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Biomedical subjects

K S Han

Publications and source records attributed to K S Han.

At least 37 records · Page 2Linked to original sources
PubMed2000

Early recurrent nephrotic syndrome after renal transplantation in children with focal segmental glomerulosclerosis.

BACKGROUND: We analysed risk factors to predict the recurrence of nephrotic syndrome and the therapeutic efficacy of plasmapheresis combined with oral cyclophosphamide (PE+CPM) in early recurrent nephrotic syndrome after transplantation in children with focal segmental glomerulosclerosis (FSGS). METHODS: Medical records after 1990 of 16 children with biopsy-proven idiopathic FSGS and renal transplantation before the age of 18 years were reviewed. RESULTS: Early recurrence of nephrotic syndrome developed in six cases (37. 5%). While early kidney graft biopsies, performed within the first week after the onset of recurrence, revealed diffuse effacement of foot process only, late biopsies contained segmentally sclerosed glomeruli as well. Among several possible risk factors, the mean duration from onset of original nephrotic syndrome to development of end-stage renal disease was shorter in the recurrent group (P=0.045) and the percentage of globally sclerosed glomeruli was higher in the non-recurrent group (P=0.001). PE+CPM therapy resulted in complete remission of nephrotic syndrome if it was started early and if there was no evidence of accompanying acute rejection. CONCLUSION: These results support more liberal use of living-related donors for renal transplantation of children with FSGS and ESRD, considering the shortage of cadaveric donors in our society and relatively good efficacy of the early and intensive PE+CPM therapy for early recurrent nephrotic syndrome.

Adolescent↗
PubMed2000

Gastrointestinal first-pass effect of furosemide in rats.

The first-pass effect of furosemide was investigated in rats. Furosemide intravenous solution (20 mg kg(-1) Lasix), was administered via the jugular vein and the portal vein, orally, and instilled directly into the duodenum of rats. The first-pass effects of furosemide by lung, heart, and liver seemed to be negligible in rats. The absolute bioavailability of furosemide was 28.9 and 48.3% after oral and intraduodenal administration, respectively. Based on the gastrointestinal (GI) recovery study, 68.3 and 69.5% of furosemide were found to have disappeared mainly due to absorption and/or metabolism from rat GI tract after oral and intraduodenal administration, respectively. The results indicate that gastrointestinal and intestinal first-pass effects of furosemide were approximately 40% (68.3-28.9%) and 20% (69.5-48.3%) of the dose, respectively.

Administration, Oral↗
PubMed2000

A successful delivery of a baby from a D--/D-- mother with strong anti- Hr0.

We describe the first reported case in Korea of a woman with a D--/ D-- phenotype, a high-titer anti-Hr0, and the successful delivery of her newborn. The mother had a history of spontaneous abortion and artificial termination. In her third pregnancy, a live infant was delivered, but died of severe hemolytic disease of the newborn due to anti- Hr0 in spite of intensive medical intervention. In her fourth pregnancy, at 22 weeks gestation, the titer of anti- Hr0 was 1024, fetal cells were direct antiglobulin test positive and the blood type was group O, D+ (CDe). We performed plasma exchanges in the mother; however, the titer of antibody rebounded to its initial level after the third plasma exchange. At 26 weeks gestation, cord blood Hb decreased to 7.1 g/dL and three intrauterine transfusions were performed using the mother's washed red blood cells (RBCs). At 34 weeks gestation, a live baby was delivered by cesarean section. The infant was hydropic with hyperbilirubinemia and severe anemia. However, after two exchange transfusions using the washed RBCs of the mother's sister, who was also D--/D--, laboratory and clinical findings returned to normal.

Journal Article↗
PubMed1999

Effect of a new chemoprotective agent, 2-(allylthio)pyrazine, on the pharmacokinetics of intravenous theophylline in rats.

