ABSTRACT
Background/Aims@#5-Aminosalicylic acid (ASA) causes intolerance reactions in some patients. This study was performed to examine the prognosis of patients with ulcerative colitis (UC) and 5-ASA intolerance, and to evaluate the potential interaction between 5-ASA intolerance and the intestinal microbiota. @*Methods@#We performed a retrospective cohort study of patients with UC who visited participating hospitals. The primary endpoint was to compare the incidence of hospitalization within 12 months between the 5-ASA intolerance group and the 5-ASA tolerance group. The secondary endpoint was to compare the risk of adverse clinical outcomes after the start of biologics between the 2 groups. We also assessed the correlation between 5-ASA intolerance and microbial change in an independently recruited cohort of patients with UC. @*Results@#Of 793 patients, 59 (7.4%) were assigned to the 5-ASA intolerance group and 734 (92.5%) were assigned to the 5-ASA tolerance group. The admission rate and incidence of corticosteroid use were significantly higher in the intolerance than tolerance group (P< 0.001). In 108 patients undergoing treatment with anti-tumor necrosis factor biologics, 5-ASA intolerance increased the incidence of additional induction therapy after starting biologics (P< 0.001). The 5-ASA intolerance group had a greater abundance of bacteria in the genera Faecalibacterium, Streptococcus, and Clostridium than the 5-ASA tolerance group (P< 0.05). @*Conclusions@#In patients with UC, 5-ASA intolerance is associated with a risk of adverse clinical outcomes and dysbiosis. Bacterial therapeutic optimization of 5-ASA administration may be important for improving the prognosis of patients with UC.
ABSTRACT
The present study was to evaluate endothelial nitric oxide synthase (eNOS) protein expression and hemodynamics of pulmonary circulation in rats of "Living high and Training low" (LH+TL). The Sprague Dawley strain of male rats were used at the age of 9 weeks. They were divided according to four conditions of a living low (LL) group, living low and training low (LL+TL) group, living high (LH) group and LH+TL group, for 10 days. We assessed the effects of LH+TL on exercise-induced pulmonary arterial pressure and blood lactic acids under sea-level altitude in catheter-implanted conscious rats. Also, we measured the pulmonary artery under anesthesia and analyzed eNOS protein expression by western blot analysis. The blood lactate levels in the LH+TL rats decreased after maximal treadmill running compared to LL, LL+TL and LH rats (p<0.05). The increase in pulmonary arterial blood pressure with exercise was significantly lower in the LH+TL group than in the LL group (p<0.05). The eNOS protein expressions of pulmonary artery were higher in the LH+TL group than in the LL group (p<0.05). This study indicates that LH+TL reduced the increase of pulmonary arterial blood pressure with exercise at below sea-level altitude. In addition, eNOS protein expressions were enhanced in the pulmonary arteries of LH+TL rats. Thus, we conclude that the high altitude training of LH+TL was a useful method for improvement of endurance exercise ability and this improvement may be associated with pulmonary arterial response.