels of primary and secondary LPO products, up-regulated activity of antioxidant enzymes in mitochondria of the heart and brain, and moderated the mitochondrial dysfunction.

Evaluation of DNA Damage in Experimental Preeclampsia by Comet Assay.

Experimental preeclampsia induced by substitution of drinking water with 1.8% NaCl during pregnancy was associated with an increase in the level of DNA damage in fetal brain and placenta measured by DNA comet assay by 35.7 and 27.8 times, respectively, in comparison with physiological pregnancy.

Effect of Phenibut and Glufimet, a Novel Glutamic Acid Derivative, on Respiration of Heart and Brain Mitochondria from Animals Exposed to Stress against the Background of Inducible NO-Synthase Blockade.

Increased oxygen consumption by heart and brain mitochondria in the absence of ADP and reduced mitochondrial respiration in the presence of ADP were observed in rats exposed to stress simulated by suspension by the dorsal neck skin fold for 24 h, which attests to uncoupling of substrate oxidation and ATP synthesis and can cause electron drain from the respiratory chain, formation of ROS, and oxidative damage to cell structures. Blockade of inducible NO synthase with aminoguanidine (single intraperitoneal dose of 50 mg/kg before stress exposure) increased coupling of respiration and oxidative phosphorylation in heart and brain mitochondria of rats exposed to immobilization-painful stress, which was especially pronounced in cardiomyocytes. The test compounds glufimet (single intraperitoneal dose of 29 mg/kg before stress exposure) and phenibut (single intraperitoneal dose of 50 mg/kg before stress exposure) limited stress-induced mitochondrial damage against the background of inducible NO synthase blockade and without it, which was seen from increased respiratory control ratio in comparison with that in untreated rats exposed to stress (control).

[The clinical laboratory analysis estimate of procedure of direct fluorimetric detection of level of extracellular DNA.]

The direct fluorimetric analysis of extracellular free DNA looks like a perspective test for diagnostic and monitoring of oncologic diseases. The major analytical parameters of this technique were evaluated and its regional reference intervals and inter-individual and intra-individual variability as well. It was established that the technique limit of detection equals 42.2 ng/ml and response is linear till 1000 ng/ml (R2>0.99). The freezing/unfreezing of plasma exerts no influence on result of analysis up to fourth cycle. The storage of blood samples during 8 hours before centrifugation has no significant effect on measuring level of extracellular free DNA. The storage of plasma samples at -20oC during a month also has no significant effect. The coefficients of analytical intraday and inter-days variations not exceeded 7.2%. The level of extracellular free DNA in plasma of healthy volunteers amounted to 305±39.5 ng/ml and 422.7±86 ng/ml in serum. The indices of individuality made up to 0.47 and 0.29 (plasma and blood serum correspondingly). Therefore, it is demonstrated that direct fluorimetric technique of quantitative detection of extracellular free DNA is characterized by acceptable for clinical studies level of quality of measurements, simplicity of procedure requiring no preliminary extraction. This technique can become perspective protocol for application in routine laboratory practice.

[Is cobalt-binding capacity of serum a new perspective diagnostic marker?].

The aim of this study was to determine the reference interval of serum cobalt-binding capacity (CoBC) and to estimate the effect of factors unrelated to oxidative modification of serum albumin on this diagnostic marker. A group of healthy volunteers (n=194), a group of patients with autoimmune diseases (n=44) and a group of patients with diabetes type 2 (n=50) participated in this study. The regional reference interval was found to be 0,462-0,744 mmol Co 2+ /l of serum. The study of serum CoBC in two groups of patients showed that the CoBC level strongly depends on the serum protein profile. Therefore, this diagnostic test may be used for diagnosing ischemia, but other pathologies associated with changes in a ratio of blood protein fractions can also influence the serum CoBC level.

[Endothelial dysfunction is a target for combination antihypertensive therapy in hypertensive patients with type 2 diabetes mellitus].

