• Title/Summary/Keyword: Liver dysfunction

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Role of Kupffer Cells in the Vasoregulatory Gene Expression during Hepatic Ischemia/Reperfusion

  • Kim, Yong-Hyuk;Lee, Sun-Mee
    • Archives of Pharmacal Research
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    • v.27 no.1
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    • pp.111-117
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    • 2004
  • Hepatic microcirculatory failure is a major component of reperfusion injury in the liver. Recent data provided some evidence that endothelium-derived vasoconstrictors and vasodilators may be functionally important to the control of the total hepatic blood flow under these conditions of circulatory failure. Since Kupffer cells provide signals that regulate the hepatic response in ischemia/reperfusion (I/R), the aim of this study was to investigate the role of Kupffer cells in the I/R-induced imbalance of vasoregulatory gene expression. Rats were subjected to 60 min hepatic ischemia, followed by 5 h of reperfusion. The Kupffer cells were inactivated by gadolinium chloride ($GdCl_3$, 7.5 mg/kg body weight, intravenously) 1 day prior to ischemia. Liver samples were obtained 5 hrs after reperfusion for RT-PCR analysis of the mRNA for genes of interest: endothelin-1 (ET-1), its receptors $ET_A and ET_B$, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). ET-1 mRNA expression was increased by I/R. mRNA levels for $ET_A$ receptors showed no change, whereas $ET_B$ receptor transcripts increased in the I/R group. The increases in ET-1 and $ET_B$ mRNA were not prevented by the $GdCI_3$ pretreatment. The mRNA levels for iNOS and eNOS significantly increased within the I/R group with no significant difference between the I/R group and the $GdCl_3$-treated I/R group. HO-1 mRNA expression significantly increased in the I/R group and this increase was attenuated by $GdCI_3$. In conclusion, we have demonstrated that an imbalance in hepatic vasoregulatory gene expression occurs during I/R. Our findings suggest that the activation of Kupffer cells is not required for I/R-induced hepatic microvascular dysfunction.

Protective effects of Populus tomentiglandulosa against cognitive impairment by regulating oxidative stress in an amyloid beta25-35-induced Alzheimer's disease mouse model

  • Kwon, Yu Ri;Kim, Ji-Hyun;Lee, Sanghyun;Kim, Hyun Young;Cho, Eun Ju
    • Nutrition Research and Practice
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    • v.16 no.2
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    • pp.173-193
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    • 2022
  • BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is one of the most representative neurodegenerative disease mainly caused by the excessive production of amyloid beta (Aβ). Several studies on the antioxidant activity and protective effects of Populus tomentiglandulosa (PT) against cerebral ischemia-induced neuronal damage have been reported. Based on this background, the present study investigated the protective effects of PT against cognitive impairment in AD. MATERIALS/METHODS: We orally administered PT (50 and 100 mg/kg/day) for 14 days in an Aβ25-35-induced mouse model and conducted behavioral experiments to test cognitive ability. In addition, we evaluated the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and measured the production of lipid peroxide, nitric oxide (NO), and reactive oxygen species (ROS) in tissues. RESULTS: PT treatment improved the space perceptive ability in the T-maze test, object cognitive ability in the novel object recognition test, and spatial learning/long-term memory in the Morris water-maze test. Moreover, the levels of AST and ALT were not significantly different among the groups, indicating that PT did not show liver toxicity. Furthermore, administration of PT significantly inhibited the production of lipid peroxide, NO, and ROS in the brain, liver, and kidney, suggesting that PT protected against oxidative stress. CONCLUSIONS: Our study demonstrated that administration of PT improved Aβ25-35-induced cognitive impairment by regulating oxidative stress. Therefore, we propose that PT could be used as a natural agent for AD improvement.

