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Biomedical subjects

S J Chung

Publications and source records attributed to S J Chung.

At least 55 records · Page 3Linked to original sources
PubMed1999

Canalicular membrane transport is primarily responsible for the difference in hepatobiliary excretion of triethylmethylammonium and tributylmethylammonium in rats.

Two structurally similar quaternary ammonium compounds, triethylmethylammonium (TEMA, M(r) 116) and tributylmethylammonium (TBuMA, M(r) 200) were used as model compounds to identify the unit process of hepatobiliary excretion that is responsible for markedly different biliary excretion of organic cations (OCs). Cumulative biliary excretion (in percentage of dose; i.v., 12 micromol/kg) was 0.17 for TEMA and 34.5 for TBuMA. In vivo uptake clearance into the liver was 0.686 +/- 0.020 ml/min for TEMA and 0.421 +/- 0.028 ml/min for TBuMA. When the uptake clearance was examined in an isolated hepatocyte system, comparable clearance between TEMA and TBuMA was obtained, consistent with the in vivo result. These observations suggest that uptake into the liver is not the major determinant for the difference in biliary excretion of the OCs. Coadministration of colchicine, an inhibitor of microtubule formation, had no effect on biliary excretion of the model compounds, and the primary site of subcellular distribution of the OCs appears to be the cytosol, suggesting that intracellular movement does not play a major role in the markedly different biliary excretion of the OCs. In contrast, in vivo excretion clearance across the canalicular membrane for TBuMA was 180-fold greater than that for TEMA, and in vitro efflux clearance of TBuMA was smaller than that of TEMA (p <.01), indicative of involvement of these processes in the markedly different biliary excretion of the OCs. Therefore, these data indicate that canalicular transport is primarily responsible for the markedly different biliary excretion of TEMA and TBuMA.

Algorithms↗
PubMed1998

Acceptor substrate-based selective inhibition of galactosyltransferases.

This paper describes the discovery of glycosyl acceptor analogs as potent and selective inhibitors of alpha-1,3- and beta-1,4-galactosyltransferases. Incorporation of an appropriate aromatic group to the aglycon position of the enzyme's acceptors results in a strong inhibition, representing the first and most potent small uncharged molecules as selective inhibitors of these two enzymes and thus providing a new strategy for the development of selective glycosyltransferase inhibitors.

Binding Sites↗
PubMed1998

Irreversible inhibition of zinc-containing protease by oxazolidinone derivatives. Novel inactivation chemistry.

alpha-Benzyl-2-oxo-1,3-oxazolidine-4-acetic acid (BOOA) having (alpha R,4S) and (alpha S,4R) configurations were designed and synthesized as a novel type of mechanism-based inactivators for carboxypeptidase A (CPA), and kinetic analysis demonstrated that they indeed inhibit the enzyme in a time-dependent manner with the second order inhibitory rate constants (kinact/KI) of 1.52 and 1.39 M-1 s-1 for (alpha S,R4)-BOOA and (alpha R,4S)-BOOA, respectively.

Carboxypeptidases↗
PubMed1998

Accelerated oral absorption of gliclazide in human subjects from a soft gelatin capsule containing a PEG 400 suspension of gliclazide.

Whether a rapid elevation of serum gliclazide concentration in human subjects can be achieved through an acceleration of dissolution of gliclazide from a formulation was examined. A soft gelatin capsule containing PEG 400, PEG 4000, Tween 20 and glycerin was prepared as a formulation that may accelerate dissolution of gliclazide. The in vitro dissolution of gliclazide at pH 7.2 was identical for the soft capsule and conventional tablets, Diamicron and Diberin. However, at pH 1, 2 and 4.0 the dissolution from the soft capsule was more rapid compared to the tablets. When bioavailability parameters were compared following oral administration of the soft capsule and Diamicron to 16 healthy Korean male subjects, the parameters representing the amount of adsorption (i.e. the area under the serum gliclazide concentration vs. time curve up to 24 h, AUC24, and the peak serum concentration Cmax) were not statistically different for both formulations. However, the time required to reach the peak (Tmax) was significantly shorter for the soft capsule than for the Diamicron. Our results, therefore, indicate that a rapid elevation of serum gliclazide concentration following oral administration of a formulation can be achieved by accelerating the in vitro dissolution of gliclazide from the formulation into the acidic buffers. Thus, the rate of gastrointestinal absorption of gliclazide appears to be dependent on its in vivo dissolution rate in gastric fluid. A soft capsule containing a PEG 400 suspension of gliclazide appears to be an appropriate formulation for accelerating the dissolution.

