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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is important to have a reliable method of assessing the dietary nitrate exposure of populations for a proper understanding of the potential health effects of the endogenous metabolites of this ion to be gained from epidemiological studies. Recently we strongly advocated the use of the nitrate analysis of 24 h urine samples as being a superior method for such studies. Our previous observations and those of others relating to nitrate pharmacology in healthy human volunteers formed the basis of this judgement. The purpose of this study was to determine whether gastric achlorhydria or hypochlorhydria has any significant gross effects on the urinary recovery of dietary nitrate and to what extent the inclusion of such individuals would compromise the results of potential epidemiological studies. The results demonstrated a significantly greater loss of dietary nitrate as measured by urinary recovery in achlorhydrics than in normochlorhydrics, presumably as a consequence of bacterial metabolism in the colonized stomach. Thus the average urinary nitrate recovery of a 1.5 mmol challenge was 33% in individuals with reduced stomach acidity as compared to 56% in normal controls. This significant further loss of nitrate (average 23%) when intragastric conditions favour bacterial colonization clearly indicates that for valid assessments and comparisons of nitrate exposure between populations it would be wise to exclude individuals with low levels of stomach acid where this is likely to lead to significant gastric colonization by nitrate-reducing bacteria (i.e. pH less than 4-5).
Carcinogenesis 1990 Aug
PMID:The effect of gastric achlorhydria on the urinary recovery of nitrate in man: relevance to urinary nitrate as a measure of dietary nitrate exposure. 238 23

It has been suggested that endogenously formed N-nitroso compounds are involved in the aetiology of gastric cancer. In the model of gastric carcinogenesis postulated by Correa, gastric atrophy is an important early stage in the progression to carcinoma which results in the loss of stomach acidity, and colonization of the stomach by bacteria. As a consequence of the metabolic activity of these bacteria intragastric nitrite (a precursor to N-nitroso compounds) and possibly carcinogenic N-nitroso compounds become elevated, which may hasten the progression to carcinoma. Vitamin C has been shown to be an effective inhibitor of acid-catalysed N-nitroso compound formation, in vivo and in vitro, and this has been attributed to its relatively rapid reaction with nitrite in contrast to the slower rates of reaction of nitrite with secondary amines. However, N-nitroso compound formation in the achlorhydric stomach must proceed by mechanisms which operate at neutral pH values. One potential mechanism involves the enzymatic catalysis of N-nitrosation by a subpopulation of the bacteria colonizing the achlorhydric stomach which catalyse these reactions and in particular denitrifying organisms. In this study, we examined the effect of vitamin C on the formation of N-nitrosomorpholine from morpholine and nitrite when mediated by cells of an actively N-nitrosating denitrifying bacterium (Pseudomonas aeruginosa, BM1030) at neutral pH. Despite the fact that vitamin C ordinarily shows little reactivity towards nitrite at neutral pH it did prove to be a potent inhibitor of bacterial N-nitrosamine formation. This study provides some justification for the use of vitamin C as an inhibitor of endogenous N-nitrosation regardless of gastric pH.
Carcinogenesis 1989 Feb
PMID:The inhibition of bacterially mediated N-nitrosation by vitamin C: relevance to the inhibition of endogenous N-nitrosation in the achlorhydric stomach. 249 12

Between 1959 and 1987, at the Innsbruck University Hospital, 359 cases of carcinoma were diagnosed in the gastric remnant. While until 1975 in 203 patients suffering from stump carcinoma the tumor stages T3 and T4 were significantly prevalent, a strong tendency towards the less advanced tumor stages T1 and T2 was observed in the last decade. Among 94 patients operated on since 1981 the tumor was located at the anastomosis in all but 5 cases, suggesting a strong connection between previous resection and stump carcinoma. In accordance with Lauren's classification no difference was found in the incidence of intestinal and diffuse lesions in 94 cases with stump carcinoma--in contrast to 69 cases of patients with a non-resected stomach. An analysis of the occurrence of acidity, atrophic gastritis and bacterial invasion in 70 patients with previous Billroth II resection and 30 patients with Billroth I resection, revealed no difference between the two types of resection. Gastric remnant carcinoma does not occur exclusively in the Bilroth II remnant, but, increasingly, following Billroth I operations. The finding of a statistically highly significant increase at the 5% level using standard chi 2-technique for a 2 x 5 table in stump carcinomas following Billroth I resections supports the thesis that there is no difference in the etiopathology of carcinogenesis in the Billroth I as compared with the Billroth II remnant.
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PMID:Gastric stump cancer: etiopathological and clinical aspects. 274 40

