Roles of endogenous prostaglandins and cyclooxygenase isozymes in healing of indomethacin-induced small intestinal lesions in rats. J Pharmacol Exp Ther 2006; 318: 691–9

ABSTRACT The role of prostaglandins (PGs)/cyclooxygenase (COX) in the healing of indomethacin-induced small intestinal ulcers was examined in rats. Animals were given indomethacin (10 mg/kg s.c.) and killed 1, 2, 3, 5, and 7 days later. Indomethacin (2 mg/kg), 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC560; COX-1 inhibitor; 3 mg/kg), and rofecoxib (COX-2 inhibitor; 3 mg/kg) were given p.o. once daily for 6 days, during the first 3 days or last 3 days of the experimental period. All COX inhibitors given for 6 days significantly impaired the healing of these ulcers. Healing was also impaired by rofecoxib given for the first 3 days or by SC560 given for the last 3 days. The expression of COX-2 mRNA in the intestine was up-regulated after ulceration, persisting for 3 days and dissipating thereafter. Mucosal PGE 2 contents decreased within 3 h after ulceration, recovered 24 h later, and increased above normal 1ϳ3 days later. The PGE 2 content at 4 days after ulceration was decreased by rofecoxib but not SC560, whereas that at 7 days was suppressed by SC560 but not rofecoxib. Vascular content in the ulcerated mucosa decreased when the healing was impaired by COX inhibitors. The deleterious effect of indomethacin on healing was mimicked by a prostacyclin E receptor (EP) 4 antagonist and reversed by coadministration of PGE 2 as well as an EP4 agonist. In conclusion, endogenous PGs play a role in the healing of intestinal ulcers through EP4 receptors, yet the COX isozyme involved differs depending on the stage of healing; COX-2 in the early stage and COX-1 in the late stage

Gastric duplication complicated by hypergastrinemia: A case report

Introduction: Gastrointestinal duplications are rare congenital anomalies that can occur anywhere throughout the intestinal tract. However, gastric duplication is very rare. A case of gastric duplication with uncommon complications, hypergastrinemia and duodenal ulcer, is described. Case report: The patient was an 11-year-old girl who presented with epigastric pain and non-bilious vomiting. The patient had a history of recurrent duodenal ulcers. Gastrin levels when the patient first presented with a duodenal ulcer at 8 years of age had reached 730 pg/mL. Computed tomography (CT) showed a cyst outside the pyloric antrum after remission of the duodenal ulcer, and it was suspected to be gastric duplication. For recurrence of the duodenal ulcer, the patient had been treated with histamine 2 receptor blockade for 3 years. At 11 years of age, the patient had stopped the medication and presented with gastric pain and vomiting. CT showed an enlarged gastric cyst and an obstructed pylorus. The patient was then referred to our hospital, and a laparotomy was performed to resect the cyst. Histological examination revealed positive staining for gastrin in the cyst wall mucosa, which is consistent with gastric duplication. Postoperative serum gastrin levels decreased, suggesting that gastric duplication had caused the hypergastrinemia. Conclusion: A case of gastric duplication was presented. Gastric duplication should be considered when treating patients with cystic disease of the pyloric region. In addition, hypergastrinemia may occur due to duplicated intestine near the pylorus, which may cause a duodenal ulcer

Effects of a changeover from other angiotensin II receptor blockers to olmesartan on left ventricular hypertrophy in heart failure patients.

Left ventricular (LV) hypertrophy (LVH) is an independent cardiovascular risk factor for heart failure (HF) patients. The renin-angiotensin system plays a key role in LVH, and since olmesartan increases plasma angiotensin-(1-7) through an increase in angiotensin-converting enzyme-related carboxypeptidase (ACE2) expression, it was hypothesized to reduce LVH, unlike other angiotensin II receptor blockers (ARBs). The objective of this study was therefore to investigate the effects of a changeover from other ARBs to olmesartan on LVH in HF patients. Participants enrolled in this prospective trial were 64 outpatients with stable HF who had received ARBs other than olmesartan for more than 1 year (age: 59 ± 13 years). Transthoracic echocardiography and laboratory tests were performed before and 6 months after administration of olmesartan. Other drugs were not changed during follow-up. The primary end point was defined as a change in LV mass index (LVMI) from baseline up to 6 months after administration of olmesartan. No significant changes were observed in blood pressures and heart rate after administration of olmesartan. LVMI showed a significant decrease from 119 ± 38 to 110 ± 24 g/m2 (p = 0.007) 6 months after administration of olmesartan, and further decreased from 110 ± 24 to 103 ± 35 g/m2 (p = 0.0003) after 12 months. Moreover, this reduction tended to be more prominent in patients with LVH. In conclusions, LVH in HF patients was reduced by the changeover to olmesartan. This finding may well have clinical implications for better management of HF patients.info:eu-repo/semantics/publishe

