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Bromides were effective in intractable epilepsy with generalized tonic-clonic seizures and onset in early childhood.

Thirty-six children with epilepsy resistant to conventional treatment were treated with bromides in addition to the current therapy. Six out of 19 cases with prevailingly or exclusively generalized tonic-clonic seizures became seizure-free and in 9 cases a reduction in seizure frequency of more than 50% was achieved. Freedom from seizures could not be obtained in 13 cases, who had frequent minor seizures in addition to generalized tonic-clonic seizures. In some, minor seizures were even activated. Tonic and focal seizures showed no response. Side effects were observed in one-third of the cases (acne, loss of appetite, loss of weight, fatigue) but in no case they did become intolerable. Fifty to 80 mg potassium bromide per kg body weight seems to be an effective daily dose range. There is a preferential indication of bromides for patients suffering from early onset epilepsy with generalized tonic-clonic seizures and/or alternating hemi-grand mal, for whom other treatment is ineffective. This disorder is characterized by a high familial incidence of epileptic seizures, onset between 6 months and 3 years of age, normal development until the onset of seizures, generalized tonic-clonic seizures and often alternating hemi-grand mal, seizure precipitation by fever, and occasional combination with or transition to myoclonic-astatic and/or myoclonic seizures. EEG is often normal or shows slight slowing in the initial phase; later it shows theta rhythms and generalized spikes and waves. Especially, if the onset is during the first year of life, the course of the epilepsy is often unfavourable.

Adolescent↗

Panniculitis due to potassium bromide.

Potassium bromide again is well known to be surprisingly effective in patients with severe myoclonic epilepsy in infants (SME). Rare side effects on the skin reappeared, such as the febrile nodular panniculitis (Weber-Christian syndrome). In 1993 we described the first three cases of necrotizing panniculitis and introduced the term 'halogen panniculitis'. It is a systemic disease with crops of subcutaneous nodules, fever, elevated sedimentation rate, hepatosplenomegalia, and abdominal pain. Later severe necrosis of the skin and adipose tissue may happen with deep ulcerations. History and course of five cases, described in this paper, suggest either an allergy or toxic reason. Histologic picture shows inflammation of adipose tissues with infiltrating lymphocytes, but lymphocyte transformation test (LTT) was not reliable in diagnosing the disease. Possibly, bromides act as a chemokine and stimulate inflammatory processes. Bromide can be transformed into a bromine radical/free electron pair under UV irradiation at 228.8 nm in aqueous solution. The bromine radical may have detrimental effects on the tissue. However, despite some research, the origin of halogen panniculitis and similar diseases remains unclear.

Adolescent↗

A validated HPLC method for the determination of pyridostigmine bromide, acetaminophen, acetylsalicylic acid and caffeine in rat plasma and urine.

A method was developed for the separation and quantification of the anti-nerve agent pyridostigmine bromide (PB; 3-dimethylaminocarbonyloxy-N-methyl pyridinium bromide), the analgesic drugs acetaminophen and acetylsalicylic acid, and the stimulant caffeine (3,7-dihydro-1,3,7-trimethyl-1-H-purine-2,6-dione) in rat plasma and urine. The compounds were extracted using C(18) Sep-Pak(R) cartridges then analyzed by high performance liquid chromatography (HPLC) with reversed phase C18 column, and UV detection at 280 nm. The compounds were separated using gradient of 1-85% acetonitrile in water (pH 3.0) at a flow rate ranging between 1 and 1.5 ml/min in a period of 14 min. The retention times ranged from 8.8 to 11.5 min. The limits of detection were ranged between 100 and 200 ng/ml, while limits of quantitation were 150-200 ng/ml. Average percentage recovery of five spiked plasma samples were 70.9+/-9.5, 73.7+/-9.8, 88.6+/-9.3, 83.9+/-7.8, and from urine 69.1+/-8.5, 74.5+/-8.7, 85.9+/-9.8, 83.2+/-9.3, for pyridostigmine bromide, acetaminophen, acetylsalicylic acid and caffeine, respectively. The relationship between peak areas and concentration was linear over range between 100 and 1000 ng/ml. The resulting chromatograms showed no interfering peaks from endogenous plasma or urine components. This method was applied to analyze these compounds following oral administration in rats.

Acetaminophen↗

[False hyperchloremia in a bromide intoxication].

