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PubMed2003

Compatibility of haloperidol and hyoscine-N-butyl bromide in mixtures for subcutaneous infusion to cancer patients in palliative care.

The administration of drugs by s.c. infusion is routinely practiced in palliative medicine for the management of patients who are no longer able to take oral medication. It is not uncommon for two or more drugs to be combined in s.c. infusion solutions. Unfortunately, the compatibility and stability of haloperidol and hyoscine- N-butyl bromide has not yet been determined. The objective of this study was to study the compatibility and stability of solutions containing both drugs in polypropylene syringes. Nine different solutions were assessed for up to 15 days following preparation. The solutions were prepared in polypropylene syringes with 0.9% saline as a diluent and stored at 4 degrees C and 25 degrees C. High-performance liquid chromatography was the analytical technique used to measure haloperidol and hyoscine- N-butyl bromide. The initial concentration ranges were 0.3125-1.25 mg/ml for haloperidol and 2.5-10.0 mg/ml for hyoscine- N-butyl bromide. Haloperidol was precipitated at a concentration of >/=1.25 mg/ml when it was combined with hyoscine- N-butyl bromide. Concentrations of hyoscine- N-butyl bromide lower than 10 mg/ml in mixtures with haloperidol or 0.625 mg/ml of haloperidol in mixtures with hyoscine- N-butyl bromide for s.c. infusion allow for the administration of both drugs without any significant loss after storage at 25 degrees C for periods of up to 15 days, with approximately >/=90% and 88%, respectively, of haloperidol and hyoscine- N-butyl bromide remaining. However, after storage of the mixtures for equivalent periods at 4 degrees C the losses of hyoscine- N-butyl bromide observed at the end of the study were higher than 20%, while the percentages of haloperidol remaining after 15 days at this temperature were >/=94.37%.

Antiemetics↗
PubMed1994

Bromide, in the therapeutic concentration, enhances GABA-activated currents in cultured neurons of rat cerebral cortex.

We investigated the effect of bromide on gamma-aminobutyric acid (GABA)-activated currents in cultured cerebral neurons of the rat, employing whole-cell voltage- and current-clamp techniques. Application of 100 microM GABA elicited currents whose reversal potential was 0 mV with equal concentrations of chloride in both pipette and bath solutions and more negative than -60 mV with 159 mM chloride extracellularly and 4 mM chloride inside. Bicuculline blocked the currents. These findings showed that the currents were composed of chloride flux through GABAA receptor-coupled channels. Reversal potential revealed a permeability ratio of bromide with respect to chloride (PBr/PCl) of 1.51. When 100 microM GABA was applied with the extracellular solution containing 140 mM bromide and 19 mM chloride, the currents were enhanced 2.00- and 1.91-fold at the holding potentials of -20 mV and 0 mV, respectively. Extracellular solutions containing various concentrations of bromide substituted for the same amount of chloride were applied with 100 microM GABA. The therapeutic concentration of 10 mM and 20 mM bromide enhanced the currents 1.28- and 1.36-fold of the control currents at the holding potential of -20 mV, respectively. Under current-clamp recording, a larger hyperpolarization was obtained by the application of GABA with a 140 mM bromide-containing solution. These findings suggest that bromide potentiated GABA-activated currents at the therapeutic concentrations ranging from 10 mM to 20 mM, causing the larger GABA-induced hyperpolarization. It is postulated that the antiepileptic effect of bromide might occur through the potentiation of inhibitory postsynaptic potentials elicited by GABA.

Animals↗
PubMed2005

Effect of n-alkyl trimethylammonium bromides on folding and stability of alkaline and acid-denatured cytochrome c: a spectroscopic approach.

