Characterization CYP1A2, CYP2C9, CYP2C19 and CYP2D6 Polymorphisms Using HRMA in Psychiatry Patients with Schizophrenia and Bipolar Disease for Personalized Medicine.

BACKGROUND: The interindividual genetic variations in drug metabolizing enzymes effects the impact and toxicity in plenty of drugs. OBJECTIVE: CYP1A2, CYP2C9, CYP2C19 and CYP2D6 gene polymorphisms were characterized using high resolution melting analysis (HRMA) in follow-up patients in psychiatry clinic as a preliminary preparation for personalized medicine. METHOD: Genotyping of CYP1A2*1F, CYP2C9 *2, *3, CYP2C19 *2, *3 and *17 and CYP2D6 *3, *4 was conducted in 101 patients using HRMA. Genotype and allele frequencies of the CYP variants were found to be in equilibrium with the Hardy-Weinberg equation. RESULTS: The frequency of the CYP1A2*1F allele in schizophrenia and bipolar disease was 0.694 and 0.255, respectively. The CYP2C9 allele frequencies were 0.087 (CYP2C9*2), and 0.549 (CYP2C9*3) for bipolar; 0.278 (CYP2C9*2) and 0.648 (CYP2C9*3) in schizophrenias. The CYP2C19*2 and *17 allele frequencies was 0.111 and 0.185 in schizophrenia and variant *2 was 0.117 and variant *17 was 0.255 in bipolar group. The frequency of the CYP2D6*3 allele was 0.027 in schizophrenias. The frequencies for the CYP2D6*4 variant were 0.092 and 0.096 in schizophrenia and bipolar groups, respectively. CONCLUSION: The knowledge in pharmacogenomic and also the developments in molecular genetics are growing rapidly. In future, this can be expected to provide new methodologies in the prediction of the activity in drug metabolizing enzymes. The HRMA is a rapid and useful technique to identify the genotypes for drug dosage adjustment before therapy in psychiatry patients.

Beneficial effects of rolipram, a phosphodiesterase 4 specific inhibitor, on testicular torsion-detorsion injury in rats.

INTRODUCTION: The aim of the study is to investigate the effect of Rolipram, a selective phosphodiesterase 4 inhibitor, on testicular torsion - detorsion injury. METHODS: Sixty young male rats were divided into five groups. In each group, the right testes of six rats were removed four hours after detorsion for biochemical analysis, and the right testes of the remaining six rats were removed 24 h after detorsion for pathological analysis. In group 1 (sham-operated) right orchiectomy was performed without torsion, and right testes were sent to the laboratory for biochemical and pathologic analyses. In group 2 (control) torsion was applied to the right testes for 60 min, and detorsion was performed without the administration of Rolipram. In group 3 torsion was applied to the right testes for 60 min. 1 mg/kg Rolipram was administered 30 min before detorsion. In group 4 torsion was applied to the right testes for 60 min, and 1 mg/kg Rolipram was administered during detorsion. In group 5 torsion was applied to the right testes for 60 min. 1 mg/kg Rolipram was administered 30 min after detorsion. The malondialdehyde and nitric oxide levels were determined. The rates of necrosis and apoptosis were evaluated by histopathological examination. RESULTS: The level of malondialdehyde was higher in the torsioned groups (Group 2, 3, 4, 5) than that in group 1 (p = 0.004). There was no statistically significant difference between the groups regarding the level of nitric oxide (p = 0.182). Apoptosis was higher in groups 2, 3 and 4 than in group 1; however, apoptosis was similar in group 1 and group 5 (p = 0.122). The level of necrosis in group 1 was similar to that in groups 4 and 5 (p = 0.194 and p = 0.847, respectively). CONCLUSION: We suggest that the administration of Rolipram can decrease the rate of necrosis and apoptosis in testicular ischaemia-reperfusion injury.

Effects of vitamin D on ovary in DHEA-treated PCOS rat model: A light and electron microscopic study.

