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At least 19 recordsLinked to original sources
PubMed1979

Bismuth toxicity in man II. Review of bismuth blood and urine levels in patients after administration of therapeutic bismuth formulations in relation to the problem of bismuth toxicity in man.

A survey of the leterature on bismuth toxicity in man in relation to blood level data, has revealed the necessity of distinguishing between lipid soluble and water soluble organic complexes of bismuth on the one hand and the simple inorganic salts of bismuth on the other hand. A characteristic feature of the former, illustrated by the water soluble bismuth complex triglycollamate, is the high bismuth levels (due to absorption of the complex as such) and the nephrotoxic properties of the compound in man. Bismuth absorption after administration of the simple inorganic salts of bismuth is postulated to occur in the form of ionic bismuth as such, low bismuth levels being characteristic features of such compounds. Bismuth blood and urine levels obtained from patients after administration of a new anti-ulcer drug (Bicitropeptide) in a well controlled clinical trial are discussed and suggest that that this bismuth containing drug behaves pharmacologically in a manner similar to the inorganic bismuth salts in man, low bismuth blood levels and the absence of toxic side effects being conspicuous features of the drug. Based on these considerations, it is proposed that the pharmacologically active bismuth compounds be divided into four different groups depending on structure, stability and solubility. The question as to what constitutes a "toxic bismuth blood level" can only be discussed in relation to the new proposed sub-division of bismuth compounds and is only meaningful if the term is defined to relate only to ionic bismuth (presumably bound to a large extent to blood proteins). Based on information gleaned from the literature and blood level values reported in the clinical trial referred to, it is suggested that bismuth blood level values below 50 micrograms/ml are highly unlikely to be associated with meaningful toxicity in man. Finally, attention is drawn to the reversibility of bismuth toxicity in man as reported by many authors irrespective of the type of bismuth compound concerned.

Animals↗
PubMed1979

Bismuth toxicity in man - I. Bismuth blood and urine levels in patients after administration of a bismuth protein complex (Bicitropeptide).

In the course of a double-blind clinical trial of treatment involving a bismuth protein complex (Bicitropeptide), an antacid and placebo, blood samples (33 patients) and urine samples (43 patients) were collected for bismuth analysis from patients on bismuth therapy at the beginning of the trial (week 0) and at weeks 3 and 6. Base line blood (2 - 11 ng/l) and urine (2 - 29 ng/l) values were not zero and appeared to have reached "saturation" values in many cases after 3 weeks (Blood : 4 - 33 ng/l and Urine 60 - 600 ng/l). After 6 weeks, blood values were 5 - 20 ng/l and urine values 63 - 780 ng/l. It is concluded that these blood and urine levels are not associated with significant toxicity in man.

Antacids↗
PubMedDate not supplied

[The relationship between the course of bismuth encephalopathy and the amount of bismuth in blood and urine].

Study of the course of bismuth encephalopathy following the ingestion of a bismuth salt in relation to blood and urinary bismuth levels indicates a close parallel between the improvement in the clinical picture and the decrease in the degree of toxic impregnation of the body. This confirms the direct responsibility of bismuth for the disorder. Regression of myocolonic movements goes with the fall in blood bismuth levels, whilst improvement in the confusional syndrome is aomewhat delayed. There is a significant correlation between bismuth levels in the blood and urine. The excretion of bismuth is slow, and the persistence of blood and urinary bismuth levels higher than normal for several weeks after the acute phases and the interruption of the ingestion of bismuth salts reflects the existence of stable bonds between the metal and cellular constituents. The authors have observed a non-negligeable solubility of bismuth sub-nitrate in certain drinking waters, which brings up the hypothesis of a possible role of the hydrosobulity of bismuth in the pathogenesis of the intoxication.

Adult↗
PubMed1979

Bismuth intoxication: bismuth level in pig brain lipids and in subcellular fractions.

