• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.245-255
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• 2012

Amyloid-${\beta}$ peptide ($A{\beta}$) is still best known as a molecule to cause Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. Thus, strategies on developing AD drugs have been focused on the reduction of $A{\beta}$ in the brain. Since accumulation of $A{\beta}$ depends on the rate of its synthesis and clearance, the metabolic pathway of $A{\beta}$ in the brain and the whole body should be carefully explored for AD research. Although the synthetic pathway of $A{\beta}$ is equally important, we summarize primarily the clearance pathway in this paper because the former has been extensively reviewed in previous studies. The clearance of $A{\beta}$ from the brain is accomplished by several mechanisms which include non-enzymatic and enzymatic pathways. Nonenzymatic pathway includes interstitial fluid drainage, uptake by microglial phagocytosis, and transport across the blood vessel walls into the circulation. Multiple $A{\beta}$-degrading enzymes (ADE) implicated in the clearance process have been identified, which include neprilysin, insulin-degrading enzyme, matrix metalloproteinase-9, glutamate carboxypeptidase II and others. A series of studies on $A{\beta}$ clearance mechanism provide new insight into the pathogenesis of AD at the molecular level and suggest a new target for the development of novel therapeutics.

• The Korean Journal of Nuclear Medicine
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• v.23 no.1
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• pp.49-54
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• 1989

Many previously described nuclear medicine procedures to assess glomerular filtration rate (GFR) required numerous blood samples obtained over a period of several hours to determine plasma concentrations of the injected radiopharmaceuticals. And other indirect methods of determining renal clearance have some problems due to individual variations in volume of distribution of the radionuclides used. Rescently reported Jackson's method have the great advantages that is a direct measurement method requiring less than 40 min of imaging time and single blood sampling. And it correctly accounts for individual variations in volume of distribution of the radiopharmaceuticals and can be done with routine renal scintrgraphy. We measured $^{99m}Tc-DTPA$ renal clearance with Jackson's method during the routine $^{99m}Tc-DTPA$ renal scintigraphy in 63 patients admitted to department of internal medicine in SNUH. In 23 cases among 63 patients creatinine clearence was accounted simultaneously. The range of $Cl_{DPDA}$ was from 19.9 ml/min to 170 ml/min and the correlation of $Cl_{DPDA}$ and creatinine clearance was discribed by Y=16.2570+0.7852 X($X=Cl_{DTPA}$ Y=creatinine clearance). And the correlation coefficient r was 0.88. We concluded that $^{99m}Tc-DTPA$ renal clearance measurement with Jackson's method was clinically useful to account GFR that can be done with routine $^{99m}Tc-DTPA$ renal scintigraphy simultaneously.

• YAKHAK HOEJI
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• v.30 no.5
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• pp.208-213
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• 1986

Rifampicin suspension was administered orally at a does of 34mg/kg to six rabbits after 5, 10 and 20mg/kg pretreatment of isoniazid twice daily for 9 days. The blood level of rifampicin was decreased significantly by isoniazid 10mg/kg 20mg/kg pretraetment. The renal clearance(CLr) of rifampicin was increased by isoniazid 20mg/kg and the biliary clearance(CLb) was incresed by isoniazid 10mg/kg and 20mg/kg pretreatmetn. Elimination rate constant(K) and time to reach maximum concentration(tmax) were increased by isoniazicl pretreatment. But half-life and maximum concentration(C max) were decreased. Relative bioavailability was decreased significantly by isoniazid 10mg/kg and 20mg/kg pretreatment.

• Journal of Pharmaceutical Investigation
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• v.8 no.3
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• pp.1-10
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• 1978

The purpose of this paper was to investigate the bioavailability of sulfadimethoxine in pathological rats and rabbits pretreated with carbon tetrachloride and mercuric chloride. The results are as follows: The absorption of sulfadimethoxine was decreased in rats damaged liver and kidney as compared with that of normal rats. Especially, absorption of sulfadimethoxine in rats damaged liver was more decreased than that of rats damaged kidney. Blood level of sulfadimethoxine administered orally was mostly decreased significantly in rabbits damaged kidney and liver, and in rabbits severely damaged kidney the blood level of sulfadimethoxine was not significant at 4 to 6 hours. Urinary clearance of sulfadimethoxine in rabbits severely damaged kidney was inhibited at 5 to 6 hours. but in rabbit damaged liver. Hepatic clearance of sulfadimethoxine was accelerated in rabbits damaged kidney but in rabbits damaged liver. Protein binding percentage of sulfadimethoxine was not affected by the various concentration of carbon tetrachloride and mercuric chloride respectively.

• Journal of Pharmaceutical Investigation
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• v.15 no.3
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• pp.113-120
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• 1985

The pharmacokinetics of lithium carbonate were investigated in rabbits with folate-induced renal failure. The blood level, the area under the blood concentration curve (AUC) and the biological half·life were increased significantly, and the urinary excretion was decreased significantly compared with those of normal rabbits. Correlation of serum creatinine concentration and AUC, biological half-life, and correlation of creatinine clearance and renal clearance of lithium carbonate have linear relationship respectively. In short, dosage regimen of lithium carbonate is considered to be adjusted in the dose size and the dosing interval by degree of experimental renal failure.

