β-拉帕醌对胃癌细胞生长与侵袭的抑制作用及机制

目的：探讨β-拉帕醌体外抑制胃癌细胞增殖和迁移及诱导凋亡的作用及机制。方法应用噻唑蓝（ MTT）及平板克隆实验检测β-拉帕醌对SGC-7901与AGS胃癌细胞增殖的影响,划痕实验检测β-拉帕醌抑制胃癌细胞的迁移能力,流式细胞术检测β-拉帕醌诱导胃癌细胞凋亡的作用。应用Western b1ot法检测β-拉帕醌处理胃癌细胞前后其增殖、迁移、上皮-间质转化（ epithe1ia1-mesenchyma1 transition,EMT）及凋亡分子标志物的变化。结果β-拉帕醌可显著抑制SGC-7901和AGS胃癌细胞的增殖能力,并下调增殖与周期相关Skp2和DEK蛋白的表达（ P均<0.05）;经β-拉帕醌处理后,胃癌细胞的迁移能力明显下降,且显著下调MMP-2/9和Ezrin蛋白以及EMT间质标志物的表达,上调EMT上皮标志物表达水平;另外,β-拉帕醌增加胃癌细胞的凋亡,下调BCL-2/Bax比值以及上调活化型Caspase-3/8/9的表达。结论β-拉帕醌对胃癌细胞有明显的抑制增殖及诱导凋亡的作用,并可通过MMPs和EMT途径抑制胃癌细胞的迁移能力。     

Rare causes of gastrointestinal hemorrhage in infancy

Gastrointestinal hemorrhage in children is a critical condition that demands quick and effective management. The differential diagnosis of gastrointestinal hemorrhage is wide. Heterotopic pancreas is a rare congenital anomaly and usually discovered incidentally. It is generally asymptomatic, but symptoms may occur when complicated by inflammation, bleeding, obstruction or malign transformation. Heterotopic pancreas may present throughout the gastrointestinal tract, but it is most commonly found in the stomach, duodenum and proximal jejunum. Juvenile polyps are common during childhood and present most often with painless rectal hemorrhage. They remain the most common colonic polyps in children. Colonoscopic polypectomy is the most effective procedure in the treatment of juvenile polyps. In this study, we describe rare causes of gastrointestinal system hemorrhage in infancy and discuss some diagnostic and therapeutic approaches.     

Operative Factors that Contribute to Post-Operative Atrial Fibrillation: Insights from a Prospective Randomized Trial

Atrial fibrillation (AF) is the most common complication following cardiac surgery and is associated with significant increases in postoperative morbidity, length of stay and cost of care. In a randomized study we assessed the impact of coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) (off-pump, n = 100), compared to conventional (on-pump, n = 100) CABG, on the frequency of postoperative AF. Arrhythmias were detected using an automated arrhythmia detector for the first 72 hours following surgery and by four hourly clinical observations thereafter. AF was defined as an irregular narrow complex rhythm (in the absence of bundle branch block) with absence of discrete P waves lasting greater then 10 minutes. There was a significant reduction in the incidence of postoperative AF in the off-pump group (11% versus 45%, P < 0.001) in addition to significant reductions in blood usage, postoperative pneumonia, inotrope requirements, and hospital and intensive care unit stay. Univariate analysis identified all these variables as risk factors for AF, however multivariate regression analysis identified CPB and cardioplegic arrest as the only independent predictor of postoperative AF (OR 7.4; 95% CI 3.4 to 17.9). This study therefore suggests that the inflammatory response to bypass, myocardial ischaemia and atrial cannulation are significant contributory factors to the development of AF following cardiac surgery. In the light of more recent trials it is apparent that this benefit may be most marked in patients with multiple perioperative risk factors for postoperative AF.     

Helicobacter pylori and gut hormones

Helicobacter pylori infection has been found to decrease the expression of antral somatostatin and to increase the release of the acid-stimulating hormone gastrin. The reversal of these changes in gut hormones by the eradication of H. pylori, and in-vivo and in-vitro studies in animals either infected with H. pylori or exposed to H. pylori-related materials may support the somatostatin-gastrin link theory in the pathophysiology of H. pylori infection. The following mechanisms have been proposed to explain the H. pylori infection-associated changes in gut hormones; (1) ammonia produced by H. pylori and monochloramine, (2) effect on somatostatin receptor subtype-2, (3) action of lipopolysaccharide from H. pylori on somatostatin receptor, (4) inflammatory cells and mediators, and (5) bacterial strain diversity. H. pylori infection can alter gastric acid secretion in both directions. The elevated acid secretion in patients with duodenal ulcer is decreased by H. pylori eradication, and is accompanied by the normalization of gut hormones in patients whose H. pylori-induced gastritis is limited to the antrum with hyperacidity. Corpus gastritis and the subsequent development of mucosal atrophy induced by H. pylori result in decreased acid secretion, although the mechanism underlying H. pylori-induced atrophy in some subjects remains unclear. Hypoacidity enhances corpus atrophy and increases gastrin secretion, mediated via a physiological suppression of somatostatin release, features that are also observed in H. pylori infection. Therefore, the capacity of acid secretion and distribution of gastritis or atrophy should be taken into consideration when we discuss the affect of H. pylori on gut hormones. Received: October 1, 2001 / Accepted: November 30, 2001     

