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Anion-exchange chromatographic determination of bromide in serum.

In this liquid-chromatographic method for the determination of bromide in human serum, an important and unique feature is pre-analysis ultrafiltration of the sample, which effectively removes proteins. The chromatographic system consists of an anion-exchange column (Whatman Partisil SAX 10-micron particles), an isocratic phosphate-buffered mobile phase, and ultraviolet detection at 195 nm. The absolute detection limit, 0.6 ng of bromide, makes this method the most sensitive assay for serum bromide yet reported. The day-to-day CV ranged from 1.6% to 4.9%. Analytical recovery of bromide added to serum samples ranged from 96.2% to 108.8%. Data on bromide in serum are presented for adults and newborns and for adults given bromide orally.

Adult↗

Automated assay of plasma bromide after a single deproteinization step.

This study aimed to simplify the spectrophotometric fluorescein method for measuring plasma bromide, improve its reproducibility, and automate it. After major modifications of the method, we obtained an essentially linear calibration curve for plasma concentrations of bromide between 0 and 5.0 mmol/L. The intraassay CV for measuring bromide in the supernatants of deproteinized plasma samples (initial plasma concentrations 2.5-5.0 mmol/L) was as low as 0.5-1.0% (n = 9). When all the procedures were incorporated, including deproteinization and dilution of plasma, the intraassay CV was 2% at 2.5 mmol/L (n = 5) and 1% at 5.0 mmol/L (n = 5). The interassay CV for measuring bromide in plasma supernatants (initial plasma bromide concentration > 2.5 mmol/L) was 1%. Analytical recovery of bromide added to plasma was 99.1% +/- 2.5%. The new method is simpler and more reproducible than other spectrophotometric methods. Conditions for its automation are described.

Autoanalysis↗

Methyl bromide intoxication in four field-workers during removal of soil fumigation sheets.

Methyl bromide is a highly toxic and penetrating compound used extensively as an insecticide for dry foodstuffs and as a soil fumigant (in greenhouses and fields) for the control of nematodes, fungi, and weeds. More than 300 cases of systemic poisoning and 60 fatalities attributable to methyl bromide have been reported [Alexeeff and Kilgore, 1983], resulting in substantial regulations concerning its handling, storage, application, and disposal. A recent exposure incident at a Connecticut nursery represents to our knowledge the first report of toxicity stemming from exposures in the field during removal of plastic sheets days after injection of methyl bromide into soil. Following removal of polyethylene sheets covering soil fumigated with methyl bromide, four field-workers developed fatigue and light-headedness and 3 workers noted progressive respiratory, gastrointestinal (GI), and neurologic symptoms. The acute systemic symptoms improved over several days, but later-onset neuropsychiatric symptoms persisted for several weeks. This incident stresses the need for improved worker education and strict adherence to safety precautions during all stages of methyl bromide fumigation and raises the possibility of an increased risk of toxicity associated with methyl bromide fumigation during a cool season.

Adult↗

Evaluation of propargyl bromide for control of barnyardgrass and Fusarium oxysporum in three soils.

With the scheduled phasing out of methyl bromide, there is an urgent need for alternatives. We evaluated the efficacy of propargyl bromide as a potential replacement for methyl bromide for the control of barnyardgrass (Echinochloa crus-galli) and Fusarium oxysporum in an Arlington sandy loam, a Carsitas loamy sand and a Florida muck soil. Soil was mixed with barnyardgrass seeds or F oxysporum colonized on millet seeds, and treated with propargyl bromide at a range of concentrations. The mortality of the fungi and weed seeds was determined after 24 h of exposure at 30 degrees C. The concentrations required to inhibit 50% barnyard seed germination (LC50) were 2.8, 2.4 and 48.5 micrograms g-1 in the sandy loam, loamy sand and muck soil, respectively. In contrast, the LC50 values for F oxysporum were 11.2, 10.8 and 182.1 micrograms g-1 in the sandy loam, loamy sand and muck soil, respectively. The low efficacy of propargyl bromide in the muck soil was a result of the rapid degradation and high adsorption of the compound in the soil. The degradation half-life (t1/2) was only 7 h in the muck soil at an initial concentration of 6.8 micrograms g-1, compared to 60 and 67 h in the sandy loam and loamy sand, respectively. The adsorption coefficients (Kd) were 0.96, 0.87 and 5.6 cm3 g-1 in the sandy loam, loamy sand and muck soil, respectively. These results suggest that registration agencies should consider site-specific properties in recommending application rates for propargyl bromide.

