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Urinary bromide levels probably dependent to intake of foods such as sea algae.

The purpose of the present study is to examine if the bromide (Br) level in urine (Br-U) varies substantially among adult general populations of either sex or of different dietary habits. For this purpose, morning spot urine samples (about 50 per group) were collected from six groups of people, i.e., one group each of men and women in a city in Japan (thus two groups in Japan) and one group each of women in two urban and two rural areas in central and northeast China (four groups in China). The samples were analyzed for Br by ECD-gas chromatography after derivatization to methyl bromide. Br-U essentially followed a normal distribution. Whereas there was only a marginal difference in Br-U between men (7.7 +/- 2.5 mg/L as an arithmetic mean and arithmetic standard deviation) and women (8.1 +/- 2.9 mg/L) in Japan, and no difference between the urban (2.3 +/- 0.8 mg/L) and rural women (2.6 +/- 1.1 mg/L) in China, the difference between Japanese (8.1 +/- 2.9 mg/L) and Chinese women (2.3 +/- 0.8 mg/L for two cities and 2.6 +/- 1.1 mg/L for two villages) was substantial. A literature survey suggested variation in dietary habits, especially that in sea algae intake, is a possible factor affecting the observed difference in Br-U between the two ethnic groups. Contribution of Br in cereals after fumigation with, e.g., methyl bromide, was also thought to be possible. The implication of difference in background Br-U levels is discussed in relation to biological monitoring of exposure to Br-containing industrial chemicals, such as 1- and 2-bromopropane.

Adult↗

Stability and compatibility of binary mixtures of morphine hydrochloride with hyoscine-n-butyl bromide.

The aim of this study was to determine the compatibility and stability of morphine hydrochloride and hyoscine-N-butyl bromide combined in solution at three different concentrations and stored in polypropylene syringes at 4 degrees C and 25 degrees C over a period of 15 days. The doses assayed were 20, 60 and 120 mg/day for morphine hydrochloride and 40, 60 and 80 mg/day for hyoscine-N-butyl bromide. These dose ranges were chosen according to daily practice. At both temperatures, all mixtures can be considered as physically compatible since no evidence of incompatibility-that is precipitation, turbidity, colour change or opacity and gas production-were observed. After 15 days of storage, the percentages of hyoscine-N-butyl bromide remaining in the drug mixtures tested ranged between 96.07% and 92.23%. At the end of the study, the percentages of morphine hydrochloride remaining in the drug mixtures were 100% at both temperatures.

Butylscopolammonium Bromide↗

Monoclonal antibodies to human A-I apolipoprotein and characterisation of cyanogen bromide fragments of apoA-I.

Several monoclonal antibodies to human A-I apolipoprotein were produced after immunising mice with pure delipidated apoA-I. These monoclonal antibodies were characterised for their ability to react with whole lipoproteins, apolipoproteins and fragments of apoA-I generated by cleavage with cyanogen bromide. The data suggest that production of monoclonal antibodies using apoA-I as antigen was influenced by two major epitopes subsequently localised to cyanogen bromide fragments 1 and 3, and have been designated antibodies 1----5 A-IB and 6----10 A-IB, respectively. Cyanogen bromide fragments were first purified to homogeneity before screening by competitive displacement or immunoblotting procedures. Definitive characterisation of one antibody series (1----5 A-IB) depended ultimately on Western blotting following isoelectric focusing of purified apoA-I fragments. This technique identified the epitope for these antibodies to fragment 1, an identification not fully concluded from competitive displacement studies. These studies have also revealed the presence of microheterogeneity in fragment 1 (as well as in fragment 4) of apoA-I, suggesting that structural variations in several regions may account for the polymorphism observed in this apolipoprotein.

Animals↗

Amino acid sequence of the carboxy-terminal cyanogen bromide peptide of the human fibrinogen beta-chain: homology with the corresponding gamma-chain peptide and presence in fragment D.

