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Pharmacokinetics of pipecurium bromide, a new non-depolarizing neuromuscular blocking agent, in humans.

The pharmacokinetics of 2 beta, 16 beta-bis-(4'-dimethyl-1'-piperazino)-3 alpha, 17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, Arduan), a new non-depolarizing neuromuscular blocking agent, was studied in surgical patients. Plasma concentration-time curves of pipecurium bromide were evaluated by fitting the data to a bi-exponential equation. The average half-lives were T 1/2 alpha = 4.1 +/- 1.4 (n = 8) and T 1/2 beta = 44 +/- 7 (n = 8) min. The pharmacokinetic parameters of pipecurium bromide were found as follows: apparent distribution volume V beta = 261 +/- 28 (n = 8) ml/kg, plasma clearance Cl = 320 +/- 55 (n = 8) ml/min. The microconstants of two-compartment open models were also calculated.

Adult↗

[Controlled clinical study on the efficacy of tiropramide hydrochloride in the treatment of irritable colon: comparison with octylonium bromide].

The effectiveness of a new calmodulin-independent spasmolytic, tiropramide hydrochloride, and octylonium bromide, an antispasmodic calmodulin-antagonist drug, was compared in a controlled trial performed in 60 patients with irritable bowel syndrome with spastic pattern. The effect of treatments was assessed according to the score reduction of following symptoms: abdominal pain, constipation, bloating and dyspepsia. Tiropramide hydrochloride administered at the daily dose of 300 mg for 30 days induced a faster and higher improvement than that observed during the administration of 120 mg daily of octylonium bromide. On 3rd and 5th day, treatment with tiropramide induced the relief of abdominal pain in a significantly greater percentage of patients (p less than 0.05). Besides, in the group of subjects treated with this drug the "pain" score was more markedly decreased. Furthermore, at the end of the study 88% of subjects treated with tiropramide and 47% with octylonium bromide had normal bowel habits. This difference was statistically significant (p less than 0.05). Both treatments are effective in reducing dyspeptic symptoms and bloating. We can conclude that tiropramide--having a significant antispasmodic effect combined with a regulating effect on bowel habits--besides eliminating spasm, would act by synchronizing and therefore normalizing the intestinal motility.

Adult↗

Identification of a propantheline analog in propantheline bromide tablets.

A major impurity in a sample of propantheline bromide tablets has been identified as 9-hydroxypropantheline on the basis of the proton magnetic resonance (PMR) and mass spectra (MS). This identification was confirmed by methanolysis of the tablet extract, which yielded a mixture of methyl xanthanoate and methyl 9-hydroxyxanthanoate. A liquid chromatographic (LC) procedure is described which will permit quantitation of 9-hydroxypropantheline bromide in the presence of propantheline bromide, xanthone, and xanthanoic acid.

Chromatography, Liquid↗

Lidocaine-pancuronium bromide retrobulbar injection: experimental studies of simultaneous neural and myoneural blockage for profound akinesia.

The akinesia of the superior rectus muscle after retrobulbar administration of lidocaine was quantitatively compared to the akinesia after retrobulbar administration of a mixture of lidocaine and pancuronium bromide. Adult cats were given halothane general anesthesia and a limited orbitotomy was performed to facilitate exposure of the superior rectus muscle and its branch of the superior division of the oculomotor nerve. The superior rectus muscle was disinserted and connected to a myograph. A suprathreshold stimulus of 3 volts was then applied to the branch of the oculomotor nerve innervating the superior rectus muscle. The strength, measured in grams, of the superior rectus muscle contraction was then quantitated with the myograph. Subsequently, retrobulbar administration of the drug was given and at 10 minute intervals thereafter the suprathreshold electrical stimulus of 3 volts was reapplied to the nerve innervating the superior rectus muscle, and the strength of the contraction was recorded with the myograph. Retrobulbar administration of 0.5 cc of 2% lidocaine was compared with retrobulbar administration of a mixture of 0.5 cc of lidocaine 2% and 0.2 mg of pancuronium bromide at a dosage of 0.04 mg per kilogram. For the first 30 minutes of the experiment, each retrobulbar administration provided profound akinesia with a total absence of measurable muscular contraction, despite suprathreshold stimulation of the nerve. From 40 to 120 minutes following the retrobulbar administration, the combination of lidocaine 2% and pancuronium bromide was associated with persistent absence of measurable superior rectus contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Local↗

[Genetic characteristics of Chinese hamster cell resistance to colchicine, actinomycin D and ethidium bromide].

