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Sample records for experimental liver damage

  1. Experimental Protoporphyria: Effect of Bile Acids on Liver Damage Induced by Griseofulvin

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    María del Carmen Martinez

    2015-01-01

    Full Text Available The effect of bile acids administration to an experimental mice model of Protoporphyria produced by griseofulvin (Gris was investigated. The aim was to assess whether porphyrin excretion could be accelerated by bile acids treatment in an attempt to diminish liver damage induced by Gris. Liver damage markers, heme metabolism, and oxidative stress parameters were analyzed in mice treated with Gris and deoxycholic (DXA, dehydrocholic (DHA, chenodeoxycholic, or ursodeoxycholic (URSO. The administration of Gris alone increased the activities of glutathione reductase (GRed, superoxide dismutase (SOD, alkaline phosphatase (AP, gamma glutamyl transpeptidase (GGT, and glutathione-S-transferase (GST, as well as total porphyrins, glutathione (GSH, and cytochrome P450 (CYP levels in liver. Among the bile acids studied, DXA and DHA increased PROTO IX excretion, DXA also abolished the action of Gris, reducing lipid peroxidation and hepatic GSH and CYP levels, and the activities of GGT, AP, SOD, and GST returned to control values. However, porphyrin accumulation was not prevented by URSO; instead this bile acid reduced ALA-S and the antioxidant defense enzymes system activities. In conclusion, we postulate that DXA acid would be more effective to prevent liver damage induced by Gris.

  2. Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage.

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    Venditti, P; Pamplona, R; Ayala, V; De Rosa, R; Caldarone, G; Di Meo, S

    2006-03-01

    Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T3)- or thyroxine (T4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most extensive damage to lipids and proteins was found in T3-treated and cold-exposed rats, respectively. Increase in oxygen reactive species released by mitochondria and microsomes was found to contribute to tissue oxidative damage, whereas the determination of single antioxidants did not provide information about the possible contribution of a reduced effectiveness of the antioxidant defence system. Indeed, liver oxidative damage in hyperthyroid rats was scarcely related to levels of the liposoluble antioxidants and activities of antioxidant enzymes. Conversely, other biochemical changes, such as the degree of fatty acid unsaturation and hemoprotein content, appeared to predispose hepatic tissue to oxidative damage associated with oxidative challenge elicited by hyperthyroid state. As a whole, our results confirm the idea that T3 plays a key role in metabolic changes and oxidative damage found in cold liver. However, only data concerning changes in glutathione peroxidase activity and mitochondrial protein content favour the idea that dissimilarities in effects of cold exposure and T3 treatment could depend on differences in serum levels of T4.

  3. Influence of matrix nature on the functional efficacy of biomedical cell product for the regeneration of damaged liver (experimental model of acute liver failure

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    S. V. Gautier

    2017-01-01

    Full Text Available Aim. A comparative analysis of the functional efficacy of biomedical cell products (BMCP for the regeneration of damaged liver based on biopolymer scaffolded porous and hydrogel matrices was performed on the experimental model of acute liver failure. Materials and methods. Matrices allowed for clinical use were employed for BMCP in the form of a sponge made from biopolymer nanostructured composite material (BNCM based on a highly purified bacterial copolymers of poly (β-hydroxybutyrate-co-β-oxyvalerate and polyethylene glycol and a hydrogel matrix from biopolymer microheterogeneous collagen-containing hydrogel (BMCH. Cellular component of BMCP was represented by liver cells and multipotent mesenchymal bone marrow stem cells. The functional efficacy of BMCP for the regeneration of damaged liver was evaluated on the experimental model of acute liver failure in Wistar rats (n = 40 via biochemical, morphological, and immunohistochemical methods. Results. When BMCP was implanted to regenerate the damaged liver on the basis of the scaffolded BNCM or hydrogel BMCH matrices, the lethality in rats with acute liver failure was absent; while in control it was 66.6%. Restoration of the activity of cytolytic enzyme levels and protein-synthetic liver function began on day 9 after modeling acute liver failure, in contrast to the control group, where recovery occurred only by days 18–21. Both matrices maintained the viability and functional activity of liver cells up to 90 days with the formation of blood vessels in BMCP. The obtained data confirm that scaffolded BNCM matrix and hydrogel BMCH matrix retain for a long time (up to 90 days the vital activity of the adherent cells in the BMCP composition, which allows using them to correct acute liver failure. At the same time, hydrogel matrix due to the presence of bioactive components contributes to the creation of the best conditions for adhesion and cell activity which accelerate the regeneration processes

  4. Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?

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    D'Argenio, Giuseppe; Cariello, Rita; Tuccillo, Concetta; Mazzone, Giovanna; Federico, Alessandro; Funaro, Annalisa; De Magistris, Laura; Grossi, Enzo; Callegari, Maria L; Chirico, Marilena; Caporaso, Nicola; Romano, Marco; Morelli, Lorenzo; Loguercio, Carmela

    2013-05-01

    Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-β, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis. © 2013 John Wiley & Sons A/S.

  5. Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage

    OpenAIRE

    Venditti, Paola; Pamplona Gras, Reinald; Ayala, Victoria; Rosa, R. de; Caldarone, G.; Di Meo, S.

    2006-01-01

    Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T-3)- or thyroxine (T-4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most ex...

  6. The metabolism of 32P-CP-PLLA seed implanted in the liver and its damage to the normal liver tissue: a study in the experimental dogs

    International Nuclear Information System (INIS)

    Tan Zhongbao; Liu Lu; Guo Jinhe; Zhu Guangyu; Wang Fuan; Nie Qi; Gao Hailin; Teng Gaojun

    2010-01-01

    Objective: To investigate the effects of intratumoral implantation of 32 P -CP-PLLA seeds on the normal canine liver tissue and to explore the metabolism of 32 P-CP-PLLA seeds implanted in the liver of experimental dogs. Methods: Twelve beagles were enrolled in this study. The dogs were randomly and equally divided into four groups: group A (185 MBq), group B (370 MBq), group C (740 MBq) and group D (0 MBq). By using laparotomy procedure 32 P-CP-PLLA seeds were implanted into dog's liver. CT scan was performed before operation as well as before the dog was sacrificed. All dogs were sacrificed three months after the implantation. Before the procedure and 1, 2, 4, 8 and 12 weeks after the procedure the blood tests and serum biochemical tests were conducted. One dog from group B and group C was selected respectively and was fed in a metabolic cage. Within one month after the procedure the cpm in feces and in urine was determined every 24 hours. One dog was picked out from each of the three groups and was punctured to get its liver tissue for pathologic exam each time at 1, 2, 4, 8 and 12 weeks after the implantation, and SPECT imaging was also performed at the same time. Pathologic study, both macroscopic and microscopic (including optical and electronic microscopy) was made to observe the liver damage after the dog was sacrificed. The statistical analysis was processed by using SPSS 13.0 software and the measuring data were expressed with mean ± standard deviation (x ± s). Results: Two months after the procedure, serological examination found that the serum alkaline phosphatase (BKP) in both group B and group C was significantly higher than that in other groups, the difference was statistically significant (P 32 P-CP-PLLA seeds was manifested as a spherical lesion which was encysted by a layer of fibrous tissue with an edematous zone peripherally. Conclusion: The implantation of 32 P-CP-PLLA seeds in dog's liver causes only localized hepatic damage with no general

  7. Kava Linked to Liver Damage

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    ... of these countries to remove kava from the market. Although liver damage appears to be rare, the ... are marketed to men, women, children, and the elderly. Advice to Consumers Safety is a concern for ...

  8. Radiation-induced liver damage

    International Nuclear Information System (INIS)

    Marcial, V.A.; Santiago-Delpin, E.A.; Lanaro, A.E.; Castro-Vita, H.; Arroyo, G.; Moscol, J.A.; Gomez, C.; Velazquez, J.; Prado, K.

    1977-01-01

    Due to the recent increase in the use of radiation therapy in the treatment of cancer with or without chemotherapy, the risk of liver radiation damage has become a significant concern for the radiotherapist when the treated tumour is located in the upper abdomen or lower thorax. Clinically evident radiation liver damage may result in significant mortality, but at times patients recover without sequelae. The dose of 3000 rads in 3 weeks to the entire liver with 5 fractions per week of 200 rads each, seems to be tolerated well clinically by adult humans. Lower doses may lead to damage when used in children, when chemotherapy is added, as in recent hepatectomy cases, and in the presence of pre-existent liver damage. Reduced fractionation may lead to increased damage. Increased fractionation, limitation of the dose delivered to the entire liver, and restriction of the high dose irradiation volume may afford protection. With the aim of studying the problems of hepatic radiation injury in humans, a project of liver irradiation in the dog is being conducted. Mongrel dogs are being conditioned, submitted to pre-irradiation studies (haemogram, blood chemistry, liver scan and biopsy), irradiated under conditions resembling human cancer therapy, and submitted to post-irradiation evaluation of the liver. Twenty-two dogs have been entered in the study but only four qualify for the evaluation of all the study parameters. It has been found that dogs are susceptible to liver irradiation damage similar to humans. The initial mortality has been high mainly due to non-radiation factors which are being kept under control at the present phase of the study. After the initial experiences, the study will involve variations in total dose and fractionation, and the addition of anticoagulant therapy for possible prevention of radiation liver injury. (author)

  9. Liver tissue tolerance for irradiation : Experimental and clinical investigations

    NARCIS (Netherlands)

    Cromheecke, M; Konings, AWT; Szabo, BG; Hoekstra, HJ

    2000-01-01

    Radiation treatment of the liver for malignant disease has gained renewed interest due to newly developed treatment modalities. Still limited specific knowledge is available concerning liver damage following irradiation. Inconsistencies between reported animal experimental studies are largely due to

  10. Experimental models of liver fibrosis.

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    Yanguas, Sara Crespo; Cogliati, Bruno; Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

    2016-05-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

  11. Experimental approach to IGF-1 therapy in CCl4-induced acute liver damage in healthy controls and mice with partial IGF-1 deficiency.

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    Morales-Garza, Luis A; Puche, Juan E; Aguirre, Gabriel A; Muñoz, Úrsula; García-Magariño, Mariano; De la Garza, Rocío G; Castilla-Cortazar, Inma

    2017-05-04

    Cell necrosis, oxidative damage, and fibrogenesis are involved in cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1) levels are diminished. This study evaluates whether the exogenous administration of low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride (CCl 4 )-induced liver damage compared to healthy controls (Wt Igf +/+ ). Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in mice with a partial deficit of this hormone (Hz Igf1 +/- ). Three groups of 25 ± 5-week-old healthy male mice (Wt Igf +/+ ) were included in the protocol: untreated controls (Wt). Controls that received CCl 4 (Wt + CCl 4 ) and Wt + CCl 4 were treated subcutaneously with IGF-1 (2 µg/100 g body weight/day) for 10 days (Wt + CCl 4  + IGF1). In parallel, three IGF-1-deficient mice (Hz Igf1 +/- ) groups were studied: untreated Hz, Hz + CCl 4 , and Hz + CCl 4  + IGF-1. Microarray and real-time quantitative polymerase chain reaction (RT-qPCR) analyses, serum aminotransferases levels, liver histology, and malondialdehyde (MDA) levels were assessed at the end of the treatment in all groups. All data represent mean ± SEM. An altered gene coding expression pattern for proteins of the extracellular matrix, fibrosis, and cellular protection were found, as compared to healthy controls, in which IGF-1 therapy normalized in the series including healthy mice. Liver histology showed that Wt + CCl 4  + IGF1 mice had less oxidative damage, fibrosis, lymphocytic infiltrate, and cellular changes when compared to the Wt + CCl 4 . Moreover, there was a correlation between MDA levels and the histological damage score (Pearson's r = 0.858). In the IGF-1-deficient mice series, similar findings were identified, denoting a much more vulnerable hepatic parenchyma. IGF1 treatment improved the biochemistry, histology, and genetic expression of pro-regenerative and cytoprotective factors in both series

  12. Using multiphoton fluorescence lifetime imaging to characterize liver damage and fluorescein disposition in liver in vivo

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    Thorling, Camilla A.; Studier, Hauke; Crawford, Darrell; Roberts, Michael S.

    2016-03-01

    Liver disease is the fifth most common cause of death and unlike many other major causes of mortality, liver disease rates are increasing rather than decreasing. There is no ideal measurement of liver disease and although biopsies are the gold standard, this only allows for a spot examination and cannot follow dynamic processes of the liver. Intravital imaging has the potential to extract detailed information over a larger sampling area continuously. The aim of this project was to investigate whether multiphoton and fluorescence lifetime imaging microscopy could detect early liver damage and to assess whether it could detect changes in metabolism of fluorescein in normal and diseased livers. Four experimental groups were used in this study: 1) control; 2) ischemia reperfusion injury; 3) steatosis and 4) steatosis with ischemia reperfusion injury. Results showed that multiphoton microscopy could visualize morphological changes such as decreased fluorescence of endogenous fluorophores and the presence of lipid droplets, characteristic of steatosis. Fluorescence lifetime imaging microscopy showed increase in NADPH in steatosis with and without ischemia reperfusion injury and could detect changes in metabolism of fluorescein to fluorescein monoglurcuronide, which was impaired in steatosis with ischemia reperfusion injury. These results concluded that the combination of multiphoton microscopy and fluorescence lifetime imaging is a promising method of assessing early stage liver damage and that it can be used to study changes in drug metabolism in the liver as an indication of liver disease and has the potential to replace the traditional static liver biopsy currently used.

  13. EFFICACY OF REMAXOL AND ADEMETHIONINE IN EXPERIMENTAL LIVER DAMAGE CAUSED BY A COMBINATION OF RESERVE-SERIES ANTITUBERCULOSIS DRUGS AND ALCOHOL

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    D. S. Sukhanov

    2014-01-01

    Full Text Available The hepatic and endothelial protective effects of remaxol and S-adenosyl-L-methionine were studied on 24 male rats with liver damage caused by reserve-series antituberculosis drugs in combination with alcohol. The test agents were found to have a unilateral hepatoprotective effect in decreasing the blood levels of triglycerides, bilirubin, and alkaline phosphatase with a concurrent significant reduction in the manifestations of hyaline-drop and hydropic dystrophy of hepatocytes. Remaxol and ademethionine have the same endothelial protective activity manifested as normalization of an endothelium-dependent vasodilation response and endothelial dysfunction coefficient.

  14. STAT3, a Key Parameter of Cytokine-driven Tissue Protection During Sterile Inflammation – the Case of Experimental Acetaminophen (Paracetamol-induced Liver Damage

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    Heiko eMühl

    2016-05-01

    Full Text Available Acetaminophen (APAP, N-acetyl-p-aminophenol, or paracetamol overdosing is a prevalent cause of acute liver injury. While clinical disease is initiated by overt parenchymal hepatocyte necrosis in response to the analgetic, course of intoxication is substantially influenced by associated activation of innate immunity. This process is supposed to be set in motion by release of danger associated molecular patterns (DAMPs from dying hepatocytes and is accompanied by an inflammatory cytokine response. Murine models of APAP-induced liver injury emphasize the complex role that DAMPs and cytokines play in promoting either hepatic pathogenesis or resolution and recovery from intoxication. Whereas the function of key inflammatory cytokines is controversially discussed, a subclass of specific cytokines capable of efficiently activating the hepatocyte signal transducer and activator of transcription (STAT-3 pathway stands out as being consistently protective in murine models of APAP intoxication. Those include foremost interleukin (IL-6, IL-11, IL-13, and IL-22. Above all, activation of STAT3 under the influence of these cytokines has the capability to drive hepatocyte compensatory proliferation, a key principle of the regenerating liver. Herein, the role of these specific cytokines during experimental APAP-induced liver injury is highlighted and discussed in a broader perspective. In hard-to-treat or at-risk patients standard therapy may fail and APAP intoxication can proceed towards a fatal condition. Focused administration of recombinant STAT3-activating cytokines may evolve as novel therapeutic approach under those ill-fated conditions.

