• Title/Summary/Keyword: Liver, disease

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Measurement of CYP450 Enzymes Activity of Bosentan in HepaRG Cell (HepaRG 세포를 이용한 Bosentan 약물의 CYP450 효소활성 측정)

  • Han, Kyoung-Moon;Jung, Jung-A;Sin, Ji-Soon;Cha, Hye-Jin;Bae, Young-Ji;Kim, Hyun-Uk;Kim, Young-Hoon;Seong, Won-Keun;Kang, Hoil
    • YAKHAK HOEJI
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    • v.58 no.4
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    • pp.255-261
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    • 2014
  • Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

Survival and Prognostic Factors for Hepatocellular Carcinoma: an Egyptian Multidisciplinary Clinic Experience

  • Abdelaziz, Ashraf Omar;Elbaz, Tamer Mahmoud;Shousha, Hend Ibrahim;Ibrahim, Mostafa Mohamed;El-Shazli, Mostafa Abdel Rahman;Abdelmaksoud, Ahmed Hosni;Aziz, Omar Abdel;Zaki, Hisham Atef;Elattar, Inas Anwar;Nabeel, Mohamed Mahmoud
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.9
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    • pp.3915-3920
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    • 2014
  • Background: Hepatocellular carcinoma (HCC) is a dismal tumor with a high incidence, prevalence and poor prognosis and survival. Management of HCC necessitates multidisciplinary clinics due to the wide heterogeneity in its presentation, different therapeutic options, variable biologic behavior and background presence of chronic liver disease. We studied the different prognostic factors that affected survival of our patients to improve future HCC management and patient survival. Materials and Methods: This study is performed in a specialized multidisciplinary clinic for HCC in Kasr El Eini Hospital, Cairo University, Egypt. We retrospectively analyzed the different patient and tumor characteristics and the primary mode of management applied to our patients. Further analysis was performed using univariate and multivariate statistics. Results: During the period February 2009 till February 2013, 290 HCC patients presented to our multidisciplinary clinic. They were predominantly males and the mean age was $56.5{\pm}7.7years$. All cases developed HCC on top of cirrhosis that was mainly due to HCV (71%). Most of our patients were Child-Pugh A (50%) or B (36.9%) and commonly presented with small single lesions. Transarterial chemoembolization was the most common line of treatment used (32.4%). The overall survival was 79.9% at 6 months, 54.5% at 1 year and 22.4% at 2 years. Serum bilirubin, site of the tumor and type of treatment were the significant independent prognostic factors for survival. Conclusions: Our main prognostic variables are the bilirubin level, the bilobar hepatic affection and the application of specific treatment (either curative or palliative). Multidisciplinary clinics enhance better HCC management.

A Study on Years of Potential Life Lost in Korea - Focus on Alcohol - (우리 나라 잠재수명 손실년수에 관한 연구)

