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Biomedical subjects

N D Kim

Publications and source records attributed to N D Kim.

At least 91 records · Page 5Linked to original sources
PubMed1994

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

The pharmacokinetics and pharmacodynamics of furosemide were investigated after intravenous (i.v.), 1 mg/100 g body weight, and oral administration, 2 mg per 100 g body weight, to spontaneously hypertensive rats (SHRs) and deoxycorticosterone acetate-salt-induced hypertensive rats (DOCA-salt rats). After i.v. administration, the 8 h urinary excretion of furosemide/g kidney (397 versus 572 micrograms) was significantly lower and the non-renal clearance (5.78 versus 3.94 ml min-1 kg-1) was significantly faster in SHRs of 16 weeks of age than in age-matched control Wistar rats. This suggested that the non-renal metabolism of furosemide could be faster in SHRs of 16 weeks of age than in age-matched control Wistar rats, and this could be supported by the significantly greater amount of 4-chloro-5-sulphamoyl anthranilic acid, a metabolite of furosemide, excreted in 8 h urine as expressed in terms of furosemide (11.1 versus 4.79% of the i.v. dose) in SHRs. It could also be supported at least in part by a study of liver homogenate; the amount of furosemide remaining per gram of liver after 30 min incubation of 50 micrograms of furosemide with the 9000g supernatant fraction of liver homogenate was significantly smaller (40.4 versus 43.7 micrograms) in SHRs of 16 weeks of age than in age-matched Wistar rats. The greater metabolic activity of furosemide in liver may also be supported by the result that the amount of hepatic cytochrome P-450 (0.7013 versus 0.5186 nmol/mg protein) and the weights of liver (3.52 versus 2.93% of body weight) were significantly greater in SHRs of 16 weeks of age than in age-matched Wistar rats. After i.v. administration of furosemide, the 8 h urine output (9.93 versus 16.5 ml) and 8 h urinary excretion of sodium (1.21 versus 2.05 mmol) and chloride (1.37 versus 2.17 mmol) per gram of kidney in SHRs of 16 weeks of age were lower than those in age-matched Wistar rats, this could be due to the significantly smaller amount of furosemide excreted in 8 h urine per gram of kidney. After oral administration, the pharmacokinetics and pharmacodynamics of furosemide were not significantly different between SHRs and the control Wistar rats of 16 weeks of age. After i.v. and oral administration of furosemide, there were no significant differences in the pharmacokinetics and pharmacodynamics between DOCA-salt rats and control SD rats of 16 weeks of age except for the significantly lower urinary excretion of potassium per gram of kidney in DOCA-salt rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1994

Arterial and venous blood sampling in pharmacokinetic studies: azosemide in rabbits.

The pharmacokinetics of azosemide were evaluated simultaneously using both arterial and venous plasma data in six rabbits after a rapid 5 s intravenous bolus dosing. Initial arterial to venous ratios at 5 s after injection were the highest with values of 81.1, 67.3, 58.7, 530, 2660, and 10.5 for rabbits 1-6, respectively. Both curves decayed, paralleling each other at the terminal phase, with the venous levels higher than the arterial levels by 15.3, 31.9, 34.1, 40.7, 30.5, and 16.5% for rabbits 1-6, respectively. An exponential term with a negative coefficient was used to account for the short and steep rising phase of venous plasma levels after injection. Detailed analysis showed significant differences in various pharmacokinetic parameters, such as initial volume of distribution, apparent volume of distribution at steady state, and mean residence time based on arterial or venous data. A plot of 1/Q (urine flow rate) versus 1/CLR (renal clearance) of azosemide yielded a straight line in six rabbits, indicating that the CLR of azosemide is urine flow dependent in rabbits.

Animals↗
PubMed1994

Pharmacokinetics and pharmacodynamics of bumetanide after intravenous and oral administration to rats: absorption from various GI segments.