  15. Imidacloprid enhances liver damage in Wistar rats: Biochemical, oxidative damage and histological assessment

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    Sana Chakroun

    2017-12-01

    Full Text Available Objective: To investigate the potential adverse effects of imidacloprid on biochemical parameters, oxidative stress and liver damage induced in the rat by oral sub-chronic imidaclopride exposure. Methods: Rats received three different doses of imidacloprid (1/45, 1/22 and 1/10 of LD50 given through gavage for 60 days. Two dozen of male Wistar rats were randomly divided into four experimental groups. Liver damage was determined by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase leakages. The prooxidant-antioxydant status in hepatic tissue homogenate was evaluated by measuring the degree of lipid peroxidation, the antioxidant enzymes activities such as catalase, superoxide dismutase and glutathione peroxidase (GPx. Results: The relative liver weight was significantly higher than that of control and other treated groups at the highest dose 1/10 of LD50 of imidacloprid. Additionally, treatment of rats with imidacloprid significantly increased liver lipid peroxidation (P ≤ 0.05 or 0.01 which went together with a significant decrease in the levels of superoxide dismutase and catalase activities. Parallel to these changes, imidacloprid treatment enhanced liver damage as evidence by sharp increase in the liver enzyme activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase. These results were also confirmed by histopathology. Conclusions: In light of the available data, it is our thought that after imidacloprid sub-chronic exposure, depletion of antioxidant enzymes is accompanied by induction of potential oxidative stress in the hepatic tissues that might affect the function of the liver which caused biochemical and histopathological alteration.

  16. PULMONARY AND LIVER DAMAGE DURING TREATMENT WITH ACETAMINOPHEN (PARACETAMOL

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    L. I. Dvoretski

    2016-01-01

    Full Text Available This is a case report of pulmonary damage in the form of intestinal pneumonitis with severe respiratory failure during administration of acetaminophen (paracetamol. In addition, significant increase of ALT and AST levels without clinical signs of liver damage was observed in this patient. After glucocorticoids administration regression of radiological abnormal findings in the lungs along with normalization of liver enzymes values were registered. The rarity of interstitial pneumonitis induced by acetaminophen (paracetamol, especially in combination with liver damage, is emphasized. The presented patient history is the first case report of drug-induced hepatopulmonary syndrome during acetaminophen (paracetamol administration.

  17. Oxidative Stress and Pulmonary Changes in Experimental Liver Cirrhosis

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    Renata Salatti Ferrari

    2012-01-01

    Full Text Available The use of carbon tetrachloride (CCl4 in rats is an experimental model of hepatic tissue damage; which leads to fibrosis, and at the long term, cirrhosis. Cirrhosis is the consequence of progressive continued liver damage, it may be reversible when the damaging noxae have been withdrawn. The aim of this study is to evaluate the changes caused by cirrhosis in lung and liver, through the experimental model of intraperitoneal CCI4 administration. We used 18 male Wistar rats divided into three groups: control (CO and two groups divided by the time of cirrhosis induction by CCI4: G1 (11 weeks, G2 (16 weeks. We found significant increase of transaminase levels and lipid peroxidation (TBARS in liver and lung tissue and also increased antioxidant enzymes SOD and CAT, as well as the expression of TNF-α and IL-1β in the lung of cirrhotic animals. We observed changes in gas exchange in both cirrhotic groups. We can conclude that our model reproduces a model of liver cirrhosis, which causes alterations in the pulmonary system that leads to changes in gas exchange and size of pulmonary vessels.

  18. Experimental microangiographic study in normal rabbit liver

    International Nuclear Information System (INIS)

    Kim, Yoon Gyoo; Park, Jong Yeon; Han, Kook Sang; Moon, Ki Ho; Choi, Chang Ho; Han, Koon Taek; Lee, Suck Hong; Kim, Byung Soo

    1994-01-01

    Microangiography is an experimental radiologic technique for evaluation of the morphology and the function of small vessels. The purpose of this study is to introduce a good microangiographic technique and to present the microangiographic appearance of normal hepatic vascular pattern. Five white rabbits weighing 2.5-2.9Kg were objected. Polyethylene catheters were inserted in portal vein and then in IVC. Heparin mixed normal saline (2cc/1000cc) was infused through portal vein and blood was drained to IVC. Barium suspension was infused via the catheter placed in portal vein until the liver surface showed satisfactory finding in barium filling. The liver was removed and this preparation was fixed in 10% formaline for 7 days. After fixation, the liver was sectioned on 1-2mm thickness. The slices were radiographed on high resolution plate using Faxitron. H-E staining of liver tissue was also done. The microbrium was well distributed in all small vessels without filling defect. And we could find the hexagonal shaped classic liver lobule, in which the central vein was located at central portion and portal vein at periphery. The enlargement was showed numerous sinusoids, but there was less dye in the central portion of lobule, but the central vein was well filled by microbarium. The peripheral portion of lobule was well filled with microbarium. So, we could find diamond shaped liver acinus, in which central vein was located at priperal portion and the center of liver acinus was terminal portal vein that growed out from a small portal space. The three acini made the complex acinus and acinar agglomerate was composed of three or four complex acini. It is considered that the liver acinus pattern of Rapparport is more acceptable on microangiography than the classic concept of hepatic lobule

  19. [Causes and management of severe acute liver damage during pregnancy].

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    Sepulveda-Martinez, Alvaro; Romero, Carlos; Juarez, Guido; Hasbun, Jorge; Parra-Cordero, Mauro

    2015-05-01

    Abnormalities in liver function tests appear in 3% of pregnancies. Severe acute liver damage can be an exclusive condition of pregnancy (dependent or independent of pre-eclampsia) or a concomitant disease. HELLP syndrome and acute fatty liver of pregnancy are the most severe liver diseases associated with pregnancy. Both appear during the third trimester and have a similar clinical presentation. Acute fatty liver may be associated with hypoglycemia and HELLP syndrome is closely linked with pre-eclampsia. Among concomitant conditions, fulminant acute hepatitis caused by medications or virus is the most severe disease. Its clinical presentation may be hyper-acute with neurological involvement and severe coagulation disorders. It has a high mortality and patients should be transplanted. Fulminant hepatic failure caused by acetaminophen overdose can be managed with n-acetyl cysteine. Because of the high fetal mortality rate, the gestational age at diagnosis is crucial.

  20. LIVER AND BONE MARROW STEM/PROGENITOR CELLS AS REGULATORS OF REPARATIVE REGENERATION OF DAMAGED LIVER

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    А. V. Lundup

    2010-01-01

    Full Text Available In this review the modern information about effectiveness of liver insufficiency treatment by stem/ progenitor cells of liver (oval cells and bone marrow (hemopoietic cells and mesenchymal cells was presented. It is shown that medical action of these cells is referred on normalization of liver cell interaction and reorganization of processes of a reparative regeneration in damaged liver. It is believed that application of mesenchymal stromal cells from an autological bone marrow is the most perspective strategy. However, for definitive judgement about regenerative possibilities of the autological bone marrow cells it is necessary to carry out large-scale double blind clinical researches. 

  1. Careful: Acetaminophen in Pain Relief Medicines Can Cause Liver Damage

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    ... Pain Relievers and Fever Reducers Careful: Acetaminophen in pain relief medicines can cause liver damage Share Tweet Linkedin Pin it More sharing options Linkedin Pin ... ingredient in many over-the-counter and prescription medicines that help relieve pain and reduce fever. More than 600 over-the- ...

  2. Liver damage and senescence increases in patients developing hepatocellular carcinoma.

    Science.gov (United States)

    Rey, Silvia; Quintavalle, Cristina; Burmeister, Katharina; Calabrese, Diego; Schlageter, Manuel; Quagliata, Luca; Cathomas, Gieri; Diebold, Joachim; Molinolo, Alfredo; Heim, Markus H; Terracciano, Luigi M; Matter, Matthias S

    2017-08-01

    Most patients with a hepatocellular carcinoma (HCC) have an underlying chronic liver inflammation, which causes a continuous damage leading to liver cirrhosis and eventually HCC. However, only a minority of cirrhotic patients develop HCC. To assess a possible differential impact of liver inflammation in patients developing HCC versus patients remaining tumor-free, we designed a longitudinal study and analysed liver tissue of the same patients (n = 33) at two points in time: once when no HCC was present and once several years later when an HCC was present. As a control group, we followed cirrhotic patients (n = 37) remaining tumor-free over a similar time frame. We analysed cell damage and senescence of hepatocytes by measuring γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, nuclear size, and telomere length. γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, in the first liver biopsy was similar in patients developing HCC later on and cirrhotic patients remaining tumor free. In contrast, γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, was significantly higher in the second non-tumoral liver biopsy of HCC patients than in the control patients. Consequently, the individual increase in γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, from the first biopsy to the second biopsy was significantly higher in patients developing HCC than in patients remaining tumor free. In addition, changes in nuclear size and telomere length revealed a more pronounced cell aging in patients developing HCC than in patients remaining tumor free. Hepatocytes from patients developing HCC go through more pronounced cell damage and senescence in contrast to cirrhotic patients remaining tumor free. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  3. The effect of apple (Malus Domestica juice on the damage of mice liver cells due to paracetamol treatment

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    Anthony Hartanto

    2009-07-01

    Full Text Available The liver is an important organ for body metabolism process. Liver disease is one of serious health problems in developing countries including Indonesia. Liver damage is caused by viral infection, toxic agent exposure (medications, alcohol, hormonal disturbance, neoplasm and autoimmune diseases. The use of high dose paracetamol to reduce pain also leads to liver damage. Apple (Malus domestica juice is a natural anti oxidant agent. This laboratory experimental study was performed to discover the effect of giving apple juice on damaged cell regeneration due to the use of paracetamol. The study was performed in 21 male mice from Swiss-Webster strain that were divided into group I, II, and III. Group, I served as control while group II received 1 mg/ml paracetamol dose for 5 days and Group III received 1 mg/ml paracetamol for 5 days and 1 ml of apple juice on the 5th to 10th day. The observation of the mice liver cells was conducted using a light microscope with 400x magnification to get the number of necrotic liver cells per view field. The results of this study showed a difference in the number of necrotic liver cells between Group II and III. ANOVA statistical test ( = 0.05 concluded that apple juice significantly helps regeneration process in damaged liver cells caused by paracetamol.

  4. Studies on the effects of ionizing radiation on the normal and diseased liver in experimental animals

    International Nuclear Information System (INIS)

    Mahmoud, S.A.

    1981-01-01

    The experiments carried out in the present study primarily concerned with the effects of ionizing radiations on the normal and diseased liver in experimental animals (mice). Different radiation intensities and different exposure schemes were used to irradiate both healthy and schistosoma mansoni infected animals. A group of uninfected and unirradiated animals were used as controls. Follow up studies were performed every 6 weeks for 30 weeks. These included histopathological studies of the liver damage at every observation periods for all animal groups

  5. Ultrastructural and DNA damaging effects of lead nitrate in the liver.

    Science.gov (United States)

    Narayana, K; Al-Bader, Maie

    2011-01-01

    A ubiquitous environmental toxicant - lead is known to affect several organ systems. This study was designed to investigate the effects of lead nitrate exposure on liver structure and DNA fragmentation. Adult male Wistar rats were treated orally with lead nitrate at the dose levels of 0%, 0.5% and 1% for 60 days and sacrificed on the next day. The liver was processed for thick sections and evaluated after toludine blue staining and by electron microscopy after staining with uranyl acetate and lead citrate. The DNA damage was assessed by DNA fragmentation assay. The liver weight was not significantly affected in the experimental groups. Hepatocyte nuclei were not shrunk, instead lead was mitogenic to hepatocytes as indicated by an increase in the number of binucleated hepatocytes (Plead-treated groups, these changes were not significantly different from that in control as evaluated by optical density. In conclusion, lead induces necrotic changes with simultaneous mitogenic activity; however, it does not induce significant DNA damage in the liver. Copyright © 2009 Elsevier GmbH. All rights reserved.

  6. Reversal of aflatoxin induced liver damage by turmeric and curcumin.

    Science.gov (United States)

    Soni, K B; Rajan, A; Kuttan, R

    1992-09-30

    The effect of certain food additives on aflatoxin production by Aspergillus parasiticus has been studied in vitro. Extracts of turmeric (Curcuma longa), garlic (Allium sativum) and asafoetida (Ferula asafoetida) inhibited the aflatoxin production considerably (more than 90%) at concentrations of 5-10 mg/ml. Similar results were also seen using butylated hydroxytoluene, butylated hydroxyanisole and ellagic acid at concentration 0.1 mM. Curcumin, the antioxidant principle from Curcuma longa did not have any effect on aflatoxin production. Turmeric and curcumin were also found to reverse the aflatoxin induced liver damage produced by feeding aflatoxin B1 (AFB1) (5 micrograms/day per 14 days) to ducklings. Fatty changes, necrosis and biliary hyperplasia produced by AFB1 were considerably reversed by these food additives.

  7. Liver Damage Associated with Polygonum multiflorum Thunb.: A Systematic Review of Case Reports and Case Series

    Directory of Open Access Journals (Sweden)

    Xiang Lei

    2015-01-01

    Full Text Available Objective. To summarize the characteristics and analysis of relevant factors and to give references for prevention and further study of liver damage associated with Polygonum multiflorum Thunb. (HSW, we provide a systematic review of case reports and case series about liver damage associated with HSW. Methods. An extensive search of 6 medical databases was performed up to June 2014. Case reports and case series involving liver damage associated with HSW were included. Results. This review covers a total of 450 cases in 76 articles. HSW types included raw and processed HSW decoction pieces and many Chinese patent medicines that contain HSW. Symptoms of liver damage occur mostly a month or so after taking the medicine, mainly including jaundice, fatigue, anorexia, and yellow or tawny urine. Of the 450 patients, two cases who received liver transplantation and seven who died, the remaining 441 cases recovered or had liver function improvement after discontinuing HSW products and conservative care. Conclusion. HSW causes liver toxicity and may cause liver damage in different degrees and even lead to death; most of them are much related to long-term and overdose of drugs. Liver damage associated with HSW is reversible, and, after active treatment, the majority can be cured. People should be alert to liver damage when taking HSW preparations.