Experimental intoxications of pigs were performed. It seems to be confirmed that bismuth crosses the blood-brain barrier. An organic derivative, trivinyl-bismuth, is more active than the inorganic salt of bismuth. In the brain, bismuth is preferentially found in synaptosomes. Bismuth is found in brain lipids of control pigs at very low levels. In intoxicated pigs, the level of bismuth is increased mainly in cerebellum and then in thalamus. Bismuth is partly associated to lipids. There is not a correlation between the level of bismuth in blood and in brain lipids. However, in the trivinyl intoxicated pig, a high level of blood bismuth is concomittant to a high level of brain lipid bismuth. The high content of this metal in cerebellum lipid extract may be of functional significance.

Animals↗
PubMed1977

[Bismuth treatment and blood bismuth levels].

The authors report the results of bismuth blood levels in 41 patients treated by oral route with bismuth salts used in gastro-enterology according to the Bensaude rule (10 to 20 g/day, 20 days/month). Median bismuth blood level during the period of treatment amounts to 13 microgram/l. It decreases to 7 microgram/l during the period of therapeutic withdrawal. In patients with bismuth encephalopathies (63 cases recorded in the literature) median values range from 680 to 700 microgram/l. The authors recommend the determination of bismuth blood levels as a monitoring method in bismuth treatment and propose the following values:--normal level during treatment : less than 50 microgram/l (in Bi metal);--alarm level : 50 to 100 microgram/l : (patients to be monitored);--toxicity level less than 100 microgram/l : (treatment to be interrupted).

Bismuth↗
PubMed1979

Double-blind controlled trial with colloidal bismuth subcitrate in the treatment of symptomatic duodenal ulcers with special references to blood and urine bismuth levels.

To test the efficacy and toxicity of colloidal bismuth subcitrate (CBS) in a double-blind trial, forty-six consecutive outpatients with active duodenal ulceration were randomly allocated either to treatment with CBS or to a placebo for a period of four weeks. Symptomatic assessment was based on frequency and severity of pain. The ulcer size was measured endoscopically before and at the end of the trial. During the trial blood and urinary bismuth concentrations were measured. The symptomatic assessment of the patients receiving CBS or placebo showed that the reduction in pain was highly significant in both groups, but there was statistically significant difference in the degree of reduction of duodenal ulcer size in favour of the colloidal bismuth subcitrate-treated group (p less than 0.025). Although a marked increase in urinary bismuth concentration was noted, the blood bismuth levels remained within the acceptable levels.

Adult↗
PubMed1978

[The intracerebral distribution of bismuth in bismuth encephalopathy. Pathological and toxicological study of 3 cases (author's transl)].

Neuropathological study of 3 patients dying from bismuth encephalopathy showed the absence of specific lesions and the probably secondary nature of the abnormalities found. Multiple samples taken from various areas of the brain were used for the purpose of the analysis of the topographical distribution of bismuth. Levels were invariably very high and to toxic agent diffusely distributed. The concentration was nevertheless higher in the grey matter than in the white matter. They hypothesis of a liposoluble compound which would explain the affinity of bismuth for cerebral tissue is probable.

Aged↗
PubMed1976

Controlled flocculation of coarse suspensions by colloidally dispersed solids I: Interaction of bismuth subnitrate with bentonite.

Deflocculated suspensions of coarse powders tend to cake as the individual particles settle out and form compact, cohesive sediments. Limited flocculation results in looser sediments because the settled-out flocs incorporate large amounts of the liquid suspending medium. Controlled flocculation of bismuth subnitrate suspensions was achieved by the addition of small amounts of bentonite. The interaction of the coarse, positively charge bismuth subnitrate particles in aqueous suspension with negatively charged, colloidally dispersed bentonite was investigated by measuring electrophoretic mobility, sedimentation volume, and viscosity. Gradual addition of bentonite dispersion to bismuth subnitrate suspensions first reduced the zeta-potential of the bismuth subnitrate particles from +28 mv to zero, then inverted it, and finally caused it to level off at -20 mv for bismuth subnitrate-bentonite weight ratios below 200. Owing to the much greater specific surface area of bentonite, the surface of the bismuth subnitrate lath-shaped crystals was completely covered by 0.5% of its weight in clay platelets. Adhesion was promoted by electrovalences between surface bismuthyl ions and cation-exchange sites of the clay and by secondary valences. The charge neutralization of bismuth subnitrate by bentonite was a heterocoagulation process: the addition of small amounts of the clay flocculated the bismuth subnitrate suspensions and eliminated caking. While the zeta-potential of the bismuth subnitrate particles leveled off when their surface was saturated with bentonite platelets, sedimentation volume and viscosity continued to increase when the clay concentration was increased further while maintaining the bismuth subnitrate concentration constant. The excess, nonadsorbed bentonite formed the characteristic house-of-cards structure, incorporating the bentonite-coated bismuth subnitrate particles as cornerstones.

