Effect of bile on lysosomal stability in the mucosa of the canine gastric antrum

The bound and free acid hydrolases from bile and bile- then acid-treated canine antral mucosa were compared with control tissue, using explants held in a series of Lucite chambers. Normal levels of activity of bound mucosal enzymes decreased as a result of bile acid insult, but "free" activity in the cytosol increased markedly. Organelle membrane stability was "tested" by submitting isolated particulate matter containing lysosomes, to hypoosmotic shock and to mechanical stress. Release of cathepsin D, only, was observed after bile treatment in vivo. Bile, followed by acid, however, damaged organelle integrity causing release or "leakage" of seven acid hydrolases.     

Isolation and identification of Helicobacter spp. from canine and feline gastric mucosa

It is known that virtually all healthy adult dogs and cats harbor spiral helicobacters in their gastric mucosa. Three species, Helicobacter felis, Helicobacter bizzozeronii, and Helicobacter salomonis have been isolated in vitro from the gastric mucosa of these animals. The aims of this study were to evaluate the efficacy of an isolation method for canine and feline gastric helicobacters that has been developed at the University of Helsinki; to estimate the prevalence and distribution of these taxa in the samples examined; and to assess the efficacy and validity of an extensive set of standardized conventional phenotypic tests, whole-cell protein profiling, and ultrastructural analysis in identifying the different species isolated from canine and feline gastric mucosa. We cultured 95 and 22 gastric mucosal biopsies from dogs and cats, respectively. Twenty-one H. bizzozeronii strains, 8 H. felis strains, 8 H. salomonis strains, 3 mixed cultures, 2 "Flexispira rappini"-like organisms, and 3 as yet uncharacterized strains were isolated from the dogs, and 3 H. felis strains were isolated from the cats. The methods used here yielded Helicobacter isolation rates of 51% from dogs and 13.6% from cats, which exceed those reported previously. The main difficulties were primary isolation, mixed cultures, and identification to the species level. In the species identification, a detailed morphological examination was found to yield important phenotypic characteristics. A large panel of biochemical and tolerance tests did not clearly differentiate the closely related species H. bizzozeronii, H. felis, and H. salomonis. Highly standardized whole-cell protein profiling was shown to be an excellent method for species identification. Improvements in culture conditions for these bacteria are still needed, especially for cats. A genetic identification method not requiring culture is needed for future studies of these very fastidious helicobacters, as the clinical significance and ecology of these species within the gastric mucosa of the domestic carnivores remain largely unknown.     

Acute erosions of the gastric mucosa in burned rats: effect of sucralfate

Endometriosis remains a significant cause of pain and ill health for women and is a significant factor in reducing quality of life for women. The ability of desquamated endometrium to attach and implant within the peritoneal cavity is dependent upon its ability to establish and maintain an adequate blood supply. New vascularization is therefore a key part in the progression of endometriosis. Increased angiogenic activity is present in the peritoneal cavity of patients who suffer from the disease and more recently the potent angiogenic growth factor VEGF has been shown to be increased in the peritoneal fluid in patients with this disease. Whilst the desquamated endometrium itself under the influence of hypoxia further to retrograde menstruation is a likely rich source of VEGF, activated peritoneal fluid macrophages and infiltrating macrophages are also a rich source of this angiogenic growth factor. Surprisingly, steroidal regulation of macrophage expression of VEGF also appears to be a feature of this disease.     

Direct cytotoxic and cytoprotective effects of some drugs on isolated cells of gastric mucosa from rats

Toxic effect of ethanol and indomethacin, and the cytoprotective effect of prostacyclin were studied. In absence of other aggressive factors, the indomethacin was found to be non-toxic, but it could enhance the necrotizing effect of ethanol, this effect could be counteracted by prostacyclin preincubation. These observations suggest that there is an endogenous prostaglandin system in rat gastric mucosal cells that may protect against the toxic effect of indomethacin; administered prostacyclin may have a cytoprotective effect when this endogenous prostaglandin system's protective function does not more function. Gastric mucosal cytoprotection may include cellular level processes, which are able to operate without the existence of tissue integrity.     

