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B Pignatelli - One of the best experts on this subject based on the ideXlab platform.
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mutagens n nitroso compounds and their precursors in Gastric Juice from patients with and without precancerous lesions of the stomach
European Journal of Cancer, 1993Co-Authors: B Pignatelli, C Malaveille, A Hautefeuille, P Thuillier, Nubia Munoz, B Moulinier, F Berger, A Rogatko, H De Montclos, R LambertAbstract:This study examined whether elevated risk of Gastric cancer is associated with high levels of total N-nitroso compounds (NOC), their precursors and nitrosation-dependent genotoxins in Gastric Juice (GJ). An improved method for quantifying total NOC was used and genotoxicity was assayed in E. coli. Results from patients (n = 210) with or without precancerous lesions of the stomach and living in three areas with up to 8-fold variations in Gastric cancer risk (U.K., France, Colombia) were compared. The level of nitrite (range 4 and highest in samples from Colombia. The results (a) provide no support that intraGastric total NOC levels are elevated in subjects with precancerous stomach lesions or living in a high risk area for stomach cancer; (b) confirm that a high nitrite level and elevated pH in GJ are strongly associated, the level of nitrite being associated with precancerous stomach conditions only in Colombia; (c) reveal the presence of precursor compounds in GJ, that after nitrosation yield direct mutagens that probably contain NOC and other substances. As their concentrations were significantly higher in achlorhydric subjects and highest in Colombian patients, these data together provide support for a role of intraGastrically formed nitrite-derived direct mutagens in Gastric cancer aetiology.
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studies in Gastric carcinogenesis v the effects of ascorbic acid on n nitroso compound formation in human Gastric Juice in vivo and in vitro
Carcinogenesis, 1991Co-Authors: Soterios A. Kyrtopoulos, B Pignatelli, G Karkanias, B Golematis, J EsteveAbstract:The concentrations of nitrite, thermo- and acetic acid-labile TEA-responsive compounds (TACs) and N-nitroso compounds (NOCs) as a group were measured in human Gastric Juice collected just before and 1, 2 and 4 h after oral ingestion of 1 g ascorbic acid (AA) or 200 mg sodium nitrate, separately or in combination. Individual responses of Gastric [nitrite] following ingestion of AA alone varied widely, with both decreases and increases being observed, and showed no correlation with Gastric pH. While a mixed response was also noted for [NOC] and [TAC], substantial decreases were observed in 5/6 individuals with initial [NOC] greater than 0.2 microM and 3/3 individuals with initial [TAC] greater than 0.2 microM, implying that (i) AA effectively inhibited Gastric nitrosation and (ii) a basal amount of NOCs and TACs was present in Gastric Juice which could not be lowered by AA ingestion. Statistical analysis indicated that global mean values of Gastric [NOC] were significantly reduced (P less than 0.02) 1-4 h after ingestion of AA. Ingestion of 200 mg sodium nitrate alone resulted in increases in Gastric [NOC], which in some cases were very substantial. While nitrosation appeared lower following ingestion of the same dose of nitrate in combination with 1 g AA, the difference from the effects of nitrate alone was not statistically significant. In aqueous buffer, pH 2.5, and in the presence of 1 mM AA, 50 microM nitrite was consumed with a t1/2 of 50 min only if molecular oxygen had first been removed from the system. In the presence of oxygen, no consumption of nitrite could be detected in 50 min, reflecting nitrite recycling (oxidation of nitric oxide to higher oxides of nitrogen and hydrolysis back to nitrite). It is likely that nitrite recycling occurring after collection of Gastric Juice accounted for the inconsistent responses of Gastric nitrite following ingestion of AA. Incubation of human Gastric Juice, pH 2.5, in vitro in the presence of 50 microM sodium nitrite for 60 min resulted in an increase of [NOC] and [TAC] from 0.10 to 0.70 and 1.10 microM respectively. Nitrosation was efficiently inhibited by AA, 2.27 mM AA resulting in 87 and 100% inhibition respectively. Removal of oxygen from the reaction mixture did not have any significant effect on the extent of nitrosation in the presence or absence of AA.