AIM: The aim of this study was to investigate the effects of vitamin D treatment on ovary in experimentally designed polycystic ovary syndrome of female rats using light and electron microscopic techniques. METHODS: Twenty-four female pre-pubertal rats were divided into control, DHEA and DHEA+Vit.D groups. In DHEA group, the PCOS rat model was developed by 6mg/kg/day dehydroepiandrosterone administration as subcutaneously injections. In DHEA+Vit.D group, 6 mg/kg/day DHEA and 120ng/100g/week 1,25(OH)2D3 was performed simultaneously. Controls were injected with vehicle alone. At the end of the 28 days, blood samples were collected and the ovarian tissues were taken for histological examinations. RESULTS: FSH, LH levels, LH/FSH ratio, and testosterone levels showed a significant increase in DHEA group when compared with the control group. Moreover, these measurements were lower in the treatment group than the DHEA group. In DHEA group, increased number of atretic follicles and cystic follicles were seen with light microscopic analysis. Cystic follicles with attenuated granulosa cell layers and thickened theca cell layers and lipid accumulation in interstitial cells were observed by electron microscope. It is observed that atretic and cystic follicles were decreased as a result of vitamin D treatment. CONCLUSION: Our results indicate the curative role of vitamin D treatment on the androgen excess in PCOS rat model which causes abnormalities in ovarian morphology and functions. Vitamin D has positive effects on the hormonal and structural changes observed in PCOS, but it has been concluded that long-term use may be more beneficial.

Noninvasive prenatal diagnosis experience in the Çukurova Region of Southern Turkey: detecting paternal mutations of sickle cell anemia and ß-thalassemia in cell-free fetal DNA using high-resolution melting analysis.

OBJECTIVE: This study used a high-resolution melting (HRM) technique to detect paternal mutations for the noninvasive prenatal diagnosis (NIPD) of ß-thalassemia and sickle cell anemia (HbS). We also determined the levels of cell-free fetal DNA and total cell-free DNA. METHODS: We used the HRM technique for fetal genotyping of paternal mutations in maternal plasma from 32 pregnancies at risk of ß-thalassemia and 57 pregnancies at risk of HbS. The DNA levels in maternal plasma were measured using real-time quantitative PCR. Multiples of the median (MoM) values were calculated in women at risk for ß-thalassemia or HbS. RESULTS: Twenty-two paternal mutations were detected in 89 pregnant women. Although we were successfully able to detect the paternal ß-thalassemia mutations, the mutant HbS fetuses could not be distinguished from maternal background in the early weeks of pregnancy. The detection of DYS14 in male fetuses was 100%. The MoM values of women at high risk of having HbS-affected fetuses were higher than those for the other groups. CONCLUSION: High-resolution melting is a useful method for NIPD of ß-thalassemias by detecting paternal mutations in the maternal plasma. Cell-free fetal DNA quantification and MoM values were not informative for HbS or ß-thalassemias in early pregnancy.

Ultrastructural evaluation of the effect of N-acetylcysteine on methotrexate nephrotoxicity in rats.

The aim of this study is to investigate the possible protective effect of N-Acetylcysteine (NAC) against the likely methotrexate (MTX) toxicity on the kidney using ultrastructural together with biochemical data. Moreover, the immunohistochemical detection of Ki67 nuclear antigen is to be evaluated. Fifteen male Wistar albino rats, weighing 240-290 g, were divided into three equal groups: Rats receiving MTX alone, rats receiving MTX plus NAC treatment, and rats comprising the control group. MTX (18 mg/kg/day, body weight) in dissolved physiologic saline was administered intraperitoneally to rats during 3 days. For the MTX plus NAC group, N-Acetylcysteine (300 mg/kg/day, body weight) was administered together with MTX. At the end of the third day, all the rats were killed with cervical dislocation to obtain blood and tissue samples. Application of MTX principally induced prominent large vacuolization in the proximal convoluted tubule cells, and focal thickening in the glomerular basal lamina of some glomeruli. A decrease in tissue SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase), and an increase in serum urea nitrogen and creatinine and in tissue MDA (malondialdehyde) levels were also seen in the MTX group. These changes were significantly reversed in the MTX-plus-NAC-treated group. Most of the vacuoles in the proximal convoluted tubule cells disappeared. Furthermore, an increase in antioxidant enzyme activities, a decrease in serum urea nitrogen and creatinine, and tissue MDA levels were all significant. Additionally, an increase in the number of Ki67 positive-stained cells in proximal tubules was also noted. In conclusion, NAC may be a promising substance against MTX-induced renal damage. It might be useful to use NAC supplementally to minimize MTX-induced nephrotoxicity.