Biomedical subjects

Young H Choi

Publications and source records attributed to Young H Choi.

13 recordsLinked to original sources

PubMed2007

Pharmacokinetics of 5-fluorouracil in mutant Nagase analbuminemic rats: faster metabolism of 5-fluorouracil via CYP1A.

It has been reported that plasma albumin concentrations were significantly lower in cancer patients than those in the healthy volunteers, and the expression and mRNA level of hepatic microsomal cytochrome P450 (CYP) 1A2 increased in mutant Nagase analbuminemic rats (NARs). After intravenous administration of 5-fluorouracil at a dose of 30 mg/kg to NARs, the time-averaged nonrenal clearance (Clnr) of the drug was significantly faster than the controls (51.3 versus 28.8 ml/min/kg), possibly due to an increase in the expression and mRNA level of CYP1A2 in NARs. In order to determine whether 5-fluorouracil is metabolized via CYP1A2 in male Sprague-Dawley rats, the rats were pretreated with 3-methylcholanthrene (a main inducer of CYP1A1/2 in rats). The Clnr of 5-fluorouracil was significantly faster (34.3 versus 27.3 ml/min/kg) in rats pretreated with 3-methylcholanthrene. The aforementioned data indicate that CYP1A is involved in the metabolism of 5-fluorouracil in rats.

Acetylglucosaminidase↗

PubMed2006

Pharmacokinetics of DA-6034, an agent for inflammatory bowel disease, in rats and dogs: Contribution of intestinal first-pass effect to low bioavailability in rats.

The pharmacokinetics of DA-6034 in rats and dogs and first-pass effect in rats were examined. After intravenous administration, the dose-normalized AUC(0-infinity) values at 25 and 50mg/kg were significantly smaller than that at 10mg/kg. This could be due to significantly slower Cl(r) values than that at 10mg/kg, possibly due to saturated renal secretion at doses of 25 and 50mg/kg. After oral administration, the dose-normalized AUC(0-12h) values at 50 and 100mg/kg were significantly smaller than that at 25mg/kg, possibly due to poor water solubility of the drug. The low F-value (approximately 0.136%) of DA-6034 at a dose of 50mg/kg in rats could be due to considerable intestinal first-pass effect (approximately 69% of oral dose) and unabsorbed fraction from the gastrointestinal tract (approximately 30.5%). The effect of cola beverage, cimetidine, or omeprazole on the AUC(0-24h) of DA-6034 was almost negligible in rats. Pharmacokinetic parameters of DA-6034 after intravenous and oral administration at various doses were dose-independent in dogs. DA-6034 was not accumulated in rats and dogs after consecutive 7 and 28 days oral administration, respectively. The stability, blood partition, and protein binding of DA-6034 were also discussed.

Administration, Oral↗

PubMed2006

Dose-independent pharmacokinetics of metformin in rats: Hepatic and gastrointestinal first-pass effects.

Pharmacokinetic parameters of metformin were evaluated after intravenous and oral administration (50, 100, and 200 mg/kg) in rats. The hepatic, gastric, and intestinal first-pass effects were also measured after intravenous, intraportal, intragastric, and intraduodenal administration (100 mg/kg) in rats. The total area under the plasma concentration-time curve from time zero to time infinity (AUC) values were dose-proportional after both intravenous and oral dose ranges studied. After oral administration (100 mg/kg), approximately 4.39% of oral dose was not absorbed and extent of absolute oral bioavailability (F) value was approximately 29.9%. The gastrointestinal first-pass effect of metformin was approximately 53.8% of oral dose in rats (the gastric and intestinal first-pass effects were approximately 23.1 and 30.7%, respectively), and the hepatic first-pass effect was approximately 27.1% after absorption into the portal vein. Since approximately 41.8% of oral metformin was absorbed into the portal vein, the value of 27.1% is equivalent to 11.3% of oral dose. The first-pass effects of metformin in the lung and heart were almost negligible in rats. The low F value of metformin in rats was mainly due to considerable gastrointestinal first-pass effects. The stability of metformin, distribution of metformin between plasma and blood cells, and factors affecting protein binding of metformin to 4% human serum albumin were also discussed.

Administration, Oral↗

PubMed2006

Activity of quinones from teak (Tectona grandis) on fungal cell wall stress.

Teak ( Tectona grandis L.f., Verbenaceae) sawdust extract inhibited the growth of Aspergillus niger. Centrifugal partition chromatography was used to isolate the active compounds. By (1)H-NMR the active compounds were identified as deoxylapachol and tectoquinone. Two A. niger transgenic strains which show induction of 1,3 -alpha-D-glucan synthase were used as a cell wall damage model. The result showed that deoxylapachol from T. grandis extract induced fungal cell wall stress.

Antifungal Agents↗

PubMed2006

Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous ipriflavone in rats.

