The role of the gastric antrum in the pathogenesis of reflux gastritis

The effect of antrectomy on the histopathologic changes of alkaline reflux gastritis was investigated in an effort to elucidate a possible protective role for the gastric antrum in the pathogenesis of this postgastrectomy syndrome. A canine model for reflux gastritis was utilized in 10 animals, 5 of which were antrectomized. Evaluating parameters of gastritis, parietal cell and mitotic counts, and mucosal dimensions, we found significantly more severe gastritis, parietal cell atrophy, and mucus cell hyperplasia in the antrectomized animals as compared with those which were not antrectomized. It is concluded that the gastric antrum does exert a protective effect on gastric mucosa which is chronically exposed to duodenal contents. Possible mechanisms for this protection and the pathogenesis of alkaline reflux gastritis are reviewed, and clinical implications are proposed.     

Hemorrhage in erosive gastritis]

The authors have examined 381 patients admitted with acute hemorrhage from the upper portion of the gastrointestinal tract. In 58 patients erosive gastritis was found by means of urgent gastroduodenoscopy. The clinical picture of this severe affection, the possibilities of diagnosis and the policy of treatment are described. Electron-microscopic studies of the gastric mucosa in erosive gastritis have evidenced different genesis of the erosions.     

The role of Toll-like receptors in the pathogenesis of renal disease

Toll-like receptors (TLRs) are an essential component of innate immunity, the first line of defense against invading pathogens. However, in addition to activating antimicrobial effector responses directly, TLRs lead to the induction of signals that control the activation of adaptive responses including autoimmune responses and allorecognition. This ability of TLR to control both innate and adaptive immunity has a broad applicability to the development of novel immunotherapies and antimicrobial strategies. This review discusses the basic biology of TLR and their contribution to renal disease.     

Role of pepsin in species differences in erosive gastritis.

This controlled study shows that the rabbit is more vulnerable to erosive gastritis after stress of operation, weight loss, and hypersecretion or acute ischemia than is the cat. Rabbit gastric juice also produces more erosions in the Shay rat preparation after four hours than does cat gastric juice (P less than .05). In vitro, rabbit pepsin has 1.5 times greater specific activity and possesses other kinetic differences. The deleterious effect of these qualitative differences on gastric mucosa may also be augmented by quantitative differences. Hypersecretion of pepsin has been reported once the mucosa is damaged. We conclude that demonstration of species-related differences in pepsin activity helps to explain an apparent discrepancy noted by others--namely, why the rabbit is so much more susceptible to stress-produced erosions than the cat or other experimental animals.     

The key role of apoptosis in the pathogenesis and treatment of pulmonary hypertension.

In recent years, the process of the programmed cell death has gained much interest because it has important pathophysiological consequences contributing to the deletion of unwanted cells in the vessel wall, loss of pulmonary smooth muscle cells and therefore in reversing the pulmonary pressure. For the reason that most patients with pulmonary hypertension present with limited reversibility with vasodilators, antiremodeling approach for treatment appears to be feasible. Induction or enhancement of vascular smooth muscle cells apoptosis may be targeted to develop novel therapeutic approaches for pulmonary vascular remodeling in patients with pulmonary hypertension. This review summarizes the current mechanisms, investigate the roles and provide novel insights into the potential therapeutic value of apoptosis in the pulmonary artery remodeling of pulmonary hypertension.     

The role of the intestinal microbiota in the pathogenesis and treatment of inflammatory bowel diseases

In little over a half century, the incidence and prevalence of inflammatory bowel diseases (IBD) has increased dramatically on a time scale that would be difficult to explain by genetic drift. The impact that IBD has on patients, particularly children and young adults, can be devastating, as there are no cures or preventive therapies. Although some insights have been gained in the conceptual development of IBD pathogenesis, the complexity and interplay of genetic, environmental and microbial factors that converge to trigger and sustain human IBD remain unclear. Over the past decade, cultivation-independent investigations together with gnotobiotic models and advances in bioinformatic analysis platforms have dramatically improved our knowledge of the role of intestinal microbiota in IBD; but further studies are needed to determine the functional and causative effect of intestinal dysbiosis for our understanding of aberrant host–microbe interactions resulting in the development of IBD. These efforts will lead to the establishment of novel microbiota-base therapeutic strategies to achieve the cure and prevention for IBD.     