A false hyperchloremia in a patient with a history of depression suspected bromide intoxication. The diagnosis was confirmed by an increased bromide concentration > 20 mmoL.L-1. Rehydration was effective and allowed to decrease bromide concentration. In conclusion, hyperchloremia associated with a negative anion gap is a clue to the diagnosis.

Bromides↗

Simultaneous determination of bromide and iodide as acetone derivatives by gas chromatography and electron capture detection in natural waters and biological fluids.

Oxidation of bromide and iodide ions in acidic solutions in the presence of acetone forms the corresponding acetone derivatives. Iodate was reduced with thiosulfate prior to the determination. After extraction with benzene the bromo- and iodoacetone were measured by gas chromatography using electron capture detection. The bromide and iodide contents of rainwater, drinking water, river water, seawater, oil brine, common salt, cow milk, and human blood serum were determined. The relative standard deviations for bromide at 10(-7) M and for iodide at 10(-8) M concentration were 1.9% and 3.0%, respectively, using a 10-mL sample for the determination without preconcentration.

Acetone↗

Tribromopyrrole, brominated acids, and other disinfection byproducts produced by disinfection of drinking water rich in bromide.

Using gas chromatography/mass spectrometry (GC/MS), we investigated the formation of disinfection byproducts (DBPs) from high bromide waters (2 mg/L) treated with chlorine or chlorine dioxide used in combination with chlorine and chloramines. This study represents the first comprehensive investigation of DBPs formed by chlorine dioxide under high bromide conditions. Drinking water from full-scale treatment plants in Israel was studied, along with source water (Sea of Galilee) treated under carefully controlled laboratory conditions. Select DBPs (trihalomethanes, haloacetic acids, aldehydes, chlorite, chlorate, and bromate) were quantified. Many of the DBPs identified have not been previously reported, and several of the identifications were confirmed through the analysis of authentic standards. Elevated bromide levels in the source water caused a significant shift in speciation to bromine-containing DBPs; bromoform and dibromoacetic acid were the dominant DBPs observed, with very few chlorine-containing compounds found. Iodo-trihalomethanes were also identified, as well as a number of new brominated carboxylic acids and 2,3,5-tribromopyrrole, which represents the first time a halogenated pyrrole has been reported as a DBP. Most of the bromine-containing DBPs were formed during pre-chlorination at the initial reservoir, and were not formed by chlorine dioxide itself. An exception wasthe iodo-THMs, which appeared to be formed by a combination of chlorine dioxide with chloramines or chlorine (either added deliberately or as an impurity in the chlorine dioxide). A separate laboratory study was also conducted to quantitatively determine the contribution of fulvic acids and humic acids (from isolated natural organic matter in the Sea of Galilee) as precursor material to several of the DBPs identified. Results showed that fulvic acid plays a greater role in the formation of THMs, haloacetic acids, and aldehydes, but 2,3,5-tribromopyrrole was produced primarily from humic acid. Because this was the first time a halopyrrole has been identified as a DBP, 2,3,5-tribromopyrrole was tested for mammalian cell cytotoxicity and genotoxicity. In comparison to other DBPs, 2,3,5-tribromopyrrole was 8x, 4.5x, and 16x more cytotoxic than dibromoacetic acid, 3-chloro-4-(dichloromethyl)-5-hydroxy-2-[5H]-furanone [MX], and potassium bromate, respectively. 2,3,5-Tribromopyrrole also induced acute genomic damage, with a genotoxic potency (299 microM) similar to that of MX.

Bromides↗

Design of N-spiro C2-symmetric chiral quaternary ammonium bromides as novel chiral phase-transfer catalysts: synthesis and application to practical asymmetric synthesis of alpha-amino acids.

A series of C(2)-symmetric chiral quaternary ammonium bromides 10 and 11 have been designed as a new, purely synthetic chiral phase-transfer catalyst, and readily prepared from commercially available optically pure 1,1'-bi-2-naphthol as a basic chiral unit. The details of the synthetic procedures of each requisite chiral binaphthyl subunit have been disclosed, and the structures of the assembled N-spiro chiral quaternary ammonium bromides 11a and 11f were unequivocally determined by single-crystal X-ray diffraction analysis. The reactivity and selectivity of these chiral ammonium bromides as chiral phase-transfer catalysts have been evaluated in the asymmetric alkylation of the benzophenone Schiff base of glycine ester 7 under mild liquid-liquid phase-transfer conditions, and the optimization of the reaction variables (solvent, base, and temperature) has also been conducted. Further, the scope and limitations of this asymmetric alkylation have been thoroughly investigated with a variety of alkyl halides, in which the advantage of the unique N-spiro structure of 11 and dramatic effect of the steric as well as the electronic properties of the aromatic substituents on the 3,3'-position of one binaphthyl moiety have been particularly emphasized. Finally, the potential synthetic utility of the present method for the practical asymmetric synthesis of structurally diverse natural and unnatural alpha-amino acids has been demonstrated by its successful application to the facile asymmetric syntheses of (S)-N-acetylindoline-2-carboxylate, a key intermediate in the synthesis of the ACE inhibitor, and l-Dopa (l-3,4-dihydroxyphenylalanine) ester and its analogue.