  8. ASOTHEMIA EFFECT UPON THE LIVER ARGINASE ACTIVITY IN THE ACUTE KIDNEY DAMAGE

    Directory of Open Access Journals (Sweden)

    Jelena Djordjevic

    2002-07-01

    Full Text Available The acute damage of the kidney function leads to an outstanding disbalance of many homeostatic mechanisms in the organism that emerges as a consequence of the reduced glomerulic filtration and the accompanying oliguria. This conditions the emergence of asothemia, that is, the state caracterized by an increase of the level of urea, creatinine and other ureic toxins in the blood. The results of the previous exami-nations show that the acute renal insufficiency is a disturbance accompanied with ac-celerated protein catabolism. The urea is a terminal product of the protein catabolism whose synthesis is mainly taking place in the liver; that is why the research aimed at examining the liver arginase activity, terminal enzyme in the urea synthesis cycle in various experimental models of the acute renal insufficiency. The acute asothemia is experimentally caused upon the male Spraque Dawlly rats by means of two models, namely, the model of bilateral binding of the urethra (BPU and the clycerolic model. The arginase activity in the liver tissue homogenate is measured by the Porembsky and Cedra method on the basis of the liberated ornithine liberation. In the plasma of the experimental animals the level of urea and creatinine was measured for the sake of estimating the renal function. In both the models of the acute kidney damage there was a considerable increase of the urea and creatinine concentration in the plasma (p<0,001 which is followed by a significant increase of the hepatic arginase activity with respect to the control group of the animals. On the basis of the obtained results it can be conclude that asothemia in the acute renal insufficiency is followed by an in-crease in the liver arginase activity.

  9. CT quantitative diagnosis in fatty liver. An experimental study

    International Nuclear Information System (INIS)

    Zhao Hong; Li Binxiang; Zhang Lizhong; Liang Jianfang

    1997-01-01

    Purpose: To evaluate the relation between liver fat content and CT value in animal experiment for the diagnosis and treatment of fatty liver in clinical practice. Materials and methods: Fatty liver model was established in 30 Wistar rats (experimental group), 5 rats was used as the control group. The 5 rats of the control group and 5 rats randomly chosen from experimental group at the first, second, third, and the fourth weekends, were measured for the CT number of total liver. Three pieces of liver specimen from each rats were removed from left, central and right lobes for histologic examination. The ratio of liver fat content to liver volume (Vv value) was measured by microscopic image pattern analyzer. Results: Significant linear negative correlation (r = -0.950, t = 12.90, P<0.001) was found between CT and Vv values. Conclusion: Using CT monitoring, the degree and amount of liver fat could be assessed and liver biopsy obviated in the diagnosis and follow up during treatment of fatty liver

  10. Free methionine supplementation limits alcohol-induced liver damage in rats

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Bode, C.; Bode, J.C.

    1998-01-01

    Alcohol feeding to rats that were submitted to a jejunoileal bypass operation has been shown to result in liver damage being comparable with alcohol-induced liver disease in man. In the present study, a striking effect of free methionine consumption on histological liver injury, triglyceride accu...

  11. Applications of 1H-NMR relaxometry in experimental liver studies

    International Nuclear Information System (INIS)

    Holzmueller, P.

    1992-01-01

    Purpose of this study was to investigate applications of proton nuclear magnetic resonance ( 1 H-NMR) relaxometry in experimental medicine. Relaxometry was performed by measurements of spin-lattice (T 1 ) and spin-spin (T 2 ) relaxation time parameters on liver biopsies up to four hours after biopsy excision. Variations of relaxation times due to species and strain, different sample handling and different liver damage models, ethionine fatty liver and paracetamol liver necrosis, were investigated. Cell integrity effects were studied on homogenized liver samples. Relaxation time parameters, especially 'main' components T 1A and T 2A of biexponential model fit, were identified to react very sensitive after tissue damages as well as to cell viability. Thus, investigation of stored liver grafts was performed in order to evaluate the possibility of a rapid liver graft viability testing method for human liver transplantation surgery by 1 H-NMR relaxometry. Another series of measurements was performed to investigate the applicability of isoflurane anesthesia for in vivo NMR experiments. This study proved the good appropriateness of isoflurane for that purpose provided that physiological monitoring and individual adjustment of anesthesia are performed. In these investigations it could be revealed that mainly T 1A and T 2A are influenced by tissue condition and that different information is inherent in these two parameters, with T 2A reflecting tissue viability and changes of tissue conditions very sensitively but rather unspecifically in respect to the damage applied. Based on these results the following future applications of 1 H-NMR relaxometry are suggested : (1) model investigations, (2) investigation of given pathologies, (3) investigation of basic requirements for in vivo NMR and (4) application in a liver graft viability testing protocol, which seems to be the most important future application of 1 H-NMR relaxometry in medicine. (author)

  12. Ideal Experimental Rat Models for Liver Diseases

    OpenAIRE

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and dive...

  13. Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage.

    Science.gov (United States)

    Shirazi, Alireza; Mihandoost, Ehsan; Ghobadi, Ghazale; Mohseni, Mehran; Ghazi-Khansari, Mahmoud

    2013-01-01

    Ionizing radiation interacts with biological systems to induce excessive fluxes of free radicals that attack various cellular components. Melatonin has been shown to be a direct free radical scavenger and indirect antioxidant via its stimulatory actions on the antioxidant system.The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury to the rat liver after whole body irradiation. In this experimental study,thirty-two rats were divided into four groups. Group 1 was the control group, group 2 only received melatonin (30 mg/kg on the first day and 30 mg/kg on the following days), group 3 only received whole body gamma irradiation of 10 Gy, and group 4 received 30 mg/kg melatonin 30 minutes prior to radiation plus whole body irradiation of 10 Gy plus 30 mg/kg melatonin daily through intraperitoneal (IP) injection for three days after irradiation. Three days after irradiation, all rats were sacrificed and their livers were excised to measure the biochemical parameters malondialdehyde (MDA) and glutathione (GSH). Each data point represents mean ± standard error on the mean (SEM) of at least eight animals per group. A one-way analysis of variance (ANOVA) was performed to compare different groups, followed by Tukey's multiple comparison tests (p<0.05). The results demonstrated that whole body irradiation induced liver tissue damage by increasing MDA levels and decreasing GSH levels. Hepatic MDA levels in irradiated rats that were treated with melatonin (30 mg/kg) were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group. The data suggest that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation.

  14. Nadolol for lithium tremor in the presence of liver damage.

    Science.gov (United States)

    Dave, M; Langbart, M M

    1994-03-01

    Lithium-induced tremor classically responds to treatment with propranolol. Since it is metabolized in the liver, propranolol may not be the drug of choice in those patients who have compromised liver function or who are recovering from prior liver diseases. Another nonselective beta-adrenergic blocker, nadolol, has no hepatic biotransformation. We present here the first case report of successful treatment of lithium-induced tremor with nadolol, which was selected because the patient had compromised liver function. The patient's liver function tests remained stable with the therapy.

  15. Experimental study of oxidative DNA damage

    DEFF Research Database (Denmark)

    Loft, Steffen; Deng, Xin-Sheng; Tuo, Jingsheng

    1998-01-01

    Animal experiments allow the study of oxidative DNA damage in target organs and the elucidation of dose-response relationships of carcinogenic and other harmful chemicals and conditions as well as the study of interactions of several factors. So far the effects of more than 50 different chemical ...

  16. Slow elimination of DNA damaged bases in the liver of old gamma-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Gaziev, A I; Malakhova, L V; Fomenko, L A [AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki

    1981-01-01

    Elimination of the DNA damaged bases in the liver of old and young mice after their gamma-irradiation is studied. It is established that the incision rate of DNA gamma-damaged bases in the liver of old mice is lower than in the liver of the young ones. It is supposed to be connected with the decrease of the activity of DNA reparation ferments or with the presence of limitations in chromatin for the access of these ferments to the damaged parts of DNA in the cells of old animals.

  17. Ideal Experimental Rat Models for Liver Diseases.

    Science.gov (United States)

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-05-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes.

  18. Protective Effect of the Persian Gulf brittle star Ophiocoma Erinaceus extract on carbon tetrachloride (CCl4 induced liver damage in adult male Wistar rats

    Directory of Open Access Journals (Sweden)

    Aida Soheili

    2015-12-01

    Full Text Available Background and Aim:  Brittle star possess  bioactive compounds which confer the wound healing capacity and regenerative potency of damaged  arms and organisms to this creature. The aim of the current study was to assess the   protective  effect  of  the  star extract on liver damages induced by carbon tetrachloride in adult male Wistar rats. Materials and Methods: In this experimental study, 32 adult male rats were randomly divided into 4 equal groups: control, Sham exposed, experimental 1 (treated with %25 extract and experimental 2 (treated with %50 extract of star Ophiocoma Erinaceus. The control group received no treatment. The sham exposed groups received carbon tetrachloride .(50% in olive oil .0.5 ml/kg for 7 days. The experimental groups firstly received carbon tetrachloride, then received %25, %50 brittle star extract as intragastric for 7 days. Finally, the animals were sacrificed, and their bodies and livers were weighed. Then, the livers sections were prepared and were examined by means of light microscope. Finally, the obtained  quantitative data was analyzed using SPSS (V; 20, Mini Tab software, ANOVA, and Tukey. at the significant level of P<0.001. Results: Carbon tetrachloride significantly decreased the rats’ body weight, but it increased their livers weight (P<0.001. Histopathological evaluations showed .extensive liver damage. On the other hand, treatment with brittle star extract .ncreased liver weight, reduced. body weight and significantly altered other induced changes by carbon tetrachloride on liver structure such as hepatocytes number, Kupffer cells, and arteritis, which indicated  the improvement of damaged liver tissue (P<0.001. Conclusion: It was found that brittle star extract can exert protective effects on  liver damages induced by carbon tetrachloride on male Wistar rat.

  19. Study in radiation tolerance of damaged liver induced by dimethylaminoazobenzene. Histological study using Wistar rats

    International Nuclear Information System (INIS)

    Izumiyama, Kazutaka; Kodama, Akihisa; Kono, Michio

    1997-01-01

    We studied to determine the tolerable dose of radiation in damaged liver using Wistar male rats aged 4 weeks. A damaged liver group fed on low-protein animal chow containing 0.07% dimethylaminoazobenzene (DAB) ad libitum. Rats feeding on the chow without DAB served as the normal liver group. In both groups, two rats each underwent irradiation of the right half of the liver with doses of 5 Gy, 10 Gy, 15 Gy, or 20 Gy using a 15 MeV electron beam. The animals were sacrificed 2 or 4 weeks after irradiation, and the irradiated and non-irradiated parts of the liver were compared histologically with respect to hepatocellular necrosis, the extent of degeneration, and the degree of inflammatory cell infiltration, as well as the degree of inflammatory cell infiltration and fibrosis in Glisson's capsule. Secondly, in the normal liver group, 6 rats were irradiated with dose of 20 Gy, and in the damaged liver group, 6 rats each were irradiated with doses of 10 Gy, 12 Gy, 15 Gy or 20 Gy, and the same study was performed. In the normal liver group, no histological differences were seen between the irradiated and non-irradiated parts of the liver even when irradiated with 20 Gy dose. In the damaged liver group, there were no differences between the irradiated and non-irradiated parts of the liver in animals given 15 Gy or 10 Gy. In the 12 Gy group, however, one out of three rats each showed more severe changes in the irradiated part at 2 and 4 weeks after irradiation. One out of six rats in the 15 Gy group and four out of six rats in the 20 Gy group died in the first week after irradiation. In the damaged liver group, a single irradiation of up to 10 Gy delivered to one half of the liver was tolerable. At doses of 12 Gy or higher, however, irreversible changes occurred in some animals, and deaths occurred at 15 Gy or 20 Gy. Since even 20 Gy was tolerated in the normal liver group, damaged liver showed a lower tolerance than normal liver. (author)

  20. Consumption of Coprinus comatus polysaccharide extract causes recovery of alcoholic liver damage in rats

    NARCIS (Netherlands)

    Ozalp, F.O.; Canbek, M.; Yamac, M.; Kanbak, G.; Griensven, van L.J.L.D.; Uyanoglu, M.; Senturk, H.; Karlkava, K.; Oglakci, A.

    2014-01-01

    Excess use of alcohol is known to be associated with liver diseases such as fatty liver, alcoholic hepatitis, and cirrhosis. Various practices may be applied to prevent or treat the damage caused by chronic alcoholism. Coprinus comatus (O.F. Müll.) Pers. (Agaricaceae) is a macrofungus that has been

  1. The role of xanthine oxidase in ischemia/reperfusion damage of rat liver

    NARCIS (Netherlands)

    Frederiks, W. M.; Bosch, K. S.

    1995-01-01

    Oxygen radicals have been proposed to be involved in the induction of liver cell damage during reperfusion after ischemia. The role of xanthine oxidase in this process and the potential of the antioxidant system have been studied in a model of in vivo ischemia of rat liver followed by 1 h

  2. Experimental Damage Identification of a Model Reticulated Shell

    Directory of Open Access Journals (Sweden)

    Jing Xu

    2017-04-01

    Full Text Available The damage identification of a reticulated shell is a challenging task, facing various difficulties, such as the large number of degrees of freedom (DOFs, the phenomenon of modal localization and transition, and low modeling accuracy. Based on structural vibration responses, the damage identification of a reticulated shell was studied. At first, the auto-regressive (AR time series model was established based on the acceleration responses of the reticulated shell. According to the changes in the coefficients of the AR model between the damaged conditions and the undamaged condition, the damage of the reticulated shell can be detected. In addition, the damage sensitive factors were determined based on the coefficients of the AR model. With the damage sensitive factors as the inputs and the damage positions as the outputs, back-propagation neural networks (BPNNs were then established and were trained using the Levenberg–Marquardt algorithm (L–M algorithm. The locations of the damages can be predicted by the back-propagation neural networks. At last, according to the experimental scheme of single-point excitation and multi-point responses, the impact experiments on a K6 shell model with a scale of 1/10 were conducted. The experimental results verified the efficiency of the proposed damage identification method based on the AR time series model and back-propagation neural networks. The proposed damage identification method can ensure the safety of the practical engineering to some extent.

  3. Experimental models of hepatotoxicity related to acute liver failure

    Energy Technology Data Exchange (ETDEWEB)

    Maes, Michaël [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Vinken, Mathieu, E-mail: mvinken@vub.ac.be [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Jaeschke, Hartmut [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City (United States)

    2016-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. - Highlights: • The murine APAP model is very close to what is observed in patients. • The Gal/ET model is useful to study TNFα-mediated apoptotic signaling mechanisms. • Fas receptor activation is an effective model of apoptosis and secondary necrosis. • The ConA model is a relevant model of auto-immune hepatitis and viral hepatitis. • Multiple time point evaluation needed in experimental models of acute liver injury.

  4. Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice.

    Science.gov (United States)

    Salgueiro, Andréia Caroline Fernandes; Folmer, Vanderlei; da Silva, Marianne Pires; Mendez, Andreas Sebastian Loureiro; Zemolin, Ana Paula Pegoraro; Posser, Thaís; Franco, Jeferson Luis; Puntel, Robson Luiz; Puntel, Gustavo Orione

    2016-01-01

    This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.

  5. Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Andréia Caroline Fernandes Salgueiro

    2016-01-01

    Full Text Available This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF tea on oxidative stress and liver damage in streptozotocin (STZ-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1 BF chemical composition; (2 glucose levels; (3 liver/body weight ratio and liver transaminases; (4 reactive oxygen species (ROS, lipid peroxidation, and protein carbonylation in liver; (5 superoxide dismutase (SOD and catalase (CAT activities in liver; (6 δ-aminolevulinate dehydratase (δ-ALA-D and nonprotein thiols (NPSH in liver; (7 Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.

