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Biomedical subjects

T Chang

Publications and source records attributed to T Chang.

At least 271 records · Page 15Linked to original sources
PubMedDate not supplied

Preparation of diastereomeric beta-d-glucuronides of the bronchodilator procaterol using immobilized rabbit liver microsomal enzymes.

Liver microsomal pellets from a phenobarbital induced New Zealand white male rabbit were prepared, solubilized, and reacted with cyanogen bromide activated Sepharose beads to form an immobilized microsomal enzyme preparation. Viability of bound enzymes was determined using established methods. Racemic erythro-[3H]-procaterol hydrochloride was incubated with immobilized microsomal enzymes at room temperature in 0.1 M potassium phosphate buffer (pH 7.4) together with cofactors magnesium chloride and UDPGA for 16 h. The incubation mixture was filtered and the filtrate fractionated by a C18 solid phase extraction procedure. Two polar reaction products were isolated and characterized by TLC, HPLC-RAM (homogeneous flow-through radioactivity detection), [1H]-NMR, and Fast-Atom Bombardment mass spectrometry as diastereomeric aryl-O-glucuronides of erythro-procaterol. Based on HPLC-RAM analysis, glucuronidation of racemic procaterol proceeds with regiostereoselectivity. In addition, both diastereomers are formed in nearly equal amounts indicating lack of enantioselectivity in this reaction. Combined yield of both diastereomers was approx. 60%.

Animals↗
PubMedDate not supplied

CT and myelogram findings of os odontoideum.

We reviewed the findings of CT and myelogram of cases of os odontoideum. The diagnosis was confirmed by conventional tomogram in all these cases. Four cases were further confirmed by trans-oral decompression. Cartilage was found between the os odontoideum and the odontoid process during operation in these 4 cases. Four of them had no history of trauma and 2 of them had an associated anomaly; one was Down's syndrome, and the other was barrel chest and congenital dislocation of hips. CT findings of os odontoideum in these cases were a constriction and/or a gap of bony structure between the os odontoideum and the odontoid process. Myelograms showed spinal stenosis as a result of atlanto-axial dislocation, or anterior extradural compression from overgrown cartilage and posteriorly dislocated tip of shortened odontoid process.

Adolescent↗
PubMedDate not supplied

Epithelioid hemangioendothelioma of spleen with intrasplenic metastasis: ultrasound and computed-tomography appearance.

The US and CT appearances of epithelioid hemangioendothelioma of the spleen with intrasplenic metastasis have not been previously reported. We described a 29-yr-old female with such a disease. Abdominal US study revealed a large mass in the upper pole and multiple small nodules in the rest of the spleen. CT scan also showed similar lesions of hypodensity which were not apparently enhanced by contrast medium.

Adult↗
PubMedDate not supplied

Identification of a pyridinium metabolite in human urine following a single oral dose of 1-[2-[bis[4-(trifluoromethyl)phenyl]methoxy]ethyl]- 1,2,5,6-tetrahydro-3-pyridinecarboxylic acid monohydrochloride, a gamma-aminobutyric acid uptake inhibitor.

Single-dose administration of 50 mg of 1-[2-[bis[4- (trifluoromethyl)phenyl]methoxy]ethyl]-1,2,5,6-tetrahydro-3- pyridinecarboxylic acid monohydrochloride resulted in temporary neurological and psychological symptoms in two subjects. Because of the nature of adverse effects, urine from a subject who received CI-966 orally was extracted to investigate the metabolism of CI-966 in man. An unknown urinary component was identified as a pyridinium metabolite of CI-966 based on HPLC-MS and 1H and 19F NMR. Structural confirmation was achieved by chromatographic and spectroscopic comparisons to a reference standard. In several in vitro screens and preclinical studies, the pyridinium metabolite appears to possess minimal pharmacological activity.

Administration, Oral↗
PubMedDate not supplied

Colitis induced by Clostridium difficile.

Clostridium difficile has been implicated as the major cause of antibiotic-associated pseudomembranous colitis. The current laboratory diagnostic test of choice is a tissue culture assay that demonstrates the presence of a cytopathic toxin neutralized by antitoxin to Clostridium sordellii. This toxin was found in stools from 42 of 43 patients with antibiotic-associated pseudomembranous colitis and in stools from 12 of 78 patients with antibiotic-associated diarrhea. Specimens from patients with gastrointestinal conditions unrelated to administration of antibiotics and those from healthy controls were uniformly negative. Neutralization of toxin by antitoxin to C. sordellii appears to represent antigenic cross-reactivity, since broth cultures of C. difficile also contain a cytopathic toxin neutralized by this antitoxin. Strains of C. difficile are susceptible to vancomycin, and the initial clinical experience with oral administration of this agent shows promising results.

