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Biomedical subjects

K S Han

Publications and source records attributed to K S Han.

At least 55 records · Page 3Linked to original sources

Pharmacokinetics of a chemoprotective agent, 2-(allylthio)pyrazine, after intravenous administration to rabbits.

The pharmacokinetics of 2-(allylthio)pyrazine (2-AP) were evaluated after intravenous administrations of the drug to rabbits. The reason for the multiple peaks in the plasma concentration of 2-AP after intravenous administration of the drug to rabbits were also investigated. After intravenous administration of 2-AP, 10, 20, and 50 mg/kg, to rabbits, the pharmacokinetic parameters of 2-AP, such as the total area under the plasma concentration-time curve from time 0 to 12 h (261, 672, and 1190 micrograms min/ml), the total body clearance (38.3, 42.0, 44.6 ml/min/kg), and the percentages of intravenous dose of 2-AP excreted in 24 h as unchanged drug (0.0306, 0.0252, and 0.0492%), were independent of the dose ranges studied. Since the amount of 2-AP excreted in 12-h bile as unchanged drug after intravenous administration of 2-AP, 20 mg/kg, was only 0.0241 +/- 0.00156%, and some of 2-AP excreted in gastrointestinal tract as unchanged drug was reabsorbed, the reason for the appearance of multiple peaks after intravenous administration of 2-AP could be at least partly due to gastrointestinal excretion of the drug.

Animals↗

Stability, blood partition, and pharmacokinetics of a new proton pump inhibitor, YJA-20379-8.

Stability, blood partition, and pharmacokinetics (including tissue distribution and biliary excretion) of YJA-20379-8 were studied using an HPLC analysis. YJA-20379-8 was stable for up to 48 h incubation in a water-bath shaker kept at 37 degrees C and at a rate of 50 oscillations per min in pH solutions ranging from 1 to 14. YJA-20379-8 rapidly reached equilibrium between plasma and blood cells of three rabbit blood, and the equilibrium plasma to blood cell concentration ratios were independent of the initial YJA-20379-8 blood concentrations; the mean values were 1.42-1.56 for three rabbit blood at initial YJA-20379-8 blood concentrations of 1-5 micrograms/ml. As expected from blood partition of the drug between plasma and blood cells, there was no in vitro 'blood storage effect' of YJA-20379-8. After intravenous administration of YJA-20379-8, 10, 20, and 50 mg/kg, to rats, the values of t1/2, MRT, Vss, and CL were dose-independent. However, after intravenous administration of the drug, 5, 10, and 20 mg/kg, to rabbits, the values of t1/2, MRT, and Vss were dose-dependent. After oral administration of the drug, 20, 50, and 100 mg/kg, to rats, the F values (9.00, 16.7, and 11.3% for 20, 50, and 100 mg/kg, respectively) were low considering considerable absorption of the drug from rat gastrointestinal tract (98, 80, and 76% for 20, 50, and 100 mg/kg, respectively) and this could be due to hepatic, gastric, and/or intestinal first-pass metabolism. YJA-20379-8 was under detection limit in urine samples and the contribution of biliary excretion of unchanged YJA-20379-8 to nonrenal clearance of the drug was negligible (less than 0.5% of intravenous dose) in rats, suggesting that the CL (or nonrenal clearance) of YJA-20379-8 could represent metabolic clearance in rats. YJA-20379-8 had a good affinity to almost all rat tissues studied and this was supported by a relatively high value of Vss (3.93-3.93 ml/kg) after intravenous administration of the drug to rats.

Administration, Oral↗

Pharmacokinetics of a new proton pump inhibitor, YJA-20379-8, in rats with 48-hour water deprivation.

The pharmacokinetics of YJA-20379-8 after the intravenous, 20 mg/kg, and oral, 50 mg/kg, administration of the drug, and tissue distribution of YJA-20379-8 after intravenous administration of the drug, 20 mg/kg, to control and 48-h water-deprived rats were reported. After 15-min intravenous infusion of YJA-20379-8, the drug was not detected in urine and less than 0.5% of intravenous dose of the drug was excreted in bile, suggesting that YJA-20379-8 is essentially completely metabolized in rats. Therefore, the CL (clearance) of YJA-20379-8 represents the CLNR (metabolic clearance) of the drug in rats. After oral administration of YJA-20379-8, the F values were low; the values were 21.2 and 19.4% for control and water-deprived rats, respectively. The values were considerably low considering that 93.4 and 84.6% orally administrated YJA-20379-8 were absorbed from rat GI tract of control and water-deprived rats, respectively. This could be due to considerable first-pass (hepatic, gastric, and intestinal) effects. Recently, it was found that gastric and intestinal first-pass effects of YJA-20379-8 were considerable in rats. The amounts of YJA-20379-8 in small intestine, brain, lung, stomach, and kidney increased significantly in water-deprived rats. However, the T/P ratios were comparable (not significantly different) for both groups of rats, indicating that tissue distribution of the drug was not affected by water deprivation.

