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Biomedical subjects

T Chang

Publications and source records attributed to T Chang.

275 records · Page 16Linked to original sources
PubMedDate not supplied

Occlusion of arteriovenous malformations of the cavernous sinus via the superior ophthalmic vein.

The treatment of five patients with dural arteriovenous malformations (AVMs) of the cavernous sinus via the superior ophthalmic vein (SOV) is reported. The procedure was performed by transcutaneous puncture of the SOV under the guidance of real-time digital subtraction angiography. Complete resolution of the ocular symptoms was achieved in all cases. Angiograms after embolization showed complete obliteration of the malformation in four cases and partial obliteration in one. This method can cure dural AVMs of the cavernous sinus, with preservation of blood flow in the internal carotid artery. It is particularly indicated when the SOV is enlarged and when (1) dural AVMs of the cavernous sinus are fed by small branches of the internal carotid artery or direct carotid cavernous fistulas with small tears; (2) dural AVMs of the cavernous sinus are fed by multiple branches from both the internal and external carotid arteries, one or both sides; or (3) dural AVMs of the cavernous sinus or direct carotid cavernous fistulas recur after trapping of the internal carotid artery. Transcutaneous puncture and catheterization of the SOV was performed safely with the aid of digital subtraction angiography. The SOV approach was able to treat the fistula with preservation of the internal carotid artery.

Adult↗
PubMedDate not supplied

Bioactivation and irreversible binding of the cognition activator tacrine using human and rat liver microsomal preparations. Species difference.

Tacrine's [1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate, (THA)] metabolic fate was examined using human and rat liver microsomal preparations. Following 1-hr incubations with human microsomes, [14C]THA (0.4 microM) was extensively metabolized to 1-hydroxyTHA with trace amounts of 2-, 4-, and 7-hydroxyTHA also produced. Poor recovery of radioactivity in the postreaction incubates suggested association of THA-derived radioactivity with precipitated microsomal protein. After exhaustive extraction, 0.034, 0.145, 0.126, and 0.012 nmol eq bound/mg protein/60 min of THA-derived radioactivity was bound to human liver preparations H109, H111, H116, and H118, respectively. Preparations H109 and H118 were lower in P4501A2 content and catalytic activity as compared with preparations H111 and H116. Incubations of equimolar [14C]1-hydroxyTHA with human liver microsomes also resulted in binding to protein, although to a lesser extent than observed with THA. [14C]THA (0.4 microM) was incubated for 1 hr with rat liver microsomes (1 microM P-450) prepared from noninduced (N), phenobarbital (PB), isoniazid (I), and 3-methylcholanthrene (3-MC)-pretreated animals. In all incubations, 1-hydroxyTHA was the major biotransformation product detected. After exhaustive extraction, 0.048, 0.054, 0.049, and 0.153 nmol eq/mg protein/60 min of THA-derived radioactivity was bound to microsomal protein from N, PB, I, and 3-MC pretreated rats. Increased binding with 3-MC induced rat liver preparations suggests the involvement of the P-450 1A subfamily in THA bioactivation. Glutathione (5 mM) coincubation inhibited the irreversible binding of THA-derived radioactivity in both human and 3-MC-induced rat liver preparations, whereas human epoxide hydrase (100 micrograms/incubate) had a relative minor effect. A mechanism is proposed involving a putative quinone methide(s) intermediate in the bioactivation and irreversible binding of THA. A species difference in THA-derived irreversible binding exists between human and noninduced rat liver microsomes, suggesting that the rat is a poor model for studying the underlying mechanism(s) of THA-induced elevations in liver marker enzymes found in clinical investigations.

Animals↗
PubMedDate not supplied

Biodisposition studies with the acyl-coenzyme A: cholesterol acyltransferase inhibitor 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide, CI-976.

2,2-Dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide, CI-976, is a newly developed fatty acid anilide being evaluated as a plasma lipid regulator and antiatherosclerotic agent. Disposition studies with CI-976 were conducted in rats and monkeys. In rats, CI-976 (suspension, 50 mg/kg) was approximately 30% bioavailable, with 46% of the administered radioactivity recovered in urine suggesting presystemic metabolism. The intravenous elimination half-life of CI-976 in rats was approximately 8 hr. Radioactivity derived from [14C]CI-976 was almost completely recovered in rats after either oral or intravenous administration. In bile duct-cannulated rats receiving either an oral or intravenous dose, biliary excretion was the major route of drug-derived radioactivity elimination. There was no evidence for unchanged drug in urine or bile. In monkeys, 13% urinary recovery and 5% bioavailability was achieved after a single 50 mg/kg suspension dose. Similar values were obtained following a 250 mg/kg dose. Monkeys displayed a CI-976 elimination half-life of 0.6 hr after a 2 mg/kg intravenous dose. No unchanged drug was excreted in urine. In summary, CI-976 exhibits moderate absorption and bioavailability in the rat, but lower absorption and bioavailability in monkey. A special difference in CI-976 elimination half-life was observed consistent with in vitro metabolism results.

Administration, Oral↗