• BMB Reports
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• 제40권4호
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• pp.467-474
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• 2007

Autosomal recessive polycystic kidney disease (ARPKD) is one of the important genetic disorders in pediatric practice. Mutation of the polycystic kidney and hepatic disease gene 1 (PKHD1) was identified as the cause of ARPKD. The gene encodes a 67-exon transcript for a large protein of 4074 amino acids termed fibrocystin, but its function remains unknown. The neoplastic-like in cystic epithelial proliferation and the epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) axis overactivity are known as the most important characteristics of ARPKD. Since the misregulation of $Ca^{2+}$ signaling may lead to aberrant structure and function of the collecting ducts in kidney of rat with ARPKD, present study aimed to investigate the further mechanisms of abnormal proliferation of cystic cells by inhibition of PKHD1 expression. For this, a stable PKHD1-silenced HEK-293T cell line was established. Then cell proliferation rates, intracellular $Ca^{2+}$ concentration and extracellular signal-regulated kinase 1/2 (ERK1/2) activity were assessed after treatment with EGF, a calcium channel blocker and agonist, verapamil and Bay K8644. It was found that PKHD1-silenced HEK-293T cell lines were hyperproliferative to EGF stimulation. Also PKHD1-silencing lowered the intracellular $Ca^{2+}$ and caused EGF-induced ERK1/2 overactivation in the cells. An increase of intracellular $Ca^{2+}$ in PKHD1-silenced cells repressed the EGF-dependent ERK1/2 activation and the hyperproliferative response to EGF stimulation. Thus, inhibition of PKHD1 can cause EGF-induced excessive proliferation through decreasing intracellular $Ca^{2+}$ resulting in EGF-induced ERK1/2 activation. Our results suggest that the loss of fibrocystin may lead to abnormal proliferation in kidney epithelial cells and cyst formation in ARPKD by modulation of intracellular $Ca^{2+}$.

• 대한약리학회지
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• 제21권1호
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• pp.1-11
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• 1985

이물질(xenobiotics) 대사에 관여하는 간장 microsome과 cytosol 효소 활성에 indole, indole-3-carbinol 및 benzofuran이 미치는 영향을 검색하기위하여 마우스에 이들 약물을 각각 5 mmole/kg씩 10일간 투여하여 다음 몇 가지의 성적을 얻었다. Benzofuran은 microsome 효소인 aniline hydroxylase, 7-ethoxycoumarin O-deethylase, p-nitrophenol UDPGA-transferase, epoxide hydrolase와 cytosol 효소인 glutathione S-tranferase, NADH : quinone reductase, UDP-glucose dehydrogenase의 활성도를 증가시켰다. 그러나 benzofuran과는 구조적으로 furan ring내의 N원소가 O원소로 치환되었을 뿐 주된 구조가 유사한 indole과 indole-3-carbinol 투여로는 UDPGA-transferase와 NADH: quinone reductase의 활성도 증가를 볼 수 없었으며, 특히 indole은 NADPH : cytochrome C reductase만을 증가시킨데 비하여 구조상 indole에 carbinol (methanol)기가 붙은 indole-3-carbinol은 수종의 mixed function oxidase와 아울러 특히 epoxide hydrolase의 활성도 역시 증가시켰다. 이러한 결과는 benzofuran과 indole-3-carbinol에 의한 epoxide hydrolase 활성도 증가의 기전의 일부를 설명할 수 있을 것으로 생각된다.

• 보험의학회지
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• 제2권1호
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• pp.218-232
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• 1985

