Effects of Oral Pirfenidone on Colon Anastomosis Healing and Adhesion Formation in Rats.

INTRODUCTION: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis. METHODS: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis. RESULTS: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04). CONCLUSIONS: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.

Genetic Analyses and Genomic Predictions of Root Rot Resistance in Common Bean Across Trials and Populations.

Root rot in common bean is a disease that causes serious damage to grain production, particularly in the upland areas of Eastern and Central Africa where significant losses occur in susceptible bean varieties. Pythium spp. and Fusarium spp. are among the soil pathogens causing the disease. In this study, a panel of 228 lines, named RR for root rot disease, was developed and evaluated in the greenhouse for Pythium myriotylum and in a root rot naturally infected field trial for plant vigor, number of plants germinated, and seed weight. The results showed positive and significant correlations between greenhouse and field evaluations, as well as high heritability (0.71-0.94) of evaluated traits. In GWAS analysis no consistent significant marker trait associations for root rot disease traits were observed, indicating the absence of major resistance genes. However, genomic prediction accuracy was found to be high for Pythium, plant vigor and related traits. In addition, good predictions of field phenotypes were obtained using the greenhouse derived data as a training population and vice versa. Genomic predictions were evaluated across and within further published data sets on root rots in other panels. Pythium and Fusarium evaluations carried out in Uganda on the Andean Diversity Panel showed good predictive ability for the root rot response in the RR panel. Genomic prediction is shown to be a promising method to estimate tolerance to Pythium, Fusarium and root rot related traits, indicating a quantitative resistance mechanism. Quantitative analyses could be applied to other disease-related traits to capture more genetic diversity with genetic models.