• 생명과학회지
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• 제11권6호
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• pp.543-553
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• 2001

마늘 속에서 중금속 중독 시에 킬에이트 작용을 일으킬수 있다는 다량의 황 화합물이 함유되어 있으므로 납 중독 흰쥐에서 그 효과를 확인하고자 본 연구를 실시한 결과 마늘 500mg/kg 투여 흰쥐군에서 유의한 납 배설량의 증가가 있었으며, 납과 마늘의 동시에 투여했을 경우에는 납 단독 투여군 보다 신장에서의 병리조직학적 변화가 경미한 것을 관찰할수 있었다. 이러한 결과는 마늘이 납 중독에대한 킬레이트제로서의 이용 가능성이 있음을 나타내고 있다.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.709-717
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• 2002

Hypoxemia is known to induce various physiological changes which can result in alteration in drug pharmacokinetics. To examine the effect of acute moderate hypoxemia on metoclopramide (MCP) pharmacokinetics, a continuous 14-hour infusion of MCP during a normoxemic, hypoxemic and subsequent normoxemic period was conducted in eight adult sheep. Arterial blood and urine samples were collected to examine the effects on the pharmacokinetics of MCP and its deethylated metabolites. MCP and its mono- and di-deethylated metabolites were quantitated using a GC/MS method. Steady-state concentrations of MCP were achieved in each of the three periods. During hypoxemia, MCP plasma steady-state concentration increased significantly from 50.72$\pm$1.06 to 63.62$\pm$1.79 ng/mL, and later decreased to 55.83$\pm$1.15 ng/mL during the post-hypoxemic recovery period. Total body clearance ($CL_{TB}$) of MCP was significantly decreased from 274.2$\pm$48.0 L/h to 205.40$\pm$28.2 L/h during hypoxemia, and later restored to 245.8$\pm$44.2 L/h during the post-hypoxemic period. Plasma mono-deethylated MCP concentration (32.78$\pm$1.73 ng/mL) also increased, compared to the control group (21.20$\\pm$1.39 ng/mL), during hypoxemia and subsequent normoxemic period. Renal excretion of MCP and its metabolites was also decreased during hypoxemia, while urine flow was increased with a concomitant decrease in urine osmolality. Thus, the results indicate that acute moderate hypoxemia affects MCP pharmacokinetics.

• Clinical and Experimental Pediatrics
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• 제55권4호
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• pp.136-142
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• 2012

Purpose: Urinary excretion of N acetyl-beta-D glucosaminidase (NAG) and ${\beta}_2$-microglobulin (${\beta}_2$-M) was increased in the presence of proximal tubular damage. Based on these urinary materials, we investigated the ability of expecting renal function in chronic glomerular diseases. In this study, we evaluated the relationship between glomerular filtration rate (GFR) urinary NAG, and urinary ${\beta}_2$-M. Methods: We evaluated 52 children with chronic kidney disease at the Chung-Ang University Hospital between January 2003 and August 2009. We investigated the 24-hour urinalysis and hematologic values in all 52 patients. Serum creatinine, creatinine clearance (Ccr), serum cystatin C, urinary ${\beta}_2$-M and urinary NAG were measured. Results: Out of 52 patients, there were 13 children with minimal change in disease, 3 children with focal segmental glomerulosclerosis, 17 children with immunoglobulin A nephropathy, 15 children with Henoch-Sch$\ddot{o}$nlein purpua nephritis, 3 children with poststreptococcal glomerulonephritis, and 1 child with thin glomerular basement membrane disease. In these patients, there were significant correlation between the Ccr and urinary NAG (r=-0.817; $P$ <0.01), and between the GFR (as determined by Schwartz method) and urinary NAG (r=-0.821; $P$ <0.01). In addition, there was a significant correlation between the GFR (as determined by Bokencamp method) and urinary NAG (r=-0.858; $P$ <0.01). Conclusion: In our study, there was a significant correlation between the GFR and urinary NAG, but there was no correlation between the GFR and urinary ${\beta}_2$-M, suggesting that the GFR can be predicted by urinary NAG in patients with chronic glomerular disease.

