Suppression of contractile activity in the small intestine by indomethacin and omeprazole.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat a number of conditions, and proton pump inhibitors (PPIs) are often used to prevent NSAID-induced gastric mucosal damage; however, the effects of NSAIDs on intestinal motility are poorly understood. The purpose of the present study is to determine the effects of a prototypical NSAID, indomethacin, either alone or in conjunction with the PPI omeprazole, on intestinal motility. Rats were randomly divided into four groups treated with vehicle, omeprazole, indomethacin, or a combination of indomethacin and omeprazole. Intestinal motility and transit were measured along with inflammatory mediators in the intestinal smooth muscle, markers of mucosal damage, and bacterial counts in the intestinal wall. Indomethacin, but not omeprazole, caused mucosal injury indicated by lower gut bleeding; however, both omeprazole and indomethacin suppressed contractile activity and frequency in the distal part of the small intestine. Cotreatment with omeprazole did not reduce indomethacin-induced intestinal bleeding. Furthermore, although indomethacin caused increased inflammation as indicated by increased edema development and inflammatory mediators, cotreatment with omeprazole did not reduce inflammation in the intestinal smooth muscle or prevent the increased bacterial count in the intestinal wall induced by indomethacin. We conclude that both NSAID and PPI treatment suppressed contractile activity in the distal regions of the small intestine. The suppression of intestinal contractility was associated with increased inflammation in both cases; however, indomethacin and omeprazole appear to affect intestinal motility by different mechanisms.

In vitro and in vivo protection against indomethacin-induced small intestinal injury by proton pump inhibitors, acid pump antagonists, or indomethacin-phosphatidylcholine.

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) are widely used to prevent nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcers. NSAIDs produce small intestinal injury and some PPIs have been reported to protect against NSAID-induced small bowel injury in rats. The aim of this study was to compare PPIs, revaprazan, and phosphatidylcholine-associated indomethacin (Indo-PC) for protection against indomethacin (Indo)-induced small bowel injury. METHODS: Rat intestinal epithelial cells (IEC-6) were pretreated with omeprazole, lansoprazole, or revaprazan prior to exposure to Indo or Indo-PC. Cell viability was assessed by methyl thiazolyl tetrazolium assay. Omeprazole, lansoprazole, or revaprazan was administered orally to rats prior to the vehicle or Indo. Indo-PC was administered alone. After 24 h, small intestinal erosions were counted; intestinal bleeding was assessed as the hemoglobin concentration of small intestinal fluid. RESULTS: Omeprazole, lansoprazole, and revaprazan did not protect against Indo-induced IEC-6 cell injury. Indo-PC was less damaging in vitro than Indo alone. In vivo, neither omeprazole nor lansoprazole protected against Indo-induced small bowel injury; however, revaprazan pretreatment and Indo-PC resulted in significantly fewer erosions (>50% reduction) or bleeding (>80% reduction). CONCLUSION: PPIs showed no small bowel protective effect in vitro or in vivo. Revaprazan showed a small bowel protective effect in vivo, whereas Indo-PC was protective both in vitro and in vivo.

Solitary metastasis of ampullary carcinoma to the spleen: a case report.

Here, we report a first case of ampullary cancer with solitary metastasis of the spleen, which was successfully treated with pancreatoduodenectomy and splenectomy and was discharged 7 days after the operation with outpatient chemotherapy. In such cases, physicians should consider splenectomy as an effective treatment option.

Rehabilitation for tibial plateau fractures in adults: a scoping review protocol.

REVIEW OBJECTIVE: Based on the observation that rehabilitation practices for tibial plateau fractures are inconsistent and lack uniformity in the published literature, this scoping review will seek to identify all relevant studies that have reported on rehabilitation for tibial plateau fractures in order to comprehensively map the characteristics of the practices. This scoping review will then be used to identify commonalities across the included studies in order to identify potential focus questions for subsequent systematic reviews.

Characteristics of postoperative weight bearing and management protocols for tibial plateau fractures: Findings from a scoping review.

OBJECTIVE: To identify and describe the characteristics of existing practices for postoperative weight bearing and management of tibial plateau fractures (TPFs), identify gaps in the literature, and inform the design of future research. METHODS: Seven electronic databases and clinical trial registers were searched from inception until November 17th 2016. Studies were included if they reported on the surgical management of TPFs, had a mean follow-up time of ≥1year and provided data on postoperative management protocols. Data were extracted and synthesized according to study demographics, patient characteristics and postoperative management (weight bearing regimes, immobilisation devices, exercises and complications). RESULTS: 124 studies were included involving 5156 patients with TPFs. The mean age across studies was 45.1 years (range 20.8-72; 60% male), with a mean follow-up of 34.9 months (range 12-264). The most frequent fracture types were AO/OTA classification 41-B3 (29.5%) and C3 (25%). The most commonly reported non-weight bearing time after surgery was 4-6 weeks (39% of studies), with a further 4-6 weeks of partial weight bearing (51% of studies), resulting in 9-12 weeks before full weight bearing status was recommended (55% of studies). Loading recommendations for initial weight bearing were most commonly toe-touch/<10kg (28%), 10kg-20kg (33%) and progressive (39%). Time to full weight bearing was positively correlated with the proportion of fractures of AO/OTA type C (r=0.465, p=0.029) and Schatzker type IV-VI (r=0.614, p<0.001). Similar rates of rigid (47%) and hinged braces were reported (58%), most frequently for 3-6 weeks (43% of studies). Complication rates averaged 2% of patients (range 0-26%) for abnormal varus/valgus and 1% (range 0-22%) for non-union or delayed union. CONCLUSIONS: Postoperative rehabilitation for TPFs most commonly involves significant non-weight bearing time before full weight bearing is recommended at 9-12 weeks. Partial weight bearing protocols and brace use were varied. Type of rehabilitation may be an important factor influencing recovery, with future high quality prospective studies required to determine the impact of different protocols on clinical and radiological outcomes.

Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci.

NSAIDuse is limited due to the drugs' toxicity to the gastrointestinal mucosa, an action incompletely understood. Lower gut injury induced byNSAIDs is dependent on bile secretion and is reported to increase the growth of a number of bacterial species, including an enterococcal species,Enterococcus faecalis This study examined the relationships between indomethacin (INDO)-induced intestinal injury/bleeding, small bowel overgrowth (SBO) and dissemination of enterococci, and the contribution of bile secretion to these pathological responses. Rats received either a sham operation (SO) or bile duct ligation (BDL) prior to administration of two daily subcutaneous doses of saline orINDO, and 24 h later, biopsies of ileum and liver were collected for plating on selective bacterial media. Fecal hemoglobin (Hb) and blood hematocrit (Hct) were measured to assess intestinal bleeding. Of the four treatment groups, onlySO/INDOrats experienced a significant 10- to 30-fold increase in fecal Hb and reduction in Hct, indicating thatBDLattenuatedINDO-induced intestinal injury/bleeding. Ileal enterococcal colony-forming units were significantly increased (500- to 1000-fold) inSO/INDOrats. Of all groups, only theSO/INDOrats demonstrated gut injury, and this was associated with enterococcal overgrowth of the gut and dissemination to the liver. We also demonstrated thatINDO-induced intestinal injury andE. faecalisovergrowth was independent of the route of administration of the drug, as similar findings were observed in rats orally dosed with theNSAID Bile secretion plays an important role inINDO-induced gut injury and appears to support enterococcal overgrowth of the intestine.NSAID-induced enterococcalSBOmay be involved either as a compensatory response to gut injury or with the pathogenic process itself and the subsequent development of sepsis.