• Environmental Analysis Health and Toxicology
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• 제13권3_4호
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• pp.87-94
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• 1998

The use of cisplatin is limited by severe side effects such as renal toxicity. Our platinum-base drug discovery is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (II) complex analogue [Pt (cis-DACH)(DPPP)]. 2NO$_3$ (PC) containing cis-1,2-diaminocyclohexane as a carrier ligand and 1,3-bis(diphenylphosphino) propane as a leaving group. Furthermore, nitrate was added to improved the solubility. In this study, its structure was determined and its antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma, and in vitro cytotoxicity was determined against primary cultured rabbit kidney proximal tubular and renal cortical cells of human kidney using colorimetric MTT assay. PC demonstrated acceptable antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma and significant activity as compared with that of cisplatin. The toxicity of PC was found quite less than that of cisplatin using MTT and $^3$H-thymidine uptake tests in rabbit proximal tubular cells and human kidney cortical cells. PC was used for human cortical tissue in 7 weeks hitoculture by the glucose-consumption tests. We determined that the new platinum drug has lower nephrotoxicity than cisplatin. Based on these results, this novel platinum (II) complex compound (PC) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• The Korean Journal of Physiology
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• 제22권2호
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• pp.281-293
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• 1988

가토 신장 근위세뇨관에서 분리한 brush border membrane vesicle(BBMV)과 basolateral membrane vesicle(BBMV)에서 rapid filtration 방법으로 PAH 이동에 대한 pH의 영향을 관찰하였다. BLMV에서 용액내 Na이 없을 때 외부 $pH(pH_0)$를 8.0에서 5.5까지 감소시켰을 때 probenecid-sensitive PAH 이동은 유의하게 증가되었다. 용액내 Na이 있을 때 $pH_0$가 8.0에서 6.0까지 변화하여도 PAH 이동에는 영향이 없었으나 5.5까지 더욱 감소시켰을 때 PAH 이동이 증가하였다. 그러나 vesicle 내 외에 pH gradient없이 $pH_0$를 내부 $pH(pH_1)$와 동일하게 변화시켰을 때 PAH 이동은 영향을 받지 않았다. PH gradient가 없을 때 시험된 pH범위에서 Na은 PAH 이동을 증가시켰다. BBMV에서도 BLMV에서와 유사한 pH 의존성을 보였으나 Na의 존재는 PAH 이동에 영향을 미치지 못하였다. BLMV에서 동력학적 분석 결과 일정한 $pH(pH_1)$에서 $pH(pH_0)$ 감소는 Km에 변화없이 PAH 이동에 대한 Vmax를 유의하게 증가시켰다. 이러한 결과로 BBMV에서 PAH 이동에 대한 pH의 영향은$OH^-/PAH$교환기전에 기인하는 것으로 추측되나 BLMV에서 pH 의존성은 음이온 교환기전만으로 설명될 수 없다. 또한 BLMV에서는 PAH 이동이 Na에 의존하나 BBMV에서는 Na에 의존하지 않음을 가르킨다.

• The Korean Journal of Physiology
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• 제22권2호
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• pp.307-318
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• 1988

가토 신장 피질에서 Percoll density gradient방법으로 분리한 basolateral membrane vesicle (BLMV)에서 rapid filtration technique을 이용하여 succinate의 이동 특성을 관찰하였다. $Na^+$은 succinate의 이동을 증가시켜 "overshoot"현상을 보였으며 이러한 효과는 $K^+,{\;}Li^+,{\;}Rb^+,{\;}choline$과 같은 다른 양이온들에 의해 나타나지 않았다. $Na^+$농도변화에 따른 succinate의 이동율은 sigmoid모양을 보였고, $Na^+$에 대한 Hill coefficient는 2.0이었다. soccinate의 이동은 vesicle 내부가 음전압일 때 더욱 증가되었다. BLMV에서 succinate이동은 용액내 pH변화에 따라 영향을 받았으나 brush border membrane vesicle (BBMV)에서는 영향을 받지 않았다. 동력학적 분석결과 succinate의 Km값은 $15.5{\pm}0.94{\;}{\mu}M$이었고 Vmax는 $16.22{\pm}0.25{\;}n{\;}mole/mg{\;}protein/min$이었다. succinate의 이동은 $4{\sim}5$탄소를 가진 dicarboxylate들에 의해 강력하게 억제되었으나 monocarboxylate나 다른 유기음이온들에 의해 영향을 적게 받거나 받지 않았다. succinate의 이동은 DIDS, SITS, furosemide와 같은 음이온 이동 억제제와 harmaline과 같은 $Na^+$ 이동 억제제에 의해 억제되었다. 이들 결과들은 BLMV에서 succinate는 $Na^+$에 의존하여 이동하며 다른 Krebs cycle중간 산물들과 동일한 운반기전을 이용함을 가르킨다. 또한 BLMV에서 succinate의 이동은 그 기질특이성에 있어서 다른 연구자에 의해 보고된 BBMV에서 이동특성과 유사함을 보였다.

