• Asian-Australasian Journal of Animal Sciences
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• 제21권9호
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• pp.1244-1251
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• 2008

The aim of the present study was to delineate the expression and secretion of insulin-like growth factor (IGF) system components by pig liver cells. Hepatocytes were prepared from 3-wk-old weanling piglets following a two-step collagenase perfusion procedure, after which the cells were incubated for 24 or 48 h at a density of $2{\pm}10^5$ cells per 35-mm dish in 2-ml Williams' medium E. The cells were found to express the genes encoding IGF-I, IGF-binding proteins (IGFBPs)-2 and -3 and acid-labile subunit (ALS) by reverse transcription-polymerase chain reaction (RT-PCR) following the culture. However, IGF-I was localized to hepatocytes by immunohistochemical analysis, whereas IGFBP-3 was localized to endothelial cells, but not to hepatocytes. This indicated that the IGFBP-3 gene expression detected by RT-PCR was likely to have been contributed by unidentified non-parenchymal cells that had not been removed during the hepatocyte preparation. The conditioned culture medium (CCM) of the cells contained immunoreactive IGF-I and IGF-II, with the latter being seven-fold more abundant than the former. The CCM also contained 43-, 40-, 34-, 31-kDa doublet and 26-kDa IGFBPs as examined by Western ligand blotting. The 40-, 34- and 31-kDa doublet IGFBPs were approximately three-fold as abundant as the 43- and 26-kDa IGFBPs. Moreover, the 43- and 40-kDa doublet and the 34-kDa IGFBPs were immunoprecipitable with IGFBP-3 and IGFBP-2 antibodies, respectively. Overall, these results are similar to those known in the rat, which suggests that the IGF system components are likely to be expressed and secreted in pig liver in a manner similar to that in rat liver.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.98-98
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• 1997

This study was done to investigate the effect of vitamin E on hypoxia/reoxygenation-induced hepatic injury in isolated perfused rat liver. Rats were pretreated with vitamin E or vehicle(soybean oil). Isolated livers from fasted 18 hours were subjected to 45min of low flow hypoxia or N$_2$ hypoxia followed by reoxygenation for 30min. The perfusion medium used was KHBB(pH 7.4) and 50${\mu}$㏖/$\ell$ of ethoxycoumarin was added to the perfusate to determine the ability of hepatic drug-metabolizing systems, In low flow hypoxia model, total glutathione and oxidised glutathione levels were significantly increased by hepoxia/reoxygenation with slight increase in LDH levels. These increases were prevented by vitamin E pretreatment. In N$_2$ hypoxia model, LDH, total glutathione and oxidized glutathione levels were increased significantly by hypoxia but restored to normal level by reoxygenation. Vitamin E had little effect on this hypoxic damage. There were no significant changes in the rate of hepatic oxidation of 7-EC to 7-HC in both hepoxic models. But, the subsequent conjugation of 7-HC by sulfate or glucuronic acid were significantly decreased by hypoxia, but restored by reoxygenation in both hypoxia models. As opposed to our expectation, treatment with vitamin E aggrevated the decrease of the rate of conjugation and even inhibited the restoration by reoxygenation. Our findings suggest that hypoxia/reoxygenation diminishes phase II drug metabolizing function and this is, in part, related to decreased energy level.

• Journal of Pharmaceutical Investigation
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• 제36권4호
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• pp.263-269
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• 2006

Deficiencies in the early ADMET(absorption, distribution, metabolism, elimination and toxicity) information on drug candidate extract a significant economic penalty on pharmaceutical firms. Microscale cell culture analogue-microscale gastrointestinal(${\mu}CCA-{\mu}GI$) device using Caco 2, L2 and HEp G2/C3A cells, which mimic metabolic process after absorption occurring in humans was used to investigate the toxicity of the model chemical, acetaminophen(AAP). The toxicity of acetaminophen determined after induction of CYP 1A1/2 in Caco 2 cells was not significant. In a coculture system, although no significant reduction in viability of HEp G2/C3A and L2 cells was found, approximately 5 fold increase in the CYP 1A1/2 activity was observed. These results appear to be related to organ-organ interaction. The oral administration of a drug requires addition of the absorption process through small intestine to the current ${\mu}CCA$ device. Therefore, a perfusion coculture system was employed for the evaluation of the absolution across the small intestine and resulting toxicity in the liver and lung. This system give comprehensive and physiologic information on oral uptake and resulting toxicity as in the body. The current ${\mu}CCA$ device can be used to demonstrate the toxic effect due to organ to organ interaction after oral administration,

• Nuclear Engineering and Technology
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• 제55권1호
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• pp.248-253
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• 2023

Directly, it is not possible to measure the absorbed dose of radiopharmaceuticals in the organs of the human body. Therefore, simulation methods are utilized to estimate the dose in distinct organs. In this study, individual organs were separately considered as the source organ or target organ to calculate the mean absorption dose, which SAF and S factors were then calculated according to the target uptake via MIRD method. Here, ^99mTc activity distribution within the target was analyzed using the definition and simulation of ideal organs by summing the fraction of cumulative activities of the heart as source organ. Thus, GATE code was utilized to simulate the Zubal humanoid phantom. To validate the outcomes in comparison to the similar results reported, the accumulation of activity in the main organs of the body was calculated at the moment of injection and cardiac rest condition after 60 min of injection. The results showed the highest dose absorbed into pancreas was about 21%, then gallbladder 18%, kidney 16%, spleen 15%, heart 8%, liver 8%, thyroid 7%, lungs 5% and brain 2%, respectively, after 1 h of injection. This distinct simulation model may also be used for different periods after injection and modifying the prescribed dose.