Administration, Oral↗
PubMed1998

A novel type of structurally simple nonpeptide inhibitors for alpha-chymotrypsin. Induced-fit binding of methyl 2-allyl-3-benzenepropanoate to the S2 subsite pocket.

Unexpectedly, methyl and benzyl esters of 2-allyl-3-benzenepropanoic acid were found to be not substrates but potent competitive inhibitors for alpha-chymotrypsin. The inhibitory property of the structurally simple nonpeptidic compounds is ascribed to their high binding affinity to the enzyme at the S2 rather than S1 subsite pocket. These inhibitors exist in a flexible form in solution, but as they bind to the enzyme bulky contrained conformers present in a minute concentration play an important role, forming tighter enzyme.inhibitor complexes by binding to the large hydrophobic S2 pocket. The contrained conformers are thought to be resulted from intramolecular CH/pi interactions between a vinylic proton and the aromatic pi-electron cloud in the inhibitor molecules. These compounds constitute novel examples of the induced-fit binding inhibitor of possibly simplest structure.

Allyl Compounds↗
PubMed1998

Chemokines, osteopontin, ICAM-1 gene expression in cultured rat mesangial cells.

To investigate whether MCP-1, CINC, RANTES, osteopontin and ICAM-1 mRNA could be induced in cultured rat mesangial cells by interleukin-1beta(IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS), and whether MCP-1 and CINC gene expression could be modulated by dexamethasone, Northern blot assays were performed. IL-1beta induced MCP-1, CINC, RANTES and ICAM-1 gene expression in a time dependent manner. IL-1beta-induced MCP-1, CINC and ICAM-1 mRNA amount were maximal at 3 hours exposure around 14.5, 15.7, 2.2 folds increase and IL-1beta-induced RANTES mRNA at 24 hours around 2.0 folds. TNF-alpha and LPS also induced MCP-1 and ICAM-1 gene expression. TNF-alpha also induced RANTES gene expression but LPS did not. On the other hand, IL-1beta, TNF-alpha and LPS had little effect on osteopontin gene expression but fetal calf serum could increase osteopontin mRNA. Dexamethasone suppressed the IL-1beta-induced MCP-1 and CINC mRNA. These results suggest that, through these gene expressions, mesangial cells are able to communicate directly or indirectly with macrophages or neutrophils, which may lead to glomerulosclerosis.

Animals↗
PubMed1998

Bioequivalence of Neoplanta capsule to Sandimmune Neoral, microemulsion formulations of cyclosporin A in human subjects.

A bioequivalence study of the Neoplanta capsule to the Sandimmune Neoral capsule, microemulsion formulations of cyclosporin A (CyA), was conducted. Twenty-four healthy Korean male subjects received each formulation at the CyA dose of 175 mg in a 2 x 2 crossover study. There was a 2-week washout period between the doses. Blood concentrations of CyA were monitored by a radioimmunoassay for over a period of 48 h after the administration. AUCinf (area under the blood concentration/time curve from time zero to infinity) was calculated by the linear-log trapezoidal method. Cmax (maximum blood drug concentration) and Tmax (time to reach Cmax) were compiled from the blood concentration-time data. Analysis of variance was carried out using logarithmically transformed AUCinf and Cmax and untransformed Tmax. There were no significant differences between the formulations in these parameters. The point estimates and 90% confidence intervals for AUCinf (parametric), Cmax (parametric) and Tmax (nonparametric) were, in point estimate (90% confidence interval), 0.978 (0.937 approximately 1.02), 0.954 (0.900 approximately 1.01) and 0.000 (-0.125 approximately 0.000), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the U.S. Food and Drug Administration guidelines. Moreover, the modified Pitman-Morgan's adjusted F test and equal variance test (1-sided) indicated that the 2 formulations were comparable in intra- and interindividual variability in CyA bioavailability. Therefore, these results indicate that the 2 formulations of CyA are bioequivalent and, thus, may be prescribed interchangeably.

