Treatment with obestatin : a ghrelin gene-encoded peptide : reduces the severity of experimental colitis evoked by trinitrobenzene sulfonic acid

Obestatin is a 23-amino acid peptide derived from proghrelin, a common prohormone for ghrelin and obestatin. Previous studies showed that obestatin exhibited some protective and therapeutic effects in the gut. The aim of our presented study was to examine the effect of treatment with obestatin on trinitrobenzene sulfonic acid (TNBS)-induced colitis. In rats anesthetized with ketamine, colitis was induced through intrarectal administration of 25 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Obestatin was administered intraperitoneally at doses of 4, 8, or 16 nmol/kg, twice per day for four consecutive days. The first dose of obestatin was given one day before the induction of colitis, and the last one was given two days after administration of TNBS. Fourteen days after the induction of colitis, rats were anesthetized again with ketamine, and the severity of colitis was determined. The administration of obestatin had no effect on the parameters tested in rats without the induction of colitis. In rats with colitis, administration of obestatin at doses of 8 or 16 nmol/kg reduced the area of colonic damage, and improved mucosal blood flow in the colon. These effects were accompanied by a reduction in the colitis-evoked increase in the level of blood leukocytes, and mucosal concentration of pro-inflammatory interleukin-1β. Moreover, obestatin administered at doses of 8 or 16 nmol/kg reduced histological signs of colonic damage. The administration of obestatin at a dose of 4 nmol/kg failed to significantly affect the parameters tested. Overall, treatment with obestatin reduced the severity of TNBS-induced colitis in rats. This effect was associated with an improvement in mucosal blood flow in the colon, and a decrease in local and systemic inflammatory processes

Mortality Following Clostridioides difficile Infection in Europe : A Retrospective Multicenter Case-Control Study

We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from seven European countries. A total of 624 patients were included, of which 415 were deceased (cases) and 209 were still alive 90 days after a CDI diagnosis (controls). The most common antibiotics used previously in both groups were β-lactams; previous exposure to fluoroquinolones was significantly (p = 0.0004) greater in deceased patients. Multivariate logistic regression showed that the factors independently related with death during CDI were older age, inadequate CDI therapy, cachexia, malignancy, Charlson Index, long-term care, elevated white blood cell count (WBC), C-reactive protein (CRP), bacteraemia, complications, and cognitive impairment. In addition, older age, higher levels of WBC, neutrophil, CRP or creatinine, the presence of malignancy, cognitive impairment, and complications were strongly correlated with shortening the time from CDI diagnosis to death. CDI prevention should be primarily focused on hospitalised elderly people receiving antibiotics. WBC, neutrophil count, CRP, creatinine, albumin and lactate levels should be tested in every hospitalised patient treated for CDI to assess the risk of a fatal outcome

Effects of Cyclic Hexapeptide Analog of Somatostatin on Pancreatic Secretion in Dogs

Abstract The effects of a cyclic hexapeptide analog of somatostatin, [cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe)] (cyclo-SS), administered intravenously (iv) or instilled into the duodenum (id) on the pancreatic response to endogenous (meal and duodenal acidification) and exogenous (secretin, CCK) stimulants were compared in five dogs with esophageal, gastric, and pancreatic fistulae. Cyclo-SS given iv in graded doses against a constant background stimulation with secretin caused a similar and dose-dependent inhibition of pancreatic HCO3 and protein secretion being about twice as potent as somatostatin-14 (SS-14). Cyclo-SS, whether applied topically to the duodenal mucosa in a dose of 1 μg/kg or given iv at a dose of 0.5 μg/kg-hr, resulted in a similar inhibition of pancreatic secretion induced by feeding a meat meal, sham-feeding, duodenal acidification, or infusion of secretin or CCK. The inhibition of pancreatic secretion by cyclo-SS was due in part to direct inhibitory action on the exocrine pancreas as well as to the suppression of the release of secretin, insulin, and pancreatic polypeptide. It is concluded that cyclo-SS is a more potent inhibitor of pancreatic secretion than SS-14 and that it is active when administered both parenterally and intraduodenally