The effect of 2-(allylthio)pyrazine (2-AP) pretreatment on the pharmacokinetics of theophylline and its metabolites was investigated after 1-min intravenous administration of aminophylline, 5 mg/kg as theophylline, to rats pretreated with three consecutive daily oral administration of 2-AP, 100 mg/kg. The AUC0-2 h of a metabolite of theophylline, 1,3-dimethyluric acid, 1,3-DMU (62.3 versus 106 microg/min per ml), and the percentages of intravenous dose of theophylline excreted in 24-h urine as 1,3-DMU (12.4% versus 20.8%, expressed in terms of theophylline) decreased significantly in 2-AP-pretreated rats when compared with those in control rats. Since CYP1A2 and CYP2E1 are involved in the formation of 1,3-DMU from theophylline, and 2-AP considerably suppressed CYP2E1 and tended to suppress CYP1A2 in rats, decreased formation of 1,3-DMU in 2-AP-pretreated rats could be mainly due to suppression of the CYP2E1 expression by pretreatment with 2-AP.

Animals↗
PubMed1999

Gender differences in pharmacokinetics and pharmacodynamics of azosemide in rats.

Gender differences in pharmacokinetics and pharmacodynamics of azosemide were evaluated after intravenous, 10 mg kg(-1), and oral, 10 mg kg(-1), administration to male and female rats. After intravenous administration to male rats, the percentages of intravenous dose of azosemide recovered from entire gastrointestinal tract at 24 h (13.2 versus 3.93%) was significantly greater than those in female rats. In male rats, the nonrenal clearance of azosemide tended (p<0.066) to be faster and kidney weight tended (p<0.068) to be greater than those in female rats. After oral administration of azosemide to male rats, the 8-h urinary excretion of potassium (0.395 versus 0.766 mmol g(-1) kidney) and 8-h kaluretic efficiency (55.9 versus 284 mmol mg(-1)) decreased significantly compared with female rats.

Administration, Oral↗
PubMed1999

Pharmacokinetics of a new proton-pump inhibitor, YJA-20379-8, after intravenous and oral administration to rats with streptozotocin-induced diabetes mellitus.

Because physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of a new proton pump inhibitor, YJA-20379-8, were investigated after intravenous and oral administration of the drug (50 mg kg(-1)) to control rats and to rats with streptozotocin-induced diabetes mellitus (SIDM). After intravenous administration of YJA-20379-8 to SIDM rats, plasma concentrations of the drug were significantly higher and this resulted in a significantly greater AUC (area under the concentration-time curve; 2520 +/- 366 compared with 1870+/-272 microg min mL(-1)). This was because of significantly slower clearance (CL; 19.5+/-2.88 compared with 27.2+/-3.93 mL min(-1) kg(-1)) in SIDM rats. The significantly slower metabolism of YJA-20379-8 in SIDM rats was confirmed by an in-vitro tissue metabolism study; the amounts of YJA-20379-8 remaining in the liver (27.1+/-5.19 compared with 18.9+/-8.24 microg(g tissue)(-1)) were significantly greater after 30-min incubation of the drug (50 microg) with supernatant fractions obtained from the tissues by centrifugation at 9000 g. After oral administration of YJA-20379-8 to SIDM rats the plasma concentrations of the drug were significantly lower and this resulted in significantly smaller AUC (128+/-31.0 compared with 219+/-45.6 microg min mL(-1)). This was because of reduced gastrointestinal absorption of YJA-20379-8 in SIDM rats; the amounts of the oral dose recovered as unchanged drug from the entire gastrointestinal tract after 24h were significantly greater (32.9 compared with 19.2%) in SIDM rats. The tissue distribution of YJA-20379-8 was not affected by SIDM.

Administration, Oral↗
PubMed1999

Gastrointestinal absorption of a new reversible proton pump inhibitor, YJA-20379-8, and its pharmacokinetics after oral administration in acetic acid-induced gastric ulcer in rats.

