Biomedical subjects

A Slomiany

Publications and source records attributed to A Slomiany.

At least 91 records · Page 5Linked to original sources

PubMed1995

Sucralfate affects the susceptibility of Helicobacter pylori to antimicrobial agents.

BACKGROUND: Infection with Helicobacter pylori is regarded as a primary factor in the pathogenesis of gastric disease, and successful therapies now include a combination of antiulcer drugs with antimicrobial agents. In this study, we investigated the effect of sucralfate and omeprazole on the vitro anti-H. pylori activity of metronidazole, erythromycin, tetracycline, and amoxycillin. METHODS: Aliquots of H. pylori culture were transferred to the wells containing different concentrations of antibiotics either alone or in the presence of various doses of sucralfate and omeprazole and incubated for 3 days for MIC evaluation. RESULTS: The assays in the absence of sucralfate and omeprazole gave MIC value 0.10 mg/l for erythromycin, 0.12 mg/l for amoxycillin, 0.15 mg/l for tetracycline, and 14 mg/l for metronidazole. Inclusion of sucralfate evoked a 28% enhancement in the MIC of metronidazole, 2.5-fold in tetracycline, 8-fold in erythromycin, and 2-fold in amoxycillin. In the presence of omeprazole, the MIC of erythromycin improved 4-fold, tetracycline 1.6-fold, and amoxycillin, 2-fold. CONCLUSIONS: The results demonstrate that sucralfate enhances the anti-H. pylori activity of antibiotics and that this effect is comparable to that of omeprazole.

Amoxicillin↗

PubMed1995

Inhibition of Helicobacter pylori urease activity by ebrotidine.

Helicobacter pylori is considered a primary factor in the pathogenesis of gastric disease, and the successful mucosal colonization is linked to its urease activity. In this study, we assessed the effect of antiulcer agent, ebrotidine, on the in vitro activity of H. pylori urease. The results of assays showed a dose-dependent inhibition of the urease activity. A maximum inhibition (77%) in H. pylori urease activity occurred at 2.1 microM ebrotidine. A known H2-blocker, ranitidine, in a parallel experiment gave a maximal inhibition of 73% at a considerably higher concentration (6.4 microM). The results demonstrate that ebrotidine with its combined acid suppressant and anti-H. pylori activities offers an excellent choice in the treatment of H. pylori associated gastric disease.

Anti-Ulcer Agents↗

PubMed1995

Susceptibility of Helicobacter pylori to antimicrobial agents: effect of ebrotidine and ranitidine.

Convincing evidence now exists that infection with H. pylori is a primary factor in the pathogenesis of gastric disease, and new therapy regimens include a combination of H2 blockers with antimicrobial agents. In this study, was assessed the effect of ebrotidine and ranitidine on the in vitro anti-H. pylori activity of amoxicillin, erythromycin, tetracycline, and metronidazole. The assays of the antiulcer drugs alone gave MIC value of 150 mg/L for ebrotidine and 1600 mg/L for ranitidine. Inclusion of ebrotidine in the antimicrobial agent assays evoked at its optimal concentration of 75 mg/L a 28% enhancement in the MIC of metronidazole, 2.5-fold enhancement in the MIC of erythromycin, 2-fold in amoxicillin and 1.7-fold in tetracycline, while ranitidine caused noticeable changes in the MIC values of the tested antimicrobial agents only a the dose of 1600 mg/L. The results demonstrate that ebrotidine enhances anti-H. pylori activity of antimicrobial agents at doses well below that of ranitidine.

Anti-Bacterial Agents↗

PubMed1994

Intracellular processes associated with vesicular transport from endoplasmic reticulum to Golgi and exocytosis: ethanol-induced changes in membrane biogenesis.

