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Cytofluorescence localization of ethidium bromide in the nervous system of the mouse. I. Ethidium bromide: its distribution in regions within and without the blood-brain barrier after intravenous injection.

A direct fluorescence-microscopic technique was effected to determine in the central nervous system (CNS) of the mouse the distribution of ethidium bromide after intravenous (i.v.) injection. The compound was visualized in thin cryostat sections of the brain fixed by vascular perfusion through the heart with a 10% buffered formalin solution. Ethidium bromide emitted a bright red fluorescent light in model experiments. The compound could not be detected in the vessel walls or brain parenchyma of the cerebral gray and white matters after i.v. injection indicating the presence of a blood-brain barrier (BBB) phenomenon to this compound. Signs of extravasation of ethidium bromide were present in the choroid plexus, the postremal area, the Gasserian ganglion, and in the circumventricular organs of the brain (neurohypophysis, organum vasculosum lamina terminalis, and median eminence) 3 min after the i.v. injection. Intense fluorescence was present in the nucleus and the cytoplasm of the cells in these areas, located outside of the BBB. Fluorescence had disappeared 24 h after the injection. Unexpectedly, red fluorescent material was seen in the parenchyma of the olfactory lobes of some animals, indicating, possibly, the presence of ethidium bromide. Ethidium bromide is known to suppress RNA, DNA, and protein synthesis in mammalian cells and has been used previously in neuropathology for studies on myelin lesions after injury to oligodendroglial cells. It can now, by a simple fluorescence-microscopic method, be traced directly in fixed tissue. Correlations can therefore be made between localization of the compound and its cytotoxic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ethidium bromide complexes with self-complementary deoxytetranucleotides. Demonstration and discussion of sequence preferences in the intercalative binding of ethidium bromide.

The binding of ethidium bromide to the self-complementary deoxytetranucleotides containing guanine and cytosine bases has been studied by circular dichroism, visible absorption, and fluorescence spectroscopies. The circular dichroism spectrum of each of the four deoxytetranucleotides was measured and compared to the spectrum calculated by a nearest-neighbor approximation method which utilized the circular dichroism spectra of the deoxydinucleotides as a basis set. Reasonable agreement was obtained between the calculated and experimental spectra for three of the four deoxytetranucleotides; however, pdC-dC-dG-dG exhibited poor agreement between the actual and nearest-neighbor calculated spectra, which suggests that pdC-dC-dG-dG may exist in an unusual conformation. A nearest-neighbor method was also used to calculate the extinction coefficients for each of the deoxytetranucleotides: these values differ substantially from values recently published by Patel and Canuel [(1977), Proc. Natl. Acad. Sci. U.S.A. 74, 2624--2628] in which the method used for the determination of the extinction coefficients was not stated. The magnitude of the extinction coefficients is important in determining the stoichiometry of complex formation as well as the relative sequence preferences for ethidium binding. The visible absorption titrations, the fluorescence titrations, and the circular dichroism titrations with ethidium bromide clearly show that two ethidiums will intercalate into a (pdC-dG-dC-dG).(pdC-dG-dC-dG) double helix presumably at the two (dC-dG).(DC-dG) sequences. Results from the pdG-dC-dG-dC titrations with ethidium bromide are not as definitive. Raising the temperature from approximately 2 to 26 degrees C diminishes the strength of complex formation for the EthBr plus pdC-dG-dC-dG system and makes it more difficult to unequivocally determine the stoichiometry of the complex formation. These data thus confirm and extend our earlier observation that ethidium bromide preferentially binds to pyrimidine-purine sequences as opposed to purine-pyrimidine sequences. Experiments monitoring the binding of ethidium bromide to pdC-dC-dG-dG and pdG-dG-dC-dC indicate that ethidium will bind strongly to the (dG-dG).(dC-dC) sequence. We conclude that the relative ordering of the sequence preferences for the binding of ethidium to the three sequences available in the tetranucleotides studied is (dC-dG).(dC-dG) congruent to (dG-dG).(dC-dC) greater than (dG-dC).(dG-dC).

Base Sequence↗

Bromide intoxication due to propantheline bromide.

An elderly woman presented with pneumonia and mental status changes and was found to have bromide poisoning due to ingestion of propantheline bromide over a 2-month period. The interference of bromide with serum chloride measurements on an ion-selective electrode resulted in spurious hyperchloremia and was crucial in making the diagnosis. To our knowledge, bromide intoxication due to propantheline bromide has not been reported previously.