Bumetanide, 2, 8, and 20 mg/kg, was administered both intravenously and orally to determine the pharmacokinetics and pharmacodynamics of bumetanide in rats (n = 10-12). The absorption of bumetanide from various segments of GI tract and the reasons for the appearance of multiple peaks in plasma concentrations of bumetanide after oral administration were also investigated. After i.v. dose, the pharmacokinetic parameters of bumetanide, such as t1/2 (21.4, 53.8 vs. 127 min), CL (35.8, 19.1 vs. 13.4 ml/min per kg), CLNR (35.2, 17.8 vs. 12.6 ml/min per kg) and VSS (392, 250 vs. 274 ml/kg) were dose-dependent at the dose range studied. It may be due to the saturable metabolism of bumetanide in rats. After i.v. dose, 8-hr urine output per 100 g body weight increased significantly with increasing doses and it could be due to significantly increased amounts of bumetanide excreted in 8-hr urine with increasing doses. The total amount of sodium and chloride excreted in 8-hr urine per 100 g body weight also increased significantly after i.v. dose of 8 mg/kg, however, the corresponding values for potassium were dose-independent. After oral administration, the percentages of the dose excreted in 24-hr urine as unchanged bumetanide were dose-independent. Bumetanide was absorbed from all regions of GI tract studied and approximately 43.7, 50.0, and 38.4% of the orally administered dose were absorbed between 1 and 24 hr after oral doses of 2, 8, and 20 mg/kg, respectively. Therefore, the appearance of multiple peaks after oral administration could be mainly due to the gastric emptying patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Seasonal variations in the concentrations of cadmium, copper, lead and zinc in leaves of the horse chesnut (Aesculus hippocastanum L.).

The concentrations of cadmium, copper, lead and zinc have been measured in the leaves of a deciduous tree the horse chestnut (Aesculus hippocastanum L.) over the period of their lifetime (7 months). The average concentrations for the total sample based on ash weight are: (microg g(-1)) cadmium, 0.197; copper, 129; lead, 294; and zinc, 299. The temporal trends in the concentrations of the metals can be related to their dominant source. Copper and zinc concentrations are highest in the new leaves and decrease with time, suggesting the main source of the elements are uptake from the soil. The decrease occurs partly because of dilution by leaf material as it increases over the growing period. In the case of zinc, however, aerial deposits appear to be also a significant source. Lead concentrations, on the other hand, show an increase with time, which can be related to increasing deposits from aerosol lead arising from the combustion of petrol lead. The increase is enough to offset the dilution effect. For cadmium there is no significant trend, but the tendency is a decrease with time. It is not possible, however, to distinguish between soil uptake and aerial deposit as both are small compared with increase in leaf material.

Journal Article↗
PubMed1994

Ginsenosides evoke endothelium-dependent vascular relaxation in rat aorta.

1. Ginsenoside (10-100 mg/kg, i.v.) lowered blood pressure in a dose-dependent manner in rats. 2. Ginsenoside (10(-5)-3 x 10(-4) g/ml) relaxed the aorta after contractions were induced by 10(-6) M phenylephrine in the aorta with endothelium but not in that without endothelium. 3. The relaxation induced by ginsenoside was attenuated by 3 x 10(-7) M methylene blue (MB) and 10(-4) M NG-monomethyl-L-arginine (L-NMMA) but not inhibited by 10(-5) M indomethacin. 4. Ginsenoside (10(-4) g/ml for 2 min) increased the accumulation of cGMP in rings with endothelium. L-NMMA and MB inhibited the accumulation of cGMP induced by ginsenoside. 5. These data suggest that vascular relaxations induced by ginsenoside are mediated by release of endothelium-drived nitric oxide which enhances the accumulation of cGMP.

Animals↗
PubMed1994

Piperine effects on the expression of P4502E1, P4502B and P4501A in rat.