The absorption of YJA-20379-8 (3-butyryl-4-[5-(R)-(+)-methylbenzylamino]-8-ethoxy-1,7-naphthyrid ine) from various rat gastrointestinal segments was evaluated using in-situ closed-loops. The pharmacokinetics of the drug were also evaluated after oral administration to rats with acetic acid-induced gastric ulcer (AIURs). The concentrations of YJA-20379-8 in the biological samples were analyzed by HPLC. The absorption of YJA-20379-8 from stomach and jejunum was fast, but approximately 50% of the drug was recovered from each segment at 24 h. The total areas under the plasma concentration-time curves from time zero to 24h (AUC(0-24h)) were 161, 392, 233, 365, and 226 microg min mL(-1) for stomach, duodenum, jejunum, ileum, and colon, respectively. After oral administration of the drug, the plasma concentrations and the resultant AUC (0- 12h) were not significantly different between control and AIURs. The detection limits of YJA-20379-8 in human plasma and urine were 50 and 100 ng mL(-1), respectively. The results suggest that modification of the oral dose of YJA-20379-8 may not be required in gastric ulcer patients if the present rat pharmacokinetic data could be extrapolated to man.

Acetic Acid↗
PubMed1999

Gastrointestinal first-pass effect of YJA-20379-8, a new reversible proton pump inhibitor, in rats.

Since low bioavailability of YJA-20379-8 (3-butyryl-4-[5-R-(+)-methylbenzylamino]-8ethoxy-1,7-naph thy ridine), a new reversible proton pump inhibitor, has been reported after oral administration of the drug to rats, the first-pass organ of the drug was investigated in rats. YJA-20379-8, 50 mg kg(-1), was infused over 1 min via the jugular vein (n=5) or the portal vein (n=5), or was instilled directly into the stomach (n=5) or the duodenum (n=5). After intravenous or intraportal infusion of the drug, the total body clearance of YJA-20379-8 (18.1 and 19.7 mL min(-1) kg(- 1) based on plasma data) was considerably lower than the reported cardiac output (296 mL min(-1) kg(-1) based on blood data) in rats. This data indicated that the first-pass effect of YJA-20379-8 by the lung and heart was negligible. The areas under the plasma concentration-time curve from time zero to time infinity (AUC) after intravenous or intraportal administration of YJA-20379-8 (2760 and 2540 microg min mL(-1)) were not significantly different, indicating that the hepatic first-pass effect of the drug was also negligible in rats. After intragastric or intraduodenal instillation of YJA-20379-8, the extent of absolute oral bioavailability was 18.2 and 33.8%, respectively. Based on gastrointestinal recovery studies, approximately 86.5 and 91.2% of YJA-20379-8 was absorbed from rat gastrointestinal tract after intragastric or intraduodenal instillation, respectively. The data indicated that gastrointestinal and intestinal first-pass effects of YJA-20379-8 were approximately 68% (86.5-18.2) and 57% (91.2-33.8), respectively. The AUC(0-24h) values of YJA-20379-8 were significantly different between intragastric and intraduodenal instillation, indicating that the gastric first-pass effect of the drug was approximately 10% in rats. Therefore, it could be concluded that the low F value of YJA-20379-8 after oral administration of the drug could be due to a considerable (approx. 60%) intestinal first-pass effect in rats.

Animals↗
PubMed1999

National blood program in Korea.

Transfusion requirements for red cells and platelets have been completely fulfilled by voluntary donations since 1980 in Korea. However, Korea imports 300,000 liters of plasma each year to produce plasma fractionation products. Korean Red Cross Blood Center supplies 96 percent of blood consumed in Korea. The remaining 4 percent is supplied by 95 hospital blood centers. Measures to supply safer blood, to achieve national self-sufficiency of plasma, and to improve quality assurance are under way.

Adolescent↗
PubMed1999

Enhanced absorption of oral furosemide by bile juice in rats.

The effect of bile juice on gastrointestinal absorption of furosemide was investigated in rats. Furosemide intravenous solution (Lasix), 20 mg/kg, was administered orally with (n = 5) or without (n = 6) bile juice administration after bile duct cannulation. With bile juice administration, the plasma concentrations of furosemide were considerably higher and AUC(0-8) h was significantly greater (2570 versus 658 microg x min/ml) suggesting that absorption of furosemide increased significantly by bile juice. This was supported by significantly smaller in the percentages of oral dose of furosemide recovered from entire gastrointestinal tract at 24 h: the values were 29.5% and 58.0% with and without bile juice administration, respectively.

