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Biomedical subjects

T Chang

Publications and source records attributed to T Chang.

At least 217 records · Page 12Linked to original sources

Effect of butalbital and phenobarbital pretreatment on antipyrine clearance in the rat.

The disposition kinetics of antipyrine after a single i.v. dose (75 mg/kg) of [14C]antipyrine were examined in control rats and in rats pretreated with butalbital and phenobarbital. Blood antipyrine data indicated that daily administration of phenobarbital (50 mg/kg) for 14 days resulted in significantly more rapid elimination of antipyrine than that observed after equal doses of butalbital, which was in turn significantly faster than the control values. Results of additional antipyrine tests after phenobarbital pretreatment for 2 and 5 days showed considerable enzyme induction after only 2 days of exposure to phenobarbital; the mean antipyrine clearance after the 2-day pretreatment was not significantly different from those after the 5- and 14-day pretreatments. The data suggested that the maximum increase in antipyrine clearance, ca. 190% of the control value, was achieved after approximately 5 daily doses of phenobarbital and maintained until the end of the 14-day pretreatment period. The subsequent decline in the induced enzyme activity, assessed by the antipyrine clearance values on days 1, 3, 6, and 9 post-phenobarbital treatment, appeared to be mono-exponential with a half-time of 3.8 days. Thus, the enzyme activity would return to baseline at ca. 15 days after the last dose of phenobarbital. In these studies, consistent increases in liver weight with increasing antipyrine clearance were observed, while no apparent relationship between antipyrine distribution volume and barbiturate pretreatment was found.

Animals↗

Effect of difluoromethylornithine on host and tumor polyamine metabolism during total parenteral nutrition.

Clinical and experimental data suggest that erythrocyte (RBC) polyamine (PA) levels are markers of tumor proliferation during total parenteral nutrition (TPN). The purpose of this experiment was to determine whether the inhibition of PA synthesis during TPN was greater in tumors than in normal host tissue. Rats bearing a subcutaneous fibrosarcoma were randomized to receive a chow diet (n = 5), TPN (n = 5), or TPN + difluoromethylornithine (DFMO) (an irreversible inhibitor of ornithine decarboxylase (ODC), at 1000 mg/kg body wt/day n = 4) for 6 days by continuous central venous infusion. TPN + DFMO resulted in a higher plasma albumin level and lower tumor ODC activity compared with chow feeding or TPN. Liver ODC activity was similar for the chow fed, TPN, and TPN + DFMO groups. RBC putrescine, tumor putrescine, and tumor spermidine levels were significantly lower in the TPN + DFMO group compared with the chow fed and TPN groups. RBC spermidine, RBC spermine, and tumor spermine levels were significantly increased with TPN + DFMO compared with TPN alone. DFMO did not produce diarrhea or weight loss. Increased RBC spermidine may indicate a toxic effect of DFMO on the tumor, resulting in leakage of tumor spermidine into the extracellular space. The data suggest that DFMO during TPN can selectively inhibit tumor PA synthesis and may improve host utilization of nutrients.

Animals↗

Isolation and identification of piperacillin amide as an impurity in piperacillin.

Piperacillin amide (IV) was successfully identified as the predominant impurity in commercial lots of piperacillin monohydrate (III). The impurity was isolated via a preparative liquid chromatographic scheme utilizing Florisil as the adsorbent and a mobile phase of water-acetonitrile (4:96, v/v). The isolated component had nearly the same reverse-phase HPLC properties as piperacillin and was chemically and thermally unstable. This labile impurity was spectroscopically identified by field desorption (FD), fast atom bombardment (FAB) with collision activation decomposition (CAD), and desorption chemical ionization (DCI) mass spectrometries , and NMR and IR spectrometries . Identity was confirmed on comparison of the chromatographic and spectrometric data of the impurity with an independently synthesized sample of piperacillin amide.

Chemical Phenomena↗

Influence of mode of intravenous administration and blood sample collection on rat pharmacokinetic data.

The influence of the mode of intravenous dosing and blood sample collection on the pharmacokinetics of 4-[(3-methoxyphenyl)-methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza-2, 6-disilacyclohexane hydrochloride (I) was studied in the rat. Blood samples obtained from the tail and by exsanguination following injection of the 14C-labeled drug into the caudal vein, the jugular vein, and the heart were analyzed for total radioactivity, and the concentration profiles from the different treatments were compared. Dosing and sampling from the tail vein resulted in significantly different blood levels (and related pharmacokinetic parameters) when compared to other methods, probably attributable to a local depot effect. Intracardiac administration tended to cause higher drug levels in the heart than intravenous doses, although no significant differences were found between the respective blood concentrations. The results showed that caudal vein injection is a simple and adequate method of intravenous administration in rats designated for exsanguinated blood and tissue collection. For serial blood sampling in individual animals, the dose may be given via the jugular vein and the blood collected from the cut tail. These methods require little or no surgical preparations and are particularly suitable for prolonged sampling in studies where a relatively large number of animals are involved.

Animals↗

Congenital short bowel.

Congenital short bowel with malrotation or nonrotation but without atresia is a very rare anomaly. Two male siblings having the same condition are reported here and in addition the other four cases previously cited in the English literature are reviewed.

Colon↗

The clinical pharmacokinetics and tolerance of enoxacin in healthy volunteers.

In a single-dose tolerance and pharmacokinetics study, enoxacin doses ranging from 200 to 1600 mg were administered orally to 12 healthy normal volunteers. Plasma assays demonstrated rapid absorption of enoxacin with first-order elimination and a half-life averaging 3.4-6.4 h. Renal clearance accounted for approximately 40% of total body clearance of drug. In a second placebo-controlled study, 18 normal volunteers received enoxacin in doses of 400, 600 or 800 mg twice daily for 14 days. Plasma concentrations and pharmacokinetic parameters obtained after the first dose were not significantly different from those observed in the single-dose study. With repeated administration, steady-state plasma concentrations were achieved in three days or less. Steady-state pharmacokinetics were characterized by prompt absorption, first-order elimination, and high urinary concentrations of enoxacin. The most frequently-reported adverse experiences involved the gastro-intestinal tract, the central nervous system, and the skin.

Clinical Trials as Topic↗

Primary vertebral tumor in an adolescent girl.

A 13-year-old girl presented with a 6-month history of back pain, a palpable paravertebral mass, and a left third lumbar radiculopathy. Radiologic studies were consistent with a primary vertebral neoplasm. Posterior biopsy yielded material consistent with osteoblastoma. Anterior tumor excision and vertebral reconstruction followed. Elements consistent with aneurysural bone cyst were present in the resected tumor.

Adolescent↗