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Combined treatment with ipratropium bromide and beta-2-adrenoceptor agonists in childhood asthma.

The effect of adding ipratropium bromide to treatment with beta-2-adrenoceptor agonists was studied in 13 asthmatic children in a double-blind cross-over trial. In the acute phase of the study inhalation of salbutamol 0.1 mg/kg followed by inhalation of 0.25 mg of ipratropium bromide was found to improve pulmonary function variables to a significantly greater extent than salbutamol followed by placebo. The combined therapy also provided significantly better protection than salbutamol plus placebo against exercise-induced asthma. Maintenance treatment with ipratropium bromide (two inhalations four times daily, 20 micrograms per inhalation) in combination with oral terbutaline and aerosolized salbutamol did not alleviate asthmatic symptoms or pulmonary function variables to a degree beyond that achieved with the beta-stimulants alone. There were no side effects associated with the ipratropium bromide treatment. These data suggest that higher doses of ipratropium bromide than are presently used should be tested for maintenance treatment of chronic asthma.

Administration, Oral↗

[Pharmacology of the bronchospasmolytic oxitropium bromide].

The anticholinergic substance (8r)-6 beta, 7 beta-epoxy-8-ethyl-3 alpha-[(-)-tropoyloxyl]-1 alpha H, 5 alpha H-tropanium bromide (oxitropium bromide, Ba 253 BR, Ventilat) is a competitive antagonist of acetylcholine. In vitro, it is many times as effective as atropine. In vivo, oxitropium bromide, following i.v. administration, is also more effective than atropine. Due to its quaternary structure, a central anticholinergic effect cannot be demonstrated. Furthermore, poor enteral resorption is to be expected. Locally administered, as an aqueous aerosol, the effect of the substance is distinctly greater than that of atropine, both in potency and duration of action. This is also true when administered by metered-dose inhaler compared with ipratropium bromide. As, following aerosol administration, the margin between major effect and the most sensitive side-effect is in the ratio 1 : 100, side-effects are unlikely even with marked inhalational overdosage. Oxitropium bromide can be described, therefore, as a preparation free of side-effects which represents in prophylactic use in many cases of obstructive airway disease, an alternative to beta-mimetics and xanthine derivatives.

Acetylcholine↗

Evidence that eosinophils catalyze the bromide-dependent decarboxylation of amino acids.

Human eosinophils from subjects with or without myeloperoxidase (MPO) deficiency and guinea pig eosinophils are able to decarboxylate L-alanine in the presence of the cationic detergent cetyltrimethylammonium bromide (CTAB) but not in the presence of the nonionic detergent Triton X-100. Instead, both normal human neutrophils and guinea pig neutrophils decarboxylate L-alanine in the presence of either detergent. When the non-bromide-containing cationic detergent cetyltrimethylammonium hydroxide (CTAOH) is used instead of CTAB, the eosinophils from MPO-deficient subjects are unable to decarboxylate L-alanine. Decarboxylation occurs with the combination CTAOH-Br-, but not with the combinations CTAOH-I-, CTAOH-CI-, or CTAOH-F-. Bromide in the absence of CTAOH does not promote decarboxylation. Triton X-100 and deoxycholate are much less effective in promoting decarboxylation in the presence of bromide. L-Lysine and L-aspartic acid are decarboxylated to a considerably lower rate than L-alanine in the presence of CTAOH and Br-. It is concluded that the eosinophils can catalyze the bromide-dependent decarboxylation of the apolar amino acid L-alanine in the presence of a cationic detergent.

Alanine↗

[Clinical pharmacological trials of a new metered dose inhaler, IK-6, a combination of the bronchodilators fenoterol and ipratropium bromide (author's transl)].

IK-6, a combination of the sympathomimetic fenoterol (low dose) and the anticholinergic ipratropium bromide (normal dose), was tested single-blind and cross-over in outpatients with intrinsic asthma and in healthy volunteers. In 12 patients IK-6 resulted in a good acute bronchodilatation, the onset was as quick as following fenoterol and the maximum was as good as following ipratropium bromide. In another 12 patients the protective effect against an acetylcholine-induced bronchoconstriction was better after IK-6 than after ipratropium bromide and much better than after salbutamol. In these patients IK-6 caused no unwanted side effects. In 10 healthy volunteers the effect on heart rate was tested after inhalation of 20 puffs of bronchodilators applied by metered dose inhaler. The anticholinergics (ipratropium bromide, oxitropium bromide, dibenzothiepine-derivative) caused no effect. Following fenoterol a marked increase in heart rate could be observed, whereas the combination IK-6 caused only a slight increase.