Membrane biogenesis, expressed in endoplasmic reticulum (ER) by formation of transport vesicles, was studied in the liver of ethanol-fed and pair-fed rats. In ER of ethanol-fed animals, the endogenous synthesis of phosphatidylcholine (PC) and its contribution to ER transport vesicles were reduced by 50%, as compared to that in pair-fed controls. Reduction of PC synthesis and of its presence in ER-transport vesicles was also observed in pair-fed controls when the native cytosol was replaced with that from ethanol-fed animals. In contrast, preincubation of ER membranes from ethanol-fed animals with cytosol from controls led to the stimulation of PC synthesis in ER and its contribution to ER-transport vesicles. Analysis of water soluble metabolites of [methyl-14C]choline phosphate revealed the accumulation of CDP-choline precursor in samples derived from ethanol-fed rats. Concomitantly, the endogenous synthesis of phosphatidylinositol (PI) in the ER of ethanol-fed animals was stimulated up to 400-500%, but declined when the cytosol from ethanol-fed rats was replaced with that from the controls. The restoration of PC synthesis, the normalization of PI synthase activity, and, similar to control, the contribution of PC to ER-transport vesicles in ethanol-fed animals was achieved when ER membranes were preincubated with diglycerides or the cytosol was treated with ethylene glycol bis (beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA). Conversely, addition of CaCl2-EGTA buffer containing 3 microM free Ca2+ to control samples, led to a reduction in PC synthesis. The studies on the effect of free Ca2+ on PI synthase and phosphatidic acid (PA) phosphatase activity established that in the presence of 1-3 microM free Ca2+, PI synthase activity remained constant, whereas that of PA phosphatase was reduced by 40% at 1 microM Ca2+, and no activity was detected when free Ca2+ was adjusted to 3 microM. The results suggest that modified membrane biogenesis in the liver of ethanol-fed rats is connected to the elevated free Ca2+ in the cytosol, which appears to regulate phosphatase activity. Accumulation of CDP-choline, decreased activity of PA phosphatase, and increased contribution of PI lipids to ER-transport vesicle membrane suggest that in ethanol-fed animals diglycerides are depleted and PA is utilized in a CDP-diacylglycerol pathway, thus leading to the generation of a different group of phospholipids and consequently modified ER-transport vesicle membrane.

Alcohol Drinking↗

PubMed1994

Biosynthesis of mucin derived from a 60-kDa precursor protein in the human stomach.

We studied the biosynthesis of mucin in the human stomach using an anti-mucin core peptide monoclonal antibody, 3G12. Human stomach mucosa was labeled with [35S]methionine, and chased for 3 h. An approximately 60-kDa subunit of human gastric mucin precursor protein was detected in the intracellular product. Under nonreducing conditions, dimer, trimer, and tetramer mucin precursor protein (120, 180, 240 kDa) were detected. Treatment with tunicamycin or endo-beta-N-acetylglucosaminidase H had no effect on the 60-kDa subunit and its oligomers. Extracellular products contained only the high molecular weight mucin, and the secretion was not affected by tunicamycin. By treatment with monensin or brefeldin A, the mature mucin was not secreted extracellularly. These findings suggested that a 60-kDa subunit of the mucin precursor protein was biosynthesized into mature mucin after oligomerization to tetramers, and that neither the oligomerization nor the intracellular transport of the mucin in the human stomach was associated with N-glycosylation.

Antibodies, Monoclonal↗

PubMed1994

Biochemical characterization of epidermal growth-factor receptor in Syrian hamster buccal pouch.