Risk Stratification of Future Left Ventricular Dysfunction for Patients with Indications for Right Ventricular Pacing due to Bradycardia.

Although right ventricular (RV) pacing is the only effective treatment for patients with symptomatic bradycardia, it creates left ventricular (LV) dyssynchrony, which can induce LV dysfunction and heart failure. The current criterion for consideration of cardiac resynchronization therapy (CRT) is LV ejection fraction (LVEF) ≤ 35%, but indication for CRT in patients required for RV pacing with LVEF > 35% remains unclear.We studied 40 patients, all LVEF ≥ 35%, who had undergone implantable cardioverter-defibrillator implantation with RV pacing < 5%. Echocardiography was performed at baseline and during RV pacing. LV dyssynchrony was defined as anteroseptal-to-posterior wall delay from the mid-LV short-axis view using two-dimensional speckle-tracking radial strain (significant: ≥ 130 ms). Patients were divided into two groups based on baseline LVEF: normal LVEF ( ≥ 50%; n = 20) and mildly reduced LVEF (35-50%; n = 20).LVEF and LV dyssynchrony in patients with mildly reduced LVEF deteriorated significantly during RV pacing compared to those in patients with normal LVEF. Moreover, changes in LV dyssynchrony during RV pacing significantly correlated with changes in LVEF (r = -0.44, P < 0.01). Multivariate logistic regression analysis showed that baseline LVEF was the only independent predictor and baseline LVEF < 48% predictive of significant LV dyssynchrony during RV pacing.The extent of RV pacing-induced LV dysfunction may be associated with baseline LV function. These adverse effects on patients with mildly reduced LVEF of 35-50% and indications for RV pacing due to bradycardia can thus be prevented by CRT.info:eu-repo/semantics/publishe

Right ventricular relative wall thickness as a predictor of outcomes and of right ventricular reverse remodeling for patients with pulmonary hypertension.

Mid-term right ventricular (RV) reverse remodeling after treatment in patients with pulmonary hypertension (PH) is associated with long-term outcome as well as baseline RV remodeling. However, baseline factors influencing mid-term RV reverse remodeling after treatment and its prognostic capability remain unclear. We studied 54 PH patients. Mid-term RV remodeling was assessed in terms of the RV area, which was traced planimetrically at the end-systole (RVESA). RV reverse remodeling was defined as a relative decrease in the RVESA of at least 15% at 10.2 ± 9.4 months after treatment. Long-term follow-up was 5 years. Adverse events occurred in ten patients (19%) and mid-term RV reverse remodeling after treatment was observed in 37 (69%). Patients with mid-term RV reverse remodeling had more favorable long-term outcomes than those without (log-rank: p = 0.01). Multivariate logistic regression analysis showed that RV relative wall thickness (RV-RWT), as calculated as RV free-wall thickness/RV basal linear dimension at end-diastole, was an independent predictor of mid-term RV reverse remodeling (OR 1.334; 95% CI, 1.039-1.713; p = 0.03). Moreover, patients with RV-RWT ≥0.21 showed better long-term outcomes than did those without (log-rank p = 0.03), while those with RV-RWT ≥0.21 and mid-term RV reverse remodeling had the best long-term outcomes. Patients with RV-RWT <0.21 and without mid-term RV reverse remodeling, on the other hand, had worse long-term outcomes than other sub-groups. In conclusions, RV-RWT could predict mid-term RV reverse remodeling after treatment in PH patients, and was associated with long-term outcomes. Our finding may have clinical implications for better management of PH patients.info:eu-repo/semantics/publishe