1. Treatment of rat with piperine (PIP) (1.4 mmol/kg, 3 days ip injections) resulted in an approximate two-fold increase in total liver microsomal P450 content relative to that in uninduced animals. 2. 4-Nitrophenol and aniline hyroxylase activities in the hepatic microsomes prepared from rat treated with PIP decreased by 30 and 28% respectively as compared with control. Immunoblot analyses also revealed decreased P4502E1 levels in hepatic microsomes from PIP-treated animals. 3. In contrast with P4502E1 suppression, hepatic 2B1 and 2B2 levels were significantly increased in PIP-induced animals, as evidence by both metabolic activity and immunoblot analysis of the liver microsomal fractions. The rate of hexobarbital hydroxylase activity in microsomes from PIP-treated animals was markedly elevated and was inhibited by approximately 62% in the presence of monoclonal anti-P4502B IgG. Immunoblot analyses demonstrated that P4502B1 and 2B2 levels in hepatic microsomes from PIP-treated animals were comparable with those from phenobarbital-treated animals. 4. 7-Ethoxycoumarin deethylase activity was elevated approximately two-fold in PIP-induced animals and was 17% of that derived from 3-methylcholanthrene-induced animals. 7-ethoxycoumarin deethylase activity in PIP-induced hepatic microsomes was inhibited 63% in the presence of monoclonal anti-P4501A antibody. Immunoblot analysis confirmed the increase in P4501A levels by PIP, which was 15% of that in hepatic microsomes from 3-methylcholanthrene-induced animals. 5. PIP treatment failed to affect microsomal epoxide hydrolase (mEH) and glutathione S-transferases (GST) expression, as indicated by immunoblot analyses using polyclonal antibodies toward mEH and GST subunits Ya, Yb1, Yb2 and Yc. 6. These results demonstrate that PIP treatment suppressed P4502E1 expression and enhanced 2B and 1A expression, whereas this agent failed to affect hepatic mEH and GST expression.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1993

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↗
PubMed1993

Characterization of rat mammary epithelial cell subpopulations by peanut lectin and anti-Thy-1.1 antibody and study of flow-sorted cells in vivo.

A cell separation method was developed for studies of the growth kinetics of rat mammary epithelial cell (RMEC) subpopulations in grafts and in culture in vitro. By flow cytometry of RMEC stained with fluorescein isothiocyanate-peanut agglutinin and phycoerythrin-anti-Thy-1.1 monoclonal antibody, we could distinguish four cell subpopulations from primary cultures of 7- to 8-week-old F344 female rat mammary glands: both negative (B-), PNA+, Thy-1.1+, and both positive (B+). We studied the growth patterns of these subpopulations in vitro for 1 to 14 days in complete hormone medium (CHM) containing 10% fetal bovine serum and prolactin, 17 beta-estradiol, cortisol, progesterone, and insulin. The fractions of PNA+ and B- cells steadily decreased with time in culture. The fraction of Thy-1.1+ cells steadily increased with time in culture. There were small numbers of B+ cells. We grafted RMEC in hyperprolactinemic recipient rats. The mean numbers of transplanted cells required to produce at least one alveolar unit in 50% of the graft sites (AD50 values) are inversely related to the clonogenic fractions. AD50s of RMEC are as follows: unsorted mammary cells cultured in CHM for 1 to 4 days, approximately 220; unsorted cells cultured in CHM for 7 days, approximately 550; sorted PNA+ RMEC from outgrowths of 3-day cultures, approximately 82; B+, approximately 350; B-, approximately 545; Thy-1.1+, approximately 9372. We conclude that the PNA+ cell subpopulation includes most of the clonogenic cells. Thy-1.1+ cells appear to be terminally differentiated; they are likely to be myoepithelial cells.

Animals↗
PubMed1993

Primary culture of flow cytometry-sorted rat mammary epithelial cell (RMEC) subpopulations in a reconstituted basement membrane, Matrigel.

We studied the growth of rat mammary epithelial cell (RMEC) subpopulations cultured in Matrigel. Mammary glands were removed, minced, and enzymatically dispersed. Mammary organoids (ductal and endbud fragments) were collected, enzymatically monodispersed, filtered, and labeled with fluorescein isothiocyanate-peanut agglutinin (PNA) and phycoerythrin-anti-Thy-1.1 monoclonal antibody. By flow cytometry, we separated four RMEC subpopulations: cells negative to both reagents (B-), PNA-positive cells (PNA+), Thy-1.1-positive cells (Thy-1.1+), and cells positive to both reagents (B+). The ultrastructural characteristics of sorted cells were examined by transmission electron microscopy. Thy-1.1+ cells appeared to be myoepithelial cells with actin filaments. PNA+, B-, and B+ cells were morphologically similar. Sorted RMEC subpopulations, unsorted mixed cells, and undispersed organoids were seeded in Matrigel and cultured in either a complete hormone medium (CHM) with 10% fetal bovine serum, progesterone, estradiol, hydrocortisone, insulin, and prolactin or a serum-free medium containing EGF, insulin, hydrocortisone, and human transferrin. Several types of colonies were observed: stellate, ductal, webbed, squamous, and lobuloductal colonies. At the immunocytochemical and electron micrograph levels, casein proteins were predominantly localized near the apical surfaces of the cells or in the lumina of ductal or lobuloductal colonies. Laminin and collagen IV were detected only in the basal lamina of ductal structures cultured in CHM. RMEC and subpopulations from immature virgin rats developed the capacity to synthesize and secrete lipid and casein when grown in Matrigel in serum medium or under defined serum-free conditions.

