Biomedical subjects

C T Chang

Publications and source records attributed to C T Chang.

At least 55 records · Page 3Linked to original sources

PubMed1997

A randomized trial of concurrent chemoradiotherapy versus radiotherapy in advanced carcinoma of the uterine cervix.

The purpose of our study was to determine whether the chemoradiation is better than radiotherapy alone with respect to survival and treatment toxicity in patients with advanced carcinoma of the cervix. From October 1990 to April 1995, a total of 122 patients with advanced cervical carcinoma were included in this study and randomly assigned to either radiotherapy or concurrent chemotherapy and radiotherapy. The patients in the concurrent group received cisplatin, vincristine, and bleomycin every 3 weeks for a total of four courses, in combination with radiotherapy concurrently. Sixty patients were randomized to the concurrent chemoradiotherapy, and 62 were randomized to the radiotherapy alone. A tumor response was observed in 88.3% of the patients in concurrent group and in 74.2% of the patients in radiotherapy group (P = 0.04). After a median follow-up of 46.8 months, the overall disease-free survival and actuarial survival rate at 3 years were 51.7 and 61.7% in the concurrent group, and 53.2 and 64.5% in the radiotherapy group, respectively. Treatment-related toxicity appears to be higher with the combination of radiotherapy and chemotherapy compared with radiotherapy alone (36.7% versus 17.7%, P = 0.02). However, analysis by Kaplan-Meier method showed that the actuarial survival was not statistically different between the chemoradiotherapy and radiotherapy groups (mean survival time: 38.1 months versus 41.5 months, P = 0.27). In conclusion, this study showed that concurrent multiagent chemoradiotherapy did not prove to be a superior definitive therapy over radiotherapy alone for patients with advanced cervical carcinoma.

Adult↗

PubMed1997

New aporphine alkaloids and cytotoxic constituents of Hernandia nymphaeifolia.

Two new aporphine alkaloids, (+)-N-hydroxyhernangerine (1) and N-formyldehydroovigerine (2) as minor bases, along with four known aporphines, (+)-magnoflorine, (+)-hernovine, (+)-N-methylhernovine, and (+)-laurotetanine, two known isoquinolones, thalifoline and northalifoline, and one benzylisoquinoline, (+)-reticuline, have been additionally isolated from the trunk bark of Hernandia nymphaeifolia. The structures of these compounds were elucidated by spectroscopic evidence. Six of the isolated compounds show significant cytotoxic activities (ED50 values < 1 microgram/ml) against P-388, KB16, A549, or HT-29 cell lines.

Alkaloids↗

PubMed1997

Description of blood pressure changes in patients beginning cyclosporin A therapy.

Cyclosporin A (CyA) is the primary immunosuppressive agent for the prophylaxis of rejection episodes in renal, cardiac, liver, and other transplants. Recently, its use in autoimmune diseases has been investigated as well. Although several studies have produced promising results, nephrotoxicity and hypertension can result from CyA treatment, and their development must be understood in order to facilitate patient management. This article describes the diastolic blood pressure (DBP) responses in two populations of patients during three months of CyA therapy. Study A involved psoriasis patients and Study B involved postoperative renal transplant patients. The relationship between blood pressure and systemic CyA exposure and other covariates was evaluated using linear mixed effects modeling. Temporal patterns of blood pressure changes with varying duration of CyA exposure were investigated. In Study A, the psoriasis patients showed transient exposure-related increases in DBP on CyA. These elevations, while statistically significant, were clinically insignificant. In Study B, the renal transplant patients showed no CyA-related rises in DBP. In neither study was there evidence for a difference in effect on DBP between Sandimmune and Neoral, the two formulations of CyA presently approved for marketing by the Food and Drug Administration, after differences in CyA exposure were taken into account.

Adult↗

PubMed1997

Equivalence of cyclosporine blood level assays in patients receiving cyclosporine microemulsion or cyclosporine. The Sandoz Neoral Study Group N103.

