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Kucherenko A.,NASU Institute of Molecular Biology and Genetics | Kucherenko A.,Taras Shevchenko National University | Pampukha V.,NASU Institute of Molecular Biology and Genetics | Bobrova I.,Ukrainian Treatment and Diagnostic Center | And 2 more authors.
Cytology and Genetics | Year: 2015

The aim of this study was to clarify the association between the inosine triphosphate pyrophosphatase (ITPA) gene variants and PEG-IFNα/RBV combination treatment induced anemia in chronic hepatitis C (CHC) Ukrainian patients. The data were collected from 80 CHC patients with HCV genotype 1 infection. All study participants received standard doses of PEG-IFNα and RBV. According to the Hb level changes patients were distributed into: case group—42 patients with combination treatment induced anemia, and control group—38 patients with no signs of anemia. Genotyping for ITPA gene rs1127354 and rs7270101 variants was performed using PCR followed by RFLP assay. Fisher’s exact test was used to estimate the difference in genotype and allelic distribution. Distribution of rs7270101 genotypes was not significantly different between groups of CHC patients with RBV-induced anemia and without it. The frequency of rs1127354 A allele carriers was significantly higher (P < 0.05) in group of CHC patients without anemia (23.7%) comparing to the group of patients with anemia (7.3%). The respective allele frequency in control group (13.2%) was almost 3-fold higher (P < 0.05) comparing to the case group (4.9%). Significant association of ITPA gene rs1127354 with protection against RBV-induced hemolytic anemia was found in Ukrainian patients with CHC infection. Rs1127354 variant may assist as a pharmacogenetic marker in HCV antiviral therapy correction for side effect avoidance. © 2015, Allerton Press, Inc.

Pampukha V.M.,NASU Institute of Molecular Biology and Genetics | Kravchenko S.A.,NASU Institute of Molecular Biology and Genetics | Moroz L.V.,NASU Institute of Molecular Biology and Genetics | Moroz L.V.,National Pirogov Memorial Medical University | Livshits L.A.,NASU Institute of Molecular Biology and Genetics
Biopolymers and Cell | Year: 2011

Aim. The goal of our study was to develop an accurate detection of the SNP rs12979860 by RFLP-based method and to evaluate the polymorphic genotype distribution for this SNP among individuals with unknown HCV status from Ukraine. Methods.The SNP rs12979860 was tested by PCR RFLP-based method in 99 individuals from Ukraine. Results. The method of accurate detection of the SNP rs12979860 was developed. The genotypes distributions were: CC - 56 %, CT - 34 %, TT - 10 %. Conclusions. Due to the high incidence of CC genotype, found in our study, the SNP rs12979860 analysis may be useful for Ukrainian patients to predict responses to the treatment considering the HCV genotype and viral load. © Institute of Molecular Biology and Genetics, NAS of Ukraine, 2011.

Butov D.O.,Kharkiv National Medical University | Kuzhko M.M.,National Institute Of Phthisiology And Pulmonology Named After F G Yanovskyi Nams Of Ukraine | Makeeva N.I.,Kharkiv National Medical University | Butova T.S.,Kharkiv National Medical University | And 2 more authors.
Pneumonologia i Alergologia Polska | Year: 2016

Introduction: Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. Material and methods: We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. Results: Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. Conclusions: Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines’ production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB. © 2016 PTChP.

Vernygorodskyi S.V.,National Pirogov Memorial Medical University | Degtiariova L.V.,Bogomolets National Medical University | Iatsyna O.I.,National Cancer Institute | Blume Y.B.,Ukrainian Academy of Sciences | Yemets A.I.,Ukrainian Academy of Sciences
Cytology and Genetics | Year: 2015

The analysis of intestinal differentiation transcription factor CDX2 in the gastric mucosa biopsies has been carried out. It was established that CDX2 by its own promoter activation pathway can obtain intestinal phenotype for gastric mucosa cells. The loss of CDX2 expression in the nuclei of metaplastic epithelium may serve as a predictor of gastric mucosa malignization. © 2015, Allerton Press, Inc.

Calabrese J.R.,Case Western Reserve University | Frye M.A.,Mayo Medical School | Yang R.,Teva Pharmaceuticals | Ketter T.A.,Stanford University | And 65 more authors.
Journal of Clinical Psychiatry | Year: 2014

Objective: To examine the efficacy and safety of adjunctive armodafinil for major depressive episodes associated with bipolar I disorder. Method: Adults meeting DSM-IV-TR criteria for bipolar I disorder and currently experiencing a major depressive episode while taking at least 4 weeks of conventional maintenance medication were enrolled in a placebocontrolled evaluation of adjunctive armodafinil 150 or 200 mg (conducted January 2010-March 2012). The primary efficacy measure was change from baseline to week 8 on the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) total score in the 150-mg armodafinil group versus placebo. Results: Of 786 patients screened, 433 were randomized (placebo, n = 199; armodafinil 150 mg, n = 201; armodafinil 200 mg, n = 33). The 200-mg armodafinil group was discontinued by protocol amendment due to lower than expected patient enrollment. For the 150-mg armodafinil group versus placebo, there was a significantly greater decrease in least squares mean (standard error of mean [SEM]) IDS-C30 total score at week 8 (-21.7 [1.1] vs -17.9 [1.1]; P = .0097; Cohen d therapeutic effect size = 0.28). The proportion of IDS-C30 responders (≥ 50% decrease from baseline) was significantly higher for the 150-mg armodafinil group versus placebo at final visit (46% [91/197] vs 34% [67/196]; P = .0147). The proportion of IDS-C30 remitters (total score ≤ 11) was 21% (42/197) for armodafinil 150 mg versus 17% (34/196) for placebo (P = .3343) at final visit. Adverse events (AEs) observed in > 5% of either the armodafinil 150 mg or placebo groups and more frequently with 150 mg armodafinil were diarrhea (9% [17/198] vs 7% [13/199]), and nausea (6% [11/198] vs 5% [9/199]), respectively. In the 200-mg armodafinil group, there were 2 serious AEs (n = 1, hepatic failure leading to death; n = 1, acute hepatitis). The death was not considered related to study treatment. Conclusions: Adjunctive armodafinil 150 mg significantly improved symptoms of major depressive episodes associated with bipolar I disorder versus placebo and was generally well tolerated. © Copyright 2014 Physicians Postgraduate Press, Inc.

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