The molten globule (MG) state can be an intermediate in the protein folding pathway; thus, its detailed description can help understanding protein folding. Alkyl trimethylammonium bromides including dodecyl trimethylammonium bromide, DTAB; tetradecyl trimethylammonium bromide, TTAB; and hexadecyl trimethylammonium bromide, HTAB; cationic surfactants that are commonly used to mimic hydrophobic binding environments such as cell membranes, are known to denature some native state proteins, including horse cytochrome c (cyt c). In this article, refolding of alkaline and acid-denatured cyt c are studied under the influence of n-alkyl trimethylammonium bromides to form MG-like states at both low concentration (pH 11) and above the critical micelle concentration (pH 2) using ultraviolet and visible absorption, fluorescence and circular dichroism (CD). The addition of n-alkyl trimethylammonium bromides to the unfolded state of cyt c in alkaline and acidic condition appears to support the stabilized form of the MG state. The m-values of the refolded state of cyt c by DTAB, TTAB and HTAB showed substantial variation. The enhancement of m-values as the stability criterion of the MG state corresponded with increasing chain length of the cited n-alkyl trimethylammonium bromides. Based on the results obtained, the merits of two models of the protein-surfactant structure are discussed for various n-alkyl trimethylammonium bromides concentration in inducing the MG state at two different pH conditions. Therefore, hydrophobic interactions play a dominant role in stabilizing the MG state.

Acids↗
PubMed2006

[Efficacy of tiotropium bromide (Spiriva) in patients with chronic-obstructive pulmonary disease (COPD) of different severities].

BACKGROUND: Aim of this study was to evaluate the efficacy of inhaled Tiotropium bromide in COPD patients of different severities in pneumological practices during a three months clinical trial. METHODS: A randomized, double blind, placebo controlled study including COPD-patients (FEV1/FVC < 70 %, FEV1 < or = 70 % predicted; age > or = 40 years; > or = 10 pack years) of different severities was performed. The efficacy of 18 microg Tiotropium bromide once daily on lung function and exacerbations over 12 weeks was evaluated by respective pulmonary function tests (spirometry) before (trough value) and 2 hours after inhalation of study medication. RESULTS: 1639 patients (1236 Tiotropium bromide, 403 placebo; FEV1 reversibility after 200 microg Ipratropium bromide + 200 microg Fenoterol: 7.9 +/- 7.5 % predicted [mean +/- sd]) were randomized. After 12 weeks of treatment Tiotropium bromide led to significant increases of trough FEV1 (23 - 24 h after last inhalation; + 79 +/- 17 ml), and 2 h after Tiotropium bromide inhalation (+ 128 +/- 19 ml) (all values vs. placebo, adjusted mean +/- se, p < 0.0001). FVC and IVC were also improved significantly. In mild COPD (FEV1 > or = 50 - 70 %) improvements were most pronounced (trough FEV1 + 113 +/- 29 ml, 2 h post-inhalation + 181 +/- 33 ml; all values vs. placebo., p < 0.0001). 14.6 % of patients treated with Tiotropium bromide had a COPD exacerbation vs. 19.9 % of patients treated with placebo (p = 0.0151). The time to first exacerbation was prolonged (p = 0.0092 vs. placebo). CONCLUSION: Tiotropium bromide 18 microg once daily led to a persistent improvement of lung function and a reduction of exacerbations in patients with COPD of different severities.

Adult↗
PubMed2003

Bromism from daily over intake of bromide salt.

Bromide intoxication today is an infrequent disease, but preparations containing bromide are still available in nonprescription compounds, on the French market. We report a casewith bromide intoxication due to daily over intake (approximately 20 tablets per day; i.e. total elemental bromide intake approximately 6 g/day) of calcium bromo-galactogluconate (Calcibronat) for 1.5 months. A 30-year-old woman with a long history of psychotropic drug abuse was hospitalized in a psychiatric department for neuropsychological manifestations. She presented a seriously disturbed mental status with confusion, disorientation, auditory and visual hallucinations, and loss of short-time memory. A markedly increased serum bromide level of 1717 mg/L (21.5 mEq/L) measured on the first day after her admission confirmed the diagnosis of chronic bromism suspected based on her symptomatology. During her hospitalization, bromide plasma concentrations were measured and monitored using inductively coupled plasma mass spectrometry, a sensitive and very specific method. After withdrawal of the drug, the symptoms improved within 8 days. Serial bromide concentrations gradually declined throughout nearly 2 months of monitoring, until she was discharged from the hospital. We found an elimination half-life of bromide in blood of approximately of 10 days. This case demonstrates that, while today bromism occurs infrequently, it should still be included in the differential diagnosis of neuropsychiatric symptoms.