The carboxy-terminal cyanogen bromide fragment of the human fibrinogen beta-chain has been isolated and its structure determined. It is a nonapeptide with the sequence Lys-Ile-Arg-Pro-Phe-Phe-Pro-Gln-Gln and is homologous with a portion of the carboxy-terminal cyanogen bromide fragment of the gamma-chain. The peptide has also been isolated in full yield from cyanogen bromide digests of the plasmin-derived fragment D, indicating that the carboxy-terminal region of the beta-chain is resistant to plasmin digestion. In contrast, a small portion of the corresponding gamma-chain carboxy-terminal region was missing in the same fragment D.

Amino Acid Sequence↗

Species specificity in the acceleration of tissue-type plasminogen activator-mediated activation of plasminogens, by fibrinogen cyanogen bromide fragments.

Activation of human plasminogen by human tissue-type plasminogen activator (t-PA) is accelerated in the presence of cyanogen bromide digests of human fibrin(ogen). In the present study a possible species specificity of this phenomenon was investigated. All combinations of the plasminogens, fibrin monomers and cyanogen bromide digests of the fibrinogens of man, pig, rat, cat and monkey (Macaca mulatta), and three t-PA species (man, rat and pig) were studied. No species differences were noted with the fibrin monomers i.e. the activation rate of all five plasminogens increased more than 20-fold in the presence of all five fibrin monomer species, irrespective if man, rat or pig t-PA was used. However, we found that species specificities come to expression when cyanogen bromide digests of the corresponding fibrinogens were used as accelerators. Our results indicate that the plasminogen species and not the source of t-PA or fibrinogen dictates if accelerated activation occurs in the presence of a fibrinogen CNBr digest. The plasminogens can be roughly divided in two groups: --One group, comprising human, monkey and cat plasminogen, which are activated at a higher rate by all three t-PA species in the presence of fibrinogen digest independent on the fibrinogen species from which the digest was prepared. --Another group, comprising pig and rat plasminogen, which is not or only marginally more quickly activated by the 3 t-PA species, irrespective of the fibrinogen species from which the CNBr digest was prepared.

Animals↗

Effect of sodium bromide on endocrine parameters in the rat as studied by immunocytochemistry and radioimmunoassay.

Male rats were fed a normal or sodium bromide-enriched diet for 4 or 12 weeks. Sodium bromide concentrations were 0, 20, 75, 300, 1200 and 19,200 mg/kg diet. At the end of the experiments the pituitary gland, thyroid and testes were examined by histopathological and immunocytochemical techniques, while serum hormone levels were established by radioimmunoassay. Histopathological examination revealed an activation of the thyroid and a decreased spermatogenesis in the testes in the highest dose group. Using immunocytochemical techniques a decrease was noted in the amount of thyroxine in the thyroid. No effect was found in growth hormone-producing cells in the pituitary gland, while immunoreactivity for thyroid-stimulating hormone and for adrenocorticotropic hormone was increased. The concentration of thyroxine, testosterone and corticosterone in the serum appeared to be decreased. Due to feedback regulation, the pituitary gland was stimulated to produce and release thyroid-stimulating hormone, follicle-stimulating hormone, adrenocorticotropic hormone and insulin, whereas the release of growth hormone was suppressed. Most of these changes were restricted to rats on the highest treatment level. It is concluded that sodium bromide, at least in high doses, directly disturbs the function of the thyroid, testes and adrenals.

Animals↗

Effects of bromide on behaviour of mice.

Groups of mice, housed individually in standard cages placed in a frame especially designed for the recording of locomotive behaviour, were fed diets containing sodium bromide at a level of 0, 400, 1200, 3600 or 10,800 ppm for 36 days. A fully automated system was used to record and process measurements of the nocturnal motility of the mice, together with three other variables (evasion time, spontaneous treadmill performance and body weight), for a total of 128 days before, during and after administration of the test diets. The data obtained, analysed statistically by univariate and multivariate analysis of variance, indicated that for sodium bromide, the 'effect limit' based on behavioural variables and body weight lay for mice between 400 and 1200 ppm in the diet. The fact that the overall effect of the 10,800 ppm dietary level was not completely reversible seemed to be largely attributable to the effect of this level of sodium bromide administration on body weight.

