• Journal of Pharmaceutical Investigation
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• v.27 no.1
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• pp.1-10
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• 1997

For the purpose of improving the chemotherapeutic index of acyclovir(ACV), it was conjugated with asialofetuin(AF), which has been reported to enter into hepatocytes. When $[H^3]$ acyclovir in itself or its conjugate were administered to rats, the latter was taken up more selectively by the liver than any other tissues. The stability of ACVMP-AF conjugate in phosphate buffer (pH 5.0) and rat liver homogenate showed a pseudo-first order profile. ACVMP-AF, however, was relatively stable in pH7.4 phosphate buffer and rat plasma. The conjugate was added to the isolated rat hepatocyte and cellular uptake was monitored by scintillation counting for up to 6 hours at $37^{\circ}C$. Hepatocytes incubated with the conjugate exhibited radioactivities significantly enhanced over control levels dose-dependently, i.e., a 3-40 fold increase in radioactivities was observed over controls at the conjugate concentrations of $0.1-10\;{\mu}g/ml$. The AUQ in the liver, kidney, spleen, intestine and lung was higher in treatment with ACVMP-AF than that in treatment with ACV. In treatment with ACVMP-AF, the weighted-average overall drug targeting efficiency(Te) for the liver was higher than in treatment with ACV(57.00 vs 13.31 %), and the weighted-average tissue exposure(Re) was 5.03 for the liver. These results indicated that ACVMP-AF conjugate was rapidly taken up by hepatocytes and could be an efficient and selective hepatic targeting system.

• Journal of Pharmacopuncture
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• v.20 no.1
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• pp.45-51
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• 2017

Objectives: This study aimed to evaluate the hypoglycemic effects of an ethanol extract of Cassia abbreviata (ECA) bark and the possible mechanisms of its action in diabetic albino rats. Methods: ECA was prepared by soaking the powdered plant material in 70% ethanol. It was filtered and made solvent-free by evaporation on a rotary evaporator. Type 2 diabetes was induced in albino rats by injecting 35 mg/kg body weight (bw) of streptozotocin after having fed the rats a high-fat diet for 2 weeks. Diabetic rats were divided into ECA-150, ECA-300 and Metformin (MET)-180 groups, where the numbers are the doses in mg.kg.bw administered to the groups. Normal (NC) and diabetic (DC) controls were given distilled water. The animals had their fasting blood glucose levels and body weights determined every 7 days for 21 days. Oral glucose tolerance tests (OGTTs) were carried out in all animals at the beginning and the end of the experiment. Liver and kidney samples were harvested for glucose 6 phosphatase (G6Pase) and hexokinase activity analyses. Small intestines and diaphragms from normal rats were used for ${\alpha}-glucosidase$ and glucose uptake studies against the extract. Results: Two doses, 150 and 300 mg/kg bw, significantly reduced the fasting blood glucose levels in diabetic rats and helped them maintain normal body weights. The glucose level in DC rats significantly increased while their body weights decreased. The 150 mg/kg bw dose significantly increased hexokinase and decreased G6Pase activities in the liver and the kidneys. ECA inhibited ${\alpha}-glucosidase$ activity and promoted glucose uptake in the rats' hemi-diaphragms. Conclusion: This study revealed that ECA normalized blood glucose levels and body weights in type 2 diabetic rats. The normalization of the glucose levels may possibly be due to inhibition of ${\alpha}-glucosidase$, decreased G6Pase activity, increased hexokinase activity and improved glucose uptake by muscle tissues.