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levels of nitrite nitrate n nitroso compounds ascorbic acid and total bile acids in Gastric Juice of patients with and without precancerous conditions of the stomach
Carcinogenesis, 1991Co-Authors: G M Sobala, C. J. Schorah, Marion Sanderson, M F Dixon, B Pignatelli, H Bartsch, S Shires, R F G King, A T R AxonAbstract:To determine the relevance of Gastric Juice factors to Gastric carcinogenesis, 56 patients with unoperated stomachs undergoing endoscopy for dyspepsia had Gastric Juice aspirated and analysed for pH, ascorbic acid, total bile acids, nitrite, nitrate and total nitroso compounds (NOCs). Plasma was obtained for vitamin C estimation. Antral and body biopsies were assessed for gastritis, Helicobacter pylori, atrophy and intestinal metaplasia (IM). Patients with chronic atrophic gastritis (n = 17) had lower Gastric Juice ascorbic acid concentrations (P less than 0.001), higher pH (P less than 0.05) and higher incidence of H. pylori infection (P less than 0.001) than normal subjects (n = 12). Patients with reflux gastritis (n = 9) had higher total bile acids (P less than 0.01). Patients with chronic gastritis and IM (n = 11) had higher Gastric Juice pH (P less than 0.01) and total bile acid concentrations (P less than 0.05), and lower Gastric ascorbic acid concentrations (P less than 0.01) than those with chronic gastritis and no IM (n = 24). In chronic gastritis, high nitrite concentrations were associated with high pH (P less than 0.01). However, there were no significant differences in plasma vitamin C or Gastric nitrite, nitrate or total NOC concentrations in relation to Gastric histology. We conclude that the premalignant condition IM is associated with H. pylori infection, low Gastric ascorbic acid levels and elevated total bile acids, but not to elevation in nitrite or total NOCs in fasting Gastric Juice.
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n nitroso compounds genotoxins and their precursors in Gastric Juice from humans with and without precancerous lesions of the stomach
IARC scientific publications, 1991Co-Authors: B Pignatelli, C Malaveille, C K Chen, A Hautefeuille, P Thuillier, Nubia Munoz, B Moulinier, F Berger, De Montclos H, Hiroshi OhshimaAbstract:We are investigating the interrelationships between levels of total N-nitroso compounds (NOC), genotoxic activity (both before and after nitrosation), degree of bacterial colonization in Gastric Juice and degree of severity or absence of precancerous lesions of the stomach. The mean level of constitutive total NOC in Gastric Juice was similar in the different groups of patients, but it was higher in acidic Gastric Juice (n = 30) than in Gastric Juice at pH greater than 4.5 (n = 12). Acid-catalysed nitrosation of Gastric Juice in vitro increased the concentration of total NOC by up to several thousand fold, to a maximum of 1330 mumol/l. Genotoxicity, expressed as SOS-inducing potency per 100 microliters of Gastric Juice was measurable in only 20% of Gastric Juice samples tested. After acid-catalysed nitrosation, however, all samples showed genotoxic activity, the mean SOS-inducing potency being four to seven times greater than the corresponding constitutive value. There was no association between the mean SOS-inducing potency of Gastric Juice and the severity of precancerous lesions. The mean SOS-inducing potency of neutral or basic Gastric Juice was slightly greater than that of acidic samples. In a kinetic study on N-nitrosation of Gastric Juice in vitro, a mixture of amino and amido substrates was nitrosated; both qualitative and quantitative individual differences in nitrosatable substrates in Gastric Juice were seen. Fractionation of acidic, neutral and basic nitrosated Gastric Juice samples revealed a preponderance of nonvolatile, unknown NOC with varying polarities. The results of our study suggest that only pH determines the nature and level of precursors of NOC and of nitrosation-dependent genotoxins in Gastric Juice.
A T R Axon - One of the best experts on this subject based on the ideXlab platform.
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acute helicobacter pylori infection clinical features local and systemic immune response Gastric mucosal histology and Gastric Juice ascorbic acid concentrations
Gut, 1991Co-Authors: G M Sobala, C. J. Schorah, M F Dixon, J E Crabtree, J D Taylor, B J Rathbone, R V Heatley, A T R AxonAbstract:The symptomatology of a case of acute infection with Helicobacter pylori is described, together with the accompanying changes in Gastric mucosal histology, local and systemic humoral immune response, and Gastric ascorbic acid concentration. The patient was an endoscopist, previously negative for the carbon-14 urea breath test, who had a week of epiGastric pain and then became asymptomatic. H pylori was detected by culture of antral biopsy specimens and was still present after 74 days. Five days after infection the histological findings showed acute neutrophilic gastritis; by day 74 changes of chronic gastritis were evident. The patient seroconverted by IgG enzyme linked immunosorbent assay by day 74, but a mucosal IgM and IgA response was evident as early as day 14. Infection was accompanied by a transient hypochlorhydria but a sustained fall in Gastric Juice ascorbic acid concentration.