Amino Acids↗

Aqueous hydroxide as a base for palladium-catalyzed amination of aryl chlorides and bromides.

The amination of aryl halides in the presence of inexpensive and air-stable alkali metal hydroxide bases and Pd[P(t-Bu)3]2 as catalyst gave arylamines in high yields. The reactions were conducted with a catalytic amount of cetyltrimethylammonium bromide as phase-transfer agent and either aqueous hydroxide or solid hydroxide in the presence of water. This combination of alkali metal hydroxide base, H2O, and the ammonium salt performed as well as NaO-t-Bu in the amination of p-chlorotoluene with dibutylamine. Hydroxide base was suitable for reactions of a wide range of aryl chlorides and bromides with aliphatic and aromatic amines. Some functional groups that were intolerant of tert-butoxide base, such as esters, enolizable ketones, nitriles, and nitro groups, were tolerated by the combination of hydroxide base, H2O, and cetyltrimethylammonium bromide in toluene solvent.

Bromides↗

Analysis of chloride, bromide and iodide using miniaturised isotachophoresis on a planar polymer chip.

A new method has been developed to allow the determination of the halide anions chloride, bromide and iodide using isotachophoresis. This method employs a new electrolyte system which incorporates the novel application of indium(III) as a complexing agent. This electrolyte system was devised based on the findings of an investigation into the potential for using indium(III) as a complexing counter ion to selectively manipulate the effective mobilities of halide ions. A leading electrolyte incorporating 3.5 mmol dm(-3) of indium(III) allowed the simultaneous determination of chloride, bromide and iodide to be successfully achieved. The new procedure allows such separations to be made without interference from common inorganic anions such as sulfate and nitrate. Separations were performed using a miniaturised planar poly(methyl methacrylate) chip with integrated platinum wire conductivity detection electrodes. Using this instrumentation the limits of detection were calculated to be 0.7 mg dm(-3), 1.7 mg dm(-3) and 2.2 mg dm(-3) for chloride, bromide and iodide respectively.

Anions↗

Safety and efficacy of glucagon as a premedication for upper gastrointestinal endoscopy--a comparative study with butyl scopolamine bromide.

BACKGROUND: Glucagon inhibits digestive motility and is used for endoscopic premedication; however, its effect on cardiopulmonary function during endoscopy has not yet been fully investigated. AIM: To clarify the efficacy and safety of glucagon compared with butyl scopolamine bromide as upper gastrointestinal endoscopy premedication. METHODS: Two hundred and forty consecutive patients over 40 years of age, referred for upper gastrointestinal endoscopy, without any complications, were studied. These patients were randomly premedicated with butyl scopolamine bromide (SC group) or glucagon (G group). Time course changes in blood pressure, arterial oxygen saturation, heart rate and the number of retching episodes during endoscopy were examined. The efficacy of glucose tablets after upper gastrointestinal endoscopy to prevent hypoglycaemia caused by glucagon was evaluated. Cardiopulmonary parameters were also examined in 77 complicated patients with glucagon premedication (GC group). RESULTS: A continuous increase in heart rate during upper gastrointestinal endoscopy was observed in the SC group, but not in the G and GC groups. Blood pressure, arterial oxygen saturation and number of retching episodes were not different between the groups. Hypoglycaemia-related symptoms were frequent in the G group without glucose tablets, but were prevented by the administration of glucose. CONCLUSIONS: Glucagon has a weaker effect on cardiopulmonary function during upper gastrointestinal endoscopy than butyl scopolamine bromide. Glucose administration prevents hypoglycaemia-related symptoms caused by glucagon.

Aged↗

[Bromism or chronic bromide poisoning].