Bentonite↗
PubMed1979

Induced synthesis of chromochelatin, the low molecular weight bismuth-binding protein in rat kidneys.

Bismuth administered subcutaneously to rats as BiCl3 is deposited in the kidneys, where it is bound to two classes of proteins: one of high molecular weight and a fraction of molecular weight approx. 7500 (chromochelatin). The latter fraction prevails on repeated exposure to bismuth. The bismuth-binding protein is heterogenous and using polyacrylamide gel may be divided into three fractions of which all contain bismuth and copper. In parallel with increasing concentration of chromochelatin due to bismuth administration, the incorporation of L-[35S]cysteine is elevated in all three fractions. The incorporation is augmented especially if repeated administration of bismuth is applied. Cycloheximide (CH) completely abolishes the inducing effect of bismuth on the incorporation of L-[35S]cysteine into chromochelatin both following single and repeated administration of bismuth. Actinomycin D (AcD) eliminates the incorporation only in the case of single dose of bismuth. The obtained results suggest that the elevation of chromochelatin levels in the kidney following administration of bismuth is due to the induction of the de novo protein synthesis.

Animals↗
PubMed1978

Effect of selenium on the organ distribution and binding of bismuth in rat tissues.

Subcutaneous administration of bismuth, both single and multiple, resulted in deposition of this metal mainly in the kidneys which contained over 50% of the 'accessible pool' of bismuth. In the kidneys bismuth was bound mainly by the soluble fraction in which it was complexed with a protein of molecular weight of about 7000. Multiple administration of bismuth increased the level of this protein. Selenite administration brought about an increase in the 'accessible pool' of bismuth, probably due to a drop in excretion, and also changes in the organ distribution of this metal. The retention in the kidneys was diminished while those in the liver and in other tissues were augmented. These changes were accompanied by a change in the chemical form of bismuth present in the kidneys manifested by the total disappearance of the protein complex of molecular weight of 7000. The increased synthesis of this protein due to bismuth administration was not abolished completely.

Animals↗
PubMed1977

Bismuth subsalicylate inhibits activity of crude toxins of Escherichia coli and Vibrio cholerae.

The inhibition of the activity of enterotoxins by bismuth salts was assessed in laboratory models. In the Y-1 adrenal cell tissue culture system, a commercial preparation containing bismuth subsalicylate reduced the activity of crude toxin from Vibrio cholerae by 10(4)-fold as compared with the activity of controls. Similar results were obtained with use of the adult rabbit ligated intestinal loop model. The preparation failed to affect crude Escherichia coli or cholera toxin activity once these toxins had become bound to intestinal mucosa. Pretreatment of ligated loops with the preparation reduced the fluid accumulation mediated by crude E. coli and cholera toxins by 78% and 91%, respectively. Bismuth subsalicylate and the complex vehicle of the preparation also inactivated toxin; however, bismuth subsalicylate was more effective when combined with the vehicle. Bismuth subcarbonate failed to inhibit fluid accumulation in ligated loops. Preparations containing bismuth subsalicylate may be effective in the prevention of diarrhea mediated by toxigenic E. coli.

Animals↗
PubMed1978

Nucleoprotein localization by bismuth staining.

