Репозиторий Университета

© 2018 Background and aim: The non-glycosylated glycoform of transferrin (Tf), known as asialo-Tf, was not selected (in favor of disialo-Tf) as the measurand for the standardization of carbohydrate deficient transferrin (CDT) determination because of a lower diagnostic sensitivity provided with the currently available analytical procedures for sera. However, asialo-Tf could provide an additional value to disialo-Tf in the CDT analysis employed in forensic toxicology contexts. The present work aimed at developing an easy sample preparation based on PEG precipitation in order to improve the detectability of asialo-Tf in capillary electrophoresis (CE). Methods: Equal volumes (35 μL) of serum and of 30% PEG-8000 were mixed and briefly vortexed. After centrifugation, the supernatant was iron saturated with a ferric solution (1:1, v/v). The mixture was analyzed in CE for asialo-Tf and disialo-Tf determination. Results: PEG-8000 precipitation allowed the improvement of the baseline in the electropherograms in terms of interferences reduction particularly in the asialo-Tf migration region. The detection of asialo-Tf was possible in 89% of samples with disialo-Tf above the cut-off limit, whereas only 16% of them showed asialo-Tf by employing the traditional sample preteatment. Conclusions: Asialo-Tf represents an additional value to disialo-Tf as a biomarker of alcohol abuse in forensic toxicology.

© 2018, Pleiades Publishing, Ltd. Phospholipase D (PLD; EC 3.1.4.4) is one of the key enzymes catalyzing hydrolysis of cell membrane phospholipids. This review considers and summaries current knowledge about six human PLD isoforms, their structure and a role in physiological and pathological processes. Comparative analysis of PLD isoforms structure is presented. The review considers the mechanism of hydrolysis and transphosphatidylation performed by PLD, the role of PLD1 and PLD2 in the pathogenesis of some types of cancer, infectious, thrombotic, and neurodegenerative diseases is analyzed. The prospects of development of PLD isoformselective inhibitors are considered in the context of their clinical use and inclusion into various therapeutic schemes; the latter is especially important in the case of already developed PLD inhibitors. Phosphatidylethanol (PEth) formed in the human body during phospholipid transphosphatidylation catalyzed by PLD is considered as an alcohol abuse biomarker.

© 2018, Pleiades Publishing, Inc. This is the first study to observe a 25% atrophy of m. vastus lateralis and a decrease in the size of type I and II muscle fibers (by 35 and 44%, respectively) using magnetic resonance imaging (MRI) in women after five to seven years of alcohol intoxication. The decrease in muscle volume is due to the predominant destruction of contractile apparatus as compared with other components.

© 2017 Elsevier B.V. The need for investigating alcohol abuse by means of objective tools is worldwide accepted. Among the currently available biomarkers of chronic alcohol abuse, carbohydrate-deficient transferrin (CDT) is one of the most used indicator, mainly because of its high specificity. However, some CDT analytical and interpretation aspects are still under discussion, as witnessed by numerous research papers and reviews. The present article presents a critical review of the literature on CDT appeared in the period from 2007 to 2017 (included). The article is organized in the following sections: (1) introduction, (2) pre-analytical aspects (3) analytical aspects (4) diagnostic aspects (5) concluding remarks. As many as 139 papers appeared in the international literature and retrieved by the search engines PubMed, Web of Science and Scopus are quoted.

The tendency to anxiety is a characteristic feature of alcohol abusers, and anxiety can be a symptom of alcohol withdrawal as well as comorbid disorder. The frequent comorbidity of alcohol use disorders and anxiety is due to a number of reasons including general hereditary predisposition, mutual conditioning and similar pathogenesis. Pharmacological therapy of anxiety disorders in alcohol-dependent patients is carried out on the basis of general principles of anxiety treatment and involves the use of benzodiazepines, antidepressants and, in some cases, antipsychotics as second-line medicines.

© 2018 Nutritec. All Rights Reserved.  The aim of this study was to examine the effect of polyphenol quercetin on morphological changes in nonalcoholic fatty liver disease (NAFLD) in rats fed high-fructose diet. Material and methods. For 20 weeks animals (n=8 in each group) of the 1 st group were given standard diet and water; the 2 nd group - standard diet and 20% fructose solution; the 3 rd group - standard diet with quercetin supplementation (0.1%) and 20% fructose solution. Formalin-fixed and paraffin-embedded liver samples were sectioned, stained (hematoxilin and eosin, Van Gieson's stain), evaluated with the use of the SAF and NAS scales. Results and discussion. Histological assessment did not reveal pathology in the structure of the liver of the 1 st group rats (SOAOFO; NAS - 0, fibrosis - 0). The 2 nd group rat livers disclosed micro-, mid- and macrovesicular steatosis, inflammation without ballooning, pericellular and periportal fibrosis (S2A1F2; NAS - 3, fibrosis - 2). Quercetin-treated rats exhibited in liver significantly less steatosis without significant changes in inflammation and fibrosis features (S1A1F2; NAS - 2, fibrosis - 2) compared with rats of the 2 nd group. Conclusion. The data obtained demonstrate the ability of quercetin to inhibit the development of NAFLD in rats fed a diet with a high content of fructose, by reducing the severity of hepatostatosis.