• Journal of Pharmaceutical Investigation
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• 제34권3호
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• pp.161-168
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• 2004

5-Fluorouracil (5-FU) is an antimetabolite anticancer agent active against many types of solid tumors. Tegafur (TF), a prodrug of 5-FU, is frequently used in combination with uracil as dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine. We studied the stability of 5-FU and TF in biological fluids of rats and determined their bioavailability (BA) and excretion into bile, and urine. The drug concentrations were analyzed by an HPLC method. At room temperature, there was a 14-30% decrease in the concentration of 5-FU and TF in bile, urine, and plasma specimen at 10 and $100\;{\mu}g/ml$ over 240 min. No significant difference was noted among the sample types or between two different concentrations of 10 and $100{\mu}g/ml$. The decrease in drug concentration was significantly less in samples kept on ice (6-12%) for both drugs. These data indicate that biological fluid samples containing 5-FU or TF in plasma, urine, or bile should be placed on ice during the sample collection. Following these storage guidelines, samples were collected after administration 50 mg/kg of each drug via i.v. or oral route. BA was 1.5 folds greater for TF (60%) than that of 5-FU (42%). Approximately 0.52 and 3.3% of the i.v. doses of 5-FU and TF was excreted into bile, respectively. Renal clearance of 5-FU was about 16% of its total body clearance. These results suggest that instability of 5-FU and TF in biological fluids should be considered in pharmacokinetic or pharmacogenomic studies.

• The Korean Journal of Physiology and Pharmacology
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• 제15권5호
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• pp.273-277
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• 2011

Nitric oxide (NO) and atrial natriuretic peptide (ANP) may induce vascular relaxation by increasing the production of cyclic guanosine monophosphate (cGMP), an important mediator of vascular tone during sepsis. This study aimed to determine whether regulation of NO and the ANP system is altered in lipopolysaccharide (LPS)-induced kidney injury. LPS (10 $mg{\cdot}kg^{-1}$) was injected in the tail veins of male Sprague-Dawley rats; 12 hours later, the kidneys were removed. Protein expression of NO synthase (NOS) and neutral endopeptidase (NEP) was determined by semiquantitative immuno-blotting. As an index of synthesis of NO, its stable metabolites (nitrite/nitrate, NOx) were measured using colorimetric assays. mRNA expression of the ANP system was determined by real-time polymerase chain reaction. To determine the activity of guanylyl cyclase (GC), the amount of cGMP generated in response to sodium nitroprusside (SNP) and ANP was calculated. Creatinine clearance decreased and fractional excretion of sodium increased in LPS-treated rats compared with the controls. Inducible NOS protein expression increased in LPS-treated rats, while that of endothelial NOS, neuronal NOS, and NEP remained unchanged. Additionally, urinary and plasma NOx levels increased in LPS-treated rats. SNP-stimulated GC activity remained unchanged in the glomerulus and papilla in the LPS-treated rats. mRNA expression of natriuretic peptide receptor (NPR)-C decreased in LPS-treated rats, while that of ANP and NPR-A did not change. ANP-stimulated GC activity reduced in the glomerulus and papilla. In conclusion, enhancement of the NO/cGMP pathway and decrease in ANP clearance were found play a role in the pathogenesis of LPS-induced kidney injury.

• Toxicological Research
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• 제28권4호
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• pp.235-240
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• 2012

$^{99m}Tc$ tricarbonyl glycine monomers, trimers, and pentamers were synthesized and evaluated for their radiolabeling and in vivo distribution characteristics. We synthesized a $^{99m}Tc$-tricarbonyl precursor with a low oxidation state (I). $^{99m}Tc(CO)_3(H_2O)_3^+$ was then made to react with monomeric and oligomeric glycine for the development of bifunctional chelating sequences for biomolecules. Labeling yields of $^{99m}Tc$-tricarbonyl glycine monomers and oligomers were checked by high-performance liquid chromatography. The labeling yields of $^{99m}Tc$-tricarbonyl glycine and glycine oligomers were more than 95%. We evaluated the characteristics of $^{99m}Tc$-tricarbonyl glycine oligomers by carrying out a lipophilicity test and an imaging study. The octanol-water partition coefficient of $^{99m}Tc$ tricarbonyl glycine oligomers indicated hydrophilic properties. Single-photon emission computed tomography imaging of $^{99m}Tc$-tricarbonyl glycine oligomers showed rapid renal excretion through the kidneys with a low uptake in the liver, especially of $^{99m}Tc$ tricarbonyl triglycine. Furthermore, we verified that the addition of triglycine to prototype biomolecules (AGRGDS and RRPYIL) results in the improvement of radiolabeling yield. From these results, we conclude that triglycine has good characteristics for use as a bifunctional chelating sequence for a $^{99m}Tc$-tricarbonyl-based biomolecular imaging probe.