  6. Oxidative damage in liver after perinatal intoxication with lead and/or cadmium.

    Science.gov (United States)

    Massó, Elvira Luján; Corredor, Laura; Antonio, Maria Teresa

    2007-01-01

    Lead acetate (300 mg Pb/L) and/or cadmium acetate (10mg Cd/L) in blood and liver were administrated as drinking water to pregnant Wistar rats from day 1 of pregnancy to parturition (day 0) or until weaning (day 21), to investigate the toxic effects in blood and in the liver. Both metals produced mycrocitic anaemia in the pups as well as oxidative damage in the liver, as suggested by the significant increase in TBARS production and the high catalase activity. Moreover, intense alkaline and acid phosphatase activity, used as biomarkers of liver adaptation to damaging factors, was observed. In addition, the toxikinetics are different for Pb and Cd: while Cd is a hepatotoxic from day 0, Pb is not until day 21. Finally, simultaneous perinatal administration of both metals seems to protect, at least, in the liver TBARS production against the toxicity produced by Cd or Pb separately.

  7. Acrolein scavengers, cysteamine and N-benzylhydroxylamine, reduces the mouse liver damage after acetaminophen overdose.

    Science.gov (United States)

    Koyama, Ryo; Mizuta, Ryushin

    2017-01-10

    Our previous study suggested that the highly toxic α,β-unsaturated aldehyde acrolein, a byproduct of oxidative stress, plays a major role in acetaminophen-induced liver injury. In this study, to determine the involvement of acrolein in the liver injury and to identify novel therapeutic options for the liver damage, we examined two putative acrolein scavengers, a thiol compound cysteamine and a hydroxylamine N-benzylhydroxylamine, in cell culture and in mice. Our results showed that cysteamine and N-benzylhydroxylamine effectively prevented the cell toxicity of acrolein in vitro and acetaminophen-induced liver injury in vivo, which suggested that acrolein is involved in the liver damage, and these two drugs can be potential therapeutic options for this condition.

  8. Alpha-Lipoic acid counteracts the promoted oxidative DNA damage in the liver of septic rats

    International Nuclear Information System (INIS)

    Abd-Allah, Adel R.A.

    2006-01-01

    Viral, parasitic infections and chemical carcinogens are among the etiological factors of liver cancer. It seems important to study the initiating and promoting agents to evaluate the etiology and prevention of such life threatening disease. Intestine-derived bacteria product, lipopolysaccharide (LPS), is mainly detoxified by the liver. It has shown to induce a state of oxidative DNA damage is not fully investigated. Increased oxidative DNA damage and rate of cell proliferation may initiate or even promote cancer. In the present work, the capability of LPS to induce 8-hydroxydeoxyguanosine (8-HDG), a specific DNA adduct for oxidative DNA damage, in rat livers is tested. Furthermore, a possible protective effect of alpha lipoic acid (ALA) is also assessed. Investigated parameters are liver contents of glutathione (GSH), lipid peroxides (MDA), nitric oxide (NO) and 8-HDG in the liver-extracted DNA. Serum activities of ALT, AST and GGT as liver-function markers as well as IL2 are assessed. Moreover, liver histology is examined. LPS was given doses of 1, 3, 5, 7 and 9 mg/kg once i.p. while, the rat mortality was examined 24 hours later. ALA was given in doses of 50, 100 and 200 mg/kg once i.p. 3h before LPS is found to be 5mg/kg. LPS increased the level of 8-HDG, MDA and NO in the liver. It also induced acute liver necrosis and inflammatory cell infiltration as shown in liver-histopathology and in the significant increase in the activities of ALT, AST and GGT. LPS increased the serum level of IL2 as well. The dose 200mg/kg of ALA revealed a 100% protection against LPS-induced lethality. It also, prevented the LPS-induced increase in 8-HDG in liver extracted DNA, the liver contents of MDA and NO. ALA also rescued the LPS-induced GSH depletion. It corrected the liver function as shown by the prevention of increases in the activity of ALT, AST and GGT with a remarkable improvement in the liver histology. Moreover, it prevented the increase in serum level of IL2. These

  9. Experimental evaluation of the primary damage process: neutron energy effects

    Energy Technology Data Exchange (ETDEWEB)

    Goland, A.N.

    1979-01-01

    Experimental evaluation of the neutron energy dependnece of the primary damage stage depends upon a number of theoretical concepts. This state can only be observed after low- or perhaps ambient-temperature, low-fluence irradiations. The primary recoil energy spectrum, which determines the character of the displacement cascades, can be calculated if dosimetry has provided an accurate neutron spectrum. A review of experimental results relating neutron-energy effects shows that damage energy or damage energy cross section has often been a reliable correlation parameter for primary damage state experiments. However, the forthcoming emphasis on higher irradiation temperatures, more complex alloys and microstructural evolution has fostered a search for additional meaningful correlation parameters.

  10. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    Directory of Open Access Journals (Sweden)

    Herxheimer Andrew

    2002-03-01

    Full Text Available Abstract Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis.

  11. Experimental assessment of borehole wall drilling damage in basaltic rocks

    International Nuclear Information System (INIS)

    Fuenkajorn, K.; Daemen, J.J.K.

    1986-06-01

    Ring tension tests, permeability tests, and microscopic fracture studies have been performed to investigate the borehole damage induced at low confining pressure by three drilling techniques (diamond, percussion and rotary). Specimens are drilled with three hole sizes (38, 76, and 102 mm diameter) in Pomona basalt and Grande basaltic andesite. The damaged zone is characterized in terms of fractures and fracture patterns around the hole, and in terms of tensile strength reduction of the rock around the holes. Experimental results show that the thickness of the damaged zone around the hole ranges from 0.0 to 1.7 mm. A larger drill bit induces more wall damage than does a smaller one. Different drilling techniques show different damage characteristics (intensity and distribution). Damage characteristics are governed not only by drilling parameters (bit size, weight on bit, rotational speed, diamond radius, and energy), but also by properties of the rock. The weaker rock tends to show more intense damage than does the stronger one. Cracks within grains or cleavage fractures are predominant in slightly coarser grained rock (larger than 0.5 mm grain size) while intergranular cracks are predominant in very fine grained rock (smaller than 0.01 mm grain size). The damaged zones play no significant role in the flow path around a borehole plug

  12. Hepatoprotective effect of methanolic Tanacetum parthenium extract on CCl4-induced liver damage in rats

    Directory of Open Access Journals (Sweden)

    Yavar Mahmoodzadeh

    Full Text Available The purpose of this study was to investigate the effects of Tanacetum Parthenium Extract (TPE on Lipid peroxidation, antioxidant enzymes, biochemical factors, and liver enzymes in the rats damaged by Carbon Tetrachloride (CCl4.54 male Wistar rats were divided into 9 groups each consisting of 6 rats. Two of the groups were control groups (normal and damage control groups, 4 of them were exposure groups which were respectively administered with 40, 80, and 120 mg/kg of TPE and silymarin for 14 days before being damaged by CCl4, and the other 3 groups were post-treatment groups which received 80 and 120 mg/kg of TPE and silymarin 2, 6, 24, and 48 h after being injected with CCl4. At the end of the study, biochemical factors, serum liver enzymes, malondialdehyde level, antioxidant enzymes, and liver morphology were assayed.Pre- and post-treatment with TPE could significantly decrease ALT, AST, ALP, TG, LDL, TC, and glucose levels and increase HDL, and albumin levels and catalase, SOD, and GPx activities compared to the CCl4-damaged control group.The results of this study are indicative of the antioxidant activity of TPE, its potential hepatoprotective effects, and its probable therapeutic properties for laboratory animals damaged by CCl4. Keywords: Tanacetum parthenium, Carbon tetrachloride, Oxidative stress, Antioxidant enzymes, Liver damage

  13. REGENERATIVE PECULIARITIES OF LIVER TISSUE AFTER HEMOSTASIS BY NONEQUILIBRIUM PLASMA ON 90TH AND 180TH DAY (EXPERIMENTAL STUDY

    Directory of Open Access Journals (Sweden)

    Ye. V. Semichev

    2014-01-01

    Full Text Available Liver damages occur to 17.8% of blunt abdominal trauma cases. Postoperative mortality in liver damage is a high. It amounts to 4–10% in case of stab wounds, to 30.4–35,2% in case of closed injury, to 39.3% in case of concomitant injury. Complete hemostasis without damage to organ parenchyma is needed for liver surgical operation.The aim of research is to evaluate the regenerative characteristics of liver tissue after hemostasis by nonequilibrium plasma in a long-term period.Material and methods. Research was performed on 20 laboratory rats, 3 experimental groups. 10 intact animals and 5 animals in groups on 90th and 180th day. Surgery is resection of liver left lobe and coagulation with cold plasma coagulator. The biochemical control (glucose, ALT, AST, total bilirubin, direct, alkaline phosphatase, total protein, urea, α-amylase, CRP, fibrinogen, aPTT, PTT, INR, morphological study of rat liver were performed.Results. After surgery with cold plasma hemostasis animals are active, early begin to eat. Fatal cases are not. Analysis of biochemical markers doesn't reveal statistically significant differences from the norm for the majority of indicators. Decrease of glucose concentration in the blood serum is observed in a long-term period. Histological analysis reveals an increase of the central and interlobular veins and moderate signs of edema on the 90th day. Hepatocytes with pronounced signs of protein and fatty degeneration are identified. Liver histology corresponds to the usual structure and is represented by liver lobules, separated by a small layer of connective tissue on the 180th day.Conclusion. Cold plasma coagulation in liver surgery showed effective hemostasis, minimal trauma of organ parenchyma, the lack of systemic effect and the subsequent complete regeneration of liver tissue in the treatment area.

  14. Effectiveness of FDA's new over-the-counter acetaminophen warning label in improving consumer risk perception of liver damage.

    Science.gov (United States)

    Goyal, R K; Rajan, S S; Essien, E J; Sansgiry, S S

    2012-12-01

    The Food and Drug Administration (FDA) issued new organ-specific warning label requirements for over-the-counter (OTC) analgesic products in order to make consumers aware of the risk of liver damage when using acetaminophen. However, awareness of a health risk alone cannot ensure consumers' engagement in safe and preventive behaviour. In this study, we attempted to: (i) measure consumer risk perception of liver damage due to the OTC acetaminophen products and (ii) analyse the effectiveness of the new organ-specific warning label in improving consumer risk perception of liver damage and intention to perform protective behaviours while using OTC acetaminophen products. This within-subject experimental study used a convenience sample of English-speaking adults visiting OTC segments of selected pharmacy stores in Houston. Participants were randomly exposed to the old and new warning labels and their respective risk perception (measured on a visual analogue scale, 0%, no risk, to 100%, extreme risk) and behavioural intention (measured on a 7-point Likert scale) were recorded using a validated, self-administered questionnaire. Descriptive statistics and non-parametric Wilcoxon signed-rank tests were performed using sas statistical software (v 9.2) at a priori significance level of 0.05. Majority of participants (74.4%) were not aware of the new warnings; however, majority (67.8%) had prior knowledge of the risk. The mean risk perception score for the new warning label was found to be significantly higher (72.2% vs. 65.9%, P risk perception of potential liver damage and may encourage protective behaviour. However, future studies are essential to assess the impact of the new label on actual changes in consumer behaviour and subsequent reduction in acetaminophen-related morbidity and mortality. © 2012 Blackwell Publishing Ltd.

  15. Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

    Directory of Open Access Journals (Sweden)

    Tobias Eggert

    Full Text Available Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL, while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

  16. Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

    Science.gov (United States)

    Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar; Kruhlak, Michael J; Korangy, Firouzeh; Greten, Tim F

    2014-01-01

    Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

  17. Experimental damage analysis of steels after exploitation loading

    Directory of Open Access Journals (Sweden)

    B. Augustyniak

    2010-06-01

    Full Text Available Development of creep damage at elevated temperatures and structural degradation due to plastic deformation at room temperature were assessed using destructive and non-destructive methods in steels commonly applied in power plants (40HNMA, 13HMF and P91. As destructive methods the standard tension tests were carried out after every kind of prestraining. Subsequently, an evolution of the selected tension parameters was taken into account for damage identification. In order to assess a damage development during the creep and plastic deformation the tests for the steels were interrupted for a range of the selected strain magnitudes. The ultrasonic and magnetic techniques were used as the non-destructive methods for damage evaluation. The experimental programme also contained microscopic observations.

  18. Dmbt1 does not affect a Western style diet-induced liver damage in mice

    DEFF Research Database (Denmark)

    Reichold, Astrid; Brenner, Sibylle A; Förster-Fromme, Karin

    2013-01-01

    of non-alcoholic fatty liver disease. Concerning liver diseases, it is known that Deleted in malignant brain tumors 1 is amongst others related to liver injury and repair. In addition Deleted in malignant brain tumors 1 seems to play a role in regard to the maintenance of the intestinal homeostasis...... Western style diet fed groups gained significant more weight than the controls and developed a mild non-alcoholic steatohepatitis. The presence/absence of functional Deleted in malignant brain tumors 1 had no effect on parameters like food intake, weight gain, fasting glucose, and liver damage......In the last three decades the prevalence of non-alcoholic fatty liver disease has markedly increased. Results from epidemiologic studies indicate that not only a general overnutrition but rather a diet rich in sugar, fat and cholesterol (= Western style diet) maybe a risk factor for the development...

  19. Experimental data available for radiation damage modelling in reactor materials

    International Nuclear Information System (INIS)

    Wollenberger, H.

    Radiation damage modelling requires rate constants for production, annihilation and trapping of defects. The literature is reviewed with respect to experimental determination of such constants. Useful quantitative information exists only for Cu and Al. Special emphasis is given to the temperature dependence of the rate constants

  20. Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats.

    Science.gov (United States)

    Menon, B Rajalakshmy; Rathi, M A; Thirumoorthi, L; Gopalakrishnan, V K

    2010-10-01

    The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observed in extract treated liver injured experimental rats. Histopathological examination of the liver tissues supported the hepatoprotection. It is concluded that the ethanolic extract of Bacopa monieri plant possess good hepatoprotective activity.

  1. A half century (1961-2011) of applying microsurgery to experimental liver research

    Science.gov (United States)

    Aller, Maria-Angeles; Arias, Natalia; Prieto, Isabel; Agudo, Salvador; Gilsanz, Carlos; Lorente, Laureano; Arias, Jorge-Luis; Arias, Jaime

    2012-01-01

    The development of microsurgery has been dependent on experimental animals. Microsurgery could be a very valuable technique to improve experimental models of liver diseases. Microdissection and microsutures are the two main microsurgical techniques that can be considered for classifying the experimental models developed for liver research in the rat. Partial portal vein ligation, extrahepatic cholestasis and hepatectomies are all models based on microdissection. On the other hand, in portacaval shunts, orthotopic liver transplantation and partial heterotopic liver transplantation, the microsuture techniques stand out. By reducing surgical complications, these microsurgical techniques allow for improving the resulting experimental models. If good experimental models for liver research are successfully developed, the results obtained from their study might be particularly useful in patients with liver disease. Therefore experimental liver microsurgery could be an invaluable way to translate laboratory data on liver research into new clinical diagnostic and therapeutic strategies. PMID:22855695

  2. Epicardial Adipose Tissue (EAT Thickness Is Associated with Cardiovascular and Liver Damage in Nonalcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Anna Ludovica Fracanzani

    Full Text Available Epicardial adipose tissue (EAT has been proposed as a cardiometabolic and hepatic fibrosis risk factor in patients with non alcoholic fatty liver disease (NAFLD. Aim of this study was to evaluate the role of EAT in NAFLD by analyzing 1 the association between EAT, the other metabolic parameters and the severity of steatosis 2 the relationship between cardiovascular (cIMT, cplaques, E/A, liver (presence of NASH and significant fibrosis damage and metabolic risk factors including EAT 3 the relationship between EAT and genetic factors strongly influencing liver steatosis.In a cross-sectional study, we considered 512 consecutive patients with NAFLD (confirmed by biopsy in 100. EAT, severity of steatosis, carotid intima-media thickness (cIMT and plaques were evaluated by ultrasonography and results analysed by multiple linear and logistic regression models. Variables independently associated with EAT (mm were female gender (p = 0.003, age (p = 0.001, BMI (p = 0.01, diastolic blood pressure (p = 0.009, steatosis grade 2 (p = 0.01 and 3 (p = 0.04, fatty liver index (p = 0.001 and statin use (p = 0.03. Variables independently associated with carotid IMT were age (p = 0.0001, hypertension (p = 0.009, diabetes (p = 0.04, smoking habits (p = 0.04 and fatty liver index (p = 0.02, with carotid plaques age (p = 0.0001, BMI (p = 0.03, EAT (p = 0.02, and hypertension (p = 0.02, and with E/A age (p = 0.0001, diabetes (p = 0.005, hypertension (p = 0.04 and fatty liver index (p = 0.004. In the 100 patients with available liver histology non alcoholic steatohepatitis (NASH was independently associated with EAT (p = 0.04 and diabetes (p = 0.054 while significant fibrosis with EAT (p = 0.02, diabetes (p = 0.01 and waist circumference (p = 0.05. No association between EAT and PNPLA3 and TM6SF2 polymorphisms was found.In patients with NAFLD, EAT is associated with the severity of liver and vascular damage besides with the known metabolic risk factors.

