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[Neuromuscular blocking effects of Org 9426 (rocuronium bromide); a comparative study with vecuronium bromide in Japanese patients].

BACKGROUND: Efficacy and safety of Org 9426 were compared with those of vecuronium bromide in Japanese patients. METHODS: We studied 88 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of 0.6 mg x kg(-1), 0.9 mg x kg(-1) of Org 9426 or 0.1mg x kg(-1) of vecuronium. Following an intubation dose, patients received maintenance doses of 0.1, 0.15 or 0.2 mg x kg(-1) of Org 9426 or 0.025 mg x kg(-1) of vecuronium. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: The onset times of the 0.6 and 0.9 mg x kg(-1) of Org 9426 groups were 84.6 and 77.1 sec respectively, which showed statistical difference between the onset time of 0.1 mg x kg(-1) of vecuronium, 125.7 sec. The intubation condition was similar among three treatment groups. The clinical durations of 0.6 and 0.9 mg x kg(-1) of Org 9426 and 0.1 mg x kg(-1) of vecuronium were 53.4, 73.4 and 59.9 min, respectively. Clinical duration and spontaneous recovery time of maintenance dose of 0.15 mg x kg(-1) of Org 9426 were similar to those of 0.025 mg x kg(-1) of vecuronium. CONCLUSIONS: Org 9426 showed more rapid onset time than that of vecuronium and similar clinical duration and recovery times to those of vecuronium in Japanese patients.

Androstanols↗

Nucleosome dynamics V. Ethidium bromide versus histone tails in modulating ethidium bromide-driven tetrasome chiral transition. A fluorescence study of tetrasomes on DNA minicircles.

Protein and DNA contributions in the chiral transition of DNA minicircle-reconstituted tetrasomes (the particles made of DNA wrapped around the histone (H3-H4)(2) tetramer) to a right-handed conformation have been investigated in a recent article from this laboratory. As the evidence for a protein contribution, a sterical hindrance introduced at the H3/H3 interface of the two constituent H3-H4 dimers by oxidation of H3 cysteine 110 blocked the tetramer in a half-left-handed or semi-right-handed conformation, depending on the SH-reagent used. The DNA contributed at the level of the dyad region, which appeared to act through its sequence-dependent deformability in modulating both the loop threshold positive constraint required to trigger the transition, and the tetrasome lateral opening. This opening, which electron microscopic visualizations directly showed to be associated with the transition, is expected to help remove the clash between the entering and exiting DNAs. In this work, the transition mechanism was further investigated by applying a positive constraint in the loop through ethidium bromide (EtBr) intercalation. This technique, including the determination of binding isotherms, has first been used with mononucleosomes on DNA minicircles, and has revealed that these particles could tolerate large positive supercoilings without disruption, owing to the loop ability to cross positively in a histone tail-dependent manner. The transition of 359 bp tetrasomes was found to go to completion in lower salt (10 mM), but not in higher salt (100 mM), whereas the transition of 256 bp tetrasomes was already hindered in lower salt. Histone acetylation relieved that lower salt hindrance but enhanced the higher salt hindrances. These data again pointed to the DNA in the dyad region as a regulator of the transition. The block was indeed expected to originate from a local EtBr intercalation in that DNA, which opposed its overtwisting during the transition. The occurrence of the block, or its relief, then depended on the outcome of the competition between the tails and EtBr for binding to that region, that is, on whether the tails could prevent EtBr intercalation before the ongoing transition hampered both bindings. Destabilization of the tails in the course of the transition is documented in an accompanying article through a relaxation study of a 351-366 bp tetrasome series.

Acetylation↗

Comparison of the effects of ethidium bromide and of ethidium bromide-deoxyribonucleic acid complex in fibroblasts cultivated in vitro.

Chick embryo fibroblasts cultivated in vitro were treated with ethidium bromide (E.B.) or with DNA-E.B. complex (DNA-E.B.). E.B. (5 mug/ml) provokes morphological alterations and cell death, inhibits DNA synthesis and mitotic activity. DNA-E.B. (E.B. 5 mug/ml) is less toxic to the fibroblasts as far as cell structure, DNA synthesis and mitotic activity are concerned. DNA alone has no apparent effect on the fibroblasts. As shown by fluorescence microscopy, the lower toxicity of DNA-E.B. seems to be related to its mode of penetration into the cells.

Animals↗

Kinetics of manganese(III) acetate in acetic acid: generation of Mn(III) with Co(III), Ce(IV), and dibromide radicals; reactions of Mn(III) with Mn(II), Co(II), hydrogen bromide, and alkali bromides.

The reaction of cobalt(III) acetate with excess manganese(II) acetate in acetic acid occurs in two stages, since the two forms Co(IIIc) and Co(IIIs) are not rapidly equilibrated and thus react independently. The rate constants at 24.5 degrees C are kc = 37.1 +/- 0.6 L mol-1 s-1 and ks = 6.8 +/- 0.2 L mol-1 s-1 at 24.5 degrees C in glacial acetic acid. The Mn(III) produced forms a dinuclear complex with the excess of Mn(II). This was studied independently and is characterized by the rate constant (3.43 +/- 0.01) x 10(2) L mol-1 s-1 at 24.5 degrees C. A similar interaction between Mn(III) and Co(II) is substantially slower, with k = (3.73 +/- 0.05) x 10(-1) L mol-1 s-1 at 24.5 degrees C. Mn(II) is also oxidized by Ce(IV), according to the rate law -d[Ce(IV)]/dt = k[Mn(II)]2[Ce(IV)], where k = (6.0 +/- 0.2) x 10(4) L2 mol-2 s-1. The reaction between Mn(II) and HBr2., believed to be involved in the mechanism by which Mn(III) oxidizes HBr, was studied by laser photolysis; the rate constant is (1.48 +/- 0.04) x 10(8) L mol-1 s-1 at approximately 23 degrees C in HOAc. Oxidation of Co(II) by HBr2. has the rate constant (3.0 +/- 0.1) x 10(7) L mol-1 s-1. The oxidation of HBr by Mn(III) is second order with respect to [HBr]; k = (4.10 +/- 0.08) x 10(5) L2 mol-2 s-1 at 4.5 degrees C in 10% aqueous HOAc. Similar reactions with alkali metal bromides were studied; their rate constants are 17-23 times smaller. This noncomplementary reaction is believed to follow that rate law so that HBr2. and not Br. (higher in Gibbs energy by 0.3 V) can serve as the intermediate. The analysis of the reaction steps then requires that the oxidation of HBr2. to Br2 by Mn(III) be diffusion controlled, which is consistent with the driving force and seemingly minor reorganization.

Journal Article↗

In situ study of water-induced segregation of bromide in bromide-doped sodium chloride by scanning polarization force microscopy.

The adsorption of water on Br-doped NaCl crystals has been studied in situ using scanning polarization force microscopy, a noncontact electrostatic atomic force microscopy operation mode. Both topography and contact potential images were acquired as a function of relative humidity at room temperature, from 0% to more than 55%. It was found that the surface of the freshly cleaved crystal has an inhomogeneous electrical surface potential distribution with the steps more negative than the terraces below 40% relative humidity. This difference disappears when the humidity reaches 40% and higher. Below 40% the step morphology experiences only small changes due to water adsorption; however, above 40% major changes take place due to solvation, segregation, and redistribution of lattice ions. Bromide-rich islands and crystallites segregate to the surface above 40% relative humidity followed by drying. These islands and crystallites have a negative surface potential relative to the rest of the surface. These effects are attributed to the preferential solvation and segregation of Br- ions.

Journal Article↗

Adsorption of dodecyltrimethylammonium bromide and sodium bromide on gold studied by liquid chromatography and flow adsorption microcalorimetry.

Here, we report on a new aspect of the adsorption of Br- on the surface of gold. The adsorption of dodecyltrimethylammonium bromide (C12TABr) from aqueous solutions onto macroporous gold particles was studied by continuous flow frontal analysis solid/liquid chromatography and flow adsorption microcalorimetry. The material balance and enthalpy balance of adsorption and the change in the solution pH were measured simultaneously. Initially, Br- is irreversibly bound to high-affinity surface sites counterbalanced by the adsorption of H+ from the aqueous phase. The surface speciation is accompanied by the formation of C12TAOH, which in turn results in a significant pH increase in the bulk solution. The net process was found to be strongly exothermic (-280 kJ.mol(-1)), which is indicative of the occurrence of chemisorption. The specific adsorption of Br- is followed by the reversible adsorption of C12TABr to produce a firmly bound monolayer in a head-to-surface arrangement (-53 kJ.mol(-1)). In a relatively narrow range of the surface coverage, various composite structures may develop on the top layer and eventually transform to full-cylindrical surface aggregates. The surface aggregation was found to be reversible, with an enthalpy change of -11 kJ.mol(-1). The importance of the specific binding of Br- to the surface of gold was confirmed by measurement of the initial adsorption of NaBr on the microparticles. The initial adsorption was found to be irreversible, with an enthalpy change of approximately -240 kJ.mol(-1). This process involved the formation of an AuBr-/H+ electric double layer at the gold/water interface, accompanied by a dramatic increase in the solution pH due to the release of a copious amount of OH- in the bulk liquid phase.

Journal Article↗

Description of toluene inhibition of methyl bromide biodegradation in seawater and isolation of a marine toluene oxidizer that degrades methyl bromide.

Methyl bromide (CH3Br) and methyl chloride (CH3Cl) are important precursors for destruction of stratospheric ozone, and oceanic uptake is an important component of the biogeochemical cycle of these methyl halides. In an effort to identify and characterize the organisms mediating halocarbon biodegradation, we surveyed the effect of potential cometabolic substrates on CH3Br biodegradation using a 13CH3Br incubation technique. Toluene (160 to 200 nM) clearly inhibited CH3Br and CH3Cl degradation in seawater samples from the North Atlantic, North Pacific, and Southern Oceans. Furthermore, a marine bacterium able to co-oxidize CH3Br while growing on toluene was isolated from subtropical Western Atlantic seawater. The bacterium, Oxy6, was also able to oxidize o-xylene and the xylene monooxygenase (XMO) pathway intermediate 3-methylcatechol. Patterns of substrate oxidation, lack of acetylene inhibition, and the inability of the toluene 4-monooxygenase (T4MO)-containing bacterium Pseudomonas mendocina KR1 to degrade CH3Br ruled out participation of the T4MO pathway in Oxy6. Oxy6 also oxidized a variety of toluene (TOL) pathway intermediates such as benzyl alcohol, benzylaldehyde, benzoate, and catechol, but the inability of Pseudomonas putida mt-2 to degrade CH3Br suggested that the TOL pathway might not be responsible for CH3Br biodegradation. Molecular phylogenetic analysis identified Oxy6 to be a member of the family Sphingomonadaceae related to species within the Porphyrobacter genus. Although some Sphingomonadaceae can degrade a variety of xenobiotic compounds, this appears to be the first report of CH3Br degradation for this class of organism. The widespread inhibitory effect of toluene on natural seawater samples and the metabolic capabilities of Oxy6 indicate a possible link between aromatic hydrocarbon utilization and the biogeochemical cycle of methyl halides.

Biodegradation, Environmental↗

Standard and double dose ipratropium bromide and combined ipratropium bromide and inhaled metaproterenol in COPD.

Inhaled ipratropium bromide (IPR) is effective in the management of COPD. The purpose of this study was to determine if doubling the standard dose of IPR resulted in greater bronchodilation and if the addition of an inhaled beta-agonist was superior to standard dose IPR alone. Twelve male patients with stable COPD completed a double blind, randomized trial. On each of three consecutive days, following baseline spirometry, all patients inhaled two puffs of IPR. This was followed by either two additional puffs of IPR, two puffs of metaproterenol (META), or two puffs of placebo. All inhalants were delivered by an InspirEase spacer. Spirometry was repeated at 30, 60, 120, and 180 minutes. The group mean percentage increases in the FEV1 and FVC from baseline were similar at all times tested for the three protocols. In conclusion, for the group, there was no objective benefit to doubling the standard dose of IPR or combining IPR with META. Two of 12 patients benefited from combining the two bronchodilators. A potential sequence for bronchodilator testing is suggested.

Administration, Inhalation↗

[Ipratropium Bromide, an Anticholinergic Bronchodilator/Behavior of airways resistance in patients with reversible respiratory obstruction following inhalation of various doses of ipratropium bromide].

A dose- and time-response study using different doses of an inhaled derivative of atropine, (8r)-3alpha-hydroxy-8-isopropyl-1 aH, 5aH-tropaniumbromide-(+/-)-tropate (Sch 1000, ipratropium bromide, Atrovent) was performed in 12 patients with reversible chronic obstructuve airways disease. The drug was shown to be an effective bronchodilator with the typical action of reducing airways resistance with 2 puffs (0.02 mg per puff). Increasing the dose to 4 and 8 puffs did not produce any relevant difference in time response. The onset of action was rapid and reached a maximum between 30 and 60 min after inhalation. The duration of bronchodilation was maintained during the observation period of 3 h. 30 min after inhalation the results corresponded to those following the inhalation of 2 puffs of orciprenaline (0.75 mg per puff). Isolated side-effects were independent of the dosage.

Adult↗

[Otilonium bromide-diazepam in the treatment of the irritable colon. A controlled study versus otilonium bromide].

Octylonium bromide (OB) is a drug with spasmolytic properties acting selectively on the smooth muscle of the gastrointestinal tract by interfering with calcium mobilization from extra- and intra-cellular deposits. The etiopathogenetic implications of a psychosomatic nature of the irritable bowel syndrome amply justify the use of a spasmolytic (OB) with a benzodiazepine. In our study, we compared the combination OB + DZ (20 mg + 2 mg) T.I.D. versus OB alone (20 mg) in 30 patients suffering from irritable bowel syndrome. The double-blind study lasting 3 weeks was aimed at evaluating gastrointestinal symptoms (bowel motions, aspect of faeces, abdominal pain, pre-evacuation pain, bloating) during the three days preceding the study and during the last five days of treatment, as well as the anxiogenic situation as assessed by the STAI scale (State Tract Anxiety Inventory) before and at the end of the treatment period. The results obtained showed that both treatments considerably reduced gastrointestinal symptoms even though OB alone did not appear to be equally effective and the anxiety component was significantly reduced only by treatment with the combination. The absence of side effects and the perfect tolerability of both treatments showed the OB + D combination T.I.D. to be the treatment of choice for patients suffering from irritable bowel syndrome.

Adult↗