• 대한핵의학회지
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• 제24권1호
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• pp.49-55
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• 1990

For the development of $^{99m}Tc-labelled$ 3-iodo-2,4,6-trimethyl-iminodiacetic acid $(^{99m}Tc-IOTIDA)$, various experiments such as synthesis of IOTIDA, establishment of labelling conditions, determination of radiochemical purity, examination of stability, and organ distribution of rat were carried out. 1) IOTIDA was synthesized with a total yield of 42% from the starting material of 2,4-6-trimethylaniline via chloroacetylation, iodination, and condensation with iminodiacetic acid (IDA). 2) Freeze-dried instant labelling kits were prepared from aqueous solution $(pH\;5.8\sim6.0)$ so as to contain 40 mg IDA compound and 0.4 mg $SnCl_2$, per vial. Labelling of the contents of kit vials with $Na^{99m}TcO_4$, exhibited formation of two kinds of complex which was identified by ITLC-SA. After labelling, complex ( I ) was gradually converted to complex (II) with time. Labelling yield and radiochemical purity were above 99.5% based on the two complexes over-all. 3) $^{99m}Tc-IOTIDA$ maintained high radiochemical purity of above 99% until 6 hours after preparation at room temperature. Instant labelling kits stored at $4^{\circ}C$ for 6 month period also exhibited high labelling yield of above 99%. 4) Results obtained from animal experiments showed that most of the $^{99m}Tc-IOTIDA$ was rapidly excreted through hepatobiliary track into the intestines but with negligible renal excretion.

• 방사선산업학회지
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• 제12권4호
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• pp.355-363
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• 2018

A novel $N_3S_1$ chelate, Pro-Lys-Cys (PKC) to cyclic RGD to radiolabel with $^{99m}Tc$ was conjugated in an effort to decrease the high intestinal accumulation observed for $^{99m}Tc$-labeled PGC-RGD. The target specificity of the resulting PKC-RGD was similar to that of PGC-RGD as determined by a cell binding assay and a competition binding assay. The $^{99m}Tc$ radiolabeling of PKC-RGD resulted in radiochemical yields of 98% under mild conditions at high specific activities. Biodistribution data in normal mice clearly showed a significant decrease in intestinal uptake at 2 h postinjection for the $^{99m}Tc-PKC-c$ (RGDyK) compared to the $^{99m}Tc-GC-c$ (RGDyK) (from $19.65%ID{\cdot}g^{-1}$ to $7.31%ID{\cdot}g^{-1}$ for the GI tract). The $^{99m}Tc-PKC-c$ (RGDyK) biodistribution was also shown by a higher retention of radioactivity in the whole body, but with kidney accumulation over 8-fold higher than observed with $^{99m}Tc-PGC-c$ (RGDyK) at 2 h ($12.62%ID{\cdot}g^{-1}$ for PKC-RGD and $1.54%ID{\cdot}g^{-1}$ for PGC-RGD, respectively). These results show that the biodistribution may be altered especially concerning lipophilicity resulting in renal rather than hepatobiliary excretion. This comparative study made it possible to explore the effects of lipophilicity on the biodistribution of $^{99m}Tc$-labeled c (RGDyK) through the use of different tripeptide $N_3S_1$ chelators. Therefore, $^{99m}Tc-PKC-c$ (RGDyK) may be an attractive alternative for the in vivo imaging of integrin receptors.