Animals↗
PubMedDate not supplied

Pharmacokinetics and efficacy of pirmenol hydrochloride in the treatment of ventricular dysrhythmia.

Pirmenol hydrochloride (CI-845), a new antiarrhythmic agent available for both oral and intravenous administration, was given to seven patients with chronic ventricular dysrhythmia in an open-label fashion. After intravenous infusion of 150 mg over 30 min, the mean (+/- SD) peak plasma concentration achieved was 2.14 +/- 0.75 microgram/ml. The terminal elimination half-life, the volume of the central compartment, and the total body clearance averaged 6.5 h, 0.70 +/- 0.36 L/kg, and 3.0 +/- 2.6 ml/min/kg, respectively. After a single 150-mg oral dose, the peak plasma concentration of 1.3 +/- 0.55 microgram/ml was achieved 1 to 3 h after dosing. The mean apparent elimination half-life was 7.6 h. An estimated absorption lag time ranging from 14 to 37 min was observed in all but one patient. The mean absolute bioavailability for the oral dose was 87%. Dysrhythmia data were available in six patients. Complete (100%) suppression of ventricular ectopic beats occurred in four patients for 1/2 to 15 h after intravenous infusion, and in three patients for 7 to 25 h after oral dose. This suppression occurred with a plasma pirmenol level as low as 0.4 microgram/ml. No significant side effects were observed.

Administration, Oral↗
PubMedDate not supplied

Lack of interaction of gabapentin with carbamazepine or valproate.

Gabapentin (GBP) studies were conducted in patients with epilepsy receiving carbamazepine (CBZ, n = 12) or valproate (VPA, n = 14) monotherapy. The effects of GBP coadministration on steady-state CBZ or VPA concentrations and of these antiepileptic drugs (AEDs) on GBP pharmacokinetics were investigated. GBP (400 mg) was coadministered every 8 h for 3 1/3 days with CBZ or for 5 1/3 days with VPA. GBP was well tolerated. Mean steady-state plasma CBZ/CBZ-10,11-epoxide (CBZ-E) and serum VPA concentrations before, during, and after GBP administration were not significantly different. Mean steady-state GBP pharmacokinetic parameters during CBZ or VPA coadministration were similar to steady-state parameters reported in healthy subjects. Thus, no pharmacokinetic interaction exists between CBZ or VPA and GBP. No dosage adjustment is necessary when GBP and CBZ or VPA are coadministered.

Acetates↗
PubMedDate not supplied

Metabolism of the acyl-CoA:cholesterol acyltransferase inhibitor 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide in rat and monkey. Omega-/beta-oxidation pathway.

2,2-Dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide (CI-976) is a newly developed hypocholesterolemic agent. In pharmacokinetic studies, CI-976 was found to have a much shorter elimination half-life in monkey (0.6 hr) compared to rat (8 hr). Radioactivity analysis of biological samples from rats and monkeys administered [14C]CI-976 either iv or orally showed CI-976 to be extensively metabolized to a single major common metabolite. This metabolite was isolated and its structure determined by GC/MS, LC/MS, and NMR spectroscopy as a 6-carbon chain-shortened carboxylic acid derivative, 5,5-dimethyl-6-oxo-6-[(2,4,6-trimethoxyphenyl)amino]-hexanoic acid. A potential pathway leading to this carboxylic acid derivative may involve initial omega-oxidation followed by beta-oxidation. A potential species difference in omega-/beta-oxidative biotransformation capabilities appears to exist.

Administration, Oral↗
PubMedDate not supplied

Metabolic disposition of trimetrexate, a nonclassical dihydrofolate reductase inhibitor, in rat and dog.