乌司他丁对体外循环患者肺灌洗液中炎性因子和肺功能的影响

目的:探讨丝氨酸蛋白酶抑制剂乌司他丁对体外循环下心脏直视手术患者肺灌洗液中炎性因子和肺功能的影响。方法:将30例拟行瓣膜置换术患者随机分为乌司他丁组和对照组,各15例。左心室射血分数<0．45、左心室舒张末直径>70 mm、心胸比率>0．7、血流动力学不稳定以及肝、肾功能障碍和急症手术的患者不选。乌司他丁组:在劈胸骨和升主动脉开放前分别给予乌司他丁0．6 KIU／kg;对照组:与乌司他丁组同时点只给予等量生理盐水。在术前和升主动脉开放后30分钟进行右肺中叶灌洗,采集肺灌洗液,用酶联免疫法测定中性粒细胞弹性蛋白酶和白细胞介素-8浓度,并在术前、升主动脉开放后30分钟、2小时和6小时记录呼气末二氧化碳(PETCO2)、采集桡动脉血行血气分析,计算肺功能指标:肺泡-动脉氧分压差[P(A-a)DO2]、氧合指数(PaO2／FiO2)和死腔率(VD／VT)。结果:①对照组肺灌洗液中白细胞介素-8浓度在升主动脉开放后30分钟升高,与术前比较差异有统计学意义(P< 0．05);乌司他丁组肺灌洗液中白细胞介素-8浓度在升主动脉开放后30分钟也较术前升高,但无显著差异(P>0．05),但乌司他丁组低于对照组同时点水平,差异有统计学意义(P<0．05);②对照组体外循环后各时点P(A-a)、DO2、VD／VT均较术前升高。P(A-a)DO2在升主动脉开放后30分钟、升主动脉开放后2小时升高与术前相比有统计学意义(P<0．05), VD／VT在升主动脉开放后30分钟升高达峰值(P<0．05);乌司他丁组在体外循环后各时点P(A-a)DO2、VD／VT也较术前升高,但无显著差异(P>0．05),在升主动脉开放后30分钟均低于对照组,差异有统计学意义(P<0．05);③对照组PaO2／FiO2体外循环后各时点与术前相比均降低,在升主动脉开放后30分钟降到最低值(P<0．05);乌司他丁组PaO2／FiO2在体外循环后各时点也降低,但无显著差异(P>0．05),在升主动脉开放后30分钟显著高于对照组(P<0．05)。结论:体外循环下心脏直视手术可致肺功能损伤,乌司他丁可抑制肺内炎性因子白细胞介素-8和弹性蛋白酶释放而具有肺保护作用。     

Effects of cyclosporin A on water-immersion stress-induced gastric lesion and gastric secretion in rats

Cyclosporin A is an immunosuppressive agent which is well known as a specific inhibitor of calcineurin (protein phosphatase 2B). In this study, we investigated the effects of cyclosporin A on water-immersion stress-induced gastric ulcer formation and gastric acid secretion in rats. We also examined the localization of calcineurin immunohistochemically. Calcineurin was specifically expressed in gastric parietal cells and chief cells of the gastric mucosa. The intraperitoneal administration of cyclosporin A dose-dependently suppressed the development of gastric mucosal lesions induced by water-immersion stress and inhibited gastric acid secretion, as assessed by pylorus ligation. These results indicated that calcineurin may play an important role in gastric acid secretion. Received: October 14, 1999 / Accepted: January 28, 2000     

Impaired gastric emptying and altered intragastric meal distribution in diabetes mellitus related to autonomic neuropathy?