Adult↗
PubMed1997

Comprehensive life table of computer-assisted predictive mathematical relationship between age and life expectancy, survival probability or death rate in US adults.

A microcomputer program in BASIC for predicting life expectancy by age in US adults was designed. Formulas used in this study were derived from the data reported by the National Center for Health Statistics. A comprehensive life table that shows the relationship between age and death rate, survival probability or life expectancy for each year between 25 and 85 years of age was obtained in this study, using a newly designed computer program for predicting life expectancy by age and the program for survival probability previously published by the author. The comprehensive life table may be useful for clinical evaluation of patients and further helpful for biomedical investigation and epidemiological evaluation of US adults.

Adult↗
PubMed1997

Pharmacokinetics of 1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1- piperazinyl)-1,4-dihydro-4-oxoquinolone-3-carboxylic acid hydrochloride (DW-116), a new quinolone antibiotic in rats.

The objectives of this study were to characterize the pharmacokinetics of 1-5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1- piperazinyl)-1,4-dihydro-4-oxoquinolone-3-carboxylic acid hydrochloride (DW-116), a newly developed quinolone antibiotic, and to compare these kinetics with those of ciprofloxacin and rufloxacin, representative quinolone antibiotics, in rats. Rats were subjected to surgery involving catheterization of the femoral vein and artery. DW-116 (4, 20, or 200 mg/kg), ciprofloxacin (20 mg/kg), or rufloxacin (20 mg/kg) was administered either intravenously (iv) or orally. Blood samples were collected at various times and subjected to an HPLC assay for the quinolones. Temporal profiles of plasma concentration after iv administrations of DW-116 at doses of 4, 20, and 200 mg/kg exhibited an apparent multiexponential decline. In the three doses examined, systemic clearance and steady-state volume of distribution of DW-116, calculated by model-independent methods, were in the range 0.17 approximately 0.23 L/h/kg and 2.90 approximately 4.44 L/kg, respectively. When DW-116 was given orally at doses of 4, 20, or 200 mg/kg, the AUC values were nearly identical to those following iv administration, indicating an almost complete absorption (i.e., the percent bioavailability was 90.0 for 4 mg/kg, 99.0 for 20 mg/kg, and 98.3 for 200 mg/kg) in the dose range examined. The absorption of DW-116 appears to be extremely rapid because the mean residence time calculated from the oral administration data was not significantly different from that for the iv administration. At a dose of 20 mg/kg, the mean residence time for iv administered ciprofloxacin and rufloxacin was smaller than that of DW-116, indicating that DW-116 remains in the body longer than the other quinolones. Absolute percent bioavailabilities of ciprofloxacin (69.9%) and rufloxacin (84.9%) were smaller than that obtained for DW-116 (99.0%). Because it has been reported that the in vivo antibacterial activity of DW-116 is comparable or superior to that of rufloxacin and ciprofloxacin, despite the fact that the in vitro activity is significantly lower, the pharmacokinetics of this antibiotic may be responsible, at least in part, for the enhanced in vivo antibacterial activity of DW-116.

Animals↗
PubMed1997

Taurine transport in cultured choroid plexus.