The relationships between fiber consumption and human cancer rates have been examined, together with an analysis of the effects of individual dietary fibers on the experimental induction of large bowel cancer. The human epidemiology indicates an inverse correlation between high fiber consumption and lower colon cancer rates. Cereal fiber sources show the most consistent negative correlation. However, human case-control studies in general fail to confirm any protective effect due to dietary fiber. Case-control studies indicate that if any source of dietary fiber is possibly antineoplastic then it is probably vegetables. These results may mean that purified fibers alone do not inhibit tumor development, whereas it is likely that some other factors present in vegetables are antineoplastic. Experiments in laboratory animals, using chemical induction of large bowel cancer, have in general shown a protective effect with supplements of poorly fermentable fibers such as wheat bran or cellulose. In contrast, a number of fermentable fiber supplements including pectin, corn bran, oat bran, undegraded carageenan, agar, psyllium, guar gum, and alfalfa have been shown to enhance tumor development. Possible mechanisms by which fibers may inhibit colon tumorigenesis include dilution and adsorption of any carcinogens and/or promoters contained within the intestinal lumen, the modulation of colonic microbial metabolic activity, and biological modification of intestinal epithelial cells. Dietary fibers not only bind carcinogens, bile acids, and other potential toxins but also essential nutrients, such as minerals, which can inhibit the carcinogenic process. Fermentation of fibers within the large bowel results in the production of short chain fatty acids, which in vivo stimulate cell proliferation, while butyrate appears to be antineoplastic in vitro. Evidence suggests that if dietary fibers stimulate cell proliferation during the stage of initiation, then this may lead to tumor enhancement. Fermentation also lowers luminal pH, which in turn modifies colonic microbial metabolic acidity, and is associated with increased epithelial cell proliferation and colon carcinogenesis. Because dietary fibers differ in their physiochemical properties it has been difficult to identify a single mechanism by which fibers modify colon carcinogenesis. Clearly, more metabolic and physiological studies are needed to fully define the mechanisms by which certain fibers inhibit while others enhance experimental colon carcinogenesis.
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PMID:Relationship between dietary fiber and cancer: metabolic, physiologic, and cellular mechanisms. 302 86

This paper reviews the relationship between gastric acid secretion and infection and the protective role of gastric acid as a primary bactericidal barrier and modulator of gastrin section. Gastric acid is bactericidal at pH 3 or less, but reduction of acidity predisposes to infection with a wide variety of bacteria. Bacterial infections or hyperpyrexia may be associated with a marked reduction in gastric acid secretion, and Campylobacter pylori has been suggested as one cause of epidemic hypochlorhydria. Achlorhydria is also associated with hypergastrinaemia with levels 20-fold higher in pernicious anaemia patients than normal subjects. Treatment with antisecretory drugs is associated with hypergastrinaemia with gastrin levels 2- to 5-fold higher than with placebo, and the gastrin levels correlate with the degree of acid suppression. The possible relationship among infection, acid suppression, hypergastrinaemia, and the development of enterochromaffin cell hyperplasia and possible carcinogenesis is reviewed.
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PMID:The protective role of gastric acid. 306 34