Adult↗
PubMed2001

Ipratropium bromide hydrofluoroalkane inhalation aerosol is safe and effective in patients with COPD.

STUDY OBJECTIVE: To compare the efficacy and safety of ipratropium bromide reformulated with the chlorofluorocarbon (CFC)-free propellant hydrofluoroalkane (HFA)-134a (ipratropium bromide HFA) to that of the marketed ipratropium bromide inhalation aerosol (containing CFC) in patients with COPD. DESIGN: This was a randomized, double-blind, parallel-group, placebo-controlled, multicenter trial. The primary efficacy parameter was acute bronchodilator response. The primary end points were peak change in FEV(1) from baseline and area under the response-time curve. SETTING: Thirty-one clinical centers in the United States participated in this project. PATIENTS: A total of 507 patients with moderate-to-severe COPD were randomized, and 444 patients completed the trial. INTERVENTIONS: Twelve weeks of treatment four times daily with one of the following: ipratropium bromide HFA, 42 microg; ipratropium bromide HFA, 84 microg; HFA placebo; ipratropium bromide inhalation aerosol, 42 microg; or CFC placebo. MEASUREMENTS AND RESULTS: Patients in all active treatment groups had significant bronchodilator responses as shown by increases in mean FEV(1) from baseline of at least 15%. Bronchodilator response in all active treatment groups was also significantly more than their respective placebo treatments based on FEV(1), area under the time-response curve from 0 to 6 h, and peak response. FVC results were similar to those seen with FEV(1). There were no significant differences in adverse events, laboratory findings, or ECG findings among the treatment groups. CONCLUSIONS: Ipratropium bromide HFA, 42 and mgr;g, provided bronchodilation comparable to the marketed ipratropium bromide CFC, 42 and mgr;g, over 12 weeks of regular use.

Adult↗
PubMed1989

Eosinophils preferentially use bromide to generate halogenating agents.

Human eosinophils preferentially utilize bromide to generate a brominating agent, even at physiological halide concentrations, where chloride (140 mM) is over 1000-fold greater than bromide (20-100 microM). Under the same conditions, neutrophils use chloride to generate a chlorinating agent. The total amount of active halogen trapped by 1,3,5-trimethoxybenzene from eosinophils increases by over 2-fold as the added bromide concentration increases from 0 to 100 microM, with approximately 40 nmol of halogen trapped per million cells at the highest bromide level. At least 25-35% of the oxygen consumed by stimulated eosinophils is directed toward the generation of halogenating species. Since the relative halogenating behavior of eosinophil peroxidase and neutrophil myeloperoxidase in this bromide range is essentially identical to that of the cells, the specificity of eosinophils toward bromide is intrinsic to eosinophil peroxidase and not to any special cellular properties. These results suggest that human eosinophils use bromide in vivo and that a deficiency of bromide may influence their ability to produce halogenating agents.

Bromides↗
PubMed1986

Sweat bromide excretion in cystic fibrosis.

Sweat reabsorption of bromide and chloride was studied in controls, obligate carriers of the cystic fibrosis gene, and individuals with cystic fibrosis. Sweat and serum ultrafiltrate concentrations of bromide and chloride were determined by an anion-exchange chromatographic method. The reabsorption of each ion was determined by the ratio of the sweat concentration to the serum ultrafiltrate concentration. Sweat bromide reabsorption paralleled chloride reabsorption in each of the groups. The mean bromide reabsorption ratio for 12 controls was 0.10 +/- 0.10 (range 0 to 0.26), for 11 obligate carriers 0.09 +/- 0.09 (range 0 to 0.24), and for 13 individuals with cystic fibrosis 0.86 +/- 0.26 (range 0.47 to 1.38). The mean chloride reabsorption ratio for the controls was 0.24 +/- 0.11 (range 0.06 to 0.45), for the obligate carriers 0.22 +/- 0.10 (range 0.10 to 0.45), and for individuals with cystic fibrosis 0.95 +/- 0.09 (range 0.76 to 1.1). Thus, there was a significant decrease in bromide reabsorption in individuals with cystic fibrosis compared with controls (P less than 0.001) and heterozygotes (P less than 0.001), which was similar for chloride. As with chloride reabsorption, no difference was found in bromide reabsorption between obligate carriers and controls, indicating that this measurement could not be used for heterozygote detection. In each of the three groups bromide reabsorption was greater than chloride reabsorption. This finding is consistent with a size-dependent anion channel in the sweat epithelial cell because bromide has a smaller hydrated radius than chloride.

