Identification of ethylsuccinylcarnitine present in some human urines.

Ethylsuccinylcarnitine, a previously undescribed acylcarnitine, was identified in urines obtained from 81% of adult volunteers. Its chemical structure was obtained by 1H nuclear magnetic resonance spectroscopy of the urinary purified compound and confirmed by its chemical synthesis. Its urinary excretion followed a circadian rhythm with a maximum occurring between 8 p.

Multiresidue determination of pesticides in drinking and related waters by solid-phase extraction and liquid chromatography with ultraviolet detection: interlaboratory study.

As part of a project funded by the European Commission (EC) for the development and evaluation of multiresidue methods for analysis of drinking and related waters, 17 European laboratories evaluated a method using styrene-divinylbenzene copolymer solid-phase extraction followed by liquid chromatography with diode array detection. The main aim of the study was to evaluate whether the method meets the requirements of EC Drinking Water Directive 98/83 in terms of accuracy, precision, and detection limit for 21 pesticides according to the following requirements: limit of detection, < or =0.025 microg/L; accuracy expressed as recovery, between 75 and 125%; and precision expressed as repeatability relative standard deviation of the method, <12.

Multiresidue determination of pesticides in drinking and related waters by gas chromatography/mass spectrometry after solid-phase extraction: interlaboratory study.

As part of a project funded by the European Commission (EC) for the development and evaluation of multiresidue methods for analysis of drinking and related waters, 15 European laboratories evaluated a method using styrene-divinylbenzene co-polymer solid-phase extraction followed by gas chromatography/mass spectrometry. The main aim of the study was to evaluate whether the method meets the requirements of EC Directive 98/83 in terms of accuracy, precision, and detection limit for 22 pesticides according to the following requirements: limit of detection, < or = 0.025 microg/L; accuracy, expressed as recovery between 75 and 125%; and precision, expressed as repeatability relative standard deviation of the method of < 12.

Community care: exploring the priorities of clients, mental health professionals and community providers.

Co-ordinated joint service planning by all stakeholders is widely accepted as a valuable principle in the development of community support services for persons with severe mental illness. Even so, relatively little is known of the views and priorities of the different parties with regard to the elements that should make up the care and support system. This paper reports on a Dutch study in which clients, mental health care workers and community service professionals offered their opinions on what constitutes a support system that enables individuals with long-term mental illness to participate in the community.

Identification of undescribed medium-chain acylcarnitines present in urine of patients with propionic and methylmalonic acidemias.

In urine of patients with propionyl-CoA carboxylase deficiency or with methylmalonic acidemia, carnitine esters of 2-methyl-branched fatty acids of all chain lengths between 4 and 9 atoms of carbon were identified during the acute phase of the diseases. The chemical structure of these compounds was obtained by gas chromatography-mass spectrometry analysis of their fatty acid moieties in their free and picolinyl ester forms. We suggest mechanisms for the biosynthesis of these branched fatty acids, and their accumulation in urine during episodes of caloric imbalance.

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and early-onset liver cirrhosis in two siblings.

Unlabelled: We present the clinical, pathological, biochemical, and molecular results on an infant girl with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency and data on her deceased elder brother for whom this condition was retrospectively diagnosed. Clinical signs were liver enlargement and elevated liver enzymes, failure to thrive, and neurological disease (coma, seizures) triggered by an infectious stress. In the second child hepatic failure and status epilepticus developed during the onset of a rotavirus gastroenteritis.

Identification of new medium-chain acylcarnitines present in urine of a patient with medium-chain acyl-CoA dehydrogenase deficiency.

Previously undescribed medium-chain acylcarnitines were identified in a urine sample from a patient with medium-chain acyl-CoA dehydrogenase deficiency. These are the 4-methylvaleryl, 4- and 5-methylhexanoyl, 6-methylheptanoyl-, 6-methyloctanoyl-, 4,5-dimethylhexanoyl- and 4,7-decadienoylcarnitines. Their chemical structures were obtained by gas chromatographymass spectrometry analysis of their fatty acid moieties as picolinyl esters.

Nosology of lysosomal glycogen storage diseases without in vitro acid maltase deficiency. Delineation of a neonatal form.

We describe a boy with an early lethal hypertrophic vacuolar cardiomyopathy of neonatal onset. Abnormal intra- and extralysosomal glycogen storage disease was demonstrated in heart and skeletal muscles. Glycogen content was twice the normal in muscles and over 3-fold the normal in the heart.

Identification of new medium-chain acylcarnitines present in normal human urine.

Analysis of urinary medium-chain acylcarnitines extracted on C18 cartridges and gas chromatography mass spectrometry of their fatty acid moieties as picolinyl esters allowed the determination of the chemical structure of previously unidentified acylcarnitines in normal human urine. These are the 2,6-dimethylheptanoyl-, the 2,6-dimethyl-5-heptenoyl-, and the trans- and cis-3,4-methylene heptanoylcarnitines, also named 3-cyclopropane octanoylcarnitines. Assessment of the structure of these cyclopropane derivatives was obtained by 1H and 13C nuclear magnetic resonance spectroscopy.