  • Jo, Jeanman;Lim, Dar-Oh
    • The Korean Journal of Emergency Medical Services
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    • v.3 no.1
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    • pp.65-76
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    • 1999
  • Objectives: This study sought to examine the impact of alcohol use and misuse on mortality in korea during the 1991-l997. Methods: Alcohol-Related Disease Impact estimation software and Korea vital statistics data were used to calculate alcohol related-mortality, mortality rates, and YPLL(years of potential life lost). The major findings are as follows : An estimated 23,528 Korean died during 1997 from causes related to alcohol. Such deaths accounted for 17,052(12.60%) of all deaths for men and 6,206(5.88%) for women. Motor vehicle accidents were major contributors to the total estimated number of alcohol related deaths and years of potential life lost before age 65. Alcohol related mortality rates were significantly higher for men. For men, major causes of the deaths were motor vehicle accidents(4,147 deaths, 17.90 per 100,000 population), cancer of the stomach(1,467 deaths, 16.60 per 100,000 population) and chronic liver diseases and cirrhosis(1,233 deaths, 13.10). For women, the largest contributors to alcohol related mortality were motor vehicle accidents(1,509 deaths, 6.61), cerebrovascular diseases(1,114 deaths, 11.3) and cancer of the stomach(810 deaths, 8.24). Kleinman's method was used for obtaining on regional(Dongs, ups and Myons) differential of the alcohol related mortality in 1995. In general, The alcohol-related death rate for men was significantly higher than that for women, and the rate for ups and myons was significantly higher than that for dongs During 1997, approximately 356,667(male: 282, 510, female: 74, 157)YPLL to age 65 and 572,708(male:424,338, female:148,370)YPLL to life expectancy were attributable to alcohol related causes. Men accounted for 79% of the total YPLL to age 65 and 74% of the total YPLL to life expectancy The major contributors to these alcohol related years lost were the diagnostic categories of unintentional injuries. Particullary, In male, Motor vehicle accidents and accidental drowning-YPLL are considerably higher for other causes. Male-female YPLL differentials were greatest for mental disorder. Male-female mean-YPLL to age 65, accidental drowning(male;36.47, female;37.67) is higher for other causes. In both sexes, The YPLL and M-YPLL to life expectancy was significantly higher than the YPLL and M-YPLL to life expectancy.

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Growth Performance and Antibody Response of Broiler Chicks Fed Yeast Derived β-Glucan and Single-strain Probiotics

  • An, B.K.;Cho, B.L.;You, S.J.;Paik, H.D.;Chang, H.I.;Kim, S.W.;Yun, C.W.;Kang, C.W.
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.7
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    • pp.1027-1032
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    • 2008
  • A study was conducted to evaluate the effects of dietary yeast derived ${\beta}$-glucan and single-strain probiotics on the growth performance and antibody response in broiler chicks. Six hundred and thirty 1-d-old male broiler chicks were divided into seven groups, placed into three pens per group (30 birds per pen) and fed one of seven non-medicated corn-SBM based experimental diets containing 0.025, 0.05 or 0.1% Saccharomyces cerevisiae ${\beta}$-glucan and 0.05, 0.1 or 0.2% Bacillus amyloliquefaciens (BA-pro, $1.3{\times}10^9/g$) or devoid of them for 5 wk. The body weight gains in groups fed diets containing 0.025 or 0.1% ${\beta}$-glucan, 0.1% or 0.2% BA-pro were significantly higher (p<0.05) than the control over 1-35 d. Feed conversion rates of groups fed ${\beta}$-glucan and BA-pro tended to be improved compared to the control group. There were no significant differences in the relative weights of liver, abdominal fat and breast muscle. No significant differences were observed in the activities of serum enzymes and concentrations of various cholesterol fractions. The antibody titers against Newcastle disease or infectious bronchitis virus in the chicks fed diets containing ${\beta}$-glucan and BA-pro were significantly higher (p<0.05) than in the control. The concentrations of cecal lactic acid bacteria in all groups fed BA-pro were significantly increased (p<0.05) compared to the control. These results indicated that dietary yeast derived ${\beta}$-glucan and BA-pro exerted growth-promoting and immune-enhancing effects in broiler chickens. In addition, BA-pro added to the diets modulated the profiles of cecal microflora, reflecting a potential to be beneficial microorganisms in chickens.

External Radiation Therapy Combined with Hyperthermia in the Carcinoma of Extrahepatic Biliary System (간외 담관계암의 방사선치료와 온열치료의 병용요법)