Aerosols↗

Neurobehavioral effects of methyl bromide inhalation exposures.

Methyl bromide, a neurotoxic agent with a permissible US exposure limit of 20 ppm, is used primarily as a fumigant by an estimated 75,000 workers in the United States. This project was developed to evaluate the neurobehavioral effects of chronic and subchronic exposure to methyl bromide. One group of rats and rabbits was exposed to 65 ppm of methyl bromide for a total exposure of four 25-h weeks, or 100 h, and rats were exposed to 55 ppm of methyl bromide for a total exposure of 36 30-h weeks, or 1,080 h. Comparable control groups were given similar treatment, but no exposure. Behavioral tests of open field activity and limb coordination were conducted weekly during both phases of the experiment with rats, and eyeblink reflexes were measured weekly in rabbits. Nerve conduction velocity measurements were taken weekly from both rats and rabbits during the 65-ppm four-week exposures and monthly from rats during the 55-ppm 40-week exposures. Exposure to 65 ppm for four weeks significantly reduced eyeblink responses and nerve conduction velocity in rabbits but had no effect on rats. Exposure to 55 ppm of methyl bromide for 36 weeks had no effect on nerve conduction velocity, open-field activity, or coordination in rats.

Animals↗

Use of thiazole orange homodimer as an alternative to ethidium bromide for DNA detection in agarose gels.

Detection of polymerase chain reaction-amplified DNA fragments is commonly accomplished by visualizing the products in electrophoretic agarose beds with the use of ethidium bromide under ultraviolet light. However, ethidium bromide is mutagenic, and special handling and disposal precautions must be used. We report the use of a nonmutagenic dye, thiazole orange dimer (TOTO), which can be substituted for ethidium bromide. The excitation maximum for TOTO under ultraviolet light is 488 nm, and the absorption maximum is 510 nm, necessitating photographic filters different from those used for ethidium bromide for optimal results. Of particular importance in TOTO's use is the quantity used for each gel lane, since excess TOTO will cause unacceptable product mobility retardation. TOTO is only slightly more expensive than ethidium bromide. Overall, this stain provides very good visualization of polymerase chain reaction--amplified DNA bands in agarose gels. We believe the use of this safer reagent will become more widespread with increased regulation of laboratory activities.

Base Sequence↗

[Effects of aerosol oxitropium bromide and fenoterol on maximal exercise capacity in chronic obstructive pulmonary disease and their correlation with air flow during exercise and with parameters of maximal exercise].

To examine the effects of bronchodilators on maximal exercise capacity and their correlation with airflow during exercise in patients with chronic obstructive pulmonary disease (COPD), we conducted a double-blind, randomized comparison between inhaled fenoterol (beta 2-agonist) and oxitropium bromide (anticholinergic agent) in 8 patients with stable COPD (mean age 73 years, mean FEV1 1.1 L, mean FEV1% 50%). Only oxitropium bromide resulted in statistically significant improvement in FEV1 40 min after inhalation. On maximal exercise, fenoterol did not affect oxygen uptake (VO2 max), minute ventilation (VEmax), respiratory frequency (Rfmax), ventilatory efficacy (VEmax/VO2 max), peak expiratory flow during exercise (PEFmax), heart rate (HRmax) and dyspnea (Borg Scale Slope). After oxitropium bromide, dyspnea during exercise and HRmax decreased significantly, but PEFmax and other parameters did not change significantly compared with control. There was no correlation between changes in dyspnea during exercise and changes in FEV1 and PEFmax after oxitropium bromide inhalation. We conclude that inhaled oxitropium bromide, an anticholinergic agent, reduces dyspnea during exercise in patients with COPD. This favorable effect was not due to change of airflow limitation during exercise, and other factors can thus influence reduction of dyspnea during exercise in these patients.