Bromism, the chronic intoxication with bromide is rare and has been almost forgotten. In the recent past bromide is rediscovered as an anticonvulsive drug. The increasing frequency of bromism in children coming to admission induced this report. We describe the cause, the symptoms and the pseudohyperchloremia associated with bromism. If unclarified neurological or psychiatric symptoms are associated with the determination of an elevated serum chloride concentration and a diminished anion gap chronic intoxication with bromide has to be excluded.

Adult↗

Ordering of cyanogen bromide peptides of type III collagen based on their homology to type I collagen: preservation of sites for crosslink formation during evolution.

The order of the cyanogen-bromide-derived peptides from alpha 1 (III) chains of pepsin-solubilized calf skin collagen was found to be 3A-3B-3C-7-6-1,8,2-4-5-9A-9B. The amino-acid sequences of the NH2-terminal region of all peptides were determined by Edman's automated degradation procedure. The alignment of the peptides along the peptide chain was established by searching for the best homology between the partial sequences of the cyanogen bromide peptides from the alpha 1 (III) chain and the completely known sequence of the alpha 1 (I) chain. Characterization of three cyanogen-bromide-derived double peptides provided confirmation of the deduced order. A sequence Gly-Met-Hyl-Gly-His-Arg-Gly-Phe- was established near the NH2-terminus and a sequence Gly-Ile-Hyl-Gly-His-Arg-Gly-Phe near the COOH-terminus of the alpha 1(III) chain. Identical sequences have been found in the corresponding regions of the alph 1(I) chain. They include hydroxylysine, a site for intermolecular crosslink formation. Because these sequences are conserved during evolution of the collagen molecule, they are probably important for collagen structure and function.

Amino Acid Sequence↗

Formation of sodium dodecyl sulfate-stable fibronectin multimers. Failure to detect products of thiol-disulfide exchange in cyanogen bromide or limited acid digests of stabilized matrix fibronectin.

Fibronectin exists in a soluble form in body fluids and as a fibrillar component of the extracellular matrix. Matrix fibronectin associates as large complexes in SDS unless a reducing reagent is also present. This observation suggests that complex formation is due to interprotomeric disulfides that form by thiol-disulfide exchange. To localize the presumptive new disulfides, we labeled protomeric fibronectin by the chloramine-T method or with 125I-Bolton-Hunter reagent, incorporated 125I-fibronectin into the matrix of cultured fibroblasts, and subjected matrix fibronectin to acid or cyanogen bromide digestion. When cyanogen bromide digests of matrix 125I-fibronectin and protomeric 125I-fibronectin labeled with Bolton-Hunter reagent were analyzed by two-dimensional polyacrylamide gel electrophoresis in SDS, with the first dimension being nonreducing and the second reducing, we were not able to identify any fragments of matrix fibronectin that migrated as high molecular weight complexes in the first dimension. Limited acid digestion of matrix 125I-fibronectin also dissociated the majority of the high molecular weight complexes. Since we could account for all of the parts of fibronectin that contain cysteine or cystine, we conclude that matrix fibronectin is not stabilized by interprotomeric disulfides. We propose, instead, that stabilization is mediated by noncovalent protein-protein interactions that are sensitive to reduction, cyanogen bromide digestion, or limited acid digestion.

Acids↗

Isolation and purification of cyanogen bromide-derived peptides of type II collagen directly from tissue (Swarm chondrosarcoma).

A preparative procedure is described for isolating type II collagen-fragments directly from tissue. Swarm chondrosarcoma from rat, a cartilagenous tissue rich in type II collagen, was digested by cyanogen bromide in 70% formic acid. The resulting crude extract was desalted (G 25 column chromatography) and lyophylized. The yield of peptide mixture was about 1 250 mg obtained from 100 g tissue. The method of purification commonly used for type II collagen prior to cyanogen bromide-cleavage yielded 20 mg peptides from 100 g tissue. Separation of the cyanogen bromide-derived fragments was performed by gel filtration. The column was run at 43 degrees C (denaturing-temperature of collagens) to avoid fibril formation, and a volatile buffer was used (ammonium formate buffer, pH 7.5) so that the effluent fractions could be easily lyophylized. Two-dimensional gel electrophoresis of the main peaks of the column profile demonstrated that this purification step resulted in a good separation of the fragment mixture, although additional steps may be necessary for complete separation of the peptides. The most striking advantages of the method for direct digestion of tissue outlined here are the increase in yield (about 60-fold) and the reduction of purification steps (avoiding type II collagen purification).