Absorption↗
PubMed1984

Comparison of effects of nifedipine, propantheline bromide, and the combination on esophageal motor function in normal volunteers.

Both intracellular calcium ions and neural input are important in esophageal smooth muscle contraction. The aim of this study was to compare the effects of well-tolerated doses of the calcium-channel blocker, nifedipine (20 mg sublingually/buccally) with the anticholinergic, propantheline bromide (15 mg orally) and the combination of these two agents on esophageal motor function. Seven healthy volunteers underwent manometric evaluation after nifedipine, propantheline bromide, the combination, and placebo on different days. Lower esophageal sphincter pressure decreased significantly (P less than 0.05 vs basal and placebo) by 32% after nifedipine, but fell only 21% after propantheline bromide. After the combination lower esophageal sphincter pressure fell by 45% (P less than 0.05 vs basal and placebo and nifedipine alone). Contraction amplitude in the body of the esophagus decreased significantly (P less than 0.05 vs basal and placebo) by 26% after propantheline bromide, but fell only 11% after nifedipine. The combination led to a decrease of 37% in contraction amplitude, but this was not significantly different from that obtained with propantheline bromide alone. No drug or combination had any effect on other manometric parameters. These data show that in the normal subjects studied with the above doses: (1) nifedipine has a greater effect than propantheline bromide on the lower esophageal sphincter; (2) propantheline bromide has a greater effect than nifedipine on esophageal contraction amplitude; and (3) the combination of nifedipine and propantheline bromide has an enhanced effect on both lower esophageal sphincter pressure and esophageal contraction amplitude.

Administration, Oral↗
PubMed2006

Physicochemical and in vitro deposition properties of salbutamol sulphate/ipratropium bromide and salbutamol sulphate/excipient spray dried mixtures for use in dry powder inhalers.

The physicochemical and aerodynamic properties of spray dried powders of the drug/drug mixture salbutamol sulphate/ipratropium bromide were investigated. The in vitro deposition properties of spray dried salbutamol sulphate and the spray dried drug/excipient mixtures salbutamol sulphate/lactose and salbutamol sulphate/PEG were also determined. Spray drying ipratropium bromide monohydrate resulted in a crystalline material from both aqueous and ethanolic solution. The product spray dried from aqueous solution consisted mainly of ipratropium bromide anhydrous. There was evidence of the presence of another polymorphic form of ipratropium bromide. When spray dried from ethanolic solution the physicochemical characterisation suggested the presence of an ipratropium bromide solvate with some anhydrous ipratropium bromide. Co-spray drying salbutamol sulphate with ipratropium bromide resulted in amorphous composites, regardless of solvent used. Particles were spherical and of a size suitable for inhalation. Twin impinger studies showed an increase in the fine particle fraction (FPF) of spray dried salbutamol sulphate compared to micronised salbutamol sulphate. Co-spray dried salbutamol sulphate:ipratropium bromide 10:1 and 5:1 systems also showed an increase in FPF compared to micronised salbutamol sulphate. Most co-spray dried salbutamol sulphate/excipient systems investigated demonstrated FPFs greater than that of micronised drug alone. The exceptions to this were systems containing PEG 4000 20% or PEG 20,000 40% both of which had FPFs not significantly different from micronised salbutamol sulphate. These two systems were crystalline unlike most of the other spray dried composites examined which were amorphous in nature.

Aerosols↗
PubMed2002

Effect of perfluorocarbon (perfluorooctyl bromide) vapor on tidal volume measurement during partial liquid ventilation.