Binding of [125I]-epidermal growth factor (EGF) to the membrane of the adult hamster buccal pouch was specific and protein concentration dependent, and was significantly higher than that of rat buccal tissue (hamster versus rat; 12.1 +/- 0.9 versus 9.77 +/- 0.22 fmol/mg protein, mean +/- SD, n = 5, p < 0.01). The higher binding was due to a higher receptor number (Bmax). Western blot analysis using anti-EGF receptor antibody revealed four immunoreactive protein bands of 170, 150, 116 and 55 kDa in hamster buccal membrane preparations. In a separate experiment, the EGF concentration in the phosphate-buffered saline extract of the hamster submandibular gland was determined by radioimmunoassay; the level was significantly much lower (p < 0.01) than that of rat or mouse (hamster, rat, mouse; 24.2 +/- 2.6, 123 +/- 17, 5950 +/- 171 ng/g wet tissue; mean +/- SD, n = 3). The findings suggest that hamster buccal pouch is particularly well suited to the study of the biological functions of oral EGF receptor.

Animals↗

PubMed1994

Activation of arachidonoyl phospholipase A2 in prostaglandin-mediated action of sucralfate.

1. The mechanism of sucralfate-induced gastric mucosal prostaglandin generation was investigated using mucosal cells labeled with [14C]choline and [3H]arachidonic acid. 2. In comparison to the controls, the cells maintained in the presence of sucralfate showed a concentration dependent increase in lysophosphatidylcholine (LPC) synthesis and PGE2 generation. The maximal effect was attained at 25 microM sucralfate giving a 45.7% increase in LPC and 70% increase in PGE2. 3. Pretreatment with indomethacin prior to sucralfate, while causing inhibition in PGE2 generation, had no effect on LPC production and led to accumulation of free arachidonic acid. In the case of pretreatment with NDGA, the sucralfate caused increased LPC synthesis accompanied by enhanced PGE2 generation without free arachidonic acid accumulation. 4. The stimulatory effect of sucralfate on LPC synthesis and PGE2 generation was inhibited by phospholipase A2 inhibitors, mepacrine and BPB. The inhibitory effect was concentration dependent and attained maximum at 40 microM for BPB and 80 microM for mepacrine. 5. The results for the first time demonstrate that the enhancement in gastric mucosal prostaglandin generation by sucralfate results from the stimulation of mucosal phospholipase A2 for arachidonic acid release.

Animals↗

PubMed1994

Gastroprotective agents in mucosal defense against Helicobacter pylori.

1. Convincing evidence now exists that infection with H. pylori plays a major role in the pathogenesis of gastric disease. Having a niche bordering two major perimeters of mucosal defenses, the bacterium apparently exerts its detrimental effect on the mucus layer as well as the gastric epithelium. Therefore, gastroprotective agents capable of counteracting these detrimental effects of H. pylori are gaining importance in the treatment of gastric disease. 2. The colonization of gastric mucosa by H. pylori involves specific glycolipid receptors bearing acidic substituents, a process inhibited by gastric sulfomucins. Two antiulcer agents bearing sulfated sugar groups have been demonstrated to possess the ability to interfere with H. pylori colonization process. These are sucralfate and sulglycotide. The two agents are also potent inhibitors of H. pylori glycosulfatase activity directed against indigenous mucosal defenses. 3. A variety of extracellular enzymes such as proteases, lipases and phospholipases, elaborated by H. pylori cause the weakening of the integrity of gastric mucus coat and render the underlying epithelium vulnerable to noxious luminal contents. Among the most potent agents capable of countering the proteolytic activity of H. pylori are nitecapone, ebrotidine and sulglycotide, while ebrotidine and sulglycotide were found to be most effective inhibitors of H. pylori lipolytic activities. 4. The gastric epithelial integrity is compromized by the H. pylori cell-wall lipopolysaccharide untoward effect on the epithelial surface receptors. The interference of the lipopolysaccharide with the laminin receptor was found to be most efficiently countered by ebrotidine, sulglycotide and sucralfate, whereas sulglycotide is the most potent in the reversal of the inhibitory effect of the lipopolysaccharide on mucin receptor binding.

Animals↗

PubMed1994

Inhibition of gastric mucosal mucin receptor by Helicobacter pylori lipopolysaccharide: effect of sulglycotide.

