Citogenetičko oštećenje u turskih radnika na koksnim pećima izloženih policikličkim aromatskim ugljikovodicima: povezanost s genskim polimorfizmima CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1 i GSTP1

The aim of this study was to determine the frequencies of chromosomal aberrations (CA) and cytochalasinblocked micronuclei (CBMN) in peripheral blood lymphocytes from Turkish coke oven workers and the influence of CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 gene polymorphisms on these biomarkers. Cytogenetic analysis showed that occupational exposure significantly increased the CA and CBMN frequencies. Gene polymorphisms, on the other hand, did not affect CA or CBMN in either exposed or control subjects. However, due to the limited sample size, our findings need to be verified in future studies with a larger sample.Cilj je ovog ispitivanja bio utvrditi učestalost kromosomskih aberacija (CA) i mikronukleusa (CBMN) u limfocitima periferne krvi turskih radnika na koksnim pećima te utjecaj genskih polimorfizama CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1 i GSTP1 na te biopokazatelje. Profesionalna je izloženost ovih radnika značajno povećala učestalost CA i CBMN, ali genski polimorfizmi nisu utjecali na ove parametre bez obzira na to je li se radilo o radnicima ili o kontrolnoj skupini. Međutim, značaj je naših rezultata ograničen zbog malog uzorka te su potrebna daljnja istraživanja s većim uzorkom da ih se potvrdi

The Effect of Enantiomer Elution Order on the Determination of Minor Enantiomeric Impurity in Ketoprofen and Enantiomeric Purity Evaluation of Commercially Available Dexketoprofen Formulations

In a recent study, opposite enantiomer elution order was observed for ketoprofen enantiomers on two amylose-phenylcarbamate-based chiral columns with the same chemical composition of the chiral selector but in one case with coated while in the other with an immobilized chiral selector. In the present study, the influence of this uncommon effect on method validation parameters for the determination of minor enantiomeric impurity in dexketoprofen was studied. The validated methods with two alternative elution orders for enantiomers were applied for the evaluation of enantiomeric impurity in six marketed dexketoprofen formulations from various vendors. In most of these formulations except one the content of enantiomeric impurity exceeded 0.1% (w/w)

Genotype and Allele Frequency of CYP3A4-392A > G in Turkish Patients with Major Depressive Disorder

OZEL-KIZIL, ERGUVAN TUGBA/0000-0001-9657-1382; ozguven, halise/0000-0002-9355-2757; Suzen, Sinan/0000-0003-1779-5850WOS: 000438973100013PubMed: 32454661Objectives: Genetic polymorphisms may help for individualized drug dosing and improved therapeutics. CYP3A4 is responsible for the metabolism of more than 50% of the commonly used drugs and metabolizes typical antipsychotic medications and antidepressant drugs. The objective of the study was to assess the genotype and allele frequencies of CYP3A4 -392A>G in Turkish patients with major depressive disorder receiving any SSRIs and to compare these results with the frequencies of other ethnic groups. Materials and Methods: Genotyping analyses of CYP3A4 -3921>G was conducted on 84 Turkish patients using the PCR-RFLP technique. Results: The allele frequencies were found as 0.982 (A) and 0.018 (G) for CYP3A4 -392A>G. The genotype frequencies were determined as 0.976 (AA), 0.012 (AG), and 0.012 (GG). The genotype frequencies were consistent with the Hardy-Weinberg equilibrium. Conclusion: The genotype and allele frequencies of CYP3A4 -392A>G were determined to be low in Turkish patients with major depressive disorder receiving SSRIs. Furthermore, the results of the study were compared with those of other ethnic groups and they displayed pronounced differences among other ethnic groups, especially black subjects.Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S147]This work was supported by the Scientific and Technological Research Council of Turkey (Project: 109S147)

Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients

ozguven, halise/0000-0002-9355-2757; Suzen, Sinan/0000-0003-1779-5850; OZEL-KIZIL, ERGUVAN TUGBA/0000-0001-9657-1382WOS: 000374326900029PubMed: 26830411Background Genetic polymorphisms in CYP2B6 and CYP2C19 may cause variability in the metabolism of sertraline, a widely used antidepressant in major depressive disorder treatment. Objective This study investigates the impact of CYP2B6*4 (785A > G), CYP2B6*9 (516G > T), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (685G > A), CYP2C19*17 (-3402C > T) polymorphisms on plasma concentrations of sertraline and N-desmethyl sertraline in major depression patients treated with sertraline [n = 50]. Setting Participants were patients who admitted to an adult psychiatry outpatient unit at a university hospital. These were DSM-IV major depression diagnosed patients with a stable sertraline medication regimen [for at least one month]. Methods CYP2B6*4 (rs 2279343; 785A > G), CYP2B6*9 (516G > T; rs 3745274), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (rs 4244285; 685G > A), CYP2C19*17 (rs 11188072; -3402C > T), polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Plasma concentrations were measured by high-performance liquid chromatography in patients treated with SERT. Main outcome measure The distribution of CYP2B6*4, *6, *9 and CYP2C19*2, *17 among patient group and the association between genotype and sertraline metabolism. Results Sertraline, N-desmethyl sertraline, N-desmethyl sertraline/sertraline and dose-adjusted plasma concentrations were statistically compared between individuals with wild-type and variant alleles both for CYP2B6 and CYP2C19 enzymes. The mean N-desmethyl sertraline/sertraline value, was significantly lower in all subgroups with *6 and *9 variant alleles (p < 0.05). Sertraline/C values were significantly higher (p < 0.05) and N-desmethyl sertraline/C values were lower in all subgroups with *6 and *9 variant alleles compared to wild-type subgroup. Conclusion CYP2B6*6 and *9 variant alleles had a significant decreasing effect on sertraline metabolism in major depression patients which might result as variations in sertraline therapy