• Title/Summary/Keyword: Serum bile acid

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Statin Intolerance: an Overview of the Current Status and Possible Treatment Options

  • Suh, Sunghwan;Jung, Chang Hee;Hong, Soon-Jun;Kim, Jung-Sun;Choi, Sung Hee
    • Journal of Lipid and Atherosclerosis
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    • v.7 no.2
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    • pp.77-87
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    • 2018
  • Lowering serum low-density lipoprotein cholesterol (LDL-C) is the mainstay for reduction of risk of cardiovascular disease (CVD), the second most common cause of death in Korea. The 2015 Korean guidelines for management of dyslipidemia strongly recommend the use of statins in patients at risk of CVD. Statin therapy, which is the gold standard for CVD, reduces LDL-C level by 40% to 60% and is generally well tolerated. However, many patients are intolerant to statins and discontinue therapy or become nonadherent to therapy because of actual/perceived side effects. The most common of these side effects is the statin-associated muscle symptom (SAMS). Discontinuation and repetitive re-challenge with statins can help identify SAMS. If serum creatinine kinase level is more than 10 times the upper limit of normal, statin therapy must be stopped immediately, and the physician should identify possible causes including rhabdomyolysis and treat appropriately. In other patients, it might help to switch to a less potent statin or to use statins at intermittent non-daily dosing. To achieve target LDL-C level, non-statin lipid-lowering therapies such as dietary modifications, ezetimibe, and bile acid sequestrants may be added. Several new drugs have recently been approved for lowering LDL-C level. Alirocumab and evolocumab are monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9, and both drugs cause large reductions in LDL-C, similar to statins. Lomitapide and mipomersen are orphan drugs used as adjuncts to other lipid-lowering therapies in patients with homozygous familial hypercholesterolemia.

Effect of Sosiho-tang on a Thioacetamide-induced Liver Fibrosis Mouse Model (소시호탕(小柴胡湯)이 thioacetamide로 유발된 간섬유증 동물 모델에 미치는 영향)

  • Lee, Se Hui;Oh, Min Hyuck;Shin, Mi-Rae;Lee, Ji Hye;Roh, Seong-Soo
    • The Journal of Internal Korean Medicine
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    • v.42 no.6
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    • pp.1223-1236
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    • 2021
  • Objectives: The aim of the current study was to investigate the effect of Sosiho-tang on thioacetamide (TAA)-induced liver fibrosis in mice and to elucidate its underlying mechanisms. Methods: The mice were divided into 4 groups: Normal mice (Normal), TAA-induced control mice (Control), TAA-induced and silymarin-treated (50 mg/kg) mice (Silymarin), and TAA-induced and Sosiho-tang treated (200 mg/kg) mice (SSHT). Liver fibrosis was induced via intraperitoneal injection of TAA three times a week for 8 weeks. Silymarin and Sosiho-tang were concomitantly administered for 8 weeks. Serum and liver tissues were then collected and the anti-oxidant and inflammatory protein levels in the liver tissues were evaluated using western blotting. Results: SSHT administration significantly reduced the levels of AST, ALT, ammonia, and MPO in the serum. SSHT also significantly down-regulated liver NADPH oxidase and regulated the Nrf2/Keap1 signaling pathway. SSHT treatment downregulated the liver NF-κB levels and suppressed inflammatory cytokines. SSHT treatment also decreased bile acid-related factors, such as CYP7A1 and NTCP, and fibrosis-related factors, such as α-SMA and Collagen I. Conclusions: Taken together, these data suggest that SSHT administration suppressed the progression of liver fibrosis by activating the Nrf2/Keap1 pathway and inhibiting NF-κB.

Effects of Methanol Extract of Prosomillet on Cholesterol and Fatty Acid Metabolism in Rat