The Effect of Fat Diet on Inflammatory Markers and Blood Coagulation System in Rats

  • Choi, Seok-Cheol;Seok, Seong-Ja
    • Biomedical Science Letters
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    • v.18 no.3
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    • pp.237-243
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    • 2012
  • This study was undertaken to know the effect of fat diet (for eight weeks) on changes of inflammatory markers [tumor necrosis factor (TNF-${\alpha}$) and prostaglandin $E_2$ ($PGE_2$)] and blood coagulation system [platelet aggregation function (PAF), prothrombin time (PT), activated partial thromboplastin time (aPTT)] in rats. Serum TNF-${\alpha}$, $PGE_2$, biochemical markers, PAF, PT, aPTT, and body weight were measured and compared between the control (normal diet-rats) and the fat group (fat diet-rats). The weights in the fat group were higher than those of the control group. TNF-${\alpha}$, $PGE_2$, glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine levels were greater in the fat group compared with the control group. The degree of platelet aggregation was lower, whereas PT and aPTT levels were longer in the fat group than in the control group. These findings have shown that fat diet may cause inflammatory response, diabetes, liver and renal dysfunction, and disturbances of fibrinolysis and coagulation system.

Therapeutic potential of targeting kinase inhibition in patients with idiopathic pulmonary fibrosis

  • Kim, Suji;Lim, Jae Hyang;Woo, Chang-Hoon
    • Journal of Yeungnam Medical Science
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    • v.37 no.4
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    • pp.269-276
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    • 2020
  • Fibrosis is characterized by excessive accumulation of extracellular matrix components. The fibrotic process ultimately leads to organ dysfunction and failure in chronic inflammatory and metabolic diseases such as pulmonary fibrosis, advanced kidney disease, and liver cirrhosis. Idiopathic pulmonary fibrosis (IPF) is a common form of progressive and chronic interstitial lung disease of unknown etiology. Pathophysiologically, the parenchyma of the lung alveoli, interstitium, and capillary endothelium becomes scarred and stiff, which makes breathing difficult because the lungs have to work harder to transfer oxygen and carbon dioxide between the alveolar space and bloodstream. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis and scarring of the lung tissue. Recent clinical trials focused on the development of pharmacological agents that either directly or indirectly target kinases for the treatment of IPF. Therefore, to develop therapeutic targets for pulmonary fibrosis, it is essential to understand the key factors involved in the pathogenesis of pulmonary fibrosis and the underlying signaling pathway. The objective of this review is to discuss the role of kinase signaling cascades in the regulation of either TGF-β-dependent or other signaling pathways, including Rho-associated coiled-coil kinase, c-jun N-terminal kinase, extracellular signal-regulated kinase 5, and p90 ribosomal S6 kinase pathways, and potential therapeutic targets in IPF.

A Clinical Review of the 100 Cases of Pneumonectomy (일측폐 전적출술 100례에 대한 임상적 고찰: 특히 합병증의 원인에 대하여)

  • 김진식;김의윤;손재현
    • Journal of Chest Surgery
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    • v.3 no.1
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    • pp.3-12
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    • 1970
  • During the last 10 years of period, one hundred patients with various pulmonary diseases were pneumonectomized upon at the Department of Chest Surgery of Pusan University Hospital. This paper is concerned with the clnical results of these patients along with the serious postoperative complications such as postoperative intrapleural infection and hemorrhage. The results were obtained as follows. 1.Left pneumonectomy was done in sixty-six of 100 patients [66 %] and the right one was done in the rest thirty-four[34 %]. The ratio between left and right was nearly 2:1. 2.Of all oostoperative complications, the intrapleural infection was most common, and these were 53 % in empyema thoracis and 12.7 % in pulmonary tuberculosis respectively. 3.More postoperative complications could be seen after right pneumonectomy than the left one. 4.It was thought that the postoperative intrapleural infection was closely correlated with the methods of pleural dissection at pneumonectomy,postoperatlve tube drainage, time of operation, massive hemorrhage during operation, prolongation of bleeding time, and dysfunction of the liver. 5.The repeated thoracenteses with infusion of neomycin into the infected thoracic cavity and intravenous administrations of the high units of penicillin were effective in treatment of the postoperative intrapleural infection, however, the refractory cases have to be cured by thoracoplasty with open window. 6.Immediate secondary open thoracotomy appears to be the method of choice in life saving who developed massive intrathoracic hemorrhage after pneumonectomy. 7.The mortality rate was 10 % in our cases and the main causes of death were postoperative respiratory insufficiency, pulmonary edema, hemorrhage and sudden cardiac arrest.