Attenuation by genistein of sodium-chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats

The effects of prolonged administration of genistein, a tyrosine-kinase inhibitor, on sodium-chloride-enhanced induction of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labeling and apoptotic indices and vessel counts in the gastric mucosa and gastric cancers, were investigated in Wistar rats. After 25 weeks of the carcinogen treatment, rats were fed chow pellets containing 10% sodium chloride and were given s.c. injections of genistein at dosages of 15 mg/kg or 30 mg/kg body weight every other day. In week 52, the incidence of gastric cancers was significantly greater in rats fed sodium chloride than in untreated control rats. Prolonged administration of genistein at a dosage of 30 mg/kg, but not 15 mg/kg, body weight significantly reduced the incidence of gastric cancers, which was increased by oral treatment with sodium chloride. Genistein at the higher dose significantly decreased the labeling index and vessel counts of the antral mucosa and the gastric cancers (which were increased by treatment with sodium chloride) and significantly increased the apoptotic index of the antral mucosa and the cancers (which was lowered by the treatment with sodium chloride). These findings suggest that genistein attenuates gastric carcinogenesis promoted by sodium chloride, by inducing increased apoptosis and lower cell proliferation and angiogenesis of antral mucosa and gastric cancers.     

Effect of histamine on canine gastric mucosal adenylate cyclase

The effects of histamine, Nalpha-dimethylhistamine, 4,5-methylhistamine, Ntau-methylhistamine, pentagastrin, carbachol, and NaF on the adenylate cyclase activity from canine gastric mucosa were investigated in cell-free preparations. In gastric fundic mucosa, histamine (10(-4) M), Nalpha-dimethylhistamine (10(-4) M), 4,5-methylhistamine (10(-4 M), and NaF (10)-2) M) significantly (P less than 0.001) increased adenylate cyclase activity (means+/-SE) by 44.7+/-6.6, 49.4+/-6.7, 34.0+/-6.4, and 572.0+/-100%, respectively, above basal activity. The effect of histamine and Na-dimethyl histamine was dose-dependent. In contrast, other tested agents failed to stimulate the formation of cyclic AMP in gastric fundic mucosa. Metiamide (10(-4) M) blocked the stimulation of fundic mucosa adenylate cyclase by histamine and Nalpha-dimethylhistamine, without significantly altering basal and NaF-induced adenylate cyclase activity. Histamine, however, did not stimulate the adenylate cyclase activity from the gastric antral mucosa. The findings support the proposal that the canine gastric acid response to histamine may be mediated by cyclic AMP formed in response to stimulation of histamine H2-receptors.     

Detection of genotoxic effects in human gastric and nasal mucosa cells isolated from biopsy samples

To assess genotoxic burdens from chemicals, it is necessary to relate observations in experimental animals to humans. The success of this extrapolation would be increased by including data on chemical activities in human tissues. Therefore, we have developed techniques to assess DNA damage in human gastric and nasal mucosa (GM, NM) cells. Biopsy samples were obtained during gastroscopy from macroscopically healthy tissue of the stomach or from healthy nasal epithelia during surgery. The specimens were incubated for 30-45 min at 37 degrees C with a digestive solution. We obtained 1.5-8 x 10(6) GM cells and 5-10 x 10(5) NM cells per donor, both with viabilities of 80-95%. The cells were incubated in vitro for 1 hr at 37 degrees C with the test compounds added in their appropriate solvents. In GM cells, we studied N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), sodium dichromate (Na2Cr2O7), nickel sulphate (NiSO4), cadmium sulphate (CdSO4), and lindane. In NM cells, lindane was investigated. Each compound was assessed for DNA damaging activity in cells of at least three different human donor samples using the microgel single cell assay. Similar studies were performed with GM and NM cells obtained from Sprague-Dawley rats. We have found human GM cells to be more sensitive to the genotoxic activity of MNNG than rat GM cells (low effective concentration [LEC] = 0.16 and 0.625 micrograms/ml for human and rat, respectively). Human cells were also more sensitive to the cytotoxic/genotoxic activity of NiSO4 (LEC = 5 and 19 mumoles/ml for human and rat, respectively). CdSO4 was genotoxic in human GM cells (LEC = 0.03-0.125 mumoles/ml), whereas no dose-related genotoxicity was observed in rat GM at concentrations up to 0.5 mumoles/ml. In contrast, approximately equal responses regarding genotoxicity and cytotoxicity were observed in rat and human GM for Na2Cr2O7 (0.25-1 mumoles/ml). Lindane, however, was genotoxic in three out of four rat GM but not in human GM cells (0.5-1 mumoles/ml), whereas it was active in both rat and human NM cells. Together with other recently published in vivo findings, our results with lindane can be interpreted according to a parallelogram approach. In view of possible human exposure situations and the sensitivities of the two target tissues from both species, the data imply that lindane will pose a health risk to humans by inhalation but not by ingestion.     

