• The Korean Journal of Physiology and Pharmacology
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• v.11 no.2
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• pp.71-77
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• 2007

Cisplatin treatment increases the excretion of inorganic phosphate in vivo. However, the mechanism by which cisplatin reduces phosphate uptake through renal proximal tubular cells has not yet been elucidated. We examined the effect of cisplatin on $Na^+$-dependent phosphate uptake in opossum kidney (OK) cells, an established proximal tubular cell line. Cells were exposed to cisplatin for an appropriate time period and phosphate uptake was measured using $[^{32}P]$-phosphate. Changes in the number of phosphate transporter in membranes were evaluated by kinetic analysis, $[^{14}C]$phosphonoformic acid binding, and Western blot analysis. Cisplatin inhibited phosphate uptake in a time- and dose-dependent manner, and also the $Na^+$-dependent uptake without altering $Na^+$-independent uptake. The cisplatin inhibition was not affected by the hydrogen peroxide scavenger catalase, but completely prevented by the hydroxyl radical scavenger dimethylthiourea. Antioxidants were ineffective in preventing the cisplatin-induced inhibition of phosphate uptake. Kinetic analysis indicated that cisplatin decreased Vmax of $Na^+$-dependent phosphate uptake without any change in the Km value. $Na^+$-dependent phosphonoformic acid binding was decreased by cisplatin treatment. Western blot analysis showed that cisplatin caused degradation of $Na^+$-dependent phosphate transporter protein. Taken together, these data suggest that cisplatin inhibits phosphate transport in renal proximal tubular cells through the reduction in the number of functional phosphate transport units. Such effects of cisplatin are mediated by production of hydroxyl radicals.

• The Korean Journal of Nuclear Medicine Technology
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• v.19 no.1
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• pp.37-43
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• 2015

Purpose $^{99m}Tc-DMSA$ renal scintigraphy serves as location, size and shape of kidney, so it has been used for diagnosis and passage observation after the operation or treatment. There are 3 methods of calculating the relative renal uptake ratio such as geometric mean of the counts from the anterior and posterior views, arithmetical mean from the only posterior view and posterior view which applied the renal depths. In this study, we seek to correlation between the change of total relative uptake ratio according to different inspection methods of obtaining the renal count rate. Materials and Methods The phantom experiments proceeded 5 times depending on each renal depth with the kidney phantom and tissue equivalent materials. In the clinical research, we investigated 36 adult patients who had visited our hospital from february to october, 2014 and received $^{99m}Tc-DMSA$ renal scan. The equipment was used as a gamma camera named INFINIA (General Electric Healthcare, milwaukee, USA) and we drew the region of interests through semiautomatic method by using Xeleris Ver. 2.1220 of GE. In addition, we obtained the lateral view of kidney to measure the renal depth of each patient. Then the results were compared with 3 methods of calculating relative renal uptake ratio. Results The phantom studies show when the difference between the left ant right kidney depth were less than 1 cm, there were no statistically significant difference among values calculated through anterior and posterior views and only posterior view (P>0.05), while the excess of 1cm, the results showed a statistically significant change in the value (P<0.05). In case of clinical research, the correlation between total relative uptake ratio by obtaining both sides of image and posterior view applied the kidney depth (r=0.999) was higher than by obtaining only posterior view and applying the kidney depth to one side image (r=0.988). Conclusion This study has found that, the difference of calculating total relative uptake ratio compared with obtaining anterior and posterior views and only posterior view. In order to reduce the error, we recommend the method of obtaining anterior and posterior views and is considered to be useful, particularly the patients have similar uptake ratio of left and right kidney and difficulties of measurements of kidney depth.

• Korean Journal of Veterinary Research
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• v.37 no.1
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• pp.111-117
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• 1997

This study was carried out determine the effect of renal ischemia on amino acid transport in rabbit renal cortical slices. The animal models of renal ischemia induced experimentally by clamping the renal artery. These results were summarized as follows: 1. The uptake of amino acids lysine and ${\alpha}$-aminobutyrate(AIB), dicarboxylate succinate and organic anion PAH in cortical slices was normal or increased after 30 or 60 min of ischemia in vivo. 2. In a 30 min ischemic kidney, the slice uptake of amino acids was returned to the control level by 30 min of reflow. In a 60 or 90 min ischemic kidney, the lysine uptake was returned to the control level after of reflow, but the uptake of AIB and succinate was significantly reduced during reflow period of 30-120 min. 3. Oxygen consumption in cortical slices was increased after 30 min of ischemia but was not altered by 60 min of ischemia. This results indicat that transient ischemia caused increasing of amino acid uptake in renal cortical slices without metabolic disorder of renal proximal tubule.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.5
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• pp.529-538
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• 1999