Animals↗

The effect of ethidium bromide on mitochondrial DNA synthesis and mitochondrial DNA structure in HeLa cells.

The synthesis of mitochondrial DNA (mDNA) in HeLa cells is selectively inhibited by relatively low concentrations of ethidium bromide. After exposure of cells to strongly inhibitory concentrations of the drug, the apparent superhelix density of mDNA is rapidly increased, as judged by its buoyant density in CsCl in the presence of ethidium bromide. Mitochondrial DNA synthesized in the presence of partially inhibitory concentrations of ethidium bromide is also altered in its buoyant density in the presence of the dye, but is more heterogeneous in this respect. However, the change in buoyant density of newly synthesized mDNA may be explained by changes in structure other than a change in superhelix density, as indicated by its increased resistance to digestion by pancreatic DNase.

Amines↗

DXA body composition studies are not affected by extracellular water measurements using stable sodium bromide dilution.

Body composition studies using dual energy x-ray absorptiometry (DXA) are being increasingly reported in the literature. When DXA body composition measurements are combined with body water studies, stable bromide is often administered to measure extracellular water. Bromine attenuates x-rays significantly more than soft tissue and so could affect DXA body composition analysis. DXA scans were performed on 26 adults (12 F, 14 M) before and after the intravenous injection of 3 g sodium bromide (NaBr). No significant differences were noted pre- and post-NaBr infusion for whole-body fat mass, fat-free soft tissue mass and bone mineral content. These findings were supported by a simple mathematical analysis of the likely effect of the sodium bromide infusion. This showed that when 3 g NaBr was introduced into the body, the effect on fat mass estimates was expected to be marginally less than the precision of the DXA technique.

Absorptiometry, Photon↗

Analysis of debromination of 1,2-dibromoethane by cytochrome P-450-linked hydroxylation systems as observed by bromide electrode.

Debromination of 1,2-dibromoethane (DBE) by a rabbit liver microsomal preparation and a reconstituted cytochrome P-450 enzyme system was investigated. The reaction was performed in our newly constructed reaction vessel, in which a bromide electrode was installed. During the reaction, the liberated bromide ion was continuously measured by the bromide electrode, and the amount was recorded. In the microsomal preparation, the DBE-debromination rate per nmol cytochrome P-450 was enhanced by phenobarbital-pretreatment of rabbits compared with the untreated microsomes, whereas it was diminished by 3-methylcholanthrene-pretreatment. The debromination reaction was reconstituted in a purified enzyme system containing phenobarbital-inducible rabbit liver microsomal cytochrome P-450 (P-450PB), NADPH-cytochrome P-450 reductase, and NADPH. The optimum conditions required the presence of dilauroylphosphatidylcholine and cytochrome b5. Cytochrome b5 was found not to be an obligatory component for the DBE-debromination in the reconstituted system, but it stimulated the activity about 3.4-fold. Preincubation of the reconstituted mixture with guinea pig anti-cytochrome P-450PB antiserum markedly inhibited the debromination reaction.

Animals↗

Enhanced neutrophil function in children on bromide therapy.

The final step in neutrophil bacterial killing is formation of a toxic halide complex. For this reason, we studied neutrophil function in children receiving bromide anticonvulsant therapy. Whole blood and serum were obtained from 7 patients with seizure disorders treated orally with triple bromide elixir to examine neutrophil function as measured by luminol enhanced chemiluminescence (CL). Serum bromide concentrations [Br-] were determined concomitantly. There was a direct correlation between [Br-] and CL activity of neutrophils (r = 0.87) with peak CL responses significantly higher than controls when [Br-] were in the therapeutic range (10-20 mM). With [Br-] above 25 mM, CL activity was reduced. Serum from patients also enhanced CL of control neutrophils with a similar relationship to measured [Br-]. To confirm that enhanced neutrophil activity was attributable to [Br-] use, [Br-] ranging from 0-50 mM were added to control neutrophils in otherwise normal physiologic conditions and the CL assay was performed. Results expressed as percent of control values were as follows: [Br-] 5 mM, 110%; 10 mM, 158%; 15 mM, 194%; 20 mM, 252%; 25 mM, 136%; 30 mM, 364%; and 50 mM, 205%. These data demonstrate that Br- enhances phagocytic and bactericidal activity of neutrophils and suggest that Br- therapy may augment host defense capabilities.

Blood Bactericidal Activity↗