• Journal of Haehwa Medicine
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• v.21 no.1
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• pp.11-21
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• 2012

New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. The purpose of this study is to develop novel immune suppressants for PTDM using of action mechanism of them. The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to ${\beta}$-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of ${\beta}$-cells to therapeutical levels of tacrolimus (FK506) or cyclosporin A(CsA). The immunosuppressive drug cyclosporine(CsA) is a potent agent widely used after organ transplantations and various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity. The renal or vascular toxicity is influenced by the degree of the endothelial damage. FK506(tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of Immunosuppressant. In this study, we investigated gene expression patterns induced by Immunosuppressant in RIN-m5F of rat insulinoma cell line. Gene expressions evaluated using cDNA microarry in two clusters were increased or decreased. this study provides comprehensive comparison of the patterns of gene expression changes induced by CsA and FK506 in ${\beta}$-cells. This study could establish that the mode of action mechanism by which currently used insulin inhibitors inducing PTDM could be elucidated at least in part, which raises the possibility that novel immune suppressive PTDM can be developed. The molecular biological study on PTDM will also contribute the progress in diabetes research field as well as in that of PTDM.

• Journal of Veterinary Clinics
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• v.8 no.1
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• pp.31-45
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• 1991

Present experiment was performed in order to establish the optimal reaction conditions for determination of urinary AAP and GRS activities and to investigate the applicability of urinary AAP and GRS in nephrotoxicity test in rat. The results were as follows ; 1. The optimal pH of phosphate buffer for determination of urinary AAP activity was 7.8. 2. The Michaelis constant of urinary AAP ranged from 0.8 to 1.0mmol/$\ell$ 3. The optimal wave length for determination of urinary GRS activity was 405nm. 4. The optimal pH of acetate buffer for determination of urinary GRS activity was 5.6. 5. The Michaelis constant of urinary GRS ranged from 0.65~0.79mmo1/$\ell$. 6. The AAP activities in gel-filtered samples were significantly higher than those in crude samples. Mean values of AAP activities in gel-filtered samples and crude samples were 29$\pm$20 and 20$\pm$13U/$\ell$, respectively. 7. There was not significant difference between gel-filtered samples and crude samples in urinary GRS activities. Mean values of GRS activities in gel-filtered samples and crude samples were 57$\pm$40 and 56$\pm$39U/$\ell$, respectively. 8. Limits of linearity of urinary AAP and GRS activities were 2.0 and 3.6U/$\ell$, respectively. 9. Within-run imprecisions of the assays, were acceptable, as the coefficients of the AAP activities ranged from 5.5 to 6.3% and those of GRS activities ranged from 1.4 to 6.2%, respectively. 10. Urinary AAP excretion was 675$\pm$227mu/24hrs.kg before administration of potassium dichromate, and increased significantly to 4246$\pm$2567mU/24hrs.kg within 24 hours after administration of potassium dichromate. 11. Urinary GRS excretion did not increase significantly after administration of potassim dichromate. 12. From these findings it is concluded that urinary AAP excretion is early and sensitive Indicator to detect kidney damage in nephrotoxicity experiment.

• Journal of Veterinary Clinics
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• v.29 no.6
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• pp.441-446
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• 2012

The purpose of present study is to observe the hepato-protective effect of ginger aqueous extracts on carbon tetrachloride($CCl_4$)-induced mouse. Ginger groups received ginger aqueous extracts (500 mg/kg) orally for 3 days and given a single dose of $CCl_4$ (4 mL/kg). Silymarin group was treated with silymarin (50 mg/kg) orally for 3 days and then aministration of $CCl_4$ (4 mL/kg). Control group was only administered $CCl_4$ (4 mL/kg). In the ginger groups, the AST, ALT levels were significantly (p < 0.05) decreased compared to the control groups. Histopathological evaluation, hepatic parenchyma and kidney parenchyma of ginger groups were significantly (p < 0.05) decreased compared to control group. The results obtained in this study suggest that ginger aqueous extracts are able to protect the liver $CCl_4$-induced injury.