  • Bae, Hoon-Sik
    • Radiation Oncology Journal
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    • v.10 no.1
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    • pp.49-58
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    • 1992
  • From January 1985 to September 1990, 7 patients with carcinoma of the extrahepatic biliary system received external radiaiton therapy combined with hyperthermia. Of the 3 patients with extrahepatic bile duct cancer, two were primary cholangiocarcinoma and one was metastatic peripancreatic carcinoma. Of the 4 patients with carcinoma of the gallbladder, two were locor-egionally advanced and unresectable carcinoma and the remaining two were local-regional recurrence after cholecystectomy. They were all pathologicallly proven adenocarcinoma. The radiation dose received ranged from 3000 cGy/2weeks to 5040 cGy/7 weeks. The hyperthermia was done once or twice a week and 4 to 12 sessions in total. The tumor response was confirmed by T-tube cholangiography, percutaneous transhepatic cholangiography and CT scan. 6 out of 7 ($86\%$) showed partial regression of the tumor. The median survival time was 7 months (range $4\~11$ months).6 out of 7 patients were dead: one died of septicemia, 4 of primary disease, one of distant metastases. Only one out of 7 patients is still alive but new metastatic lesion was found. There was not any treatment related deaths. There was also no evidence of treatment related problems with liver, stomach and duodenum, although the observation period was short.

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Ursodeoxycholic Acid Ameliorates Pain Severity and Cartilage Degeneration in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

  • Moon, Su-Jin;Jeong, Jeong-Hee;Jhun, Joo Yeon;Yang, Eun Ji;Min, Jun-Ki;Choi, Jong Young;Cho, Mi-La
    • IMMUNE NETWORK
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    • v.14 no.1
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    • pp.45-53
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    • 2014
  • Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-$1{\beta}$, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-$1{\beta}$-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.

Effects of Korean Wheat on LDL Oxidation and Atherosclerosis in Cholesterol-Fed Rabbits (고콜레스테롤혈증 유발 가토를 이용한 우리밀의 LDL산화 및 동맥경화 예방 효과)

  • Choe, Myeon;Kim, Hyun-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.1
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    • pp.104-108
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    • 2002
  • Numerous studies have suggested the involvement of oxidative processes in the pathogenesis of atherosclerosis and especially of oxidized low density lipoproteins (LDL). We studied the effect of Korean wheat on the oxidizability of LDL and the development of experimental atherosclerosis in rabbits on cholesterol diet. For the approach of the aim, antioxidative activity of wheat extracts against oxidation of LDL was investigated. The antiatherogenic effect of wheat was studied against Newzealand whithe (NZW) rabbits fed containing the wheat powder for 12 weeks. PBS extracts of Korean and imported wheats decreased LDL oxidation induced by copper ion by 62.3%, 52.6% respectively in comparison with control. Liver thiobarbituric acid reactive substance (TBARS ) levels of rabbits were significantly lowered in Korean wheat fed group (0.397$\pm$ 0.029 nmol MDA/mg protein, p<0.05) compared to control (0.496$\pm$0.021 nmol MDA/mg protein) and imported wheat group (0.478$\pm$0.019 nmol MDA/mg protein). TBARS levels of kidney showed no significant difference among treatment groups. The aorta of cholesterol-fed rabbits showed typical atherosclerotic lesions when compared with the controls, but the microscopic differences between groups was not clear. The present study suggests that Korean wheat may have higher antioxidative capacity than imported wheat and have more beneficial effects for the treatment of disease by inhibiting the oxidation of LDL.

A Case of Sarcoidosis with Pancytopenia as Resulting from Bone Marrow Involvement (골수를 침윤하여 범혈구감소증을 나타낸 유육종증 1예)

  • Park, Tai Sun;Kim, Dae-Young;Park, Seo-Jin;Kim, Yi Rang;Na, Soo Young;Park, Jin Wook;Oh, Dong Wook;Choi, Jun Seok;Jo, Jung Min;Chang, Youjin;Kim, Won Young;Choi, Chang-Min
    • Tuberculosis and Respiratory Diseases
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    • v.67 no.6
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    • pp.560-564
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    • 2009
  • Sarcoidosis is a granulomatous disease that can involve any organ, although it primarily involves the lungs, intrathoracic lymph nodes, skin, and eyes. We present a case of sarcoidosis with pancytopenia, resulting from bone marrow involvement. A 35-year-old man was admitted to hospital for chronic cough and blurred vision. On chest computed tomography, there were multiple pulmonary nodules and mediastinal lymph nodes enlargement. As the patient also showed pancytopenia, we performed a bone marrow biopsy, as well as a transbronchial lung biopsy. Both biopsies showed non-caseating granulomas. We diagnosed the patient with sarcoidosis with pulmonary, bone marrow, uvea, liver and spleen involvement. After oral steroid therapy, the patient's symptoms as well as his pancytopenia improved. We present this case to demonstrate the significance of bone marrow biopsy in cases of sarcoidosis with pancytopenia, as well the possibility of clinical improvement with steroid treatment.