PURPOSE: Taurine, a beta-amino acid, is a neuromodulator which interacts functionally with the glycinergic, GABAergic, cholinergic and adrenergic systems. Although a continuous cell culture model is not available for the choroid plexus epithelia, we recently described a primary cell culture of rabbit choroid plexus epithelia. The goal of the current study was to determine the suitability of this primary cell culture for the study of the Na(+)-taurine transporter in the rabbit choroid plexus. METHODS: A primary cell culture of rabbit choroid plexus epithelial cells was grown on semi-permeable filters and kinetics of 3H-taurine uptake were ascertained. RESULTS: Taurine transport in the cultured choroid plexus cell was Na(+)-dependent and saturable (Km = 156 microM). The beta-amino acids, beta-alanine and taurine, significantly inhibited Na(+)-driven taurine transport whereas L-alanine partially inhibited taurine transport in the cultured cells. In addition, we observed that the activity of the Na(+)-taurine transporter is affected by exposure to taurine in the media. CONCLUSIONS: These results-demonstrate that a Na(+)-taurine transporter with characteristics similar to those in the intact tissue is expressed in cultured choroid plexus epithelial cells. The transporter may undergo adaptive regulation and play a role in taurine homeostasis in the central nervous system.

Animals↗
PubMed1997

Decreased oral availability of cyclosporin A at second administration in humans.

AIMS: The objective of this study was to determine the extent of period effect on the pharmacokinetics of cyclosporin A (CsA) during consecutive dosing. METHODS: Sandimmune Neoral and Neoplanta capsules were administered to twenty-four healthy Korean male subjects at a single CsA dose of 175 mg in a 2 x 2 crossover investigation with a 2-week wash-out phase. Concentrations of CsA in blood were measured by a r.i.a. method for a period of 48 h. RESULTS: The two formulations were found bioequivalent, but analysis of variance (ANOVA) indicated that there is a significant (P < 0.01) period effect in AUC(0,last) (area under the blood concentration-time curve above the assay limit) and Cmax (maximum blood concentration) between the administrations. A 6 and 9% decrease in the AUC(0,last) and Cmax, respectively was seen at the second administration. CONCLUSIONS: This period effect on the pharmacokinetics of CsA may be relevant for the patients who need consecutive administration of the drug.

Administration, Oral↗
PubMed1996

Rectal absorption of omeprazole from suppository in humans.

The oral absorption of omeprazole is incomplete, in part due to first-pass metabolism. We investigated the feasibility of rectal administration of omeprazole by comparing its absorption from a Witepsol H15-based rectal suppository and an orally administered commercial gelatin capsule in 10 male volunteers. Profiles of plasma concentration between two preparations (20 mg) were not statistically different, indicating that the rate and the extent of absorption were similar. Paired t-test revealed no significant differences in area under the curve, mean residence time, and time to peak concentration between two preparations. On the other hand, lag time of absorption and peak concentration were statistically different (p < 0.05) between these preparations. Under these experimental conditions, the rectal route did not produce an improvement in the extent of absorption over an oral capsule.

Area Under Curve↗
PubMed1996

Exogenous pulmonary surfactant replacement therapy in a neonate with pulmonary hypoplasia accompanying congenital diaphragmatic hernia--a case report.

Pulmonary hypoplasia(PH) commonly occurs in association with oligohydramnios and other congenital anomalies, especially congenital diaphragmatic hernia (CDH). Pulmonary hypoplasia is an important factor, as persistent pulmonary hypertension, in the prognosis of CDH. In some reports, there is a decrement of pulmonary surfactant in PH accompanying CDH. Recently, there are some reports that exogenous pulmonary surfactant therapy is effective in experimental animal model and neonatal respiratory distress with PH. We report a case of a 5 day-old male neonate, who had shown dyspnea and diagnosed as left pulmonary hypoplasia accompanying CDH. The CDH was surgically treated and the ipsilateral PH, with intratracheal administration of exogenous pulmonary surfactant postoperatively. After exogenous pulmonary surfactant application, the left lung volume was increased on chest roentgenogram and lung perfusion scan findings, and there was an improvement in oxygenation and clinical manifestations. We suggest that postoperative exogenous pulmonary surfactant replacement therapy is effective in the case of PH and further trials are needed to clarify the optimal dose and timing of supplementation of surfactant for treatment of infants with PH accompanying CDH.

Hernias, Diaphragmatic, Congenital↗
PubMed1996

In vitro effect of meconium on the physical surface properties and morphology of exogenous pulmonary surfactant.