Administration, Oral↗

Stability, blood partition, and protein binding of a chemoprotective agent, 2-(allylthio)pyrazine.

The stability of 2-AP, a chemoprotective agent, in various pH solutions and human gastric juice, the blood partition of 2-AP between plasma and blood cells, and the factors influencing the binding of 2-AP to 4% human serum albumin (HSA) were evaluated. 2-AP was stable in human gastric juice and pH solutions ranging from 1 to 12, however, 2-AP was unstable in pH 13 solution; the disappearance rate constant was 0.00759/h. 2-AP reached equilibrium rapidly between plasma and blood cells of rabbit blood. The equilibrium plasma/blood cells partition ratios were independent of initial rabbit blood concentrations of 2-AP, 1, 5, and 10 micrograms/ml; the values were in the range of 5.99-11.8. Binding of 2-AP to 4% HSA was dependent on HSA concentration, incubation temperature, 'the buffer' pH, and addition of acetylsalicylic acid. The binding of 2-AP was independent of buffers containing various concentrations of chloride ion, heparin, and alpha-1-acid glycoprotein.

Animals↗

Pharmacokinetic changes of a new proton pump inhibitor, YJA-20379-8, after intravenous and oral administration to rats with uranyl nitrate-induced acute renal failure.

Because the physiological changes that occur in patients with acute renal failure could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of YJA-20379-8, a new reversible proton pump inhibitor, were investigated after 15-min intravenous (20 mg/kg) and oral (50 mg/kg) administration to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF). The impaired kidney function was observed in rats with U-ARF on the basis of physiological parameters. After intravenous administration of YJA-20379-8, the pharmacokinetic parameters were not significantly different between two groups of rats except significant increase in volume of distribution at steady state in rats with U-ARF (8000 versus 4520 ml/min). However, after oral administration to rats with U-ARF, AUC(0-16)hr was significantly smaller (126 versus 293 microg min/ml) and this was due to decreased absorption of YJA-20379-8 from gastrointestinal tract; the percentages of oral dose of YJA-20379-8 recovered from gastrointestinal tract at 24 hr as unchanged drug was significantly greater (19.9% versus 6.61%) in rats with U-ARF.

Acute Kidney Injury↗

Changes in the alpha 2-adrenergic receptor subtypes gene expression in rat dorsal root ganglion in an experimental model of neuropathic pain.

We examined changes in expression of genes coding for alpha 2-AR subtypes in the dorsal root ganglion (DRG) in a rat model (spinal nerve ligation) or neuropathic pain. The present study demonstrates that the majority of DRG neurons express alpha 2C-AR mRNA and a small proportion of neurons express alpha 2A-AR mRNA, while few neurons express alpha 2B-AR mRNA in non-operated animals. In addition, alpha 2C- and alpha 2A mRNA levels in the DRG showed a significant decrease and increase, respectively in ligated animals. These findings suggest that alpha 2A- and alpha 2C-ARs in the DRG may play an important role in generating sympathetically maintained neuropathic pain.

Animals↗

Determination of a new proton pump inhibitor, YH1885, in human plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for the determination of a new proton pump inhibitor, YH1885 (I), in human plasma and urine, and rat blood and tissue homogenate using fenticonazole as an internal standard. The sample preparation was simple: a 2.5 volume of acetonitrile was added to the biological sample to deproteinize it. A 50-microliter aliquot of the supernatant was injected onto a C8 reversed-phase column. The mobile phase employed was methanol-0.005 M tetrabutylammonium dihydrogenphosphate (77:23, v/v), and it was run at a flow-rate of 1.0 ml/min. The column effluent was monitored using an ultraviolet detector at 270 nm. The retention times for I and the internal standard were 9.0 and 10.3 min, respectively. The detection limits for I in human plasma and urine, and in rat tissue homogenate (including blood) were 50, 100 and 100 ng/ml, respectively. The coefficients of variation of the assay (within- day and between-day) were generally low (below 8.84%) for human plasma and urine, and for rat tissue homogenate. No interferences from endogenous substances were found.