The more rapid absorption of the cyclosporin A (CyA) microemulsion formulation (Neoral, NEO) compared to Sandimmune (SIM) might bypass intestinal metabolism resulting in differing amounts of CyA metabolites in blood as compared to SIM. If true, then CyA levels obtained with a CyA monoclonal antibody assay (TDx) that has metabolite cross-reactivity might differ depending on the CyA formulation received by the patient, thereby affecting safety and efficacy. Fifty-one NEO vs. 50 SIM treated de novo renal transplant recipients from a multicenter double-blind randomized trial had morning, whole-blood, trough-samples obtained at the ends of weeks 1, 4, 8, and 12 post-transplant assayed for CyA by HPLC and TDx. The slopes (ratio of TDx value to HPLC value) for the regression lines between TDx and HPLC levels as a function of time post-transplant and CyA formulation were determined using a general linear model. For NEO, the slopes at each week (1.21-1.41 x HPLC) did not differ significantly (p = 0.82). For SIM, the week 1 slope (1.2) was significantly (p = 0.006) less than the other weeks (1.4-1.44). The slopes (NEO vs. SIM) were not different at either week 1 (1.21 vs. 1.22, p = 0.82) or at pooled weeks 4, 8, and 12 (1.33 vs. 1.4, p = 0.1). These results indicate that despite the improved absorption, TDx values obtained on NEO are qualitatively similar to those obtained on SIM.

Absorption↗

PubMed1996

The pharmacokinetics of a microemulsion formulation of cyclosporine in primary renal allograft recipients. The Neoral Study Group.

This study was a randomized, double-blind, 12-week comparison of the pharmacokinetics, safety, and tolerability of two cyclosporine (CsA) formulations, cyclosporine emulsion capsules and oral solution for microemulsion and cyclosporine, in the postoperative management of renal transplant patients. Of the 101 patients, aged 18 to 65, who entered the study, 89 were evaluable for pharmacokinetics. Initial dosage was 10 mg/kg per day, administered twice daily in two equal doses. Dosages were adjusted to achieve target CsA concentrations. The pharmacokinetic (PK) parameters (dose-normalized) of greatest interest were maximum blood concentration (C(max)/dose), time to reach maximum concentration (t(max), area under the blood concentration-vs.-time curve (AUC/dose), and trough blood concentrations (Co h/dose). The relative CsA bioavailabilty was found to be significantly enhanced with cyclosporine emulsion compared with cyclosporine with a 16% to 31% increase in AUC and a 32% to 42% increase in C(max). Intrapatient variability of PK parameters was significantly lower with cyclosporine emulsion than with cyclosporine for AUC, C(oh), t(max), and C(max) in many instances. This indicates a more consistent, rapid, and more complete total absorption of CsA. Despite higher CsA C(max) levels and AUCs with cyclosporine emulsion, safety and tolerability (detailed in a parallel report) were comparable to those of cyclosporine. The PK advantages of cyclosporine emulsion over cyclosporine are either independent of food conditions or possibly reflective of more consistent absorption of CsA with cyclosporine emulsion. The findings suggest that de novo use of cyclosporine emulsion may simplify and improve management of organ transplant recipients and that the PK advantages of cyclosporine emulsion may translate into clinical benefits.

Adolescent↗

PubMed1996

The pharmacokinetics and bioavailability of clemastine and phenylpropanolamine in single-component and combination formulations.