Administration, Oral↗
PubMed1999

Pharmacokinetics of a chemoprotective agent, 2-(allylthio)pyrazine, after intravenous and oral administration to rats: hepatic and gastric first-pass effects.

Pharmacokinetic parameters of 2-(allylthio)pyrazine (2-AP) were evaluated after i.v. administration of the drug (10, 20, 50, and 100 mg/kg body weight) and oral administration of the drug (10, 50, and 100 mg/kg body weight) to rats. The hepatic, gastric, and intestinal first-pass effects of 2-AP were also measured after i.v., intraportal, intraduodenal, and oral administration of the drug (10 and 50 mg/kg body weight) to rats. After i.v. administration, the pharmacokinetic parameters of 2-AP were dose-independent at the dose ranges studied. However, after oral administration, the dosenormalized total area under the plasma concentration-time curve from time zero to time infinity values (43.5, 125, and 205 microg min/ml, based on 10 mg/kg body weight) increased significantly with increasing doses. The extent of absolute oral bioavailability (F) values also increased with increasing oral doses; the values were 19. 6, 56.7, and 93.6% for 10, 50, and 100 mg/kg body weight, respectively. The oral data above could be due to saturable hepatic, gastric, and/or intestinal first-pass effects. This was proved by saturable gastric first-pass effect (the significant area under the plasma concentration-time curve from time zero to time infinity difference between oral and intraduodenal administration of 2-AP); the values were 62.6 and 26.6% at 2-AP doses of 10 and 50 mg/kg body weight, respectively. Approximately 20% of oral dose was eliminated by liver (hepatic first-pass effect) for both oral doses of 10 and 50 mg/kg body weight. However, the first-pass effects of 2-AP in the intestine, heart, and lung were almost negligible. The low F value after oral administration of 2-AP at low dose (10 mg/kg body weight) was mainly due to gastric first-pass effect in rats.

Administration, Oral↗
PubMed1998

Determination of a chemoprotective agent, 2-(allylthio)pyrazine, in plasma, urine and tissue homogenates by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for the determination of a chemoprotective agent, 2-(allylthio)pyrazine (I), in human plasma and urine, and in rat blood and tissue homogenate using diazepam as an internal standard. The sample preparation was simple; 2.5 volumes of acetonitrile were added to the biological sample to deproteinize it. A 50-100 microl aliquot of the supernatant was injected onto a C18 reversed-phase column. The mobile phase employed was acetonitrile-water (55:45, v/v), and it was run at a flow-rate of 1.5 ml/min. The column effluent was monitored using an ultraviolet detector at 330 nm. The retention times for I and the internal standard were 4.0 and 5.1 min, respectively. The detection limits of I in human plasma and urine, and in rat tissue homogenate (including blood) were 20, 20 and 50 ng/ml, respectively. The coefficients of variation of the assay (within-day and between-day) were generally low (below 6.1%) in a concentration range from 0.02 to 10 microg/ml for human plasma and urine, and for rat tissue homogenate. No interferences from endogenous substances were found.

Animals↗
PubMed1998

Pharmacokinetics of a new reversible proton pump inhibitor, YH1885, after intravenous and oral administrations to rats and dogs: hepatic first-pass effect in rats.