• 대한수의학회지
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• 제37권2호
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• pp.301-310
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• 1997

Diabetes mellitus is associated with a wide range of pathophysiological in the kidney. This study was designed to examine the effects of high glucose concentration on IGF-I binding and glucose transporters in renal proximal tubule cells. The results were as follows : The binding of $^{125}I-IGF-I$ reached the peak at the 30 minutes and gradually decreased by the time dependent manner. The binding of $^{125}I-IGF-I$ was inhibited by the unlabelled IGF-I($10^{-14}{\sim}10^{-8}M$) in a concentration dependent manner. The relative affinity of IGF-I receptor for IGF-I, IGF-II and insulin exhibited typical type 1 binding(IGF-I > insulin > IGF-II). However IGF-II did not compete for the cultured cell membrane $^{125}I-IGF-I$ binding site at $10^{-14}{\sim}10^{-8}M$. Under optimal conditions, IGF-I binding to the membranes from 5mM and 20mM glucose treated cells was analyzed. It was found that 20mM glucose treated cells exhibited higher binding activity for IGF-I. In order to further substantiate this increase in IGF-I binding sites, we performed affinity-labelling studies. The cross-linked cell membrane subjected to SDS-PAGE; labelled material was detected by autoradiography. 20mM glucose treated cells exhibited higher levels. The initial rate of $methyl-{\alpha}-D-glucopyranoside({\alpha}-MG)$ uptake was significantly lower($74.41{\pm}6.71%$) in monolayers treated with 20mM glucose than those of 5mM glucose. However, 3-O-methyl-D-glucose(3-O-MG) uptake was not affected by glucose concentration in culture media. IGF-I significantly increased ${\alpha}-MG$ uptake in both 5mM and 20mM glucose treated cells. However, 3-O-MG uptake was not affected by IGF-I in both conditions. In conclusion, 20mM glucose increased binding sites of $^{125}I-IGF-I$, inhibited Na/glucose cotransporter activity. But 20mM glucose did not change facilitated glucose transporter.

• Korean Journal of Radiology
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• 제24권10호
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• pp.1017-1027
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• 2023

Objective: The assessment of cortical integrity following renal injuries with planar Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy depends on measuring relatively decreased cortical uptake (i.e., split renal function [SRF]). We analyzed the additive values of the volumetric and quantitative analyses of the residual cortical integrity using single-photon emission computed tomography (SPECT) compared to the planar scintigraphy. Materials and Methods: This prospective study included 47 patients (male:female, 32:15; age, 47 ± 22 years) who had non-operatively managed renal injuries and underwent DMSA planar and SPECT imaging 3-6 months after the index injury. In addition to planar SRF, SPECT SRF, cortical volume, and absolute cortical uptake were measured for the injured kidney and both kidneys together. The correlations of planar SRF with SPECT SRF and those of SRF with volumetric/quantitative parameters obtained with SPECT were analyzed. The association of SPECT parameters with renal function, grades of renal injuries, and the risk of renal failure was also analyzed. Results: SPECT SRF was significantly lower than planar SRF, with particularly higher biases in severe renal injuries. Planar and SPECT SRF (dichotomized with a cutoff of 45%) showed 19%-36% of discrepancies with volumetric and quantitative DMSA indices (when dichotomized as either high or low). Absolute cortical uptake of the injured kidney best correlated with glomerular filtration rate (GFR) at follow-up (ρ = 0.687, P < 0.001) with significant stepwise decreases by GFR strata (90 and 60 mL/min/1.73 m²). Total renal cortical uptake was significantly lower in patients with moderate-to-high risk of renal failure than those with low risk. However, SRF did not reflect GFR decrease below 60 mL/min/1.73 m² or the risk of renal failure, regardless of planar or SPECT (count- or volume-based SRF) imaging. Conclusion: Quantitative measurements of renal cortical integrity assessed with DMSA SPECT can provide more clinically relevant and comprehensive information than planar imaging or SRF alone.