Aged↗

Early bronchodilating effect of oxitropium bromide in comparison with ipratropium bromide.

The bronchodilating effects of a metered aerosol dose of 40 micrograms ipratropium bromide and of 200 micrograms oxitropium bromide are similar 15 min. after administration. The bronc hodilating activity of ipratropium bromide appears earlier (i.e., 75-90 s after administration) than that of oxitropium bromide but later than that of ibuterol, a beta2-agonist. Ipratropium bromide administered at the close of 80 micrograms provokes a bronchodilation about double of that obtained with 40 micrograms. An adaptation of the usual dosage should be considered.

Airway Resistance↗

Some aspects in the pharmacology of diclonium bromide (2-(3,4-dicholoroanilino)quinolizinium bromide). Part II: Gastric acid-antisecretory and antiulcerogenic actions.

Diconium bromide, 2-(3,4-dichloroanilino)-quinolizinium bromide, a potent antispasmodic in the lower bowel of the dog, was found in the present study to exert gastric acid-antisecretory and antiulcerogenic activities in the rat stomach. These effects were demonstrated by means of short- and long-term pyloric ligation, acetylsalicylic acid (ASA)-induced ulcerogenesis, and cold-and-restraint stress studies. A reduction of gastric acid concentration by the drug was probably responsible for the decrease in the degree of ulceration and hemorrhagic lesion formation. The drug's inhibition of stress hemorrhagic lesions may be related to an effect both on gastric HCl secretion and on the vasculature in the glabdular mucosa. The delay of gastric emptying by diclonium bromide results from its known antispasmodic or smooth-muscle depressant action. The toxicity of diclonium bromide, perorally, was low in rats and overt signs of drug effect were not evident until toxic doses were administered. It is concluded that diclonium bromide may represent a useful non-anticholinergic drug effective in treating both peptic ulcers and spasticity of the colon (irritable-colon syndrome) in man.

Animals↗

Bromide kinetics and distribution in the rat. I. Biokinetics of 82Br-bromide.

Biological half-lives of bromine in 15 different organs and tissues of the rat, in addition to the whole-body half-life, were determined by measuring the radioactive concentration of 82Br-bromide in samples of tissues collected at the time intervals of 12-396 h from animals that continuously (up to 17 d) received 82Br-labeled bromide in their drinking water. The half-life values, calculated from the experimental data by the method of gradual estimates of the parameters in question with the SPSS statistical program, ranged from 94.3+/-14.6 h in the thyroid gland to 235.0+/-88.9 h in liver. In most of the studied tissues, the biological half-lives of bromine were shorter than in the whole body, in which it equaled 197.8+/-22.2 h. Significant correlation between the values of the steady-state concentration of bromide and of the biological half-life was found for most tissues (except for liver). The steady-state concentrations of 82Br in tissues are probably proportional to the magnitude of bromide space, and, consequently, of chloride space.

Animals↗

Bromide kinetics and distribution in the rat. II. Distribution of bromide in the body.

The distribution of 82Br-bromide in 15 different organs and tissues of rats has been determined by high-resolution gamma-ray spectrometry and by the scintillation counting technique at different times after the application of Na 82Br, either by subcutaneous injection or by continuous administration in the drinking water. The amount of 82Br-bromide in the various tissues reached its largest uptake within a few hours, and the concentration ratio of 82Br in the tissues to blood remained practically constant between 8 and 396 h after the application. The whole stomach of rats was the only organ of those investigated that had a larger uptake of 82Br than blood. Contrary to some previous findings, the concentration of radiobromide in the thyroid was found not to exceed that in the blood. A remarkably high concentration of 82Br was found in the skin, which represented, because of its large mass, the most abundant depot of bromide in the body of rats. The demonstrated excretion of bromide was mainly renal, at a rate of approximately 5% of the administered dose per 24 h.

Animals↗

Neonatal bromide intoxication: prenatal ingestion of a large quantity of bromides with transplacental accumulation in the fetus.