Experiments on isolated mouse liver muclei involving enzyme digestion, the crosslinking of amino groups and alkaline hydrolysis demonstrate that bismuth binds to nucleoproteins through amino and phosphate groups. Analysis of the nucleoproteins extracted with salt and acid solutions in conjunction with bismuth staining after these treatments suggests that: (1) a bismuth amino group interaction occurs on ribonucleo-protein particles, histones and perhaps some non-histone chromosomal proteins, and (2) bismuth phosphate binding is specific for one, or all, of three distinct species of non-histone proteins. These results suggest that histones not tightly bound to DNA through their amino groups are present on interchromatin granules, the presumed transcriptionally active regions of chromatin. Phosphorylated non-histone proteins are also localized at these sites. Staining with heavy metals such as bismuth may be the best method for high resolution localization of nucleoproteins involved with regulating gene activity and maintaining chromatin structure.

Animals↗
PubMed1976

[Myoclonic encephalopathy due to bismuth salts. Negative search for an associated toxic element].

Five cases of bismuth associated encephalopathy have been observed in the area of Geneva (Switzerland). Thy typical clinical picture is described and the blood and urinary bismuth levels are analyzed in comparison with a group of patients on bismuth treatment but without encephalopathy. A link is established between these observations and previously reported cases of bismuth toxicity, and also with other toxic encephalopathies. With regard to pathogenesis, two hypotheses are discussed: alkylation of bismuth in vivo, and association with another neurotoxic element. With this in view, the urinary excretion of arsenic, lead and mercury was measured. The results were within normal limits.

Aged↗
PubMed1976

Antinauseant and antiemetic properties of bismuth subsalicylate in dogs and humans.

Laboratory and clinical investigations were carried out to determine the effectiveness of bismuth subsalicylate in allaying nausea by preventing the physical symptom of emesis. In normal conscious dogs, a bismuth subsalicylate formulation caused a dose-related reduction in the incidence of vomiting in response to an emetic dose of ipecac syrup. In normal human subjects, a bismuth subsalicylate suspension, unlike the placebo formulation, successfully subdued nausea and vomiting in 66.7 and 80% of the subjects, respectively, in response to ipecac syrup. Both findings demonstrate that bismuth subsalicylate can provide antiemetic action and that the decreases in the occurrence of emesis in humans and dogs parallels the decrease in nausea found in humans and the nausea suspected to occur prior to emesis in dogs.

Adult↗
PubMed1979

Measurement of bismuth in bone by pulse polarography with anodic stripping voltammetry. Application to two cases of arthropathy.

Pulse polarography with anodic stripping has shown the presence of very high levels (2 005 microgram/kg and 6 760 microgram/kg) of bismuth in bone of two patients treated with bismuth, one parenterally and the other orally. The presence of high levels of bismuth in bone of these patients must be considered in the etiology of their athropathies. Pulse polarography with anodic stripping now permits very precise measurement of bismuth impregnating bones.

Aged↗
PubMed1978

[Tomodensitometric aspects of 3 cases of acute bismuth encephalopathy (author's transl)].

A study of 3 cases of acute bismuth encephalopathy by C. T. scanner revealed indisputable evidence of abnormal hyperdensity in certain brain regions. These hyperdensities, or rather hyperattenuations, are very typical in case no. 1, where the central grey nuclei, especially the caudate nuclei and cerebral cortex, have an important hyperdence appearance. The images are heterogenous, sometimes granular, and are not modified by the injection of a contrast medium. There are also ventricular and cisternal dilatations which are even more remarkable when the age of the patients (less than 45 years) is considered. Cases Nos. 2 and 3 showed hyperdensity which was mainly in the cortical hemispheres. Blood bismuth levels vary according to the date of bismuth stoppage, lying between 850 and 1.350 microgram p. 1.000 ml. The pathogenesis of these tomodensitometric images are discussed as a function the of atomic number of bismuth metal and its unequal distribution in the cerebral parenchyma and the meninges.

Adult↗