bismuth-tripotassium-dicitrate and Disease-Models--Animal

Topics: Antacids; Anti-Ulcer Agents; Bismuth; Clinical Trials as Topic; Disease Models, Animal; Duodenal Ulcer; Gastrointestinal Hemorrhage; Humans; Organometallic Compounds; Peptic Ulcer; Recurrence; Stomach Ulcer

THE AIM OF INVESTIGATION: To study the effect of schemes second line quadruple therapy on the state of gastric mucosal barrier and NO formation in experimental ulcer.. The study included 60 white male rats weighing 150-190 gr, mixed population. The effect of the standard second-line regimens on the content of the fractions of insoluble glycoproteins, on indicators of NO formation and anaerobic glycolysis in gastric mucosal tissue in experimental ulcer.. Quadruple therapy consisting of omeprazole, de-nol, amoxicillin and tetracycline stimulates mechanisms of protective barrier, which has a positive effect on the mechanisms of NO formation. Scheme with omeprazole, de-nol, tetracycline and metronidazole inhibits the synthesis of mucosal barrier, the key mechanisms of NO formation.. In the plan of correction of mechanisms of cytoprotection in the gastric mucosal tissue quadruple therapy with omeprazole, de ethanol, amoxicillin, and tetracycline is considered to be effective.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Disease Models, Animal; Drug Therapy, Combination; Gastric Mucosa; Male; Nitric Oxide; Omeprazole; Organometallic Compounds; Rats; Stomach Ulcer; Tetracycline

Current combination therapies cure Helicobacter pylori infection in 75 to 85% of cases. However, many treatment failures are not explained by antibiotic resistance. Our goal was to explore treatment failures under in vivo conditions by using the H. pylori Sydney strain (SS1) mouse model. Mice infected with H. pylori (SS1) were treated with monotherapies or combination therapies used in human trials. Bacterial levels and distribution of organisms within the stomach were assessed 24 h after treatment to determine clearance and location of treatment failures and 29 days after treatment to determine cure rates. Except for treatment with metronidazole, mono- and dual therapies did not cure infection but resulted in decreases in bacterial levels and differences in distribution within the stomach. In cases of treatment failure when clarithromycin was used, omeprazole and dual therapy with omeprazole and amoxicillin resulted in organisms being cleared from the antrum, but organisms remained in the antrum-body transitional zone. The triple therapies of OMC and bismuth subcitrate, metronidazole, and tetracycline were successful in eradicating infection. Except for metronidazole monotherapy and triple therapy with OAC, there was good correlation between the Sydney strain mouse model and humans with respect to the success of antimicrobial therapy. The antrum-body transitional zone was identified as a sanctuary site in treatment failure. This could result from antimicrobial agents not functioning effectively at this site or bacteria in this location expressing products that protect them against antimicrobial agents. This is the first demonstration of a possible sanctuary site as a reason for failure of therapy.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Disease Models, Animal; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Metronidazole; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Omeprazole; Organometallic Compounds; Penicillins; Pyloric Antrum

Colloidal bismuth subcitrate (CBS), a drug for treatment of peptic ulcers, has been reported in the literature to be nephrotoxic in humans when taken in high overdoses. To investigate the mechanism of bismuth nephropathy, we developed an animal model by feeding rats single doses of CBS containing 3.0 mmol Bi/kg body weight. Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling assay, immunostaining for active caspase-3, and electron microscopy showed that proximal tubular epithelial cells die by necrosis and not by apoptosis within 3 h after CBS administration. Exposure of the renal epithelial cell lines NRK-52E and LLC-PK1 to Bi(3+) in citrate buffer served as an in vitro model of bismuth nephropathy. NRK-52E cells exposed to 100 microM Bi(3+) or more died by necrosis, as was demonstrated by nuclear staining with Hoechst 33258 and flow cytometry using Alexa(488)-labeled Annexin-V and the vital nuclear dye TOPRO-3. Bismuth-induced cell death of NRK-52E cells was not prevented by the caspase-3 inhibitor z-VAD-fmk, whereas this inhibitor did prevent cisplatinum-induced apoptosis. Mitochondrial dysfunction and induction of free radicals were shown not to be involved in bismuth nephrotoxicity. The early time point of damage induction in vitro as well as in vivo and the early displacement of N-cadherin, as found in previous studies, suggest that bismuth induces cell death by destabilizing the cell membrane. In conclusion, we showed that high overdose of bismuth induced cell death by necrosis in vivo as well as in vitro, possibly by destabilization of the cell membrane.