• 핵의학기술
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• 제13권3호
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• pp.48-55
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• 2009

목적 : 현재 원자력법에 환자의 입원치료, 외래치료의 기준 용량(mCi)과 선량률(${\mu}Sv/h$)이 명확히 고시되어 있지 않아, (IAEA, BSS)기준에 따라 환자를 퇴원시킨다. 그래서 $^{131}I$ 3700 MBq (100 mCi)를 투여하는 갑상선암 치료환자에게 입원기간 동안 선량률(${\mu}Sv/h$)을 측정하여 선량률(${\mu}Sv/h$)과 잔류량(mCi), 배설률(%)에 따라 $^{131}I$ 3700 MBq (100 mCi)가 70%가 감소하여 1110 MBq (30 mCi)가 되는 시간을 확인하여 치료환자들의 퇴원기준 설정에 참고 자료가 되고자 한다. 실험재료 및 방법 : 갑상선제거수술을 받고 $^{131}I$ 3700 MBq (100 mCi)을 투여하는 환자 중 신장 기능에 이상이 없는 42명을 대상으로 하였다. 측정기는 Thermo사의 FH40G-L을 사용하여 $^{131}I$ Capsule을 개봉하고서 $^{131}I$ 3700 MBq (100 mCi)을 투여 후 즉시부터, 거리와 높이 1m에서 1, 2, 4, 8, 20, 24, 40시간째 소변 전/후 20초간 평균 측정하였다. 결과 및 결론 : (IAEA, BSS) 기준에 따라 $^{131}I$ 3700 MBq (100 mCi)를 투여한 후 20시간째 $49{\pm}13\;{\mu}Sv/h$로 100%에서 78%가 배설하여 체내에 814 MBq (30 mCi)가 잔류하여 퇴원 가능한 체내 잔류량 1110 MBq (30 mCi) (1 m에서 $66\;{\mu}Sv$/h) 이하를 만족하였다.

• 한국식품위생안전성학회지
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• 제24권4호
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• pp.378-384
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• 2009

카드뮴에 대한 다양한 인체안전기준이 알려지고 있고, 각 국가마다 신장기능이상을 나타내는 뇨 중 카드뮴 농도에 차이를 나타내고 있어 국내의 역학자료를 고려한 카드뮴 인체안전기준을 검토 제안하므로 위해관리의 효율을 향상시키고자 본 연구를 수행하였다. WHO, USEPA, ATSDR에서 식이섭취량과 뇨 중 카드뮴 농도와의 상관관계를 PBPK 모델로 정립 제안한 방법 등이 검토되었으며, 최종적으로 WHO의 1일 인체섭취량 산출 모델에 따라 계산하였다. 국내 역학자료(병산리 폐광지역 인체역학조사)에 의하면 뇨 중 카드뮴 최고농도인 11.63 ug/g creatinine 수준에서도 단백뇨 등의 신장기능이상이 확인되지 않아, WHO 등 국외 역학자료를 검토하여 신장이상을 나타내기 시작하는 뇨 중 카드뮴 농도를 2.5 ug/g creatinine으로 결정하였다. 카드뮴 오염원 노출과 무관할 것으로 예측되는 우리나라 성인의 뇨 중 카드뮴 수준 0.38 ug/g creatinine과 최근에 평가된 식품섭취를 통한 카드뮴 섭취량(8.3~10.4 ug/day)의 비율이 21.8~27.3 수준에 해당됨을 확인하여 이를 WHO에서 제안된 모델에 적용하였다. 식이섭취량과 신장 이상과의 상관관계 중 카드뮴 생체이용률 10%, 흡수된 카드뮴의 배출량을 50%로 가정한 결과를 국내 인체안전기준 설정에 적용한 결과(이 가정에서 사용된 식이섭취량에 대한 뇨 중 카드뮴 농도의 비율은 24), 신장이상이 발생되기 시작하는 뇨 중 카드뮴 농도인 2.5 ug/g creatinine에 대해 예측된 카드뮴 1일 섭취량은 1 ug/kg bw/day여서, 이를 근거로 국내 카드뮴 PTWI를 7 ug/kg bw/week로 제안하였다.