Congenital hereditary disease is in devided into Infantile type and Adult type, Adult type is hidden for many years and keeps normal renal function till middle age. Cyst is stimultaneously made in both sides and becomes lowered in renal function in 30's to 40's. Infantile type is generally born with the big kidneys, renal failure, undergrowth of intrahepatic bile duct. Both infantile and childhood type have ureteral dilatation and portal hypertension In infantile type, it is mostly developed into renal failure, but generally faces death as a result of hepatic disease. The reason of death is that an abnormal condition of recessive autosome affects the liver and kidneys. While the incidence of infantile type is rare as $0.017{\sim}0.07%$ and it is autosomal recessive heredity, Adult type can rarely exist in infantile period. Though it exists in middle period, 50% of patients can live for 2-4 years after the first symptom incidence and 25% can less than 2 years. It is hard to cure completely in medicine and surgery. Three difficulties in familial incidence are comparative decrease of the donor who have no affection on renal transplantation. For another consideration it is to show the family history for several generations. We, the Med. Dept. of Dae Han Kyouk Life Insurance Co. Ltd., used the ultrasonic apparatus in diagnosing the one case of adult type bilateral polycystic kidney and then doubted the family history. As a result of inspecting the family we experienced bilateral polycystic kidney from 3 persons out of 4 who can be inspected. The results are as follows: 1) We could confirm the polycystic kidney from 3 persons out of 4(75%). 2) Then when they came for check up, chief complaint was the pain in all 3 cases(100%). 3) Accompanying disease was hypertension in 2 cases(67%). 4) In early disease incidence, we couldn't observe the specific change in pathological opinion. 5) All 3 cases are not accompanied with cystic lesion in liver, spleen, pancreas.

• Toxicological Research
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• 제34권3호
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• pp.221-229
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• 2018

Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman's space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

• Tuberculosis and Respiratory Diseases
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• 제68권2호
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• pp.62-66
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• 2010

Background: Extracorporeal membrane oxygenation (ECMO) during severe acute respiratory failure helps to recover the pulmonary function. This study evaluated our experience with veno-venous ECMO in adult patients with acute respiratory failure. Methods: From January 2007 to July 2009, ECMO was used on 54 patients. Of these 54 patients, 7 were placed on veno-venous ECMO for acute respiratory failure. The indications of ECMO were based on the lung dysfunction measured as a $PaO_2/FiO_2$ ratio <100 mm Hg on $FiO_2$ of 1.0, or an arterial blood gas pH <7.25 due to hypercapnia despite the optimal treatment. $EBS^{(R)}$, $Bio-pump^{(R)}$, and Centrifugal Rotaflow $pump^{(R)}$ were used and all cannulations were performed percutaneously via both femoral veins. When the lung function was improved, an attempt was made to wean on ECMO at moderate ventilator settings followed by decannulation. Results: Five of the 7 patients were male and the mean age was $46.3{\pm}18.3$. The causes of acute respiratory failure were 3 cases of pneumonia, 2 near-drownings, 1 pulmonary hemorrhage due to acute hepatic failure and 1 mercury vapor poisoning. The mean support time of ECMO was $17.3{\pm}13.7$ days. Of the 7 patients implanted with ECMO, 5 patients (71%) were weaned off ECMO and 3 patients (43%) survived to hospital discharge after a mean 89.6 hospital days. Conclusion: The early use of ECMO for acute respiratory failure in adults due to any cause is a good therapeutic option for those unresponsive to the optimal conventional treatments.

• 대한한방내과학회지
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• 제44권3호
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• pp.354-365
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• 2023

Objective: This study aimed to assess the safety and effect on glucose level of Bojungikgi-tang in patients with type 2 diabetes mellitus. Methods: To review patients' clinical characteristics and laboratory tests retrospectively, we investigated 15 hospitalized patients with type 2 diabetes mellitus who took Bojungikgi-tang at Kyung Hee University Korean Medical Hospital for at least one day between January 2012 and December 2022. The blood glucose levels, including fasting blood sugar (FBS), 2-hour postprandial glucose (PP2) levels, and glycated hemoglobin level, were collected to determine the effect of the Bojungikgi-tang on blood sugar changes. Furthermore, to evaluate the safety of Bojungikgi-tang, hepatic function and renal function tests were implemented, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyltransferase, blood urea nitrogen, creatinine, and Modification of Diet in Renal Disease estimated glomerular filtration rate. Results: When Bojungikgi-tang and a standard treatment for diabetes were administered for patients with type 2 diabetes, it was confirmed that there were no statistically significant changes in FBS and PP2 levels in the analysis of each medication taken. There was no significant difference in the safety profile after taking Bojungikgi-tang. Conclusions: The combined administration of Bojungikgi-tang with standard hypoglycemic medication for patients with type 2 diabetes may not affect blood glucose levels and safety.