Development of erosive gastritis in a canine model of esophageal varices

We designed a reproducible canine model of esophageal varices, based on the concept of a regional hyperdynamic state in the upper stomach. Arterialization of the left gastric vein concomitant with the distal splenorenal shunt led to a stable hyperdynamic state and reproducible esophageal varices occurred. In the long-term follow-up of these dogs with varices, the erosive gastritis seen in the upper stomach learly resembled clinically observed lesions. Hemodynamic and morphological studies revealed that gastric mucosa of these animals was in an ischemic state, even though there was a remarkable increase in blood flow in the submucosal area. It is suggested that the decrease in mucosal blood flow, as induced by the hyperdynamic state caused erosive gastritis.     

Development of erosive gastritis in a canine model of esophageal varices

We designed a reproducible canine model of esophageal varices, based on the concept of a regional hyperdynamic state in the upper stomach. Arterialization of the left gastric vein concomitant with the distal splenorenal shunt led to a stable hyperdynamic state and reproducible esophageal varices occurred. In the long-term follow-up of these dogs with varices, the erosive gastritis seen in the upper stomach clearly resembled clinically observed lesions. Hemodynamic and morphological studies revealed that gastric mucosa of these animals was in an ischemic state, even though there was a remarkable increase in blood flow in the submucosal area. It is suggested that the decrease in mucosal blood flow, as induced by the hyperdynamic state caused erosive gastritis.     

糜烂性胃炎385例内镜分析

本文通过分析385例糜烂性胃炎(EG)的内镜表现、病理学检查及幽门螺杆菌(HP)感染发现：胃窦部EG发病率男女接近，胃底、胃体部男性明显多于女性。发病年龄均以30-70岁最多，平均年龄接近。分型上胃窦部多见隆起糜烂型和平坦糜烂型，胃底、胃体部多见平坦糜烂型。HP感染胃窦部占71．9％，胃底、胃体部占58．0％。HP总感染率为68．3％。2个部位均有1例早期胃癌。笔者认为内镜检查加上病理学及HP感染等检查，对本病具有重要的诊断价值，是发现早期胃癌的重要途径。     

The maintenance of gastric mucosal barrier during the early erosive gastritis component of stress ulceration.

The spectrum of gastric stress ulceration includes early erosive gastritis, which develops within 48 hours of injury, as well as a late ulcerative component. Previous clinical studies with young healthy volunteers as controls have implicated increased back diffusion of hydrogen ions in the pathogenesis of stress ulceration. The present study compares the gastric mucosal integrity of injured patients to an age-matched control population of patients who had undergone elective intra-abdominal operations. These control patients suffered operative injury similar to that of the injured patients and yet, unlike injured patients, they did not develop clinically overt stress ulceration. The patients were studied during the first 2 days following injury and/or operation. No differences were found in the gastric mucosal permeability to hydrogen ions, as measured by back diffusion of hydrogen ions (H+BD) and by absorption of lithium (delta(Li/PSP), between the injured patients and their age-matched controls, despite the subsequent development of clinically overt stress ulceration in 25% of the injured patients. Likewise, there were no differences between the traumatized patients who developed stress ulceration and either their age-matched controls or the remainder of the traumatized patients. These date suggest that increased back diffusion of hydrogen ions cannot be implicated in the erosive gastritis which is the early component of stress ulceration.     

The role of synovitis in osteoarthritis pathogenesis

Research into the pathophysiology of osteoarthritis (OA) has focused on cartilage and peri-articular bone, but there is increasing recognition that OA affects all of the joint tissues, including the synovium (SM). Under normal physiological conditions the synovial lining consists of a thin layer of cells with phenotypic features of macrophages and fibroblasts. These cells and the underlying vascularized connective tissue stroma form a complex structure that is an important source of synovial fluid (SF) components that are essential for normal cartilage and joint function. The histological changes observed in the SM in OA generally include features indicative of an inflammatory "synovitis"; specifically they encompass a range of abnormalities, such as synovial lining hyperplasia, infiltration of macrophages and lymphocytes, neoangiogenesis and fibrosis. The pattern of synovial reaction varies with disease duration and associated metabolic and structural changes in other joint tissues. Imaging modalities including magnetic resonance (MRI) and ultrasound (US) have proved useful in detecting and quantifying synovial abnormalities, but individual studies have varied in their methods of evaluation. Despite these differences, most studies have concluded that the presence of synovitis in OA is associated with more severe pain and joint dysfunction. In addition, synovitis may be predictive of faster rates of cartilage loss in certain patient populations. Recent studies have provided insights into the pathogenic mechanisms underlying the development of synovitis in OA. Available evidence suggests that the inflammatory process involves engagement of Toll-like receptors and activation of the complement cascade by degradation products of extracellular matrices of cartilage and other joint tissues. The ensuing synovial reaction can lead to synthesis and release of a wide variety of cytokines and chemokines. Some of these inflammatory mediators are detected in joint tissues and SF in OA and have catabolic effects on chondrocytes. These inflammatory mediators represent potential targets for therapeutic interventions designed to reduce both symptoms and structural joint damage in OA. This article is part of a Special Issue entitled "Osteoarthritis".     