• Journal of Pharmaceutical Investigation
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• v.9 no.2
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• pp.1-10
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• 1979

The purpose of this paper was to investigate the bioavailability of oxytetracycline in pathological rats and rabbits pretreated with carbon tetrachloride and mercuric chloride. The results are as follows: The blood level of oxytetracycline administered orally was mostly decreased significantly in rabbits damaged kidney and liver, and in rabbits severely damaged kidney, the blood level of oxytetracycline was not significant at 4 to 6 hours. Urinary clearance of oxytetracycline in rabbits severely damaged kidney was inhibited at 5 to 6 hours but in rabbits damaged liver. Hepatic clearance of oxytetracycline was accelerated in rabbits damaged kidney but in rabbits damaged liver. AUC of oxytetracycline orally administered in rabbits damaged liver and kidney was largely decreased. The absorption of oxytetracycline was decreased in rats damaged liver and kidney as compared with that of normal rats. Especially, absorption of oxytetracycline in rats damaged liver was more decreased than that of rats damaged kidney. The absorption of oxytetracycline was inhibited by combinated administration of carbon tetrachloride and mercuric chloride.

• YAKHAK HOEJI
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• v.28 no.3
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• pp.149-160
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• 1984

In order to certify the diuretic mechanism of dopamine, this study was performed in dog. The following results were obtained. Dopamine, when given intravenously, produced diuresis, and increased glomerular filtration rate (GFR), renal plasma flow (RPF), and amount of sodium excreted in urine. When infused directly into a renal artery, dopamine elicited a marked diuresis confined only to the infused side, with concomitant rises in osmolar clearance and sodium excretion as well as a slight increase in free water clearance. Simultaneously total renal plasma flow and medullary plasma flow increased markedly with a increase of glomerular filtration rate and renal plasma flow. Medullary concentration gradient of sodium also markedly lowered in the infused kidney. These changes were not observed during mannitol diuresis and renal action of dopamine were not apparent in dog pretreated with haloperidol. From the above experimental results, it is thought that dopamine, when given into a vien or infused directly into a renal artery, induces diuresis, and the mechanism of its action is due to dual actions which are hemodynamic effect along with glomerular filtraction rate, and the increased response in the medullary blood flow.

• Toxicological Research
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• v.14 no.4
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• pp.557-562
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• 1998

Allyl alcohol is metabolized in the liver through two steps, first to reactive acrolein by alcohol dehydrogenase (ADH), subsequently to acrylic acid by aldehyde dehydrogenase (ALDH). Since ethanol could compete the same enzymes to be metabolized in the liver, we have determined the plasma concentrations of allyl alcohol and ethanol followed by combined treatment. Pretreatment of rats with 2g/kg ethanol followed by ip administration of 40mg/kg allyl alcohol increased the lethality significantly. Determination of in vivo blood concentrations revealed that ethanol pretreatment caused the apparent decrease in allyl alcohol clearance, whereas acetaldehyde level in blood increased significantly by allyl alcohol treatment, as determined by head space GC analysis. Treatment of 4-methylpyrazole, an inhibitor of ADH, delayed allyl alcohol elimination significantly and reduced its lethality. Collectively, these findings suggested that reduction of allyl alcohol clearance in the presence oj ethanol was mediated through ADH competitive inhibition.

• YAKHAK HOEJI
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• v.35 no.1
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• pp.38-44
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• 1991

It has been reported that the pharmacokinetic behaviors of drugs which are mostly metabolized in the liver are significantly different in patients with renal failure. Theophylline(TP) is mainly metabolized in the liver (approximately 90%) and renal clearance of the drug is negligible (less than 10%). Therefore, we have investigated the changes in pharmacokinetics of theophylline in normal, G-ARF and U-ARF rats after an intravenous administration. The total body clearance of TP decreased approximately 40% in U-ARF rats. The reduced CL$_{T}$, value in U-ARF rats could be due to reduced hepatic intrinsic clearance by up to 40% since it has been published that plasma protein binding of TP and liver blood flow does not change in U-ARF rats.

• Journal of Ginseng Research
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• v.19 no.3
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• pp.225-230
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• 1995

The effect of long-term ginseng (Panax ginseng C.A. Meyer) administration on the clearance of carboxyhemoglobin (CO-Hb) and the property of blood gases was investigated in rats. Rats were received ginseng water extract (0.025% in drinking water) for 42 weeks starting at the age of 6 weeks. They were exposed to the diluted mainstream smoke generated from 15 filter cigarettes for 20 min in a round polycarbonate chamber (D37 cmXH13 cm). Under this condition, the mean CO-Hb content of control and the ginseng-treated rats immediately after the exposure was nearly the same as 13.8$\pm$2.9 f) and 13.9$\pm$1.6%, respectively. However, CO-Hb was more rapidly removed from blood in the ginseng treated rats than in untreatEd control with the laps of time, namely, its biological half life In the former was 36.9$\pm$1.5 min and in the latter was 56.9$\pm$13.2 min. Although long-term ginseng treatment did not affect the content of hemoglobin and blood pH of rats, it slightly increased blood oxygen content and its partial pressure value, and decreased levels of carbon dioxide and bicarbonate. These results suggest that long-term administration of rats with ginseng extract accelerate the elimination of CO from the blood. This effect seems to be related to the enhancement of oxygen consumption of the rat by a certain action of ginseng components as previously reported.