Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. 312: G550-G558, 2017. First published March 30, 2017; doi:10.1152/ajpgi.00256.2016.-Inflammatory bowel diseases (IBD) comprise a group of common and debilitating chronic intestinal disorders for which currently available therapies are often unsatisfactory. The naturally occurring secondary bile acid, ursodeoxycholic acid (UDCA), has well-established anti-inflammatory and cytoprotective actions and may therefore be effective in treating IBD. We aimed to investigate regulation of colonic inflammatory responses by UDCA and to determine the potential impact of bacterial metabolism on its therapeutic actions. The anti-inflammatory efficacy of UDCA, a nonmetabolizable analog, 6α-methyl-UDCA (6-MUDCA), and its primary colonic metabolite lithocholic acid (LCA) was assessed in the murine dextran sodium sulfate (DSS) model of mucosal injury. The effects of bile acids on cytokine (TNF-α, IL-6, Il-1β, and IFN-γ) release from cultured colonic epithelial cells and mouse colonic tissue in vivo were investigated. Luminal bile acids were measured by gas chromatography-mass spectrometry. UDCA attenuated release of proinflammatory cytokines from colonic epithelial cells in vitro and was protective against the development of colonic inflammation in vivo. In contrast, although 6-MUDCA mimicked the effects of UDCA on epithelial cytokine release in vitro, it was ineffective in preventing inflammation in the DSS model. In UDCA-treated mice, LCA became the most common colonic bile acid. Finally, LCA treatment more potently inhibited epithelial cytokine release and protected against DSS-induced mucosal inflammation than did UDCA. These studies identify a new role for the primary metabolite of UDCA, LCA, in preventing colonic inflammation and suggest that microbial metabolism of UDCA is necessary for the full expression of its protective actions. On the basis of its cytoprotective and anti-inflammatory actions, the secondary bile acid ursodeoxycholic acid (UDCA) has well-established uses in both traditional and Western medicine. We identify a new role for the primary metabolite of UDCA, lithocholic acid, as a potent inhibitor of intestinal inflammatory responses, and we present data to suggest that microbial metabolism of UDCA is necessary for the full expression of its protective effects against colonic inflammation.
We demonstrate a differential neural response to washer-relevant disgust in washers and checkers: only washers demonstrate a neural response to washer-relevant disgust associated with emotion perception rather than attention to non-emotive visual detail.
In depersonalization disorder, autonomic response to unpleasant stimuli is reduced. The fact that patients with depersonalization disorder respond earlier to a startling noise suggests that they are in a heightened state of alertness and that the reduced response to unpleasant stimuli is caused by a selective inhibitory mechanism on emotional processing.
SYNOPSIS Abnormalities in central serotonin function have been implicated in the pathogenesis of anorexia nervosa. It is difficult, however, to separate neuroendocrine abnormalities induced by weight loss and malnutrition from those related primarily to the disorder itself. To minimize these influences, this study assessed long-term weight restored anorexics. A correlation between persistent eating-related psychopathology, co-morbid illness and serotonin dysfunction was sought. Nine female weight-restored out-patients who had previously fulfilled DSM-III-R criteria for anorexia nervosa and nine healthy controls participated. Following baseline estimation, prolactin and cortisol responses to 30 mg p.o. of D-fenfluramine were measured over a 5 h period. Eating related psychopathology was assessed using the Eating Disorders Inventory and Eating Attitudes Test. Depressive and obsessional symptoms were measured using the Beck Depressive and Maudsley Obsessive-Compulsive Inventories respectively. The Tridimensional Personality Questionnaire assessed impulsivity. The weight-restored anorexic group exhibited persistent eating-related psychopathology and significant co-morbid symptomatology. There was no difference between long-term weight restored anorexics and controls in their endocrine response to D-fenfluramine. Long-term weight-recovered anorexic subjects continued to exhibit behavioural and attitudinal disturbances characteristic of anorexia nervosa. The results suggest that abnormalities in 5HT activity do not contribute significantly to trait status in anorexia nervosa.
The idea that these cases may represent a form of OCD has implications for management, as, if this is correct, they should be able to respond to appropriate behavioural and/or pharmacological strategies used in OCD.
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