Animals↗

The influence of sodium bromide in man: a study in human volunteers with special emphasis on the endocrine and the central nervous system.

Sodium bromide was administered orally in capsules to healthy volunteers in doses of 0, 4 or 9 mg Br-/kg/day using a double-blind design. Each treatment was given to seven males for 12 weeks and to seven non-pregnant females (not using oral contraceptives) over three full cycles. Special attention was paid to possible effects on the endocrine and central nervous systems. At the start and end of the study, a full medical history, the results of a physical examination, haematological studies and standard clinical chemistry and urine analyses were recorded for each subject. These showed no changes for individuals following treatment, except for some incidence of nausea associated with bromide-capsule ingestion. Mean plasma-bromide concentrations at the end of treatment were 0.08, 2.14 and 4.30 mmol/litre for males and 0.07, 3.05 and 4.93 mmol/litre for females of the 0-, 4- and 9-mg Br-/kg/day groups, respectively. Plasma half-life was about 10 days. In the females taking 9 mg Br-/kg/day (but in no other group) there was a significant (P less than 0.01) increase in serum thyroxine and triiodothyronine between the start and end of the study but all concentrations remained within normal limits. No changes were observed in serum concentrations of free thyroxine, thyroxine-binding globulin, cortisol, oestradiol, progesterone or testosterone, or of thyrotropin, prolactin, luteinizing hormone (LH) and follicle-stimulating hormone before or after the administration of thyrotropin-releasing hormone and LH-releasing hormone. Analysis of neurophysiological data (EEG and visual evoked response) showed a decrease in delta 1- and delta 2-activities and increases in beta-activities and in mean frequency (Mobility parameter) in the groups on 9 mg Br-/kg/day, but all the findings were within normal limits.

Adult↗

Sodium bromide treatment influences the plasticity of somatosensory responses in the rat cortex as induced by enucleation.

Effects of sodium bromide were studied on central neuroplasticity induced by early binocular enucleation. It has previously been found that enucleation on the day of birth, but not later than the first postnatal week, resulted in changes in the occipital cortex, such as the invasion of somatosensory evoked activity into the visual cortex areas. The present results showed that sodium bromide treatment extended at least up to 15 days after birth, the critical period during which somatosensory projections could be modified by visual deafferentation. Together with observations of Frost [J. comp. Neurol. (1981) 203, 227-256; Devl Brain Res. (1982) 3, 627-636], the present results suggest a mutual dependency of visual and somatosensory projection development. The present study is the first demonstration that the critical period of development, during which a specific type of neural plasticity can be induced, may be prolonged by pharmacological means, i.e. by chronic treatment with sodium bromide.

Animals↗

Localization of the approximately 12 kDa M(r) discrepancy in gel migration of the mouse glucocorticoid receptor to the major phosphorylated cyanogen bromide fragment in the transactivating domain.

The intact wild-type mouse glucocorticoid receptor has a theoretical molecular weight of approximately 96 kDa based on amino acid sequence, but on SDS-polyacrylamide gel electrophoresis it migrates as a protein of approximately 98 kDa. It is not known where the unusual primary structure or covalent modification responsible for this anomalous migration is located within the amino acid chain. In the course of examining the pattern of fragmentation of 32P-labeled glucocorticoid receptors from Chinese hamster ovary (CHO) cells containing amplified mouse receptor cDNA, we have found a localized region in the amino-terminal half of the receptor that accounts for this anomalous behavior. Cyanogen bromide treatment of the intact receptor produces a 23.4 kDa (theoretical) fragment consisting of residues 108-324 and containing all of the identified phosphorylated serines within the receptor. We find that the only large resolvable 32P-labeled receptor fragment produced after complete cyanogen bromide cleavage of intact receptors migrates with an apparent molecular weight of approximately 35 kDa. Because the apparent difference between the theoretical and the experimentally observed molecular weights of this cyanogen bromide fragment is essentially the same as the difference between the theoretical and experimental molecular weights of the intact mouse glucocorticoid receptor, we propose that some feature lying within this fragment accounts for slower migration. Although the existence of an additional phosphorylation site lying within the 15 kDa tryptic receptor fragment containing the DNA-binding domain has been contested, we also demonstrate that this fragment of the mouse glucocorticoid receptor is phosphorylated in vivo upon incubation of CHO cells in growth medium containing [32P]orthophosphate.