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levels of nitrite nitrate n nitroso compounds ascorbic acid and total bile acids in Gastric Juice of patients with and without precancerous conditions of the stomach
Carcinogenesis, 1991Co-Authors: G M Sobala, C. J. Schorah, Marion Sanderson, M F Dixon, B Pignatelli, H Bartsch, S Shires, R F G King, A T R AxonAbstract:To determine the relevance of Gastric Juice factors to Gastric carcinogenesis, 56 patients with unoperated stomachs undergoing endoscopy for dyspepsia had Gastric Juice aspirated and analysed for pH, ascorbic acid, total bile acids, nitrite, nitrate and total nitroso compounds (NOCs). Plasma was obtained for vitamin C estimation. Antral and body biopsies were assessed for gastritis, Helicobacter pylori, atrophy and intestinal metaplasia (IM). Patients with chronic atrophic gastritis (n = 17) had lower Gastric Juice ascorbic acid concentrations (P less than 0.001), higher pH (P less than 0.05) and higher incidence of H. pylori infection (P less than 0.001) than normal subjects (n = 12). Patients with reflux gastritis (n = 9) had higher total bile acids (P less than 0.01). Patients with chronic gastritis and IM (n = 11) had higher Gastric Juice pH (P less than 0.01) and total bile acid concentrations (P less than 0.05), and lower Gastric ascorbic acid concentrations (P less than 0.01) than those with chronic gastritis and no IM (n = 24). In chronic gastritis, high nitrite concentrations were associated with high pH (P less than 0.01). However, there were no significant differences in plasma vitamin C or Gastric nitrite, nitrate or total NOC concentrations in relation to Gastric histology. We conclude that the premalignant condition IM is associated with H. pylori infection, low Gastric ascorbic acid levels and elevated total bile acids, but not to elevation in nitrite or total NOCs in fasting Gastric Juice.
G M Sobala - One of the best experts on this subject based on the ideXlab platform.
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acute helicobacter pylori infection clinical features local and systemic immune response Gastric mucosal histology and Gastric Juice ascorbic acid concentrations
Gut, 1991Co-Authors: G M Sobala, C. J. Schorah, M F Dixon, J E Crabtree, J D Taylor, B J Rathbone, R V Heatley, A T R AxonAbstract:The symptomatology of a case of acute infection with Helicobacter pylori is described, together with the accompanying changes in Gastric mucosal histology, local and systemic humoral immune response, and Gastric ascorbic acid concentration. The patient was an endoscopist, previously negative for the carbon-14 urea breath test, who had a week of epiGastric pain and then became asymptomatic. H pylori was detected by culture of antral biopsy specimens and was still present after 74 days. Five days after infection the histological findings showed acute neutrophilic gastritis; by day 74 changes of chronic gastritis were evident. The patient seroconverted by IgG enzyme linked immunosorbent assay by day 74, but a mucosal IgM and IgA response was evident as early as day 14. Infection was accompanied by a transient hypochlorhydria but a sustained fall in Gastric Juice ascorbic acid concentration.