Adsorption↗

The protective effects of ipratropium bromide and terbutaline on distilled water-induced bronchoconstriction.

In a randomized, double-blind, placebo-controlled study, we investigated the protective effects of ipratropium bromide 160 micrograms and 320 micrograms and terbutaline 500 micrograms on ultrasonically nebulized distilled water (UNDW)-induced bronchoconstriction in nine stable asthmatic patients. Both drugs caused a significant increase (P < 0.001) in baseline FEV1 with no significant differences between the drugs or both doses of ipratropium bromide. Pre-inhalation of ipratropium bromide 320 micrograms and terbutaline 500 micrograms inhibited UNDW-induced bronchoconstriction (P < 0.01), whereas ipratropium bromide 160 micrograms had no protective effect. The protective effects of ipratropium bromide showed a large interindividual variation. There was no correlation between the increase in baseline FEV1 and PD20 UNDW, indicating that the protective effect on UNDW-induced bronchoconstriction is not dependent on the bronchodilation induced by terbutaline and ipratropium bromide. It also appears that the UNDW-induced bronchoconstriction is at least partly vagally mediated.

Administration, Inhalation↗

Effect of cimetropium bromide on esophageal motility and transit in patients affected by primary achalasia.

The effect of cimetropium bromide, a new anticholinergic agent, in patients with primary achalasia was studied. Twenty such patients (12 females and 8 males, mean age 38 years, range 15-56) were studied. Diagnosis was performed by radiology, endoscopy, and manometry. Lower esophageal sphincter pressure and body wave amplitude were measured by means of a five-channel catheter constantly perfused by a low-compliance pneumohydraulic pump. Patient received cimetropium bromide 10 mg intravenously over 3 min or placebo in a double-blind manner. In five patients esophageal transit evaluated by scintiscanning was studied on separate occasions after cimetropium bromide or placebo. Baseline mean lower esophageal sphincter pressure was 46 +/- 5 mm Hg and mean amplitude of body waves was 30 +/- 8 mm Hg. Cimetropium bromide induced a significant decrease in sphincter pressure and body wave amplitude that measured 13 +/- 3 mm Hg and 8 +/- 4 mm Hg, respectively, 15 min after the end of infusion. The decrease was maintained for 45 +/- 5 min. A marked reduction in repetitive body waves was also noted. Esophageal transit was also accelerated with cimetropium bromide. Maximal stomach radioactivity was observed after 8 +/- 1.8 sec while with placebo this was reached after 65 +/- 1.5 sec (P < 0.01). It is concluded with cimetropium bromide reduces LES pressure and shortens transit in primary esophageal achalasia. It may be useful in the treatment of this esophageal motility disorder.

Adolescent↗

Direct determination of bromide ions in seawater by capillary zone electrophoresis using polyethyleneimine-coated capillaries.

A rapid and simple capillary electrophoretic method was developed for the direct determination of bromide ion in seawater. We have found an effective method, based on the use of polyethyleneimine-coated capillaries and the addition of sodium chloride to the background electrolyte. The use of coated capillaries with a cationic polymer changes the direction of the electroosmotic flow in the capillary, which favors the migration speed of the bromide ion and enables the use of low salt concentrations in the separation electrolyte. Bromide ion in seawater can be determined within 2 min using this system and 20 mmol L(-1)NaCl-containing separation electrolyte. The detection limit for the bromide ion was 0.45 microg ml(-1). The method was applied to the determination of bromide ion in seawater samples collected from the Bosphorus and the Black Sea. Bromide contents in samples from 0 to 72 m depths varied between 33.2 and 72.8 mg L(-1) with a mean 3.0% RSD.

Journal Article↗

Comparison of pinaverium bromide, manganese chloride and D600 effects on electrical and mechanical activities in rat uterine smooth muscle.