The current therapeutic approach to peptic ulcer disease includes agents that reduce gastric acidity and hence peptic activity, inactivate or adsorb pepsin, create a physical barrier against the effects of acid and pepsin, or enhance mucosal defence. Profound gastric acid reduction may predispose to infection, and it has been suggested that carcinogenesis is possible, although a cause-effect relationship has never been established. The side-effects of therapy are well-described, and may limit the therapeutic approach. Healing rates correlate closely with acid suppression in duodenal ulcer, but not entirely in gastric ulcer. Maintenance therapy lowers the relapse rate, but does not alter the ulcer diathesis. The optimal strategy for long-term management remains unclear, but in the future one should consider outcome measures which include a decrease in pain, improvement in the quality of life, reduction work loss, and a reduction of complications, in addition to ulcer healing. The ideal therapy should be efficacious, safe, and convenient--with no side-effects--and cost-effective. New agents should suppress acid and peptic activity, while enhancing the gastric mucosal defence mechanisms (such as mucosal blood flow, mucus, and bicarbonate secretion) and stimulating gastric cellular regeneration and restitution.
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PMID:The limitations of current therapy in peptic ulcer disease. 330 47

A 24 hour gastric aspiration study was carried out on nine Polya gastrectomy, eight pernicious anaemia, and nine matched control subjects. Intragastric pH, bacteria, nitrite, and N-nitroso compounds were assessed half hourly whilst ambulant and hourly when in bed. Both total and nitrate reducing bacterial counts were positively related to pH (chi 2 = 279.3; p less than 0.001), as was nitrite concentration (F = 19.1; p less than 0.0001). By contrast, total (F = 40.6; p less than 0.0001) and stable (F = 257.4; p less than 0.0001) N-nitroso compound concentrations were negatively related to pH. Clear differences in these gastric juice factors were not apparent between matched control and either pernicious anaemia, or Polya gastrectomy because the Polya gastrectomy and matched control groups were heterogeneous for gastric acidity. Thus, although eight of eight pernicious anaemia subjects were hypoacidic (defined as intragastric pH greater than 4 for greater than 50% of both daytime and night time periods), only five of nine Polya gastrectomy and two of nine matched control subjects were hypoacidic. When subjects were rearranged into hypoacidic (n = 15) and acidic (n = 11) groups, bacterial counts (p less than 0.01) and nitrite concentrations (p less than 0.01) were higher, whereas N-nitroso compounds tended to be lower (NS) in the hypoacidic group. These data suggest that, although hypoacidity predisposes to bacterial overgrowth and nitrite generation, it does not enhance nitrosation. Instead, this is maximal at low pH, suggesting chemical rather than bacterial nitrosation, contrary to the nitrosamine hypothesis of gastric carcinogenesis.
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PMID:Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions. 369 60

The ECL-cell hyperplasia and ECL-cell carcinoids occurring during long-term treatment with ciprofibrate, have been attributed to hypergastrinemia secondary to an inhibitory effect on acid secretion. However, nobody has given any explanation of the mechanism by which ciprofibrate and related phenoxyisobutyrate derivates inhibit acid secretion. Moreover, the reported inhibition of acid secretion has only been moderate, in contrast to the profound inhibition of acid secretion needed to induce similar ECL-cell changes. To re-examine the effect of ciprofibrate on gastric acidity and serum gastrin, we randomly assigned 33 male Fisher rats into three treatment groups (100 or 20 mg/kg/day of ciprofibrate and control) during a period of 4 weeks. Daily assessments of gastric acidity was done by gastric intubation, using a tube with a diameter of 2.0 mm allowing the introduction of an infant pH-catheter. Measurements were done in all animals 5 days a week. Ciprofibrate did not raise gastric pH. On the contrary, the highest dose increased the acidity. Serum gastrin levels measured in blood taken by vein puncture before the initiation of the drug treatment and on the last day of the 4 week treatment period, revealed a dose-related significant hypergastrinemic effect of ciprofibrate. The slight increase in gastric acidity in the ciprofibrate high-dose group is most likely due to the hypergastrinemia provoked by the drug. This hypergastrinemia is therefore not secondary to an inhibition of acid secretion, but may be due to a direct effect of ciprofibrate on the G-cell. The ECL-cell hyperplasia and the ECL-cell carcinoids, which develop during treatment with peroxysome-proliferators are thus due to hypergastrinemia, which is not secondary to inhibition of acid secretion.
Carcinogenesis 1996 Oct
PMID:The peroxisome-proliferator ciprofibrate induces hypergastrinemia without raising gastric pH. 889 82