We have tried to study genetics of Chinese hamster cellular drug resistance to colchicine, actinomycin D and ethidium bromide. Resistant variants arising at a frequency 10(-5) to 10(-7) were selected from a sensitive population. Pretreatment with MNNG increased this frequency 106, 9-15, 12-26 times for colchicine, actinomycin D and ethidium bromide, respectively. Fluctuation test analysis allows to suppose that phenotypic expression of drug resistance is genetically determined and resulted from random genetical events. Significant values of particular correlation coefficients for selecting resistant variants in a set of independently originated subpopulations suggest the genetical identity of the majority of variants selected by colchicine and actinomycin D. At the same time, the significant portion of colchicine-resistant cells may be selected using ethidium bromide. It is not unlikely that under above experimental conditions, each selective agent reveals genetically different resistant variants. The possible genetic mechanisms of resistance to the drugs used are discussed.

Animals↗

Mouse skin carcinogenicity tests of the flame retardants tris(2,3-dibromopropyl)phosphate, tetrakis(hydroxymethyl)phosphonium chloride, and polyvinyl bromide.

The flame retardants tris(2,3-dibromopropyl)phosphate, tetrakis(hydroxymethyl)phosphonium chloride, and polyvinyl bromide were tested for carcinogenic activity by skin application 3 times weekly in random-bred female ICR/Ha Swiss mice for 420 to 496 days. Tris(2,3-dibromopropyl)phosphate at two dose levels (30 mg and 10 mg/application) induced benign and malignant tumors of the skin, forestomach, and oral cavity (tongue and gingiva) in a statistically significant number of mice (30/group). A statistically significant incidence of papillary tumors of the lung was observed at both dosages, and the higher dose also resulted in one mouse with a tubular adenoma of the kidney. Tetrakis(hydroxymethyl)phosphonium chloride (2 mg/application, 60 mice) and polyvinyl bromide (0.1 ml latex suspension/application, 30 mice) were inactive. Polyvinyl bromide was also injected s.c. into another group of female ICR/Ha Swiss mice once weekly for 48 weeks, and the mice were observed for a total of 60 weeks. Liposarcomas were induced in 19 of 30 mice, which was ascribed to physical carcinogenesis. Appropriate solvent and no-treatment control groups were included.

Administration, Topical↗

Effects of ethidium bromide on the extractability of nuclear receptor-estrogen complex.

In previous reports we challenged the concept that uterine nuclei of rats contain two forms of estrogen receptors, one salt extractable and the other salt resistant. Although it is likely that a certain fraction of the nuclear bound receptor-estrogen complex exists as a ternary high-affinity acceptor-receptor-estrogen complex, current salt extraction procedures do not allow discrimination between receptor-17beta-estradiol complexes associated with high-affinity and low-affinity nuclear binding sites. Recent reports suggested that the DNA-intercalating agent ethidium bromide selectively extracted those sites that appeared to be salt resistant. In view of contradictory reports to this effect, we have attempted to clarify this issue. The data presented indicate that ethidium bromide is not a useful tool for the identification of a specific class ("salt-resistant") of nuclear binding sites for receptor-17beta-estradiol complexes. This conclusion is based on measurement of nuclear bound receptor-17-beta-estradiol following KCl and/or ethidium bromide extraction by using both the direct assay and the nuclear exchange assay.

Animals↗

Inhibitory effect of pinaverium bromide on gastrointestinal contractile activity in conscious dogs.

The inhibitory effect of 4-(6-bromoveratryl)-4-(2-[2-(6,6-dimethyl-2-norpinyl)-ethoxy]-ethyl)-morpholinium hydroxide (pinaverium bromide), a quaternary ammonium derivative, on the contractile activity of the gastrointestinal tract from the stomach to the colon was investigated in six conscious dogs. Gastrointestinal motor activity was monitored by means of chronically implanted force transducers. Pinaverium bromide was continuously administered i.v. for 30 min in doses of 10 and 20 mg/kg/h during both the digestive and interdigestive states. It was found that pinaverium bromide strongly inhibited gastrointestinal contractile activity during both the digestive and interdigestive states; contractions in the stomach were most strongly inhibited; however, those in the small and large bowels were also significantly inhibited. No significant side effects in the circulatory and respiratory systems and the gastrointestinal tract such as nausea, vomiting or diarrhea were observed during and after the infusion of this agent.

Animals↗

[Changes in the alkaline cation transport across the plasma membrane of CHO-K1 cell lines resistant to ethidium bromide].

