• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.222.2-223
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• 2003

Renal dipeptidase (RDPase, EC 3.4.13.19), an ectoenzyme of renal proximal tubules, is covalently bound to outer leaflet of lipid bilayer via glycosylphosphatidylinositol (GPI)-anchor. Chitin is a major component of the shells of crustacea such as crab, shrimp and crawfish. This study was conducted to examine the effect of chitosan on RDPase release from renal proximal tubules. Nitric oxide (NO), highly reactive free radical, inhibits the release of RDPase from porcine proximal tubules. (omitted)

• Archives of Pharmacal Research
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• 제22권4호
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• pp.367-371
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• 1999

Effects of several durgs on rabbit renal proximal tubules were examined for the applicability of renal dipeptidase (RDPase, EC 3. 4. 13. 11) release as a model system to study nephrotoxicity. The proximal tubule prepared by the method of Taub (1990) released RDPase spontaneously in the control experiment which was confirmed by Western blotting. RDPase was also released form cisplatin, lipopolysaccardie (LPS), and indomethacin-treated tubules. Gentamicin inhibited RDPase release in a concentration-dependent manner. This RDPase release system may not be a general model to screen nephrotoxicity but could be a useful source of RDPase purification in a simple and inexpensive way.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.319.2-319.2
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• 2002

Chitin is a major component of the shells of crustacea such as crab. shrimp and crawfish. Renal dipeptidase (RDPase. EC 3.4.13.19), an ectoenzyme of renal proximal tubules. is covalently bound to outer leaflet of lipid bilayer via glycosylphosphatidylinositol (GPI)-anchor. The biological role of RDPase was suggested as the hydrolysis of dipeptide into free-amino acids before renal reabsorption. The underlying biochemical mechanism of decreased RDPase release was suggested as nitric oxide (NO) production. (omitted)

• Animal cells and systems
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• 제7권4호
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• pp.309-315
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• 2003

Renal dipeptidase (RDPase, membrane dipeptidase, dehydropeptidase 1, EC 3.4.13.19) has been widely studied since it was first purified from porcine kidney brush border membrane. It was reported that RDPase activity in urine samples of acute and chronic renal failure patients decreases. Nitric oxide (NO) is a highly reactive free radical involved in a number of physiological and pathological processes. NO is able to act in a dual mode, leading either to induction of apoptosis or to blunted execution of programmed cell death. NO inhibited the RDPase release from porcine renal proximal tubules, which could be blocked by L-NAME. Chitosan, the linear polymer of D-glucosamine in $\beta$(1\longrightarrow4) linkage, not only reversed the decreased RDPase release by NO but also increased NO production in the proximal tubule cells. The stimulatory effect of NO on RDPase release from proximal tubules in the presence of chitosan must be different from the previously proposed mechanism of RDPase release via NO signaling pathway. Chitosan stimulated the RDPase release in the proximal tubules and increased RDPase activity to 220% and 250% at 0.1% and 1%, respectively. RDPase release was decreased to about 40% in the injured proximal tubules and was recovered in proportion to the increase of chitosan. Chitosan may be useful in recovery of renal function from $HgCl_2$injury.

• Childhood Kidney Diseases
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• 제27권1호
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• pp.19-25
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• 2023

Proteinuria is an important risk factor for renal and cardiovascular disease. It is associated with a risk for glomerulonephritis, chronic kidney disease, and end-stage renal disease. Therefore, if persistent proteinuria is detected, kidney biopsy is considered to diagnose and treat the underlying disease. Recently, variants in the cubilin (CUBN) gene, which is associated with albuminuria, have been reported. This gene encodes cubilin, a membrane glycoprotein receptor expressed in the renal proximal tubules. Cubilin is a component of the megalin and cubilin-amnionless complex that mediates albumin reabsorption into the proximal tubules through endocytosis. A defect in cubilin leads to a reduction in albumin reuptake, resulting in albumin-dominant proteinuria. Although numerous controversies exist, several reports suggest that cubilin defects lead to proteinuria with a high portion of albuminuria but may not impair renal filtration function. If albuminuria due to reduced cubilin function is confirmed as a benign condition, we can consider using genetic studies to detect CUBN mutations in patients with proteinuria and they may not require any treatment or kidney biopsy. Here, we review recent papers on CUBN mutations and discuss the prognosis and management of individuals with this mutation.

• 한국식품위생안전성학회지
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• 제8권4호
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• pp.195-204
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• 1993

Basolateral and brush border membrane (BLM and BBM) vesicles of renal proximal tubules were prepared from adult male New Zealand White rabbits to evaluate as a potential model for assessment of nephrotoxicity. PAH uptakes using BLMV, glucose and leucine uptakes using BBMV were measured in the rabbits treated cephaloridine. In addition, urinalysis and histopathological studies were performed to investigate the correlationship with membrane vesicle uptakes. The results were as follows: (1) the activite of Na+, K+ -ATPase was enriched 12.3-fold in vasolateral memvrane vesicles (BLMV) and the specific activity of alkaline phosphatase in purified brush border memvrane vesicles (BBMV) was enriched 10.1-fold compared with each of microsomal homogenate. (2) In the uptake experiments, cephaloridine decreased initial and probenecid-sensitive PAH uptakes in BLMV. (3) Cephaloridine tested decreased initial and phlorizin-sensitive glucose uptakes in BBMV. (4) Cephaloridine tested decreased initial and Na+-dependent leucine uptakes in BBMV. (5) Cephaloridine tested significantly increased the urinary excretion of glucose and activity of ${\gamma}$-GTP. (6) Cephaloridine tested caused moderate necrotic changes in renal tubular cells and formation of urinary cast in the lumina of Henle's loop and collecting tubules besides the swelling of renal tubules.