Histamine metabolism of the guinea-pig gastric mucosa

(1) Preparative dodecyl sulfate gel electrophoresis of human erythrocyte membrane proteins has been used to isolate dodecylsulfate band 3 containing the M,N-glycoprotein and the major "intrinsic" membrane protein (Fairbanks, G., Steck, T.L. and Wallach, D.F.H. (1971) Biochemistry 10, 2606-2617; Bretscher, M.S. (1971) J. Mol. Biol. 59,351-357; Bretscher, M.S. (1971) Nat. New Biol. 231, 229-232 and Marchesi, V.T. and Andrews, E.P. (1972) Science 174, 1247-1248). Subsequent isoelectric focusing in polyacrylamide gels containing Triton X-100 separates these two entities and allows their simultaneous purification. (2) The proteins thus obtained retain their antigenic properties. They are pure according to electrophoretic and immunoelectrophoretic criteria. However, crossed immunoelectrophoresis yields evidence for molecular microheterogeneity of the major "intrinsic" protein. (3) Analyses utilizing crossed immunoelectrophoresis with antibodies absorbed with intact erythrocytes show that the major "intrinsic" protein possesses antigenic determinants on both membrane surfaces and therefore spans the erythrocyte membrane. All determinants of the M,N-glycoprotein detectable with our antibodies were found solely on the exterior membrane surface. (4) Neither the major "intrinsic" membrane protein nor the major M,N-glycoprotein bound significantly to concanavalin A in crossed immunoaffinoelectrophoresis.     

Oragnotypic culture of the rabbit gastric mucosa

A case is reported in which obstetric management resulted in 52 minutes elapsing between the induction of anaesthesia and delivery by Caesarean section. The mother was induced and maintained on Althesin and minimal methoxyflurane throughout this period without detriment to the neonate.     

Hemorrhage from acute ulcers of gastric mucosa

The work analyses the results of management of 429 patients with acute erosive-ulcerative gastritis in a specialized department. The most frequent causes are duodeno- or enterogastric reflux (24.7%), abuse of alcohol (23.6%), medication with mucosa irritating drugs (22.5%). Particular attention is drawn to gastritis of a reflux character which is dangerous not only because of recurrent bleeding but also because of the possibility of structural reorganization of the gastric mucosa leading to development of carcinoma. Attention is focused on the errors in nonoperative and surgical treatment and the need for taking into consideration the etiopathogenesis of acute ulcers. In ulcerations of a reflux character it is recommended that after bleeding is arrested by conservative measures, an operation for removal of the reflux is performed in a planned order. In the other cases, in emergency situations, deep stitching of the erosions with vagotomy and pyloroplasty must be resorted to. The author considers acute ulcers of the stomach to be a precancer marker and believes it necessary to register all patients for regular medical control.     

Effect of gastric secretion on penetration of N-3H-methyl-N-nitro-N-nitrosoguanidine into gastric mucosa of rats

Clinical conditions with low gastric acid secretion have been associated with increased risk of gastric cancer. There has also been concern about gastric acid inhibition and N-nitroso compound formation in the stomach. This study investigates the effect of gastric acid secretion on the penetration of N-3H-methyl-N-nitro-N-nitrosoguanidine, an N-nitroso compound and gastric carcinogen, into the gastric mucosa of rats. Gastric acid secretion was stimulated by pentagastrin (40 microg/kg/hr) and inhibited by omeprazole (40 micromol/kg) before mucosal exposure to N-3H-methyl-N-nitro-N-nitrosoguanidine. Penetration of the carcinogen was evaluated by light microscopic identification of cells in the S-phase labeled with N-3H-methyl-N-nitro-N-nitrosoguanidine. This population of double-labeled cells is considered at risk from N-methyl-N-nitro-N-nitrosoguanidine-induced carcinogenesis. The percentage of double-labeled cells was significantly higher in antrum than in corpus mucosa (P < 0.0001). Stimulation or inhibition of gastric acid secretion did not affect the penetration of N-3H-methyl-N-nitro-N-nitrosoguanidine in antrum or corpus mucosa. We conclude that modulation of gastric acid secretion does not affect the penetration of the carcinogen into the gastric mucosa nor does it explain the different penetration of the carcinogen into corpus and antrum mucosa.     