We have identified cotton rats with a high female-predominant occurrence of spontaneous gastric carcinomas localized to the oxyntic mucosa, classified as malignant enterochromaffin-like (ECL) omas. The present study was made to further characterize these ECLomas and surrounding oxyntic mucosa, both morphologically using histochemical and immunohistochemical methods, and for gene expression by northern blot analysis. Among eight female cotton rats, three had an irregularly thickened oxyntic mucosa, increased stomach weight and a high serum gastrin level. Histopathological examination showed adenomatous hyperplasia of the thickened oxyntic mucosa with areas of an invasive neoplastic tumour. Immunohistochemistry, using the general neuroendocrine cell marker chromogranin A (CgA) and the specific ECL cell marker histidine decarboxylase (HDC), showed a considerably increased ECL cell density. These ECL cells displayed active proliferation, with hyperplasia, dysplasia and neoplasia. Parietal cells were not found in the tumour tissue. Parietal cell density was only slightly reduced in the surrounding oxyntic mucosa. The antral mucosa was histopathologically normal with a normal number of gastrin-immunoreactive cells. Likewise, somatostatin-immunoreactive cells did not show any differences in the antral and oxyntic mucosa between rats with pathological and normal oxyntic mucosa. Northern blot analysis revealed increased expression of CgA and HDC mRNA in the thickened oxyntic mucosa, whereas H(+)/K(+) ATPase mRNA was similar in the oxyntic mucosa of those with thickened and normal oxyntic mucosa. Gastrin mRNA in the antral mucosa was high in animals with thickened oxyntic mucosa. Somatostatin mRNA expression was similar in the antral mucosa of control animals and animals with a thickened oxyntic mucosa. We conclude that the spontaneous gastric carcinoma occurring in female cotton rats is an ECLoma developing secondary to hypergastrinaemia due to reduced intragastric pH. The mechanism for reduced acidity is not known, but is not gastric atrophy.
Carcinogenesis 2000 Jan
PMID:Spontaneous ECLomas in cotton rats (Sigmodon hispidus): tumours occurring in hypoacidic/hypergastrinaemic animals with normal parietal cells. 1060 29

Tumour angiogenesis is triggered by various signals characteristic of the tumour microenvironment, including low oxygen tension, low extracellular pH and low glucose concentration. Tumour microvasculature is chaotic, producing perfusion heterogeneities which can be visualized by MRI and other modalities. Inefficient perfusion in tumours produces regions of transient and chronic hypoxia. Tumour hypoxia is associated with adverse clinical outcomes and reduced patient survival. Hypoxia may be a factor in activation of extracellular matrix-degrading proteases, and some studies have correlated primary tumour hypoxia with likelihood of tumour cell dissemination. Exposure to hypoxia either induces or selects for cells that are hyperglycolytic, and this in turn produces local acidosis which is also a common feature of solid tumours. Increased glucose uptake in hyperglycolyzing tumour cells is the basis of lesion-visualization in positron emission tomography using 18F-fluorodeoxyglucose. Tumour acidity can reduce the effectiveness of weak-base drugs, but can be exploited to increase the anti-tumour activity of weak-acid chemotherapeutics. Evidence linking tumour acidity with increased activity of several extracellular matrix-degrading enzyme systems is examined. High levels of lactate, another end-product of glycolysis, in primary lesions have been correlated with increased likelihood of metastasis. In the numerous studies correlating hypoxia, acidity and lactate with metastasis, the direction of the causality has not been adequately established. We hypothesize that adoption of a hyperglycolytic phenotype is a necessary feature of carcinogenesis itself, and confers a survival and proliferative advantage to tumour cells over surrounding normal cells. Empirical evidence supporting this "acid-mediated tumour invasion" model is discussed.
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PMID:Microenvironmental and cellular consequences of altered blood flow in tumours. 1545 10


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