• Journal of Nutrition and Health
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• v.33 no.7
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• pp.725-732
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• 2000

The purpose of this study was to investigate the effects of green tea catechin on renal dysfunction and blood presure change in chronic cadmium poisoned rats. Sprague-Dawley male rats weighing 100$\pm$10g were randomly assigned to one normal group and three cadmium poisoned groups. Cadmium groups were classified to catechin free diet(Cd-0C group) 0.25% catechin diet(Cd-0.25C group) and 0.5% catechin diet(Cd-0.5C group) according to the levels of catechin supplement. Animals were raids for 20weeks. Cadmium were supplied as drinking water of 50ppm Cd2+ Morphological changes shown through a light microscope and an electro-microscope revealed the mitochondria and tubule epithelial cell edema in Cd -0C group but they were alleviated in catechin supplementation. The urinary $\beta$2-microglobulin that measured to observe the glomerular injury were higher in Cd-poisoned groups than in normal group but they was lowered by catechin supplementation. Glomerular filtration ratios(GFR) in Cd-poisoned groups were significantly lower than in normal group but that of catechin supplementation group was similar to normal group. This suggested that catechin protected the kidney from the functional damage. Angiotensin converting enzyme(ACE) activity and blood pressure(BP) in Cd-poisoned groups were significantly higher than in normal group. Heart rate was tended to increase in Cd-poisoned groups. The results indicate that green tea catechin supplementation on chronic cadmium-poisoned rats normalized the renal dysfunction and blood pressure system.

• Journal of Nutrition and Health
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• v.33 no.7
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• pp.703-711
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• 2000

The purpose of this study was to investigate the effect of butanol(BuOH) fraction of Polygonatum odoratum with selenium tr-eatment on blood glucose levels and lipid peroxidations in streptozotocin(STZ) induced diabetric rats. Male Sprague-Dawly rats weighing(180-200g) were divided into five groups : normal STZ-control and three expreimental groups(P, odoratum group P, odo-Se group and Se group) Diabetes mellitus was induced by injection STZ in the tail vein at the dose of 45mg/kg B.W The BuOH fraction of Polygonatum odoratum(500mg/kg. B,W) given orally administered for 14 days. The Se treated group were fed a AIN-76 recommendation diet mixed with Na2Seo3(2mg/kg diet). Diabetic rats showed the lower weight gain compared to the normal rats. the plasma glucose levels of the P. odo-Se group were significantly lower than the other experimental groups. The plasma cholesterol levels were higher in STZ-control and Se groups compared toP.odoratum and P. odo-Se groups and HDL-cholesterol levels were increased in the diabetic experimental groups fed on BuOH fraction of P. odoratum with Se supplementation. The liver and muscle glycogen levels were not significantly differ among all groups. The plasma free fatty acid levels were lower in diabetic experimental groups fed on BuOh fraction of P. odoratum or Se sup-plementation than STZ-control and Se groups. Diabetics rats showed the higher levels of triglyceride in plasma andlower levels in liver compared with the normal group. Supplementation with Se decreased significantly the liver triglyceride level. The MDA levels in liver and kidney were significantly reduced in all the experimental groups. In conclusion administration of BuOH fraction of Polygonatuum odoratum with selenium supplementation reduced blood glucose levels and peroxdative tissue damage in STZ induced diabetic rats showing the possibility of preventiave and therapeutic use of the wild edible plant to the diabetes mellitus.

