Effects Of Colloidal Bismuth Subcitrate Research Articles

In vitro evaluation of the antibacterial effect of colloidal bismuth subcitrate on Porphyromonas gingivalis and its biofilm

ObjectiveTo investigate the antibacterial and anti-biofilm effects of colloidal bismuth subcitrate (CBS) on Porphyromonas gingivalis (P. gingivalis) in its planktonic and biofilm forms and also compare it with that of 0.2% chlorhexidine (CHX). DesignThe minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CBS were determined by the microdilution method; the bacteriostatic rate of CBS was determined by the MTT assay; the effect of CBS on the membrane integrity of P. gingivalis was investigated by the flow cytometric methods. The effects of CBS on the biomass and bacterial activity of biofilm were investigated. Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) were used to investigate the activity and structure of biofilms. ResultsThe MIC and MBC values were 18.75 µg/mL and 37.5 µg/mL. CBS could damage the cell membrane of P. gingivalis. CBS effectively inhibited biofilm formation and promoted dissociation at higher concentrations of 37.5 µg/mL and 75 µg/mL, respectively. The results also indicated an altered biofilm structure and reduced biofilm thickness and bacterial aggregation. ConclusionsCBS affected the metabolic and physiological processes of P. gingivalis, inhibited the formation of biofilm, and disrupted the mature biofilm.

Therapeutic effects of colloidal bismuth subcitrate in rabeprazole-based quadruple therapy

Therapeutic effects of colloidal bismuth subcitrate in rabeprazole-based quadruple therapy

Relief of dyspeptic symptoms by colloidal bismuth subcitrate in Helicobacter-negative and -positive patients: results of a study in general practice

Background: The role of H. pylori in non-ulcer dyspepsia is controversial. Colloidal bismuth subcitrate (CBS) is known to suppress H. pylori. We hypothesized that if H. pylori is a causal factor in dyspepsia, then suppression of H. pylori would lead to a decrease in symptoms. Aim: To assess the relationship between H. pylori status and the effect of CBS on dyspeptic symptoms in patients visiting their general practitioner for dyspeptic complaints. Methods: In total 446 patients between 17 and 81 years of age (median 44 years) were included. All patients were treated with CBS (240 mg Bi2O3) twice a day for 4 weeks. Symptoms were scored at baseline, and after 2 and 4 weeks of treatment. At the first visit, blood was taken for serological H. pylori testing. Results: During follow up, 65 patients were lost due to violation of protocol. Positive H. pylori serology was found in 110 (24.7%) of the 446 initially selected patients, and in 90 (23.6%) of the 381 patients who completed the protocol (NS). The mean overall symptom score decreased significantly after 4 weeks of CBS (P<0.001). This reduction in overall symptom score was not significantly different between the H. pylori-positive and -negative groups. Conclusions: The H. pylori status does not influence the outcome of CBS therapy in patients who consult their general practitioner for dyspepsia. This finding suggests that H. pylori does not play an important role in the etiology of dyspepsia in patients seen by the general practitioner.

Cytoprotective effects of colloidal bismuth subcitrate in patients with ulcer disease

Helicobacter pylori is capable of altering the structure of the mucus gel adhering to the surface of the gastric antral wall. Thirty patients (22 men and 8 women) with endoscopic evidence of active duodenal ulcer and histologically confirmed H pylori antral gastritis participated in this prospective study. The study objective was to evaluate the effects of 6 weeks of treatment with colloidal bismuth subcitrate (two 120-mg tablets twice daily) on peptic secretion and the gastric mucosal barrier. Samples of gastric juice were collected during endoscopy to measure pepsin levels. Also during endoscopy, four biopsies were taken (two antral and two from the body/fundus) for histological examination, H pylori detection, and the quantification of pepsinogen group A (PGA), gastrin, and pepsin in the tissues. All of the above parameters were repeated with endoscopy after 6 weeks of treatment. Ulcer healing was obtained in 26 (87%) of 30 patients after treatment. H pylori infection was cleared in 15 (50%) patients. No significant changes were detected in concentrations of pepsin in the gastric juice or concentrations of PGA, gastrin, or pepsin in the tissues. Mucus depletion was visibly lower after treatment, suggesting that colloidal bismuth subcitrate may alter the bacterial microenvironment, regenerating the quantity of mucus.

Studies on the mechanism of action of colloidal bismuth subcitrate. II. Interaction with pepsin.