The effects of pinaverium bromide, were compared with those of D600 and manganese chloride (Mn), on membrane potentials, ionic currents and isometric contractions in uterine smooth muscle strips from pregnant rats. Pinaverium bromide (10(-7) - 10(-6) M) depressed twitch contractions and K-contractures within 15-20 min while D600 (2 X 10(-6) M) and Mn (10(-3) M) abolished both contractions. D600 and pinaverium bromide were more potent inhibitors in K-depolarized preparations than in polarized tissues. At a supramaximal dose (10(-5) M), pinaverium bromide decreased the rate of rise, amplitude, and rate of repolarization of the action potential, and prolonged the potential duration. The inward Ca current was depressed and the reduction in Cai was responsible for the decrease in K current. Pinaverium bromide (10(-5) M) depressed the myometrial contractions induced in Ca-free solution by acetylcholine (10(-4) M) and by prolonged membrane depolarizations. Mn (2.5 X 10(-3) M) only reduced the Ach-induced contraction and D600 (10(-5) M) had no effect on intracellular Ca stores. The results indicate that pinaverium bromide has Ca channel blocking properties similar to those of currently used Ca antagonists; it may also exert an effect to depress contractions supported by intracellular Ca release.

Action Potentials↗

Regression of methyl bromide-induced forestomach lesions in the rat.

There is continuing concern about the role of irritation in cancer development. Methyl bromide, a widely used fumigant and known irritant reported to cause forestomach carcinomas in rats, was dissolved in peanut oil and given by gavage at 50 mg/kg body wt to Wistar rats five times per week for 13 to 25 weeks. Starting at Week 13, methyl bromide administration was discontinued for half of the methyl bromide-treated rats (stop treatment group). After that, rats from both the continuous treatment and stop treatment groups were terminated at 4-week intervals to follow the progression of the stomach lesions. Forestomach lesions were not found in control rats receiving peanut oil and killed at 13 or 25 weeks. At 13 weeks the forestomachs from rats receiving methyl bromide were contracted and adherent to the liver and spleen. Inflammation, acanthosis, fibrosis, and a high incidence of pseudoepitheliomatous hyperplasia were found microscopically in treated animals. At 25 weeks, 100% of the rats receiving methyl bromide continuously had hyperplastic lesions of the forestomach which were more severe than those at 13 weeks. Evidence of malignancy was seen in one rat and the lesion was considered a very early carcinoma. In the stop treatment group that received methyl bromide for 13 weeks, there was regression of the stomach lesions, but at the 12-week final sacrifice, adhesions, fibrosis, and mild acanthosis remained. This study illustrates the need for regression experiments for complex forestomach lesions in rodents, especially when an irritating chemical is given by gavage.

Administration, Oral↗

Control of the hypersecretion of vasomotor rhinitis by topical ipratropium bromide.

A randomized, double-blind, placebo-controlled trial of ipratropium bromide nasal spray was performed with 25 patients with vasomotor rhinitis. Criteria for selection of patients were (1) clear watery nasal discharge more than 1 hour each day, (2) absent or mild nasal obstruction, (3) no known allergic cause, and (4) no satisfactory response to previous alternative medications. Ipratropium bromide, two sprays (20 micrograms per spray) in each nasal cavity four times daily, for 3 weeks, produced a major reduction in nasal discharge severity and duration (p less than 0.00005 for daytime reduction in both). There was a decreased daily use of nasal tissues (p = 0.0017). At the end of the trial, 21 patients preferred the drug, two preferred placebo, one had no preference, and one patient dropped out for a reason unrelated to symptoms or treatment. This drug preference in favor of active medication was statistically significant at the 0.01 level. Local mild side effects were reported in 21/25 (84%) with ipratropium bromide and 8/25 (32%) with placebo (p = 0.0004). Pulse and blood pressure were not affected. In an ensuing 1-year open trial in which the frequency of use of ipratropium bromide nasal spray was selected by the subjects, the dosage chosen was considerably lower than that used in the controlled trial. There were seven dropouts caused by insufficient benefit or local side effects. Seventeen subjects continued the use of ipratropium bromide for 1 year and reported good results and no side effects. Topical nasal ipratropium bromide is highly effective in the control of the rhinorrhea of vasomotor rhinitis. Drug dosage is a major determinant of local nasal side effects.

Administration, Topical↗

Ipratropium bromide aqueous nasal spray for patients with perennial allergic rhinitis: a study of its effect on their symptoms, quality of life, and nasal cytology.