Sodium and potassium intracellular concentration, rate constants of sodium and potassium and rubidium influx were determined for cultured CHO-K1 cell lines, both sensitive and resistant to ethidium bromide. The emission technique was used to measure cation fluxes into potassium and sodium-free magnesium medium. Ethidium bromide sensitive and resistant cell have similar potassium concentrations, whereas sodium concentration in the latter is by almost 2.5 times higher than that in the former. A wide range of changes both in ouabain-sensitive and ouabain-resistant fluxes was found in resistant cells: the ouabain-inhibited rubidium influx is by 3-5 times lower, the ouabain-sensitive sodium efflux is practically absent, and ouabain-inhibited potassium efflux appears. In resistant cells the ouabain-insensitive influx of rubidium is decreased by almost 2 times. It is assumed that the selection of cells for resistance to ethidium bromide is accompanied by ":pleiothypic" changes of cell membrane, involving both active and passive cation transport.

Animals↗

[Effect of ethidium bromide on the electrical activity of nerve cells].

The interaction of ethidium bromide with stretch receptor neurons of the crayfish has been studied. The fluorescent staining of the neuron axon membrane was shown to be accompanied with the inactivation of its electrical action potential generation capacity. Taking into account the high specificity of ethidium bromide fluorescence rising under condition of its complexation with nucleic acids especially, the existence of RNA in composition of axon membrane electrogenic channels is suggested. The modification of RNA by ethidium bromide may lead to the inactivation of electrogenic channels in the axon membrane.

Animals↗

[On the problems with respect to the formation of N-nitroso compound precursors when using alkylating agents in the fumigation of foodstuffs. II. N-methylation of various amino acids by the action of methyl bromide (author's transl)].

The aim of this investigation was to determine whether the insecticide, methyl bromide, used in the treatment of foodstuffs reacts with the amino group of various amino acids in the sense of an N-methylation, thus generating substrates which can be converted to nitroso compounds, i.e. those which are the precursors of cancerogenic compounds. Cooled liquid methyl bromide was added to the aqueous solutions of five amino acids at different pH values. Samples for thin layer chromatographic separation of the derivatives formed were taken after 1, 2, 3, 4, and 8 hours. The method of proving used was at ninhydrine reaction. The results show that methyl bromide reacts with the amino acids glycine, alanine, valine, leucine and glutamic acid to degrees depending upon the pH value and the length of the reaction. The corresponding N-methyl derivatives are formed, namely sarcosine, N-methyl alanine, N-methyl valine, N-methyl leucine, and N-methyl glutamic acid.

Alanine↗

The use of DAPI as a replacement for ethidium bromide in forensic DNA analysis.

Ethidium bromide is used extensively for the visualization of DNA in forensic applications. This is usually accomplished by the addition of dye to the gel and buffer before electrophoresis or by staining the gel after the run. In both procedures considerable ethidium bromide containing buffer is generated that must be decontaminated. We demonstrate that another fluorescent DNA binding dye, 4',6-diamidino-2-phenylindole dihydrochloride (DAPI), can be used in place of ethidium bromide for yield and restriction gels, and to stain the visual marker of analytical gels. A low concentration of DAPI is added directly to the DNA. Most of the stain is immediately bound to the DNA and remains bound during electrophoresis.

DNA↗

Effect of ipratropium bromide and/or sodium cromoglycate pretreatment on water-induced bronchoconstriction in asthma.

The mechanisms underlying water-induced bronchoconstriction are still not fully understood. Cholinergic reflexes and mast cell mediator release are currently believed to play an important pathogenetic role. In order to evaluate the relative contribution of each of these mechanisms, we studied the effect of ipratropium bromide (80 micrograms), a muscarinic antagonist, and sodium cromoglycate (20 mg), an inhibitor of mast cell mediator release, administered alone and in combination, in the prevention of bronchospasm induced by ultrasonic mist of distilled water (UMDW). Fifteen patients with documented atopic asthma and hyperresponsiveness to distilled water were selected for this randomized, placebo-controlled, double-blind study. Airway responses to pharmachological agents and bronchial challenge were measured by change in specific airways conductance (sGaw). Sodium cromoglycate had no effect on bronchial calibre, whilst ipratropium bromide and the combination of the two drugs produced a significant bronchodilation 30, 60 and 90 min after treatments. The maximal increase in sGaw (mean % +/- SD) was observed at 90 min: 63 +/- 28% and 58 +/- 22% after ipratropium bromide and the combined drugs respectively. UMDW (2, 4, 8, 16 ml water) caused a -36 +/- 19%, -42 +/- 19%, -49 +/- 18%, -56 +/- 15% mean % +/- SD fall in sGaw after placebo. Pretreatment with sodium cromoglycate abolished the bronchoconstriction to 2 ml (fall sGaw -5 +/- 23% NS) and significantly reduced the effect of 4 (-15 +/- 22%), 8 (-21 +/- 20%) and 16 ml (-24 +/- 18%) water.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

[The effect of inhaling pirenzepine--selective M1 receptor antagonist and ipratropium bromide on lung ventilation in patients with bronchial asthma].