Animals↗

Distribution of ABO genotypes and allele frequencies in a Korean population.

The genotypes of the ABO blood group system were investigated in Korean living in Kangwon-Do area by PCR-RFLP analysis of the seven polymorphic nucleotide positions 261, 467, 526, 646, 703, 796 and 803 of the cDNA from A1 transferase. In 253 unrelated Korean individuals, 15 genotypes were found and the allele frequencies of A(Pro), A(Leu), B, O(T) and O(A) were 0.022, 0.209, 0.209, 0.360 and 0.200, respectively, with no deviation from Hardy-Weinberg expectations (chi 2 = 2.145, d.f. = 6, 0.90 < p < 0.95). As for the distribution of allele frequencies, a significant difference was noticed between the Korean and a Japanese (chi 2 = 30.87, d.f. = 4, p < 0.001) and a German (chi 2 = 127.76, d.f. = 4, p < 0.001) populations.

ABO Blood-Group System↗

A case of fatal hemolytic disease of the newborn associated with-D-/-D-phenotype.

-D- is a rare haplotype that determines D without C, c, E or e, and exalted D activity. The extremely rare homozygote propositi (-D-/-D-) are usually ascertained through their immune antibodies, anti-Rh17 (Hro), which react with red cells of all common Rh phenotypes. The authors experienced the first case in Korea of a woman with -D- phenotype. She had a history of spontaneous abortion, therapeutic termination and red cell transfusion, and at her third pregnancy she delivered a baby with severe hemolytic disease of the newborn. In spite of intensive medical intervention, the baby died of hydrops fetalis. An immune antibody to high incidence Rh antigen, namely anti-Rh17(Hro), was demonstrated in the woman's serum. A family study revealed that the -D- gene complex was present in all its members and one of the woman's sisters was also -D- homozygote. In the serum of this sister, anti-Rh17(Hro) was also present.

Erythroblastosis, Fetal↗

Frequency of neutrophil-specific antigens among Koreans using the granulocyte indirect immunofluorescence test (GIFT).

NA1, NA2, NB1, NB2, NC1, and NE1 are a group of antigens specifically expressed on neutrophils. Antibodies against neutrophil-specific antigens are involved in alloimmune neonatal neutropenia (ANN), autoimmune neutropenia (AIN), and transfusion-related acute lung injury (TRALI). We investigated the frequencies of NA1, NA2, NB1, and Mart antigens in 105 healthy Korean blood donors (65 males, 40 females) by the granulocyte indirect immunofluorescence test (GIFT) employing flow cytometry. Antigen and gene frequencies were: NA1, 0.78 and 0.53, respectively; NA2, 0.75 and 0.50, respectively; and NB1, 0.86 and 0.62, respectively. The Mart antigen was positive in all 105 subjects included in this study. The proportions of NB1-positive neutrophils among NB1-positive individuals were variable with a mean value of 72.0 +/- 20.2% (range, 27-100%). Differences in the frequency of the NA1 antigen have been reported between Asian and Caucasian populations. Our data support this variation. In addition, it was found that the frequency of the NA1 antigen in Koreans is significantly lower than in Japanese and Chinese populations (p < 0.05).

Journal Article↗

Stability, blood partition, and pharmacokinetics of a new reversible proton pump inhibitor, YJA-20379-1.

The pharmacokinetics of YJA-20379-1 were evaluated after intravenous (i.v.) administration to rats (10-50 mg/kg) and rabbits (10-50 mg/kg), and oral administration to rats (200 and 500 mg/kg). The stability and blood partition between plasma and blood cells were also investigated. After i.v. administration of YJA-20379-1, 10-50 mg/kg, to rats, the pharmacokinetic parameters of YJA-20379-1 were dose-independent, however, they were dose-dependent in rabbits. After oral administration of YJA-20379-1 to rats, the AUC of YJA-20379-1 seemed to increase with increasing doses (73.4 +/- 28.5 and 130 +/- 100 micrograms min/ml for 200 and 500 mg/kg, respectively). The extent of absorption after oral administration (F) was 6.47 and 4.74% for 200 and 500 mg/kg, respectively. The low F values were not due to incomplete absorption and could be due to extensive first-pass metabolism. YJA-20379-1 was unstable in pH solutions of 2-5, 12, and 13, very unstable in pH solutions of 1 and 14, however, stable in pH solutions of 6-11. YJA-20379-1 reached equilibrium rapidly between plasma and blood cells of rabbit blood at 1-5 micrograms/ml, an the mean blood cells/plasma concentration ratio was 5.24 +/- 1.21.