Ipratropium bromide is an anticholinergic agent with topical activity that has been studied as a freon-propelled aerosol spray for therapy of nonallergic rhinitis. This is the first report of its use both as an aqueous nasal spray and in perennial allergic rhinitis. In this study 123 patients who had symptoms of perennial allergic rhinitis were randomized to receive ipratropium bromide 21 micrograms or 42 micrograms or placebo, one spray per nostril three times a day for 4 weeks. Patients maintained daily diaries of duration and severity of nasal symptoms and were evaluated weekly. Mean duration and severity of rhinorrhea was decreased in both ipratropium bromide treatment groups by comparison with placebo, with consistently greatest improvement in the group treated with ipratropium bromide 42 micrograms per nostril three times a day. No statistically significant differences occurred among treatment groups in duration or severity of postnasal drip, congestion, or sneezing. Seventy percent of patients treated with 42 micrograms of ipratropium bromide thought it had good or excellent effect on rhinorrhea (p less than 0.05 vs placebo); significantly more patients thought that it had improved the quality of life (p = 0.02). No changes occurred in nasal cytology, and no significant local or systemic adverse events occurred. These data indicate that ipratropium bromide significantly decreases the rhinorrhea of perennial allergic rhinitis.

Administration, Intranasal↗

Analysis of methylbenactyzium bromide in human urine by thin-layer chromatography and pyrolysis gas chromatography.

A rapid and simple method of utilizing thin-layer chromatography (TLC) and pyrolysis gas chromatography (PyGC) for the identification and determination of methylbenactyzium bromide in human urine was studied in this report. Methylbenactyzium bromide was extracted from urine with ODS-cartridge (Sep-Pak C18), then spotted onto a silica gel 60 F254 TLC plate. After development, the separated spot of methylbenactyzium bromide was scraped and wrapped with a ferromagnetic foil without extraction by any organic solvents. The sample was applied into PyGC analysis. The optimum temperature for pyrolysis was 590 degrees C. The main degradation product of methylbenactyzium bromide was identified as diphenylmethane in this procedure by gas chromatography/mass spectrometry (GC/MS). A calibration graph prepared by absolute calibration method showed a good linearity over the concentration range of 1-75 micrograms/spot for methylbenactyzium bromide. The coefficient of variation obtained for eleven replicate analyses of the 3 micrograms/spot of standard methylbenactyzium bromide was 3.8%. The detection limit of this compound by this procedure was 0.1 micrograms/spot.

Calibration↗

In Pseudomonas aeruginosa ethidium bromide does not induce its own degradation or the assembly of pumps involved in its efflux.

Xu et al. [Biochem. Biophys. Res. Commun. 305 (2003) 941] reported that, when a mutant strain of Pseudomonas aeruginosa lacking its major multidrug efflux pump complex, MexAB-OprM, was incubated with 100 microM ethidium bromide, the fluorescence, caused by its binding to DNA following its entry into cells, decreased gradually. The authors concluded that the intracellular ethidium bromide "induced" either its degradation or its efflux through the assembly of unknown efflux pumps. We found, through quantitation of ethidium bromide by absorption spectroscopy, that the total amount of ethidium bromide in the system remained constant under these conditions, indicating the absence of its degradation. Furthermore, intracellular ethidium bromide kept increasing during the experiment, showing that the decrease of fluorescence was due to self-quenching, and that ethidium bromide is not pumped out by a newly assembled efflux system.

Bacterial Outer Membrane Proteins↗

Otilonium bromide enhances sensory thresholds of volume and pressure in patients with irritable bowel syndrome.