Administration, Inhalation↗

[Effects of oxitropium bromide on exercise and lung function in patients with pulmonary emphysema].

Anticholinergic drugs have been reported to be effective in pulmonary emphysema. We studied the effects of the anticholinergic drug oxitropium bromide on exercise capacity and lung function in patients with this disease. We studied 11 men and 1 women, aged 69.3 +/- 4.5 yrs, in whom chest radiography showed pulmonary emphysema. Before and after the subjects inhaled two puffs of oxitropium bromide, they walked in a corridor for 12 minutes, and the distance they walked and spirometric data were recorded. FVC and FEV1 were significantly higher after inhalation of the drug. FEV1% did not change, and the distance walked increased slightly. We also studied symptoms and peak expiratory flow rate in 37 patients with pulmonary emphysema before and after the start of therapy with inhaled oxitropium bromide. Symptom scores of wheezing and sleep improved, and peak expiratory flows increased significantly. We conclude that inhaled oxitropium bromide can improve lung function and slightly increase exercise capacity in patients with pulmonary emphysema. These effects may be caused by bronchodilation-induced increases in FEV1 and FVC. Monitoring of peak expiratory flow in patients with pulmonary emphysema may be useful for evaluating the clinical effectiveness of oxitropium bromide.

Aged↗

Facile alkylation of methionine by benzyl bromide and demonstration of fumarase inactivation accompanied by alkylation of a methionine residue.

Benzyl bromide is a selective alkylator of sulfur nucleophiles including methionine and cysteine. Only the mercaptide ion is a more efficient nucleophile than is the sulfur ether of methionine. Alkylation rates relative to methionine are 200: less than or equal to 0.03: less than or equal to 0.03: less than or equal to 0.02 for GS-, histidine, tryptophan, and GSH, respectively. Alkylation of methionine by benzyl bromide is more than 50 times faster than alkylation by iodoacetate. Fumarase is readily inactivated by exposure to benzyl bromide at pH 6.6 to 6.8 accompanied by alkylation of close to 1 methionine residue/subunit. Fumarase fully inactivated by exposure to benzyl bromide shows no detected alkylation of amino acid residues other than methionine. The rate of inactivation of fumarase by benzyl bromide is decreased about 4-fold by the presence of excess substrates. Denaturation of fumarase in 6 M urea at pH 6.5 exposes additional methionine as well as cysteine residues to alkylation.

Animals↗

Copper bromide laser treatment of facial telangiectasia: results of patients treated over five years.

BACKGROUND AND OBJECTIVE: Various yellow light lasers have been used over the past decade in an attempt to eradicate facial telangiectasia. Based on their power output, spot size, and pulsing characteristics, these lasers belong to one of two categories that exist at either end of a spectrum--high power, short pulse, and large spot size, or low power, long exposure, and small spot size. The copper bromide laser clearly belongs in the latter group, but with higher available power than most other lasers in this group, it exists further along the spectrum toward the region in which the laser parameters might be considered closer to theoretical ideals for treating certain cutaneous vascular pathologies. The objective of this study was to ascertain the role and efficacy of the copper bromide laser on treatment of a variety of facial telangiectasia. STUDY DESIGN/MATERIALS AND METHODS: A total of 570 patients with facial telangiectasia of different diameters and on different regions of the face were treated with the copper bromide laser one or more times and followed up over 5 years. RESULTS: More than 75% clearance was achieved in 70% patients, 50-75% clearance in 17.4% patients, and < 50% clearance in 12.6% patients. Poor results were correlated with anatomical location on the nasal alae and nasal tip and also with vessel size. Very small (< 100 microns) and very large (> 300 microns) vessels did not respond as well as vessels in the 100-300-micron diameter group. Very large vessels responded better to a combination of sclerotherapy and laser treatment. There were no reported long-term adverse effects. CONCLUSION: The copper bromide laser is a safe and effective modality for the treatment of the majority of facial telangiectasia. It is less suited to treating very small vessel lesions such as diffuse erythema, and conversely very large vessels as well as those of the nasal alae. These latter two groups respond better and more permanently to combined sclerotherapy and laser treatment.