This study was undertaken to examine the effect of ethanol on $Na^+ -dependent$ phosphate $(Na^+-P_i)$ uptake in opossum kidney (OK) cells, an established renal proximal tubular cell line. Ethanol inhibited ^Na^+-dependent$ component of phosphate uptake in a dose-dependent manner with $I_{50}$ of 8.4%, but it did not affect $Na^+-independent$ component. Similarly, ethanol inhibited $Na^+-dependent$ uptakes of glucose and amino acids (AIB, glycine, alanine, and leucine). Microsomal $Na^+-K^+-ATPase$ activity was not significantly altered when cells were treated with 8% ethanol. Kinetic analysis showed that ethanol increased $K_m$ without a change in $V_{max}$ of $Na^+-P_i$ uptake. Inhibitory effect of n-alcohols on $Na^+-P_i$ uptake was dependent on the length of the hydrocarbon chain, and it resulted from the binding of one molecule of alcohol, as indicated by the Hill coefficient (n) of 0.8-1.04. Catalase significantly prevented the inhibition, but superoxide dismutase and hydroxyl radical scavengers did not alter the ethanol effect. A potent antioxidant DPPD and iron chelators did not prevent the inhibition. Pyrazole, an inhibitor of alcohol dehydrogenase, did not attenuate ethanol-induced inhibition of $Na^+-P_i$ uptake, but it prevented ethanol-induced cell death. These results suggest that ethanol may inhibit $Na^+-P_i$ uptake through a direct action on the carrier protein, although the transport system is affected by alterations in the lipid environment of the membrane.

• The Korean Journal of Nuclear Medicine Technology
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• v.17 no.2
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• pp.25-30
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• 2013

Purpose: To evaluate kidney function, renal relative uptake is very important and is affected by kidney and the setting of background region of interest (ROI). In particular, in the case of patients with hydronephrosis to the naked eyes, such as size, position and shape etc. can be difficult to identify. So according to ROI to be set by user, the results are many differences. This study assumes the ROI of a constant kidney. According to the change of background ROI by analyzing renal relative uptake affect how the results are intended to study. Materials and Methods: From January 2012 to February 2013, we analyzed 27 patients with hydronephrosis who were examined MAG3 test in nuclear medicine department of Samsung medical center. After patients were received intravenous injection of $^{99m}Tc-MAG3$ 185 MBq (5 mCi) data were obtained. While we reconstructed images of patients, we've changed background ROI in the process of setting up ROI. First, in the process of renal processing, automatic ROI which set automatically and background ROI which needed to set manually were compared. Second, we set the ROI position separated by above, lateral and bottom of kidney. Third, background setting time were compared with 1-2 min and 2-3 min. Results: The relative uptake occurred in 3.7%p of the errors on average in Automatic & Manual ROI study. And comparison of background ROI position study, located in the lower position was more accurate results. Above, lateral, bottom each of the values 74.6%, 67.6% and 62.0% showed respectively. The standard value was 59.9%. finally, split function range test doesn't show significant difference. Conclusion: The study shows that relative uptake of kidney is affected in the background ROI. Therefore, it should be set by considering various dependent factors.

• The Korean Journal of Nuclear Medicine Technology
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• v.16 no.1
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• pp.27-33
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• 2012

Purpose: Most of diagnosis in the pediatric hydronephrosis patients have been performed $^{99m}Tc$-DMSA renal scan. Then the region of interest (ROI) is set for comparative analysis of uptake ratio in left-right kidney after acquiring the image. But if the equipment set an automatic ROI, the ROI could include expanded renal pelvis due to hydronephrosis and the uptake ratio of left-right kidney will be incorrect result. Therefore this study compared both ROIs including expanded renal pelvis and excluding renal pelvis through experiment using normal kidney phantom and expanded renal pelvis phantom and suggested setting method of improved ROI. In addition, this study have been helped by readout doctor for investigate distinction radiopharmaceutical uptake between renal cortex and remained urine by expanded renal pelvis. Materials and Methods: The both of renal phantoms were filled with water and shacked with $^{99m}TcO_4$ 111 MBq. In order to describe the expanded renal pelvis, the five latex balloon were all filled with 10 mL water and each of balloon was mixed with $^{99m}TcO_4$ 18.5, 37, 55.5, 74, 92.5 MBq. And we made phantom with fixed $^{99m}TcO_4$activity of 37 MBq and mixed water 5, 10, 15, 20, 25 mL in each balloon. The left kidney was fixed its shape and the right kidney was modified like as hydronephrosis kidney by attached the latex balloons. And the acquiring counts were 2 million. After acquisition, we compared the image of ROI with Expanded renal pelvis and the image of ROI without renal pelvis for analyzing difference in the uptake ratio of left-right kidney and for reproducibility, set the ROI 5 times in the same images. Patients were injected $^{99m}Tc$-DMSA 1.5~1.9 MBq/kg and scanned 3 to 4 hours after injection. The each of 3 skillful radio technologists performed the comparing estimation by setting ROI. To determine statistical significance between two data, SPSS (ver. 17) Wilcoxon Signed Ranks Test was used. Results: As a result of renal phantom's experiment, we compared with average of counts Background (BKG) ratios in the setting of ROI including expanded renal pelvis and setting of excluding expanded renal pelvis. Therefore, they can obtain changed counts and changed ratios. Patient also can obtain same results. In addition, the radiopharmaceutical uptake in expanded renal pelvis was come out the remained urine that couldn't descend to ureter by the help of readout doctor. Conclusion: As above results, the case of setting ROI including expanded renal pelvis was more abnormally increasing uptake ratio than the case of setting ROI excluding expanded renal pelvis in analysis the uptake ratio in left-right kidney of hydronephrosis. Because of the work convenience and prompted analysis, the automatic ROI is generally used. But in case of the hydronephrosis study, we should set the manual ROI without expanded renal pelvis for an accurate observation of the uptake ratio of left-right kidney since the radiopharmaceutical uptake in expanded renal pelvis is the remained urine.