Animals↗

Analysis of bromate and bromide in blood.

Bromate is a regulated disinfection byproduct primarily associated with the ozonation of water containing bromide, but also is a byproduct of hypochlorite used to disinfect water. To study the pharmacokinetics of bromate, it is necessary to develop a robust and sensitive analytical method for the identification and quantitation of bromate in blood. A critical issue is the extent to which bromate is degraded presystemically and in blood at low (environmentally relevant) doses of ingested bromate as it is delivered to target tissue. A simple isolation procedure was developed using blood plasma spiked with various levels of bromate and bromide. Blood proteins and lipids were precipitated from plasma using acetonitrile. The resulting extracts were analyzed by ion-chromatography with inductively-coupled plasma mass spectrometry (IC-ICP/MS), with a method reporting limit of 5 ng/mL plasma for both bromate and bromide. Plasma samples purchased commercially were spiked with bromate and stored up to 7 days. Over the 7 day storage period, bromate decay remained under 20% for two spike doses. Decay studies in plasma samples from spiked blood drawn from live rats showed significant bromate decay within short periods of time preceding sample freezing, although samples which were spiked, centrifuged and frozen immediately after drawing yielded excellent analytical recoveries.

Bromates↗

Quantification of aqueous cyanogen chloride and cyanogen bromide in environmental samples by MIMS.

Membrane introduction mass spectrometry (MIMS) was developed and verified for the direct quantification of cyanogen chloride (CNCl) and cyanogen bromide (CNBr) in environmental samples without any sample workup. Factors including the membrane temperature and the liquid flow rates were examined for system optimization. The MIMS method provided linear responses for three orders of magnitude of concentrations. The instrument detection limits of CNCl and CNBr were 1.2 and 3.8 microg/L, respectively, and the method detection limits of CNCl and CNBr were both 1.7 microg/L. Effects of pH and the water matrix including synthetic water, saline water, natural surface water, and wastewater, on the responses were also examined. A pH ranging from 3 to 10 did not affect the quantification. The average recoveries of CNCl and CNBr in the water matrixes tested were 98.5% and 92.7%, respectively. The use of the MIMS method in on-line monitoring of the formation of cyanogen halide was demonstrated in chlorination of aqueous solutions containing glycine and bromide ions. The results indicated the important role of bromide ions in cyanogen halide speciation.

Chlorine↗

Antimicrobial activity of some N-alkyl substituted of (E)-4-azachalconium and (E)-3'-hydroxy-4-azachalconium bromides.

Twelve new N-substituted (E)-azachalconium bromides were synthesized and tested for antimicrobial and antifungal activities. Compounds 5c, 5d and 5h-5l showed very good antimicrobial activity against Staphylococcus aureus, Enterococcusfaecalis as well as Bacillus subtilis and 5h-5j showed moderate activity against Escherichia coli. In particular, (E)-N-dodecyl-4-azachalconium bromide (5i) and (E)-N-tetradecyl-4-azachalconium bromide (5j) showed the most intensive activity against all tested microorganisms.

Anti-Infective Agents↗

Effect of bromide ions on genotoxicity of halogenated by-products from chlorination of humic acid in water.