Administration, Oral↗

The largest isoform of platelet membrane glycoprotein Ib alpha is commonly distributed in eastern Asian populations.

Platelet membrane glycoprotein Ib alpha has at least two polymorphisms which affect phenotype. One is the dimorphism at codon 145, and the other is a molecular weight polymorphism due to variable numbers of tandem repeats (TR) in the macroglycopeptide region. These two polymorphisms are in linkage disequilibrium. The frequencies of these polymorphisms differ considerably depending on race, and the largest variant with four TR is almost exclusively present in the Japanese population. We examined the genotypes of HPA-2 and TR polymorphism in three different races from Eastern Asia; the Japanese (n = 103), Korean (n = 101) and Chinese population (n = 177). The gene frequency of HPA-2 differed significantly among these three populations. Among HPA-2b-positive individuals, the A isoform with four TR and B with three TR were present in all three populations and A dominated over B. Individuals homozygous for the A isoform were found in both Japanese and Korean populations. These findings indicate that the largest haplotype is common in the Eastern Asian region.

Antigens, Human Platelet↗

Spinal cord compression in renal osteodystrophy.

A patient undergoing regular haemodialysis for chronic renal insufficiency developed neck pain followed by progressive spinal cord compression due to subluxation at the level C3-4. Decompression, laminectomy and osteosynthesis led to an almost complete recovery. A review of all the histological specimens suggested that hyperparathyroidism and not amyloidosis caused the vertebral destruction.

Chronic Kidney Disease-Mineral and Bone Disorder↗

Histological study of the circulatory system of human dental pulp from individuals under local anesthesia and electro-acupuncture.

A transmission electron microscopic (TEM) study was conducted on dental pulp obtained from patients under acupuncture or infiltration local analgesia. It was difficult to differentiate lymphatic circulation in the dental pulp that received infiltration anesthesia, because the vessels were constricted, congested, and showed stasis and thrombosis. On the other hand, the dental pulp that received acupuncture showed normal arterioles, capillaries, and venules, as well as some lymph capillaries and small efferent lymphatic vessels that measured about 8 microns and 100 microns in diameter, respectively. The lymphatic endothelial walls had many intercellular gaps, an imperfect basal lamina, and a few discontinuous pericytes. Between the openings in the lymphatic vessels, there were bundles of junctional filaments extending towards the dental pulp connective tissue. Therefore, the lymphatic system, which contains mainly B-3-alpha capillaries, is a leaky tissue for regulating fluid in the dental pulp.

Acupuncture Analgesia↗

Pharmacokinetics and pharmacodynamics of bumetanide after intravenous and oral administration to spontaneously hypertensive rats and DOCA-salt induced hypertensive rats.

The pharmacokinetics and pharmacodynamics of bumetanide were investigated after intravenous (i.v.) administration, 10 mg kg-1, and oral administration, 20 mg kg-1, to spontaneously hypertensive rats (SHRs) and deoxycorticosterone acetate-salt induced hypertensive rats (DOCA-salt rats). After i.v. administration, the pharmacokinetic and pharmacodynamic parameters of bumetanide did not vary significantly between SHRs and the control Wistar rats. Similar results were also shown between DOCA-salt rats and the control Sprague-Dawley (SD) rats. After oral administration, the AUC0-12 h decreased significantly (186 versus 335 micrograms min ml-1) in SHRs and this resulted in decreased F(15.4 versus 23.6 and 2.78 versus 5.76% using two equations) in SHRs when compared with the control Wistar rats, although none of the other pharmacokinetic parameters varied significantly between SHRs and Wistar rats. This effect seemed to be due to the decreased enterohepatic recirculation of bumetanide in SHRs: the amounts of both bumetanide and its glucuronide product, which are capable of enterohepatic recirculation, excreted in 8 h bile juice decreased significantly in SHRs (11.3 versus 37.4 micrograms as expressed in terms of bumetanide) when compared with Wistar rats. The pharmacodynamic parameters did not vary significantly between SHRs and Wistar rats after oral administration of bumetanide. The pharmacokinetic and pharmacodynamic parameters of bumetanide did not vary significantly between DOCA-salt rats and SD rats after oral administration of the drug. The liver weights compared to body weight increased significantly in SHRs when compared with Wistar rats and the corresponding values for the kidney increased significantly in DOCA-salt rats when compared with SD rats.