UNLABELLED: Visceral hyperalgesia has been suggested to play a role in the development of symptoms presented by irritable bowel syndrome patients. Otilonium bromide was developed to block smooth muscle Ca release to control cramping pain of these patients. AIMS: to determine whether otilonium bromide can influence sensory thresholds of patients suffering from irritable bowel syndrome. METHODS: 15 patients with Rome-II positive IBS were tested by Synectics Visceral Stimulator Barostat using rapid phasic distension (870 ml/min). The sensory threshold for first sensation, stool, pain and maximum tolerable volume and pressure were measured. All of the parameters were tested before and 1 week after the initiation of otilonium bromide (Spasmomen, Berlin Chemie, 3x40 mg) therapy. RESULTS: The perceptual thresholds for first sensation, stool, pain and maximum tolerable distention were, 8.8+/-1.7 Hgmm, 19.2+/-2.1 Hgmm, 26.3+/-2.8 Hgmm, 28.7+/-2.8 Hgmm for pressure, 90+/-21 ml, 145+/-28 ml, 208+/-25 ml, 213+/-28 ml for volume, before treatment, respectively. Otilonium bromide treatment did not influence the thresholds for first sensation and stool, 7.4+/-1.4 Hgmm, 20.7+/-4.6 Hgmm and 83+/-21 ml, 178+/-35.8 ml, respectively. The pressure threshold of pain was significantly higher 1 week after treatment (26.3+/-2.8 Hgmm vs. 29.1+/-5.5 Hgmm, P<0.05), but the volume threshold of this sensation remained unchanged (208+/-25 ml vs. 234+/-39 ml, not significant). The pressure (28.7+/-2.8 Hgmm vs. 38.1+/-3.4 Hgmm, P<0.05) and volume (213+/-28 ml vs. 278+/-27 ml, P<0.05) thresholds for maximum tolerable volume were increased by 7 days otilonium bromide treatment. CONCLUSION: These data suggest that otilonium bromide enhances sensory thresholds to recto-sigmoideal distention.

Adult↗

The effect of ipratropium bromide on maximal exercise capacity in asthmatic and non-asthmatic men.

The effect of 0.5 mg nebulized ipratropium bromide (IB) on the cardio-respiratory responses to a progressive maximal cycle exercise test was compared with a matched placebo (P) in eight mild asthmatic and eight non-asthmatic men. The forced expiratory volume in l s (FEV1) in the asthmatic group was higher after ipratropium bromide both at rest [IB, mean 4.07 (SD 1.18) l versus P, 3.83 (1.29) l, P less than 0.05] and after exercise [IB, 3.64 (1.31) l versus P, 3.30 (1.40) l, P less than 0.02]. Since the percentage fall in the FEV1 after exercise was not significantly changed by ipratropium bromide [IB, -12 (11)% versus P, -16 (14)%], the improvement in the post-exercise FEV1 in the asthmatic group is attributable to the pre-exercise bronchodilatation. The resting and post-exercise FEV1 in the non-asthmatic group were also significantly higher after ipratropium bromide. However, neither group showed any differences in the cardio-respiratory, haemodynamic or subjective responses to the progressive maximum exercise test when ipratropium bromide was compared with placebo. These results demonstrate the absence of significant cardio-respiratory effects during exercise with this relatively high dose of ipratropium bromide, in patients with mild asthma and in non-asthmatic subjects. No ergogenic effect on maximal exercise performance was shown to question its use by asthmatic athletes engaged in high level competition.

Adult↗

A comparison of bronchodilating effects of salmeterol and oxitropium bromide in stable chronic obstructive pulmonary disease.

Anti-cholinergic agents are generally regarded as the bronchodilator therapy of first choice in the treatment of stable chronic obstructive pulmonary disease (COPD), considering that they may be more effective than in inhaled beta 2-agonist. However, results of the authors' recent studies conflict to some extent with this suggestion because they demonstrate that this is true only for short acting beta 2-agonists but not for long-acting beta 2-agonists. Oxitropium bromide is an anti-cholinergic drug that has been shown to produce a similar degree of bronchodilation to that obtained with ipratropium bromide, but with a longer-lasting effect. In the present study, the time course of inhaled oxitropium bromide bronchodilation in comparison to that of inhaled salmeterol in a group of patients with partially reversible COPD was evaluated. Twelve male patients with moderate to severe COPD participated in the study. The study had a single-bind, cross-over, randomized design. The bronchodilator activity of 50 micrograms salmeterol hydroxynaphthoate, 200 and 400 micrograms oxitropium bromide and placebo, which were all inhaled from a metered-dose inhaler, was investigated on several non-consecutive days. The highest FVC and FEV1, obtained from one or the other of the reproducible curves, were kept for analysis. Measurements were performed at the following times: immediately before inhalation of treatment, and at 15, 30, 60, 120, 180, 240, 300, 360, 480, 600 and 720 min after inhalation of the individual treatment. Salmeterol tended to have a delayed time to peak effect, but had a longer duration of effect than oxitropium. The response to salmeterol exceeded the response to 200 micrograms oxitropium for 12 h, but its responses were significantly (P < 0.05) greater than those to 200 micrograms oxitropium from 10 to 12 h. From 3 to 12 h, salmeterol also surpassed 400 micrograms oxitropium but differences were not significant (P < 0.05). The mean FEV1 area under the curve was significantly (P < 0.05) larger after salmeterol when compared to 200 micrograms oxitropium bromide, but there was no significant difference (P < 0.05) between salmeterol and 400 micrograms oxitropium bromide. No significant changes in pulse rate, blood pressure or electrocardiograms were found among the four groups as compared with placebo group. These findings confirm and extend what has been demonstrated by the authors' previous studies, and show that salmeterol compares conveniently with anti-cholinergic drugs in terms of effects on lung function at clinically recommended doses.