• 대한핵의학회지
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• 제39권4호
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• pp.246-251
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• 2005

목적: 심근관류 스펙트 검사에서 감쇠의 영향을 보정하기 위해 여러 가지 방법들이 사용되어 왔다. 본 연구는 CT를 이용한 감쇠보정이 관상동맥조영술이 정상인 환자들을 대상으로 하였을 때 어떠한 영향을 주는지 알아보고 기존의 감쇠보정방법들과 차이가 있는지를 알아보고자 하였다. 대상 및 방법: 관상동맥질환이 의심되어 심근 SPECT/CT를 시행한 환자들 중 관상동맥조영술상 정상소견을 보인 25명에서, Pryor 등의 방법으로 관상동맥질환의 위험도가 5.0% 미만인 15명의 환자를 대상으로 하였다. (남 6, 여 9, 평균연령 $58{\pm}8$세). CT가 장착된 Millennium VG (GE) 카메라로 감쇠보정을 하였으며, 영상의 판독은 육안분석과 극성지도를 이용한 정량적 분석을 시행하였다. 정량적 분석의 경우 극성지도 상에서 각 심근벽의 섭취율(최대 섭취율에 대한 %)을 구하여 감쇠보정을 하지 않은 영상과 감쇠보정을 한 영상을 비교하였다. 결과: 육안분석에서 감쇠보정을 한 경우 하벽의 섭취는 증가한 반면, 전벽과 심첨부 및 격벽의 섭취는 감소하였다. 간에서의 섭취도 감쇠보정을 한 경우에 증가하였다. 정량분석에서는 심첨부의 경우 감쇠보정 후 섭취율이 감소하였고, 하벽의 경우 증가하였다. 하벽의 경우 감쇠보정을 하여 판독에 도움을 받을 수 있었고, 반면 전벽이나 심첨부의 경우 감쇠보정 후 판독에 어려움이 있었다. 결론: 하벽의 경우 CT를 이용한 감쇠보정을 한 경우 판독에 도움이 되었으며, 감쇠보정전 영상이 정상인 경우 심첨부나 전벽등의 판독시는 주의가 필요하다.

• Investigative Magnetic Resonance Imaging
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• 제2권1호
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• pp.73-82
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• 1998

목적 : 간특정 MR 조영제를 이요하여 간세포의 세포막을 통한 물분자의 교환 및 세포막 투과율을 정확히 측정 할 수 있는 MR 기법을 개발하고자 하였다. 대상 및 방법 : 쥐의 간세포를 분리하여 낸 후 NMR 측정을 시도하엿다. 모든 실험은 0.02MHz부터 60 MHz까지 양성자의 Larmor 주파수를 변화시킬 수 있는 IBM형 field cycling relaxometer를 사용하여 시행하였으며 spin-echo 펄스열을 사용하여 T1 자기이완시간을 측정하였다. 전오도의 간특정 조영제인 Gd-EOB-DTPA를 함유하고 있는 간세포 샘플로부터 획득한 T1 데이터를 연속분포 분석법을 사용하여 분석하였으며 이때 이론적 모델로는 Two compartmental exchange 모델을 이용하였다. 결과 : 간세포내의 물분자의 평균 거주시간은 약 250 msec이며 간세포막의 투과율에 대한 최저치는 $(1.3{\pm}0.1){\;}{\times}{\;}10^{-3}cm/sec$ 이었다. 자기이완시간의 연속적인 분포도를 구할 수 있는 CONTIN 분석기법을 적용한 결과 확산적 물분자 교환이 일어남을 밝혔고 이러한 확산적 교환의 정도가 간세포의 경우 세포내 공간에서는 작지 않다는 사실을 규명 할 수 있었다. 결론 : 연속분포 분석기법을 적용하는 경우 Gd-EOB-DTPA는 간세포에서의 물분자의 교환정도 및 세포막의 물분자에 대한 투과율을 측정하는데 매우 유용한 방법임을 확인하였고 간세포에서의 물분자의 교환속도는 적혈구에서의 물분자 교환 속도에 비해 매우 느리다는 사실을 확인하였다. 따라서 조직 특정 조영제는 해당 조직 혹은 세포의 세포막 투과율과 같은 생리학적 정보를 알아낼 수 있는 기능적 조영제로서의 유용성을 입증할 수 있었다.