OBJECTIVE: To compare measured tidal volumes with and without perfluorocarbon (perfluorooctyl bromide) vapor, by using tidal volumes in the range suitable for neonates ventilated with partial liquid ventilation. We also aimed to determine the correction factor needed to calculate tidal volumes measured in the presence of perfluorooctyl bromide vapor. DESIGN: Prospective, experimental study. SETTING: Neonatal research laboratory. INTERVENTIONS: Reproducible tidal volumes from 5 to 30 mL were produced with a rodent ventilator and drawn from humidifier chambers immersed in a water bath at 37 degrees C. Control tidal volumes were drawn from a chamber containing oxygen and water vapor, and the perfluorocarbon tidal volumes were drawn from a chamber containing oxygen, water vapor, and perfluorooctyl bromide vapor. MEASUREMENTS AND MAIN RESULTS: Tidal volumes were measured by a VenTrak respiratory mechanics monitor with a neonatal flow sensor and a Dräger pneumotachometer attached to a Dräger neonatal ventilator. All tidal volumes measured with perfluorooctyl bromide vapor were increased compared with control. The VenTrak-measured tidal volumes increased by 1.8% to 3.5% (an overall increase of 2.2%). The increase was greater with the Dräger hot-wire anemometer: from 2.4% to 6.1% (an overall increase of 5.9%). Regression equations for mean control tidal volumes (response, Y) vs. mean perfluorooctyl bromide tidal volumes (predictor, X) are as follows: for the VenTrak, Y = -0.026 + (0.978 x X), r =.9999, p <.0001; and for the Dräger, Y = 0.251 + (0.944 x X), r =.9996, p <.0001. CONCLUSIONS: The presence of perfluorooctyl bromide vapor in the gas flowing through pneumotachometers gives falsely high tidal volume measurements. An estimate of the true tidal volume allowing for the presence of perfluorooctyl bromide vapor can be made from regression equations. Any calculation of lung mechanics must take into account the effect of perfluorooctyl bromide vapor on the measurement of tidal volume.

Fluorocarbons↗
PubMed1992

The influence of terfenadine and ipratropium bromide alone and in combination on bradykinin-induced nasal symptoms and plasma protein leakage.

Nasal instillation of bradykinin elicits many of the characteristic features of rhinitis. To assess the relevance of histamine release from metachromatic cells and the activation of cholinergic pathways, we investigated the effects of terfenadine, a histamine H1-receptor antagonist, and ipratroprium bromide, a selective antimuscarinic agent, on bradykinin induced rhinorrhoea, nasal airways resistance (NAR), nasal pain and plasma protein leakage. Oral terfenadine (120 mg) or matched placebo and nasal ipratropium bromide (80 micrograms) or matched placebo were administered at 4 hr and 30 min respectively prior to bradykinin nasal challenge in two randomized, double-blind and cross-over studies on eight non-rhinitic subjects. Thus subjects received either double-placebo, oral terfenadine and nasal placebo, oral placebo and nasal ipratopium bromide or oral terfenadine and nasal ipratropium bromide, as pretreatment. Bradykinin challenge induced mean maximal increases of 57%, 59%, 77% and 72% in NAR on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratropium bromide pretreatment days respectively. These increments were not significantly different. Similarly rhinorrhoea and nasal pain induced by bradykinin nasal challenge were not significantly different on the four challenge days. Bradykinin nasal challenge caused a mean maximal increase in albumin levels in recovered nasal lavages of 11.5, 13.0, 12.2 and 12.3 times of baseline levels on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratroprium bromide pretreatment days respectively. Similarly total protein levels achieved a mean maximal increase of 8.0, 8.2, 7.9 and 8.8 times of baseline levels on these challenge days. The increments in both albumin and total protein did not significantly differ on the 4 challenge days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

Dose response study of ipratropium bromide aerosol on maximum exercise performance in stable patients with chronic obstructive pulmonary disease.