  • Cho, Sung-Hee;Jung, Seung -Eun;Lee, Hye-Kyung;Ha, Tae-Youl
    • Preventive Nutrition and Food Science
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    • v.4 no.3
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    • pp.188-192
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    • 1999
  • To study effects of methanol extract of prosomillet on lopid metabolism , five groups of male Sprang-Dawley rats weighing 116$\pm$9 g were fed test diets for four weeks. The five diets consisted of one low fat(5% w/w) diet containing starch as carbohydrate source(normal) and four high fat diets(15% w/w) containing 40.5%(w/w)sucrose(control) and additional 80% nethanol extractof prosomillet at the levels of 0.3% and 1%(w/w) or prosomillet powder at the level of 20%(w/w). Serum level of total cholesterol was a little higher but that of triglyceride was 41% lower in 20% (w/w) prosomillet powder group than in the control group. The cholesterol levels of two Liver cholesterol levels were lower and phospolipid levels higher in all three prosomillet powder group . Fecal excretionof bile acid was most increased in the prosomillet powder group among all five test groups. Acitivity of liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase was significantly lower in 0.3% methanol extract fed group than the control and also appeared to be reduced in 1% extract fed one, wherease those of 20 cholesterol 7$\alpha$-hydroxylase were not different among the five groups. Activities of liver cytosilic glucose-6-phosphate dehydrogenase(G6PDH) and malic enzyme were decreased in 0.3% prosomillet methanol extract and 20% powder groups. The results indicate that in addition to fiber, certain active components in prosomillet have potential to exert hypolipidemic effects via regulating hepatic cholesterogenesis and lipogenesis.

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Tc-99m EHIDA Scintigraphic Demonstrability of Biliary Elements and Liver Function Tests in Hepatobiliary Diseases (몇가지 간담도질환에서 간기능에 따른 Tc-99m EHIDA의 담도영상능)

  • Kim, Choon-Yul;Lee, Myung-Hee;Bahk, Yong-Whee
    • The Korean Journal of Nuclear Medicine
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    • v.16 no.2
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    • pp.71-80
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    • 1982
  • In the present communication, the results will be reported on a clinical study of how well scintigraphic visualization of the hepatobiliary elements and several commonly used clinical liver function tests correlate each other in various diseases oft hepatobiliary system. The demonstrability of the biliary tract, gallbladder (GB) and duodenum was rather closely paralleled to serum bilirubin level and less closely to alkaline phosphatase and rather poorly to SGOT and SGPT. The biliary tree could not be visualized scintigraphically when bilirubin exceeded 10.5mg/dl. The usefulness of Tc-99m EHIDA [N-(2,6-diethylacetanilido) iminodiacetic acid, made by Amersham, England] hepatobiliary scintigraphy (Tc EHIDA HBS) in settling diagnostic controversy and ambiguity raised by oral cholecystography, intravenous cholangiography and ultrasonography in many hepatobiliary diseases is well known. The purpose of this investigation was to semiquantitatively evaluate the scintigraphic demonstrability of the hepatobiliary tract, GB and duodenum following intravenous injection of Tc-99m EHIDA in normal subjects and in patients with a disturbed liver function from various hepatobiliary diseases. The hepatobiliary scintigraphy was performed in 10 normal subjects and 39 patients with various hepatobiliary diseases (Table 1) at the Dept. of Radiology, St. Mary's Hospital Catholic Medical College, Seoul, Korea during 2 years period from September 1979. Scintigraphic examination was started at end of 3 minutes after intravenous injection of Tc-99m EHIDA in the amount of $50{\mu}Ci/kg$ and was continued until after 30 minutes at 5 minutes interval. The imaging was usually terminated when the tracer could be seen in the duodenum. Late scintigrams were obatained at 1 1/2, 3, 4 and 6 hours when reeded. Scintigrams were analyzed in terms of promptness and clarity of visualization of the biliary tree, GB and duodenum and demonstrability of these anatomical landmarks was correlated with the values of liver function tests. The demonstrability of the common hepatic duct, common bile duct, GB and duodenum was closely paralleled to the level of serum bilirubin when it is less than 10.5 mg/dl as shown in figure 1. However when the bilirubin exceeded 10.5 mg/dl the time of visualization between protracted reaching a flat curve or plateau around 10.5 mg/dl. The biliary tract could not be visualized when the bilirubin was higher than 10.5 mg/dl. The correlability between scintigraphic demonstration and serum alkaline phosphatase was less strong and between scintigraphic demonstration and SGOT and SGPT was rather poor. The present clinical study confirmed the usefulness and limitation of Tc-99m EHIDA hepatobiliary scintigraphy in visulizing and diagnosing the biliary system and duodenum when radiogrpahy and ultrasonography failed to provide useful informations. Scintigraphy was very helpful in the diagnosis of neonatal hepatitis, biliary atresia, cholecystitis and extrahepatic biliary obstruction. The hepatobiliary system and duodenum were visualized when serum bilirubin level was less than 10.5 mg/dl, SGOT 135 units, SGPT 114 units and alkaline phosphatase 52.2 KAU.