• 대한본초학회지
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• 제32권6호
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• pp.23-29
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• 2017

Objective : Hyperuricemia is a metabolic disease characterized by elevated blood uric acid levels, and its prevalence is rapidly increasing worldwide. Alpiniae Oxyphyllae Fructus (AO) belonging to Zingiberaceae is one of well-known traditional medicines in China and Korea, and has been used to treat intestinal disorders, urosis, diuresis, and chronic glomerulonephritis traditionally. However, the effect of AO has not been studied. In this study we investigated the anti-hyperuricemic effect of AO, and the mechanisms underlying the effect in potassium oxonate (PO)-induced hyperuricemic rats. Methods : To examine the anti-hyperuricemic effects of the AO extract, serum uric acid levels were analyzed in normal and PO-induced hyperuricemic rats. The mechanism underlying the effects of the AO extract on uric acid levels was studied through xanthine oxidase (XOD) activity test and uric acid uptake assay in vitro. The chemical finger printing of the AO extract was analyzed using HPLC-DAD. Results : The AO extract significantly reduced serum uric acid levels in normal as well as PO-induced hyperuricemic rats. It also significantly inhibited the uptake of uric acid in oocytyes and human embryonic kidney cells (HEK293) expressing urate transporter (URAT)1, but not XOD activity in vitro. The chemical finger printing analysis of the AO extract showed nootkatone as a main component. Conclusion : The AO extract exhibits anti-hyperuricemic effects, and these effect were accompanied by increasing excretion of uric acid in kidney. Therefore, the AO extract could be used for prevention or treatment of hyperuicemia and gout.

• 대한수의학회지
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• 제11권2호
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• pp.105-116
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• 1971

The effects of aconite root in rats and rabbits were studied following oral administration of the powder which was prepared by lyophilization of the decoction of the salted aconite roots. The $LD_{50}$ of the powder, the blood picture, total blood volume, uptake rate of ${42}^K$ and ${24}^Na$ in various organs, oxygen consumption, thyroid activity, and histopathological changes in various organs, were observed. The results obtained were as follows: 1. The $LD_{50}$ of the powder of decoction of the aconite root was 4.07g/kg of body weight in mice which is equivalent to approximately 40g/kg of the salted aconite roots. 2. The number of erythrocytes and leukocytes, hematocrit value, and the amount of hemoglobin in blood were increased in the rats administered daily dosages of 0.1, 0.5, and 1.0g/kg respectively. No significant differences were observed in the differential count of leukocytes. A slight tendency of hemoconcentration was recognized. 3. No changes in the erythrocyte volume, plasma volume and total blood volume were observed in the rats after administration of the powder for one, three, and six days. However, those were decreased in rats treated for ten days. 4. Generally, in various organs of rats the uptake rate of ${24}^Na$ showed a tendency of increasing but that of ${42}^K$ slowed a decreasing tendency. 5. The oxygen consumption was markedly decreased in rats administered the powder. 6. Iodine-131 uptake of thyroid gland was markedly decreased in the rabbits following administration of the powder. 7. In rabbits administered 0.5g/kg for 20 days, fatty changes of hepatic cells, cloudy swelling of the epithelial cells of proximal convoluted tubules of the kidney and the dilation of splenic sinuses were observed, however, milder changes were found in rabbits treated with 0.1g/kg for the same period.

• 약학회지
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• 제39권2호
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• pp.161-168
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• 1995

Brain dopamine systems play a central role in the control of movement, hormone release, and many complex behavior. The action of dopamine at its synapse is terminated predominately by high affinity reuptake into presynaptic terminals by dopamine transporter (DAT). The dopamine transporter(DAT) is membrane protein localized to dopamine-containing nerve terminals and closely related with cocaine abuse, Parkinsonism, and schizophrenia. In present study, the recombinant plasmid pRc/CMV-DAT, constructed by subcloning of a cDNA encoding a bovine DAT into eukaryotic expression vector pRc/CMV, was stably transfected into CV-1 cells(monkey kidney cell line). The DAT activities in the cell lines selected by Geneticin$^{R}$ were determined by measuring the uptake of $[^3H]$-dopamine. The transfected cell lines showed 30-50 fold higher activities than untransfected CV-1 cell line, and this result implies that DAT is well expressed and localized in transfected cells. The transfected cells accumulated $[^3H]$-dopamine in a dose-dependent manner with a $K_{m}$ of 991.6nM. Even though high doses of norepinephrine, epinephrine, serotonin, and choline neurotransmitters inhibited the uptake of $[^3H]$-dopamine, DAT in transfected cell line was proven to be much more specific to dopamine. The psychotropic drugs such as GBR12909, CFT, normifensine, clomipramine, desipramine, and imipramine inhibited significantly the dopamine uptake in tissue culture cells stably transfected with DAT cDNA. Radioactive in situ hybridization was done to map the cellular localization of DAT mRNA-containing cells in the adult rat central nervous system. The strong hybridization signals were detected only in the substantia nigra pars compacta and ventral tegmental area. The restricted anatomical localization of DAT mRNA-containing cells confirms the DAT as a presynaptic marker of dopamine-containing cells in the rat brain.