Studies were conducted in healthy male volunteers (n = 171; age range, 19-49 years; 22-27 subjects per study) to examine the following: pharmacokinetics and dose proportionality of the antihistamine clemastine; the effect of coadministration of phenylpropanolamine and clemastine on the pharmacokinetics of the two drugs; and the bioavailability of clemastine tablets and combination tablets of clemastine and sustained-release phenyl-propanolamine under fasted and fed conditions after single-dose administration and at steady state. All studies used crossover designs, with randomized drug treatments separated by a 7-day washout period for the single-dose studies, and with administration every 6 or 12 hours for 7 days per treatment for the steady-state studies. After single oral doses of clemastine solution (1,2, and 4 mg), the area under the concentration-time curve (AUC) and maximum concentration (Cmax) were dose proportional. Clemastine showed a first-pass reduction in the extent of absorption, with oral bioavailability calculated as 39.2 +/- 12.4%. Extravascular distribution of drug was suggested by the high volume of distribution (799 +/- 315 L) and low Cmax (0.577 +/- 0.252 ng/mL/mg) observed at 4.77 +/- 2.26 hours after administration, and by the biphasic decline in plasma concentration. The terminal elimination half-life (t1/2) of clemastine was 21.3 +/- 11.6 hours. Steady-state concentrations of clemastine were consistent with linear pharmacokinetic processes, and clearance was unaffected by age in the range studied, or by race. Clemastine solution and tablets were bioequivalent, and food had no significant effect on rate and extent of absorption of clemastine. The 1- and 2-mg clemastine tablets showed proportional bioavailability. Coadministration of clemastine with phenylpropanolamine did not significantly influence the pharmacokinetics of clemastine or the AUC and elimination t1/2 of phenylpropanolamine, but reduced the rate of absorption of phenylpropanolamine. Combination tablets containing 1 mg or 2 mg of immediate-release clemastine plus 75 mg of sustained-release phenylpropanolamine for twice daily administration were bioequivalent to the separate components and showed no significant interaction with food.

Adult↗

PubMed1996

Coumarins and antiplatelet aggregation constituents from Formosan Peucedanum japonicum.

Four new khellactone esters, (-)-trans-3'-acetyl-4'-senecioylkhellactone, (+-)-cis-3'-acetyl-4'-tigloylkhellactone, (+-)-cis-4-tigloylkhellactone, (+)-trans-4'-tigloylkhellactone, together with 14 known coumarins, isoimperatorin, psoralen, bergapten, xanthotoxol, cnidilin, (-)-selinidin, (-)-deltoin, (+)-pteryxin, (+)-peucedanocoumarin III, xanthotoxin, imperatorin, (+)-marmesin, (+)-oxypeucedanin hydrate, (+)-peucedanol and three chromones, eugenin, (-)-hamaudol, (+)-visamminol, have been isolated from the root of Formosan Peucedanum japonicum. The structures of the new compounds were elucidated by spectral data. The identities of (+)-trans-3'-tigloyl-4'-acetylkhellactone, formerly reported as a new compound, and (+)-cis-3'-angeloyl-4'-acetyl-khellactone, with the known (+)-peucedanocoumarin III and (+)-pteryxin, respectively, are discussed. Among the isolates, seven compounds, eugenin, (-)-selinidin, (+)-pteryxin, imperatorin, bergapten, cnidilin and (+)-visamminol, show strong antiplatelet aggregation activity in vitro.

Coumarins↗

PubMed1996

Safe coadministration of terbinafine and terfenadine: a placebo-controlled crossover study of pharmacokinetic and pharmacodynamic interactions in healthy volunteers.

