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Biomedical subjects

W K Cheung

Publications and source records attributed to W K Cheung.

32 records · Page 2Linked to original sources
PubMed1991

Pathogenic properties of Edwardsiella species.

The pathogenic characteristics of 35 Edwardsiella strains from clinical and environmental sources were investigated. Overall, most Edwardsiella tarda strains were invasive in HEp-2 cell monolayers, produced a cell-associated hemolysin and siderophores, and bound Congo red; many strains also expressed mannose-resistant hemagglutination against guinea pig erythrocytes. Edwardsiella hoshinae strains bound Congo red and were variable in their invasive and hemolytic capabilities while Edwardsiella ictaluri strains did not produce either factor; neither E. hoshinae nor E. ictaluri expressed mannose-resistant hemagglutination nor elaborated siderophores under the tested conditions. Selected strains of each species tested for mouse lethality indicated strain variability in pathogenic potential, with E. tarda strains being the most virulent; 50% lethal doses in individual strains did not correlate with plasmid content, chemotactic motility, serum resistance, or expression of selected enzyme activities. The results suggest some potential important differences in pathogenic properties that may help explain their environmental distribution and ability to cause disease in humans.

Animals↗
PubMed1989

Comparative pharmacokinetics of coumarin anticoagulants. XLIX: Nonlinear tissue distribution of S-warfarin in rats.

The serum protein binding of the oral anticoagulant drug warfarin varies widely among rats and largely accounts for corresponding variations in the total serum clearance of the drug. The hepatic uptake of warfarin is concentration dependent despite the concentration independence of the free fraction of warfarin in serum over a wide concentration range. This investigation was designed to determine the distribution of the S enantiomer of warfarin in rats as a function of warfarin concentration, free fraction in serum, dose, and time. Two groups of rats, one with relatively low (0.0043) and the other with relatively high (0.0105) average serum free fraction values, were selected from a large number of adult male Sprague-Dawley rats. All animals received an iv injection of S-warfarin, either 0.25 or 1.0 mg/kg, and were sacrificed at intervals over a period of 10 d. Concentrations of S-warfarin in serum, liver, kidneys, muscle, and fat were determined by HPLC. The tissue:serum concentration ratio (T:S) of the drug was highly concentration dependent, but was independent of dose, time, and (except for fat) free fraction in serum. The T:S for fat was higher in animals with the larger serum free fraction values. The T:S of S-warfarin for the liver was greater than 10 at low concentrations and reached a limiting value of 0.25 at relatively high concentrations of the drug. In general, the T:S versus concentration profiles of S-warfarin are consistent with the presence of two classes of binding sites in the tissues, one with very high affinity and low capacity, the other with lower affinity and apparently unlimited capacity under the experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1988

Importance of oral dosing rate on the hemodynamic and pharmacokinetic profile on nilvadipine.

Nilvadipine was administered as an oral solution formulation to 12 normotensive subjects in a three-way randomized crossover study at a dose of 16 mg as three different dosing regimens: 1) as a single 16 mg dose, 2) as a 1.6 mg dose given hourly for 10 doses, and 3) as an initial dose of 4.8 mg, followed by 1.6 mg doses given every hour for seven additional doses. After each dose, clinical effects, hemodynamic changes and the pharmacokinetic profile of the drug were determined. The mean maximum changes in diastolic (DBP) and systolic (SBP) blood pressure and heart rate (HR) after dosing regimens 1, 2, and 3 were: -33, -13 and +46%; -17, -14 and +38%; and -24, -14 and +36%, respectively. There was a relationship between the changes in DBP and HR and plasma concentrations of nilvadipine only after dosing regimen 1. The effect-concentration relationships were fit to a modified Emax model. There was no relationship between the change in SBP and plasma concentration after any of the dosing regimens. While there were no significant differences in the mean area under the plasma concentration-time curve (AUC0----infinity) between dosing regimens 2 (38.7 ng.hr/mL) and 3 (42.1 ng.hr/mL) (P greater than 0.05), the mean AUC0----infinity after regimen 1 (76.3 ng.hr/mL) was significantly greater than after dosing regimens 2 or 3 (P less than 0.05). The mean maximal plasma concentrations (Cmax) were 31.6, 1.3 and 6.3 ng/mL after dosing regimens 1, 2 and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Pharmacokinetic evaluation of a sustained-release formulation of trihexyphenidyl in healthy volunteers.

Twenty-four male subjects were randomized to receive two oral dosage forms of trihexyphenidyl HCl (alpha-cyclohexyl-alpha-phenyl-1-piperidinepropanol HCl). The dosage regimens were (1) a 5-mg immediate release (IR) tablet given twice daily at time zero and 12 h later, and (2) two 5-mg sustained-release (SR) capsule formulations given daily. The number of adverse experiences following the SR formulation were approximately 50% of those for the IR formulation, the peak concentration (Cmax) after the SR formulation was significantly lower (p less than 0.05) than that after the first dose of the IR formulation, and the time to reach Cmax (tmax) was significantly longer after the SR formulation (p less than 0.05). The SR formulation maintained serum concentrations above 50, 60, and 70% of Cmax values for average time periods of 11.7, 9.4, and 5.9 h, respectively, compared with values of 1.8, 1.2, and 0.9 h after the IR formulation; the differences were all significant (p less than 0.05). The mean elimination half-life (t1/2) was similar (p greater than 0.05) after the SR (10.1 h) and IR (8.7 h) formulations. The statistical power of the study was 98.1% to detect a 20% difference in the area under the curve from time zero to time infinity (AUC0----infinity) between formulations. Although the AUC0----infinity after the SR formulation was statistically smaller (p less than 0.05) than after the IR tablet, the difference was less than 20%. Therefore, the SR formulation was bioequivalent to the IR tablet formulation of trihexyphenidyl.