Genotoxicity of halogenated by-products obtained by chlorination of humic acid in water was evaluated in the presence of bromide ions (Br-). After the halogenated humic acid solution was made to flow through CSP800 cartridge, absorbed substances were eluted with dimethyl sulfoxide or acetone, and subjected to mutagenicity assays and to analysis of trihalomethanes (THMs). Mutagenic activity was measured by Ames tests using S. typhimurium TA100 strain without metabolic activation, and by the frequencies of micronuclei formation using cultured Chinese hamster lung cells (CHL/IU) in vitro. A powerful effect of bromide ions in chlorinated humic acid solutions was observed on the reverse mutation and micronuclei formations. The formations of total THMs and more brominated THMs were also enhanced in the presence of bromide ions. The ratio of [Br-/Cl-] regulated the composition and concentrations of THMs intensely, and the rate of substitution of Br- was greater than that of chloride ions (Cl-). The increments of the mutagenicity and total THMs formed in chlorinated solutions were observed in parallel with the concentration of Br- or Cl-. From the observations, it was concluded that the increasing mutagenicity might be caused by the increasing chlorinated and/or brominated by-products.

Animals↗

Effects of bromide on the formation of THMs and HAAs.

The role of bromide in the formation and speciation of disinfection by-products (DBPs) during chlorination was investigated. The molar ratio of applied chlorine to bromide is an important factor in the formation and speciation of trihalomethanes (THMs) and halogenacetic acids (HAAs). A good relationship exists between the molar fractions of THMs and the bromide incorporation factor. The halogen substitution ability of HOBr and HOCl during the formation of THMs and HAAs can be determined based on probability theory. The formation of HAAs, and their respective concentrations, can also be estimated through use of the developed model.

Acetic Acid↗

Isolation and characterization of the cyanogen bromide peptides of the collagen 2 alpha chain from a transplantable rat chondrosarcoma.

The rat collagen 2 alpha chain was isolated from a transplantable Swarm chondrosarcoma following limited pepsin proteolysis. The chromatographically purified 2 alpha chain when cleaved with cyanogen bromide yields nine peptides which have been isolated and characterized with respect to their molecular weight and their amino acid composition. Eight of these peptides can be rapidly separated by gel-permeation high-performance liquid chromatography and retrieved for further purification by ion-exchange chromatography. The nine peptides are recovered in equimolar amounts and together account for a total of 1,014 amino acid residues. The features of the isolated cyanogen bromide peptides of the 2 alpha chain clearly differentiate it from other known collagen polypeptides. The possible homologies between the 2 alpha chain and other collagen alpha chains are noted. Comparison of the cyanogen bromide peptides indicates a close relationship of the 2 alpha to the alpha 1(V) chain.

Amino Acids↗

Skin injuries afflicting three oil workers following contact with calcium bromide and/or calcium chloride.

Calcium bromide brine is a highly concentrated aqueous solution of calcium bromide and calcium chloride. It is used extensively in the oil industry. This solution and its components are recognized as causes of skin injury and information is available from the manufacturers on their safe use and handling. Two patients who were injured following unprotected skin exposure to this solution and one patient who was injured following exposure to calcium chloride powder are reported. All sustained skin injuries characterised by an absence of pain and a delayed clinical appearance of the full extent of the injury. Furthermore healing was complicated by graft loss or was slow. Although organic bromine compounds are recognized as a cause of skin injuries, no previous reports of such injuries to humans secondary to calcium chloride or bromide exposure were found in the medical literature. Our experience with these patients is described.

Adult↗

Two successful cases of bromide therapy for refractory symptomatic localization-related epilepsy.

Potassium bromide was tried for two children with daily convulsive focal motor seizures with unconsciousness and focal motor seizure status. The treatment resulted in complete cessation of the attacks. It has been reported that bromide is effective for generalized tonic-clonic seizures and not for complex partial seizures, such as convulsive focal motor seizures with unconsciousness. However, our experiences provide evidence that bromide is one of the useful therapeutic agents for intractable symptomatic localization-related epilepsy.

Bromides↗