The pharmacokinetic and pharmacodynamic interactions of terbinafine (Lamisil) and terfenadine (Seldane) were assessed in 26 healthy volunteers randomized to receive either terbinafine (250 mg tablet) or its placebo (terbinafine placebo), which were administered in a double-blind manner once daily for 18 days. On days 12 through 18, terfenadine was coadministered (60 mg twice daily, unblinded). Pharmacokinetic profiles were obtained for terbinafine and its desmethyl metabolite on day 11 (in the absence of terfenadine), day 12, and day 18. Terfenadine and terfenadine acid metabolite levels were also assayed on days 12 and 18. After a 4-week washout period, subjects were crossed over to the alternate treatment (terbinafine or terbinafine placebo). Pharmacodynamic measures were electrocardiographic (ECG) rhythm abnormalities, corrected QT interval (QTc), and plasma ALT levels. Terfenadine levels were evaluated; however, only eight of 1502 samples assayed were above the limit of quantitation. No effect of terbinafine administration on pharmacokinetic parameters for the terfenadine acid metabolite was observed, except for a decrease of approximately 20% in through terbinafine concentrations (C0hr; p < 0.05) on the last day of terfenadine plus terbinafine coadministration. Pharmacokinetic parameters for terbinafine were unchanged on the first day of terfenadine coadministration, and only small increases in area under the plasma concentration versus time curve from 0 to 24 hours and peak plasma concentrations (16.1%[p < 0.01] and 6.63% [p < 0.05]) were observed on the last day of terfenadine and terbinafine coadministration. Values for C0hr were also about 20% to 25% higher (p < 0.05). Steady-state levels of the terfenadine acid metabolite were achieved after 2 days of terfenadine coadministration, and steady-state levels of terbinafine and its desmethyl metabolite were achieved after 14 days of terbinafine administration. The incidence of ECG rhythm abnormalities was not significantly higher in any treatment group; however, the incidence of prolongation of QTc > 10% above baseline was significantly higher in the groups treated with terfenadine. No QTc prolongation occurred in the absence of terfenadine treatment. Both terbinafine and terfenadine were well tolerated when coadministered during this study, as indicated by the low incidence of complaints, abnormalities, and adverse events. The results of this study indicate that terbinafine and terfenadine can be safely coadministered.

Adult↗

PubMed1996

Purification and properties of chitinase from cabbage stems with roots.

Chitinase has been purified from the extract of cabbage stems with roots through successive steps of ammonium sulfate fractionation, Sephadex G-75 gel filtration, chromatofocusing and Sephacryl S-200 HR gel filtration. By these steps, the purity of the enzyme increased by 63 fold and the recovery of the enzyme activity was 18%. The purified enzyme was homogeneous when analyzed by SDS-PAGE. It showed an optimal pH of 6 and optimal temperature of 60 degrees C for hydrolysis of ethylene glycol chitin (EGC). The molecular mass of the enzyme was 41 kDa, as determined by SDS-PAGE. Heavy metal ions (1.5 mM) Ag+, Hg2+ and Fe2+, and chemical modification agents NAI (1 mM), NBS (0.5 mM) and CHD (0.5 mM) significantly or completely inhibited the activity of the enzyme. Substrate EGC at high concentrations also inhibited the activity. BSA (0.05%), Triton X-100 (0.5%) and glycerol (50%) provided significant protection of the enzyme from freezing inactivation.

Ammonium Sulfate↗

PubMed1996

Reproducibility of the first-phase insulin release in the intravenous glucose tolerance test.

Insulin-dependent diabetes mellitus (IDDM) is a slowly progressive autoimmune disease. In the prediabetic phase of IDDM, the intravenous glucose tolerance test (IVGTT) demonstrates a progressive decline in the first-phase insulin response. The first-phase insulin response to intravenous glucose may enable individuals at risk of IDDM to be identified and preventive therapy to be instituted. However, the reproducibility of the first-phase insulin response is controversial. The aim of this study was to determine the variability of the first-phase insulin response to intravenous glucose. Ten healthy normal volunteers underwent two IVGTT within a 1 week interval, using the Islet Cell Antibody Register User's Study (ICARUS)-recommended standard protocol. The first-phase insulin response to intravenous glucose was expressed as the sum of the 1- and 3-minute insulin concentrations (muU/mL) and the total 0 to 10 minute insulin area under the curve (muU.min.mL-1). Variability was represented by the coefficient of variation (CV). The within-subject median CV was 21.2% for the sum of the 1- and 3-minute insulin concentrations and 23.9% for the total 0 to 10 minute insulin area under the curve. In conclusion, the reproducibility of the first-phase insulin response to intravenous glucose is poor. Hence, caution should be exercised when the IVGTT is applied to prediabetic IDDM patients for longitudinal study.