  3. Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis.

    Science.gov (United States)

    Ivanovski, Ivan; Ješić, Miloš; Ivanovski, Ana; Garavelli, Livia; Ivanovski, Petar

    2017-11-28

    The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liver damage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.

  4. The effect of phytosterol protects rats against 4-nitrophenol-induced liver damage.

    Science.gov (United States)

    Chen, Jiaqin; Song, Meiyan; Li, Yansen; Zhang, Yonghui; Taya, Kazuyoshi; Li, ChunMei

    2016-01-01

    We investigated the effect of phytosterol (PS) in regard to liver damage induced by 4-nitrophenol (PNP). Twenty rats were randomly divided into four groups (Control, PS, PNP, and PNP+PS). The PS and PNP+PS groups were pretreated with PS for one week. The PNP and PNP+PS groups were injected subcutaneously with PNP for 28 days. The control group received a basal diet and was injected with vehicle alone. Treatment with PS prevented the elevation of the total bilirubin levels, as well as an increase in serum alkaline transaminase and aspartate transaminase, which are typically caused by PNP-induced liver damage. Histopathologically showed that liver damage was significantly mitigated by PS treatment. However, there was no significant change in antioxidant enzyme activities, and the Nrf2-antioxidant system was not activated after treatment with PS. These results suggest that PS could mitigate liver damage induced by PNP, but does not enhance antioxidant capacity. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Protective function of complement against alcohol-induced rat liver damage.

    Science.gov (United States)

    Bykov, Igor L; Väkevä, Antti; Järveläinen, Harri A; Meri, Seppo; Lindros, Kai O

    2004-11-01

    The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.

  6. Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

    Science.gov (United States)

    Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

    2011-01-01

    It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

  7. DNA damage detected by the alkaline comet assay in the liver of mice after oral administration of tetrachloroethylene

    DEFF Research Database (Denmark)

    Cederberg, H.; Henriksson, J.; Binderup, Mona-Lise

    2010-01-01

    in hepatocytes, indicating that tetrachloroethylene induced DNA damage in the liver. No effect on DNA damage was observed in the kidney. The results are in agreement with carcinogenicity data in mice, in which tetrachloroethylene induced tumours in the liver but not in the kidney, and support that a genotoxic...... mode of action might be involved in liver carcinogenicity in mice. An alternative interpretation of the results conveyed by the Study director at the test facility, involving that tetrachloroethylene did not induce DNA damage in the liver and kidney of mice, is also presented and discussed....

  8. Temozolomide-induced liver damage. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Becker, F.; Hecht, M.; Schmidtner, J.; Semrau, S.; Fietkau, R. [University of Erlangen-Nuremberg, Department of Radiation Oncology, Erlangen (Germany)

    2014-04-15

    Temozolomide (TMZ) is an alkylating agent used in chemoradiotherapy and adjuvant chemotherapy regimens for treatment of newly diagnosed or recurrent glioblastoma. In Germany alone, 900,000 daily doses of the drug are prescribed each year. Therefore, all severe side effects of TMZ, even those rarely observed, are relevant to radiotherapists. We report a case of severe drug-induced toxic hepatitis that developed during chemoradiotherapy with TMZ in a patient with glioblastoma multiforme. Transaminase elevation was observed after 5 weeks of TMZ treatment, followed by severe jaundice symptoms which only subsided 2 months later. These findings were consistent with diagnosis of the mixed hepatic/cholestatic type of drug-induced toxic hepatitis. Due to the early termination of treatment, no life-threatening complications occurred in our patient. However, rare reports of encephalopathy and fatality as complications of TMZ therapy can be found in the literature. When using TMZ for treatment of glioblastoma, monitoring of liver enzyme levels should be performed twice weekly to prevent fatal toxic hepatitis. In the case of any drug-induced hepatitis, TMZ must be discontinued immediately. (orig.)

  9. Liver biopsy in type 2 diabetes mellitus: Steatohepatitis represents the sole feature of liver damage.

    Science.gov (United States)

    Masarone, Mario; Rosato, Valerio; Aglitti, Andrea; Bucci, Tommaso; Caruso, Rosa; Salvatore, Teresa; Sasso, Ferdinando Carlo; Tripodi, Marie Francoise; Persico, Marcello

    2017-01-01

    Recent studies report a prevalence of non-alcoholic fatty liver disease (NAFLD) of between 70% and 80% in patients with metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Nevertheless, it is not possible to differentiate between simple steatosis and non-alcoholic steatohepatitis (NASH) with non-invasive tests. The aim of this study was to differentiate between simple steatosis and NASH by liver biopsy in patients with hypertransaminasemia and MS or T2DM. Two hundred and fifteen patients with increased ALT levels and MS, and 136 patients at their first diagnosis of T2DM regardless of ALT values were consecutively admitted to a tertiary hepatology center between January 2004 and November 2014. Exclusion criteria were other causes of liver disease/ALT increase. Each patient underwent a clinical, laboratory and ultrasound evaluation, and a liver biopsy. Gender distribution, age, and body mass index were similar in the two groups of patients, whereas cholesterol levels, glycemia and blood pressure were significantly different between the two groups. The prevalence of NAFLD was 94.82% in MS patients and 100% in T2DM patients. NASH was present in 58.52% of MS patients and 96.82% of T2DM. Consequently, this study reveals that, by using liver biopsy, almost all patients with T2DM or MS have NAFLD, which in patients with T2DM means NASH. Importantly, it suggests that NASH may be one of the early complications of T2DM due to its pathophysiological correlation with insulin resistance.

  10. Liver biopsy in type 2 diabetes mellitus: Steatohepatitis represents the sole feature of liver damage.

    Directory of Open Access Journals (Sweden)

    Mario Masarone

    Full Text Available Recent studies report a prevalence of non-alcoholic fatty liver disease (NAFLD of between 70% and 80% in patients with metabolic syndrome (MS and type 2 diabetes mellitus (T2DM. Nevertheless, it is not possible to differentiate between simple steatosis and non-alcoholic steatohepatitis (NASH with non-invasive tests. The aim of this study was to differentiate between simple steatosis and NASH by liver biopsy in patients with hypertransaminasemia and MS or T2DM. Two hundred and fifteen patients with increased ALT levels and MS, and 136 patients at their first diagnosis of T2DM regardless of ALT values were consecutively admitted to a tertiary hepatology center between January 2004 and November 2014. Exclusion criteria were other causes of liver disease/ALT increase. Each patient underwent a clinical, laboratory and ultrasound evaluation, and a liver biopsy. Gender distribution, age, and body mass index were similar in the two groups of patients, whereas cholesterol levels, glycemia and blood pressure were significantly different between the two groups. The prevalence of NAFLD was 94.82% in MS patients and 100% in T2DM patients. NASH was present in 58.52% of MS patients and 96.82% of T2DM. Consequently, this study reveals that, by using liver biopsy, almost all patients with T2DM or MS have NAFLD, which in patients with T2DM means NASH. Importantly, it suggests that NASH may be one of the early complications of T2DM due to its pathophysiological correlation with insulin resistance.

  11. USING OF MSC WITH DIFFERENT ONTOGENETIC MATURITY FOR CORRECTION OF CHRONIC FIBROSING LIVER DAMAGE

    Directory of Open Access Journals (Sweden)

    M. Y. Shagidulin

    2013-01-01

    Full Text Available Aim. To compare the effectiveness of MSC with different degree of ontogenetic maturity (MSC bone marrow – MSC BM and MSC umbilical cord – MSC UC on regenerative processes in injured liver. Methods. In 4 groups of experiments on Wistar rats (n = 80 with a model of fibrotic toxic liver damage (FLD it was studied the effect of MSCs with different degree of ontogenetic maturity on recovery processes at the regeneration of damaged liver: 1 gr. – Control, 2 gr. and 3 gr. introduction of MSC BM, included in Sphero®GEL-long in doses of 2.5 ×106 and 5.0 x 106 cells, respectively, and 4 gr. – introduction of MSC UC in the form of cell-spheroids (8–10 × 105 cells. The cells were injected into the damaged liver in 7 days after the end of FDL-modeling. The effect of cell therapy was studied during 180 days. The effectiveness of corrective therapy was evaluated by the results of functional and morphological investigations of livers (histological control of parenchymal and nonparenchy- mal liver tissue. Results. MSC BM in both doses and MSC UC contributed to a more rapid normalization of liver enzyme indices compared with the control (1 gr., but the differences in the rate of recovery of disturbed enzymatic liver functions between groups 2, 3 and 4 – were absent. In 90 days after the cell application it was determined a more pronounced recovery activity of cells in groups 3 and 4; in 180 days the more pronounced activation of recovery processes was observed in group 3; but in group 4 the sclerotic processes were more pro- nounced in this period. Conclusion. For the induction of recovery processes in damage liver it is advisable not to use the MSC UC, but to use MSC BM in the Sphero®GEL, because MSC BM exert not only local but also systemic immune-regulatory effect, increasing the pool of T-reg. cells, which are additional carriers of regenera- tion information in organism. 

  12. Liver damage caused by hepatitis C viral infection and ethyl alcohol consumption

    Directory of Open Access Journals (Sweden)

    Kostić Velimir

    2006-01-01

    Full Text Available Background/Aim. Hepatitis C virus infection (HCV is a complex disease, most commonly chronicle (80-85%. The aim of this research was to determinate the level of the liver damage in the patients cansed by HCV in conjunction with consuming ethyl alcohol. Methods. The research included 15 patients with chronic HCV infection supported by the misuse of ethyl alcohol, as well. The diagnosis of C infection hepatitis was proved using the ELISA test and PCR method. Results. The results of the study showed the liver damage by both HCV infection and ethyl alcohol, which was verified by the presence of biochemical changes and patohystological processing of the patients (liver biopsy and prosection. Patohystological changes were at the level of liver cirrhosis and carcinoma (2 patients. There was a signficant difference between the two subgroups (p < 0.001 regarding the examined values γ-GT, PLT and PTV. The basic therapeutic procedure was to introduce this category of patients into alcohol abstinence, and, in a few patients, to apply the antivirus therapy, as well. Conclusion. Based on the number of the examined patients (n = 15, we could conclude that a prolonged ethyl alcohol misuse with the presence of HCV infection was in a correlation with the liver disease progression.

  13. Alcohol intake, alcohol dehydrogenase genotypes, and liver damage and disease in the Danish general population

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Gronbaek, M.; Tybjaerg-Hansen, A.

    2009-01-01

    the Copenhagen City Heart Study. Biochemical tests for the detection of liver damage were specific for alanine aminotransferase (ALT), aspartate aminotransferase (AST)-to-ALT ratio (AST/ALT), gamma-glutamyl transpeptidase (gamma-GT), albumin, bilirubin, alkaline phosphatase, coagulation factors, and erythrocyte...... volume. RESULTS: Increasing alcohol intake was associated with increasing erythrocyte volume, AST/ALT, and levels of ALT, gamma-GT, albumin, bilirubin, coagulation factors, and with decreasing levels of alkaline phosphatase. Multifactorially adjusted hazard ratios for alcoholic liver disease overall were...

  14. The Protective Role of Zinc Sulphate on Ethanol -Induced Liver and Kidney Damages in Rats

    International Nuclear Information System (INIS)

    Al-Damegh, Mona Abdalla

    2007-01-01

    Around the world more and more people suffer from alcoholism. Addiction problems, alcoholism and excessive use of drugs both medical and nonmedical, are major causes of liver and kidney damage in adults. The purpose of this study was to investigate on the protective role of zinc sulphate on liver and kidney in rats with acute alcoholism. Wistar albino rats were divided into four groups. Group I; control group, group 2; given only Zinc Sulphate (100 mg/kg/day for 3days), group 3; rats given absolute ethanol (1 ml of absolute ethanol administrated by gavage technique to each rat), group 4 given Zinc sulphate prior to the administration of absolute ethanol. The results of this study revealed that acute ethanol exposure caused degenerative morphological changes in the liver and kidney. Significant difference were found in the levels of serum, liver, kidney super oxide dismutase(SOD), catalase (CAT), nitric oxide(NO), and malondialdehyde (MDA) in the ethanol group compared to the control group. Moreover ,serum urea, creatnine, uric acid, alkaline phoshpatase and transaminases activities (GOTand GPT) were increased in the ethanol group compared to the control group. On the other hand,administration of zinc sulphate in the ethanol group caused a significant decrease in the degenerative changes, lipid peroxidation, antioxidant enzymes, and nitric oxide in serum, liver, and kidney. It can be concluded that zinc Sulphate has a protective role on the ethanol induced liver and kidney injury. In addition ,nitric oxide is involved in the mechanism of acute alcohol intoxication. (author)

  15. Celastrol ameliorates liver metabolic damage caused by a high-fat diet through Sirt1

    Directory of Open Access Journals (Sweden)

    Yinliang Zhang

    2017-01-01

    Full Text Available Objective: Celastrol was recently identified as a potential novel treatment for obesity. However, the effect of Celastrol on nonalcoholic fatty liver disease (NAFLD remains elusive. The aim of this study is to evaluate the role of Celastrol in NAFLD. Methods: Functional studies were performed using wild-type C57BL/6J (WT mice and liver specific Sirt1-deficient (LKO mice. The molecular mechanism was explored in primary mouse liver and primary hepatocytes. Results: When WT mice receiving a high-fat diet (HFD were treated with Celastrol, reductions in body weight, subcutaneous and visceral fat content, and liver lipid droplet formation were observed, along with reduced hepatic intracellular triglyceride and serum triglyceride, free fatty acid, and ALT concentrations. Furthermore, Celastrol decreased hepatic sterol regulatory element binding protein 1c (Srebp-1c expression, enhanced the phosphorylation of hepatic AMP-activated protein kinase α (AMPKα, and increased the expression of hepatic serine–threonine liver kinase B1 (LKB1. Additionally, Celastrol treatment improved glucose tolerance and insulin sensitivity in WT mice fed the HFD. Celastrol administration also improved the anti-inflammatory and anti-oxidative status by inhibiting nuclear factor kappa B (NFκB activity and the mRNA levels of proinflammatory cytokines and increasing mitochondrial DNA copy number and anti-oxidative stress genes expression in WT mice liver, in vivo and in vitro. Moreover, Celastrol induced hepatic Sirt1 expression in WT mice, in vivo and in vitro. These Celastrol-mediated protective effects in WT mice fed a HFD were abolished in LKO mice fed a HFD. It was more interesting that Celastrol aggravated HFD-induced liver damage in LKO mice fed a HFD by inhibiting the phosphorylation of AMPKα and boosting the translocation of NFκB into the nucleus, thereby resulting in the increase of Srebp-1c expression and the mRNA levels of liver proinflammatory cytokines

  16. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-05

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights

  17. Pulsed total dose damage effect experimental study on EPROM

    International Nuclear Information System (INIS)

    Luo Yinhong; Yao Zhibin; Zhang Fengqi; Guo Hongxia; Zhang Keying; Wang Yuanming; He Baoping

    2011-01-01

    Nowadays, memory radiation effect study mainly focus on functionality measurement. Measurable parameters is few in china. According to the present situation, threshold voltage testing method was presented on floating gate EPROM memory. Experimental study of pulsed total dose effect on EPROM threshold voltage was carried out. Damage mechanism was analysed The experiment results showed that memory cell threshold voltage negative shift was caused by pulsed total dose, memory cell threshold voltage shift is basically coincident under steady bias supply and no bias supply. (authors)

  18. Radioprotective effects of Asparagus racemosus extracts against free radical damage in rat liver mitochondria

    International Nuclear Information System (INIS)

    Boloor, K.K.; Kamat, J.P.; Devasagayam, T.P.A.; Venkatachalam, S.R.