1. A receptor for mucin was isolated from the solubilized gastric epithelial cell membrane by affinity chromatography on Sepharose-bound wheat germ agglutinin. 2. The receptor protein displayed a molecular weight of 97 kDa and exhibited specific affinity towards mucin-coated surfaces. The optimum for mucin binding occurred at 60-100 micrograms/ml, while the values for the receptor were 2.0-3.1 micrograms/ml. 3. The mucin binding to the receptor was susceptible to Helicobacter pylori lipopolysaccharide which caused maximum inhibition of 91% at 30 mu/ml. This inhibitory effect of the lipopolysaccharide was abolished by a gastroprotective agent, sulglycotide. 4. The effect of sulglycotide was dose dependent and at 50 micrograms/ml produced a 94% restoration in receptor-mucin binding. Furthermore, sulglycotide was also capable of enhancing (97%) the mucin binding to its receptor in the absence of the lipopolysaccharide. 5. The results demonstrate that H. pylori through its lipopolysaccharide interferes in the interaction of mucin with gastric epithelial surfaces and that a gastroprotective agent, sulglycotide, counteracts this effect, and hence is capable of preventing the loss of mucin coat continuity occurring with H. pylori infection.

Animals↗

PubMed1994

Effect of sofalcone on tyrosylprotein sulfotransferase.

1. Gastric mucus glycoproteins are actively involved in the maintenance of mucosal integrity and the impairment in their elaboration is often a prominent feature in gastric pathology. In this study, we investigated the effect of an antiulcer drug, sofalcone, on the activity of tyrosylprotein sulfotransferase enzyme involved in the secretion of proteins and glycoproteins in male 8 week old rats. 2. Using poly-Glu6, Ala3, Tyr1 (EAY) as sulfate acceptor, and 3'phosphoadenosine 5'-phosphosulfate (PAPS) as sulfate donor the optimum Golgi TPST activity was obtained at pH 6.8, in presence of 0.5% Triton X-100, 20 mM MnCl2, 50 mM NaF and 2 mM 5'-AMP. 3. Introduction of sofalcone to the reaction mixture led to the enhancement in TPST activity. The rate of stimulation was proportional to the drug concentration up to 30 micrograms, at which concentration, a 55% increase in TPST activity was attained. 4. The results attest further to the value of sofalcone as a potent mucosal strengthening agent, and suggest that the agent may promote mucin secretion via activation of tyrosine sulfation.

Animals↗

PubMed1994

Enhancement of gastric mucus phospholipid secretion by an antiulcer agent, ebrotidine.

1. Rat gastric mucosal cells, subjected to phospholipid labeling by incubating the cell suspension in DMEM with [3H]choline, were exposed to different concentrations (0-150 microM) of H2-receptor antagonists, ebrotidine and ranitidine, and the phospholipid secretory responses were evaluated. 2. In the absence of the drugs, the secretion of choline-containing phospholipids over a 1 hr period averaged 3.97% of the total cellular labeled phospholipids. Ebrotidine caused a dose-dependent increase in the rate of phospholipid secretion which was most pronounced at 1 hr and persisted for at least 2 hr. The maximal effect was attained at 120 microM ebrotidine giving a 36% increase in phospholipid secretion. 3. The phospholipid secretory response to ebrotidine was accompanied by an increase in gastric mucosal cell cAMP level which reached a maximum value of 2.1-fold over that of controls at 1 hr. Ranitidine, in contrast, neither evoked increase in cAMP level nor caused any stimulation in phospholipid secretion. 4. The results indicate that the gastroprotective properties of ebrotidine are associated with the ability of the drug to elicit a rapid stimulation in gastric mucus phospholipid secretion, and that ranitidine does not possess such property.

Animals↗

PubMed1994

Gastric mucosal laminin receptor expression with ulcer healing by ebrotidine.