AIM: To evaluate the impact of combination antihypertensive therapy with lisinopril + amlodipine (Ekvator) on endothelial dysfunction in patients with hypertension and concurrent type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: The trial enrolled 30 patients aged 40 to 65 years with Stages II-Ill hypertension concurrent with T2DM. All the patients received combination antihypertensive therapy with lisinopril + amlodipine (ekvator) for 12 weeks. Endothelial function was studied from serum and urinary NO and endothelin-1 concentrations and occlusion test results. 24-hour blood pressure (BP) monitoring and echocardiography were performed; arterial elastic properties and renal function were investigated. RESULTS: After 12-week therapy, 93.3% of the patients achieved BP goals. Endothelial function was improved in hypertensive patients with T2DM: there were increases in both serum and urinary NO production (by 53.5 and 57.1%, respectively) and decreases in serum and urinary endothelin-1 secretion (by 27.7 and 69.6%, respectively). The number of patients with normal microcirculation increased from 13.3 to 73.3% (p < 0.001). There was significant improvement in 24-hour AP monitoring readings and reductions in the left ventricular mass index by 10.7% and microalbuminuria by 27.7%; the number of patients with increased pulse wave velocity along the elastic arteries declined by 30%. CONCLUSION: Twelve-week treatment with the combined antihypertensive medication ekvator is highly effective and safe for recovering endothelial function and improving the state of target organs in hypertensive patients with T2DM.

[The algorithms of evaluation of economic effectiveness of laboratory technologies].

The article considers several practical situations requiring estimation of economic effectiveness. The protocols of estimation, costs and effectiveness accounting requirements of practical public health are proposed. The necessity of development of correct epidemiological model is demonstrated to estimate profit of innovations of diagnostic stage. The estimation "costs-effectiveness" is made for troponins at diagnostic of cardiac infarction and prostate-specific antigen under screening of prostate cancer.

[The population study of total antioxidant activity of human blood serum and urine].

Many diseases are accompanied with the development of oxidation stress. The analysis of total antioxidant activity is one of the techniques to assess the oxidation-reduction balance. In spite of availability of normative documents recommending to apply this examination the antioxidant activity analysis technique is used in practice not very often. The absence of reference values of this indicator is one of the reasons of this situation. The article presents the results of the study of total antioxidant activity of human blood serum and single portion of urine. On the basis of the results the reference limits were estimated. The correlation analysis of interrelationship between antioxidant activity analysis technique assessment and age, gender and content of substances mostly inputting into analysis results.

[The characteristics of interpretation of results of analysis of protein amount in urine of pregnant women].

The adequacy of implementation of present proteinuria diagnostic thresholds under examination of pregnant women was examined. The analysis was applied to all urine samples of pregnant women from December 2009 to March 20010. The amount of protein in urine was concurrently evaluated by turbidimetric analysis with sulfosalicylic acid, colorimetric analysis with pyrogallol red, "dry chemistry" technology (the diagnostic strips). It is established that the mentioned techniques of analysis of protein in urine provide independent results. The results of colorimetric analysis are characterized by better precision and adequacy. However, in case of pregnant women the diagnostic threshold of protein concentration should be shifted from 0.120 to 0.150 g/l.

[The alteration of threshold of clinical decision making in connection with the implementation of direct detection of cholesterol-low density lipoproteins in laboratory practice].

The retrospective study included 494 patients (the triglycerides level was less than 4.2 mole per liter) examined during January-March 2010 in four medical institutions of Volgograd and Voljsky. The comparative analysis was made of results of the Friedewald equation test and direct test of cholesterol-low density lipoproteins in the same samples. The correlation between the results of different tests of cholesterol-low density lipoproteins was low (R2=0.65). The labeling of patients as particular category according the results of testing of cholesterol-low density lipoproteins with different techniques matched only in 55% of cases. At the same time, under direct testing of cholesterol-low density lipoproteins in 40% of cases the patients were labeled as low risk category.

[The comparative analysis of electrophoretic fractionating of blood serum proteins in diagnostics of multiple plasma cell myeloma].

The choice of technology of electrophoretic fractionating of blood serum proteins is determined, besides the analytical characteristics, by its economic component. The electrophoresis technologies developed by the R&D production facility "Astra" (Russia) and the firm "PZ Cormay S.A." (Poland) are compared from a viewpoint of applicability in routine laboratory, practice and diagnostics of multiple plasma cell myeloma in particular. It is established that under the comparable economic, "consumer" and analytic characteristics of technologies in the diagnostic process the application of the technology in agarose gel ("PZ Cormay S.A.") is more preferable.

[Molecular genetic analysis of Pseudomonas aeruginosa strains isolated from environment and patients in health care facilities].

