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Biomedical subjects

S L Chang

Publications and source records attributed to S L Chang.

131 records · Page 8Linked to original sources

Immunoassay detection of drugs in racing horses: detection of ethacrynic acid and bumetanide in equine urine by ELISA.

We have raised antibodies and developed one-step enzyme-linked immunosorbent assays (ELISA) for the diuretics ethacrynic acid and bumetanide as part of a panel of pre- and post-race tests for high potency drugs in racing horses. These ELISA tests are rapid (completed within one hour), sensitive, and can be read by eye. The ELISA detects ethacrynic acid at a drug concentration for half-maximal inhibition (I-50) of about 2.5 ng/mL for the parent drug. After dosing horses intravenously with 5 mg ethacrynic acid per horse, the parent drug or its metabolites are detectable in urine for at least 8 hours. The bumetanide ELISA has an I-50 for the parent drug of about 2.0 ng/mL and will detect bumetanide or its metabolites for about 8 hours in urine after intravenous administration of a 1.7-mg dose per horse. Both antibodies are relatively specific for each drug and do not cross-react with other commonly used diuretics or other acidic compounds often found in post-race equine urine samples. Ethacrynic acid and bumetanide are potent diuretics suspected of being illegally substituted for furosemide in certain racing jurisdictions. Development of these rapid, sensitive, and simple tests for these agents will allow more effective pre- and post-race control of the use of these agents in racing horses. Both tests have recently uncovered several "positives" for these medications in a midwestern racing jurisdiction.

Animals↗

Bone mineral content in growing children.

In order to establish the normal values of bone mineral content (BMC) (g/cm2), the BMC of 140 healthy growing children including 49 girls (aged 5 to 16 years) and 91 boys (aged 7 to 17 years) was measured using Dual Photon absorptiometry (DPA) at L2-L4 level of the spine. The BMC increased significantly with age, after stratification by age. Both male and female children aged 7 to 10 years had similar BMC, but female children had significantly higher BMC at 12 to 13 years of age. We also established regression equations. Female: BMC = 0.38 + 0.021 x age. Male: BMC = 0.45 + 0.017 x age. They may be useful in estimating BMC in unknown individuals

Adolescent↗

Studies on the biotransformation in the perfused rat liver of 2-n-propyl-4-pentenoic acid, a metabolite of the antiepileptic drug valproic acid. Evidence for the formation of chemically reactive intermediates.

The metabolism of 2-n-propyl-4-pentenoic acid (delta 4-VPA), a putative toxic biotransformation product of valproic acid (VPA), was examined in the isolated perfused rat liver. Metabolites excreted into perfusion medium and bile were characterized by GLC and GC/MS techniques and their identities were verified by synthesis. A total of eight metabolites was detected, the structures of which could be best accounted for by initial oxidation reactions catalyzed by either cytochrome P-450 or the fatty acid beta-oxidation complex. Evidence was obtained which indicates that metabolism of delta 4-VPA by each of these enzyme systems can lead to the generation of chemically reactive intermediates which may contribute to the hepatotoxic properties of VPA.

Animals↗

Inhibitory effect of valproic acid on the disposition of carbamazepine and carbamazepine-10,11-epoxide in the rat.

The effects of valproic acid on the disposition of carbamazepine and carbamazepine epoxide were studied in conscious rats. Each animal received a constant rate infusion of carbamazepine and an iv bolus dose of epoxide in the presence and absence of valproate. The latter was maintained within its therapeutic range by iv infusion. Carbamazepine steady state clearance was decreased by 20.2 +/- 12.7% in the presence of valproate. The formation clearance of carbamazepine epoxide, which accounts for 50% of the total clearance, was decreased on the average by 22.7%. Also, a significant increase in the level of carbamazepine epoxide formed from carbamazepine was found in the presence of valproate. This increase in metabolite level was explained by the large reduction in epoxide clearance (41.6 +/- 13.1%) observed after single doses of epoxide. Based on this finding, a separate study examined the effect of valproate on the non-renal component of the clearance of carbamazepine epoxide. The non-renal clearance of epoxide was decreased by 59.9 +/- 11.9% in the presence of valproic acid.

Animals↗