• Animal Bioscience
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• 제37권1호
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• pp.131-141
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• 2024

Objective: This experiment aimed to explore the protective action of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata on lipopolysaccharide (LPS)-induced liver injury in broilers. Methods: Total 216 healthy broilers were selected in a 21-d trial and assigned randomly to the following 3 treatments: control (CON) group, LPS group, and LPS+IA group. The CON and LPS groups were provided with a basal diet, whereas the LPS+IA group received the basal diet supplemented with 0.6 mg/kg Macleaya cordata IA. Broilers in LPS and LPS+IA groups were intraperitoneally injected with LPS (1 mg/kg body weight) at 17, 19, and 21 days of age, while those in CON group were injected with equivalent amount of saline solution. Results: Results showed LPS injection caused systemic and liver inflammation in broilers, inhibited immune function, and ultimately lead to liver injury. By contrast, supplementation of IA ameliorated LPS-induced adverse change in serum parameters, boosted immunity in LPS+IA group. Furthermore, IA suppressed the elevation of hepatic inflammatory cytokines and caspases levels induced by LPS, as well as the expressions of genes related to the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway. Conclusion: Dietary inclusion of 0.6 mg/kg Macleaya cordata IA could enhance immune function of body and inhibit liver damage via inactivating TLR4/MyD88/NF-κB signaling pathway in broilers.

• 생명과학회지
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• 제16권6호
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• pp.1060-1065
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• 2006

동물 모델에서의 간기능의 비침습적 평가는 하나의 과제로 남아있다. 간신티그라피는 간의 크기 및 모양의 변화에 대한 정보를 제공할 뿐 아니라 간의 전체적인 기능을 파악할 수 있게 해 주며 간이식의 주요 합병증인 간염, 거부반응 및 담도계 합병증의 진단에도 편리하게 사용될 수 있다. 이에 본 연구에서는 미니돼지의 간 기능을 평가하기 위해 사람에서 주로 사용되는 방사성의약품인 $^{99m}Tc-Tin$ colloid와 $^{99m}Tc-DISIDA$를 이용하여 간 및 간담도 신티그라피를 시행하였다. 그 결과, 사람의 간신티그라피와 달리 미니돼지에서는 $^{99m}Tc-Tin$ colloid가 폐, 간, 위벽 및 신장에 섭취되고 폐와 간의 영상이 겹쳐져 간의 관심영역을 설정할 수 없었다. 그러나 $^{99m}Tc-DISIDA$를 사용한 간담도 신티그라피에서는 심장, 폐, 간, 담낭 및 십이지장으로의 연속적 방사능섭취를 관찰할 수 있었다. 따라서 미니돼지에서의 $^{99m}Tc-Tin$ colloid의 사용은 비특이적 결합력으로 인해 간 기능 평가를 위한 영상에는 적합하지 않으나 $^{99m}Tc-DISIDA$는 간담도 기능을 파악하는데 있어 좋은 수단이 될 수 있을 것으로 생각된다.

• Investigative Magnetic Resonance Imaging
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• 제22권1호
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• pp.1-9
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• 2018

