The Effect of the iNOS Inhibitor S-Methylisothiourea and Hyperbaric Oxygen Treatment on Radiation Colitis in Rats.

INTRODUCTION: External radiotherapy is one of the main treatment modalities for a variety of malignancies. However, the lower gastrointestinal tract is sensitive to the ionizing radiation. Hyperbaric oxygen treatment (HOT) has been suggested as a viable treatment for refractory radiation colitis, but the effect of S-Methylisothiourea (SMT) in the radiation colitis have not reported. To investigate the effect of SMT, HOT and the combination of both in an acute radiation-induced enterocolitis model. METHODS: Sixty Sprague-Dawley rats were divided randomly into five equal groups. A single dose of gamma irradiation (25 Gy) was administered through the colorectal region to anesthetized rats. In the control group, we applied 2 ml of saline solution intraperitoneally for five days. In the HOT group, 100-per-cent oxygen at 2.5 atm pressure was applied for five days. In the SMT group, 10 mg/kg/day of SMT was applied intraperitoneally for five days. In the HOT+SMT group, HOT and SMT were both applied in the same dosages as in the preceding two groups. At the end of five days, the rats were sacrificed and colon samples were collected for histological grading. Blood samples were collected to test for : tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-1ß, transforming growth factor-ß (TGF-ß) and intercellular adhesion molecule-1 (ICAM-1) mRNA. RESULTS: The TNF-α, IL-1ß, IL-10 and TGF-ß levels were reduced by SMT, HOT and HOT+SMT applications (p < 0.05). However ICAM-1 mRNA levels were not significantly lower (p:0.19). The microscopic scores differed significantly between the SMT, HOT and HOT+SMT groups and the control group. There was significant improvement histologically, especially in the HOT+SMT group. When we compared the weight of the rats before and after the study, weight loss was significantly lower in the SMT, HOT and HOT+SMT groups compared with the control group (p < 0.05). CONCLUSION: HOT and SMT together were significantly more effective in preventing weight loss and in reducing inflammation and the severity of colitis histology when compared with HOT and SMT separately.

Comparison of environmental risk factors for esophageal atresia, anorectal malformations, and the combined phenotype in 263 German families.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and anorectal malformations (ARM) represent the severe ends of the fore- and hindgut malformation spectra. Previous research suggests that environmental factors are implicated in their etiology. These risk factors might indicate the influence of specific etiological mechanisms on distinct developmental processes (e.g. fore- vs. hindgut malformation). The present study compared environmental factors in patients with isolated EA/TEF, isolated ARM, and the combined phenotype during the periconceptional period and the first trimester of pregnancy in order to investigate the hypothesis that fore- and hindgut malformations involve differing environmental factors. Patients with isolated EA/TEF (n = 98), isolated ARM (n = 123), and the combined phenotype (n = 42) were included. Families were recruited within the context of two German multicenter studies of the genetic and environmental causes of EA/TEF (great consortium) and ARM (CURE-Net). Exposures of interest were ascertained using an epidemiological questionnaire. Chi-square, Fisher's exact, and Mann-Whitney U-tests were used to assess differences between the three phenotypes. Newborns with isolated EA/TEF and the combined phenotype had significantly lower birth weights than newborns with isolated ARM (P = 0.001 and P < 0.0001, respectively). Mothers of isolated EA/TEF consumed more alcohol periconceptional (80%) than mothers of isolated ARM or the combined phenotype (each 67%). Parental smoking (P = 0.003) and artificial reproductive techniques (P = 0.03) were associated with isolated ARM. Unexpectedly, maternal periconceptional multivitamin supplementation was most frequent among patients with the most severe form of disorder, i.e. the combined phenotype (19%). Significant differences in birth weight were apparent between the three phenotype groups. This might be attributable to the limited ability of EA/TEF fetuses to swallow amniotic fluid, thus depriving them of its nutritive properties. Furthermore, the present data suggest that fore- and hindgut malformations involve differing environmental factors. Maternal periconceptional multivitamin supplementation was highest among patients with the combined phenotype. This latter finding is contrary to expectation, and warrants further analysis in large prospective epidemiological studies.

Evaluation of the long-term effects of oleum origani on the toxicity induced by administration of streptozotocin in rats.

Oleum origani, the essential oil of Origanum onites L., is a traditional plant material used in Turkey for the treatment of several diseases, including diabetes mellitus. This study has evaluated the effect of oleum origani on streptozotocin-induced tissue injury and haematological changes. The effect of oleum origani on glycaemia was also studied. Long-term administration of oleum origani resulted in significant improvement of tissue injury induced by streptozotocin treatment. No effect on blood glucose levels was detected. In addition, any visible toxicity or disturbance of haematological parameters and tissue structure attributable to the long-term use of oleum origani were not established in normal rats. The data indicate that long-term use of oleum origani might be effective in preventing or at least in retarding the development of some complications of diabetes mellitus. Further investigation is required to determine the underlying mechanism(s) of the protective effect against tissue injury induced by streptozotocin-treatment of rats.