• The Korean Journal of Nuclear Medicine
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• v.33 no.1
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• pp.84-93
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• 1999

Purpose: We investigated the direct labeling method of antibody with $^{99m}Tc$ and $^{188}Re$ and examined the stability and function of these labeled compounds in in vitro and in vivo. Materials and Methods: Disulfide bond of nonspecific human IgG was reduced to -SH group by 2-mercaptoethanol. Stannous ion was used to reduce $^{99m}Tc$ and $^{188}Re$. The stability of $^{99m}Tc$-IgG and $^{188}Re$-IgG was estimated upto 24 hrs. Biodistribution was evaluated in abscess bearing rats at 4 and 24 hr post-injection of $^{99m}Tc$ or $^{188}Re$ labeled IgG. Results: The number of -SH group per reduced IgG molecule was 2.34. The labeling yield of $^{99m}Tc$-IgG and $^{188}Re$-IgG were 90% and 95%, respectively The stability of $^{99m}Tc$-IgG at 1, 4, 6 and 24 hr was 91%, 83%, 78%, 7% and that of $^{188}Re$-IgG at 1, 4, 16 and 24 hr was 94%, 80%, 47%, 42%, respectively. At 4 hr post-injection of $^{99m}Tc$-IgG, high uptake was found on kidney, blood, stomach and abscess ($9.42{\pm}0.68,\;1.43{\pm}0.24,\;0.86{\pm}0.18,\;0.72{\pm}0.10$ %ID/g, respectively). The uptakes at 24 hr were kidney, abscess,.itomach, and blood in descending order. In case of $^{188}Re$-lgG, high uptake at 4 hr post injection appeared on kidney, blood, abscess and stomach ($3.92{\pm}0.62,\;1.32{\pm}0.08,\;0.88{\pm}0.01,\;0.26{\pm}0.06$, respectively). The uptakes at 24 hr were kidney, abscess, blood and stomach in descending order. The abscess to blood uptake ratio of $^{99m}Tc$-IgG was 0.5 at 4 hr and 2.02 at 24 hr and that of $^{188}Re$-IgG was 0.67 and 1.29. Conclusion: $^{99m}Tc$-IgG and $^{188}Re$-IgG canbe labeled efficiently with direct labeling method. However, $^{99m}Tc$-IgG and $^{188}Re$-IgG, labeled with direct method, was unstable. Further study is needed to enhance the stability of the antibody labeling.

• Journal of Acupuncture Research
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• v.20 no.6
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• pp.128-139
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• 2003

Juglans sinensis Dode has been reported to have antioxidant activity. However, the effect of Juglans sinensis Dode aquacupuncture(JS) on reactive oxygen species(ROS)-induced alterations in membrane transport function in renal tubular cells. This study was performed to evaluate the effect of JS on the organic hydroperoxide t-butylhydroperoxide(tBHP)-induced inhibition of $Na^+$-dependent phosphate($Na^+$-Pi) uptake in opossum kidney (OK) cells, an established renal proximal epithelial cell line. tBHP inhibited $Na^+$-Pi uptake in a time-dependent manner. The inhibitory effect of tBHP was prevented by JS over concentration range of 0.05-1mg/100ml in a dose-dependent manner. Kinetic studies showed that tBHP caused an decrease in Vmax for $Na^+$-Pi uptake without any a significant change in Km. $Na^+$-dependent phosphonoformic acid binding, a irreversible inhibitor of renal $Na^+$-Pi uptake, was decreased by tBHP treatment. The reduction in Vmax and phosphonoformic acid binding by tBHP was prevented by JS. tBHP induced lipid peroxidation and its effect was completely inhibited by JS and antioxidant N,N'-diphenyl-p-phenylenediamine. These data suggest that the oxidant inhibits phosphate uptake by a reduction in the number of active carrier across the membrane. JS may prevent oxidant-induced inhibition of membrane transport function by a mechanism similar to antioxidants in renal epithelial cells. Although the precise constituents remain to be explored, JS may be employed as a useful candidate herb for drug development to prevent and treat oxidant-mediated renal failure.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.5
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• pp.529-535
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• 1997