Effect of histamine on technetium-99m excretion by gastric mucosa

The ability of histamine to increase excretion of 99mtechnetium by gastric mucosa was investigated in dogs with Heidenhain pouches and denervated antral pouches. Histamine increased Heidenhain pouch 99mtechnetium output in a dose-related manner, and 99mtechnetium output was related linearly to acid output. Antral pouch 99mtechnetium output was unchanged by increasing doses of histamine. The study suggests that concomitant use of histamine may improve the accuracy of 99mtechnetium scanning in the clinical diagnosis of conditions caused by ectopic gastric mucosa.     

Effect of selective and non-selective muscarinic blockade on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats

The effects of baclofen, a gamma-amino-n-butyric acid receptor B agonist, on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine and how its effects are influenced by selective (M1) and non-selective (M1 and M2) pharmacological blockade of muscarinic receptors were investigated in inbred Wistar rats. Rats were given s.c. injections of 8 mg/kg body wt baclofen with and without 0.5 mg/kg body wt atropine (non-selective M1 and M2 muscarinic receptor antagonist) or 1.0 mg/kg body wt pirenzepine (selective M1 muscarinic receptor antagonist) every other day after a 25 week carcinogen treatment. At week 52 baclofen significantly decreased the incidence of gastric cancers. Concomitant treatment with atropine significantly attenuated the inhibition by baclofen of gastric carcinogenesis, but combined use with pirenzepine had no significant effect on the inhibition by baclofen of gastric carcinogenesis. Baclofen also significantly decreased the labeling index of the antral mucosa. Baclofen plus atropine attenuated the decrease in the labeling index of the antral mucosa due to baclofen, but baclofen plus pirenzepine had no significant effect on the labeling index. These results suggest that the inhibition of gastric carcinogenesis by baclofen is mediated through muscarinic receptors and M2 receptors, but not M1 receptors, are involved in this response.     

Cold exposure enhances nitroxidergic nerve-mediated vasodilatation in canine nasal mucosa

An intercomparison using two popular survey meters was arranged to assess the ability of participants to test surface contamination monitors in compliance with the requirements of the Ionising Radiations Regulations 1985. The instruments were circulated and the data returned were compared with the NRPB values. The major inconsistencies were caused by differences in the interpretation of what constitutes 1 Bq of 90Sr+ 90Y and in the conversion of the emission rate from (129)I plaques into a value of equivalent (125)I activity.     

Charcoal deposits in the esophageal and gastric mucosa

We report the case of a 75-yr-old woman referred for gastrointestinal endoscopy to investigate severe iron deficiency anemia. Black linear lesions were observed in the distal esophagus and stomach. Biopsies revealed aggregates of coarse black foreign material, which was later identified as charcoal. The patient's previous medical history included an antidepressant overdose 5 yr before the current admission. The patient had a gastric lavage, using a large bore orogastric tube, followed by the administration of activated charcoal. The patient had no other history of charcoal ingestion. We propose that the charcoal became entrapped in mucosal tears caused by the traumatic intubation 5 yr previously, causing the incidental mucosal tattooing seen at endoscopy.     

Protective effect of "wei tong ling" on gastric mucosa and influence on quality of gastric ulcer healing

The acute gastric ulcer rat models were induced by dehydrated alcohol, 0.6 N hydrochloric acid and 0.6 N sodium hydroxide, and the chronic gastric ulcer rat models were established by means of acetic acid, the protective effect of Chinese medicine "Wei Tong Ling" (WTL) on gastric mucous membrane was studied. Using histochemical mucin stain, AgNOR stain and immunohistochemical technique the regenerated mucosa of healed gastric ulcer induced by acetic acid in rats was observed quantitatively. They were compared with that of WTL. The results showed that the regenerated mucosa of healed gastric ulcer might be the morphological basis for the recurrence of gastric ulcer and be associated with canceration. WTL could not only accelerate the healing of ulcer but also raise the quality of gastric ulcerous healing which was beneficial for the prevention of ulcer recurrence and canceration. The protective effect of WTL on gastric mucosa was confirmed by various assays.