摘要:

Abstract.Acute gastric ulceration induced by haemorrhagic shock is associated with profound intramucosal acidification due to diffusion of luminal H+into the mucosa. High‐HCO3−metabolic alkalosis protects the mucosa against this ulceration, whereas low‐HCO3−respiratory alkalosis does not, suggesting that lack of systemic and intramucosal HCO3−. rather than tissue acidosisper se, renders the mucosa susceptible to ulceration. In normal mucosa, disruption of the mucosal barrier by taurocholate, ethanol or acetylsalicylic acid leads to efflux of alkali (HCO3−) from the mucosa, with generation of an alkaline buffer layer at the epithelial surface to protect the mucosa from further damage. In ischaemic mucosa no such protective alkaline layer is formed, and exposure to luminal acid leads to severe acidification of and damage to the mucosa. The efflux of alkali may be driven by capillary hydrostatic pressure, since no such protective alkaline efflux occursin vitro, but rather exposure to luminal acid and barrier‐breaking agents results in intracellular acidification. The potential pathogenetic role of a disrupted intramucosal acid‐base balance, as well as the protective effect of systemic and intramucosal HCO3−in acute gastric stress ulceration is further substantiated by thein vitrofindings that perfusion conditions simulatingin vivoulcerogenic conditions provoke intracellular acidosis, and serosal HCO3−significantly contributes to the maintenance of normal intracellular pH in surface epithelial cells expo

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1990.tb01474.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Subcutaneous administration of cysteamine and mepirizole (at ulcerogenic and non‐ or weakly ulcerogenic doses) to fasted rats induced villous damage to the duodenum within 4 h. Only the damage induced by ulcerogenic doses progressed to macroscopically visible ulcers 10–12 h later. A considerable increase in gastric content was observed for more than 6–8 h after administration of the ulcerogenic dose of agents, but normal contents were noted 12 h later. The intraduodenal pH remained low for up to 16–20 h when ulcerogenic doses were given, but returned to control levels within 8–12 h when non‐ulcerogenic doses were given. Histamine similarly caused villous damage to the duodenum, yet there was no progression to an ulcer. Accumulation of gastric contents and a lower intraduodenal pH with histamine persisted for only 2 h and 1 h, respectively. We conclude that prolonged accumulation of gastric contents for up to 8 h together with a decreased lower intraduodenal pH for 16–20 h are necessary for the developmental progression of villous damage to well‐defined ulcers in the presenc

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1990.tb01475.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.The occurrence of auto‐antibodies in patients with the autoimmune disease pernicious anaemia and in patients with active duodenal ulcers was investigated. In order to characterize antigenic structures, various cellular and subcellular fractions were prepared from pig gastric mucosa and from a homogenate of duodenal mucosa. By means of an enzyme‐linked immunosorbent assay and immunoblotting, both the H+,K+‐ATPase and pepsinogen/pepsin were shown to constitute the major antigens. All of the seven pernicious‐anaemia sera that were tested contained auto‐antibodies against both antigens, and the epitopes of the H+,K+‐ATPase were shown to be localized on its cytoplasmic face. In 75% (18/24) of the sera from patients with duodenal ulcers, auto‐antibodies were detected when using purified antigens. Six sera reacted with H+,K+‐ATPase and twelve reacted with pepsinogen, one reacted with both antigens, and four sera reacted with the duodenal mucosal antigen. The occurrence of auto‐antibodies indicates that there is a mucosal lesion and that immunological factors may be involved in the pathogenesis of the disease

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1990.tb01476.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.The mucus barrier is a layer of water‐insoluble gel adherent to the gastroduodenal epithelium. In man most previous studies have focused on luminal mucus or histological assessment of presecreted, intracellular mucus—neither of which can be directly correlated with the protective capacity of the adherent mucus barrier. We here describe direct observation of adherent mucus thickness in man, and changes in peptic ulceration.Adherent mucus gel on human antral mucosa is a continuous homogeneous layer of variable thickness, in the range 50–450 μm (median 180 μm), comprising 67% polymeric mucin. In gastric ulcer patients, adherent antral mucus is significantly increased in thickness (median 240 μm), but is very heterogeneous and structurally a substantially weaker gel, comprising only 35% polymeric mucin. Adherent antral mucus from duodenal ulcer patients is homogeneous, significantly thinner (median 110 μm), and structurally a weaker gel, comprising 50% polymeric mucin. The adherent mucus layer from patients with gastric carcinoma resembled that from subjects with gastric ulcer in that it was very heterogeneous, of significantly increased thickness (median 240 μm) and structurally a very weak gel (23% polymeric mucin). These results are discussed in the context of gastroduodenal mucosal protection against acid and pepsin in the gas

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1990.tb01477.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.In vivomicroscopy of the gastric surface, and pH‐sensitive dyes, were used to study the movement of acid formed in the gastric crypts across the mucus layer adherent to the gastric surface and into the lumen. Rats were anaesthetized and the stomach gently exteriorized. When the pH‐sensitive dye Congo red was applied luminally to stain the gel, predominantly red spots (pH>5) and occasional blue spots (pH<3), located above the outlets of the crypts, were observed in spontaneously‐secreting mucosae. Maximal stimulation of acid secretion (pentagastrin, 40 μg kg−1h−1) resulted in the appearance only of blue spots, but the pH in the mucus gel between the crypts remained more alkaline, as indicated by pink staining. The fluorescence dye acridine orange was injected intravenously to an estimated blood concentration of 10−5M in another type of experiment. This dye is concentrated and secreted by the parietal cells. Pronounced fluorescence was observed within spots of the gastric surface corresponding to the outlets of the gastric crypts, but no fluorescence was detected outside these areas. The results obtained with both dyes strongly suggest that acid (and pepsin) is transported across the mucus gel only at rest