Previous studies in diabetic patients suggested a relationship between delayed gastric emptying and increased ingesta retention in either proximal or distal stomach, but the determinants underlying these abnormalities remained obscure. We aimed at assessing the impact of cardiovascular autonomic neuropathy, blood glucose concentration, long-term glycemic control, and other factors in 34 type I and 43 type II diabetic patients (ages 21–67 and 34–81 years, respectively). Emptying was slower (P < 0.04) in type I diabetic patients than in 20 healthy control subjects (ages 23–63 years). Patients with autonomic neuropathy (N = 45) had slower gastric emptying (P < 0.02) and retained more in the distal stomach (P < 0.0001) than patients without neuropathy (N = 32). Multiple regression analyses revealed that slow emptying and increased distal retention were significantly associated with autonomic neuropathy (P < 0.043, P < 0.0002), whereas blood glucose, glycemic control, diabetes duration, age, and other factors had no discernible influence. Thus, both slow emptying and increased distal ingesta retention seem primarily referable to autonomic neuropathy.     

Motor mechanisms associated with slowing of the gastric emptying of a solid meal by an intraduodenal lipid infusion

The aim of this study was to define better the motor phenomena associated with the slowing of gastric emptying by a duodenal lipid infusion. Antral, pyloric and duodenal motility were recorded in 10 healthy subjects with a manometric assembly which incorporated multiple perfused side-holes and a sleeve sensor positioned astride the pylorus. The gastric emptying of a standard solid meal and the distribution of the ingesta between the proximal and distal stomach were monitored with a radionuclide technique. A triglyceride emulsion was infused into the duodenum for 45 min once 25% of the meal had emptied. The infusion caused significant slowing in the rate of gastric emptying (P less than 0.01). This slowing in gastric emptying was associated with the suppression of pressure waves in the distal antrum (P less than 0.01) and proximal duodenum (P less than 0.01), the induction of pressure waves isolated to a narrow pyloric segment (P less than 0.01), and a redistribution of ingesta from the distal to proximal stomach. These findings suggest that pressure waves isolated to the pylorus, changes in the intragastric distribution of ingested food, and changes in proximal duodenal motility may all act in concert with changes in antral motility to regulate the gastric emptying of solids.     

Adverse effects of vagotomy on ethanol-induced gastric injury in the rat

Truncal vagotomy is known to aggravate the damaging effects of alcohol-induced gastric injury and prevent the occurrence of adaptive cytoprotection against such injury by a mild irritant. This study was undertaken to determine whether aberrations in glutathione (GSH) metabolism were responsible for these vagotomy-induced effects. Fasted rats (6–8/group) were subjected to truncal vagotomy and pyloroplasty or sham vagotomy and pyloroplasty. One week later they were given 2 ml of oral saline or the mild irritant, 25% ethanol (EtOH). Thirty minutes following such treatment, animals were either sacrificed or orally received 2 ml of 100% EtOH and then were sacrificed 5 min later. At sacrifice, in each experimental group, stomachs were removed and either evaluated macroscopically for the degree of injury involving the glandular gastric epithelium or samples of the mucosa were prepared for measurement of total GSH levels or GSH peroxidase (GPX) and GSH reductase (GRT) activity. In nonvagotomized animals, saline treatment prior to 100% EtOH exposure resulted in injury to the glandular epithelium involving approximately 18%. Treatment with 25% EtOH prior to 100% EtOH exposure virtually abolished this injury. In vagotomized animals, 100% EtOH elicited almost three times the amount of injury observed in the nonvagotomized state and the protective effect of 25% EtOH pretreatment was prevented. Effects of the various treatment modalities on GPX and GRT activity were not significantly different from control values. When mucosal GSH results were plotted against the presence or absence of gastric injury among the various groups studied, no significant correlation was apparent. Thus, aberrations in glutathione metabolism do not explain the absence of adaptive cytoprotection following vagotomy or the exacerbation of alcohol-induced damage under conditions of vagal denervation.This work was supported by research grant DK 25838 from the National Institutes of Health.     

Regression of atypical lymphoid hyperplasia after eradication ofHelicobacter pylori

A rare case of endescopic and histological regression of a gastric lymphoid mucosal lesion after eradication ofHelicobacter pylori is reported. A 72-year-old man was suspected of having a low-grade B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma by endoscopic and histological findings. Histology of biopsy specimens showed massive infiltration of atypical lymphocytes and lymphoepithelial lesions. Immunohistochemical staining revealed kappa light chain expression in the infiltrated atypical lymphocytes to be twofold that of lambda light chain. The above diagnosis was thus highly suspected but not confirmed. Antibiotic therapy was given on the basis of evidence ofH. pylori infection. Successful eradication ofH. pylori resulted in remarkable improvement of endoscopic and histological findings. Follow-up studies were carried out 8 months after eradication, with no evidence of relapse. The eradication ofH. pylori appears to be an effective alternative therapy for B-cell lymphoproliferative disease, although longer follow-up and further studies are needed before this treatment can be establisted.