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.151.3-152
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• 2000

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.158.3-159
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• 2002

• 대한약리학회지
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• 제7권1호
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• pp.67-76
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• 1971

The excretion of uric acid in man has been of great interest because of its importance as an end product in purine metabolism as well as of its role in causing gout. There are many differences in the modes of renal handling of urate among various species of animals. Uric acid actively secreted by the renal tubules of most vertebrate including amphibians, reptiles, and birds. On the other hand, in most mammals net tubular reabsorption of urate appears to be occurred with some exception, such, as Dalmatian dog. In the rabbits, however, the mechanism of renal excretion of uric acid has long been a subject of controversial results. Within a given group it was possible to find individuals with either net secretion or net reabsorption of urate depend on the experimental conditions. Excretion of urate can be depressed or enhanced by a variety of drugs belonging mainly to the aromatic acid group. Diodrast, probenecid, cinchophen and salicylates have been reported as uricosuric agents, on the other hand, lactate, benzoate, pyrazinoic acid, acetazolamide and chlorothiazide are known to be contraindicated to use for the patient with gout since these agents depress the excretion of uric acid from the kidney. However, complex and sometimes the paradoxical effects on the urate excretion by those above mentioned drugs are not uncommon. The experiments were designed to investigate the mechanisms of renal handling of urate as well as the effects of variety of drugs on the tubular transport of uric acid in the rabbits. Male or female white rabbits, from 1.5 to 2.5 kg in weight, were used. The experimental methods used in these studies were clearance, stop-flow, and retrograde injection techniques. The effects of saline, salicylate, chlorothiazide and probenecid were investigated in each experimental conditions. Results of the experiments were summarized as follows; 1. In the rabbits, the rate of urate clearance was always lower than the rate of inulin clearance. The filtration fraction of the urate was one third on an average, therefore, it is estimated that approximately two thirds of filtered urate was reabsorbed. 2. In the kidneys of rabbits, the urate clearance was increased significantly by administration of chlorothiazide and decreased by probenecid. The administration of salicylate had no effect on the rate of urate clearance. The filtration fraction of urate was increased by chlorothiazide and decreased by probenecid. 3. In the stop-flow studies, the U/P ratio of urate was higher than the U/P ratio of inulin in the proximal region, indicating the secretion of uric acid in the proximal tubules. The proximal peak was increased by chlorothiazide and inhibited by probenecid.4. In the retrograde injection studies, the reabsorption of urate in the proximal region was observed, and these reabsorptive transport of urate was depressed by either probenecid or by chlorothiazide. 5. No distal tubular activity was observed under any of these experimental conditions concerning urate transport. The results of these experiments show that probenecid inhibits both secretory and reabsorptive transport of uric acid in the kidney of the rabbits. The enhancement of secretory transport of urate by chlorothiazide in the clearance study was due to the secondary action of chlorothiazide which inhibits the reabsorptive transport of urate in the proximal tubules. It is evident that the urate transport in the kidneys of rabbits is bidirectional nondiffusive flux both secretory and reabsorptive directions in the proximal tubules.

• 대한수의학회지
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• 제37권1호
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• pp.41-57
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• 1997

This study was carried out to investigate the effect of selenium on the adriamycininduced renal lesions in male Sprague Dawley rats. A total of 60 Sprague-Dawley male rats were divided into 2 control groups(C1: saline, C2: selenium) and 2 treatment groups(T1: adriamycin, T2: adriamycin+selenium). The rats of the C1 and T1 groups were given normal saline(0.15ml/rat), the rats of the C2 and T2 groups were given sodium selenite(0.5mg/kg) intraperitoneally three days a week for 4 weeks. The treatment groups were dosed intraperitoneally with adriamycin(2mg/kg/day) five days at the second week. Animals were sacrificed at the 1st week, 2nd week and 3rd week after dosing with adriamycin. The morphologic abnormalities of the glomeruli and tubules in the kidney of male rats were examined histopathologically and electron microscopically.The results obtained were as follows : The mean body weight of adriamycin dosed group was significantly decreased as compared with that of control group at 4th week(p<0.05). In adriamycin and selenium dosed group, the mean body weight was decreased until the end of 2nd week but gradually increased from 3rd to 4th week. The histopathological findings of the renal corpuscle in adriamycin dosed group were parietal epithelial cell proliferation, vacuolization of glomerulus, and thickened basement membrane of the parietal epithelium. Proximal convoluted tubules were significantly dilated and the lumens were filled with renal cast. These lesions were generally not very significant in the rats given adriamycin and selenium. The electron microscopical findings of the renal glomerulus in the adriamycin dosed group were focal loss and fusion of the pedicels of the podocyte, and some vacuoles in the cytoplasm of the podocytes. There were numerous cytoplasmic vacuoles in the proximal and distal convoluted tubular cells. However, these ultrastructural changes were not significantly observed in the renal tubules of the rats of adriamycin and selenium dosed group. These results suggest that selenium may act as an inhibitor of the renal lesions induced by adriamycin in male rats.