The pharmacokinetics of YH1885 were evaluated after intravenous (iv) and oral administrations of the drug to rats and dogs. The reason for the low extent of bioavailability (F) of YH1885 after oral administration of the drug to rats and the absorption of the drug from various rat gastrointestinal (GI) segments were also investigated. After iv administration of YH1885, 5-20 mg kg(-1), to rats, the pharmacokinetic parameters of YH1885 seem to be independent of the drug at the dose ranges studied. After oral administration of YH1885, 50-200 mg kg(-1), to rats, the area under the plasma concentration-time curve from time zero to 12 or 24 h (AUC(0-12 h) or AUC(0-24 h)) was proportional to the oral dose of the drug, 50-100 mg kg(-1), however, the AUC(0-24 h) value at 200 mg kg(-1) increased with less proportion to the dose increase (324, 689, and 815 microg x min mL(-1) for 50, 100, and 200 mg kg(-1), respectively) due to the poor water solubility of the drug. This was proved by the considerable increase in the percentages of the oral dose remaining in the entire GI tract as unchanged YH1885 at 24 h (11.8, 15.3, and 42.8% for 50, 100, and 200 mg kg(-1), respectively). The F value after oral administration of YH1885 to rats was relatively low; the value was approximately 40% at the oral dose of 50 and 100 mg kg(-1). The reason for the low F in rats was investigated. The liver showed the highest metabolic activity for YH1885 based on an in vitro rat tissue homogenate study; hence, the liver first-pass effect was estimated. The value of AUC after intraportal administration of the drug, 5 mg kg(-1), was approximately 70% (116 versus 163 microg x min mL(-1)) of that after iv administration of the drug, 5 mg kg(-1), to rats; the liver first-pass effect of YH1885 in rats was estimated to be approximately 30%. The total body clearance of YH1885 after iv administration of the drug, 5-20 mg kg(-1), to rats were considerably lower than the cardiac output of rats, indicating that the lung and/or heart first-pass effect of YH1885 could be negligible in rats. After oral administration of YH1885, 50 and 100 mg kg(-1), to rats, the F value was approximately 40%, and approximately 15% of the oral dose was recovered from the entire GI tract as unchanged YH1885 at 24 h, and 30% of the oral dose disappeared with the liver first-pass effect. Therefore, the remainder, approximately 15% of the oral dose, could have disappeared with the small intestine first-pass effect and/or degradation of the drug in the GI tract. YH1885 was absorbed from ileum, duodenum, and jejunum of rat, however, YH1885 was under the detection limit in plasma when the drug was instilled into the rat stomach and large intestine. After iv administration of YH1885, 5-20 mg kg(-1), to dogs, the pharmacokinetic parameters of YH1885 also seemed to be independent of the drug at the dose ranges studied. However, after oral administration of YH1885, 0.5 and 2 g per whole body weight, to dogs, the AUC(0-10 h) values were not significantly different (96.8 versus 98.2 microg x min mL(-1)) and this could be due to the poor water-solubility of the drug. YH1885 was not detected in the urine after both iv and oral administration of the drug to both rats and dogs.

Administration, Oral↗
PubMed1998

Gene frequencies of eight human platelet-specific antigens in Koreans.

Human platelet-specific antigens (HPAs) are found on platelet membrane glycoproteins and are the target of platelet alloantibodies that mediate platelet destruction in neonatal alloimmune thrombocytopenia (NAIT), post-transfusion purpura (PTP) and refractoriness to platelet transfusion therapy. The biallelic polymorphism of all HPA systems is known to be due to a substitution of a single base pair. This study was performed to investigate the frequency of the HPA genes in Koreans, based on these substitutions. The genotypes of eight HPA systems were determined by polymerase chain reaction using sequence-specific primers (PCR-SSP) for HPA-1, -2, -4, -5, and -8 and restriction fragment length polymorphism (RFLP) for HPA-3, -6, and -7. The gene frequencies obtained from 200 unrelated Koreans were 0.99 and 0.01 for HPA-1a and -1b, 0.92 and 0.08 for HPA-2a and -2b, 0.55 and 0.45 for HPA-3a and -3b, 0.99 and 0.01 for HPA-4a and -4b, 0.98 and 0.02 for HPA-5a and -5b, and 0.98 and 0.02 for HPA-6a and -6b. All the individuals tested were homozygotes for HPA-7a and HPA-8a. It has been reported that the HPA-1b antigen is extremely rare (less than 0.3%) in Oriental populations, but this study suggests that the frequency of this antigen in Koreans (2.0%) is higher than in Japanese and Chinese populations.

Antigens, Human Platelet↗
PubMed1998

Circadian changes in the pharmacokinetics and pharmacodynamics of azosemide in rats.