BACKGROUND: Although the bronchodilating effect of inhaled anticholinergics has been established in patients with chronic obstructive pulmonary disease (COPD), their effects on exercise capacity are still controversial. Previous studies have suggested that the standard dosage hardly affects exercise tolerance, whereas higher doses might elicit an improvement. The aim of the present study was to determine the dose of ipratropium bromide aerosol that improves exercise performance using progressive cycle ergometry in patients with stable COPD. METHODS: Twenty men with stable COPD of mean (SD) age 69.2 (4.6) years and forced expiratory volume in one second (FEV1) 1.00 (0.37) 1 were studied in a randomised double blind manner. Each patient received ipratropium bromide in doses of 240 micrograms, 160 micrograms, 80 micrograms, 40 micrograms, and placebo from a metered dose inhaler (MDI) with an InspirEase spacer on five separate days. Spirometric parameters were assessed before and at 30, 60, 90, and 120 minutes after each inhalation, and pulse rate and blood pressure were also measured immediately before each spirometric measurement. Symptom limited progressive (20 watts/min) cycle ergometer exercise tests were performed 90 minutes after each inhalation. RESULTS: Ipratropium bromide in doses of 160 micrograms and 240 micrograms produced a greater increase in FEV1 than 40 micrograms or 80 micrograms ipratropium bromide at all time points. Doses of 160 micrograms and 240 micrograms ipratropium bromide also produced greater increases in maximal work load and maximal oxygen consumption than placebo, whereas 40 micrograms and 80 micrograms ipratropium bromide did not. There was a weak correlation between the change in FEV1 and the change in maximal work load (r = 0.45). No differences were found in pulse rate or blood pressure between the treatment and placebo groups, and no side effects were noted throughout the study. CONCLUSIONS: A dose of at least four times the standard dose of ipratropium bromide from an MDI with a spacer device was necessary to improve maximal cycle exercise capacity in patients with stable COPD. Although the data from cycle ergometry cannot be directly applied to exercise performed during day to day activities, it is conceivable that the recommended doses of ipratropium bromide do not elicit the optimal clinical benefits.

Aerosols↗
PubMedDate not supplied

Ipratropium bromide nasal spray 0.03% provides additional relief from rhinorrhea when combined with terfenadine in perennial rhinitis patients; a randomized, double-blind, active-controlled trial.

Medical treatment of perennial rhinitis is aimed at providing symptomatic relief of individual symptoms. Multiple agents are administered when no single agent provides complete relief. Studies assessing the benefit/risk of combined therapy are important, especially for newly available agents such as ipratropium bromide nasal spray, a topical anticholinergic agent approved for the treatment of rhinorrhea in allergic and nonallergic perennial rhinitis. The objective was to determine whether the combined use of ipratropium bromide nasal spray 0.03% (42 mcg per nostril) administered three times daily with a nonsedating antihistamine (terfenadine, 60 mg administered twice daily) is safe and provides greater clinical benefit than use of the placebo nasal spray plus terfenadine. Our method was a multicenter, 6-week, double-blind, randomized, active-controlled, crossover trial of 205 patients with perennial rhinitis (114 allergic and 91 nonallergic), 18 to 75 years of age, who had clinically significant rhinorrhea. After a 1-week run-in period, patients were treated for 2 weeks with one of the two treatment regimens, followed by a 1-week washout period, and then were treated for another 2 weeks with the other treatment regimen. Daily diary symptoms scores of rhinorrhea, congestion, and sneezing were obtained, as well as biweekly patient and physician global assessments of treatment effectiveness of each of the nasal symptoms. Ipratropium bromide nasal spray plus terfenadine was more effective than vehicle plus terfenadine in reducing the average severity (38% versus 28%) and duration (46% versus 30%) of rhinorrhea during the 2 weeks of treatment from baseline (p < 0.05). The advantage of ipratropium bromide nasal spray plus terfenadine was evident by the second day of treatment and continued throughout the 2-week treatment period. Of patients who responded more to one treatment than another, 69% responded to ipratropium bromide nasal spray plus terfenadine, compared to 31% to vehicle plus terfenadine (p < 0.05). Both physicians and patients rated control of rhinorrhea and sneezing by ipratropium bromide nasal spray plus terfenadine as superior to vehicle plus terfenadine (p < 0.05). The symptom of congestion was controlled equally well by both treatments. Combined active therapy was well tolerated with no increase in adverse events over that seen previously with ipratropium bromide nasal spray alone. The combination of ipratropium bromide nasal spray with terfenadine is more effective than vehicle plus terfenadine for the treatment of rhinorrhea, and does not result in a potentiation of adverse drug reactions.