    2000-01-01

    The possible antioxidant effect of the extracts of Asparagus racemosus against membrane damage induced by free radicals generated during γ-radiation was examined in rat liver/brain mitochondria. These extracts displayed significant antioxidant properties in mitochondria against oxidation of both lipids and proteins as assessed by lipid peroxidation, protein oxidation and depletion of thiols. The inhibitory effect of the extracts, rich in polysaccharides like galactose, was more than that of the established antioxidants glutathione and ascorbic acid. (author)

  19. Arsenite induced oxidative damage in mouse liver is associated with increased cytokeratin 18 expression

    Energy Technology Data Exchange (ETDEWEB)

    Gonsebatt, M.E. [UNAM, Ciudad Universitaria, Dept. Medicina Genomica y Toxicologia Ambiental, Instituto de Investigaciones Biomedicas, Mexico (Mexico); Razo, L.M. del; Sanchez-Pena, L.C. [Seccion de Toxicologia, CINVESTAV, Mexico (Mexico); Cerbon, M.A. [Facultad de Quimica, UNAM, Departamento de Biologia, Mexico (Mexico); Zuniga, O.; Ramirez, P. [Facultad de Estudios Superiores Cuautitlan, UNAM, Laboratorio de Toxicologia Celular, Coordinacion General de Estudios de Posgrado e Investigacion, Cuautitlan Izcalli, Estado de Mexico (Mexico)

    2007-09-15

    Cytokeratins (CK) constitute a family of cytoskeletal intermediate filament proteins that are typically expressed in epithelial cells. An abnormal structure and function are effects that are clearly related to liver diseases as non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. We have previously observed that sodium arsenite (SA) induced the synthesis of CK18 protein and promotes a dose-related disruption of cytoplasmic CK18 filaments in a human hepatic cell line. Both abnormal gene expression and disturbance of structural organization are toxic effects that are likely to cause liver disease by interfering with normal hepatocyte function. To investigate if a disruption in the CK18 expression pattern is associated with arsenite liver damage, we investigated CK18 mRNA and protein levels in liver slices treated with low levels of SA. Organotypic cultures were incubated with 0.01, 1 and 10 {mu}M of SA in the absence and presence of N-acetyl cysteine (NAC). Cell viability and inorganic arsenic metabolism were determined. Increased expression of CK18 was observed after exposure to SA. The addition of NAC impeded the oxidative effects of SA exposure, decreasing the production of thiobarbituric acid-reactive substances and significantly diminishing the up regulation of CK18 mRNA and protein. Liver arsenic levels correlated with increased levels of mRNA. Mice treated with intragastric single doses of 2.5 and 5 mg/kg of SA showed an increased expression of CK18. Results suggest that CK18 expression may be a sensible early biomarker of oxidative stress and damage induced by arsenite in vitro and in vivo. Then, during SA exposure, altered CK expression may compromise liver function. (orig.)

  20. Hepatoprotective activity of Mentha arvensis Linn. leaves against CCL4 induced liver damage in rats

    Directory of Open Access Journals (Sweden)

    Kalpana Patil

    2012-05-01

    Full Text Available Objective: To study the Hepatoprotective activity of ethanol, chloroform and aqueous extracts of Mentha arvensis leaves against CCL4 induced liver damage in rats. Methods: Hepatotoxicity was induced by CCL4 and the biochemical parameters such as serum glutamate pyruvate transminase (sGPT, serum glutamate oxaloacetate transaminase (sGOT, alkaline phosphatase (sALP, serum bilirubin (sB and histopathological changes in liver were studied along with silymarin as standard Hepatoprotective agents. Results: The Phytochemical investigation of the extracts showed presence of flavonoids, steroids, triterpenoids, alkaloids, glycosides, carbohydrates, tannins, phenolic compounds. Treatment of the rats with chloroform, ethanol and aqueous extract with CCL 4 administration caused a significant reduction in the values of sGOT, sGPT, sALP and sB (P<0.01 almost comparable to the silymarin. The Hepatoprotective was confirmed by histopathological examination of the liver tissue of control and treated animals. Conclusions: From the results it can be concluded that Mentha arvensis possesses Hepatoprotective effect against CCL4 induced liver damage in rats.

  1. Unscheduled DNA synthesis and elimination of DNA damage in liver cells of. gamma. -irradiated senescent mice

    Energy Technology Data Exchange (ETDEWEB)

    Gaziev, A.I.; Malakhova, L.V. (AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki)

    1982-10-01

    The level of 'spontaneous' and ..gamma..-radiation-induced DNA synthesis which is not inhibited with hydroxyurea (unscheduled synthesis) is considerably lower in hepatocytes of 18-22-month-old mice than that of 1.5-2-month-old mice. The dose-dependent increase (10-300 Gy) of unscheduled DNA synthesis (UDS) in hepatocytes of senescent mice is higher than in young animals. The elimination of damage in DNA of ..gamma..-irradiated hepatocytes (100 Gy) was examined by using an enzyme system (M. luteus extract and DNA-polymerase I of E. coli). It was found that the rate of elimination of the DNA damage in hepatocytes of 20-month-old mice is lower than that of 2-month-old mice although the activities of DNA-polymerase ..beta.. and apurinic endonuclease remain equal in the liver of both senescent and young mice. However, the nucleoids from ..gamma..-irradiated liver nuclei of 2-month-old mice are relaxed to a greater extent (as judged by the criterion of ethidium-binding capacity) than those of 20-month-old mice. The results suggest that there are limitations in the functioning of repair enzymes and in their access to damaged DNA sites in the chromatin of senescent mouse liver cells.

  2. Experimental studies on radiation damages of CsI(Tl) crystals

    International Nuclear Information System (INIS)

    He Jingtang; Mao Yufang; Dong Xiaoli; Chen Duanbao; Li Zuhao

    1997-01-01

    The results of experimental studies on radiation damage of CsI(Tl) crystal were reported. There are radiation damage effects on CsI(Tl) crystal. Experimental studies on recovery of damaged CsI(Tl) crystals were made. It seems that after heating at 200 degree C for 4 hours, the damaged crystals could be recovered completely

  3. Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways.

    Science.gov (United States)

    El-Sherbeeny, Nagla A; Nader, Manar A; Attia, Ghalia M; Ateyya, Hayam

    2016-12-01

    Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates. Immunohistochemistry for Bax and transforming growth factor beta (TGF-β1) and histopathology of the liver were also included. Data of the study demonstrated that nicotine administration exhibited marked liver deterioration, an increase in liver enzymes, changes in lipid profile, and an elevation in MDA with a decline in levels of SOD, GSH, and NOx (nitrate/nitrite). Also, levels of proapoptotic Bax and profibrotic TGF-β1 showed marked elevation in the liver. AGM treatment to rats in nicotine-only group ameliorated all the previous changes. These findings indicate that AGM could successfully overcome the nicotine-evoked hepatic oxidative stress and tissue injury, apoptosis, and fibrosis.

  4. ACTION OF VITAMIN E ON EXPERIMENTAL SEVERE ACUTE LIVER FAILURE.

    Science.gov (United States)

    Miguel, Fabiano Moraes; Schemitt, Elizângela Gonçalves; Colares, Josieli Raskopf; Hartmann, Renata Minuzzo; Morgan-Martins, Maria Isabel; Marroni, Norma Possa

    2017-01-01

    Severe Acute Liver Failure (ALF) is a life-threatening clinical syndrome characterized by hepatocyte necrosis, loss of hepatic architecture, and impairment of liver functions. One of the main causes of ALF is hepatotoxicity from chemical agents, which damage hepatocytes and result in increase of reactive oxygen species. The vitamin E isoform is the one with the strongest biological antioxidant activity. To evaluate the antioxidant effect of vitamin E in this ALF model. We used 56 rats (mean weight of 300 g) divided into eight groups, four groups assessed at 24 hours and 4 assessed at 48 hours after induction: control group (CO); Vitamin E (Vit. E); Thioacetamide (TAA) and Thioacetamide + Vitamina E (TAA+Vit.E). Rats were submitted to injections of thioacetamide (400 mg/kg i.p.) at baseline and 8 hours later. Vitamin E (100 mg/kg ip) was administered 30 minutes after the second dose of thioacetamide. The 48-hour group rats received two additional doses of vitamin E (24h and 36h). At 24h or 48 hours after the administration of the first dose of TAA, rats were weighed and anesthetized and their blood sampled for evaluation of liver integrity through enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Liver tissue was sampled for assessment of lipid peroxidation (LPO) by the technique TBARS, antioxidant enzymes SOD, CAT, GPx and GST activity, levels of the NO 2 /NO 3 and histology by H&E in two times. The results were expressed as mean ± standard deviation and statistically analyzed by ANOVA followed by Student-Newman-Keuls, with P E, we observed a reduction in liver enzymes AST (U/L) (101.32±19.45 in 24 hours and 97.85±29.65 in 48 hours) related to the TAA group (469.56± 0.69 in 24 hours and 598.23±55.45 in 48 hours) and ALT (U/L) (76.59±8.56 in 24 hours and 68.47±6.49 in 48 hours) compared to the TAA group (312.21±10.23 in 24 hours and 359.15±17.58 in 48 hours). There was a reduction of LPO (nmol/mg Prot) in the TAA+Vit.E group (0

  5. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Anthony Skipper

    2016-01-01

    Full Text Available Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium.  Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG2 cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay. The result of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05 increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG2 cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05 was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG2 cells.

  6. Thrombocytopenia and liver damage induced by actinomycin-D following radiotherapy in a patient with Wilms' tumor

    International Nuclear Information System (INIS)

    Watanabe, Takeshi; Kibe, Norio; Kawano, Yoshifumi; Yazawa, Kenji; Shiraga, Hiroshi; Hosoya, Ryota; Ohya, Tatsuo; Nishimura, Kozo; Yokoyama, Johtaro

    1985-01-01

    A two-year-old girl with Wilms' tumor received radiotherapy of 25.5 Gy to the right abdomen, followed by vincristine and actinomycin-D (Act). The patient developed general fatigue, anemia, thrombocytopenia, and liver damage associated with ascites. She improved by conservative therapy of two week duration. From the literature, it is suggested that such drug-related liver damage tends to occur when irradiation is given before chemotherapy, including Act. (Namekawa, K.)

  7. Enhanced depletion of glutathione and increased liver oxidative damage in aflatoxin-fed mice infected with Plasmodium berghei

    DEFF Research Database (Denmark)

    Ankrah, N A; Sittie, A; Addo, P G

    1995-01-01

    levels accompanied by a significant increase in serum cholinesterase and liver malonic dialdehyde levels in the mice fed aflatoxin compared with those in the control group. The results suggested that malaria parasites can enhance depletion of host glutathione and oxidative damage of the liver in mice fed...

  8. Usage of adenovirus expressing thymidine kinase mediated hepatocellular damage for enabling mouse liver repopulation with allogenic or xenogenic hepatocytes.

    Directory of Open Access Journals (Sweden)

    Daniel Moreno

    Full Text Available It has been shown that the liver of immunodeficient mice can be efficiently repopulated with human hepatocytes when subjected to chronic hepatocellular damage. Mice with such chimeric livers represent useful reagents for medical and clinical studies. However all previously reported models of humanized livers are difficult to implement as they involve cross-breeding of immunodeficient mice with mice exhibiting genetic alterations causing sustained hepatic injury. In this paper we attempted to create chimeric livers by inducing persistent hepatocellular damage in immunodeficient Rag2(-/- γc(-/- mice using an adenovirus encoding herpes virus thymidine kinase (AdTk and two consecutive doses of ganciclovir (GCV. We found that this treatment resulted in hepatocellular damage persisting for at least 10 weeks and enabled efficient engraftment and proliferation within the liver of either human or allogenic hepatocytes. Interestingly, while the nodules generated from the transplanted mouse hepatocytes were well vascularized, the human hepatocytes experienced progressive depolarization and exhibited reduced numbers of murine endothelial cells inside the nodules. In conclusion, AdTk/GCV-induced liver damage licenses the liver of immunodeficient mice for allogenic and xenogenic hepatocyte repopulation. This approach represents a simple alternative strategy for chimeric liver generation using immunodeficient mice without additional genetic manipulation of the germ line.

  9. Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

    International Nuclear Information System (INIS)

    Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael

    2015-01-01

    Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups (n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug

  10. Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

    Science.gov (United States)

    Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael; Motta, Mariana H.; Ribeiro, Roseane F.; dos S. Hausen, Bruna; Moresco, Rafael N.; Garcia, Solange C.; da Silva, Cristiane B.; Burger, Marilise E.