The circadian changes in the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous and oral administration of the drug (10 mg kg(-1)) to rats at 1000 or 2200 h. After intravenous administration of azosemide the percentage of the dose excreted in 8-h urine as unchanged azosemide was significantly higher in the 1000 h group than in the 2200 h group (41.7 compared with 28.9%) and this resulted in a significant increase in 8-h urine output (84.7 compared with 36.6 mL/100 g). After intravenous administration the time-averaged renal clearance (CLR) of azosemide was significantly faster (2.86 compared with 1.76 mL min(-1) kg(-1)) and urinary excretion of sodium (46.4 compared with 25.9 mmol/100 g) and chloride (35.6 compared with 18.8 mmol/100 g) increased significantly in the 1000 h group. However, after oral administration, the percentages of oral dose of azosemide excreted in 8-h urine as unchanged azosemide were significantly higher (1.88 compared with 0.67%) and the CL(R) of azosemide was significantly faster (3.64 compared with 0.79 mL min(-1) kg(-1)) in the 2200 h group. This could be at least partly because of increased absorption of azosemide from the gastrointestinal tract in the 2200 h group; the percentages of oral dose of azosemide recovered from the gastrointestinal tract in 8 h as unchanged azosemide was significantly smaller (5.7 compared with 13.2%) in the 2200 h group. The pharmacodynamic parameters of azosemide were not significantly different after oral administration of the drug to both groups of rats. If these data could be extrapolated to man, the intravenous dose of azosemide could be modified on the basis of circadian time.

Administration, Oral↗
PubMed1998

Early organogenesis and cell contacts in the proliferating hypophysis of the developing mouse.

The mouse foetal hypophysis which contains the diencephalic downgrowth (Dd) and Rathke's pouch (Rp) was examined using morphological and immunocyto/histo-chemical methods to study the cell-cell and cell-extracellular matrix (ECM) interactions that occur during early organogenesis. While many studies have described that the differentiation of ACTH cells precedes the proliferation of other endocrine cells in the Rp, light and conventional transmission electron microscopic (TEM) investigations have failed to differentiate between the various endocrine cell types in the proliferating distal lobe at the late mid-foetal stage. Conversely, TEM studies have shown that the occurrence of dense secretory vesicles in glandular cells of the presumptive pars intermedia in close apposition with the presumptive neural lobe by a basal lamina, is the earliest sign of endocrine activity in the foetal hypophysis. However, a confocal laser scanning microscopy (CLSM) and fine structure study did not observe direct cell-to-cell contacts between the Dd, Rp and their associated mesenchyme at the late mid-foetal stage. Using CLSM and TEM, we detected active cell turnover with programmed cell death in the proliferating Rp, Dd and their associated cephalic mesenchyme. Morphological findings indicated that apoptosis in the cephalic mesenchyme subsequently brings neurohypophyseal pituicytes and adenohypophyseal precursor stem cells into closer proximity, and alternations in the boundary cell surfaces might initiate signal transduction mediated via the intervening ECM at the proliferation stage.

Animals↗
PubMed1998

Hepatic and intestinal first-pass effects of a new hepatoprotective agent, YH439, in rats.

First-pass effects of YH439 were evaluated after intravenous, intraportal, oral, and intraduodenal administration of the drug, 100 mg/kg body weight, to rats. The first-pass effects of YH439 in the lung and heart seemed to be negligible based on total body clearance values after intravenous and intraportal administration of the drug to rats compared with cardiac output in rats. Approximately 60% of orally and intraduodenally administered YH439 was not absorbed from rat gastrointestinal tract and the F values of YH439 were less than 0.22% after both administration of the drug to rats. Therefore, it could be concluded that approximately 40% of orally and/or intraduodenally administered YH439 could disappeared by hepatic and/or gastrointestinal first-pass effects. The hepatic first-pass effect of YH439 absorbed into the portal vein was approximately 45% (AUC difference between intravenous and intraportal administration) in rats. The AUC0-8hr values of YH439 after oral (18.7 microg min/ml) and intraduodenal (23.4 microg min/ml) administration were significantly smaller than that after intraportal administration (3260 microg min/ml), however, the values were not significantly different between oral and intraduodenal administration, suggesting that the gastric first-pass effect seemed to be negligible and intestinal first-pass effect was considerable in rats. The low F of YH439 in rats could be mainly due to unabsorption (approximately 60%) and hepatic and intestinal first-pass effect (approximately 40%).

Animals↗