A 27-year-old woman who was 34 weeks pregnant was admitted in a semicomatose state. Five days later she gave birth to an infant who demonstrated significant CNS depression. Elevated blood levels confirmed bromide intoxication in both the mother and infant secondary to chronic maternal bromide ingestion (Nervine). Simultaneous determinations revealed a higher initial serum bromide level in the infant compared to that of the mother in spite of a subsequent more rapid rate of disappearance in the neonate. It is suggested that the drug history obtained from the pregnant woman include nonprescription medications containing bromides. This possibility should also be included in the differential diagnosis in infants exhibiting evidence of CNS depression, particularly those born to mothers classified as neurotic or psychotic.

Adult↗

Exposure to inorganic bromides from greenhouse crops where methyl bromide was applied for soil fumigation.

The Authors determined the concentration of inorganic bromides in soil and tomatoes from greenhouses where soil fumigation had been performed using methyl bromide (greenhouse B) and alternative pest control systems (greenhouse A and greenhouse B) before planting. The results obtained demonstrate that concentration of inorganic bromides in foodstuffs should be considered as a marker of exposure to methyl bromide poisoning risk.

Bromides↗

A kinetic study on the mechanism of inhibition of RNA synthesis catalyzed by DNA-dependent RNA polymerase. Differences in inhibition by ethidium bromide, 3,8-diamino-6-ethylphenanthridinium bromide and actinomycin d.

The mechanism of inhibition of RNA polymerase-catalyzed synthesis of RNA by actinomycin D and the phenan-thridinium derivatives ethidium bromide and 3,8-diamino-6-ethylphenanthridinium bromide (DEMB) is examined. A general kinetic equation describing the dependence of RNA synthesis on DNA template concentration is derived and distinct expressions corresponding to various possible mechanisms of inhibition are subsequently obtained by introducing into the equations assumptions as appropriate for the individual mechanisms. The fitting of the experimental results of inhibition into the resulting equations suggested that the ethidium bromide and DEMB inhibit RNA polymerase by forming an inhibitor-template complex which interferes with enzyme recognition of, and binding to, appropriate sites on the template (binding inhibition). The fitting of the dependence of the rate of RNA synthesis on the bound-inhibitor to DNA ratios to the derived kinetic expressions also allows a tentative distinction to be made as to whether ethidium bromide and DEMB interfere with RNA synthesis by a mechanism of 'partial' or 'complete' inhibition.

Coliphages↗

A novel cetyltrimethyl ammonium silver bromide complex and silver bromide nanoparticles obtained by the surfactant counterion.

A novel cetyltrimethyl ammonium silver bromide (CTASB) complex has been prepared simply through the reaction of silver nitrate with cetyltrimethyl ammonium bromide (CTAB) in aqueous solution at room temperature by controlling the concentration of CTAB and the molar ratio of CTAB to silver nitrate in the reaction solution, in which halogen in CTAB is used as surfactant counterion. The structure and thermal behavior of cetyltrimethyl ammonium silver bromide have been investigated by using X-ray diffraction (XRD), infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS), UV/vis spectroscopy, thermal analysis (TG-DTA), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The results show that the complex possesses a metastable layered structure. Upon heating the CTASB aqueous dispersion to above 80 degrees C, the structure change of the complex took place and CTAB-capped nanosized silver bromide particles further formed.

Journal Article↗

Cytotoxicity of methyl bromide: effect of methyl bromide on cultured mammalian cells.

Cytotoxicity of methyl bromide on cultured mammalian cells was examined. Acute toxic action was induced by methyl bromide itself and its cytotoxicity was reduced in the presence of glutathione. Its hydrolysis products or its reaction products with organic compounds in the medium was extremely low in toxicity. Although methyl bromide is known to be a methylating agent, morphological changes induced on HeLa cells were different from the changes characteristic of chemotherapeutic alkylating agents. Lethal concentration of methyl bromide on HeLa cells and primary cultured muscle, kidney and brain cells was similar (10 microgram/ml). In a detailed survey, however, there was a slight difference in the susceptibility among the cells from primary culture of brain.

Animals↗

A comparison of the action of otilonium bromide and pinaverium bromide: study conducted under clinical control.

We studied 40 patients with irritable bowel syndrome (IBS) which received in a simple-blind fashion otilonium and pinaverium bromide (15 days each drug). During each 15-day period we evaluated: number of pain episodes, intensity of pain, number of bowel movements, side effects. Otilonium bromide, (OB), compared with pinaverium bromide was able to significantly (p less than 0.05) reduce the number of pain attacks, whereas no significant differences were found between the 2 groups as regards the other parameters. The occurrence of side effects was similar in the two treatment courses. We can conclude that the two types of treatment were similarly useful in IBS, although OB seems more effective than pinaverium bromide.