    2015-04-01

    Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups ( n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

  11. Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

    Energy Technology Data Exchange (ETDEWEB)

    Roversi, Katiane, E-mail: katianeroversi@gmail.com [Universidade Federal de Santa Maria, Programa de Pós-Graduação em Farmacologia (Brazil); Benvegnú, Dalila M., E-mail: dalilabenvegnu@yahoo.com.br [Universidade Federal da Fronteira Sul (UFFS), Bioquímica e Farmacologia (Brazil); Roversi, Karine, E-mail: karineroversi-@hotmail.com [Universidade Federal de Santa Maria (UFSM), Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde (Brazil); Trevizol, Fabíola, E-mail: fatrevizol@yahoo.com.br [Universidade Federal de Santa Maria, Programa de Pós-Graduação em Farmacologia (Brazil); Vey, Luciana T., E-mail: luciana.taschetto@hotmail.com [Universidade Federal de Santa Maria (UFSM), Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde (Brazil); Elias, Fabiana, E-mail: fabiana.elias@uffs.edu.br [Universidade Federal da Fronteira Sul (UFFS), Bioquímica e Farmacologia (Brazil); Fracasso, Rafael, E-mail: rafael.fra@hotmail.com [Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Farmacêuticas (Brazil); and others

    2015-04-15

    Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups (n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

  12. Beneficial effect of honokiol on lipopolysaccharide induced anxiety-like behavior and liver damage in mice.

    Science.gov (United States)

    Sulakhiya, Kunjbihari; Kumar, Parveen; Gurjar, Satendra S; Barua, Chandana C; Hazarika, Naba K

    2015-02-26

    Anxiety disorders are commonly occurring co-morbid neuropsychiatric disorders with chronic inflammatory conditions such as live damage. Numerous studies revealed that peripheral inflammation, oxidative stress and brain derived neurotrophic factor (BDNF) play important roles in the pathophysiology of anxiety disorders. Honokiol (HNK) is a polyphenol, possessing multiple biological activities including antioxidant, anti-inflammatory, anxiolytic, antidepressant and hepatoprotection. The present study was designed to investigate the effect of HNK, in lipopolysaccharide (LPS)-induced anxiety-like behavior and liver damage in mice. Mice (n=6-10/group) were pre-treated with different doses of HNK (2.5 and 5mg/kg; i.p.) for two days, and challenged with saline or LPS (0.83mg/kg; i.p.) on third day. Anxiety-like behavior was monitored using elevated plus maze (EPM) and open field test (OFT). Animals were sacrificed to evaluate various biochemical parameters in plasma and liver. HNK pre-treatment provided significant (P<0.01) protection against LPS-induced reduction in body weight, food and water intake in mice. HNK at higher dose significantly (P<0.05) attenuated LPS-induced anxiety-like behavior by increasing the number of entries and time spent in open arm in EPM test, and by increasing the frequency in central zone in OFT. HNK pre-treatment ameliorated LPS-induced peripheral inflammation by reducing plasma IL-1β, IL-6, TNF-α level, and also improved the plasma BDNF level, prevented liver damage via attenuating transaminases (AST, ALT), liver oxidative stress and TNF-α activity in LPS challenged mice. In conclusion, the current investigation suggests that HNK provided beneficial effect against LPS-induced anxiety-like behavior and liver damage which may be governed by inhibition of cytokines production, oxidative stress and depletion of plasma BDNF level. Our result suggests that HNK could be a therapeutic approach for the treatment of anxiety and other

  13. Hepatoprotective effects of Arctium lappa on carbon tetrachloride- and acetaminophen-induced liver damage.

    Science.gov (United States)

    Lin, S C; Chung, T C; Lin, C C; Ueng, T H; Lin, Y H; Lin, S Y; Wang, L Y

    2000-01-01

    The root of Arctium lappa Linne (A. lappa) (Compositae), a perennial herb, has been cultivated for a long time as a popular vegetable. In order to investigate the hepatoprotective effects of A. lappa, male ICR mice were injected with carbon tetrachloride (CCl4, 32 microl/kg, i.p.) or acetaminophen (600 mg/kg, i.p.). A. lappa suppressed the SGOT and SGPT elevations induced by CCl4 or acetaminophen in a dose-dependent manner and alleviated the severity of liver damage based on histopathological observations. In an attempt to elucidate the possible mechanism(s) of this hepatoprotective effect, glutathione (GSH), cytochrome P-450 (P-450) and malondialdehyde (MDA) contents were studied. A. lappa reversed the decrease in GSH and P-450 induced by CCl4 and acetaminophen. It was also found that A. lappa decreased the malondialdehyde (MDA) content in CCl4 or acetaminophen-intoxicated mice. From these results, it was suggested that A. lappa could protect the liver cells from CCl4 or acetaminophen-induced liver damages, perhaps by its antioxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl4 or acetaminophen.

  14. Melatonin attenuates oxidative stress, liver damage and hepatocyte apoptosis after bile-duct ligation in rats.

    Science.gov (United States)

    Aktas, Cevat; Kanter, Mehmet; Erboga, Mustafa; Mete, Rafet; Oran, Mustafa

    2014-10-01

    The goal of this study was to evaluate the possible protective effects of melatonin against cholestatic oxidative stress, liver damage and hepatocyte apoptosis in the common rats with bile duct ligation (BDL). A total of 24 male Wistar albino rats were divided into three groups: control, BDL and BDL + received melatonin; each group contains eight animals. Melatonin-treated BDL rats received daily melatonin 100 mg/kg/day via intraperitoneal injection. The application of BDL clearly increased the malondialdehyde (MDA) levels and decreased the superoxide dismutase (SOD) and glutathione (GSH) activities. Melatonin treatment significantly decreased the elevated tissue MDA levels and increased the reduced SOD and GSH enzyme levels in the tissues. The changes demonstrate that the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells and neutrophil infiltration into the widened portal areas as observed in the BDL group. The data indicate that melatonin attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis. The α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the BDL were observed to be reduced with the melatonin treatment. These results suggest that administration of melatonin is a potentially beneficial agent to reduce liver damage in BDL by decreasing oxidative stress. © The Author(s) 2012.

  15. Total intermittent Pringle maneuver during liver resection can induce intestinal epithelial cell damage and endotoxemia.

    Directory of Open Access Journals (Sweden)

    Simon A W G Dello

    Full Text Available OBJECTIVES: The intermittent Pringle maneuver (IPM is frequently applied to minimize blood loss during liver transection. Clamping the hepatoduodenal ligament blocks the hepatic inflow, which leads to a non circulating (hepatosplanchnic outflow. Also, IPM blocks the mesenteric venous drainage (as well as the splenic drainage with raising pressure in the microvascular network of the intestinal structures. It is unknown whether the IPM is harmful to the gut. The aim was to investigate intestinal epithelial cell damage reflected by circulating intestinal fatty acid binding protein levels (I-FABP in patients undergoing liver resection with IPM. METHODS: Patients who underwent liver surgery received total IPM (total-IPM or selective IPM (sel-IPM. A selective IPM was performed by selectively clamping the right portal pedicle. Patients without IPM served as controls (no-IPM. Arterial blood samples were taken immediately after incision, ischemia and reperfusion of the liver, transection, 8 hours after start of surgery and on the first post-operative day. RESULTS: 24 patients (13 males were included. 7 patients received cycles of 15 minutes and 5 patients received cycles of 30 minutes of hepatic inflow occlusion. 6 patients received cycles of 15 minutes selective hepatic occlusion and 6 patients underwent surgery without inflow occlusion. Application of total-IPM resulted in a significant increase in I-FABP 8 hours after start of surgery compared to baseline (p<0.005. In the no-IPM group and sel-IPM group no significant increase in I-FABP at any time point compared to baseline was observed. CONCLUSION: Total-IPM in patients undergoing liver resection is associated with a substantial increase in arterial I-FABP, pointing to intestinal epithelial injury during liver surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT01099475.

  16. Murine liver damage caused by exposure to nano-titanium dioxide

    International Nuclear Information System (INIS)

    Hong, Jie; Zhang, Yu-Qing

    2016-01-01

    Due to its unique physiochemical properties, nano-titanium dioxide (nano-TiO_2) is widely used in all aspects of people’s daily lives, bringing it into increasing contact with humans. Thus, this material’s security issues for humans have become a heavily researched subject. Nano-TiO_2 can enter the body through the mouth, skin, respiratory tract or in other ways, after which it enters the blood circulation and is deposited in the liver, changing biochemical indicators and causing liver inflammation. Meanwhile, the light sensitivity of these nanoparticles allows them to become media-generating reactive oxygen species (ROS), causing an imbalance between oxidation and anti-oxidation that leads to oxidative stress and liver damage. Nano-TiO_2 can be transported into cells via phagocytosis, where the nanoparticles bind to the mitochondrial membrane, resulting in the disintegration of the membrane and the electron transport chain within the mitochondria. Thus, more ROS are produced. Nano-TiO_2 can also enter the nucleus, where it can directly embed into or indirectly affect DNA, thereby causing DNA breakage or affecting gene expression. These effects include increased mRNA and protein expression levels of inflammation-related factors and decreased mRNA and protein expression levels of IκB and IL-2, resulting in inflammation. Long-term inflammation of the liver causes HSC cell activation, and extracellular matrix (ECM) deposition is promoted by multiple signalling pathways, resulting in liver fibrosis. In this paper, the latest progress on murine liver injury induced by environmental TiO_2 is systematically described. The toxicity of nano-TiO_2 also depends on size, exposure time, surface properties, dosage, administration route, and its surface modification. Therefore, its toxic effects in humans should be studied in greater depth. This paper also provides useful reference information regarding the safe use of nano-TiO_2 in the future. (topical review)

  17. Experimental hydrothermal alteration of crystalline and radiation-damaged pyrochlore

    International Nuclear Information System (INIS)

    Geisler, T.; Seydoux-Guillaume, A.-M.; Poeml, P.; Golla-Schindler, U.; Berndt, J.; Wirth, R.; Pollok, K.; Janssen, A.; Putnis, A.

    2005-01-01

    We have performed hydrothermal experiments with a crystalline microlite and a heavily self-irradiation-damaged (i.e., X-ray amorphous) betafite in a solution containing 1 mol/l HCl and 1 mol/l CaCl 2 at 175 deg. C for 14 days. The well-crystalline microlite grains were partly (∼5-10 μm rim) replaced by a Ca and Na-poorer, defect pyrochlore phase with a larger unit-cell and a sharp chemical gradient at the interface (on a nm scale) to the unreacted core. The amorphous betafite grains (up to ∼2 mm in diameter), on the other hand, were completely transformed into an intergrowth of different crystalline phases (polycrystalline anatase and rutile, a yet unidentified Nb-Ta oxide, and a Y-REE phase), showing complex non-equilibrium structures. Our experimental observations bear a remarkable resemblance to those made on natural samples. They indicate that the processes of the fluid-pyrochlore interaction are influenced by self-irradiation structural damage and that thermodynamic equilibrium models can hardly be applied to adequately describe such systems

  18. Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage.

    Science.gov (United States)

    Müller, Liz Girardi; Pase, Camila Simonetti; Reckziegel, Patrícia; Barcelos, Raquel C S; Boufleur, Nardeli; Prado, Ana Cristina P; Fett, Roseane; Block, Jane Mara; Pavanato, Maria Amália; Bauermann, Liliane F; da Rocha, João Batista Teixeira; Burger, Marilise Escobar

    2013-01-01

    The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4±1.9 mg GAE/g), condensed tannins (58.4±2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe(2+)-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE+Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption. Copyright © 2011 Elsevier GmbH. All rights reserved.

  19. Possible Protective Effect of Kombucha Tea Ferment on Carbon Tetrachloride Induced Liver Damage in Irradiated Rats

    International Nuclear Information System (INIS)

    Gharib, O.A.; Fahim, Th.M.

    2008-01-01

    This study has shown that administration of kombucha ferment tea (KT) to rats improved the damage caused in livers of animals treated with toxic chemicals such as carbon tetrachloride (CCL 4 ) and/ or exposed to y-irradiation. This work was undertaken to evaluate the possible protective effects of treatment with KT ferment in rat liver after a long-term treatment with CCL 4 alone and with subsequent y-irradiation. Hepatic pathological changes observed in the CCL 4 -treated rats included increased serum alanine transaminase (ALT) , aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) activities as well as concentration of bilirubin in addition to a decrease in the concentration of serum albumin and total antioxidant capacity (TAC). Consistent with these changes, the increase in oxidative stress markers expressed as malondialdehyde (MDA) concentration and depletion in glutathione (GSH) contents in liver was observed. 24 h after the last dose of KT administration in a group of animals treated with CCL 4 and/ or radiation exposure cessation, the pathological changes were recovered. These results demonstrate that most of the pathological alterations in the liver in response to CCL 4 and/ or radiation exposure intoxication are recoverable upon treatment with KT ferments

  20. Prevention of CCl4-induced liver damage by ginger, garlic and vitamin E.

    Science.gov (United States)

    Patrick-Iwuanyanwu, K C; Wegwu, M O; Ayalogu, E O

    2007-02-15

    The hepatoprotective effects of garlic (Allium sativum), ginger (Zingiber officinale) and vitamin E pre-treatment against carbon tetrachloride (CCl4)-induced liver damage in male wistar albino rats were investigated. Carbon tetrachloride (0.5 mL kg(-1) body weight) was administered after 28 days of feeding animals with diets containing ginger, garlic, vitamin E and various mixtures of ginger and garlic. Serum alanine amino transferase, aspartate amino transferase and alkaline phosphatase levels, 24 h after CCl4 administration, decreased significantly (p hepatic cells decreased remarkably in pre-treated rats.

  1. Trans-Splenic Portal Vein Embolization: A Technique to Avoid Damage to the Future Liver Remnant

    International Nuclear Information System (INIS)

    Sarwar, Ammar; Brook, Olga R.; Weinstein, Jeffrey L.; Khwaja, Khalid; Ahmed, Muneeb

    2016-01-01

    Portal vein embolization (PVE) induces hypertrophy of the future liver remnant (FLR) in patients undergoing extensive hepatic resection. Portal vein access for PVE via the ipsilateral hepatic lobe (designated for resection) places veins targeted for embolization at acute angles to the access site requiring reverse curve catheters for access. This approach also involves access close to tumors in the ipsilateral lobe and requires care to avoid traversing tumor. Alternatively, a contralateral approach (through the FLR) risks damage to the FLR due to iatrogenic trauma or non-target embolization. Two patients successfully underwent PVE via trans-splenic portal vein access, allowing easy access to the ipsilateral portal veins and eliminating risk of damage to FLR. Technique and advantages of trans-splenic portal vein access to perform PVE are described.

  2. Trans-Splenic Portal Vein Embolization: A Technique to Avoid Damage to the Future Liver Remnant

    Energy Technology Data Exchange (ETDEWEB)

    Sarwar, Ammar, E-mail: asarwar@bidmc.harvard.edu; Brook, Olga R.; Weinstein, Jeffrey L. [Beth Israel Deaconess Medical Center/Harvard Medical School, Division of Interventional Radiology, Department of Radiology (United States); Khwaja, Khalid [Beth Israel Deaconess Medical Center/Harvard Medical School, Division of Transplant Surgery, Department of Surgery (United States); Ahmed, Muneeb [Beth Israel Deaconess Medical Center/Harvard Medical School, Division of Interventional Radiology, Department of Radiology (United States)

    2016-10-15

    Portal vein embolization (PVE) induces hypertrophy of the future liver remnant (FLR) in patients undergoing extensive hepatic resection. Portal vein access for PVE via the ipsilateral hepatic lobe (designated for resection) places veins targeted for embolization at acute angles to the access site requiring reverse curve catheters for access. This approach also involves access close to tumors in the ipsilateral lobe and requires care to avoid traversing tumor. Alternatively, a contralateral approach (through the FLR) risks damage to the FLR due to iatrogenic trauma or non-target embolization. Two patients successfully underwent PVE via trans-splenic portal vein access, allowing easy access to the ipsilateral portal veins and eliminating risk of damage to FLR. Technique and advantages of trans-splenic portal vein access to perform PVE are described.

  3. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    Science.gov (United States)

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

  4. Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats

    OpenAIRE

    Menon, B. Rajalakshmy; Rathi, M. A.; Thirumoorthi, L.; Gopalakrishnan, V. K.

    2010-01-01

    The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observ...