• 한국해양바이오학회지
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• 제13권2호
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• pp.86-93
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• 2021

A high salt diet contributes to kidney damage by causing hypoxia and oxidative stress. Recently, an increase in dietary salt has been reported to induce an inflammatory phenotype in immune cells, further contributing to kidney damage. However, studies on the exact mechanism and role of a high salt diet on the inflammatory response in the kidneys are still insufficient. In this study, a cisplatin-induced acute kidney injury model using C57BL/6 mice was used to analyze the effect of salt intake on kidney injury. Results showed that high salt administration aggravated kidney edema in mice induced by treatment with cisplatin. Moreover, the indicators of kidney and liver function impairment were significantly increased in the group cotreated with high salt compared with that treated with cisplatin alone. Furthermore, the exacerbation of kidney damage by high salt administration was also associated with a decrease in the number of cells in the immune regulatory system. Additionally, high salt administration further decreased renal perfusion functions along with increased cisplatin-induced damage to proximal tubules. This was accompanied by increased expression of T cell immunoglobulin, mucin domain 1 (a biomarker of kidney injury), and Bax (a pro-apoptotic factor). Moreover, cisplatin-induced expression of proinflammatory mediators and cytokines, including cyclooxygenase-2 and tumor necrosis factor-α in kidney tissue, was further increased by high salt intake. Therefore, these results indicate that the kidney's inflammatory response by high salt treatment can further promote kidney damage caused by various pathological factors.

• Journal of Ginseng Research
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• 제21권3호
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• pp.174-186
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• 1997

In this study, rat hepatocytes known to have active carbohydrate metabolism were obtained by using the liver perfusion technique to examine the hypoglycemic action of red ginseng saponin components [ginsenoside (mixture, $Rb_1$, and $Rg_1$)] and incubated in two different media-one containing insulin and glucagon (control group), and the other containing glucagon only, The specific activities of some regulatory enzymes such as glucokinase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glucose 6-phosphatase, in main pathways which were directly related to the glucose metabolism were compared between these two kinds of hepatocytes cultured in two different media. The effects of red ginseng saponin components [ginsenoside (mixture, $Rb_1$, and $Rg_1$)] under the concentration of $10^3$~$10^6$% on these enzymes In hepatocytes were also investigated, when they were added to these two media. The results were as follows. The specific activity of enzymes such as glucokinase, glucose 6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase related to glucose-consuming pathways of insulin-deficient group was much less than control one, however, their decreased activity was recovered after the addition of ginseng components at all range of concentrations. The increased specific activity of these on - zymes was shown by the addition of ginseng components to the control group. On the other hand, the specific activity of glucose 6-phosphatase related to glucose-producing pathway of insulin-deficient group was much higher than control one, but their Increased activity was decreased after the addition of ginseng components at all range of concentrations. The same results were obtained after the addition of ginseng components to the control group. These results suggest that the red ginseng saponin components might better diabetic hyperglycemia by regulating the activity of enzymes related to glucose metabolism directly and/or Indirectly though more detailed studies were needed.

• Asian-Australasian Journal of Animal Sciences
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• 제19권9호
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• pp.1328-1334
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• 2006

This paper aimed to study the toxicity of arsanilic acid on rat primary hepatocytes in vitro by a modification of the perfusion method. The conditions included concentrations of 0, 1.085, 10.85, 108.5, 1,085 and 10,850 mg/kg arsanilic acid in RPMI 1,640 medium at rat hepatocytes plates respectively, each group had five repeats at $37^{\circ}C$ for 48 h. The rat primary hepatocytes survival ratio, DNA Ladder, activities of glutathione peroxidase (GSH-px), superoxide dismutase (SOD) and catalase (CAT) in hepatocytes, activity of SOD in the medium and the expression of gene bax in hepatocytes were measured at 12 h, 24 h and 48 h respectively. The results showed that arsanilic acid decreased the activities of GSH-px and SOD, and increased the activity of CAT in all dosages, and affected as positive DNA ladder. Although the SOD activities of both hepatocytes and medium in 1.085 mg/L arsanilic acid were significantly lower than the base line at 12 h, CAT activity in 10.85 mg/L arsanilic acid was significantly higher than the base line at 48 h, and all of the DNA ladders were positive, which means 1.085 mg/L arsanilic acid induced apoptosis at 24 h. The gene expression of bax was significantly upregulated in 1.085 mg/L arsanilic acid or higher for 24 h.The parameters in 1,085 mg/L and 10,850 mg/L arsanilic acid had more severe changes than the others at any time indicating that these levels of arsanilic acid were toxic hazards for hepatocyte survival. It was concluded that arsanilic acid induced a dosage- and time-dependent gene expression of bax, 1.085 mg/L arsanilic acid could be involved in rat liver cell apoptosis at 24 h. Arsanilic acid as additives in livestock feed could present potential toxic implications for farm animals.

• Tuberculosis and Respiratory Diseases
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• 제51권2호
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• pp.161-165
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• 2001

저자 등은 다량의 흉막유출로 반대측 폐의 일부 허탈과 폐부종을 보이는 만성 간질환 환자의 호흡곤란의 경감을 위하여 시행한 흉강천자 후 발생한 양측성 재팽창성 폐부종(reexpansion pulmonary edema)과 이로 인한 급성호흡곤란증후군을 경험하고 이를 문헌고찰과 함께 보고하는 바이다.