Abdominal Pain↗

An improved X-ray spectrometric method for the determination of bromide in whole blood of workers occupationally exposed to methyl bromide.

An X-ray spectrometric method using a sequential wavelength dispersive instrument is described for the analysis of bromide in whole blood from workers occupationally exposed to methyl bromide. The method involves the direct deposition of 100 microL of whole blood onto filter paper discs. Calibration of the instrument is achieved using the standard addition technique for bromide concentrations up to 50 mg/L. Precision studies at concentrations of 6.1, 16.4, and 26.9 mg/L gave relative standard deviation values of 5.8, 4.1, and 2.8%, respectively. The detection limit for the method is 1.2 mg/L.

Bromides↗

Relative potency of the atropine-like effects of a new parasympatholytic drug, scopolamine-N-(cyclopropyl methyl) bromide and those of hyoscine-N-butyl bromide.

A double-blind crossover trial with a 4-point bioassay was carried out in 8 convalescent in-patients to study the relative potency of scopolamine-N-(cyclopropyl methyl) bromide (DA 3177), a new parasympatholytic drug, administered at doses of 2.5 mg and 5 mg i.v., and hyoscine-N-butyl bromide, administered at doses of 10 mg and 20 mg i.v., in producing atropine-like effects. The results showed that the effects on heart rate and near point of accommodation were slightly less with DA 3177, while its effects on salivary secretion were a little greater than those of hyoscine-N-butyl bromide. It is suggested that study of the pharmacodynamic effects of parasympatholytic drugs is a relatively simple way of predicting which doses should be effective spasmolytically.

Accommodation, Ocular↗

Determination of bromide ion residues in broccoli after fumigation with methyl bromide by nonsuppressed ion-chromatography.

A nonsuppressed ion chromatography method using conductivity detection was performed to determine the concentration of bromide ions in broccoli following fumigation with methyl bromide (MB). After fumigation by MB with concentration up to 40 g/m3, bromide residue (BR) was considerably increased from the trace amount on unfumigated broccoli to about 12 ppm on fumigated broccoli. For probing the location of BR, broccoli was divided into stems and florets. The BRs were measured separately, and the results indicated that BRs only appear in the florets of broccoli.

Brassica↗

Correlation of the melting points of potential ionic liquids (imidazolium bromides and benzimidazolium bromides) using the CODESSA program.

The melting points of several imidazolium-based ionic liquids or ionic liquid analogues were correlated using the CODESSA program in order to develop predictive tools for determination of suitable ionic liquid salts. The data set consisted of melting point data (degrees C) for 104 substituted imidazolium bromides divided on the basis of the N-substituents into three subsets: A-57 compounds, B-29 compounds, and C-18 compounds. The 45 benzimidazolium bromides form set D. Five-parameter correlations were obtained for (i) set A with R2 = 0.7442, (ii) set B with R2 = 0.7517, and (iii) set D with R2 = 0.6899, while set C was correlated with a three parameter equation with R(2) = 0.9432. These descriptors for predicting the melting points of the imidazolium and benzimidazolium bromides were based on the size and electrostatic interactions in the cations.

Journal Article↗

Some aspects in the pharmacology of diclonium bromide (2-(3,2-dichloroanilino)quinolizinium bromide). Part I: Antispasmodic action.

Diclonium bromide (EU-2972; 2-(3,4-dichloroanilino)quinolizinium bromide) was demonstrated to possess an effective, prolonged inhibitory action on contractions in response to stimuli or propulsive movements in the lower bowel of the dog. The compound's antagonism to contractile activity was greater in the distal colon than in the duodenum or upper bowel. Diclonium bromide was a nonselective antispasmodic but, unlike papaverine, caused profound antagonism against smooth muscle contractile responses to intrinsic motor neural excitation. The drug had weak specific anticholinergic action, but its lack of antagonistic effect on other cholinergic responses in this study indicates that the anticholinergic action contributes very little, if at all, to its overall antispasmodic effect. The compound has potential application in the treatment of spastic-colon disease.

Acetylcholine↗