• The Korean Journal of Nuclear Medicine
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• v.27 no.2
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• pp.248-255
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• 1993

To Assessment of the quantified renal uptake rates in every $^{99m}Tc$-DMSA scan tests of patients is actually difficult because of time consumption and complicated calculations required to measure the correct dose of the infused radionulide and radiation decay, the adjustment for the depth of kidney and the subtraction of background count. We've formulated two regression models for the quantified renal uptake rates[I] from the simple renal uptake rates[H] with a square shaped ROI (Region-Of-Interest) in 25 cases (Group 1) and with a kidney shaped ROI in 37 cases (Group 2), respectively. The regression model for the Group 1 was $[I]_1$=0.885 $[H]_1$-4.575 (P<0.005), and for the Group 2 was $[I]_2$=0.591 $[H]_2$-2.105 (p<0.005). The formal charts were clinically convenient to evaluate the individual renal functions in patients with $^{99m}Tc$-DMSA renal scan.

• Journal of Pharmaceutical Investigation
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• v.36 no.4
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• pp.283-286
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• 2006

The present study aimed to investigate the interaction of nucleoside analogs with human organic anion transporter 1 and 3(hOAT1 and hOAT3) that play a primary role in the tubular uptake of endogenous and exogenous organic anions in the kidney. The interactions of ddC, ara-C, ara-A and ara-U with hOAT1 and hOAT3 were examined using MDCK cells stably overexpressing hOAT1 or hOAT3. Among the tested drugs, ddC showed the highest affinity to hOAT1 with $IC_{50}$ values of 5.2 mM, while ara-A, ara-C and ara-U weakly inhibited the cellular uptake of $[^3H]-PAH$ in MDCK-hOAT1 cells at 1 mM. In contrast, all the tested drugs did not have any inhibition effect on the cellular uptake of $[^3H]-estrone$ sulfate in MDCK-hOAT3 cells over the drug concentration of 0.01-2 mM, implying that they might not interact with hOAT3. Taken all together, the present study suggests that hOAT1 could weakly interact with nucleoside analogues such as ddC, ara-C, ara-A and ara-U but the interaction with hOAT3 during the urinary excretion of these nucleoside analogues may be negligible in the kidney.

• Environmental Analysis Health and Toxicology
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• v.9 no.1_2
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• pp.25-35
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• 1994

Many nephrotoxic agents exert their effect primarily on the cells of the proximal tubules. We used the LLC-$PK_1$, kidney epithelial cell line as a model system for studies on nephrotoxicity and investigated whether the uptake of $\alpha$-methylglucose($\alpha$-MG) could serve as a parameter to assess effects of nephrotoxicants on the functional integrity of the cells at an early time of toxicity. The enzyme leakage test which has been used to be as a conventional cytotoxic parameter in vitro, was conducted to compare with $\alpha$-MG uptake. Treatment with cisplatin for 24 and 48 hours significantly increased activities of lactate dehydrogenase and $\gamma$-glutamyltransferase in culture medium at a concentration of 50$\mu$M. However, above 100$\mu$M of concentration, activities of these enzymes in media were dramatically decreased by cisplatin. These observations indicate that cisplatin has direct inhibitory effect on the activities of these enzymes and make it doutful to use enzyme leakage test to demonstrate damage of kidney cells by chemicals such as cisplatin over the appropriate range of concentration. Cisplatin inhibited $\alpha$-MG uptake at a low concentration which enzymes were not leaked. Also cadmium chloride and mercuric chloride which are acutely nephrotoxic in vivo, significantly inhibited $\alpha$-MG uptake at a low concentration. These results indicate that the uptake of $\alpha$-methylglucose in LLC-$PK_1$cell line is a useful biomarker for the study of nephrotoxicity.

• The Korean Journal of Nuclear Medicine
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• v.16 no.2
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• pp.85-89
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• 1982

Patients with diffusely increased uptake in both kindeys("hot kidney") on the $^{99m}Tc-MDP$ bone imagings were evaluated. Total incidence of the "hot kidney" was 2.7% (56/2053). Among 56 patients with "hot kidney", the most common diseases were malignancies (30), and the remainders were composed of renal diseases(11) and other disease group(16). We report the possible factors for the "hot kidney" with brief review of some literatures.