• Preventive Nutrition and Food Science
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• v.14 no.1
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• pp.21-28
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• 2009

In this study, we focused on natural water-soluble antioxidants from Tetraselmis suecica (T. suecica) and Chlorella ellipsoidea (C. ellipsoidea). They were prepared by enzymatic digestion using five carbohydrases (Viscozyme, Celluclast, AMG, Termamyl and Ultraflo) and five proteases (Protamex, Alcalase, Flavourzyme, Neutrase, and Kojizyme), and the potential antioxidant activity of each was assessed. Most enzymatic digests from T. suecica had a higher radical scavenging activity than those from C. ellipsoidea. Among the enzymatic digests, Kojizyme digest from T. suecica exhibited the highest effect on DPPH radical scavenging. Viscozyme (30.2%) and Neutrase (34.6%) digests from T. suecica exhibited higher hydroxyl radical scavenging activity. Kojizyme digest from T. suecica (81.5%) had strong alkyl radical scavenging activity. Neutrase (61.9%) and Kojizyme (61.5%) digest from T. suecica possessed the highest effects on hydrogen peroxide scavenging. Among the tested samples, Neutrase (TN) and Kojizyme (TK) digests from T. suecica showed the highest antioxidant activity (DPPH, alkyl radical, hydrogen peroxide). Therefore, TN and TK digests were selected for use in the further experiments. Those digests showed enhanced cell viability against $H_2O_2$-induced oxidative damage, and relatively good hydrogen peroxide scavenging activity in an African green monkey kidney (Vero) cell line. These results suggested that an enzymatic digestion will be an effective way for the production of a potential water-soluble antioxidant from a microalgae, T. suecica.

• Childhood Kidney Diseases
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• v.13 no.2
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• pp.99-117
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• 2009

Diabetic nephropathy is a major cause of chronic renal failure in developing countries, and the prevalence rate has markedly increased during the past decade. Diabetic nephropathy shows various specific histological changes not only in the glomeruli but also in the tubulointerstitial region. In the early stage, the effacement of podocyte foot processes and thickened glomerular basement membrane (GBM) is noticed even at the stage of microalbuminuria. Nodular, diffuse, and exudative lesions, so-called diabetic glomerulosclerosis, are well known as glomerular lesions. Interstitial lesions also exhibit fibrosis, edema, and thickened tubular basement membrane. Diabetic nephropathy is considered to be multifactorial in origin with increasing evidence that one of the major pathways involved in the development and progression of diabetic nephropathy as a result of hyperglycemia. Hyperglycemia induces renal damage directly or through hemodynamic alterations, such as, glomerular hyperfiltration, shear stress, and microalbuminuria. Chronic hyperglycemia also induces nonhemodynamic dysregulations, such as, increased production of advanced glycosylation endproducts, oxidative stress, activation of signal pathway, and subsequent various cytokines. Those pathogenic mechanisms resulted in extracellular matrix deposition including mesangial expansion and GBM thickening, glomerular hypertrophy, inflammation, and proteinuria. In this review, recent opinions on the histopathologic changes and pathophysiologic mechanisms leading to initiation and progression of diabetic nephropathy will be introduced.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.4
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• pp.409-415
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• 2013

We attempted to determine the action target of Shiitake mushroom extract with a known anti-hyperlipidemic effect in poloxamer(P) 407-induced hyperlipidemia model. We investigated the anti-hyperlipidemic effects of the water extract from Shiitake mushroom on the progress of high fat diet for 4 weeks. Experimental rats were divided into 5 different experimental groups including an normal group (normal diet; n=10), control group (hyperlipidemia; n=10), Experimental group I (hyperlipidemic rats treated with Shiitake mushroom extract (100 mg/kg, PO), n=10), Experimental group II (hyperlipidemic rats treated with Shiitake mushroom extract (300 mg/kg, PO), n=10), and Experimental group III (hyperlipidemic rats treated with Shiitake mushroom extract (500 mg/kg, PO), n=10). It is to analysis changes in body weight, visceral fat weight, blood lipid profiles, HMG-CoA reductase and histological findings. Body weight and epididymal fat weight was not significantly change in experimental groups (p>0.05). The level of total cholesterol, TG, arthrogenic index, and HMG-CoA reductase were significantly lower in experimental groups than control group (p<0.05). These results suggested that the Shiitake mushroom extract administration may act by inhibitory the release of cholesterol related factors and HMG-CoA from the hepatocyte without liver and kidney cell damage in hyperlipidemia rats.

