Povezanost genskoga polimorfizma OPRM1 A118G s ovisnosti u turskoj populaciji

Susceptibility to addiction has a complex genetic basis that includes genes associated with the action and metabolism of drugs of abuse. One important gene in that respect is OPRM1, which codes for the μ-opioid receptor and has an important role in mediating the rewarding effects of addiction substances. The aim of our study was to assess the prevalence of the OPRM1 A118G polymorphism (rs1799971) in Turkish population and to investigate its association with opioid and other substance addiction. In addition, we examined the association of rs1799971 in addicted patients who were also diagnosed with psychiatric disorders. The study included 103 patients addicted to opioids, cocaine, ecstasy, alcohol, lysergic acid diethylamide (LSD), cannabis, and sedative/hypnotic substances and 83 healthy volunteers with similar demographic features as controls. rs1799971 polymorphisms were identified with the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). The genotype frequencies were significantly higher in the addicted patients than controls (32.0 % vs 16.9 %, respectively; p=0.027). The prevalence of the G allele was 16.1 % in the addicted group and 8.4 % in the control group (p=0.031). Our study confirmed the association between the rs1799971(G) allele frequency and opioid and other substance addiction, but not with psychiatric disorders.Sklonost ovisnosti ima svoju složenu gensku pozadinu, koja obuhvaća gene povezane s djelovanjem i metabolizmom opojnih tvari i droga. U tom je smislu jedan od istaknutih gena OPRM1, koji kodira μ-opioidni receptor te ima važnu ulogu u nagradnom djelovanju tvari koje stvaraju ovisnost. Cilj je ovoga istraživanja bio utvrditi prevalenciju OPRM1 A118G polimorfizma (rs1799971) u turskoj populaciji te njegovu povezanost s ovisnosti o opijatima i drugim drogama. Usto smo istražili povezanost rs1799971 u ovisnika s dijagnozom psihijatrijskih poremećaja. Istraživanje je obuhvatilo 103 ovisnika o opioidima, kokainu, ekstaziju, alkoholu, lizergidu (LSD-u), kanabisu i o sedativima/hipnoticima, odnosno 83 zdrava dobrovoljca sličnih demografskih karakteristika koji su poslužili kao kontrolna skupina. Polimorfizmi rs1799971 utvrđeni su pomoću metode lančane reakcije polimerazom s obzirom na dužinu restrikcijskoga fragmenta (PCR-RFLP). Učestalost ciljanoga genotipa bila je značajno viša u ovisnika nego u kontrolnih ispitanika (32,0 % odnosno 16,9 %; p=0,027), a učestalost G alela iznosila je 16,1 % u ovisnika, odnosno 8,4 % u kontrolnoj skupini (p=0,031). Time je naše istraživanje potvrdilo povezanost između učestalosti rs1799971(G) alela i ovisnosti o opioidima i drugim opojnim tvarima, ali ne i povezanost s psihijatrijskim poremećajima

Assessment of DNA damage in glue sniffers by use of the alkaline comet assay

Toluene is used widely, not only in industry, but also in households where toluene exposure and abuse can occur. To estimate the genotoxic risk of toluene exposure, DNA damage was determined in peripheral lymphocytes of 20 glue sniffers and 20 age-matched controls by use of the alkaline comet assay. Urinary hippuric acid and o-cresol excretion rates, which are used as a marker for toluene exposure, were also measured in sniffers and compared with historical control values. The increase in genetic damage in sniffers was statistically significant as compared to control subjects (P < 0.0001). The mean values of the hippuric acid and o-cresol excretion rate for glue sniffers was 73- and 1582-fold higher, respectively, than in controls and confirms the putative exposure. Education of the general public and efforts to keep adolescents away from volatile solvent-based products, which may lead to a desire of sniffing in the future, would be advisable. (C) 2003 Elsevier B.V. All rights reserved

Oxidative DNA damage and total antioxidant status in rats during experimental gram-negative sepsis

Sepsis and septic shock remains as leading cause of death in adult intensive care units. It is widely accepted that gram-negative bacteria and their endotoxins cause sepsis and septic shock, predominantly. Enhanced generation of reactive oxygen species may be responsible for tissue injury in septic shock and endotoxemia. The aim of this study was to assess oxidative DNA damage and the total antioxidant status (TAS) in peripheral lymphocytes of rats during different intraperitoneal gram-negative sepsis stages. Adult male Sprague-Dawley rats were divided randomly into four groups. Control group was intraperitoneally inoculated with 2 ml, of pyrogene-free saline (Group I, n = 6), and the other rats received an intraperitoneal inoculum with 2 ml, of saline containing 2 x 10(8) CFU of Escherichia coli. The animals were killed at time zero (Group 1, n = 6), at 6th (Group 11, n = 7), 12th (Group M, n = 7), and 24th (Group IV, n = 7) hour after the E. coli inoculation. Oxidative DNA damage in peripheral lymphocytes of rats was evaluated by modified comet assay (single-cell gel electrophoresis). Formamido-pyrimidine DNA glycosylase (Fpg) and Endonuclease III (Endo III) were used to detect oxidized purines and pyrimidines, respectively. Total antioxidant quantification was carried out using ABTS+ (2,2'-Azino-di-[3 ethyl-benzthiazoline sulphonate]) radical formation kinetics (Randox kit) in serum samples. Significant elevations of basal levels of strand breaks (SB) in Group IV were observed as compared with Group I, II, and III. There was a significant increase in Fpg sites in Group III as compared with Group I and II. However, there was no significant difference in terms of Endo III sites in any of the groups. Although the TAS was decreased with the stages of sepsis, this moderate decrease was significant in only Group IV as compared with Group I. There was no statistically significant correlation between DNA damage and TAS for any of the groups