In order to find out what types of the hepatic microsomal cytochrome P450 (CYP) isozymes are involved in the metabolism of ipriflavone, ipriflavone at a dose of 20 mg kg(-1) (or 15 mg kg(-1)) was infused in male Sprague-Dawley rats. In rats pretreated with SKF 525-A (a non-specific CYP isozyme inhibitor in rats), the total body clearance (CL) of ipriflavone was significantly slower (29.9% decrease) than that in control rats. This indicates that ipriflavone is metabolized via CYP isozymes in rats, hence various enzyme inducers and inhibitors were used in in-vitro or in-vivo studies in rats. In rats pretreated with 3-methylcholanthrene and phenobarbital (main inducers of CYP1A1/2 and 2B1/2 in rats, respectively), the CL values were significantly higher (153 and 67.2% increases, respectively). In rats pretreated with sulfaphenazole (a main inhibitor of CYP2C11 in rats), the CL was significantly slower (22.5% decrease) than that in control rats. On addition of furafylline (a main inhibitor of CYP1A2 in rats), the in-vitro intrinsic clearance for the disappearance of ipriflavone was significantly slower (50.8% decrease) than that without furafylline. However, the CL values were not significantly different in rats pretreated with orphenadrine and isoniazid (a main inducer of CYP2E1 in rats), and quinine and troleandomycin (main inhibitors of CYP2D1 and 3A23/2 in rats, respectively) compared to controls. These data suggest that ipriflavone could be metabolized mainly via CYP1A1/2, 2B1/2 and 2C11 in rats.

Animals↗

PubMed2005

Liquid chromatography-diode array detection-electrospray ionisation mass spectrometry/nuclear magnetic resonance analyses of the anti-hyperglycemic flavonoid extract of Genista tenera. Structure elucidation of a flavonoid-C-glycoside.

The anti-hyperglycemic flavonoid extract obtained from Genista tenera was first studied by liquid chromatography (LC)-diode array detection (DAD) which showed the presence of two major compounds. One of them was identified as genistein-7-O-glucoside. Luteolin-7-O-glucoside was detected as a minor constituent, while luteolin-7,3'-di-O-glucoside and rutin were found in trace amounts. LC-DAD-ESI-MS and NMR were used to confirm the structure of these compounds and allowed the elucidation of the structure of the unknown major compound, which is the flavonoid 5,7,4'-trihydroxyisoflavone-8-C-glucoside.

Carbohydrate Conformation↗

PubMed2005

Pharmacokinetics of 5-fluorouracil in rats with diabetes mellitus induced by streptozotocin.

The pharmacokinetic parameters of 5-fluorouracil were compared after intravenous administration at a dose of 30 mg/kg to control Sprague-Dawley rats and to rats with diabetes mellitus induced by streptozotocin (DMIS). In DMIS rats, the area under the plasma concentration-time curve from time zero to time infinity (AUC) was significantly smaller (603 versus 909 microg min/ml) due to the significantly faster total body clearance (Cl; 47.8 versus 33.0 ml/min/kg). The faster Cl was due to the significantly faster renal (8.54 versus 4.02 ml/min/kg) and nonrenal (38.5 versus 28.7 ml/min/kg) clearances. In DMIS rats, the total amount of unchanged 5-fluorouracil excreted in 24 h urine was significantly greater (34.1% versus 13.0% of intravenous dose) due to the urine flow rate-dependent renal clearance of 5-fluorouracil in rats (the greater the urine flow rate, the greater the urinary excretion of 5-fluorouracil). Greater urinary excretion and a significantly smaller AUC resulted in a significantly faster Cl(r) in DMIS rats. The faster Cl(nr) in DMIS rats could be due to an increase in the expression and mRNA level of CYP1A1/2 in the rats.

Animals↗

PubMed2004

Proposed mechanism for retinal tears after LASIK: an experimental model.

OBJECTIVE: To demonstrate axial length changes associated with anterior shift of the lens/iris diaphragm and anterior vitreous base in human cadaver eyes during suction ring application preceding Moria LASIK, and to propose that these changes may be associated with anterior retinal tears. DESIGN: Human eye study. MATERIALS: Eight human eye bank eyes ranging in age from 65 to 73 years. Two eyes had a history of intraocular surgery involving cataract extraction and intraocular lens implantation. INTERVENTION: Measurements of intraocular pressure via internal manometer and Tono-Pen, anterior chamber depth, and axial length before and after application of a Moria LASIK suction ring. MAIN OUTCOME MEASURES: Change in anterior chamber depth and axial length after Moria LASIK suction ring application. RESULTS: Axial length increases (mean change = 1.125 mm, P = 0.02) after application of the suction ring, whereas anterior chamber depth shows no significant difference (mean change = -0.01 mm, P = 0.98), suggesting anterior movement of the vitreous base resulting in traction on the anterior retina. CONCLUSION: Axial length increase with anterior displacement of the vitreous base during suction ring placement might predispose susceptible eyes to anterior retinal tears during and after LASIK.

Aged↗

PubMed2004

Alkaloid accumulation in Catharanthus roseus cell suspension cultures fed with stemmadenine.

Feeding stemmadenine to Catharanthus roseus cell suspension culture resulted in the accumulation of catharanthine, tabersonine and condylocarpine. Condylocarpine is not an intermediate in the pathway to catharanthine or tabersonine when it is fed to the cultures. The results support the hypothesis that stemmadenine is an intermediate in the pathway to catharanthine and tabersonine.