The present study was aimed at investigating whether the vascular calcium regulation is altered in hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in rats, and their thoracic aortae were taken 4 weeks later. The isometric contractile response and calcium uptake of the endothelium-denuded aortic preparations were determined. Caffeine ($0.1{\sim}35\;mmol/L$) induced a greater contraction in 2K1C and DOCA-salt hypertension than in normotensive control. When the vascular calcium store was functionally-depleted by a repeated exposure to caffeine, it took longer to reload the store and to resume the initial contraction force in response to caffeine in both 2K1C and DOCA-salt hypertension. The vascular $^{45}Ca$ uptake following the functional depletion of the cellular store was also greater in both models of hypertension than in control. Ryanodine, calcium channel activator of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced vascular contraction, which was not affected by either 2K1C or DOCA-salt hypertension. Nifedipine, an L-type $Ca^{2+}$ channel blocker, attenuated the restoration of caffeine-induced contraction, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Nifedipine also diminished the vascular $^{45}Ca$ uptake, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Ouabain, a $Na^+,\;K^+-ATPase$ inhibitor, increased the caffeine-induced contraction by a similar magnitude in control and 2K1C hypertension, which was, however, markedly attenuated in DOCA-salt hypertension. Ouabain enhanced the vascular $^{45}Ca$ uptake, the degree of which was not affected by 2K1C hypertension, but was markedly attenuated in DOCA-salt hypertension compared with that in control. Cyclopiazonic acid, a selective inhibitor of $Ca^{2+}-ATPase$ of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced contraction, which was not affected by 2K1C hypertension, but was more marked in DOCA-salt hypertension. These results suggest that the increased vascular calcium storage may be attributed to an enhanced calcium influx in 2K1C hypertension, and to an impaired $Na^+-K^+$ pump activity of the cell membrane and subsequently increased calcium pump activity of the cellular store in DOCA-salt hypertension.

• The Korean Journal of Physiology
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• v.20 no.2
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• pp.225-235
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• 1986

Effects of anions on p-Aminohippurate (PAH) transport across the basolateral membrane (BLM) were studied. Basolateral membrane vesicles were isolated from rabbit renal cortex by using a self-orienting Percoll-gradient centrifugation and $Mg^{2+}-precipitation$. The characteristics of the membrane vesicles was examined by marker enzyme activity, membrane orientation and transport studies. The Na-K-ATPase activity in the fraction containing BLM vesicles was enriched 9·fold, and the alkaline phosphatase activity in the fraction containing BBM vesicles was increased 9-fold, compared with those of the homogenate. The transport properties of the two membrane preparations were studied by a rapid filtration technique. The uptake of PAH by BLM was sensitive to changes in medium osmolarity and inhibited by probenecid. When the uptake of $50{\mu}M$ PAH in voltage-clamped BLM vesicles was determined in the presence of various anions in the incubation medium, cis inhibitions by $SO_4\;and\;SSO_3$ were observed in the presence of sodium gradient (out>in). Sodium-dependent PAH uptake was inhibited competitively by external $SO_4$ PAH uptake in BLM vesicles loaded with 20 mM acetate and $SO_4\;or\;200\;{\mu}M$ PAH was significantly stimulated as compared with unloaded vesicles. The extent of trans-stmulation of PAH uptake by $SO_4$. was increased with the inside concentration of $SO_4$. This trans-stimulatory effect by $SO_4$, was observed to be additive in the presence of Na gradient and completely inhibited by 2 mM probenecid and 1 mM SITS. These results demonstrate that PAH/anion exchange is present in BLM of renal cortex and in this exchange mechanism inorganic as well as organic anions are involved as substrates.

• The Korean Journal of Nuclear Medicine
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• v.29 no.4
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• pp.504-510
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• 1995

Avascular necrosis(AVN) of bone can be resulted from various causes that distrub vascular supply to bone tissue, including steroid therapy after renal transplantation. In this study, we determine the prevalence of the avascular necrosis of bone after renal transplantation and compare the role of the bone scan, SPECT and MRI. In 301 patients with transplanted kidney, the prevalence of avascular necrosis was deter-mined clinically. Site of bone necrosis was evaluated by clinical symptom, bone scan, SPECT and MRI. Bone scan was done in all patients with AVN. Bone SPECT and MRI were done in six cases; and MRI was done in two cases. The prevalence of AVN was 3.3% (10/301), and the site of AVN was 16 femoral heads in 10 patients (bilateral: 60%) and bilateral calcaneal tuberosity in one patient. Bone scan showed typical AVN (cold area with surrounding hot uptake) in 13 lesions, only hot uptake in three lesions (including two calcaneal tuberosities), decreased uptake in one lesion, and normal in one lesion. Decreased uptake and normal lesion showed an equivacal cold area without surrounding hot uptake on SPECT. A symptomatic patient with positive bone SPECT showed normal finding on MRI. The prevalence of AVN of bone after renal transplantation was 3.3%, and whole body bone scan showed multiple bone involvement. Two symptomatic hip Joints without definite lesion on whole body bone scan or MRI showed cold defect on SPECT. Therefore, we conclude that bone SPECT should be perfomed in a symptomatic patient with negative bone scan or MRI in case with high risk of AVN after renal transplantation.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.sup1
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• pp.126-129
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• 2008