AIM: Analysis of genetic heterogeneity of Pseudomonas aeruginosa strains isolated in and out of hospitals. MATERIALS AND METHODS: To study the genetic diversity of 36 strains of P. aeruginosa plasmid analysis, random amplified polymorphic DNA (RAPD) technique as well as polymerase chain reaction for detection of virulence genes algD, lasB, toxA, plcH, plcN, exoS, nan1, and nan2. RESULTS: Epidemically important strains were found in different ecological niches. It was shown that these virulence factors could play important roles in pathogenesis of infection. CONCLUSION: RAPD technique was effective for analysis of P. aeruginosa isolates. Number of studied typing bands differed between related isolates for each random primer.

[Determination of troponin in the diagnosis of acute myocardial infarction in practice: clinico-economic analysis].

The authors first made a clinicoeconomic analysis of benefits from the introduction a rapid test for cardiac troponins in Russian routine clinical practice for the diagnosis of acute myocardial infarction. The economic gains associated with the reduced number of both optional hospitalizations and unwarranted refusals of hospitalization were calculated. The probable economic benefit of the improved diagnosis of myocardial infarction after total introduction of the test for troponins was 324.86 rbl. per patient. The importance of a clinicoeconomic analysis is shown to solve the problem of introducing the diagnostic tests into medical practice.

[Influence of tryptophan content in proteins on the quantitative determination of this proteins using photochemical p-dimethylaminobenzaldehyde].

The interaction of proteins containing various number of Trp residues with p-dimethylaminobenzaldehyde (pDABA) was studied. A positive correlation between tryptophan content in proteins and absorbance of protein-pDABA reaction products was found (Spearman's correlation coefficient R = 0.936; p < 0.001). Using the observed correlation we were able to predict a possible range for the absorbance of reaction products for each serum globulin and estimate the contribution of different globulins in the pDABA serum assay. We propose that the described method can be used for the determination of the globulin content in blood serum.

Effect of Citrocard on functional activity of cardiomyocyte mitochondria during chronic alcohol intoxication.

Chronic administration of 50% ethanol in a dose of 8 g/kg produces a toxic effect on functional activity of cardiomyocyte mitochondria, which manifested in decreased rates of respiration and oxidative phosphorylation. Structural GABA analogue Citrocard (phenibut citrate) and reference preparation piracetam in doses of 50 and 200 mg/kg, respectively, prevented the damaging effect of alcohol, which was seen from increased indexes of oxidative phosphorylation in treated animals compared to the control group.

[Benzimidazole derivative inhibition of the mutagenic activity of 2-aminoanthracene]. / Podavlenie mutagennoi aktivnosti 2-aminoantratsena proizvodnym benzimidazola.

The antimutagenic activity of a new benzimidazole derivative that has antioxidative properties was found in the Salmonella/microsome test. This compound reduced the level histidine revertants induced by the promutagen and carcinogen 2-aminoanthracene. Inhibition of the mutagenicity of 2-aminoanthracene appears to be associated with the inactivation of its genotoxic metabolites. The capacity of the benzimidazole derivative for antimutagenic effects is possibly due to a dihydroxyphenyl radical that is present in its structure.

[Anti-ischemic properties of the novel antioxidant enoxifol]. / Protivoishemicheskie svoistva novogo antioksidantnogo sredstva énoksifola.

The antiischemic properties of the new antioxidant drug enoxifol, representing a derivative of N9-imidazo[1,2-a]benzimidazole, was studied in rats on the models of a double-vessel occlusion of common carotid arteries under normal conditions and on the background of irradiation. In addition, we studied the effect of enoxifol on the rehabilitation of experimental animals in the early reperfusion period after total brain ischemia.

[Effectiveness of using the drug Kan-Yang in children with acute respiratory viral infection (clinico-functional data)]. / Effektivnost' primeneniia preparata Kan-Iang u detei s ostroi respiratornoi virusnoi infektsiei, po dannym kliniko-funktsional'nogo issledovaniia.

A randomized trial of the effectiveness of the preparation Kan-Yang (Sweden) consisting of andrographis and eleutherococcus extracts was performed in 53 children with acute respiratory viral infection (ARVI). 40 ARVI children given conventional treatment served control. It is shown that in early acute noncomplicated respiratory disease Kan-Yang tablets relieves considerably the treatment course and promoted cure in good tolerance.