Alkaloids↗

PubMed2002

Arctigenin protects cultured cortical neurons from glutamate-induced neurodegeneration by binding to kainate receptor.

We previously reported that arctigenin, a lignan isolated from the bark of Torreya nucifera, showed significant neuroprotective activity against glutamate-induced toxicity in primary cultured rat cortical cells. In this study, the mode of action of arctigenin was investigated using primary cultures of rat cortical cells as an in vitro system. Arctigenin significantly attenuated glutamate-induced neurotoxicity when added prior to or after an excitotoxic glutamate challenge. The lignan protected cultured neuronal cells more selectively from neurotoxicity induced by kainic acid than by N-methyl-D-aspartate. The binding of [(3)H]-kainate to its receptors was significantly inhibited by arctigenin in a competitive manner. Furthermore, arctigenin directly scavenged free radicals generated by excess glutamate and successfully reduced the level of cellular peroxide in cultured neurons. These results suggest that arctigenin exerted significant neuroprotective effects on glutamate-injured primary cultures of rat cortical cells by directly binding to kainic acid receptors and partly scavenging of free radicals.

Animals↗

PubMed2002

Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic or unresectable localized non-small-cell lung cancer.

BACKGROUND: Docetaxel is highly active in the second-line treatment of patients with metastatic or unresectable locally advanced nonsmall-cell lung cancer (NSCLC). As there is a need for first-line chemotherapy that is more effective than standard platinum-based chemotherapy, this study was undertaken to evaluate the efficacy and tolerability of a docetaxel/cisplatin combination as first-line chemotherapy in advanced NSCLC. METHODS: Newly diagnosed, chemotherapy-naive patients with histologically confirmed NSCLC (measurable stage IIIB/IV NSCLC; Karnofsky performance status, 70-100; adequate bone marrow, renal, hepatic, and cardiac function) were eligible for the study. Docetaxel 75 mg/m2 was administered IV over 1 h, followed immediately by cisplatin 75 mg/m2, given IV over 30 min, with cycles repeated every 3 weeks, for up to six or nine cycles. RESULTS: Thirty-nine patients were enrolled and treated. Their median age was 59 years (range, 32-71 years) and median performance status, 90 (range, 70-100). Histologically, 23 patients (59%) had adenocarcinoma, 12 (30.8%) had squamous cell carcinoma, and 16 patients (41%) had stage IV disease. Thirty-seven patients were eligible for inclusion. In the 39 patients evaluable for safety, significant grade 3/4 toxicities included neutropenia (82%), nausea (10.3%), fatigue (10.3%), and diarrhea (7.7%). Of the 33 patients evaluable for response, 16 patients (48.5%) achieved a partial response and 7 showed progressive disease. Median overall survival time in all eligible patients was 10.5 months. CONCLUSION: Docetaxel/cisplatin produced promising response rates that compare favorably with those of current standard platinum combinations, with manageable toxicity. Further investigations of this first-line combination in NSCLC are warranted.

Adult↗

PubMed2002

Virtual reality system for treatment of the fear of public speaking using image-based rendering and moving pictures.

The fear of speaking is often cited as the world's most common social phobia. The rapid growth of computer technology enabled us to use virtual reality (VR) for the treatment of the fear of public speaking. There have been two techniques used to construct a virtual environment for the treatment of the fear of public speaking: model-based and movie-based. Virtual audiences and virtual environments made by model-based technique are unrealistic and unnatural. The movie-based technique has a disadvantage in that each virtual audience cannot be controlled respectively, because all virtual audiences are included in one moving picture file. To address this disadvantage, this paper presents a virtual environment made by using image-based rendering (IBR) and chroma keying simultaneously. IBR enables us to make the virtual environment realistic because the images are stitched panoramically with the photos taken from a digital camera. And the use of chroma keying allows a virtual audience to be controlled individually. In addition, a real-time capture technique was applied in constructing the virtual environment to give the subjects more interaction, in that they can talk with a therapist or another subject.

Desensitization, Psychologic↗

PubMed2002

The development of virtual reality therapy (VRT) system for the treatment of acrophobia and therapeutic case.

Virtual reality therapy (VRT), based on this sophisticated technology, has been recently used in the treatment of subjects diagnosed with acrophobia, a disorder that is characterized by marked anxiety upon exposure to heights and avoidance of heights. Conventional VR systems for the treatment of acrophobia have limitations, over-costly devices or somewhat unrealistic graphic scenes. The goal of this study was to develop an inexpensive and more realistic virtual environment (VE) in which to perform exposure therapy for acrophobia. It is based on a personal computer, and a virtual scene of a bunge-jump tower in the middle of a large city. The virtual scenario includes an open lift surrounded by props beside a tower, which allows the patient to feel a sense of heights. The effectiveness of the VE was evaluated through the clinical treatment of a subject who was suffering from the fear of heights. As a result, it was proved that this VR environment was effective and realistic at overcoming acrophobia according not only to the comparison results of a variety of questionnaires before and after treatment but also to the subject's comments that the VE seemed to evoke more fearful feelings than the real situation.

Chronic Disease↗