Aged↗

Influence of higher than conventional doses of oxitropium bromide on formoterol-induced bronchodilation in COPD.

We examined the influence of higher than conventional doses of oxitropium bromide on formoterol-induced bronchodilation in patients with partially reversible stable COPD. Twenty outpatients inhaled one or two puffs of formoterol (12 microg puff(-1)), or placebo. Two hours after inhalation, a dose-response curve to inhaled oxitropium bromide (100 microg puff(-1)) or placebo was constructed using one puff, one puff, two puffs and two puffs, for a total cumulative dose of 600 microg oxitropium bromide. Doses were given at 20-min intervals and measurements made 15 min after each dose. On six separate days, all patients received one of the following: (1) formoterol 12 microg + oxitropium bromide 600 microg, (2) formoterol 12 microg + placebo, (3) formoterol 24 microg + oxitropium bromide 600 microg, (4) formoterol 24 microg + placebo, (5) placebo + oxitropium bromide 600 microg, or (6) placebo + placebo. Both formoterol 12 microg and 24 microg induced a good bronchodilation (formoterol 12 microg, 0.19-0.20 l; formoterol 24 microg 0.22-0.24 l). The dose-response curve of oxitropium, but not placebo, showed an evident increase in FEV1, with a further significant increase of respectively 0.087 l and 0.082 l after the formoterol 12 microg and formoterol 24 microg pre-treatment. This study shows that improved pulmonary function in patients with stable COPD may be achieved by adding oxitropium 400-600 microg to formoterol. There is not much difference in bronchodilation between combining oxitropium with formoterol 12 microg or 24 microg. In any case, formoterol 24 microg alone seems sufficient to achieve the same bronchodilation induced by oxitropium 600 microg alone in most patients.

Administration, Inhalation↗

Use of 0.06% ipratropium bromide nasal spray in children aged 2 to 5 years with rhinorrhea due to a common cold or allergies.

BACKGROUND: Rhinorrhea from common colds or allergies in children is similar to that in adults, yet there are few data on the use of ipratropium bromide nasal spray in children younger than 5 years. OBJECTIVE: To evaluate the safety and efficacy of 0.06% ipratropium bromide nasal spray in 2- to 5-year-old children with rhinorrhea from a common cold or allergies. METHODS: A total of 230 children (43 with common colds and 187 with allergies) participated in an open-label, multicenter study. Patients with a common cold received ipratropium bromide nasal spray (84 microg per nostril) 3 times daily for 4 days; those with allergies received ipratropium bromide nasal spray (42 microg per nostril) 3 times daily for 14 days. RESULTS: In the common cold and allergy groups, 91% and 90% of the parents, respectively, found that ipratropium bromide was either "very useful" or "somewhat useful." Furthermore, 67% and 91% of parents in the common cold and allergy groups, respectively, found that administration of a nasal spray was either "extremely easy" or "very easy." Symptom scores were improved from baseline in both groups. The nasal spray was well tolerated and was not associated with serious or systemic anticholinergic adverse effects. Most adverse events were infrequent and mild to moderate, and study discontinuation due to an adverse event occurred in less than 3% of patients. CONCLUSIONS: The 0.06% ipratropium bromide nasal spray, 42 or 84 microg per nostril 3 times daily, is easy to administer, safe, and effective for the control of rhinorrhea in children aged 2 to 5 years with a common cold or allergies.

Administration, Intranasal↗