[THE DIAGNOSTICS OF HEREDITARY DISORDERS OF METABOLISM OF PURINES AND PYRIMIDINES IN CHILDREN USING HIGH PERFORMANCE LIQUID CHROMATOGRAPHY OF ELECTRO-SPRAY TANDEM MASS-SPECTROMETRY].

The article presents data concerning new technique of diagnostic of diseases of metabolism of purines and pyrimidines using high performance liquid chromatography combined with electro-spray mass-spectrometry. The procedure of analysis is described in detail: from pre-analytical stage to interpretation of data of liquid chromatography mass-spectrometry, control of quality of data analysis, mass-spectrometry parameters and chromatographic conditions of analysis of purines, pyrimidines and their metabolites. The reference values are presented for purine and pyrimidine nucleosides and bases in urine of healthy individuals. The chemical structure of purines, pyrimidines and their metabolites and examples of chromato-mass-spectrograms under various hereditary disorders of metabolism of purines and pyrimidines are presented as well. The article is targeted to pediatricians of all profiles, medical geneticists and physicians of laboratory diagnostic.

[Effect of ω-3 polyunsaturated fatty acids on predictors of sudden cardiac death in patients with ischemic heart disease and ventricular rhythm disturbances].

OBJECTIVE: To assess the dynamics of non-invasive electrophysiologic (ventricular arrhythmias, HRV, HRT, mTWA) and humoral (red blood cells ω-3 index) SCD predictors at the background of therapy with ω-3 PUFA in patients with iscemic heart disease and ventricular arrhythmias. MATERIALS AND METHODS: The study included 80 patients. Inclusion criteria were: documented IHD (history of myocardial infarction, stable angina, previous surgical intervention on coronary arteries (coronary artery bypass grafting [CABG], percutaneous coronary intervention [PCI]), positive stress tests, signs of IHD in coronary angiography or computer tomography of coronary arteries; ventricular arrhythmias, according to registered Holter monitoring (PVCs in the number of 250 or more per day and /or intermittent ventricular tachycardia paroxysms); continuous antiarrhytmic therapy for at least 1 month before inclusion (ω-blockers and /or amiodarone), 4) informed consent to participate in the study. RESULTS: All criteria for a good anti-arrhythmic effect (reducing the number of PVCs by 75% and more, paired PVCs by 90% or more, the complete elimination of unstable ventricular tachycardia paroxysms) after 3 months of therapy were observed in 16% of patients, and 6 months after - in 46%. A small but significant increase in the number of PVCs, paired PVCs and ventricular tachycardia paroxysms was noted in the control group. As a result, after 6 months of observation the mean SDNN in patients taking ω-3 PUFA, significantly exceeded the value of the one in the control group. Six months after, the mean value of TO was significantly lower and the mean value of TS - higher than in the control group. After 6 months of therapy with ω-3 PUFA it a significant increase of red blood cells ω-3 index was show by increasing the value of both EPA (an average of 78%) and DHA (an average of 42 %). CONCLUSION: 6 months supplementation with 1 g/day ω-3 PUFA for 6 months in patients with IHD improves the effect of standard antiarrhythmic therapy, reducing the number of isolated and paired PVCs, the number of unstable ventricular tachycardia paroxysms, improves HRT, HRV, increases red blood cells ω-3 index. The long-term (more than 3 months) ω-3 PUFA supplementation must consider be taken into in mTWA assessment to avoid false-positive findings in the SCD risk stratification.

[The diagnostic of peroxisomic diseases in children].

The article presents the results of analysis of long-chained fat acids, fitanic acid and pristanic acid using gas chromatography method. The information is provided concerning the biochemical characteristics of mentioned compounds and their biologic role. The procedure of their analysis is described. The reference values of levels of main long-chained fat acids in blood plasma are presented. The dynamics of modifications of these values under various pathologies is analyzed, including the inherited peroxis diseases in children.

[The diagnostic value of the metabolites of adrenaline, norepinephrine, dopamine, and serotonin in the laboratory diagnosis of drug abuse].

The present review describes the diagnostic value of the metabolites of epinephrine, norepinephrine, dopamine, and serotonin in the laboratory diagnosis of drug abuse. The metabolism and effects of these substances in health and drug addiction are considered. A procedure for their analysis is presented.

[Photohemolysis sensitized by psoralen: dependence on pH].

The effect of pH on the hemolysis of erythrocytes photosensitized (366 nm, 23 Wt/m2) by psoralen has been studied. The dependence of the photohemolysis rate (V) on irradiation dose (D) was described by the equation V = Vo + kD, where Vo is the rate of hemolysis without irradiation (dark), and k is the constant. The index of the power at dose x was approximately equal to 2, and its value did not change as the pH of the erythrocyte suspension was changed. It was found that changes in pH led to a sharp change in the value of coefficient k and correspondingly V. The lowest rate of photohemolysis was observed in the pH range from 8.0 to 8.4. As pH was changed from 3.4 to 9.0 or from 8.0 to 7.4, the V value increased approximately twofold. At pH below 7.4, an abrupt increase (approximately fourfold) in V was observed, with the pK value being equal to 7.3. The psoralen molecule lacks titratable acidic and basic groups; therefore, the effects of pH can hardly be assigned to changes in the photophysical properties of the sensitizer. The increase in V in the alkaline region is prohably related to the acceleration of photooxidation of reduced glutathione, whereas the jump of V at pH of about 7.3 may be due to the titration of the product of psoralen photooxidation. The latter assumption is confirmed by the data of hign performance liquid chromatography. In these experiments, psoralen was oxidized in ethanol and mixed with the phosphate buffer at different pH values followed by a qualitative and quantitative analysis by high performance liquid chromatography of photoproducts. Several photoproducts of psoralen have been identified whose content depended on pH. The curve of titration of one photoproduct was similar in shape to the pH dependence of psoralen-photosensitized hemolysis.

[Photo oxidative reactions of psoralens and their role in therapy of dermatoses]. / Fotookislitel'nye reaktsii psoralenov i ikh rol' v terapii dermatozov.

Psoralenes (furocoumarins) in combination with ultraviolet (UV) A radiation (320-400 nm) are used in the treatment of vitiligo, psoriasis, cutaneous T-cell lymphoma and other skin and autoimmune diseases (PUFA therapy). The mechanism of psoralene-photosensitive modification of biologically significant molecules, such as DNA, protein unsaturated lipids, antioxidants, etc. is considered in the paper. Particular emphasis is laid on the mechanism and biomedical significance of photo reactions proceeding via the stage of formation of psoralene photo oxidation products (POP). POP causes oxidative damage to many molecules in in vitro experiments and mediates the T-cell immunity cell in vivo, as appeared as suppression of delayed hypersensitivity and contact sensitivity in mice. The use of randomized double blind control has indicated that POP has therapeutical effects on eczema. A new modality of psoralene photo chemotherapy that consists in the UV-A radiation of psoralene solution followed by its administration (POP therapy) to patients. Unlike conventional PUFA therapy, POP therapy does not require the patients' skin to be exposed to UF-A radiation, which allows adverse effects, such erythema, skin hyperpigmentation, etc. to be avoided.