Infliximab in experimental alkali burns of the oesophagus in the rat

PubMed ID: 18396745Backgrounds : We aimed to investigate the efficacy of infliximab, a chimeric TNF-? antibody, in the prevention of fibrosis in an experimental alkaline burn of the oesophagus in the rat. Methods : Thirty-two Wistar albino rats divided into four experimental groups. Caustic oesophageal burn was induced by applying 37.5% NaOH to the distal oesophagus. Infliximab was given at a dose of 5 mg/kg via the intraperitoneal route. Group A (sham) animals were uninjured, group B had untreated oesophageal burns, group C had oesophageal burns treated with a single dose of infliximab on the first day, and Group D had oesophageal burns treated with infliximab on the first and 14th days. Efficacy of the treatment was assessed on the 28th-day by measuring stenosis index of the oesophagus and histopathological damage score, and biochemically by determining tissue hydroxyproline content. Results ; There was no significant difference between the Group B and the infliximab treated Groups C and D in means of tissue hydroxyproline content and histopathological damage scores. Stenosis index was not significantly different between the Group B, Group C, and Group D. Conclusion : Anti-TNF-? treatment with infliximab does not ameliorate the degree of fibrosis in alkali burns of the oesophagus in the rat. Further evaluation of inflammatory and immunological events leading to stricture in alkaline oesophageal burns may provide new perspectives for the treatment of alkaline oesophageal burns

Ketotifen ameliorates development of fibrosis in alkali burns of the esophagus

WOS: 000223007900008PubMed ID: 15108014An experimental study was performed to investigate the efficacy of ketotifen, which is a mast cell stabilizer and histamine H-1-receptor antagonist, on the prevention of stricture development after esophageal caustic injuries in the rat. Caustic esophageal burn was created by applying 37.5% NaOH to the distal esophagus. Forty rats were divided into four equal groups. Group A (sham) animals were uninjured. Group B rats were injured but untreated. Group C rats were injured and received ketotifen (1 mg/kg/day) via the oral route. Group D rats were injured and received ketotifen (1 mg/kg/day) via the intraperitoneal route. Efficacy of the treatment was assessed on day 28 by measuring the stenosis index and histopathologic damage score and biochemically by determining tissue hydroxyproline content. The stenosis index in group B (0.93+/-0.22) was significantly increased compared with group A (0.39+/-0.06, p <0.05), group C (0.42+/-0.09, p <0.05), and group D (0.35+/-0.07, p <0.05). The hydroxyproline level (mug/mg wet tissue) was significantly increased in group B (1.31+/-0.08, p <0.05) compared with group A (0.69+/-0.16, p <0.05), group C (1.06+/-0.16, p <0.05), and group D (0.95+/-0.12, p <0.05). In group B the histopathologic damage score was significantly higher than in groups C (p <0.05) and D (p <0.05). There was no significant difference between group C and group D in terms of all parameters evaluated. Treatment with ketotifen decreased tissue hydroxyproline levels, histological damage, and the stenosis index. We conclude that ketotifen has a preventive effect in the development of fibrosis in an experimental model of corrosive esophagitis in rats

An improved zebrafish transcriptome annotation for sensitive and comprehensive detection of cell type-specific genes

The zebrafish is ideal for studying embryogenesis and is increasingly applied to model human disease. In these contexts, RNA-sequencing (RNA-seq) provides mechanistic insights by identifying transcriptome changes between experimental conditions. Application of RNA-seq relies on accurate transcript annotation for a genome of interest. Here, we find discrepancies in analysis from RNA-seq datasets quantified using Ensembl and RefSeq zebrafish annotations. These issues were due, in part, to variably annotated 3' untranslated regions and thousands of gene models missing from each annotation. Since these discrepancies could compromise downstream analyses and biological reproducibility, we built a more comprehensive zebrafish transcriptome annotation that addresses these deficiencies. Our annotation improves detection of cell type-specific genes in both bulk and single cell RNA-seq datasets, where it also improves resolution of cell clustering. Thus, we demonstrate that our new transcriptome annotation can outperform existing annotations, providing an important resource for zebrafish researchers