Topics: Amino Acid Chloromethyl Ketones; Animals; Anti-Ulcer Agents; Apoptosis; Caspase 3; Caspase Inhibitors; Caspases; Cell Death; Cell Membrane; Cysteine Proteinase Inhibitors; Disease Models, Animal; Female; Flow Cytometry; In Situ Nick-End Labeling; Kidney Diseases; Kidney Tubules, Proximal; LLC-PK1 Cells; Microscopy, Electron; Mitochondria; Organometallic Compounds; Rats; Rats, Wistar

The aims of the present study were to assess the usefulness of the Helicobacter felis mouse model in the evaluation of antimicrobial therapies and the effect of Helicobacter infection on gastric mucosal prostaglandin E2 release.. Barrier-maintained BALB/c mice were infected with H. felis and treated with different antibacterial therapies. H. felis status was determined by bacterial culture, urease test, and bacterial and histologic stainings. Release of prostaglandin E2 from the gastric mucosa was measured by radioimmunoassay.. All triple-treated mice were cleared of bacteria both 24 h and 1 month after treatment. However, tinidazole alone also resulted in 100% eradication. Monotherapies with erythromycin acistrate, tetracycline, colloidal bismuth subcitrate, and nitecapone failed to eradicate the bacteria. The release of gastric prostaglandin E2 was doubled in the infected mice (554 +/- 39, mean +/- SE) compared with the noninfected mice (270 +/- 35) (p < 0.01).. The H. felis mouse model proved satisfactory for assessing both anti-Helicobacter therapies and the prostaglandin E2 release. The reliability of this method was improved when several methods to assess the H. felis status were used in parallel.

Topics: Amoxicillin; Animals; Anti-Ulcer Agents; Catechols; Dinoprostone; Disease Models, Animal; Drug Therapy, Combination; Erythromycin; Gastric Mucosa; Helicobacter Infections; Male; Mice; Mice, Inbred BALB C; Organometallic Compounds; Pentanones; Tetracycline; Tinidazole

Ligation of the pig bile duct (BDL) results in 100% incidence of pars esophageal ulceration within 48 hours of the procedure. Usually such ulceration is uniformly fatal unless a highly selective vagotomy is performed simultaneously with the BDL. The administration of sucralfate to pigs with BDL prolonged their survival for up to 7 days, with evidence of healing of the ulcer on macroscopic and histologic observations. An increase in cell proliferation in the squamous epithelium of the ulcerated area was also seen in this sucralfate group. These features were not seen in controls, pigs with BDL only, or pigs with BDL and with magaldrate (Riopone), colloidal bismuth subcitrate (DeNol), or carbenoxolone. Analysis by Sepharose 2B gel filtration showed that there was no significant difference in the amounts of polymeric mucin in any group, with a wide scatter of the data seen especially for pigs in the untreated BDL-only group. This study suggests that sucralfate may enhance healing in this experimental pig ulcer model via a mechanism independent of the stimulation of mucus secretion. We propose that coating the mucosa with sucralfate provides a temporary substitute barrier that creates a microenvironment conducive to wound repair by mucosal proliferation.

Topics: Aluminum Hydroxide; Animals; Antacids; Bile Ducts; Chromatography, Gel; Disease Models, Animal; Gastric Mucins; Incidence; Magnesium Hydroxide; Molecular Weight; Organometallic Compounds; Peptic Ulcer; Sucralfate; Survival Rate; Swine; Wound Healing

The purpose of this study was to determine the changes in rat gastric functional morphology that take place with age and to study the action of colloidal bismuth subcitrate on the age related degeneration of the stomach. At 95 weeks of age erosions were apparent over 80% of the gastric mucosa and this was associated with a significant decline in the numbers and mucus content of the mucosal epithelial cells. The rate of stem cell proliferation in the neck region was also significantly lower than that found in 9 week old animals. The administration of 50 mg/kg colloidal bismuth subcitrate for 14 days to 9 week old animals resulted in slight hypertrophy of the mucosal epithelial cells. When 95 week animals were placed on the same regimen there was a decline in the number of deep erosions in the mucosa and an increase in the number and mucin content of the mucosal epithelial cells. A significant increase in the proliferation of the stem cell population was also observed after colloidal bismuth subcitrate administration. It is suggested that colloidal bismuth subcitrate may ameliorate the increased susceptibility to harmful agents that occurs with age.

Topics: Age Factors; Aging; Animals; Bismuth; Cell Count; Cell Division; Disease Models, Animal; Epithelium; Gastric Mucosa; Male; Organometallic Compounds; Rats; Rats, Inbred Strains; Stem Cells; Stomach; Stomach Ulcer

In pharmacological ulcer models in rats colloidal bismuth subcitrate (CBS) demonstrated anti-ulcer activity. This was neither a result of an acid neutralizing nor of an acid secretion inhibitory effect. Both in vitro and in vivo, an anti-peptic action was found. At low pH CBS precipitates and was shown to form a coating on the gastric wall especially on the ulcer crater. This coating most likely forms a protective barrier to the peptic activity of gastric juice. Low toxicity was seen following chronic daily administration of high doses of CBS for 3 months to rats and 6 months to dogs. Although the blood levels were more elevated in rats, the tissue bismuth levels were comparable in the two species (except for the caecum). The chief bismuth-excreting organs, the kidneys, showed relatively high concentrations, while the brain-concentrations were extremely low in concordance with the absence of nervous system toxicity.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Chemical Phenomena; Chemistry; Colloids; Disease Models, Animal; Gastric Acid; Organometallic Compounds; Rats; Time Factors