The pathophysiology of meconium aspiration syndrome(MAS) is related to mechanical obstruction of the airways and to chemical pneumonitis. Meconium is also suggested to cause functional deterioration of pulmonary surfactant. Recent studies have reported that meconium inhibits the physical surface properties of pulmonary surfactant, and that administration of exogenous surfactant may provide therapeutic benefits in animal models or infants with respiratory distress due to MAS. To assess the effects of meconium on physical surface properties, especially the changes on the air-liquid interface and hypophase of pulmonary surfactant in vitro, we studied the following findings; a) the surface spreading rate(SSR) and the surface adsorption rate(SAR), b) the viscosity, c) the electron microscopic changes, on a series of mixtures with various concentrations of lyophilized human meconium and Surfactant-TA(SurfactenTM). The human meconium has significantly increased the surface tension of SSR and the viscosity of pulmonary surfactant, but had decreased the surface pressure of SAR of surfactant, and changed the electron microscopic findings of surfactant. We have concluded that these findings support the concept that meconium-induced surfactant dysfunction may play a role in the pathophysiology of MAS.

Humans↗
PubMed1996

Saturable disposition of taurine in the rat cerebrospinal fluid.

Recently, we described a saturable Na(+)-dependent taurine transporter in the choroid plexus, the blood-CSF barrier (Chung et al., 1994). The goal of this study was to determine whether this transporter plays a role in the in vivo elimination of taurine from the CSF. 3H-taurine and 14C-inulin were injected into the lateral ventricle of anesthetized rats, and the concentrations of the radiolabeled compounds in the CSF were determined. The apparent clearance of taurine from the CSF was greater than the estimated CSF bulk flow (P < .005), which indicates that there is a clearance process in addition to the CSF bulk flow. Taurine distribution into the choroid plexus was at least 10-fold higher than that found in other brain areas. The apparent clearance of 3H-taurine and the distribution of taurine into the choroid plexus and cerebral cortex were dose-dependent. The Michaelis-Menten rate constant estimated from the in vivo elimination study (40 +/- 25 microM) is in the range of that obtained for taurine uptake in isolated choroid plexus tissue slices (137 +/- 67 microM). Both alpha- and beta-alanine decreased the clearance of taurine from the CSF as well as the distribution of taurine into the choroid plexus via inhibitory effects (either direct or indirect) on the Na(+)-taurine transporter in the choroid plexus. These data suggest that the previously characterized taurine transporter in the choroid plexus plays a role in the in vivo saturable disposition of taurine in the CSF.

Alanine↗
PubMed1995

Formulas expressing life expectancy, survival probability and death rate in life table at various ages in US adults.

The National Center for Health Statistics (Monthly Vital Statistics Report, 41 (1993) 1-36; Pediatrics, 92 (1993) 743-754) reported the life table for the total population of the United States, 1992, on the basis of vital statistics. The life table shows life expectancy, survival and death rate at various ages. Formulas expressing death rate, survival probability and life expectancy at various ages in US adults are constructed from the data of the National Center for Health Statistics (NCHS). A mathematical model of the 'probacent'-probability equation previously published by the author is employed in this study. Analysis of the computer-assisted predicted values and the data reported by the NCHS indicates that the formulas are accurate and reliable with a close agreement in expressing death rate, survival probability and life expectancy at various ages in US adults of 25 years of age and older. The formulas can determine the relationship between the age and the death rate, the survival probability or the life expectancy and may be of value for epidemiologic evaluation of US adults.

Adult↗
PubMed1995

Choice of antibiotics by the site of infection in a community hospital.

A total of 1578 culture and antimicrobial susceptibility results on clinical specimens from various sites of infection were analyzed, by using the software installed in the MicroScan System of an automated microbiology analyzer, and by mathematical calculation. A list of antimicrobial drugs of choice by the site of infection is determined on the basis of the computer and mathematical analysis of the above data. The list suggested in this in vitro study may be useful to clinicians for selection of an initial antimicrobial agent in hospitals or communities when an infection is suspected in a site of infection before the results of cultures and antimicrobial susceptibility tests are reported. This list may also be helpful for initial therapy in critically ill patients before ordering culture and susceptibility testing, as well as for preoperative prophylaxis.

Anti-Bacterial Agents↗