Five Genes Regulated by Oryctes rhinoceros nudivirus Infection in the Intestinal Tube of Allomyrina dichotoma (장수풍뎅이(Allomyrina dichotoma)에 Oryctes rhinoceros nudivirus 감염에 의해서 유전자 발현이 조절되는 5개의 유전자)

  • Yoo, Bo-Kyung;Kwon, Kisang;Ko, Young Hwa;Lee, Eun Ryeong;Choi, Ji-Young;Kwon, O-Yu
    • Journal of Life Science
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    • v.26 no.11
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    • pp.1336-1340
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    • 2016
  • Korean rhinoceros beetles (Allomyrina dichotoma), which can be found in broad-leaved forests in mountainous habitats and lives for around one year in wild. This beetle is currently popular as a pet and traditionally regarded as a medicine for liver-related diseases in Korea. It is reported that the economic losses in the mass-rearing facilities by virus infection have been increased since the 2010s in Korea. The causing virus for the A. dichotoma was firstly reported as an Oryctes rhinoceros nudivirus (OrNV) in 2015. We, here, observes that serious morphological changes in the intestinal tube from the OrNV-infected beetles, and report five genes, which are regulated by OrNV infection in the intestine; Krueppel-like factor 15 (Klf15), Endoplasmic reticulum aminopeptidase 2 (ERAP2), U5 small nuclear ribonucleoprotein 200 kDa helicase (Snrnp200), Muscleblind-like protein 2a (mbnl2a), and MIMI_L93. The results may provide a clue to the early diagnosis and disease treatment during the mass-rearing facilities of the A. dichotoma.

Relations between Normal Serum Gamma-glutamyltransferase and Risk Factors of Coronary Heart Diseases according to Age and Gender (연령과 성별에 따른 정상 혈청 Gamma-glutamyltransferase와 관상동맥질환 위험인자와의 관계)

  • Kwon, Se Young;Na, Young Ak
    • Korean Journal of Clinical Laboratory Science
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    • v.48 no.1
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    • pp.22-29
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    • 2016
  • Serum gamma-glutamyltransferase (GGT) has been widely used as a marker of alcohol intake and liver failure. Recently, the relativity between GGT and various diseases has been identified with growing interest. In this study, we examined relativity between GGT value and risk factors of coronary heart diseases among those with normal GGT value, excluding heavy drinkers. Specifically, we compared the differences based on age and gender. Data from the 2011 KNHNES were used (N=3,619). When the subjects were categorized according to quartile based on the serum GGT levels, there was 10~20, 21~27, 28~38, 39~71 IU/L in men, and 6~12, 13~16, 17~22, 23~42 IU/L in women. The mean of most variables was the highest in the $4^{th}$ quartile (Q4), however age and LDL Cholesterol were the highest in the $2^{nd}$ quartile (Q2) in men. The FRS and 10-year CHD risk was the highest in the $2^{nd}$ quartile in men, and the highest in the $4^{th}$ quartile in women. Increased GGT was correspondingly linked with age in women but age was the highest in GGT in the $2^{nd}$ quartile in men. In the 70's, the highest Q1 and Q2 was in men and the highest Q3 and Q4 in women. Although GGT value was within the normal range, increased GGT showed correlation with various risk factors. The FRS and 10-year CHD risk showed different patterns according to age and gender along with increased GGT value.