Flufenamic acid prevents behavioral manifestations of salicylate-induced tinnitus in the rat.

INTRODUCTION: Tinnitus is defined as a phantom auditory sensation, the perception of sound in the absence of external acoustic stimulation. Given that flufenamic acid (FFA) blocks TRPM2 cation channels, resulting in reduced neuronal excitability, we aimed to investigate whether FFA suppresses the behavioral manifestation of sodium salicylate (SSA)-induced tinnitus in rats. MATERIAL AND METHODS: Tinnitus was evaluated using a conditioned lick suppression model of behavioral testing. Thirty-one Wistar rats, randomly divided into four treatment groups, were trained and tested in the behavioral experiment: (1) control group: DMSO + saline (n = 6), (2) SSA group: DMSO + SSA (n = 6), (3) FFA group: FFA (66 mg/kg bw) + saline (n = 9), (4) FFA + SSA group: FFA (66 mg/kg bw) + SSA (400 mg/kg bw) (n = 10). Localization of TRPM2 to the plasma membrane of cochlear nucleus neurons was demonstrated by confocal microscopy. RESULTS: Pavlovian training resulted in strong suppression of licking, having a mean value of 0.05 ±0.03 on extinction day 1, which is below the suppression training criterion level of 0.20 in control tinnitus animals. The suppression rate for rats having both FFA (66 mg/kg bw) and SSA (400 mg/kg bw) injections was significantly lower than that for the rats having SSA injections (p < 0.01). CONCLUSIONS: We suggest that SSA-induced tinnitus could possibly be prevented by administration of a TRPM2 ion channel antagonist, FFA at 66 mg/kg bw.

Protein Tyrosine Phosphatase Non-receptor 22 Gene C1858T Polymorphism in Patients with Coexistent Type 2 Diabetes and Hashimoto's Thyroiditis.

BACKGROUND: A protein tyrosine phosphatase non-receptor type 22 (PTPN22) C1858T gene polymorphism has been reported to be associated with both Type 2 diabetes mellitus (T2DM) and Hashimoto's thyroiditis (HT) separately. However, no study has been conducted to explore the C1858T polymorphism in T2DM and HT coexistent cases up to now. AIMS: The study aimed to determine whether a relationship exists or not between the PTPN22 C1858T polymorphism and this coexistent patient group. STUDY DESIGN: Case-control study. METHODS: Peripheral blood samples from 135 T2DM patients, 102 patients with coexistent T2DM+HT, 71 HT patients and 135 healthy controls were collected into ethylenediaminetetraacetic acid (EDTA) anticoagulant tubes and genomic DNA was extracted. The PTPN22 C1858T polymorphism was analyzed using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) methods. RESULTS: Statistically significant differences were not observed between the patient and control groups. This study demonstrated a statistically significant association between both the CT genotype and the T allele in the female patient group with coexistent T2DM+HT (CT genotype: p=0.04; T allele: p=0.045) with a statistically significant association between the CT genotype and the mean values of body mass index (BMI) and free T3 levels (FT3) (BMI: p=0.044 and FT3: p=0.021) that was detected in the patient group with coexistent T2DM+HT. The minor genotype TT was observed in none of the groups in this study. The CT genotype frequency was [number (frequency): 5 (3.8%), 7 (6.86%), 5 (7.04%), 3 (2.22%), while the T allele frequency was 5 (1.86%), 7 (3.44%), 5 (3.53%) and 3 (1.12%)] in the T2DM, T2DM+HT, HT and control groups, respectively. CONCLUSION: Our data suggest that the PTPN22 1858T allele and the CT genotype are associated with increased risk in female patients for coexistent T2DM+HT. The CT genotype was associated with high mean BMI and free T3 values in the patient group with coexistent T2DM+HT. These results demonstrate that T allele carriers were more often in the T2DM+HT group than in the T2DM group. Therefore, the combination of T2DM and HT with female gender may have higher T allele carriage in comparison to the T2DM only and male groups.

Lack of association of 1513 A/C polymorphism in P2X7 gene with susceptibility to pulmonary and extrapulmonary tuberculosis.

INTRODUCTION: Tuberculosis, is one of the a leading causes of death worldwide, is characterized by different clinical forms including: latent, localized pulmonary infection and extrapulmonary tuberculosis. Candidate gene association studies have implicated common polymophisms in genes that may influence the development of tuberculosis. This study, aimed to elucidate the role of P2X7 gene in 1513A/C polymorphism the etiopathogenesis of tuberculosis. MATERIALS AND METHODS: The study included 160 patients with tuberculosis (71 pulmonary and 89 extrapulmonary tuberculosis) and 160 healthy controls. Genomic DNA was isolated and 1513A/C polymorphism in P2X(7) gene was genotyped by PCR-RFLP method. RESULTS: Frequency of P2X7 AA genotype was 47.5% in controls and 56.87% in patients, AC frequency was 39.37% controls and 32.5% in patients, CC genotype was 13.12% in controls and 10.62% in patients. No significant difference in allele and genotype frequencies (1513A/C polymorphism) between tuberculosis patients and controls was found. CONCLUSION: The results suggest that 1513A/C polymorphism of P2X7 gene is not associated with pulmonary and extrapulmonary tuberculosis in the Eastern Turkey.

[Investigation of CCL1 rs159294 T/A gene polymorphism in pulmonary and extrapulmonary tuberculosis patients]. / Pulmoner ve ekstrapulmoner tüberküloz hastalarinda CCL1 rs159294 T/A gen polimorfizminin arastirilmasi

INTRODUCTION: The purpose of this study is to reveal whether CCL1 rs159294 T/A polymorphism in pulmonary and extrapulmonary tuberculosis patients pose a risk to catch tuberculosis or not. MATERIALS AND METHODS: In the study, peripheral blood samples from the control group, which includes 160 patients, who consulted to Firat University Faculty of Medicine, Pulmonology Policlinic in Elazig province and who were diagnosed with tuberculosis; and 160 healthy individuals, were taken and put into tubes containing EDTA. Each tube contained 2 cc blood samples. DNA isolation was made from these blood samples and CCL1 rs159294 T/A polymorphism was defined with PCR-RFLP analysis. RESULTS: For CCL1 rs159294 T/A polymorphism, TT genotype was found in 98 (61.3%) patients, TA genotype was found in 58 (36.3%) patients, AA genotype was found in 4 (2.5%) patients among 160 patients with tuberculosis; and TT genotype was found in 50 (70.4%) patients, TA genotype in 20 (28.2%) patients, AA genotype was found in 1 (1.4%) patient among 71 patients with pulmonary tuberculosis; TT genotype was found in 48 (53.9%) patients TA genotype was found in 38 (42.7%) patients and AA genotype was found in 3 (3.4%) patients among 89 extrapulmonary tuberculosis patients. And in control group, among 160 healthy individuals, TT genotype was found in 100 (62.5%) individuals, TA genotype was found in 58 (36.3%) individuals, AA genotype was found in 2 (1.3%) individuals and no statistically significant difference was found. CONCLUSION: CCL1 rs159294 T/A polymorphism do not form an inclination to tuberculosis in our population.