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levels of nitrite nitrate n nitroso compounds ascorbic acid and total bile acids in Gastric Juice of patients with and without precancerous conditions of the stomach
Carcinogenesis, 1991Co-Authors: G M Sobala, C. J. Schorah, Marion Sanderson, M F Dixon, B Pignatelli, H Bartsch, S Shires, R F G King, A T R AxonAbstract:To determine the relevance of Gastric Juice factors to Gastric carcinogenesis, 56 patients with unoperated stomachs undergoing endoscopy for dyspepsia had Gastric Juice aspirated and analysed for pH, ascorbic acid, total bile acids, nitrite, nitrate and total nitroso compounds (NOCs). Plasma was obtained for vitamin C estimation. Antral and body biopsies were assessed for gastritis, Helicobacter pylori, atrophy and intestinal metaplasia (IM). Patients with chronic atrophic gastritis (n = 17) had lower Gastric Juice ascorbic acid concentrations (P less than 0.001), higher pH (P less than 0.05) and higher incidence of H. pylori infection (P less than 0.001) than normal subjects (n = 12). Patients with reflux gastritis (n = 9) had higher total bile acids (P less than 0.01). Patients with chronic gastritis and IM (n = 11) had higher Gastric Juice pH (P less than 0.01) and total bile acid concentrations (P less than 0.05), and lower Gastric ascorbic acid concentrations (P less than 0.01) than those with chronic gastritis and no IM (n = 24). In chronic gastritis, high nitrite concentrations were associated with high pH (P less than 0.01). However, there were no significant differences in plasma vitamin C or Gastric nitrite, nitrate or total NOC concentrations in relation to Gastric histology. We conclude that the premalignant condition IM is associated with H. pylori infection, low Gastric ascorbic acid levels and elevated total bile acids, but not to elevation in nitrite or total NOCs in fasting Gastric Juice.
Marko Duvnjak - One of the best experts on this subject based on the ideXlab platform.
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a new Gastric Juice peptide bpc an overview of stomach stress organoprotection hypothesis and bpc befitial effects
Book of abstracts of the 3th Congress of clinical and experimental gastroenterologist, 1993Co-Authors: Predrag Sikiric, Marijan Petek, Sven Seiwerth, Grabarevic željko Rotkvic Ivo, Branko Turkovic, Vjekoslav Jagic, Boris Mildner, Marko Duvnjak, Nada Lang, žarko DanilovicAbstract:The possibility that the stomach affected by general stress pathology initiates a conteracting response has not been considered in the stress theory until recently. In this, the stomach as the most sensitive part of gastrointestinal tract, the largest neuroendocrine organ in the body, has been suggested to be a crutial point, from where a full stress response against all noxius stress pathology could be purposefully initiated, mediated and organized. The end result would be a strong protection of all organs invaded by "stress". Consistent with this assumption, this coping response is best explained in terms of "organoprotection" and endogenous organoprotectors (e.g. prostaglandins, somatostatin, dopamine) are proposed as mediators. Such an endogenous counteraction could even be afforded by their suitable application. According to this concept, a new Gastric Juice peptide, M.W. 40, 000, named BPC, was recently isolated. In this, a 15 amino acid fragment (BPC 157) tought to be essential for this activity was fully characterized and effectively investigated. As it had previously been demonstrated for many organoprotective agents using different models of various tissue lesions, despite the poorly understood final mechanism, practically all organ systems appear to be included into BPC beneficial activity. Relative to the reference standards, these effects have been achieved in many species using very low dosages (mostly ug and ng/kg range) after intraperitoneal, intraGastrical as well as intramucosal (local) application. The effect was obvious already after one application. A long lasting activity was also demonstrated. Likewise, it was highly efficacious when applied in many experiments simultaneously with noxious agent or in the already established damage conditions, as well as chronically during a prolonged period. Therefore, it seems that BPC treatment does not share any of the so far known limitations for "conventional organoprotectors". No influence on different basal parameters and no toxicity were observed. Thus, whether these findings would provide a purposeful breakthrough into the stress thepry and whether BPC, as a likely endogenous free radical scavenger and organoprotection mediator, would be a useful prototype of a new class of drugs, organoprotective agents, remains to be seen.