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The Probiotic Characteristics of Lactobacillus acidophilus Isolated from Infant Feces (신생아분변 유래 Lactobacillus acidophilus의 프로바이오틱으로서의 특성)

  • Kim, Eun-Ah;Yi, Dong-Heui
    • Applied Biological Chemistry
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    • v.51 no.2
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    • pp.93-101
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    • 2008
  • This study was conducted to obtain a good probiotic strain of L. acidophilus from infant feces which have the acid and bile tolerance. The selection criteria for the strain included antimicrobial activity, serum cholesterol reduction, resistance to the hydrogen peroxide, angiotensin converting enzyme (ACE) inhibition activity and iron solubility. To this end, five probiotic Lactobacillus strains have been isolated from infant feces. Especially, L. acidophilus SD 105 had strong antimicrobial activity against Listeria sp., high deconjugation activity in the medium which contained 0.5% of glycocholate (GCA) and high resistance to the hydrogen peroxide. L. acidophilus SD 102 showed the highest ACE inhibition activity among the tested cultures and L. acidophilus SD 103 showed iron solubility of more than 70%.

A Case of Portosystemic Shunt in a Domestic Shorthair Cat (한국 집고양이의 문맥전신션트 한 증례)

  • Cho, Eunkwang;Jeong, Ye Chan;Choi, Ul Soo
    • Journal of Veterinary Clinics
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    • v.31 no.4
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    • pp.316-318
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    • 2014
  • A 3-year-old castrated male domestic shorthair cat was presented with a chief complaint of sudden onset of intermittent seizures occurring five times a day. Physical examination revealed the copper colored iris and loss of menace response at both eyes. Abnormalities of blood works and serum chemistry revealed mild erythrocytosis, severe microcytosis, and threefold increase in ALT activity. Additional liver function tests results were increased bile acid and $NH_3$ concentration. Radiographic study revealed multifocal nodules of the liver and an extrahepatic shunt was noted by ultraonography, which was confirmed by computed tomography as multiple extrahepatic shunts. The cat was scheduled for surgery applying an ameloid ring to occlude the shunt gradually. Diazepam and lactulose were instituted to the patient. However, clinical signs worsened despite medical management with shortened interval of seizures and the patient died due to cardiac arrest.

Intrahepatic Portosystemic Shunt Fixed By Transvenous Coil Embolization in a Samoyed Dog (샤모예드종 개에서 발생한 간내성 문맥-정맥 문합을 경정맥 코일장착으로 치료한 증례)

  • Lee, Moo-Hyun;Lee, Seoung-Jin;Lee, Seung-Gon;Moon, Hyeong-Sun;Lee, Joon-Seok;Choi, Ran;Park, In-Chul;Hyun, Chang-Baig
    • Journal of Veterinary Clinics
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    • v.24 no.3
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    • pp.426-431
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    • 2007
  • A 5-month-old female Samoyed dog was presented with primary complaints including exercise tolerance and neurological sign associated with hepatic encephalopathy. The major findings in clinical examination included an intermittent seizure, anemia, elevated pre- and post-prandial serum bile acid, hypoproteinemia and bilirubinuria. Diagnostic imaging studies revealed an intrahepatic portosystemic shunt (IPSS). The shunted vessel was successfully occluded by transvenous coil embolization. Clinical signs were gradually improved after shunt occlusion. This case is a rare case of IPSS in a large breed dog fixed by transvenous coil embolization.

Perilipin 5 is a novel target of nuclear receptor LRH-1 to regulate hepatic triglycerides metabolism

  • Pantha, Rubee;Lee, Jae-Ho;Bae, Jae-Hoon;Koh, Eun Hee;Shin, Minsang;Song, Dae-Kyu;Im, Seung-Soon
    • BMB Reports
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    • v.54 no.9
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    • pp.476-481
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    • 2021
  • Liver receptor homolog-1 (LRH-1) has emerged as a regulator of hepatic glucose, bile acid, and mitochondrial metabolism. However, the functional mechanism underlying the effect of LRH-1 on lipid mobilization has not been addressed. This study investigated the regulatory function of LRH-1 in lipid metabolism in maintaining a normal liver physiological state during fasting. The Lrh-1f/f and LRH-1 liver-specific knockout (Lrh-1LKO) mice were either fed or fasted for 24 h, and the liver and serum were isolated. The livers were used for qPCR, western blot, and histological analysis. Primary hepatocytes were isolated for immunocytochemistry assessments of lipids. During fasting, the Lrh-1LKO mice showed increased accumulation of triglycerides in the liver compared to that in Lrh-1f/f mice. Interestingly, in the Lrh-1LKO liver, decreases in perilipin 5 (PLIN5) expression and genes involved in β-oxidation were observed. In addition, the LRH-1 agonist dialauroylphosphatidylcholine also enhanced PLIN5 expression in human cultured HepG2 cells. To identify new target genes of LRH-1, these findings directed us to analyze the Plin5 promoter sequence, which revealed -1620/-1614 to be a putative binding site for LRH-1. This was confirmed by promoter activity and chromatin immunoprecipitation assays. Additionally, fasted Lrh-1f/f primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted Lrh-1LKO primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs, protect the liver from lipid overload, and manage the cellular needs during fasting.

