Glutamine-valine index - An aid in the detection of urea-cycle disorders.

By relating the increase in glutamine to the corresponding increase in valine following protein loading it has been possible to detect carriers of OCT deficiency.

Familial salivary gland insensitivity to aldosterone: a variant of pseudohypoaldosteronism.

Two male siblings presented in infancy with hyponatraemia. Levels of plasma renin activity and aldosterone were elevated. Sodium supplementation was necessary to maintain normal sodium balance. Urinary sodium concentration and renal epithelial exchange between sodium and potassium were normal; however, salivary sodium concentrations were markedly elevated with sweat sodium levels being in the upper normal range. Excess salivary sodium loss accounted for sodium depletion in these cases who present a new variant of pseudohypoaldosteronism associated with normal renal sodium transport.

Ginseng--is there a use in clinical medicine?

Panax ginseng occupies an important place among the tonic remedies of Oriental medicine. Pharmacological investigations show that crude ginsenosides can increase non-specific resistance of an organism to various untoward influences. The effects of purified derived derivatives have only recently become better studied in immunological and cell growth studies in animals and in man. This has now provided some evidence to suggest that ginseng is a drug that contains many derivatives with different pharmacological properties, which could be useful in clinical medicine.

Lactosylceramide in inflammatory bowel disease: a biochemical study.

A simple technique for isolating lipids from small pieces of tissue was applied to mucosal biopsies and samples of resected intestine from patients with inflammatory bowel disease. Scanning densitometry of two dimensional chromatograms showed increased concentrations of the membrane associated glycosphingolipid lactosylceramide in Crohn's disease, on comparison with ulcerative colitis (p less than 0.01), or controls (p less than 0.01). This indicates either that normal glycosphingolipid metabolism is altered, or that a novel source of lactosylceramide is present in the inflamed mucosa of patients with Crohn's disease.

In-vitro antibiotic inactivation by mammalian cell and killed bacterial preparations.

Inactivation of a range of antibiotics acting at different points in the metabolism of the bacterial cell was detected by estimating the MIC and MBC in the presence of liver and other tissue preparations. High temperature treatment and sonication of liver cells increased their ability to inactivate antibiotic action. This treatment would have almost completely destroyed enzyme activity, which was, therefore, not thought likely to be the cause of the phenomenon. The loss of antibiotic activity may be related to "protein binding" and a dialysis experiment showed that penicillin binding with liver homogenate was very much greater than with human albumin. It may be that increased disruption of tissue cells by physical methods exposes more active binding sites which reduces the bioavailability of antibiotics. Some degree of binding specificity was indicated in experiments in which DNA was shown to block antibiotics acting primarily on DNA--related synthesis and RNA blocked antibiotics acting on RNA--related metabolism. Suggestions are made for the cause of failure of antibiotic treatment in certain clinical situations.

An alternative way of presenting quantitative amino acid results.

An application of computer graphics is described which enables quantitative plasma amino reports to be presented pictorially in a way which enhances the quality of the information.

Inhibition of bovine liver lysine-ketoglutarate reductase by urea cycle metabolites and saccharopine.

Lysine-ketoglutarate reductase was purified 675-fold from bovine liver mitochondria. Product inhibition studies gave results similar to those reported for this enzyme extracted from other sources. Inhibition studies with L-citrulline exhibited mixed inhibition patterns. No inhibition of the partially-purified enzyme by ammonium salts was detected; in contrast, marked inhibition of the enzyme by ammonium was apparently observed in crude liver homogenates. This was probably due to depletion of NADPH and/or 2-oxoglutarate in the assay mixture as a result of conversion of ammonium to glutamate by glutamate dehydrogenase. A similar explanation could account for the high levels of lysine observed in humans with urea cycle disorders.

Effect of partial ornithine carbamoyltransferase deficiency on urea synthesis and related biochemical events.

The biochemical response to an intravenous alanine load of 0.25 g/kg was studied in nine adult female relatives of children with ornithine carbamoyltransferase deficiency. Six were classified as affected by partial deficiency and three as unaffected. The plasma ammonium concentration showed no change after the alanine load in the unaffected group, but marked increases occurred in all but one of the affected groups. The maximum rate of urea synthesis after the alanine load was decreased by 37% (P = 0.02) and delayed by 43% (P = 0.02) in the affected group. In the affected group a low rate of urea synthesis was associated with high urinary orotate excretion, high maximum plasma ammonium concentration and delay in the time taken to reach the maximum rate of urea synthesis (Kendall concordance W = 0.55, P less than 0.05). The effects of a higher dose of alanine and of oral protein were compared. The alanine load of 0.25 g of alanine/kg body weight was shown to provide an adequate stimulus to urea synthesis with a more rapid return of ammonium concentration to the pre-load level than with the protein load. The implication of these results in determining the distribution of flux control of urea synthesis, the discrepancy between them and predicted results and the necessary modifications to quantitative simulations are discussed.

Determination of the rate of urea synthesis from serial measurements of plasma urea concentration after an alanine load: theoretical and methodological aspects.

A method is described by which the rate of synthesis of urea can be calculated from the change of plasma concentration of urea after an alanine load. The results can be expressed in terms of f, the maximum increase in the rate of urea synthesis, and t, the time at which urea synthesis reaches its maximum. These parameters are calculated by an algebraic curve-fitting technique which is suitable for a desk computer. The method removes the need for isotopic analysis and urine collections. The effect of various errors and experimental conditions on the calculated synthesis parameters is investigated.

Neurological features and computed tomography of the brain in children with ornithine carbamoyl transferase deficiency.

The clinical features and the computed tomographic appearances of the brain in seven children with ornithine carbamoyl transferase deficiency are described. Episodic vomiting and drowsiness, acute encephalopathy, failure to thrive and developmental retardation were common, but focal neurological symptoms and signs were also observed. The CT appearances were non-specific with generalised or focal changes. They were related to the severity, the duration and the age of onset of the hyperammonaemia. Since the CT changes may suggest conditions other than metabolic disease, the emergency investigation of a child with an encephalopathy should include the estimation of plasma ammonium and, if elevated, the appropriate investigations to establish the cause.

Conditions affecting the colorimetry of orotic acid and orotidine in urine.

We studied conditions affecting a colorimetric assay of total orotic acid (orotic acid plus orotidine) in urine. Most interfering substances can be conveniently removed on a small column of cation-exchange resin, and an improved control reaction corrects for residual background color. Analytical recovery from urine is nearly complete (greater than 95%) and the absorption spectrum for analyte eluted from the column closely resembles that for an orotic acid standard. We determined reference intervals for total orotic acid, expressed as a molar ratio to creatinine, for neonates, children, and adults, and assessed the effect of age, protein intake, and pregnancy. The method is simple enough to use as a reliable and accurate urine-screening test.

Three instances of neonatal death with hyperammonaemia, each resulting from a different cause.

We report here the results of a study of three unrelated patients, K., M. and R., each of whom died in the neonatal period in St Sophia's Children's Hospital, Athens, Greece, after a normal pregnancy and delivery. Liver functions tests and blood cultures gave normal results in each case and autopsy did not reveal any specific findings. All had gross hyperammonaemia and were considered to have possible urea cycle defects.

3-Amino-2-piperidone in the urine of patients with hyperornithinemia.

3-Amino-2-piperidone, a delta-lactam of ornithine, has been detected in the urine of a number of patients with hyperornithinemia. The distinctive yellow colour formed with a ninhydrin-cadmium reagent should help in the detection of hyperornithinemia by urinary chromatography.