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a new Gastric Juice peptide bpc an overview of the stomach stress organoprotection hypothesis and beneficial effects of bpc
Journal of Physiology-paris, 1993Co-Authors: Predrag Sikiric, Marijan Petek, Sven Seiwerth, Branko Turkovic, Vjekoslav Jagic, Boris Mildner, Rudolf Rucman, Zeljko Grabarevic, Ivo Rotkvic, Marko DuvnjakAbstract:The possibility that the stomach, affected by general stress, might initiate a counter-response has not until recently been considered in theories of stress. We suggest that the stomach, as the most sensitive part of the gastrointestinal tract and the largest neuroendocrine organ in the body, is crucial for the initiation of a full stress response against all noxious stress pathology. The end result would be a strong protection of all organs invaded by 'stress'. Consistent with this assumption, this coping response is best explained in terms of 'organoprotection'. Endogenous organoprotectors (eg prostaglandins, somatostatin, dopamine) are proposed as mediators. Such an endogenous counteraction could even be afforded by their suitable application. A new Gastric Juice peptide, M(r) 40,000, named BPC, was recently isolated. Herein, a 15 amino acid fragment (BPC 157), thought to be essential for its activity, has been fully characterized and investigated. As has been demonstrated for many organoprotective agents using different models of various tissue lesions, despite the poorly understood final mechanism, practically all organ systems appear to benefit from BPC activity. These effects have been achieved in many species using very low dosages (mostly microgram and ng/kg range) after ip, ig, and intramucosal (local) application. The effect was apparent already after one application. Long lasting activity was also demonstrated. BPC was highly effective when applied simultaneously with noxious agents or in already pathological, as well as chronical, conditions. Therefore, it seems that BPC treatment does not share any of the so far known limitations for 'conventional organoprotectors'. No influence on different basal parameters and no toxicity were observed. These findings provide a breakthrough in stress theory. BPC, as a possible endogenous free radical scavenger and organoprotection mediator, could be a useful prototype of a new class of drugs, organoprotective agents.
C. J. Schorah - One of the best experts on this subject based on the ideXlab platform.
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acute helicobacter pylori infection clinical features local and systemic immune response Gastric mucosal histology and Gastric Juice ascorbic acid concentrations
Gut, 1991Co-Authors: G M Sobala, C. J. Schorah, M F Dixon, J E Crabtree, J D Taylor, B J Rathbone, R V Heatley, A T R AxonAbstract:The symptomatology of a case of acute infection with Helicobacter pylori is described, together with the accompanying changes in Gastric mucosal histology, local and systemic humoral immune response, and Gastric ascorbic acid concentration. The patient was an endoscopist, previously negative for the carbon-14 urea breath test, who had a week of epiGastric pain and then became asymptomatic. H pylori was detected by culture of antral biopsy specimens and was still present after 74 days. Five days after infection the histological findings showed acute neutrophilic gastritis; by day 74 changes of chronic gastritis were evident. The patient seroconverted by IgG enzyme linked immunosorbent assay by day 74, but a mucosal IgM and IgA response was evident as early as day 14. Infection was accompanied by a transient hypochlorhydria but a sustained fall in Gastric Juice ascorbic acid concentration.
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levels of nitrite nitrate n nitroso compounds ascorbic acid and total bile acids in Gastric Juice of patients with and without precancerous conditions of the stomach
Carcinogenesis, 1991Co-Authors: G M Sobala, C. J. Schorah, Marion Sanderson, M F Dixon, B Pignatelli, H Bartsch, S Shires, R F G King, A T R AxonAbstract:To determine the relevance of Gastric Juice factors to Gastric carcinogenesis, 56 patients with unoperated stomachs undergoing endoscopy for dyspepsia had Gastric Juice aspirated and analysed for pH, ascorbic acid, total bile acids, nitrite, nitrate and total nitroso compounds (NOCs). Plasma was obtained for vitamin C estimation. Antral and body biopsies were assessed for gastritis, Helicobacter pylori, atrophy and intestinal metaplasia (IM). Patients with chronic atrophic gastritis (n = 17) had lower Gastric Juice ascorbic acid concentrations (P less than 0.001), higher pH (P less than 0.05) and higher incidence of H. pylori infection (P less than 0.001) than normal subjects (n = 12). Patients with reflux gastritis (n = 9) had higher total bile acids (P less than 0.01). Patients with chronic gastritis and IM (n = 11) had higher Gastric Juice pH (P less than 0.01) and total bile acid concentrations (P less than 0.05), and lower Gastric ascorbic acid concentrations (P less than 0.01) than those with chronic gastritis and no IM (n = 24). In chronic gastritis, high nitrite concentrations were associated with high pH (P less than 0.01). However, there were no significant differences in plasma vitamin C or Gastric nitrite, nitrate or total NOC concentrations in relation to Gastric histology. We conclude that the premalignant condition IM is associated with H. pylori infection, low Gastric ascorbic acid levels and elevated total bile acids, but not to elevation in nitrite or total NOCs in fasting Gastric Juice.