Administration, Intranasal↗
PubMed1999

Differential expression of mRNA in human thyroid cells depleted of mitochondrial DNA by ethidium bromide treatment.

A wide variety of human diseases have been associated with defects in mitochondrial DNA (mtDNA). The exact mechanism by which specific mtDNA mutations cause disease is unknown and, although the disparate phenotypes might be explained on the basis of impaired mitochondrial gene function alone, the role of altered nuclear gene expression must also be considered. In recent years, the experimental technique of depleting cells of mtDNA by culturing them with ethidium bromide has become a popular method of studying mitochondrial disorders. However, apart from depleting mtDNA, ethidium bromide may have many other intracellular and nuclear effects. The aim of the present study was to investigate the effects of ethidium bromide treatment on nuclear gene expression. A simian-virus-40-transformed human thyroid cell line was depleted of mtDNA by culture in ethidium bromide, and differential display reverse transcriptase-PCR (DDRT-PCR) was then employed to compare mRNA expression between wild-type, mtDNA-replete (rho(+)) and ethidium bromide-treated, mtDNA-depleted (rho(0)) cells. Expression of the majority of nuclear-encoded genes, including those for subunits involved in oxidative phosphorylation, remained unaffected by the treatment. Seven clones were found to be underexpressed; three of the clones showed significant similarity with sequences of the human genes encoding RNase L inhibitor, human tissue factor and ARCN1 (archain vesicle transport protein 1), a highly conserved species which is related to vesicle structure and trafficking proteins. We conclude that the effects of ethidium bromide treatment on nuclear gene expression are not simply limited to changes in pathways directly associated with known mitochondrial function. Further studies will be required to elucidate which of these changes are due to mtDNA depletion, ATP deficiency or other disparate effects of ethidium bromide exposure. Given that most genes appear unaffected, the results suggest that depleting cells of mtDNA by ethidium bromide treatment is a valuable approach for the study of mitochondrial mutations by cybrid techniques.

Blotting, Northern↗
PubMedDate not supplied

[Study of 2.5S RNA of 1,4-alpha-glucan branching enzyme by fluorescent methods using ethidium bromide].

The fluorescence yield and lifetime of ethidium bromide complexes with 1,4-alpha-glucan branching enzyme and its free nucleic acid component 2.5S RNA were measured. Both fluorescence parameters showed a 10-fold increase in comparison with those characteristics for the free dye. This increase allows to suggest the existence of double-stranded regions in 2.5S RNA both in the free as well as in the protein bound state. The coefficients of fluorescence polarization were also determined for ethidium bromide complexed with free and protein bound 2.5S RNA. They proved to be 13 and 18% respectively. No concentration depolarization was observed in both types of ethidium bromide and ethidium bromide--enzyme--RNA complexes. This proves that the double-stranded regions are rather short and that two ethidium bromide molecules can't be bound to each of them. The binding isotherms were measured for ethidium bromide absorbed on 2.5S RNA and on the holoenzyme. Their parameters napp and rmax are identical in the cases of free and protein bound 2,5S RNA (rmax = 0.046 +/- 0.001). However the binding constants of ethidium bromide complexes with free and protein bound 2.5S RNA differ significantly (Kapp = 2.2 X 10(6) M-1 for free 2.5S RNA and Kapp = 1.6 X 10(6) M-1 for the holoenzyme). The quantity of nucleotides involved in the two double-stranded regions accessible for ethidium binding is estimated to be about 28%. Increasing of Mg2+ ion concentration up to 10(-3) results in a decrease of ethidium bromide binding with double stranded regions. It may be due to a more compact tertiary structure of 2.5S RNA in the presence of Mg2+ in the free as well as in protein bound state.

