Inhibition of pentagastrin-stimulated gastric secretion by duodenal acidification or administration of fat in normal subjects and in patients with duodenal ulcer

The inhibitory effect of duodenal acidification and intraduodenal fat infusion on pentagastrin-stimulated gastric secretion in normal subjects and in patients with duodenal ulcer was studied. Intraduodenal infusion of acid resulted in inhibition of HCl secretion found to be significant only in ulcer patients. Pepsin output, although lower during the first 15 minutes of duodenal acidification, later increased. Intraduodenal infusion of olive oil resulted in significant inhibition of HCl and pepsin output in both groups of patients, which was maximal 45–60 minutes after the beginning of fat infusion. Gastric secretion was more readily inhibited in ulcer patients than in normal subjects; this difference was particularly evident in inhibition of pepsin secretion. In addition, decrease in concentration of HCl and pepsin was observed to be significant only in ulcer patients. Mechanisms by which duodenal acidification and fat inhibit gastric secretion are discussed. The results obtained suggest that secretin, which is probably responsible for inhibition after duodenal acidification, is not the inhibitor during inhibition by fat. The ulcer patients were found to have unimpaired mechanisms of inhibition by acid and fat.     

After treat-to-target: can a targeted ultrasound initiative improve RA outcomes?

For patients with rheumatoid arthritis (RA), remission can be achieved with tight control of inflammation and early use of disease modifying agents. The importance of remission as an outcome has been recently highlighted by European League Against Rheumatism recommendations. However, remission when defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who have recently formed a research network--the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted ultrasound in RA.     

Connecting liver and gut: murine liver sinusoidal endothelium induces gut tropism of CD4+ T cells via retinoic acid

Gut-activated T cells migrating into the liver can cause extraintestinal manifestations of inflammatory bowel disease. T cells acquire a gut-homing phenotype dependent on retinoic acid (RA) provided by intestinal dendritic cells (DC). We investigated whether liver antigen-presenting cells can induce gut tropism supporting an enterohepatic lymphocyte circulation. Priming of CD4(+) T cells by liver sinusoidal endothelial cells (LSEC) supported migration into gut and gut-associated lymphoid tissue. As observed for T cells primed by intestinal DCs, this gut tropism depended on α(4) β(7) integrin and CC chemokine receptor 9 (CCR9) expression by LSEC-primed CD4(+) T cells. The induction of gut-homing molecules was mediated by RA, a derivate of vitamin A that is stored in large amounts within the liver. LSECs expressed functional retinal dehydrogenases and could convert vitamin A to RA. Conversely, the lack of signaling via the RA receptor prevented the expression of α(4) β(7) integrin and CCR9 on LSEC-primed CD4(+) T cells, consequently reducing their in vivo migration to the intestine. Other liver antigen-presenting cells failed to support high expression of α(4) β(7) integrin on CD4(+) T cells, thus, the potential to induce gut homing is restricted to LSECs. CONCLUSION: The capacity to promote gut tropism via vitamin A use is not unique for intestinal DCs but is also a feature of LSECs. Our data support the assumption that CD4(+) T cells can migrate from the liver to the gut as one branch of a postulated enterohepatic lymphocyte circulation.