© 2018 Russian Academy of Medical Sciences. All rights reserved. Phospholipase D (PLD) is one of the key enzymes that catalyzes the hydrolysis of cell membrane phospholipids. In this review current knowledge about six human PLD isoforms, their structure and role in physiological and pathological processes is summarized. Comparative analysis of PLD isoforms structure is presented. The mechanism of the hydrolysis and transphosphatidylation performed by PLD is described. The PLD1 and PLD2 role in the pathogenesis of some cancer, infectious, thrombotic and neurodegenerative diseases is analyzed. The prospects of PLD isoform-selective inhibitors development are shown in the context of the clinical usage and the already-existing inhibitors are characterized. Moreover, the formation of phosphatidylethanol (PEth), the alcohol abuse biomarker, as the result of PLD-catalyzed phospholipid transphosphatidylation is considered.

© 2018 Media Sphera Publishing Group. All rights reserved. The objective of the present study was to evaluate the possibilities for the use of the changes in the AgNOR staining patterns in the neurons of the dorsal raphe nucleus (DRN) for the purposes of the medical differential diagnostics of the cases of death from chronic alcohol intoxication. We elucidated the characteristics of the activity of protein biosynthesis including the number and the area of the nucleoli in the nuclei of the neurons of the individuals who had died from chronic alcohol intoxication (n=20) in comparison with the subjects of the control group (n=13). To reveal the morphological structures associated with protein biosynthesis in the nucleoli of the serotoninergic neurons of the dorsal raphe nucleus in the brain, the histological preparations were stained with the use of the silver-staining technique for nucleolar organizer regions (AgNOR). The comparative statistical analysis of the results thus obtained with the calculated confidence coefficients was carried out. The aggregated analysis of all the dorsal raphe subnuclei revealed the impairment of the AgNOR staining characteristics in the neurons of the subjects who had died from chronic alcohol intoxication in comparison with those of the subjects comprising the control group. It is concluded that the results of the study can be used for differential diagnostics of deaths from chronic alcohol intoxication and other causes.

© 2018, Media Sphera Publishing Group. All rights reserved. The objective of the present study was the development and validation of the rapid reproducible method for the identification of ethyl glucuronide and ethyl sulfate allowing to store and transport the study specimens without the loss of the substances of interest by placing the samples on the paper. We have developed the validated technique for the detection and quantitative determination of ethyl glucuronide and ethyl sulfate in the cadaveric blood and urine by means of low-resolution tandem mass-spectroscopy with the use of deuterated derivatives of these substances as the internal standards. The low threshold for quantitative determination of both above substances is 50 ng/ml for the blood and 100 ng/ml for the urine. The method is characterized by the accuracy and precision with the coefficient of variation below 15% and the influence of the matrix with the coefficient of variation below 15%. The evaluation of stability of the two analytes in blood when stored in the dry condition on the paper carrier during 2 weeks showed that the coefficient of variation did not exceed 6.4%. The comparative study of ethyl glucuronide and ethyl sulfate in the samples of cadaveric blood and urine containing from 0 to 5.2% of ethyl alcohol was carried out. The methods for the transportation of the biological fluids and for the extraction of ethyl glucuronide and ethyl sulfate placed on the paper carrier (Whatman 903) have been proposed. The possibility has been demonstrated to use ethyl glucuronide and ethyl sulfate as the markers of the consumption of ethyl alcohol during one’s lifetime for the purpose of investigation of the putrifactive changes of the blood components.

© 2018 Media Sphera Publishing Group. All rights reserved. The review demonstrated results and prospects of non-pharmacological and drug therapy patients with liver disease, not associated with a viral infection. The presented data emphasize the relevance of studying the problem of effective therapy of diseases of the liver and its role in improving the course and outcomes of liver disease.

© 2017 Elsevier B.V. The use of polymeric carriers to deliver hydrophobic photosensitizers has been widely discussed as a way to improve both fluorescence diagnostic and photodynamic therapy (PDT) of cancers; however, the photophysical and pharmacokinetic parameters, as well as the PDT activity, of such modifications have, until now, only been poorly investigated. The purpose of the present study was to explore the efficacy of PDT with the formulation of the photosensitizer chlorin e6 (Ce6) in combination with polyvinyl alcohol (PVA) in comparison with Ce6 alone and with the clinical drug, Photodithazine in a mouse tumor model. We also investigated the photoactivity of the Ce6-PVA in a model reaction of tryptophan oxidation, analyzed the polymer–Ce6 interaction using fluorescence spectroscopy and atomic-force microscopy, and tested the phototoxicity in vitro. Using fluorescence imaging in vivo we found that injection to mice of Ce6 in a formulation with PVA resulted in a higher tumor-to-normal ratio and greater photobleaching when compared with either the use of Ce6 alone, or with the effects of Photodithazine. Tumor growth study and histological examination of CT26 tumors revealed fast, reproducible tumor regression and more advanced necrosis after PDT with Ce6-PVA. The higher photoactivity of the Ce6-PVA complex was confirmed in a model reaction of tryptophan oxidation and in cultured cells. Therefore, encapsulation of Ce6 in PVA represents a promising strategy for further increasing the selectivity and efficacy of PDT.