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A Study for Safe Dose and Clinical Use of Glycyrrhizae Radix in Shanghanlun (『상한론(傷寒論)』 처방에서 감초(甘草) 용량의 안전성 및 임상 사용에 대한 문헌 고찰)

  • Kim, Hyeong-Seop;Lee, Soong-In
    • 대한상한금궤의학회지
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    • v.8 no.1
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    • pp.1-23
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    • 2016
  • Objectives : The purpose of this paper is to find out the safe dose and clinical use for administration of Glycyrrhizae Radix in Shanghanlun(傷寒論). Methods : Web-databases(OASIS, NDSL, Pubmed, Google) were searched with keywords including 'Licorice', 'Pseudoaldosteronism', 'Glycyrrhizin', 'Testosterone' on 14/10/2016. The searched about 40 papers and books were reveiwed. Results : Glycyrrhizin(GL) and 3-monoglucuronyl glycyrrhetinic acid(3MGA) in Glycyrrhizae Radix are found to be the main compounds vulnerable for inducing pseudoaldosteronism. The dose range of Glycyrrhizae Radix in Shanghanlun prescriptions is from 0.25 g to 12 g as a daily administration, and this dose satisfies the guidelines of WHO, European Union, ABC etc. And risk factors contributing for personal sensitivities are old age(>60), female sex, liver dysfunction, hypokalemia, prolonged gastrointestinal transit time, anorexia nervosa, decreased 11-${\ss}$-hydroxysteroid dehydrogenase-2 activity and hypertension. Conclusions : As a result, dose of Glycyrrhizae Radix in Shanghanlun(傷寒論) is safe. However, the personal sensitivity and unexpected drug interactions are independent from doses of GL, so doctors should monitor those risk factors and symptoms of pseudoaldosteronism when administering Glycyrrhizae Radix.

Protective effects of Korean red ginseng extract on cadmium-induced hepatic toxicity in rats

  • Park, Sook Jahr;Lee, Jong Rok;Jo, Mi Jeong;Park, Sang Mi;Ku, Sae Kwang;Kim, Sang Chan
    • Journal of Ginseng Research
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    • v.37 no.1
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    • pp.37-44
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    • 2013
  • Korean red ginseng is known to regulate the immune system and help the body struggle infection and disease. Cadmium is widely distributed in the environment due to its use in industry. Exposure to cadmium is problematic causing organ dysfunction. This study was conducted to evaluate the protective effect of Korean red ginseng extract (RGE) against cadmium-induced hepatotoxicity in rats. In experiments, animals were orally administrated with RGE (25, 50 mg/kg) for 7 d and then intravenously injected with cadmium ($CdCl_2$, 4 mg/kg) to induce acute hepatotoxicity. Cadmium caused the elevated levels of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase in serum. In contrast, pretreatment with RGE significantly reduced those serum indexes related with liver damage. In histopathological analysis, RGE decreased the centrilobular necrosis around central veins and the peripheral hemorrhage around portal triads. Moreover, RGE restored the deficit in hepatic glutathione level resulting from cadmium treatment. RGE also inhibited the increase in the expression of Bad, a representative apoptosis marker protein, induced by cadmium treatment. Collectively, these results demonstrate that RGE can reduce the cadmium-induced hepatic toxicity, partly via anti-oxidative and anti-apoptotic process.