Renal cell carcinoma is the most common histological type of renal malignancy, predominant in men and the primary treatment modality of this tumor is surgery. The role of diagnostic imaging in the management of this tumor is the evaluation of extent of disease as well as the detection and characterization of renal mass. US has long been a routine screening tool for kidney but tomographic imaging modalities such as CT and MRI begin to be also commonly used these days. On the other hand, the sensitivity of $^{18}F-FDG-PET$ in detection of renal mass is relatively low because of inherent limitation caused by FDG excretion pathway despite avid uptake of FDG to tumor cell per se. Many studies revealed FDG PET scan could play an important role in detection of metastatic lesions although the sensitivity for the detection of primary lesion is not so high. Furthermore, development of PET/CT scanner will make it possible to expand the indication of FDG PET scan in this malignancy.

• Journal of The Korean Radiological Technologist Association
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• v.29 no.1
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• pp.44-49
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• 2003

Purpose : $^{99m}Tc-DMSA$ renal scan can be used in the evaluation of relative renal function and some anatomy. The relative renal function can be assess by measurement of $^{99m}Tc-DMSA$ uptake by the individual kidney. Renal counts

• Childhood Kidney Diseases
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• v.1 no.1
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• pp.24-30
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• 1997

Purpose: To evaluate the diagnositc value of the absolute and relative renal uptake rates on $^{99m}Tc-DMSA$ renal scan of children with febrile UTI. Method: The absolute and relative renal uptake rates of $^{99m}Tc-DMSA$ were checked in 68 children with febrile urinary tract infection (35 with unilateral focal defect; 13 with bilateral focal defect; and 20 with diffuse bilateral defect) and 49 children with afebrile UTI and normal $^{99m}Tc-DMSA$ renal scan as control. Results: The renal absolute uptake rate in the control group were $21.8{\pm}3.9%(right),\;22.2{\pm}3.9%(left),\;and\;44.2{\pm}7.8%(total)$. The absolute uptake rate gradually increased until the age 12 months and then was stationary. In febrile UTI with unilateral focal defect on the $^{99m}Tc-DMSA$ renal scan, both relative and absolute uptake rates were similarly diagnostic ($41.2{\pm}9.7%,\;16.5{\pm}5.4%$ vs $50.0{\pm}2.6%,\;22.0{\pm}3.9%$, p<0.01). In acute pyelonephritis with bilateral focal defect on the $^{99m}Tc-DMSA$ renal scan, the absolute uptake rate was significantly more diagnostic than the relative uptake rate[$17.3{\pm}5.3%$ (right), $17.4{\pm}5.3%\;(left),\;vs\;21.8{\pm}3.9%,\;(right)\;22.2{\pm}3.9%$, (left)% p<0.01]. In febrile UTI with bilateral diffuse defects on the $^{99m}Tc-DMSA$ renal scan, the absolute uptake rate was significantly diagnostic than the relative uptake rate [$18.1{\pm}3.9%\;(right),\;18.4{\pm}3.8%\;(left),\;vs\;21.8{\pm}3.9%,\;(right)\;22.2{\pm}3.9%$(left), p<0.01]. Conclusion: In the $^{99m}Tc-DMSA$ renal scan, the absolute uptake rate was more useful than the relative uptake rate to evaluate bilateral acute pyelonephritis.