Purpose: This study was designed to optimize the flip angle (FA) and scan timing of the hepatobiliary phase (HBP) using the 3D T1-weighted, gradient-echo (GRE) imaging with controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) technique on gadoxetic acid-enhanced 3T liver MR imaging. Materials and Methods: Sixty-two patients who underwent gadoxetic acid-enhanced 3T liver MR imaging were included in this study. Four 3D T1-weighted GRE imaging studies using the CAIPIRINHA technique and FAs of $9^{\circ}$ and $13^{\circ}$ were acquired during HBP at 15 and 20 min after intravenous injection of gadoxetic acid. Two abdominal radiologists, who were blinded to the FA and the timing of image acquisition, assessed the sharpness of liver edge, hepatic vessel clarity, lesion conspicuity, artifact severity, and overall image quality using a five-point scale. Quantitative analysis was performed by another radiologist to estimate the relative liver enhancement (RLE) and the signal-to-noise ratio (SNR). Statistical analyses were performed using the Wilcoxon signed rank test and one-way analysis of variance. Results: The scores of the HBP with an FA of $13^{\circ}$ during the same delayed time were significantly higher than those of the HBP with an FA of $9^{\circ}$ in all the assessment items (P < 0.01). In terms of the delay time, images at the same FA obtained with a 20-min-HBP showed better quality than those obtained with a 15-min-HBP. There was no significant difference in qualitative scores between the 20-min-HBP and the 15-min-HBP images in the non-liver cirrhosis (LC) group except for the hepatic vessel clarity score with $9^{\circ}$ FA. In the quantitative analysis, a statistically significant difference was found in the degree of RLE in the four HBP images (P = 0.012). However, in the subgroup analysis, no significant difference in RLE was found in the four HBP images in either the LC or the non-LC groups. The SNR did not differ significantly in the four HBP images. In the subgroup analysis, 20-min-HBP imaging with a $13^{\circ}$ FA showed the highest SNR value in the LC-group, whereas 15-min-HBP imaging with a $13^{\circ}$ FA showed the best value of SNR in the non-LC group. Conclusion: The use of a moderately high FA improves the image quality and lesion conspicuity on 3D, T1-weighted GRE imaging using the CAIPIRINHA technique on gadoxetic acid, 3T liver MR imaging. In patients with normal liver function, the 15-min-HBP with a $13^{\circ}$ FA represents a feasible option without a significant decrease in image quality.

• 한국식품영양과학회지
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• 제32권4호
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• pp.603-607
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• 2003

홍국 추출물(MPE)이 알코올대사에 어떠한 영향을 미치는지를 알아보기 위하여 흰쥐에 10% ethanol에 홍국 추출물을 1%, 2.5%, 5% 함유시킨 것을 1개월간 음용시킨 뒤, 처치하여 다음과 같은 결과를 얻었다. 홍국 추출물을 첨가시킨 실험군은 정상군에 비하여 체중 증가율이 다소 낮게 나타났으며 이들 실험군 간에는 별다른 차이를 볼 수 없었다. 알코올만 투여한 대조군 및 홍국 추출물 함유 알코올 섭취군 모두 간 기능에 별다른 이상이 나타나지 않았다. 간 조직 중 alcohol dehydrogenase(ADH) 활성은 알코올 투여군이 정상군보다 87%의 유의한 증가를 보였으며 홍국 추출물 1, 2.5 및 5% 함유해서 알코올을 음용시킨 Monascus군은 알코올만 섭취한 대조군에 비해 각각 34, 29 및 21% 증가하였다. Aldehyde dehydrogenase(ALDH) 활성에 있어서는 1% Monascus군은 대조군에 비해서 32%의 유의한 증가를 보였으며, 2.5% 및 5% Monascus군 역시 대조군에 비해 증가되는 경향을 보였다. 이들 효소를 반응속도적인 측면에서 관찰해 볼 때, 1, 2.5 및 5% Monascus군은 대조군에 비하여 ADH의 Km치가 각각 40, 30 및 19% 감소되었으며, Vmax치는 알코올 투여군인 대조군은 정상군(8.26 nmole/min/mg protein)보다 43% 높게 나타났으며, 홍국 추출물함유 알코올음용군과 알코올단독음용군 간에 별다른 차이가 나타나지 않았다. 그리고 ALDH의 Vmax치는 대조군에 비해서 1, 2.5, 5% Monascus군은 대조군에 비해서 각각 88, 56, 22% 증가되었다. 한편 1% 및 5% 홍국 추출물 함유 알코올을 흰쥐에 투여한 다음 경시별로 채혈하여 혈액 중 알코올을 측정하여 알코올 농도 곡선하면적으로 환산한 결과, 1% Monascus군은 대조군에 비하여 약 18% 감소되었으며 5% Monascus군은 대조군에 비해서 약 10% 감소되는 경향을 보였다. 이상 실험 결과는 알코올에 홍국 추출물을 첨가시킴으로서 알코올대사와 더불어 알코올의 체외 배설을 촉진시키는 것을 시사해 주고 있다.