Adult↗

Bromide space, total body water, and sick cell syndrome.

Displacements of the bromide space (Br-82-C, as a marker for the extracellular fluid compartment) are caused by an enhanced anatomical space and/or increased permeability of cells to bromide. The ratio Br-82-C: total body water (TBW) was evaluated to be 0.83 +/- 0.17 in critically ill patients (n = 38) compared with the normal value of 0.46 +/- 0.04 (n = 10). Because of normal TBW in critically ill patients (TBW = 505 +/- 68 ml/kg), an increased bromide penetration into cells seems to be responsible for the enlarged ratio Br-82-C: TBW. Taking into consideration measurements in patients with malabsorption (BR-82-C: TBW = 0.56 +/- 0.13; n = 13) and carcinoma of the rectum and colon (Br-82-C: TBW = 0.66 +/- 0.24; n = 18) we think that the bromide space is a good measurement of the effective extracellular water.

Adult↗

Headspace--gas chromatographic determination of inorganic bromide residues in vegetables.

This study describes a headspace gas-chromatographic method for the quantitative determination of inorganic bromide in vegetables. Different parameters influencing the reaction of the bromide ion into 2-bromoethanol have been investigated. The analysis of 2-bromoethanol is performed by the headspace--electron capture--gas chromatographic technique using a fused silica capillary column CP wax 52 CB. Recoveries of 99.75% +/- 4.1% have been obtained for bromide concentrations of 5 up to 350 mg/kg. Sixty-nine samples have been analysed by this method. The results are in good agreement with the normal bromide extraction method. The absolute detection limit is 2 ng corresponding to 0.5 mg Br-/kg for a slit ratio of 1:10.

Bromides↗

Effect of enhanced bromide intake on the concentration ratio I/Br in the rat thyroid gland.

Interaction of bromine with iodine was studied in the rat thyroid gland under the conditions of different bromide intake. Bromine and iodine in the thyroid dry weight were determined by instrumental neutron activation analysis (INAA). It was found that with increased bromide intake the bromine concentration in the thyroid gland increased with simultaneous decrease in the iodine concentration. The change in the I/Br concentration ratio depends on a number of halogen binding positions and on the bromide supply. The I/Br parameter reacts sensitively to the changes of bromide intake already in the region of low bromine concentration levels.

Animals↗

Tramadol and hyoscine N-butyl bromide combined in infusion solutions: compatibility and stability.

BACKGROUND: More than two-thirds of patients with metastatic cancer experience pain. Tramadol is one of the most interesting and useful weak opioids used by palliative care units to treat moderate to moderately severe pain. Relief of distressful symptoms in terminally ill patients is of prime importance; a common practice is to administer opioid analgesics in conjunction with other drugs as hyoscine N-butyl bromide, which is very useful in reducing secretions in patients with inoperable malignant bowel obstruction. The pursuit for excellence in symptom control in patients unable to take oral medication has led to the administration of medications by other routes such as the subcutaneous route. PURPOSE: The purpose of this study was to fulfill the lack of information regarding the compatibility and physical stability of tramadol hydrochloride and hyoscine N-butyl bromide combined in infusion solutions. METHODS: The stability of nine admixtures (stored in polypropylene syringes) at 4 and 25 degrees C was assessed over a period of 15 days. RESULTS: Nonstatistically significant losses of tramadol HCl and a maximum loss of 7% for hyoscine N-butyl bromide were obtained. Therefore, tramadol HCl (dose range, 100-400 mg/day) can be formulated together in saline with hyoscine N-butyl bromide (dose range 40-80 mg/day) for s.c. infusion using a 60-ml drug infuser for a duration of 7 days.

Analgesics, Opioid↗

Quantification and specific detection of collagenous proteins using an enzyme-linked immunosorbent assay and an immunoblotting for cyanogen bromide peptides.

