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Biomedical subjects

Adrian C Sewell

Publications and source records attributed to Adrian C Sewell.

8 recordsLinked to original sources
PubMed2006

Inherited metabolic disease in companion animals: searching for nature's mistakes.

Inborn errors of metabolism are caused by genetic defects in intermediary metabolic pathways. Although long considered to be the domain of human paediatric medicine, they are also recognised with increasing frequency in companion animals. The diagnosis of diseased animals can be achieved by searching for abnormal metabolites in body fluids, although such screening programmes have, until now, not been widely available to the small animal clinician. A comprehensive battery of analytical tools exists for screening for inborn metabolic diseases in humans which can be applied to animals and serve not only for the diagnosis of affected patients but also to detect asymptomatic carriers and further our understanding of metabolic pathways in dogs and cats. Moreover, naturally occurring animal models of inherited metabolic diseases provide a unique opportunity to study the biochemical and molecular pathogenesis of these disorders and to investigate possible therapeutic options.

Animals↗
PubMed2006

Argininosuccinate lyase deficiency (ASL) and carbohydrate-deficient transferrin (CDT): experience with four independent CDT analysis methods--misleading results given by the %CDT TIA assay.

BACKGROUND: Chronic liver disease can cause false-positive carbohydrate-deficient transferrin (CDT) results mimicking chronic alcohol abuse. We tested whether argininosuccinate lyase deficiency (ASL), a genetic disorder of the urea cycle with hepatomegaly and biochemical hepatitis, causes increased CDT results and whether this depends on the analytical method. METHODS: Seven serum samples from four ASL patients without alcohol abuse were analyzed by capillary electrophoresis, HPLC, particle-enhanced immunonephelometry with monoclonal CDT antibodies, and microcolumn CDT and non-CDT fractionation followed by a turbidimetric immunoassay with transferrin antibodies (%CDT TIA). RESULTS: Increased CDT results (two out of four patients or five out of seven samples) were obtained by the %CDT TIA assay, but not by the remaining three CDT tests. The corresponding serum samples showed increased fractions of trisialotransferrin by HPLC (as the IFCC reference method for CDT analysis). One sample contained an elevated trisialotransferrin but a normal CDT also in the %CDT TIA test. One patient had a normal trisialotransferrin and a normal CDT as assayed by each of the four CDT methods. CONCLUSIONS: Argininosuccinate lyase deficiency is not itself a cause for increased CDT values. Increased fractions of trisialotransferrin in ASL patients appear to interfere with CDT analysis by the %CDT TIA assay. This can give false-positive CDT results. Since this can appear not only in ASL patients, microcolumn CDT and non-CDT fractionation followed by a turbidimetric immunoassay using transferrin but not CDT antibodies by the %CDT TIA assay should no longer be used for CDT measurement without confirmatory analysis by HPLC or capillary electrophoresis.

Adolescent↗
PubMed2003

Simultaneous enantioselective analysis of chiral urinary metabolites in patients with Zellweger syndrome.

Enantio-MDGC-MS analysis with heptakis-(2,3-di-O-methyl-6-O-tert.-butyl-dimethylsilyl)-beta-cyclodextrin as the chiral main column is a powerful tool for the separation of chiral compounds. This paper reports on the simultaneous stereodifferentiation of 2-hydroxyisocaproic acid (HICA), 3-methyladipic acid (3-MA), 2-hydroxyglutaric acid (2-HG), 3-(4-hydroxyphenyl)-lactic acid (HPLA), 2-hydroxysebacic acid (2-HS) and 3-hydroxysebacic acid (3-HS) in a single chromatographic run. These chiral urinary metabolites are useful in the diagnosis of peroxisomal diseases such as Zellweger syndrome (ZS). In this investigation, urine samples from nine patients with ZS were analysed in order to reveal the enantiomeric ratio of these chiral metabolites. The stereodifferentiation of the analysed chiral compounds may provide important information on their biochemical origin.

Carboxylic Acids↗
PubMed2003

Multidimensional gas chromatography-mass spectrometry for tracer studies of fatty acid metabolism via stable isotopes in cultured human trophoblast cells.

The determination of placental fatty acid metabolism using stable isotope-labeled tracers was investigated in the human placental choriocarcinoma (JAR) cell line. Stable isotope incorporation was measured by MDGC-MS. The cultured trophoblast cells incorporated and metabolized the essential fatty acids to long-chain polyunsaturated fatty acids. The described method enables the detection of a low Delta(6)-desaturase activity in this human placental cell line. The developed MDGC-MS method allows the assessment of long-chain polyunsaturated fatty acid biosynthesis in cultured cells with high sensitivity and selectivity. In this respect, tracer studies with MDGC-MS will be a powerful tool to clarify the significance of placental fatty acid metabolism.

Cells, Cultured↗
PubMed2002

Antibiotic treatment-induced tubular dysfunction as a risk factor for renal stone formation in cystic fibrosis.

OBJECTIVES: Our purpose was to characterize the decisive pathophysiologic factors that lead to renal stone formation (nephrolithiasis) in patients with cystic fibrosis (CF). METHODS: Patients with CF (n = 96) were investigated with respect to lithogenic and inhibitory factors of urolithiasis and compared with 30 healthy control patients. They were subdivided into 2 groups, 86 without renal stones and 10 with renal stones. RESULTS: All stones were exclusively composed of calcium oxalate. As a major pathogenic factor, a urinary disequilibrium between promoting and inhibitory components of stone formation, characterized mainly by hypercalciuria, hyperoxaluria, and hypocitraturia, was found in the patients with nephrolithiasis. They tended to have lower plasma phosphate concentrations and an increased urinary phosphate excretion. The citrate/calcium ratio proved to be a valuable means to discriminate patients with renal stones from control patients. Patients with stones had ingested more cotrimoxazole and ceftazidim, cumulatively, than patients without stones. There was an inverse correlation between the amounts of antibiotics ingested and the percentage of tubular phosphate reabsorption (r = -0.91, P <.0046). CONCLUSION: Renal stone formation in patients with CF is caused by a disequilibrium between promoting and inhibitory components of stone formation, which is dominated by hypercalciuria, hyperoxaluria, and hypocitraturia. Treatment with cotrimoxazole and ceftazidim, primarily, may lead to renal proximal tubular damage with an ensuing sequence of phosphate loss, increase of parathyroid hormone secretion, increased 1,25-dihydroxyvitamin D3 formation, and absorptive hypercalciuria.

Adolescent↗