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1990.tb01478.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.This report describes approaches for accurate determination of the comparative activities of stimulants of duodenal alkaline secretion. We screened about 200 standard pharmacological agents using a bullfrog‐isolated mucosal preparation in order to characterize fully the mechanisms of duodenal alkaline secretion. A variety of eicosanoids, phosphodiesterase (PDE) inhibitors, adrenoreceptor agonists and benzodiazepines, together with forskolin, 6‐hydroxydopamine, 2‐chloroadenosine, dipyridamole, dihydropyridazinone and testosterone, caused a reproducible increase in the metabolism‐dependent component of duodenal alkaline secretion. Prostaglandin E2(ED50of 0.02 μg ml−1in vitro) was the most potent and efficacious stimulant in the isolated mucosa and in the perfused cat duodenumin vivo. In the isolated duodenum, the predominant mechanism for stimulating alkaline secretion appears to be via elevation of intracellular cAMP levels, butin vivoindirect effects, for example on mucosal blood flow, may determine the overall influence of agents on duodenal alka

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1990.tb01479.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.This report summarizes data concerning the extrinsic neural control of bicarbonate secretion by the gastric and duodenal mucosa. Parasympathetic vagal effects have been studied in experimental animals and in man by means of direct electrical vagal stimulation, sham‐feeding procedures and intracerebroventricular peptide injections. The results show that the vagal nerves have a stimulatory effect on gastroduodenal bicarbonate secretion. Furthermore, both conventional nicotinic and muscarinic cholinoceptor, as well as non‐cholinergic transmission, mediate the vagal effect. Sympathetic splanchnic nerve effects have been investigated by means of nerve sections, direct electrical stimulation, reflex activation and stereotaxic electrical hypothalamic stimulation. The data show that the splanchnic nerves have a predominantly inhibitory action on gastroduodenal bicarbonate secretion by use of peripheral adrenergic neurones and receptors of the alpha‐2 subtype. The role of the adrenal glands is not fully understood. It is concluded that gastroduodenal bicarbonate secretion is under autonomic neural control, mainly in the classical antagonistic fashion; the parasympathetic vagal nerves stimulate bicarbonate output, whereas the sympathetic splanchnic nerves are mainly inhib

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1990.tb01480.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Duodenal alkaline secretion is a protective mechanism that is sensitive to changes in mucosal blood flow and arterial bicarbonate concentration (i.e. bicarbonate delivery to the mucosa). Alkaline secretion has been shown to prevent or limit damage and to facilitate the repair process once damage has occurred. A rapid restitution of the epithelial integrity has been demonstrated in the duodenum. This repair process is sensitive to alterations in nutrient HCO3supply. Removal of the necrotic cell layer before repair is complete inhibits the re‐establishment of epithelial continuity at low luminal pH. However, under optimal conditions repair is completed within a few hours, even with repeated acid challeng

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1990.tb01481.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Over the past few years, we have addressed some of the components that regulate human duodenal bicarbonate secretion (DBS) using a technique for the isolation of a 4‐cm duodenal segment from gastric, pancreaticobiliary and distal intestinal secretions. Our observations are summarized as follows. Resting DBS is, to a large extent, maintained by vagal innervation; atropine decreases basal bicarbonate secretion by approximately 80%. Luminal acidification with HCI (H+) is a major physiological stimulus of DBS, resulting in a prompt and significant increase of 3‐ to 4‐fold. H+‐stimulated DBS is likely to be mediated, at least in part, by prostaglandins of the E class, and by VIP. Each of the latter stimulates DBS independently in a dose‐related manner. Since atropine is without effect on the response induced by luminal H+and sham feeding, in both cases DBS is probably stimulated via a non‐cholinergic pathway(s). Moreover, since basal, H+‐ and PGE2‐stimulated proximal DBS are unaltered when the plasma‐to‐lumen bicarbonate concentration gradient is abolished, it may be concluded that DBS in humans involves active transport processes. It is significant that, compared to normal subjects, patients with duodenal ulcers show markedly diminished basal and H+‐stimulated proximal DBS. Furthermore, there is surprisingly little overlap between duodenal ulcer (DU) patients and normal subjects. These findings suggest that an intrinsic cellular or subcellular defect in proximal duodenal mucosal bicarbonate secretion is present in patients with d

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1990.tb01482.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Active Na+absorption by tight epithelia such as frog skin and distal colon share common features like feedback inhibition of cellular [Na+] on Na+influx through amiloride‐sensitive Na+channels. It is postulated that the negative feedback of increasing cell [Na+] is mediated via a rise in cell [Ca2+]. In this model, cell [Na+] is coupled to cell [Ca2+] via a Na+/Ca2+exchange system in the basolateral membrane. In the present study, the Ca2+transporting systems in rabbit distal colon basolateral membranes were characterized. ATP‐dependent Ca2+uptake could be demonstrated in membrane vesicles from surface cells with the following kinetic parameters: Km= 0.09 μM Ca2+and Vm= 3.8 nmol Ca2+mg−1protein min−1. The ATP‐dependent Ca2+transport was not responsive to ruthenium red and oxalate, suggesting a plasmalemmal origin. The addition of 75 mM Na+to the uptake medium, 10 min after addition of ATP, did not release Ca2+from the vesicles in significant amounts. In the absence of ATP, outwardly directed Na+gradients were incapable of stimulating Ca2+uptake. This study demonstrates that rabbit distal colon epithelium lacks a well‐defined Na+/Ca2+exchange system, and (Ca2+, Mg2+)‐ATPase appears to be the sole Ca2+extrusion system. Alternatives for the coupling of cell [Na+] to cell [Ca2+]

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1990.tb01483.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY