Valproic acid and sodium valproate approved for use in epilepsy.
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1. Two strains of Pseudomonas were grown with phenol and used to prepare cell extracts that metabolized catechol with the transient formation of 2-hydroxymuconic semialdehyde. 2. One of these preparations catalysed the conversion of 1mol. of catechol into 1mol. each of formate and 4-hydroxy-2-oxovalerate. 3. A method for the determination of 4-hydroxy-2-oxovalerate is described, together with some properties of this compound and its 2,4-dinitrophenylhydrazone. 4. Another partially purified cell extract converted 1mol. of 4-hydroxy-2-oxovalerate, formed enzymically from catechol, into 1mol. each of acetaldehyde and pyruvate. This aldolase had a pH optimum of about 8.8, was stimulated by Mg(2+) ions and appeared to attack only one enantiomer of synthetic 4-hydroxy-2-oxovalerate.
A direct photometric method for assaying neurotoxic esterase (NTE) activity of chicken brain microsomal preparation has been developed using 4-nitrophenyl esters as substrates. Paired samples of the microsomal preparation were preincubated for 20 min with paraoxon plus either (a) buffer or (b) mipafox before addition of substrate. The initial rate of NTE activity was directly recorded at 410 nm by matching the content of tube (a) against tube (b) after addition of the substrate to both of them. The 4-nitrophenyl esters of propionic, butyric, valeric, lauric, capric and caproic acids were tested as substrates. Results indicated that 4-nitrophenyl valerate and caproate, respectively, are the most hydrolyzable substrates for NTE with this method; its also enables detailed kinetic studies of NTE to be made. The Michaelis constant (Km) for the hydrolysis of 4-nitrophenyl valerate by NTe was found to be 5.55 . 10(-5) M.
A simple, selective and sensitive method for the determination of carboxylic acids has been developed. A mixture of formic, acetic, propionic, valeric, isovaleric, isobutyric, and isocaproic acids has been separated on a polymethacrylate-based weak acidic cation-exchange resin (TSK gel OA pak-A) based on an ion-exclusion chromatographic mechanism with detection using UV-photodiode array, conductivity and atmospheric pressure chemical ionization mass spectrometry (APCI-MS). A mobile phase consisting of 0.85 mM benzoic acid in 10% aqueous methanol (pH 3.89) was used to separate the above carboxylic acids in about 40 min. For LC-MS, the APCI interface was used in the negative ionization mode. Linear plots of peak area versus concentration were obtained over the range 1-30 mM (r2=0.9982) and 1-30 mM (r2=0.9958) for conductimetric and MS detection, respectively. The detection limits of the target carboxylic acids calculated at S/N=3 ranged from 0.078 to 2.3 microM for conductimetric and photometric detection and from 0.66 to 3.82 microM for ion-exclusion chromatography-APCI-MS. The reproducibility of retention times was 0.12-0.16% relative standard deviation for ion-exclusion chromatography and 1.21-2.5% for ion-exclusion chromatography-APCI-MS. The method was applied to the determination of carboxylic acids in red wine, white wine, apple vinegar, and Japanese rice wine.
Studies were performed in the years 1986-1990 and dealing with 405 clinical materials originating from infections within the abdominal cavity, maxilla, reproductive organ, post-operative wounds as well as dressings, extremities, blood, bile and other types of material and usefulness of analysis by gas chromatography of presence of lower fatty acids in materials for rapid and preliminary diagnostics with strictly anaerobic bacteria was confirmed. Presence in chromatograms of isobutyric, butyric isovaleric, valeric, isocaproic and caproic acid, and partly of propionic acid, is a good indication of infection with strictly anaerobic bacteria. Moreover, presence of succinic acid may suggest presence of anaerobic infection, similarly as presence in chromatograms of three or more various lower fatty acids. Rapid, approximative diagnosis of anaerobic bacteria by application of gas chromatography is worth of broader application. Investigation of clinical material by this method lasts only 1-2 hours and obtained results my present a basis for preliminary diagnosis of the etiological factor and for direction of chemotherapy, which is very important in most early period of treatment of infections.
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Organic acid screening of urine samples from two children with neurological disease demonstrated the presence of two unknown metabolites. The children were receiving an antiepileptic drug, sodium dipropylacetate. The major abnormal compound has been shown by gas chromatography-mass spectrometry to be 3-oxodipropylacetic acid, a previously unidentified metabolite of dipropylacetate in man, while the minor metabolite was indentified as 2-(n-propyl)-glutaric acid.
The ability of topically applied betamethasone valerate to reduce erythema produced by a variety of vasodilators was assessed. The steroid significantly reduced the erythema induced by topical arachidonic acid, intradermal histamine, and compound 48/80. We postulated that the steroid reduced endogenous phospholipase activity either before or after application of the vasodilators, or both. This action may explain the mechanism of glucocorticoid-induced vasoconstriction in the skin and part of the steroids' action in acute inflammatory skin disease.
A relatively simple gas chromatographic procedure is proposed for the analysis of the drug dipropylacetic acid in plasma. The compound is chromatographed, as the free acid after ether extraction. Prior to concentration of the solvent the acid is converted to its potassium salt, then regenerated to the free acid immediately before analysis.
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Baleen whales have a multichambered stomach divided into three distinct compartments. The forestomach (first compartment) consists of noncornified and nonglandular tissue and appears to be analogous to the tissue of the rumen. The exact function of the forestomach is unknown; however, we have detected volatile fatty acids in forestomach samples from seven bowhead (Balaena mysticetus) and four gray (Escherichtius robustus) whales. Acetic, propionic, and butyric acids were found in all samples. Seven whale samples also contained valeric, isobutyric, isovaleric, and isocaproic acids. Bacterial counts in 10 of the samples ranged from 5 X 10(8) to 630 X 10(8)/ml of fluid. The types, concentrations, and relative proportions of volatile fatty acids, the presence of significant levels of bacteria, and the morphology of the digestive tract support the hypothesis that a microbial forestomach fermentation occurs in these two species of baleen whales.
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Catabolic intermediates of sodium dipropylacetate, an anticonvulsant drug, in the urine extracts of the drug-treated rats were examined by the aid of gas chromatography mass spectrometry. Eleven drug-specific peaks were estimated as unmetabolized sodium dipropylacetate, succinic acid, 2-n-propyl-3-hydroxypentanoic acid, 2-n-propyl-4-hydroxypentanoic acid, 2-n-propyl-3-oxopentanoic acid, 2-n-propyl-5-hydroxypentanoic acid, adipic acid, 2-n-propylglutaric acid, dipropylacetic acid glucuronide, propionic acid and 3-heptanone. Administration of sodium dipropylacetate with isoleucine to rats resulted in the disappearance of 2-n-propyl-3-oxopentanoic acid and a considerable decrease in 2-n-propyl-3-hydroxypentanoic acid. These data indicated that beta-oxidation was involved in the metabolism of sodium dipropylacetate as well as glucuronide conjugation and omega oxidation.
The addition of C1-C7 alcohols (methanol, ethanol, propanol, butanol, heptanol, hexanol and heptanol) to dilute sulfuric acid as eluent in ion-exclusion chromatography using a highly sulfonated styrene-divinylbenzene co-polymer resin (TSKgel SCX) in the H+ form as the stationary phase was carried out for the simultaneous separations of both (a) C1-C7 aliphatic carboxylic acids (formic, acetic, propionic, isobutyric, butyric, isovaleric, valeric, 2-methylvaleric, isocaproic, caproic, 2,2-dimethyl-n-valeric, 2-methylhexanoic, 5-methylhexanoic and heptanoic acids) and (b) benzenecarboxylic acids (pyromellitic, hemimellitic, trimellitic, o-phthalic, m-phthalic, p-phthalic, benzoic and salicylic acids and phenol). Heptanol was the most effective modifier in ion-exclusion chromatography for the improvement of peak shapes and a reduction in retention volumes for higher aliphatic carboxylic acids and benzenecarboxylic acids. Excellent simultaneous separation and relatively highly sensitive conductimetric detection for these C1-C7 aliphatic carboxylic acids were achieved on the TSKgel SCX column (150 x 6 mm I.D.) in 30 min using 0.5 mM sulfuric acid containing 0.025% heptanol as eluent. Excellent simultaneous separation and highly sensitive UV detection at 200 nm for these benzenecarboxylic acids were also achieved on the TSKgel SCX column in 30 min using 5 mM sulfuric acid containing 0.075% heptanol as eluent.
The pharmacologic management of childhood hyperkinesis with psychostimulants has repeatedly proved its efficacy. In the case of hyperkinesis with an organic background (with eviden electrocencephalographic signs), the association with different anticonvulsants is usually beneficial although at times it gives rise to exceptionally undesirable side-effects, or to a paradoxically depressant action of the psychic activity. A clinical trial was carried out in 30 children aged from 5 10 years, with 2-dimethylaminoethanol in association with a magnesium salt of dipropylacetic acid (DAP).