The effects of colloidal bismuth subcitrate (CBS) on porcine pepsin have been studied in vitro. CBS inhibited pepsin activity in a pH-dependent manner. CBS was not active at pH 4.0 but inhibited pepsin activity at pH 1.0 (IC50: 2.3 +/- 0.09 mmol/l) and pH 2.0 (IC50: 8.9 +/- 0.7 mmol/l). This inhibition was reversible. In the presence of the sulfhydryl ligand mercaptoethanol, which prevents precipitation of CBS, the inhibitory potency of CBS increased. CBS bound to both positively (Amberlite) and negatively charged (Dowex) ion exchangers in a pH-dependent manner. With increasing acidity, binding to Amberlite increased, whereas binding to Dowex decreased. From these data we conclude that negatively charged bismuth salts derived from CBS bind at pH 2.0 and 1.0 via an ionic interaction to positively charged groups of pepsin, thereby inactivating the enzyme.

Effect of colloidal bismuth subcitrate on age related gastric lesions in the rat.

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.

Influence of soluble haemagglutinins on adherence of Helicobacter pylori to HEp-2 cells

In a study of six laboratory strains of Helicobacter pylori, two different modes of bacterial adherence to HEp-2 cells were found. Electronmicroscopy revealed that strains known to possess soluble haemagglutinin adhered intimately to the cell surfaces, with cupping of the plasma membrane and coalescence of glycocalyces at sites of attachment. Strains of H. pylori without soluble haemagglutinin also attached, but did not induce membrane cupping or show glycocalyx fusion. Light microscopy did not distinguish between these patterns of adherence. Bacterial attachment was unaffected by pre-treatment of HEp-2 cells with neuraminidase. Exposure of the bacteria to trypsin or to colloidal bismuth subcitrate (CBS) before being added to HEp-2 cells markedly impaired bacterial adherence. This effect of CBS may contribute to the known efficacy of bismuth therapy in patients with H. pylori-related gastritis.

Evaluation of putative cytoprotective properties of antiulcer drugs using quantitative histological techniques

The capacity for cytoprotection has been claimed for a number of drugs that may have a place in the treatment of peptic ulcer disease. In this study we have used quantitative histological criteria to evaluate the ability of these drugs to be cytoprotective and have compared their effects with that of natural prostaglandin E2 (PG). The standard rat model, with injury by instillation of 1 ml of absolute ethanol, has been used. Putative cytoprotective agents were administered 15 min prior to ethanol. Each animal was sacrificed 15 min after ethanol exposure. The stomach was removed and studied using an established quantitative histological technique. This technique provides a measure of the surface area of mucosa damaged and of the volume of mucosa damaged. Ethanol alone caused damage to 76% of the area of the rat stomach and 14% of the volume of the rat gastric mucosa. Pretreatment by PG (25 micrograms/ml) resulted in reduction of the area of damage to 45% and reduction of the percentage volume damage to 2.2%. The synthetic analog of PGE2, Enprostil (1 microgram/ml) achieved similar protective effects. With pretreatment with colloidal bismuth subcitrate (10 mg/kg) or sucralfate (25 mg/kg), no protection against the surface area damaged by ethanol was seen, but there was a marked reduction of the volume of mucosa damaged. Indomethacin pretreatment augmented the damage caused by ethanol. The protective effects of colloidal bismuth subcitrate and sucralfate were not blocked by pretreatment with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Participation of Phosphoinositides in Gastric Mucosal Protection by Colloidal Bismuth Subcitrate against Ethanol‐Induced Injury

The mechanism of gastric mucosal protection by an antiulcer agent, colloidal bismuth subcitrate (CBS), against ethanol-induced injury was investigated using in vivo and in vitro systems. The experiments in vivo were conducted with groups of rats with and without indomethacin pretreatment, and the animals received either a dose of CBS (100 mg/kg) or a vehicle (saline), followed 30 min later by ethanol. In the in vitro studies, gastric mucosa segments were cultured in the presence of CBS, ethanol, or both. The results of in vivo experiments revealed that in the absence of CBS, ethanol caused extensive gastric hemorrhagic lesions which were significantly reduced following CBS pretreatment and this effect of CBS was not prevented by indomethacin. The data obtained with gastric mucosal culture established that in comparison to the controls, ethanol caused a 27% decrease in mucin synthesis, while mucin synthesis in the presence of CBS increased by 48%. The increase in mucin synthesis evoked by CBS was accompanied by the enhanced metabolism of mucosal phosphoinositides, as reflected by a decrease in PI (15%) and PIP2 (30%), and an increase in IP1 (26%) and IP3 (67%). In contrast, ethanol, which exhibited detrimental effect on mucin synthesis, caused a decrease in PIP (35%), IP2 (47%) and IP3 (38%), and an increase in PIP2 (80%), and IP1 (51%). However, when the mucosal culture was carried out in the presence of both CBS and ethanol, the detrimental changes evoked by ethanol on mucin synthesis were prevented, and the phosphoinositide and inositide phosphate distribution patterns were quite similar to those in the mucosa cultured in the presence of CBS only.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of colloidal bismuth subcitrate on symptoms and gastric histology in non-ulcer dyspepsia. A double blind placebo controlled study.

