Antiplatelet agents'-ticagrelol and eptifibatide-safety in experimental colitis in mice.

BACKGROUND/AIMS: To evaluate the side effects of two antiplatelet agents - ticagrelor and eptifibatide - in mice with experimentally-induced inflammatory bowel disease. METHODS AND MATERIAL: This study was designed as a controlled, animal, drug safety investigation. C57Bl/6 mice were used to establish the ulcerative colitis model by exposure to dextran sulfate sodium (DSS), and divided into three experimental groups: eptifibatide-treated (150 µg/day intraperitoneally; n = 10), ticagrelol-treated (1 mg/day via gastric tube; n = 10), and DSS-control (plain drinking water; n = 10). An unmodeled non-DSS group served as the experimental control. Complete blood count was taken for all mice at baseline (day 0, treatment initiation) and after four days of treatment. On day 4, all animals were sacrificed for autopsy. The primary outcome measure was bleeding, and the secondary outcomes were change in platelet count, hemoglobin level, and hematocrit level. RESULTS: Neither ticagrelor nor eptifibatide treatment produced a significant effect on DSS colitis mice for the safety parameters measured. Platelet count and hemoglobin and hematocrit levels were statistically similar between the three DSS groups and the non-DSS control group (P > 0.05). Autopsy found no evidence of recent bleeding in liver, spleen, central nervous system or serous cavities. CONCLUSION: The antiplatelet agents ticagrelor and eptifibatide were safe in DSS colitis mice, suggesting their potential in humans suffering from ulcerative colitis, and supporting future safety studies.

CARD15 gene polymorphisms in Serbian patients with Crohn's disease: genotype-phenotype analysis.

OBJECTIVE: Genetic heterogeneity and incomplete phenotype penetrance complicate genetic analysis of Crohn's disease (CD). Studies in western Europe have shown that CARD15 polymorphisms increase susceptibility to CD, but frequencies vary within different European populations. The aim here was to evaluate the prevalence of CARD15 mutations and their phenotypic correlation in a Serbian population. MATERIALS AND METHODS: 131 patients with CD, 65 patients with ulcerative colitis, and 88 healthy controls were genotyped for three common mutations (R702W, G908R, Leu1007insC) by PCR-restriction fragment length polymorphism. chi and Student's t-test were used for statistical assessment. RESULTS: At least one CARD15 disease-associated allele was found in 35.11% patients with CD, 14.77% of healthy controls (P=0.001), and 7.69% patients with ulcerative colitis (P=0.0001). The L1007fs mutation showed a significant association with CD (P<0.0001). The frequency of R702W mutant allele was almost equal in the control group and CD patients Univariate analyses established that CARD15 carriers had a significantly higher risk of isolated ileal location [P=0.042; odds ratio (OR) 2.30; 95% confidence interval (CI): 1.02-5.19], fibrostenotic behavior (P<0.0001; OR 9.86; 95% CI: 4.29-22.62), surgical resection (P=0.036; OR 2.2; CI, 1.046-4.626), and earlier onset of disease (P=0.026). CONCLUSION: This study confirms that CARD15 carriers, especially L1007fs mutants, in central Europeans have an increased risk of CD and it is associated with earlier onset, ileal, fibrostenotic disease and a higher risk of surgery. Any influence of latitude is not matched by an east-west divide on the genotype frequency and phenotype of CD within Europe.