Administration, Oral↗

Studies on isosporosis in dogs. I: Isolation and sporulation of Isospora ohioensis.

Based on the morphologic characteristics of oocysts of the genus Isospora, we have demonstrated that I. ohioensis is a relatively common Isospora species in dogs which are resident in Chonbuk province, Korea. The prepatent period of I. ohioensis was four days. The size of the unsporulated oocysts in fresh stool specimens was 22.9 x 19.8 microns (R = 1.16). The size of the contracted sporonts was 17.4 x 16.3 microns (R = 1.06). By 96 hours, sporulation is complete and the ratio of length/width was constant relatively. And the sizes of oocysts and sporocysts were 22.8 x 20.5 microns (R = 1.11) and 15.0 x 10.8 microns (R = 1.39), respectively. At this time it is most reliable for the measurements of oocyst sizes of I. ohioensis to provide with the identifiable clues against the others. It is therefore recommended that the clinical fecal specimens suspected of isosporosis should first be incubated and aerated for 96 hours before a definitive parasitological diagnosis can be reached. These and other observations contribute to the understanding of the biological characteristics and laboratory and clinical diagnosis of isosporosis.

Animals↗

Prevalence of Helicobacter pylori infection in patients with peptic ulcer diseases and non-ulcer dyspepsia.

BACKGROUND: Helicobacter pylori is known to be a cause of active chronic gastritis and has been proposed as an etiologic factor in the development of peptic ulcer disease, but controversy continues regarding the pathogenic importance and mechanism. We examined the prevalence of H. pylori infection in patients with peptic ulcers and non-ulcer dyspepsia. METHOD: 749 patients (373 with duodenal ulcer, 303 with gastric ulcer, 73 with non-ulcer dyspepsia) were included. Endoscopic mucosal biopsies were done at antrum, duodenum, and, if present, ulcer margin. The specimens were tested by Gram staining, Giemsa staining, culture, urease testing for identification of H. pylori. Antibody to H. pylori was examined in 83 patient of these patients by ELISA, and the result was compared with the results of bacteriologic studies. RESULT: Prevalence of H. pylori in antral mucosa was higher in patients with duodenal ulcers (81.5%) than in patients with gastric ulcer and non-ulcer dyspepsia (56% and 52.8%) (P < 0.05). Also in the duodenal mucosa of non-ulcer sites, and the ulcer margin of patients with duodenal ulcers, the detection rates (12% and 40.7%) were higher than those in the duodenal mucosa of patients with gastric ulcer and non-ulcer dyspepsia (7% and 8%)(p < 0.005). Antibody to H. pylori was detected in all patients with duodenal and gastric ulcers and non-ulcer dyspepsia who were tested for antibody. In contrast, the detection rates of antibody in adult control and child control were 33.3% and 27%. Among patients with antibody to H. pylori, H. pylori was detected in 85.7% of patients with duodenal ulcer, 62.5% of patients with gastric ulcers and 22.2% of patients with non-ulcer dyspepsia (p < 0.05). CONCLUSION: These data suggest that H. pylori is a possible pathogen for duodenal ulcer by duodenal colonization probably via gastric metaplasia. Also the past or present infection of H. pylori in antral mucosa may play a role at least partially in generation of upper gastrointestinal symptoms.

Adolescent↗

The molecular structure of the Corynebacterium glutamicum threonine synthase gene.

The minimal region encoding the Corynebacterium glutamicum threonine synthase structural gene and its promoter was mapped by deletion analysis and complementation of the C. glutamicum thrC allele to a 1.6 kb region of the recombinant plasmid pFS80. The nucleotide sequence of this and flanking DNA was determined. The transcription and translation start points were identified by S1 mapping analysis and amino-terminal protein sequencing, respectively. The thrC gene encodes a 54481-Dalton polypeptide product. Translation of the thrC mRNA initiates only six nucleotides downstream from transcription. The length of the mRNA transcript is consistent with a single gene transcription unit. The C. glutamicum thrC gene is expressed independently of the other threonine-specific genes hom and thrB.

Alleles↗