The metabolic disposition of trimetrexate, a nonclassical inhibitor of dihydrofolate reductase, was characterized in the rat. After iv administration of 1.2 mg/kg [14C]trimetrexate (as the glucuronate), recovery of total radioactivity in urine and feces through 144 hr was greater than 96% of dose. Trimetrexate was extensively metabolized, with only 13% of the dose excreted unchanged in urine and bile. Profiling of biliary and urinary radioactivity showed three components and unchanged drug accounted for the majority of excreted radioactivity (75% of dose). Tandem mass spectral analysis of one urinary component suggested trimetrexate had undergone N-dealkylation and oxidation to 2,4-diamino-5-methyl-6-quinazolinecarboxylic acid. Structural assignment for this metabolite was confirmed by comparison to authentic reference material. Mass spectral analysis of a second component gave a quasimolecular ion (MH)+ at m/z 532 with a key fragment ion at m/z 356 (MH-176)+, characteristic of a glucuronide conjugate. The proton NMR spectrum of this component was consistent with expectations for a glucuronide conjugate of 4'-O-desmethyl trimetrexate. Possible formation of a sulfate conjugate was explored by co-administration of unlabeled trimetrexate with [35S]sulfate to rats. A 35S-labeled component was excreted in urine, which co-eluted with the third major urinary 14C-labeled component observed in the first experiment. Mass spectrum of this component was consistent with the structure of trimetrexate-4'-O-desmethyl sulfate. In dogs, the disposition of trimetrexate was examined using stable isotope-labeled material. The dose was 10 mg/kg administered iv as a 1:1 mixture of 13C2, 15N-labeled and unlabeled trimetrexate glucuronate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[The relationship of clinical severity and roentgenologic findings in beta thalassemia].

There were altogether 68 patients suffered from beta-thalassemia in the Veterans General Hospital from 1979 to 1986. However only 18 patients had abnormal roentgenologic findings. They were 7 males and 11 females. Their ages ranged from 8 months to 47 years with an average of 13 years. Clinically beta-thalassemia was divided into 3 types: 1) thalassemia major, 2) thalassemia intermediate, 3) thalassemia minor. The osteoporosis, hepatosplenomegaly, and extramedullary hematopoiesis with pseudo-tumor formation. We concluded that the roentgenologic manifestation of the patient was more in patients with major or intermediate type.

Adolescent↗
PubMedDate not supplied

CT of pineal tumors and intracranial germ-cell tumors.

We reviewed 59 cases of pineal tumors and intracranial germ-cell tumors. Most pineal tumors occurred in the first three decades of life, with the exception of pineocytomas, which were seen at a mean age of 34. A male preponderance was noted in the various pineal tumors, except for pineocytomas. The most common tumor of the pineal region was germinoma, which usually showed high density with homogeneously intense enhancement after IV administration of contrast medium. An increased prevalence of pineal calcification was also a feature of pineal germinomas. No characteristic CT features could be found to differentiate among pineal choriocarcinoma, germinoma, embryonal carcinoma, yolk-sac tumor, pineocytoma, and pineoblastoma. CT is useful in detecting intracranial tumors, but the definite diagnosis should depend on pathologic examination and detection of tumor markers in the serum and CSF.

Adolescent↗
PubMedDate not supplied

In vivo metabolism of isoxicam in rats, dogs, and monkeys.

Isoxicam is a long half-life nonsteroidal anti-inflammatory agent which undergoes extensive metabolism prior to elimination in animals and man. The major route of isoxicam transformation is hydroxylation of the methylisoxazole functionality to form hydroxymethylisoxicam, and cleavage of its benzothiazine moiety to give an oxoacetic acid metabolite. The metabolic pathway for scission of the benzothiazine moiety to the oxoacetic acid metabolite and to other potential metabolites is not known. To gain additional information on the metabolic fate of isoxicam, 14C-isoxicam labeled on the N-methyl group was administered to rats, dogs, and monkeys with urine and feces collected for metabolic profiling and identification. Identified as new metabolites of isoxicam were an open-ring sulfonamide, N-methylsaccharin, and saccharin. The formation of these metabolites suggests that isoxicam undergoes direct oxidative scission of its benzothiazine ring at carbon atom 3 to generate the observed open-ring sulfonamide, N-methylsaccharin, and oxoacetic acid metabolites.

Animals↗
PubMedDate not supplied

The pituitary mass after transsphenoidal hypophysectomy.

To understand the natural changes in the CT appearance of a pituitary mass after transsphenoidal hypophysectomy of a pituitary tumor, we obtained CT follow-up studies in 12 patients with pituitary adenoma. The heights of the pituitary masses on the coronal sections of each CT study were measured. It was found that the height of the pituitary mass did not return to normal immediately after the operation, despite complete removal of the pituitary tumor. Instead, the height gradually returned to normal between 3 and 4 months after the operation. Results of this study suggest that follow-up CT study of pituitary masses is best performed 3-4 months after transsphenoidal hypophysectomy.

Adenoma↗