Animals↗
PubMed1993

Phenytoin induction of cytochrome P4502B in mice: effects on hexobarbital hydroxylase activity.

1. Treatment of ICR and C57BL/6 mice with phenytoin (50 mg/kg, i.p., 3 days) resulted in approximately 33 and 43% increases in hepatic cytochrome P450 levels relative to uninduced microsomes, respectively. Phenytoin treatment caused a 63% decrease in hexobarbital sleeping time in ICR mice (19 versus 52 min). 2. Both Western immunoblot analysis and solid phase radioimmunoassay using monoclonal anti-rat P4502B antibody showed that P4502B was increased significantly in phenytoin-induced mouse microsomes compared with uninduced mice. P4502B9 was the predominantly induced form whereas 2B10 was elevated marginally. Phenytoin was as efficacious as phenobarbital in increasing P4502B. 3. Phenytoin treatment resulted in an approximately 8-fold increase in hexobarbital hydroxylase activity whereas phenobarbital treatment caused an approximately 13-fold increase. Addition of anti-P4502B antibody produced complete inhibition of hexobarbital oxidation in phenytoin-induced microsomes, indicating that raised P4502B in phenytoin-induced microsomes is associated with the increased hexobarbital hydroxylase activity. 4. Phenytoin failed to increase P4501A in either C57BL/6 or ICR mice, as assessed by both immunoblot analysis and metabolic activities. Although both aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase activities were raised approximately two-fold following phenytoin treatment, the metabolic activities were not inhibited by anti-P4501A antibody. 5. These results provide evidence that phenytoin induces P4502B in mice with pronounced increase in hexobarbital hydroxylase activity, and fails to induce P4501A in either C57BL/6 or ICR mice.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1991

Factors influencing the protein binding of vancomycin.

Various factors influencing the protein binding of vancomycin were examined using equilibrium dialysis method. Four per cent human serum albumin (HSA) and/or 0.08 per cent alpha-1-acid glycoprotein (AAG), dissolved in isotonic phosphate buffer, were dialyzed against isotonic phosphate buffer of pH 7.4 using Spectrapor 2 membrane. The protein binding of vancomycin to 0.08 per cent AAG was dependent on vancomycin concentrations; the values ranged from 21.1 per cent at the vancomycin concentration of 20 micrograms ml-1 to 5.30 per cent at 2400 micrograms ml-1. However, binding to 4 per cent HSA was relatively constant, 8.79 +/- 2.43 per cent over a vancomycin concentration range of 20-2400 micrograms ml-1. The values to 4 per cent HSA alone and 0.08 per cent AAG alone did not predict the greater binding of vancomycin in the presence of both proteins, especially at higher concentrations of vancomycin; the values to 4 per cent HSA with 0.08 per cent AAG were constant, 26.3 +/- 3.74 per cent, at the vancomycin concentration range of 20-2400 micrograms ml-1. This suggested an interaction between the proteins, which resulted in enhanced binding of vancomycin. The protein binding of vancomycin to 4 per cent HSA with 0.08 per cent AAG was not influenced by the different incubation temperatures (4 degrees, 22 degrees, and 37 degrees), quantities of heparin (up to 40 units ml-1) or AAG (up to 0.16 per cent), or buffers (isotonic phosphate buffer of pH 7.4, phosphate buffer of pH 7.4 and 0.9 per cent NaCl solution) at the vancomycin concentration of 80 micrograms ml-1. Vancomycin was found to be stable in human serum albumin or in isotonic phosphate buffer of pH 7.4.

Blood Proteins↗
PubMed1991

Trace elements in street and house dusts: sources and speciation.