The aim of this study was to determine the effect of colloidal bismuth subcitrate (De Nol) on symptoms and gastric histology in patients with non-ulcer dyspepsia. In a single centre trial, patients with food related upper abdominal pain not caused by ulcer disease were randomised to receive one tablet of colloidal bismuth subcitrate or matching placebo four times daily for eight weeks. Seventy three patients were entered and 51 completed the trial: 28 patients in the colloidal bismuth subcitrate group and 23 in the placebo group. Overall there was no difference between the two groups in terms of symptom relief. Among patients with histological gastritis (n = 23), however, those who took colloidal bismuth subcitrate used fewer antacid tablets (for three of four fortnightly periods) and were more likely to become asymptomatic (eight of 11 v three of 12, p less than 0.05); their gastritis was more likely to resolve (five of 10 v 0 of 12, p less than 0.025) and their gastric biopsies more likely to become negative for Helicobacter like organisms (eight of nine v 0 of 12, p less than 0.001) when compared with patients taking placebo. In contrast, patients who did not have gastritis in their index biopsies (n = 28) fared similarly whether they received colloidal bismuth subcitrate or placebo. Our results indicate that the administration of colloidal bismuth subcitrate benefited non-ulcer dyspepsia patients with gastritis but had no effect on those without.

Studies on the gastroprotective and ulcer-healing effects of colloidal bismuth subcitrate.

We investigated the gastroprotective effects of colloidal bismuth subcitrate (CBS, De-Nol) in comparison with agents such as sucralfate and methylated PGE2. Both CBS and sucralfate given orally prevented dose dependently the formation of gastric lesions by acidified aspirin, ethanol and restraint stress, CBS being more potent on a weight-to-weight basis than sucralfate. CBS and sucralfate were also equally effective in enhancing the healing rate of chronic gastric and duodenal ulcer induced by serosal application of acetic acid, while methylated PGE2 was completely ineffective in this model. Non-colloidal bismuth subnitrate, in contrast to CBS, was ineffective against stress-induced lesions. CBS stimulated mucosal generation and luminal release of PGE2 dose dependently.

Advances in the understanding of the mechanism of cytoprotective action by colloidal bismuth subcitrate.

This study was designed to compare the gastroprotective effects of colloidal bismuth subcitrate (CBS) with those of sucralfate and methylated analog of prostaglandin E2 (PGE2) against acute gastric lesions induced by absolute ethanol, acidified aspirin (ASA), and water immersion and restraint stress in rats. When given orally, both CBS and sucralfate prevented in a dose-dependent way the formation of gastric lesions induced by all three ulcerogens, CBS being about 7, 2, and 20 times more potent, respectively on a weight-to-weight basis than sucralfate. Methylated PGE2 was also highly effective against these ulcerogens. Bismuth subnitrate was ineffective against acute gastric lesions induced by stress conditions. The protection of both CBS and sucralfate was reversible when the animals were pretreated with indomethacin to suppress the generation of endogenous prostaglandins. Since CBS and sucralfate increased the production of PGE2 in the gastric mucosa, we postulate that their gastric protective action may be mediated, at least partly, by mucosal prostaglandins.

Treatment of chronic duodenal ulceration: Effectiveness of colloidal bismuth subcitrate tablets compared with cimetidine

Fifty-eight patients with chronic duodenal ulceration proven at endoscopy consented to enter a trial comparing the effect of colloidal bismuth subcitrate (CBS)tablets with that of cimetidine. Fifty-four patients completed the six-week trial. An endoscopic assessment of healing was made at four weeks. If healing had not occurred, the trial was continued for another two weeks and the endoscopy was repeated. At four weeks, healing at endoscopy was demonstrated in 82% of patients receiving CBS and in 58% of those receiving cimetidine. At six weeks, the healing rates were 93% and 81%, respectively. No side effects were noted in either group. Continued smoking was not found to have an adverse effect on the healing rate of ulcers in either treatment group.