Marked increase of methylumbelliferyl-tetra-N-acetylchitotetraoside hydrolase activity in plasma from Gaucher disease patients.

Methylumbelliferyl-tetra-N-acetylchitotetraoside hydrolase activity was increased 53- to 484-fold in plasma from Gaucher disease patients and no activator could be found. High activity was also measured in other lysosomal storage diseases including Krabbe disease, Wolman disease, GM1-gangliosidosis and to a lesser extent Niemann-Pick disease type B, but the activities were lower than the lowest values in Gaucher patients. Kinetic properties of the high activity in Gaucher plasma were similar to those of controls.

Mitochondrial respiratory chain defect: a new etiology for neonatal cholestasis and early liver insufficiency.

Two siblings presented with neonatal cholestasis and early liver insufficiency. The older was admitted for end-stage cirrhosis with severe hypoglycemia and had long-term successful liver transplant at the age of 15 months. The second child presented a similar neonatal history of cholestasis, hypoglycemia, hyperlactacidemia, liver insufficiency and progressive cirrhosis.

Fast-atom bombardment mass spectrometry and low energy collision-induced tandem mass spectrometry of tauroconjugated bile acid anions.

Fragmentation of negative ions produced by fast-atom bombardment (FAB) from 14 tauroconjugated bile acids and some of their deuterated analogs has been studied by mass spectrometry and by collision-induced dissociation (CED) tandem mass spectrometry at low energy.Low energy collision-induced dissociation of the deprotonated molecules [M - H](-) of these tauroconjugated bile acids leads to both charge-driven and charge-remote fragmentations (CRF). The former yields neutral loss from the side chain with charge migration during the fragmentation process.

Maturation of villus and crypt cell functions in rat small intestine. Role of dietary polyamines.

To evaluate the role of dietary polyamines in maturation of the rat small intestine, spermine was given orally twice daily to suckling pups from day 10 to day 14 postpartum at different doses: 0, 0.2, 0.5, 1, 2.

Prenatal exposure to ethanol in rats: effects on postnatal maturation of the small intestine and liver.

To examine the effects of prenatal exposure to ethanol on postnatal development of small intestinal and liver functions, female rats were accustomed to increasing amounts of ethanol (10 to 25%, vol/vol) in tap water for 1 mo. During pregnancy, ethanol-fed dams had higher daily caloric intake and similar weight gain compared with controls. In ethanol offspring, neonatal mortality was 28.

In vitro effects of valproate and valproate metabolites on mitochondrial oxidations. Relevance of CoA sequestration to the observed inhibitions.

The inhibitory effects of valproate (VPA) and nine of its metabolites on mitochondrial oxidations have been investigated. Valproate, 4-ene-VPE, 2,4-diene-VPA and 2-propylglutaric acid inhibited the rate of oxygen consumption by rat liver mitochondrial fractions with long- and medium-chain fatty acids, glutamate (+/- malate), succinate, alpha-ketoglutarate (+ malate) and pyruvate (+ malate) as substrates. Sequestration of intramitochondrial free CoA by valproate and these three metabolites has been demonstrated and quantified.

Progressive cardiac failure following orthotopic liver transplantation for type IV glycogenosis.

Orthotopic liver transplantation (OLT) has been proposed to treat patients with type IV glycogenosis because of early progressive cirrhosis. Reports have shown absence of disease progression in other organs after OLT and even regression of cardiac amylopectin infiltration in one case. We describe a 15-month-old child in whom a liver transplant was performed for type IV glycogenosis.

Cytochrome aa3 depletion is the cause of the deficient mitochondrial respiration induced by chronic valproate administration.

Liver mitochondria from rats fed 1% (w/w) valproic acid for 75 days displayed an approximate 30% decrease in coupled respiration rates with substrates entering the respiratory chain at complexes I and II. Uncoupling the respiration from proton-pumping, or measuring the respiration without complex IV removed this inhibition. The treatment induced a loss of activity of cytochrome oxidase consistent with a decrease in the mitochondrial content of cytochrome aa3.

Bile acids and conjugates identified in metabolic disorders by fast atom bombardment and tandem mass spectrometry.

From a study of the collision-activated fragmentation of bile acids, a qualitative analytical method based on negative ion fast atom bombardment tandem mass spectrometry has been developed. The times for sample preparation and analyses are short. Both free and conjugated bile acids are detected as they occur in biological fluids, without derivatization.

Influence of chronic administration of valproate on ultrastructure and enzyme content of peroxisomes in rat liver and kidney. Oxidation of valproate by liver peroxisomes.

Chronic administration to rats of the anticonvulsant drug, valproate, induced proliferation of liver peroxisomes and selectively increased the activity of the enzymes involved in beta-oxidation in these organelles. In kidney cortex, only a moderate increase in enzyme activity could be recorded. Valproate (1% w/w in the diet for 25 to 100 days) caused the appearance on electron micrographs of unusual tubular inclusions in the matrix of liver peroxisomes.