• Toxicological Research
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• v.34 no.2
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• pp.143-150
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• 2018

It has been demonstrated that vanadate causes nephrotoxicity. Vanadate inhibits renal sodium potassium adenosine triphosphatase (Na, K-ATPase) activity and this is more pronounced in injured renal tissues. Cardiac cyclic adenosine monophosphate (cAMP) is enhanced by vanadate, while increased cAMP suppresses Na, K-ATPase action in renal tubular cells. There are no in vivo data collectively demonstrating the effect of vanadate on renal cAMP levels; on the abundance of the alpha 1 isoform (${\alpha}_1$) of the Na, K-ATPase protein or its cellular localization; or on renal tissue injury. In this study, rats received a normal saline solution or vanadate (5 mg/kg BW) by intraperitoneal injection for 10 days. Levels of vanadium, cAMP, and malondialdehyde (MDA), a marker of lipid peroxidation were measured in renal tissues. Protein abundance and the localization of renal ${\alpha}_1-Na$, K-ATPase was determined by Western blot and immunohistochemistry, respectively. Renal tissue injury was examined by histological evaluation and renal function was assessed by blood biochemical parameters. Rats treated with vanadate had markedly increased vanadium levels in their plasma, urine, and renal tissues. Vanadate significantly induced renal cAMP and MDA accumulation, whereas the protein level of ${\alpha}_1-Na$, K-ATPase was suppressed. Vanadate caused renal damage, azotemia, hypokalemia, and hypophosphatemia. Fractional excretions of all studied electrolytes were increased with vanadate administration. These in vivo findings demonstrate that vanadate might suppress renal ${\alpha}_1-Na$, K-ATPase protein functionally by enhancing cAMP and structurally by augmenting lipid peroxidation.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.31-36
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• 1981

Heavy metals which are present as trace elements in human body have been known to modify various enzymatic reaction. These metals can be essential or non-essential. Zinc, copper and calcium are essential in maintaining some biological processes, whereas non-essential metals such as cadmium, lead and mercury produce accumulatve toxic effect. Cadmium accumulated in pancreas can cause toxicity and damage of pancreatic cells, thereby influencing CHO metabolism. Lead compounds are known to produce toxic effects on the kidney, digestive system and brain fellowed by inhibition of activity of ${\rho}-aminolevulinic$ acid and biosynthesis of hemoproteins and cytochrome. Evidence has been accumulated that zinc not only acts as a cofactor in enzyme reaction but also prevents toxic effect induced by heavy metal such as copper and cadmium. To demonstrate the effect of heavy metals on pancreatic secretion, part of uncinate pancreas was taken and incubated in Krebs-Ringer bicarbonate buffer with heavy metals used. Additional treatment with CCK-OP was performed when needed. After incubation during different period of time, medium was analyzed for amylase activity using Bernfeld's method. The present study was attempted in order to elucidate the effect of several kinds of heavy metal on exocrine pancreatic secretion in vitro. The results obtained are as follows: 1) CCK-OP stimulated significantly amylase release from pancreatic fragments in vitro. 2) CCK-OP response of amylase release from pancreatic fragments was inhibited by treatmant with cadmium, especially high doses of cadmium. 3) CCK-OP response of amylase release from pancreatic fragments was inhibited when pretreated with $10^{-4}M$ copper chloride. 4) Lead chloride at the concentration of $10^{-3}M\;and\;10^{4}M$ stimulated the basal amylase release in vitro but CCK-OP response did not augment by lead chloride. 5) Zine chloride did not affect amylase release from pancreatic fragment in vitro. From the results mentioned above, it is suggested that CCK-OP response was inhibited it the amylase release from pancreatic fragments pretreated with cadmium and copper chloride.