The sources and speciation of trace elements in street and house dusts are reviewed. Soil is a major component of both dusts, but a number of elements are enriched in both materials. These include Pb, Zn, Cu, Cd, As, Sb, Cr, Ca, Na, Au, Cl and Br. They arise from a number of contributing and polluting sources. In the case of house dust, some elements, such as Cu, Co, As, Sb, Zn, Cd, Au, Cl, C and Pb, are produced in the house. There are a number of problems associated with the determination of the speciation of trace elements in dusts. These include the low concentrations of many of the elements, and the interpretation of the results from selective sequential extractions. The mobility and potential availability of the trace elements from dust lies in the order Cd greater than Zn, Pb greater than Mn, Cu greater Fe.

Air Pollutants↗
PubMed1991

Repair of potentially lethal damage in rat mammary clonogens following irradiation in organoid culture.

In the course of investigations of radiogenic neoplasia in mammary cells in vivo, post-irradiation repair of potentially lethal damage (PLDR) was previously observed in mammary epithelial clonogens when they were irradiated and left in their tissue environment for 4-24 h after exposure. This type of PLDR increases the initial shoulder of the survival curve without significantly affecting its terminal slope. It has since been described in similarly treated thyroid and hepatic clonogens, and significantly exceeds that generally seen in most mammalian cells in culture. In this study, a ten-fold increase in the concentration of mammary clonogens which could be assayed was achieved by the isolation and short term culture (2-4 days) of mammary organoids (ductal and end-bud fragments). Assays of clonogen concentrations were carried out with cell suspensions prepared immediately following irradiation of 4-day organoid cultures or 24 h after irradiation of such organoid cultures. A near four-fold increase in clonogen survival was observed with the delay in assay after irradiation; this is comparable to the PLDR seen in mammary clonogens irradiated and left in situ for 4-24 h after exposure.

Animals↗
PubMed1991

The basal and stimulated release of EDRF inhibits the contractions evoked by endothelin-1 and endothelin-3 in aortae of normotensive and spontaneously hypertensive rats.

Endothelin-1 (ET-1) evoked concentration-dependent contractions that were slow in onset and sustained in aortae from both normotensive (Wistar and Wistar-Kyoto rats) and spontaneously hypertensive rats. The presence of a functional endothelium reduced the contractions evoked by low concentrations of ET-1 in the aortae from normotensive rats and shifted the concentration-contraction curves to the right in the hypertensive rat. NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide (NO) synthase, inhibited the influence of the endothelium. Endothelin-3 (ET-3) evoked contractions in aortae from both normotensive and hypertensive rats at concentrations greater than 3 x 10(-8) M, which were reduced by the presence of a functional endothelium. ET-1 and ET-3 evoked concentration- and endothelium-dependent relaxations in aortae contracted submaximally with phenylephrine, from both types of rats. The relaxations were reversed by methylene blue, an inhibitor of soluble guanylate cyclase, and nitro-L-arginine, a competitive inhibitor of NO synthase. These observations demonstrate that the endothelium modulates the contractile response evoked by ET-1 and ET-3 in the aorta of the rat. This inhibition is more pronounced in aortas from hypertensive compared to normotensive rats and is mediated, at least in part, by an enhanced production of endothelium-derived NO.

Animals↗
PubMed1989

Intussusception into the enteroanastomosis after Billroth II gastric resection; diagnosed by gastroscopy.

A case of retrograde intussusception (acute type) of efferent limb into Braun side-to-side jejuno-jejunal anastomosis is presented. Intussusception, though infrequent, is well recognized complication after gastric surgery. Patient was 50 year old man who was admitted with epigastric pain and abdominal mass for 6 hours. Patient had a history of total gastrectomy 2 years before admission due to stage II gastric cancer. Seven hours after admission, hematemesis developed. Emergency fiberopticgastroscopy revealed type 4 jejunogastric intussusception. Segmental resection with end-to-end reanastomosis was performed.

Humans↗
PubMed1975

Myocardial function and subcellular calcium metabolism in chronic potassium deficiency.

Myocardial contractility was examined in whole, perfused hearts and in right ventricle papillary muscles of chronic K-depleted cats. Mitochondrial and sarcoplasmic reticulum (SR) calcium binding and concentration were estimated in the perfused hearts after exposure to 45Ca. In vitro SR Ca uptake was measured by the Millipore technique. Myocardial contractility was depressed in chronic potassium depletion and the degree of depression was related to the reduced SR Ca binding. These experiments suggest altered subcellular Ca metabolism as being a mechanism of depressed myocardial contractility in chronic K depletion.

Animals↗