• 대한핵의학회지
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• 제33권1호
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• pp.49-56
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• 1999

목적: T1-201 경직장 문맥신티그라피에서 심장/간 섭취비(단락지수)는 만성 간질환 환자에서 문맥-체단락을 평가하는 데 유용한 지표로 알려져 있다. 본 연구는 만성 활동성 간염과 간경변 환자에서 T1-201 섭취 양상과 초기 간/심장 섭취속도의 유용성을 평가하고, 단락지수와의 연관성을 알아보고자 하였다. 대상 및 방법: 간생검으로 만성 간질환(만성 활동성 간염 35명, 간경화 23명)을 진단받은 58명의 환자에서 T1-201 18.5 MBq를 상부직장에 주입 후 T1-201 경직장 문맥신티그라피를 시행하였다. 간섭취 양상(1형: 균일 분포, 2형: 분절단위 불균일 분포, 3형: 비분절단위 불균일 분포)과 비장, 심장, 신장의 간외 분포양상(grade 0: 방사능 섭취 없음, grade 1: 간보다 적은 방사능 정도, grade 2: 간과 비슷한 방사능 정도, grade 3: 간보다 많은 방사능 정도), 초기 간/심장 섭취속도(처음 10분간의 간/심장 섭취비의 기울기)와 단락지수(심장/간 계수비)를 구하였다. T1-201 섭취 양상과 초기 간/심장 섭취비를 병리진단, 단락지수와 비교하였다. 결과: 간 섭취 양상은 만성 활동성 간염에서 1형과 2형의 간내 방사능 분포 양상이 많았고(만성 활동성 간염: 27/35, 간경변: 8/23), 간경변은 3형이 유의하게 많았다(만성활동성 간염. 8/35, 간경변: 15/23)(p<0.005). 간외분포양상의 grade는 간경변에서 유의하게 높았다(비장: p<0.001, 기타 연 조직 p<0.005). 초기 간/심장섭취속도는 만성 활동성 간염($0.110{\pm}$0.111)이 간경변($0.014{\pm}0.090$)보다 유의하게 높았으며(p<0.001), 간경변의 판정지표로서 0.05를 기준으로 하였을 때 예민도와 특이도는 각각 77.2%, 67.7%였다. 초기간/심장 섭취속도와 단락지수는 음의 상관관계를 보였다(r=-0.3347, p<0.01). 결론: T1-201 경직장 문맥 신티그라피에서 간 및 간외 방사능 분포와 초기 간/심장 섭취속도는 만성 간질환 환자에서 문맥-체단락을 평가하는 데 유용한 지표로 생각된다.

• 대한핵의학회지
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• 제25권2호
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• pp.227-236
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• 1991

Background: The evaluation of individual renal function is important to diagnosis and follow-up of various diseases. Ureteral catheterization of each kidney has been widely used for this purpose, but this method had some technical difficulty, frequent complications and much restriction in reapplication. Therefore we tried to applicate radiopharmaceuticals for the evaluation of individual renal function. Methods: We measured 2 hour, 4 hour and 24 hour relative renal uptake of $^{99m}Tc-DMSA$ and relative glomerular filteration rate of $^{99m}Tc-DTPA$ with 59 patients with various renal diseases to determine their usefulness for assessment of individual renal function and to compare correlations between every renal uptake of $^{99m}Tc-DMSA$ and relative glomerular filteration rate. Results: The correlations between 2 hour-, 4 hour- and 24 hour- relative renal uptake of $^{99m}Tc-DMSA$ and relative glomerular filteration rate of $^{99m}Tc-DTPA$ were R=0.9190 (p < 0.001), R: 0.9229 (p<0.001) and R=0.9917 (p<0.001). In acute obstructive uropathy, the correlations at 2 hour and 4 houre were poor as R=0.1812 (p<0.05) and R=0.4923 (p < 0.05), but the correlation at 24 hour was good as R=0.9942 (p<0.001). Conclusions: We concluded that relative renal uptake at 2 hour and 4 hour had good correlation with relative DTPA uptake ratio in the cases without chronic renal failure and obstructive uropathy. Delayed image with 24 hour relative renal uptake $^{99m}Tc-DTPA$ had the best correlation with relative glomerular filteration rate of $^{99m}Tc-DTPA$ and that might be useful in evaluation of chronic renal disease in which showed increased beckground activity or acute obstructive uropathy.