1,4-alpha-Glucan Branching Enzyme↗
PubMed2000

Simultaneous determination of bromide, nitrite and nitrate ions in seawater by capillary zone electrophoresis using artificial seawater as the carrier solution.

We describe capillary zone electrophoresis (CZE) for the simultaneous determination of bromide, nitrite and nitrate ions in seawater. Artificial seawater was adopted as the carrier solution to eliminate the interference of high concentrations of salts in seawater. The artificial seawater was free from bromide ion to enable the determination of bromide ion in a sample solution. For the purpose of reversing the electroosmotic flow (EOF), 3 mM cetyltrimethylammonium chloride (CTAC) was added to the carrier solution. A 100 microm ID (inside diameter) capillary was used to extend the optical path length. The limits of detection (LODs) for bromide, nitrite, and nitrate ions were 0.46, 0.072, and 0.042 mg/L (as nitrogen), respectively. The LODs were obtained at a signal to noise ratio (S/N) of 3. The values of the relative standard deviation (RSD) of peak area for these ions were 1.1, 1.5, and 0.97%. The RSDs of migration time for these ions were 0.61, 0.69, and 0.66%. Artificial seawater samples containing various concentrations of bromide, nitrite, and nitrate ions were analyzed by the method. The error was less than +/-12% even if the concentration ratio of bromide ion to nitrite or nitrate ion was 20-240. The proposed method was applied to the determination of bromide, nitrite, and nitrate ions in seawater samples taken from the surface and the seabed. These ions in other environmental waters such as river water and rainwater samples were also determined by ion chromatography (IC) as well as this method.

Bromides↗
PubMed2006

Removal of bromide and iodide anions from drinking water by silver-activated carbon aerogels.

The aim of this study is to analyze the use of Ag-doped activated carbon aerogels for bromide and iodide removal from drinking water and to study how the activation of Ag-doped aerogels affects their behavior. It has been observed that the carbonization treatment and activation process of Ag-doped aerogels increased the surface area value ( [Formula: see text] ), whereas the volume of meso-(V(2)) and macropores (V(3)) decreased slightly. Chemical characterization of the materials revealed that carbonization and especially activation process considerably increased the surface basicity of the sample. Original sample (A) presented acidic surface properties (pH(PZC)=4.5) with 21% surface oxygen, whereas the sample that underwent activation showed mainly basic surface chemical properties (pH(PZC)=9.5) with only 6% of surface oxygen. Carbonization and especially, activation process considerable increased the adsorption capacity of bromide and iodide ions. This would mainly be produced by (i) an increase in the microporosity of the sample, which increases Ag-adsorption sites available to halide anions, and (ii) a rise of the basicity of the sample, which produces an increase in attractive electrostatic interactions between the aerogel surface, positively charged at the working pH (pH(solution)<pH(PZC)), and the corresponding halide. To test the applicability of these aerogels in water treatment, adsorption of bromide and iodide was studied under dynamic conditions using waters from Lake Zurich. Results obtained showed that the carbonization and activation processes increased the adsorptive capacity of the aerogel sample. However, results showed that the adsorption capacity of the aerogel samples studied was considerably lower in water from Lake Zurich. Results showed X(0.02) (amount adsorbed to initial breakthrough) values of 0.1 and 4.3 mg/g for chloride anion and dissolved organic carbon (DOC), respectively, during bromide adsorption process in water from Lake Zurich. This indicates that the adsorptive capacity reduction observed may be due to (i) blocking of the porosity, caused by adsorption of dissolved organic matter on the aerogel surface, that would impede the access of bromide and iodide ions to Ag-adsorption sites, and (ii) the competition of chloride anions for the same adsorption sites. Bromide- and iodide-saturated columns were regenerated with NH(3) (0.02 M), observing little change in column characteristics. Moreover, the organic polymer precursors were not dissolved and the concentration of surface Ag-adsorption sites is not significantly changed after two adsorption/regeneration cycles. According to these results, Ag-doped activated carbon aerogels could be a very promising agents to remove bromide and iodide from drinking water.

Anions↗