Prostaglandin E2 influences the gastrointestinal endocrine cell system in the rat

Previous studies suggest that prostaglandin E2 may interact with gastrointestinal endocrine cells. Our aim was to examine whether erogenous and endogenous prostaglandins - particularly prostaglandin E2 - influence the endocrine cell system in the rat gastrointestinal tract. Indomethacin was used to inhibit the synthesis of endogenous prostaglandins in order to gain information about a potential modulator role of the prostanoids on the endocrine cells. Sprague-Dawley rats were treated with oral prostaglandin E2 or a methyl- analogue for four weeks, or with subcutaneous indomethacin or indomethacin and prostaglandin E2 for eight weeks. The total volume of immunoreactive endocrine cells was evaluated quantitively using stercological methods and the tissue and plasma concentrations of neuroendocrine peptides were analysed with radioimmunoassay. The epithelial DNA synthesis was evaluated with the labelling index. In the upper gastrointestinal tract, endogenous prostaglandins, particularly prostaglandin E2, induced an inhibitory tonus on the total volume of ECL and somatostatin cells and on the tissue concentration of somatostatin in the gastric fundus, as shown by the increased total volumes of immunoreactivc cells and increased tissue concentrations of the peptide observed in the rats given indomethacin. Incontrast. endogenous prostaglandins, particularly prostaglandin E2, induced a stimulatory tonus on the total volume of enterochromaffin cells in the antnim and on the total volumes of duodenal enterochromffin cells and CCK and GIP-producing cells. The simultaneous administration of prostaglandin E2 reversed - partially or completely - the changes elicited by indomethacin. Exogenous E2 prostaglandins influenced the ECL cells and the somatostatin cell population in the fundic mucosa and increased the plasma levels of somatostatin. Exogenous E2 prostaglandins increased the total volume of serotonin and gastiin/CCK-imunoreactive cells in the duodenum. In the lower gastrointestinal tract, endogenous prostaglandins, particularly prostaglandin E2, induced an inhibitory tonus on the synthesis and/or release of tissue somatostatin in the ileum. DNA synthesis was increased in the small intestinal crypts in animals depleted of prostaglandins, which was associated with increased tissue concentrations of neurokinin A, neurotensin and glucagon. Exogenous E2 prostaglandins influenced the total volume of glucagon/glicentin-immunoreactive cells in the jejunum. and the tissue concentration of somatostatin and glucagon. E2 prostaglandins influenced the total volume of glucagon/glicentin- and somatostatin-immunoreactive cells in the colonic mucosa. In conclusion, the modulation and/or influence of endogenous and erogenous prostaglandins, particularly prostaglandin E2, on the ECL, enterochromaffin, CCK, glucagon and somatostatin cell in the gastrointestinal tract - including synthesis and/or release of neuroendocrine peptides - suggest that endogenous and erogenous prostaglandins may indirectly participate in important biological fimctions that are modified by neuroendocrine peptides. Taken together with other observations, our findings indicate that the regulation of the the gastrointestinal endocrine cell system is multifactoiial and that intraluminal factors, particularly the colonic microflora, may mask and/or modify the actions of endogenous prostaglandins on endocrine cells

Acute interstitial nephritis in patients with inflammatory bowel disease treated with vedolizumab: a systematic review

Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in patients with inflammatory bowel disease (IBD) treated with the integrin inhibitor vedolizumab. Through systematic review of existing literature, we aimed to identify and describe cases of AIN in patients with IBD treated with vedolizumab. We searched Medline, Embase, Cochrane, and Web of Science Core Collection between 1 January 2009 and 25 April 2023. The search yielded 1473 publications. Titles and abstracts were screened by two independent reviewers. Seventy publications were reviewed in full-text. Eight met the inclusion criteria. Clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to two international adverse drug reaction probability assessment scales. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn’s disease. Mean age at AIN onset was 36 years (range = 19–58) and the majority of patients were females (n = 6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever and malaise. Creatinine levels were elevated in all patients. Five patients sustained permanent kidney injury. Our findings suggest that vedolizumab, although rarely, could cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along with monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab.</p

Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

Background: In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. Aims: To evaluate the haemostatic potential in patients with liver disease. Methods: We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n=47), Budd-Chiari syndrome (BCS, n=15) and cirrhosis (n=24) and compared the results to those obtained from healthy controls (n=21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared with an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence]/[marker measured in the absence of thrombomodulin]. Results: There were no differences between patients with BCS, patients on warfarin treatment and controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared with controls [p=0.006 for endogenous thrombin potential (ETP) and p&lt;0.001 for peak thrombin. P&lt;0.001 for both ratios ETP and peak] and patients with non-cirrhotic PVT (p=0.001, p=0.006, p&lt;0.001, p&lt;0.001 for ETP, peak, ratio ETP, ratio peak). The patients with cirrhotic PVT exhibited higher ETP (p=0.044) and peak (p=0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP ratio: p=0.001, peak ratio: p=0.001). Conclusions: Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer treatment with anticoagulants in this group