Adult↗

PubMed1995

Non-peptide fibrinogen receptor antagonists. 7. Design and synthesis of a potent, orally active fibrinogen receptor antagonist.

The design, synthesis, and pharmacological evaluation of L-734,217, a potent, low-molecular weight, orally active fibrinogen receptor antagonist, is reported. A strategy for producing low-molecular weight inhibitors from the peptide c-[(Ac)CRGDC] A, previously reported from these laboratories, is outlined. This strategy combines a retrodesign analysis of the conformationally defined cyclic peptide A with stereochemical information present in the arginine-glycine-aspartic acid (RGD) tripeptide sequence, culminating with the discovery of L-734,217. L-734,217 inhibited the aggregation of human, dog, and chimpanzee platelets at concentrations below 100 nM and was found to be > 15000-fold less effective at inhibiting the attachment of human umbilical vein endothelial cells to fibrinogen, fibronectin, and vitronectin than it was at inhibiting the aggregation of platelets. L-734,217 showed significant ex vivo antiplatelet activity following oral administration in dogs and chimpanzees at doses of 1.0 and 2.0 mg/kg, respectively, and has been selected as a clinical candidate for development as an antithrombotic agent.

Administration, Oral↗

PubMed1995

Efficacy and pharmacokinetics of two formulations of cyclosporine A in patients with psoriasis.

The efficacy and pharmacokinetic profiles of two oral formulations of cyclosporine A (Sandimmune and Neoral; Sandoz Pharmaceuticals, East Hanover, NJ) were evaluated in 37 patients with moderate to severe plaque psoriasis in a randomized, double-blind, modified, crossover study. Cyclosporine A (150 mg twice daily), administered in either formulation, reduced the severity of plaque lesions: 94% of all patients reported at least moderate improvement and 70% reported complete clearing. Approximately 2 weeks of therapy were required for drug exposure to stabilize on either formulation. Cyclosporine A exposure from Neoral was significantly greater relative to that from Sandimmune across all study weeks. At the eighth week (before crossover), AUC and Cmax values for Neoral and Sandimmune were 5618 +/- 1705 versus 3202 +/- 596 ng.h/mL and 1283 +/- 337 versus 623 +/- 173 ng/mL, respectively. In crossover analysis at steady state, the relative oral bioavailability of cyclosporine from the Neoral formulation was 54% greater than that from Sandimmune. Some pharmacokinetic parameters showed less variability both between and within groups of patients taking Neoral versus Sandimmune. Both formulations were well tolerated, in that most adverse events were of mild severity.

Chemistry, Pharmaceutical↗

PubMed1995

Purification and properties of alpha-amylase from Aspergillus oryzae ATCC 76080.

An alpha-amylase was purified from the solid cultural extract of Aspergillus oryzae ATCC 76080 by sequential steps of amylopectin affinity adsorption, DEAE-Sepharose ion-exchange chromatography and Sephacryl S-200 HR gel filtration. By these steps, the purity of the enzyme increased by 16 fold and recovery of the enzyme activity was 45%. The purified enzyme had an optimal pH between 4 to 5, optimal temperature at 50 degrees C and a Km value of 0.22% for hydrolysis of starch. About 80% of the enzyme activity was lost after incubation at 50 degrees C for 30 min. The heat denaturation constant at 50 degrees C was 0.024 min-1. The molecular weight was 52 kDa as determined by gel filtration. Mercuric ion (0.3 mM), DNFB# (6 mM), NBSI (6 mM) and NAI (6 mM) inhibited the activity of the enzyme. The main products for hydrolysis of maltoheptaose by the enzyme were maltotriose and maltotetraose.

Amino Acid Sequence↗

PubMed1994

Non-peptide fibrinogen receptor antagonists. 2. Optimization of a tyrosine template as a mimic for Arg-Gly-Asp.

Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation. Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation. Compound 23m (L-700,462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of > 24,000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors. Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with i.v. infusions of 0.1-10 micrograms/kg/min of 23m in anesthetized dogs, with 10 micrograms/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol. Platelet aggregatability returned rapidly after the termination of the 23m infusions. These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.

Adenosine Diphosphate↗

PubMed1994

Purification and properties of beta-fructofuranosidase from Aspergillus oryzae ATCC 76080.

A fructooligosaccharide-producing beta-fructofuranosidase was purified from the crude extract of Aspergillus oryzae ATCC 76080 through successive steps of ultrafiltration, DEAE-Sepharose CL-6B ion-exchange chromatography, preparative isoelectric focusing electrophoresis and Sephacryl S-200 gel filtration. The purified enzyme had an optimal pH of 5-6, an optimal temperature of 50 degrees C, a Km value of 0.53 M for catalyzing selftransfer reaction from sucrose. The molecular weight was 87 kDa by gel filtration. Mercuric ion (0.25 mM), p-hydroxymercuribenzoate (0.25 mM) and N-bromosuccinimide (0.5 mM), significantly inhibited the enzyme activity. The enzyme showed both transfructosylation and hydrolytic action in 0.5 to 50% sucrose. The transfructosylation ratio increased as the sucrose concentration increased and it was 88.5% at 50% sucrose. The main fructooligosaccharides produced from sucrose were 1-kestose and nystose.

Aspergillus oryzae↗

PubMed1993

The use of agarose gels for quantitative determination of fluid saturations in porous media.

The use of agarose gel reference standards for quantifying petrophysical properties in porous media is described. The specific interest is to determine the values of fluid saturations and porosity in oil bearing rocks; the MRI methodology for estimating these properties is discussed. It is shown that the relaxation times of the gel reference standard and the relaxation times of the fluid contained in the porous media affect the estimation process. The determination of porosity and fluid saturations can be greatly simplified if the relaxation times of the reference standard and the relaxation times of the fluid are closely matched. Gel concentration of paramagnetic impurities in the form of copper ions is used to control the longitudinal relaxation properties. The relaxation properties of agarose gels, as a function of agarose and paramagnetic impurity concentrations, have been measured at 2.0 T. The data are well fitted by a simple polynomial in agarose concentration and paramagnetic impurity concentration. Finally, a one-dimensional imaging example of use of agarose gels as reference phantoms is discussed.

Engineering↗

PubMed1993

Purification and characterization of 5'-phosphodiesterase from barley rootlets.

A phosphodiesterase was purified from barley rootlets by polyethylene glycol fractionation, calcium phosphate gel-cellulose adsorption, Sepharose CL-4B gel filtration, DEAE-Sepharose CL-6B ion exchange and preparative polyacrylamide gel electrophoresis (PAGE). The enzyme was purified by 103.6 folds and 11% of the enzyme activity was recovered. The purified enzyme was apparently homogeneous when examined on PAGE. It had a molecular weight of 100 kD, an optimum pH of 9.5, and a Km of 0.28 mM on the hydrolysis of p-nitrophenyl thymidine 5'-phosphate. SDS-PAGE revealed that the enzyme molecule might be composed of two or three subunits. Reducing agents, CuSO4, EDTA and 5'-nucleotides were inhibitory to the enzyme activity. This enzyme was able to hydrolyze RNA and denatured DNA efficiently, whereas native DNA was not a good substrate.

Chromatography, Gel↗

PubMed1993

[Dissolution rate of berberine in ermiao pills].

The dissolution rate of Ermiao Pills was determined by the Cup Method in artificial gastric juice and artificial intestinal juice. Parameter T50, T alpha and n were obtained. The F value shows no significant difference in between the two groups (P > 0.05), indicating that the above two releasing media do not markedly influence the dissolution rate of Ermiao Pills.

Berberine↗