Preliminary evidence of an association between the functional c-kit rs6554199 polymorphism and achalasia in a Turkish population.

BACKGROUND: C-kit-positive interstitial cells of Cajal (ICC) of the lower esophageal sphincter are reduced in achalasia. Two functional gene polymorphisms (rs2237025 and rs6554199) within the c-kit gene may affect its transcriptional activity. In this pilot study, we hypothesized that these polymorphisms would be associated with achalasia. METHODS: Genomic DNA was extracted and real-time PCR reactions were used to determine the rs2237025 and rs6554199 c-kit polymorphisms in 88 Turkish patients with achalasia and 101 healthy controls. KEY RESULTS: The frequency of the T allele of rs6554199 was significantly higher in patients with achalasia [odds ratio (OR): 1.55; 95% confidence interval (CI), 1.03-2.34; P = 0.038] compared with the G allele. Under a dominant model of inheritance, the carriage of at least one T allele was significantly more frequent in patients with achalasia (80.7%) than in controls (65.3%; OR: 2.21; 95% CI, 1.13-4.33; P = 0.022). No association of the c-kit rs2237025 polymorphism with achalasia was detected. CONCLUSIONS & INFERENCES: Despite the small sample size and the possibility of a false positive finding, our preliminary data support the hypothesis that the T allele of the c-kit rs6554199 polymorphism may be associated with achalasia in the Turkish population. These findings need to be replicated in other racial-ethnically diverse populations.

Antioxidant and renoprotective effects of paricalcitol on experimental contrast-induced nephropathy model.

OBJECTIVES: The aim of the study was to assess the effect of paricalcitol on the experimental contrast-induced nephropathy (CIN) model. We hypothesised that paricalcitol may prevent CIN. METHODS: 32 Wistar albino rats were divided into four groups (n=8 each): control group, paricalcitol group, CIN group and paricalcitol plus CIN group. Paricalcitol (0.4 µg kg(-1) day(-1)) was given intraperitoneally for 5 consecutive days prior to induction of CIN. CIN was induced at day 4 by intravenous injection of indometacin (10 mg kg(-1)), Nω-nitro-L-arginine methyl ester (L-NAME, 10 mg kg(-1)) and meglumine amidotrizoate (6 ml kg(-1)). Renal function parameters, oxidative stress biomarkers, histopathological findings and vascular endothelial growth factor (VEGF) immunoexpression were evaluated. RESULTS: The paricalcitol plus CIN group had lower mean serum creatinine levels (p=0.034) as well as higher creatinine clearance (p=0.042) than the CIN group. Serum malondialdehyde and kidney thiobarbituric acid-reacting substances levels were significantly lower in the paricalcitol plus CIN group than in the CIN group (p=0.024 and p=0.042, respectively). The mean scores of tubular necrosis (p=0.024), proteinaceous casts (p=0.038), medullary congestion (p=0.035) and VEGF immunoexpression (p=0.018) in the paricalcitol plus CIN group were also significantly lower. CONCLUSION: This study demonstrates the protective effect of paricalcitol in the prevention of CIN in an experimental model.