1. The effect of antiulcer agent, ebrotidine, on the expression of gastric mucosal laminin receptor during ulcer healing was investigated. 2. Rats with acetic acid-induced chronic gastric ulcers were treated twice daily for 14 consecutive days either with ebrotidine at 100 mg/kg or placebo, and then at different stages of treatment used for the isolation and quantitation of gastric mucosal laminin receptor. 3. The binding assays revealed that the ulcer healing was accompanied by an increase in mucosal expression of laminin receptor. A 2.7-fold increase in the receptor expression occurred by 4th day following the development of ulcer and reached a maximum of 8.6-fold increase by the 14th day when the ulcer was essentially healed. 4. Treatment with ebrotidine caused accelerated ulcer healing (7 days), which was accompanied by a remarkable enhancement in the laminin receptor expression. A 2.5-fold increase in the receptor expression over that of controls occurred by the 4th day of ebrotidine treatment, and a 1.7-fold increase was still observed at the 14th day of treatment. 5. The results suggest that ebrotidine, by evoking enhanced mucosal cell laminin receptor expression, promotes reepithelization and, hence, hastens the ulcer healing.

Amino Acid Sequence↗

PubMed1994

Regulation of gastric mucosal calcium channel activity by an antiulcer agent, ebrotidine.

Ebrotidine is a new H2-receptor antagonist also known for its gastroprotective effect against ethanol-induced mucosal injury. In this study, we investigated the effect of ebrotidine on the activity of the gastric mucosal calcium channels. The channel complex was isolated from the solubilized gastric epithelial cell membranes by affinity chromatography on wheat germ agglutinin. The complex following labeling with [3H] PN200-110 was reconstituted into phosphatidylcholine vesicles which exhibited active 45Ca2+ uptake into intravesicular space and responded in a concentration-dependent manner to calcium channel activator, BAY K8644, as well as to calcium channel antagonist, PN200-100. The 45Ca2+ uptake was inhibited by ebrotidine which caused maximum inhibitory effect of 54.9% at 50 micrograms/ml. The gastric mucosal calcium channels on epidermal growth factor binding (EGF) in the presence of ATP responded by an increase in tyrosine phosphorylation of 55 and 170 kDa proteins, and the vesicles containing the phosphorylated channels displayed a 48% greater 45Ca2+ uptake. This phosphorylation process was inhibited by ebrotidine which also interfered with the binding of EGF to calcium channel protein. The results point towards the importance of EGF in the maintenance of gastric mucosal calcium homeostasis, and suggest that ebrotidine has the ability to protect the cellular integrity from calcium imbalance by modulating the EGF-stimulated gastic mucosal calcium channel phosphorylation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1994

Helicobacter pylori aggregating activity of gastric mucin with ulcer healing by ebrotidine.

The mucin isolated from gastric secretion of duodenal ulcer patients before and after therapy with a new antiulcer agent, ebrotidine, was assessed for H. pylori aggregating activity and macromolecular organization. Analyses of mucin molecular forms revealed that successful therapy with ebrotidine was accompanied by a 2.6-2.9-fold increase in the high molecular weight mucin form. The H. pylori aggregation inhibition assays showed that therapy with ebrotidine evoked a 4-fold increase in mucin anti-H. pylori titer. The changes in the functional properties of mucin following ebrotidine therapy were also accompanied by a 36% increase in the content of sulfomucin. The results demonstrate that ulcer therapy with ebrotidine lead to a marked enhancement in mucin's qualities associated with maintenance of gastric mucosal integrity and strengthening the indigenous defenses against H. pylori.

Anti-Ulcer Agents↗

PubMed1994

Enhancement in gastric mucosal laminin receptor expression with ulcer healing by sucralfate.