Adult↗
PubMed1988

Changes in tissue concentrations of 14C-doxorubicin caused by mitoxantrone, mithramycin A and vinblastine in the rat.

The purpose of this study was to determine if mitoxantrone (a new antineoplastic drug) and two other anticancer agents (mithramycin A and vinblastine) could result in changes in the tissue distribution and disposition of doxorubicin in rats. Each of 16 male rats received 1 mg/kg of 14C-labeled doxorubicin on day one and received either saline, or doses of 4 mg/kg of mitoxantrone, 1.7 mg/kg of mithramycin A or 2.9 mg/kg of vinblastine on day three. All rats were sacrificed on day eight. Concentrations of radioactivity in the heart, lung, kidney and muscle were higher in the mitoxantrone treated rats than in the controls. Mithramycin A decreased the concentrations of radioactivity in liver, kidney and fatty tissues, while vinblastine increased the concentrations in heart, liver, lung, muscle and skin. In summary, mithramycin A, vinblastine and mitoxantrone caused a change in tissue concentrations of radioactivity of doxorubicin and/or its metabolites following a single I.V. dose of 14C-labeled doxorubicin in rats. This may cause elevated plasma concentrations of doxorubicin. These findings in the rat could theoretically have implications regarding doxorubicin therapy in man.

Animals↗
PubMed1988

Pharmacokinetics of nilvadipine after single oral doses in healthy volunteers.

Forty healthy male Caucasian volunteers were randomly assigned to five treatment groups to receive a placebo or a 4, 8, 12, 16 or 20 mg dose of nilvadipine. The drug was well tolerated by the subjects at all dose levels. Pharmacokinetic parameters for nilvadipine were determined using model-independent methods. There were no significant differences (p greater than 0.05) in the time to the maximum plasma concentration (Cmax) (tmax), the elimination half-life or the mean residence time among the five treatment groups. Up to doses of about 12 mg, there was a linear relationship between dose and Cmax or area under the plasma concentration-time curve (AUCO----infinity). At doses of 16 and 20 mg, the relationship between dose and Cmax or AUCO----infinity was no longer linear, suggesting that the pharmacokinetics of the drug after single oral doses greater than about 12 mg may be dose-dependent, probably due to concentration-dependent first-pass hepatic elimination of the drug.

Administration, Oral↗
PubMed1983

Activation of low density lipoprotein receptor synthesis by treatment with partially delipidated low density lipoprotein.

The role of apo-low density lipoprotein in the regulation of low density lipoprotein receptor synthesis was studied. Fibroblasts preincubated in the presence of a cholesterol-free low density lipoprotein preparation showed an increase of 50% in receptor activity. In contrast, when cells were preincubated with a similar amount of normal low density lipoproteins a 2- to 3-fold decrease of receptor activity was observed. The increase of receptor activity induced by delipidated LDL was probably due to an increase of synthesis rather than an unmasking effect since treatment with puromycin essentially abrogated the activation. The ability of the partially delipidated low density lipoproteins to elicit receptor synthesis could not be accounted for by a depletion of cellular cholesterol because a similar preparation of delipidated high density lipoproteins was unable to induce receptor synthesis but was able to reduce cellular cholesterol to the same extent. Treatment with chloroquine, a lyzosome inhibitor, blocked the ability of the delipidated low density lipoprotein to activate receptor synthesis. This suggests that degraded fragments rather than the intact delipidated lipoprotein are necessary to trigger the cell to synthesize more receptors.

Cells, Cultured↗
PubMedDate not supplied

Abortifacient activity in leaves, roots and seeds of Phytolacca acinosa.

Fresh leaves, roots and seeds of Phytolacca acinosa were individually extracted with 0.9% saline and cold acetone was added to the supernatants. The resultant precipitates were dialyzed against distilled water and lyophilized to form acetone powders (AP). The relative potencies of abortifacient activity of the APs were: seed greater than root greater than leaf. The abortifacient activity in these APs was susceptible to destruction by heat and pepsin.

Abortifacient Agents↗
PubMedDate not supplied

Diagnostic imaging of Salmonella-related mycotic aneurysm of aorta by CT.

The purpose of this study was to review the computed tomography (CT) appearance of mycotic aneurysm of the aorta caused by Salmonella infection. Eight patients were suggested to have mycotic aneurysm of the aorta by clinical presentation of fever, abdominal or back pain, leukocytosis, and pulsatile abdominal mass in addition to positive blood or tissue culture of salmonella. All underwent plain radiography, abdominal sonography, and CT for confirmation. Five patients died during hospitalization despite medical or surgical treatment. CT features of mycotic aneurysm of aorta included (a) hazy aortic wall with rupture; (b) gas-forming inflammation around the aneurysm; (c) retroperitoneal paraaortic fluid collection and vertebral erosion; and (d) thrombus formation within a false lumen after aneurysmal rupture. Because of its availability and noninvasiveness, CT is the major diagnostic modality to use for Salmonella-related mycotic aneurysm.

Aged↗