The study was carried out on 19 patients with moderate and severe bronchial asthma. During three days after the initial spirometric evaluation the patients received--on the first day 0.5 mg of pirenzepine in nebulization (P), on the second day 0.25 mg of ipratropium bromide (IB), on the third day both substances together. Ventilatory parameters were monitored on the 5th, 20th, 40th and 60th minute following nebulization. The observed parameters did not differ significantly between both groups. Pirenzepine given after ipratropium bromide increased FEV1 from 1.89 L to 2.37 L (p < 0.01). The observed results imply that pirenzepine given with ipratropium bromide induce a significant bronchodilating effect and could be added to therapy of bronchial asthma.

Administration, Inhalation↗

Double-stranded DNA analysis by capillary electrophoresis with laser-induced fluorescence using ethidium bromide as an intercalator.

We have developed a rapid and sensitive method to analyze double-stranded DNA by capillary electrophoresis equipped with a laser-induced fluorescence detector. Using ethidium bromide as an intercalator in polyacrylamide gel-filled capillaries along with a green He/Ne laser source (excitation: 543 nm; emission: 600 nm), we found the detection sensitivity for a single DNA-ethidium bromide complex was in the picogram level with a resolution of one base pair separation between two DNA fragments. In the case of the separation of a phi X174 DNA-HaeIII digest, sizes from 72 to 1353 bp were well resolved within 12 min. For the analysis of PCR-amplified DNA, low levels of amplified DNA fragments could be detected that could not be visualized in agarose gel after standard ethidium bromide staining. Considering the high resolving power and sensitivity, we believe that this method can be a useful tool for the analysis of double-stranded DNA especially for PCR-amplified DNA fragments.

Base Sequence↗

[The effects of the treatment with oxitropium bromide after one month or more in patients with pulmonary emphysema--evaluation of pulmonary function tests, exercise tests, and a questionnaire].

Chronic effects of oxitropium bromide were studied in patients with pulmonary emphysema. Pulmonary function tests, an exercise test, and a questionnaire were used. Seven subjects underwent two successive studies, including a questionnaire on QOL, pulmonary function tests, and an exercise test before and after one month or more of regular inhalation of ocitropium bromide (600 micrograms/day). The complaint of breathlessness was significantly reduced and the ability to perform activities of daily living had improved slightly after the treatment. There were no significant differences in the values of arterial oxygen pressure at rest. The VC, RV/TLC, and peak expiratory flow rate improved. A significant decrease in oxygen uptake at rest, a slight decrease in minute ventilation at rest, and a significant prolongation of exercise time were observed after the treatment. No other changes were noted. We conclude that oxitropium bromide may improve lung mechanics and reduce the work of respiratory muscles.

Administration, Inhalation↗

Cholinergic crisis following treatment of postoperative urinary retention with distigmine bromide.

Distigmine bromide is a long-acting anticholinesterase, available for the treatment of postoperative urinary retention. Its effectiveness is unproven and administration may be hazardous. We describe a case in which oral distigmine bromide was used for postoperative retention, resulting in a potentially life-threatening 'cholinergic crisis'. We review the literature and conclude that the use of oral distigmine bromide in postoperative urinary retention is not justified.

Adult↗

A modified invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay for quantitating tumor cell invasion.

Reconstituted basement membrane matrix (Matrigel) has been utilized for in vitro assay of tumor cell invasion in recent years. In the conventional chamber for the invasion assay, however, a large number of cells passed easily through the center of the Matrigel-coated filter because the Matrigel layer could not be completely uniform by the meniscus formation. To prevent the meniscus phenomenon of the Matrigel layer, we devised a water-repellent treatment of the inside wall of the assay chamber with paraffin. Consequently, very few erythrocytes passed through the Matrigel-coated filter of this modified chamber with the erythrocyte assay, which was used to demonstrate the evenness and uniformity of the Matrigel layer on the filter. For quantitating a small number of cells which invaded through the Matrigel-coated filter by the invasion assay, a tetrazolium-based colorimetric 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) assay was used. The invasive abilities of the eight different cells were determined by this invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium+ ++ bromide assay using the modified chamber with a filter coated with 70 microliters of the 0.2-mg/ml Matrigel. After 72 h of incubation, the malignant cell lines significantly exceeded the normal cell lines in the percentage of invasion (P < 0.01). Therefore, the modified invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium+ ++ bromide assay provides a simple, easily reproducible in vitro assay for quantitating tumor cell invasion.

Animals↗