The role of interleukin-6 and of its soluble receptors in the biocompatibility of dialysis treatment

Proinflammatory cytokines, in addition to their role in host defence, may be considered mediators of disease; a reduction of cytokine synthesis or effects is, therefore, becoming a target of many diseases. IL-6 is a pro-inflammatory cytokine that may play a role in several clinical problems related to dialysis treatment. An enhanced spontaneous production of IL-6 by Peripheral Blood Mononuclear Cells (PBMC) harvested from ESRD patients dialyzed with a poor biocompatible membrane has been first demonstrated by our group. These results were also obtained in patients undergoing continuous peritoneal dialysis, in absence of peritonitis. We have also demonstrated that IL-6 release was inversely correlated with serum albumin changes. Biological activities of IL-6 may be modulated by two soluble circulating receptors, namely sIL-6R and sgp130. sIL-6R may enhance the inflammatory effects of IL-6 and is, therefore, an "agonistically" acting molecule. We have recently studied sIL-6R production in ESRD patients dialyzed with different membranes; the conclusion was that poor biocompatible membranes, via the sIL-6R, might further increase the inflammatory effects of IL-6. On the contrary, sgp130 can efficiently bind the IL-6/sIL-6R complex with "antagonistic" effects. We have evaluated plasma levels of sgp130 in 18 ESRD patients regularly dialyzed with hemophan membranes (HE) and in 15 patients dialyzed with more biocompatible synthetic membranes (BIO). Our results demonstrate that plasma levels of sgp130 in HE are 33% higher than in both healthy controls and BIO. Circulating levels of sgp130 were correlated positively with C-reactive protein (r: 0.338, p<0.05) and negatively with serum albumin (r: -0.334, p<0.05). These results suggest that higher circulating levels of sgp130 are likely associated with higher IL-6 levels. These higher amounts are probably insufficient to control the activity of IL-6 and may be considered only as a marker of PBMC activation.     

Clinical significance of erosive gastritis in patients with alcoholic liver disease and upper gastrointestinal hemorrhage

Since, in many patients with alcoholic liver disease and upper gastrointestinal hemorrhage, varices and erosive gastritis frequently coexist, the purpose of this study was to assess the severity of hemorrhage, rebleeding and mortality rates when these lesions are present singly or concomitantly. In 104 patients not operated upon, 31 had both lesions present on endoscopic examination, and their clinical courses paralleled the severity of 29 patients who had bleeding varices as the sole finding. In 13 patients with alcoholic liver disease and upper gastrointestinal hemorrhage who were found to have erosive gastritis as the sole lesion, the clinical course was as benign as in 31 patients with ethanol-induced gastritis without liver disease, and their blood loss, rebleeding and mortality rates were significantly less than in patients with both varices and gastritis. It is concluded that the course and prognosis of upper gastrointestinal hemorrhage in patients with alcoholic liver disease and erosive gastritis is dependent upon the presence or absence of gastroesophageal varices.     

细胞因子在绝经后骨质疏松症发病机制中的作用

雌激素、免疫细胞因子及骨代谢三者相互作用,绝经后骨质疏松症主要与雌激素缺乏导致细胞因子激活破骨细胞的活性密切相关。雌激素缺乏导致巨噬细胞和T细胞分泌IL-1和TNFα,抑制调节性T细胞增殖和成熟,促进NFκB、IL-15和IL-17的产生,从而诱导破骨细胞发展;抑制成骨细胞和骨系细胞产生OPG,促进RANK-RANKL相互作用,导致破骨细胞活性增强;抑制成骨细胞和骨细胞的TGFβ,减少破骨细胞凋亡。