A Randomized, Double-Blind, Placebo-Controlled Trial of Early Ursodeoxycholic Acid Administration for Prevention of Total Parenteral Nutrition-Induced Hepatobiliary Complications (총정맥영양법의 간담도 합병증에 대한 Ursodeoxycholic Acid 조기투여의 이중맹검 위약대조군 연구)

  • Choe, Yon-Ho;Beck, Nam-Sun;Kim, Ji-Hee;Lee, Suk-Hyang;Park, Tae-Sung
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.5 no.2
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    • pp.174-180
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    • 2002
  • Purpose: Ursodeoxycholic acid (UDCA) is known to decrease hepatic injury by promoting the biliary secretion of retained toxic endogenous bile acids in hepatobiliary diseases complicated by total parenteral nutrition (TPN). However, most studies have focused on treatment for complications after TPN. We investigated the preventive role of early administration of UDCA in TPN-induced hepatobiliary complications by a randomized, double-blind, placebo-controlled trial. Methods: Between May 2000 and May 2002, thirteen patients, who were given TPN more than 10 days in the hospital, were assigned randomly to two groups. One was the case group (7 patients) who were given UDCA simultaneously with TPN regimen, and the other, the control group (6 patients) who were given placebo. Their age ranged from 1 day to 13 years. They were affected with diseases impossible for enteral nutrition, such as prematurity, cerebral palsy, chronic diarrhea, anorexia nervosa, pancreatitis, and cyclic vomiting. The duration of TPN ranged from 10 to 70 days. Hematologic parameters including liver function test were measured at regular intervals, and the duration, composition, administration rate, total calorie of TPN were recorded. The serum levels of total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase were compared between groups after cessation of the study. Results: The autoregressive coefficient of the control group was 0.4419 (p=0.0651) in bilirubin, -0.0431 (p=0.7923) in AST, 0.2398 (p=0.2416) in ALT, and 0.2459 (p=0.1922) in alkaline phosphatase by mixed procedure model when the parameters were referred to the case group. Conclusion: The serum level of total bilirubin did not increase in comparison with that of the control group, but statistically insignificant, when both TPN and UDCA were administered simultaneously from the beginning.

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Single Extrahepatic Portosystemic Shunt in 3 Dogs: CT Findings and Progress (3마리의 개에서 발생한 단일 간외성 문맥전신 단락 증례)

  • Lee, Hee-Chun;Ji, Chang-Moo;Moon, Jong-Hyun;Cho, Kyu-Woan;Kim, Young-Ki;Kang, Byeong-Teck;Jung, Dong-In
    • Journal of Veterinary Clinics
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    • v.29 no.6
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    • pp.488-493
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    • 2012
  • Two Maltese (2-year-old, intact female and 4-month-old, intact female) and a Pekingese (10-year-old, intact male) dogs were referred due to vomiting, anorexia, head-pressing and hypersalivation. Physical examinations, complete blood count, serum chemical analysis, radiography, ultrasonography and computed tomography (CT) were evaluated. Laboratory findings in these dogs included high hepatic enzyme, serum bile acid and ammonia concentration. Microhepatia was found on abdominal radiographs in two dogs. The existence of portosystemic shunt was presented in abdominal ultrasonography. The shunt vessel was identified in all dogs by CT imaging. Based on three-dimensional CT reconstruction, the origin and termination of each shunt vessel were defined certainly. In consequence, each dog was diagnosed single extrahepatic portosystemic shunt. After diagnosis, surgical treatment was performed in all dogs. This case report describes clinical finding, imaging characteristics, and three-dimensional CT imaging of single extrahepatic portosystemic shunt cases.