ISSN:0267-1379    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Several brain sites, including the paraventricular nucleus, dorsomedial and lateral hypothalamus, central nucleus of the amygdala, the bed nucleus stria terminalis, and the insular and medial prefrontal cortex, raphe obscurus and pallidus are likely to be involved in the regulation of acid secretion. These sites have established projections to the dorsal vagal complex and influence gastric acid secretion on chemical stimulation. A hypothalamic stimulatory control of acid secretion involving paraventricular nucleus-dorsal vagal complex oxytocin pathways and anterior hypothalamic cholinergic receptors has been described by one group of investigators. In the medulla, there is compelling evidence that would assign thyrotropin-releasing hormone terminals (which innervate the dorsal motor nucleus of the vagus) a stimulatory role in the vagal control of acid secretion in rats and cats. Preliminary data indicate that adrenergic innervation andy-aminobutyric acid, acting throughy-aminobutyric acidAreceptors in the dorsal motor nucleus, can produce a direct synaptic inhibition of parasympathetic neurons that results in a decrease of acid secretion. Newly described central inhibitors of acid secretion are interleukin- 1β and - 1α, which exert a potent antisecretory effect through prostaglandin pathways. These findings may provide new insight on interactions between the immune and gastrointestinal systems.

ISSN:0267-1379    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Gastric acid secretion is regulated by a complex interplay of neural, hormonal, and paracrine mechanisms. The main stimulants are acetylcholine, gastrin, and histamine. Pancreastatin and low concentrations of alcohol may also stimulate acid secretion. The main inhibitor of acid secretion is somatostatin, which exerts a continuous inhibitory paracrine restraint on parietal cells of the fundus and gastrin cells of the antrum. Several peptides, including bombesin, vasoactive intestinal polypeptide, cholecystokinin, and secretin may exert their inhibitory effects primarily by releasing somatostatin. Neurotensin, peptide YY, galanin, substance P, and high concentrations of alcohol also inhibit acid secretion.

ISSN:0267-1379    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

This review considers progress over the past 12 months in the elucidation of cellular mechanisms controlling gastric parietal cell hydrochloric acid secretion. The actions of the stimulatory agonists, histamine, acetylcholine, and gastrin and the secretory inhibitors, prostaglandins, somatostatin, and epidermal growth factor, are examined against a backdrop of clinically relevant actions of acid secretory inhibitors. Recent molecular characterizations of the gastric H+, K+-ATPase (proton pump) are also discussed.

ISSN:0267-1379    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Pepsins are a heterogeneous group of proteinases that include pepsin (pepsin I or A), gastricsin (pepsin II or C), and chymosin (pepsin III or rennin). They are synthesized primarily in chief cells as prozymogens that contain a leader region (signal peptide), a proregion (activation segment), and a pepsin region. Recent work focuses on the molecular biology of pepsins including gene localization and gene products. The peripheral control of pepsin secretion is complex with differences observed between species, particularly in regard to acetylcholine and histamine. Intracellular control of secretion is mediated by calcium (eg, acetylcholine, cholecystokinin, and bombesin) and cyclic AMP (isoproterenol and vasoactive intestinal polypeptide). Pepsin may play a key role in the development of peptic ulcer disease and esophagitis.

ISSN:0267-1379    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Significant advances in our understanding of a number of facets of the physiology and pathophysiology of mucosal defense have been made in the past year. The modulation of bicarbonate secretion by the gastroduodenal epithelium is becoming well characterized, with increasing evidence that this secretion is under neurohumoral control. The importance of mucosal blood flow in providing a supply of bicarbonate to the surface epithelium, particularly after superficial injury, has also been demonstrated. Through the use of pharmacologic probes such as capsaicin, the underlying mechanism for the reactive hyperemia that follows exposure of the mucosa to an irritant is becoming more clearly understood. Clinical evidence supporting a role for epidermal growth factor in mucosal defense and repair is now emerging and is consistent with earlier animal studies. Similarly, a role for polyamines and ornithine decarboxylase in mucosal repair has been supported by recent experimental evidence.

ISSN:0267-1379    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Injurious effects of aspirin and other nonsteroidal anti-inflammatory drugs to the gastric corpus are not explainable solely by drug-induced inhibition of prostaglandin synthesis. Studies of other acute effects of nonsteroidal anti-inflammatory drugs, largely in animal models, establish that endothelium in microvessels is a primary target of the drugs and also suggest that adherence by neutrophils to vessel walls accompanies or mediates injury, both by causing stasis in vessels and by neutrophil activation with release of oxygen free radicals, proteases, and other inflammatory mediators. Prevention of such processes markedly reduces mucosal damage. In addition to their effects on neutrophilic oxidases, free radical scavengers may also prevent hydroxyl radical formation by gastric mucosal peroxidases, a potentially damaging process. Neutrophil activation in other sites may lead to chronic ulcers. The presence of gastritis due toHelicobacter pylori, with associated neutrophilic infiltration, may render the antrum susceptible to neutrophil-mediated injury.

ISSN:0267-1379    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Colonization byHelicobacter pyloriis causally related to duodenal ulceration. There is also suggestive evidence that patients who develop malignancy in the upper gastrointestinal tract are more likely to be colonized by the organisms, although to date there is no suggestion of a causal link.H. pyloripossess a number of potential virulence factors that singly or together could contribute to gastric inflammation. Evidence from the past year casts doubt on the production of a mucinase enzyme byH. pylori, but has strengthened the role of the organism's urease enzyme as a virulence factor. The current belief is that the urease, by producing ammonia and altering the pH, affects the quality of the mucus barrier, altering its structure. Also, the ammonia can act as a direct cytotoxin for the gastric cells. Further work has strengthened the possible role of a proteinaceous cytotoxin produced byH. pylorias another possible virulence factor by demonstrating that cytotoxin-producing bacteria are more likely to be isolated from patients with ulceration. Further information has been gained about the surface properties ofH. pyloriand its production of inflammatory mediators, each of which could be important for colonization and stimulation of inflammation, respectively. Finally, there is an increasing appreciation of other mucosa-associated bacteria both in humans and other animals that may induce inflammation in the stomach.

ISSN:0267-1379    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The past decade has seen considerable advances in our treatment of peptic ulcer disease, with more potent antisecretory drugs, and a new armamentarium of prostaglandins, surface-active agents, and, perhaps most importantly, treatment againstHelicobacter pylori.This past year we have seen publications that suggest better rationales for treatment by acid suppression (both dose and duration), and we have evidence thatHelicobactertreatment may favorably alter the gastrin-acid physiologic mechanism. Finally, we are seeing some long-term results of treatment, with reports of 5-year periods with H2blockers. The publications of the past year, however, have been more incremental than landmark.

ISSN:0267-1379    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Peptic ulceration is a worldwide problem that often requires long-term treatment; hence, drugs used for this condition must be extremely safe. Five- to 10-year studies of patients dosed with H2-receptor antagonists are now becoming available, and no long-term adverse events have been detected. The occurrence of gastric carcinoids in some rats dosed with potent gastric antisecretory regimens has resulted in an explosion of work investigating the relationships between antisecretory drugs, plasma gastrin concentration, and proliferation of the gastric mucosa. However, there continues to be some concern that gastric antisecretory drugs may result in an increased risk of gastric cancer, with continuing research investigating possible drug-induced genotoxicity. Finally, there has been debate about a possible interaction between H2antagonists and low-dose alcohol consumption.

ISSN:0267-1379    

出版商:OVID    

年代:1991

数据来源: OVID