The expression of gastric mucosal laminin receptor during chronic ulcer healing in the presence of sucralfate treatment was investigated. Rats with induced gastric ulcers were treated twice daily for 20 consecutive days either with sucralfate at 100mg/kg or vehicle, and at different stages of treatment used for gastric mucosal laminin receptor quantitation. The assays revealed that accelerated ulcer healing (8 days) in the presence of sucralfate was accompanied by a significant enhancement in the laminin receptor expression. A 2.8-fold increase in the receptor expression over that of controls occurred by the 3rd day of sucralfate treatment, reached a maximum of 3.1-fold increase by the 7th day and remained elevated even after 20 days of treatment. The results attest to the ability of sucralfate to stimulate and promote the events associated with gastric mucosal integrity restoration.

Animals↗

PubMed1994

Enhancement in gastric mucosal epidermal growth factor receptor expression by sulglycotide.

The effect of intragastric administration of sulglycotide, a cytoprotective sulfated glycopeptide, on the expression of gastric mucosal epidermal growth factor receptor was investigated. The experiments were conducted with groups of rats, one receiving twice daily for 5 consecutive days a dose of 200mg/kg sulglycotide, and the other only vehicle. Mucosal cell membranes were isolated from the stomachs at 16, 40 and 88h after the last dose, and used for EGF receptor assays. The binding assays revealed a marked increase in mucosal EGF receptor expression with sulglycotide. Compared to the controls, the sulglycotide-treated group showed a 4-fold increase in the EGF receptor expression at 16h after the last dose of sulglycotide, a 4.7-fold increase in the EGF receptor was observed by the 40h, and a 4.2-fold increase was still evident at 88h following the treatment. The results demonstrate that sulglycotide exhibits remarkable ability to enhance the gastric mucosal expression of EGF receptor.

Animals↗

PubMed1994

Association of salivary bacterial aggregating activity with sulfomucin.

The requirements of human salivary mucins for aggregating potential towards the common cariogenic oral bacteria, S. mutans and S. sanguis, were investigated. Agglutination inhibition assays demonstrated that the aggregating capacity towards bacteria resides in the acidic mucin fraction. The inhibitory activity of the acidic mucin decreased only 2-4-fold following removal of sialic acid, whereas the desulfation caused a complete loss of the inhibitory potential against both bacteria. Furthermore, the aggregating capacity of mucin-derived sulfated oligosaccharide was found to be 16-fold higher than that of the sialic acid containing oligosaccharide. The results point towards the importance of salivary sulfomucins as a predominant factor in the defense of oral cavity against cariogenic bacteria.

Adult↗

PubMed1994

Gastric mucosal EGF and PDGF receptor expression with ulcer healing by ebrotidine.

OBJECTIVES: Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) play important roles in the process of mucosal repair and restitution, and their biological effects are mediated by receptors located on the target cell surfaces. The purpose of this study was to assess the effect of the antiulcer agent, ebrotidine, on the expression of EGF and PDGF receptors with chronic ulcer healing. METHODS: Chronic gastric ulcers were developed in the rat by acetic acid technique. The animal were divided into two groups and were treated twice daily for 14 consecutive days, either with ebrotidine at 100 mg/kg, or placebo. At different stages of treatment, the animals were sacrificed and used for the isolation and quantification of gastric mucosal EGF and PDGF receptors. RESULTS: The binding assays revealed that ulcer healing was accompanied by an increase in mucosal expression of both types of receptors. A 1.7-1.8-fold increase in PDGF and EGF receptors occurred by the 4th day after the development of ulcer and reached a maximum of 3-fold increase by the 14th day, when the ulcer was essentially healed. Treatment with ebrotidine caused accelerated ulcer healing (7 days) which was accompanied by a significant enhancement in receptor expression. Compared to the controls, a 1.5-fold increase in EGF and 1.7-fold increase in PDGF receptor expression occurred by the 7th day of ebrotidine treatment, and a 1.4- to 1.5-fold increase was still observed at the 14th day of treatment. CONCLUSIONS: The results suggest that ebrotidine is capable of enhancement of gastric mucosal proliferative activities associated with ulcer healing through the stimulation of EGF and PDGF receptor expression.

Animals↗