A method for the detection of collagenous proteins within cyanogen bromide digests of tissues has been devised. The peptides produced by digestion with cyanogen bromide were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to a nitrocellulose filter. They were stained on the filter by incubation first with antibodies to collagen and then with a second antibody covalently linked to horseradish peroxidase, 4-chloro-1-naphthol was added, and the bound enzyme was assayed. This procedure is useful for the identification and characterization of collagens of types I, III, IV, and V in tissues. In addition, we have developed a sensitive and specific competitive enzyme-linked immunosorbent assay (ELISA) which is convenient for quantifying collagens (types I, III, and IV) in tissues. In this kind of assay, soluble cyanogen bromide peptides compete with cyanogen bromide peptides adsorbed onto a solid-phase support for rabbit anti-collagen antibodies. We determined the amount of bound antibody by using goat anti-rabbit immunoglobulin G covalently conjugated to horseradish peroxidase and then provided a substrate for the enzymatic reaction. The sensitivity range of the ELISA is 0.09 micrograms/ml in the region of 90 to 10% binding.

Animals↗

Effect of dietary chloride content on the elimination of bromide by dogs.

The effect of dietary chloride content (0.2, 0.4 and 1.3 per cent chloride on a dry matter basis) on the disposition of a single oral dose of bromide (14 mg kg-1) was evaluated in normal beagles. Increasing the dietary chloride content from 0.2 to 1.3 per cent resulted in a significant decrease in the mean apparent elimination half-life from 69 +/- 22 days to 24 +/- 7 days. The mean area under the concentration curve (AUC) for dogs fed 1.3 per cent chloride was significantly smaller than the AUC for dogs fed 0.2 per cent chloride. Dietary chloride had no effect on the maximum serum concentrations (Cmax) or on the time (Tmax) to reach the maximum concentrations. The steady-state serum bromide concentrations predicted from the single dose data for daily doses of 14 mg kg-1 of bromide were significantly lower in dogs fed 1.3 per cent chloride (310 +/- 150 mg litre-1) than in dogs fed 0.2 per cent chloride (1950 +/- 1140 mg litre-1). The predicted mean daily doses of bromide necessary to maintain serum levels within the therapeutic range for dogs fed 1.3 per cent chloride (43 +/- 13 mg kg-1) were almost twice as high as the dose estimated for dogs fed 0.4 per cent chloride (22 +/- 3 mg kg-1) and nearly three times as high as the dose estimated for dogs fed 0.2 per cent chloride (15 +/- 4 mg kg-1). These differences were statistically significant (P = 0.002).

Animals↗

Antigenic determinants of influenza virus hemagglutinin. II. Antigenic reactivity of the isolated N-terminal cyanogen bromide peptide of A/Memphis/72 hemagglutinin heavy chain.

Gel filtration of a cyanogen bromide digest of pure intact hemagglutinin from A/Memphis/102/72 influenza virus allowed the isolation of a variety of fragments. One of these fragments consists of three cyanogen bromide peptides (CNl and CN3 from HA1, and CNl from HA2) which remain linked together by disulphide bonds. This fragment was found to be antigenically active, as it was able to form antigen-antibody complexes (detected by affinity chromatography of radioiodinated peptide-IgG mixtures on protein A-Sepharose) with IgG directed against the protein moiety of viral hemagglutinin. The three cyanogen bromide peptides present in this disulphide-linked fragment were separated by gel filtration, carried out under reducing conditions, and tested for antigenic activity after controlled reoxidation of the individual peptides. Only one cyanogen bromide peptide, CNl from HA1, showed significant binding to antibody. The results indicate that antigenic activity of A/Mem/1O2/72 hemagglutinin resides within the N-terminal 170 amino acid residues of the hemagglutinin heavy chain.

Antibodies, Viral↗

Bromide-ion residues in food and feedstuffs.

The daily intake of bromide ion by humans was estimated from two total-diet studies conducted in the summer of 1976 and in the winter of 1978 and involving in each case investigation of 100 samples. The average daily intake found was 7.8 mg/person in the first study and 7.6 mg/person in the second study (with ranges of 2.9-15.0 and 1.8-17.2 mg/person/day, respectively). National surveys, covering several thousands of samples, showed that certain leafy vegetables and some herbs could occasionally contain high residues of bromide ion (greater than 200 mg/kg). An important source of these high residues is the treatment of soils with methyl bromide against nematodes. Action has been taken to minimize contamination of the human diet with bromide ion by this route.

Animal Feed↗