Study on Clinical Diseases of Blood Stasis Pattern (어혈증(瘀血證)의 임상 질환 범위에 대한 고찰)

  • Park, Mi Sun;Kim, Yeong Mok
    • Herbal Formula Science
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    • v.21 no.1
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    • pp.1-15
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    • 2013
  • Objectives : This article is a study on to which categories of modern diseases blood stasis patterns are assigned and the meaning of blood stasis interpreted with perspectives of Korean Medicine and modern medicine. Methods : We reviewed "Neijing", "Shanghanlun", "Yilingaicuo", "Xuezhenglun" and other books and modern clinical papers related with blood stasis. Results : 1. Blood stasis patterns are related with disorders of hemorrheology, hemodynamics, platelet function, microcirculation, microelements and endothelial damage. 2. From the types of syndrome differentiation, diverse diseases classified in type of qi deficiency with blood stasis and type of blood stasis due to qi stagnation are reported, which reflects qi and blood are closely connected. And many diseases are classified in type of kidney deficiency with blood stasis, which has something in common with chronic diseases can achieve effect from treatment considering blood stasis. 3. Diseases related with kidney involve menopausal disorder, mazoplasia, prostatitis, erectile dysfunction, chronic nephritis, renal calculus, osteoporosis and bursitis. Diseases related with heart involve coronary artery disease, arrhythmia and cerebral thrombosis. Diseases related with spleen involve gastritis, colonitis and digestive organ ulcer. Diseases related with liver involve hepatitis, hyperthyroidism and stroke. Diseases related with lung involve neurodermatitis, bronchitis and paranasal sinusitis. Conclusions : Blood stasis pattern which is one of the areas to draw medicine's attention has broad clinical application.

Diagnostic Radioopacity in Chloroform Ingestion -A Case Report- (방사선 비투과성 클로로포름 음독 1례)

  • Lee Sung Woo;Choi Sung Hyuk;Hong Yun Sik;Kim Su Jin;Moon Sung Woo;Moon Jun Dong;Jung Sang Hyun;Park Jong Su
    • Journal of The Korean Society of Clinical Toxicology
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    • v.3 no.1
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    • pp.48-51
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    • 2005
  • Diagostic imaging can help in management of toxicologic emergencies. We report a patient who presented to the emergency department with coma and suppressed respiration after ingestion of unknown substance. We documented chloroform with radiopaque material in bowel on abdominal radiograph. We used activated charcoal and laxative to decontaminate bowel. Hepatotoxicity occurred on 3rd admission day and elevation of liver enzyme reached peak level on 5th admission day. The patient received hemoperfusion, N-acetylsystein and supportive cares. The patient was improved from hepatic dysfunction and discharged without complication on 11th admission day. Radiograph in toxicology may confirm a diagnosis and assist in therapeutic intervention.

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Four-Week Repeated-Dose Toxicity Studies of Hyrubicin ID6105, a Novel Anthracycline Anticancer Agent, in Rats (랫드에서 새로운 Anthracycline계 항암제 Hyrubicin ID6105에 대한 4주 반복투여 독성연구)

  • 장호송;서동석;인창훈;황재식;이수해;정미숙;신지순;이홍섭;유정수
    • Toxicological Research
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    • v.18 no.4
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    • pp.375-384
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    • 2002
  • Repeated-dose toxicity of hyrubicin ID6105, a novel anthrarycline anticancer agent, was investigated in Sprague-Dawley rats. ID6105 was injected intravenously to rats at dose levels of 0.04, 0.2 or 1.0 mg/kg/day for 4 week. As a result, there were no dose-related mortality and specific clinical signs of all animals treated with the drug. However body weight gain of both male and female rats treated with a high dose (l.0 mg/kg/day) of ID6105 significantly decreased compared to control. Interestingly, the numbers of RBC and platelets, and concentration of hemoglobin remarkably increased, while protein synthesis was suppressed, which may be related to the atrophy of spleen, thymus and liver. Moreover there were severe lymphocytic depletion in spleen and thymus as well as decrease in the number of hematopoietic cells in bone marrow. Also, degeneration of cardiac muscles and testicular germinal epithelia were observed. Taken together, it is suggested that Long-term administration of ID6105 at high doses over 0.2 mg/kg/day might cause hematopoietic and male reproductive system injuries, in addition to hepatic dysfunction.