  5. ERAD defects and the HFE-H63D variant are associated with increased risk of liver damages in Alpha 1-Antitrypsin Deficiency

    Science.gov (United States)

    Di Martino, Julie; Ruiz, Mathias; Garin, Roman; Restier, Lioara; Belmalih, Abdelouahed; Marchal, Christelle; Cullin, Christophe; Arveiler, Benoit; Fergelot, Patricia; Gitler, Aaron D.; Lachaux, Alain; Couthouis, Julien

    2017-01-01

    Background The most common and severe disease causing allele of Alpha 1-Antitrypsin Deficiency (1ATD) is Z-1AT. This protein aggregates in the endoplasmic reticulum, which is the main cause of liver disease in childhood. Based on recent evidences and on the frequency of liver disease occurrence in Z-1AT patients, it seems that liver disease progression is linked to still unknown genetic factors. Methods We used an innovative approach combining yeast genetic screens with next generation exome sequencing to identify and functionally characterize the genes involved in 1ATD associated liver disease. Results Using yeast genetic screens, we identified HRD1, an Endoplasmic Reticulum Associated Degradation (ERAD) associated protein, as an inducer of Z-mediated toxicity. Whole exome sequencing of 1ATD patients resulted in the identification of two variants associated with liver damages in Z-1AT homozygous cases: HFE H63D and HERPUD1 R50H. Functional characterization in Z-1AT model cell lines demonstrated that impairment of the ERAD machinery combined with the HFE H63D variant expression decreased both cell proliferation and cell viability, while Unfolded Protein Response (UPR)-mediated cell death was hyperstimulated. Conclusion This powerful experimental pipeline allowed us to identify and functionally validate two genes involved in Z-1AT-mediated severe liver toxicity. This pilot study moves forward our understanding on genetic modifiers involved in 1ATD and highlights the UPR pathway as a target for the treatment of liver diseases associated with 1ATD. Finally, these findings support a larger scale screening for HERPUD1 R50H and HFE H63D variants in the sub-group of 1ATD patients developing significant chronic hepatic injuries (hepatomegaly, chronic cholestasis, elevated liver enzymes) and at risk developing liver cirrhosis. PMID:28617828

  6. Dysregulation of the DNA Damage Response and KMT2A Rearrangement in Fetal Liver Hematopoietic Cells.

    Directory of Open Access Journals (Sweden)

    Mai Nanya

    Full Text Available Etoposide, a topoisomerase 2 (TOP2 inhibitor, is associated with the development of KMT2A (MLL-rearranged infant leukemia. An epidemiological study suggested that in utero exposure to TOP2 inhibitors may be involved in generation of KMT2A (MLL rearrangement. The present study examined the mechanism underlying the development of KMT2A (MLL-rearranged infant leukemia in response to in utero exposure to etoposide in a mouse model. Fetal liver hematopoietic stem cells were more susceptible to etoposide than maternal bone marrow mononuclear cells. Etoposide-induced Kmt2a breakage was detected in fetal liver hematopoietic stem cells using a newly developed chromatin immunoprecipitation (ChIP assay. Assessment of etoposide-induced chromosomal translocation by next-generation RNA sequencing (RNA-seq identified several chimeric fusion messenger RNAs that were generated by etoposide treatment. However, Kmt2a (Mll-rearranged fusion mRNA was detected in Atm-knockout mice, which are defective in the DNA damage response, but not in wild-type mice. The present findings suggest that in utero exposure to TOP2 inhibitors induces Kmt2a rearrangement when the DNA damage response is defective.

  7. Photo-oxidative damage to isolated rat liver mitochondria induced by phenothiazines

    Directory of Open Access Journals (Sweden)

    T. RODRIGUES

    2009-01-01

    Full Text Available

    Photosensitization is a well-known side-effect of phenothiazines that could involve photochemically promoted oxidative damage to mitochondria, leading to the impairment of metabolic functions and apoptosis. In this work, for the first time, we investigated the effects of photoexcited thioridazine (TR, trifluoperazine (TFP and fluphenazine (FP on isolated rat liver mitochondria. Under UV irradiation, the presence of these phenothiazines led to a dose-dependent lack of the respiratory control ratio. These effects were not accompanied by significant swelling and oxidation of protein thiol groups but were accompanied by lipid peroxidation. Lycopene and sorbate, well-known quenchers of singlet oxygen and triplet species, respectively, were ineffective at protecting mitochondrial lipids against the damage promoted by the excited phenothiazines, suggesting that photochemically-produced cation radicals were the prooxidant species. Corroborating this proposal, butylated hydroxytoluene (BHT completely inhibited the lipid peroxidation induced by UV irradiation in the presence of phenothiazines. These novel results make a significant contribution to the understanding of the photochemical properties of phenothiazines in biological systems. Keywords: Trifluoperazine, thioridazine, fluphenazine, rat liver mitochondria, oxidative stress, photochemistry, photodamage, respiratory chain.

  8. Protective effect of Urtica dioica on liver damage induced by biliary obstruction in rats.

    Science.gov (United States)

    Oguz, Serhat; Kanter, Mehmet; Erboga, Mustafa; Ibis, Cem

    2013-10-01

    The aim of this study was to evaluate the possible protective effects of Urtica dioica (UD) against liver damage in the common bile duct-ligated rats. A total of 24 male Sprague Dawley rats were divided into three groups, namely, control, bile duct ligation (BDL) and BDL + received UD groups, containing eight animals in each group. The rats in UD-treated groups were given UD oils (2 ml/kg) once a day intraperitoneally for 2 weeks starting 3 days prior to BDL operation. The change demonstrating the bile duct proliferation and fibrosis in expanded portal tracts includes the extension of proliferated bile ducts into the lobules; inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with UD attenuated alterations in liver histology. The α-smooth muscle actin, cytokeratin-positive ductular proliferation and the activity of terminal deoxynucleotidyl transferase dUTP nick end labeling in the BDL were observed to be reduced with the UD treatment. The data indicate that UD attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis.

  9. Novel Experimental Techniques to Investigate Wellbore Damage Mechanisms

    Science.gov (United States)

    Choens, R. C., II; Ingraham, M. D.; Lee, M.; Dewers, T. A.

    2017-12-01

    A new experimental technique with unique geometry is presented investigating deformation of simulated boreholes using standard axisymmetric triaxial deformation equipment. The Sandia WEllbore SImulation, SWESI, geometry, uses right cylinders of rock 50mm in diameter and 75mm in length. A 11.3mm hole is drilled perpendicular to the axis of the cylinder in the center of the sample to simulate a borehole. The hole is covered with a solid metal cover, and sealed with polyurethane. The metal cover can be machined with a high-pressure port to introduce different fluid chemistries into the borehole at controlled pressures. Samples are deformed in a standard load frame under confinement, allowing for a broad range of possible stresses, load paths, and temperatures. Experiments in this study are loaded to the desired confining pressure, then deformed at a constant axial strain rate or 10-5 sec-1. Two different suites of experiments are conducted in this study on sedimentary and crystalline rock types. The first series of experiments are conducted on Mancos Shale, a finely laminated transversely isotropic rock. Samples are cored at three different orientations to the laminations. A second series of experiments is conducted on Sierra White granite with different fluid chemistries inside the borehole. Numerical modelling and experimental observations including CT-microtomography demonstrate that stresses are concentrated around the simulated wellbore and recreate wellbore deformation mechanisms. Borehole strength and damage development is dependent on anisotropy orientation and fluid chemistry. Observed failure geometries, particularly for Mancos shale, can be highly asymmetric. These results demonstrate uncertainties in in situ stresses measurements using commonly-applied borehole breakout techniques in complicated borehole physico-chemical environments. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering

  10. Oxidative Damage Does Not Occur in Striped Hamsters Raising Natural and Experimentally Increased Litter Size.

    Directory of Open Access Journals (Sweden)

    Xiao-Ya Zhao

    Full Text Available Life-history theory assumes that animals can balance the allocation of limited energy or resources to the competing demands of growth, reproduction and somatic maintenance, while consequently maximizing their fitness. However, somatic damage caused by oxidative stress in reproductive female animals is species-specific or is tissue dependent. In the present study, several markers of oxidative stress (hydrogen peroxide, H2O2 and malonadialdehyde, MDA and antioxidant (catalase, CAT and total antioxidant capacity, T-AOC were examined in striped hamsters during different stages of reproduction with experimentally manipulated litter size. Energy intake, resting metabolic rate (RMR, and mRNA expression of uncoupling protein 1 (UCP1 in brown adipose tissue (BAT and UCP3 in skeletal muscle were also examined. H2O2 and MDA levels did not change in BAT and liver, although they significantly decreased in skeletal muscle in the lactating hamsters compared to the non-reproductive group. However, H2O2 levels in the brain were significantly higher in lactating hamsters than non-reproductive controls. Experimentally increasing litter size did not cause oxidative stress in BAT, liver and skeletal muscle, but significantly elevated H2O2 levels in the brain. CAT activity of liver decreased, but CAT and T-AOC activity of BAT, skeletal muscle and the brain did not change in lactating hamsters compared to non-reproductive controls. Both antioxidants did not change with the experimentally increasing litter size. RMR significantly increased, but BAT UCP1 mRNA expression decreased with the experimentally increased litter size, suggesting that it was against simple positive links between metabolic rate, UCP1 expression and free radicals levels. It may suggest that the cost of reproduction has negligible effect on oxidative stress or even attenuates oxidative stress in some active tissues in an extensive range of animal species. But the increasing reproductive effort may

  11. Protective Effect of Brazilian Propolis against Liver Damage with Cholestasis in Rats Treated with α-Naphthylisothiocyanate

    Directory of Open Access Journals (Sweden)

    Tadashi Nakamura

    2013-01-01

    Full Text Available We examined the protective effect of Brazilian propolis against liver damage with cholestasis in rats treated with α-naphthylisothiocyanate (ANIT in comparison with that of vitamin E (VE. Rats orally received Brazilian propolis ethanol extract (BPEE (25, 50, or 100 mg/kg, VE (250 mg/kg or vehicle at 12 h after intraperitoneal injection of ANIT (75 mg/kg and were killed 24 h after the injection. Vehicle-treated rats showed liver cell damage and cholestasis, judging from the levels of serum marker enzymes and components. The vehicle group had increased serum total cholesterol, triglyceride, phospholipid, and lipid peroxide levels, increased hepatic lipid peroxide, reduced glutathione, and ascorbic acid levels and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. BPEE (50 mg/kg administered to ANIT-treated rats prevented liver cell damage and cholestasis and attenuated these serum and hepatic biochemical changes except hepatic ascorbic acid, although administered BPEE (25 or 100 mg/kg was less effective. VE administered to ANIT-treated rats prevented liver cell damage, but not cholestasis, and attenuated increased serum lipid peroxide level, increased hepatic lipid peroxide level and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. These results indicate that BPEE protects against ANIT-induced liver damage with cholestasis in rats more effectively than VE.

  12. Polyphenolic screening and protective properties of some vegetables against CCl4 liver damage

    International Nuclear Information System (INIS)

    Salawu, S.O.; Akindahunsi, A.A.

    2007-12-01

    In the present study, we screened for the polyphenolic compounds present in some selected tropical vegetables and the protective effect of the vegetable extract against CCl 4 -induced hepatotoxicity in rats as a way of evaluating their medicinal potential in addition to their nutritional values. The use of HPLC/DAD/MS revealed the presence of some phenolic compounds in the studied vegetables. Crassocephalum crepidioides; caffeoyl derivatives, Talinum triangulare; rutin and kaempferol derivatives, Amaranthus hybridus; caffeoyl derivative, rutin and kaempferol derivative, Hibiscus esculentus; caffeoyl derivative, quercetin derivative and an unidentified flavonoid, Xanthosoma mafaffa; six unidentified flavonoids with similar absorption maximum at different retention times) and Celocia argentia (luteolin derivative and four unidentified flavonoids. Carbon tetrachloride at a dose of 0.5ml/kg body weight (b.w) produced liver damage in rats as manifested by the rise in the levels of ALT (IU/l), AST (IU/l) and total protein (g/l) in the serum (40.60 ± 3.50, 80.60 ± 5.10, 73.20 ± 1.87), in the liver homogenate (1300.00 ± 7.38, 1660.00 ± 13.69, 250.00 ± 7.51) and MDA content (nmol TBARS/mg Liver Protein) in the liver homogenate (82.00 ± 0.02, 82.00 ± 0.07) compared to the control. The result revealed a reduction of the serum marker enzymes (ALT, AST and Total protein), compared with the CCl 4 treated group after the administration of the various polyphenolic extract. In a similar manner, the extract brings about a reduction of the MDA content. It could be concluded that the protective properties exhibited by the vegetables could be amongst other factor due to the presence of some polyphenols. (author)

  13. Antioxidants as recipes for efavirenz-induced liver damage: A study in albino rats

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    Elias Adikwu

    2018-03-01

    Full Text Available Objective: Hepatotoxicity is a clinical challenge associated with the use of efavirenz (EFV. This study investigated the effects of n-acetylcysteine (NAC, vitamins C and E on EFV-induced hepatotoxicity in albino rats. Methods: Rats were divided into groups and administered with NAC (20mg/kg, Vit C (50mg/kg, Vit  E (50mg/kg, Vit C+ E and 60mg/kg of EFV respectively. Rats were also divided into groups and pretreated with NAC, Vit C, E, and combined doses of Vit C+E prior to treatment with EFV for 15 days respectively. After drug administration rats were sacrificed and serum was collected and evaluated for liver function parameters. Rats were dissected, liver was collected weighed and evaluated for alkaline phosphatase (ALP, alanine aminotransferase (AST, aspartate aminotransferase (ALT, gamma glutamyl transferase (GGT, lactate dehydrogenase (LDH, malondialdehyde (MDA, super oxide dismutase (SOD, catalase (CAT, glutathione (GSH, gluthatione peroxidase (GPX levels and pathological damage. Results: Effects were not significant (p>0.05 on body and liver weights, however, the levels of AST, ALT, AST, GGT, LDH, CB, TB and MDA were increased significantly (p<0.05 whereas SOD, CAT, SOD, GSH and GPX were decreased significantly (p<0.05 in EFV-treated rats in comparison to control. The liver of EFV-treated rats showed necrosis of hepatocytes. Nevertheless, EFV-induced alterations in the above parameters were significantly (p<0.05 ameliorated in antioxidants pretreated rats.  The combined doses of Vit C and E produced the best and significant (p<0.05 ameliorative effects in comparison to their individual doses. Conclusion: This study shows the prospects of antioxidants as candidates for the treatments of efavirenz-induced hepatotoxicity.

  14. Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism.

    Science.gov (United States)

    Li, Shuang; Wang, S U; Guo, Zhi-Gang; Huang, Ning; Zhao, Fan-Rong; Zhu, Mo-Li; Ma, Li-Juan; Liang, Jin-Ying; Zhang, Yu-Lin; Huang, Zhong-Lin; Wan, Guang-Rui

    2015-11-01

    The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism.

  15. Peroxisomal enzymes in the liver of rats with experimental diabetes mellitus type 2.

    Science.gov (United States)

    Turecký, L; Kupčová, V; Uhlíková, E; Mojto, V

    2014-01-01

    Diabetes mellitus is relatively frequently associated with fatty liver disease. Increased oxidative stress probably plays an important role in the development of this hepatopathy. One of possible sources of reactive oxygen species in liver is peroxisomal system. There are several reports about changes of peroxisomal enzymes in experimental diabetes, mainly enzymes of fatty acid oxidation. The aim of our study was to investigate the possible changes of activities of liver peroxisomal enzymes, other than enzymes of beta-oxidation, in experimental diabetes mellitus type 2. Biochemical changes in liver of experimental animals suggest the presence of liver steatosis. The changes of serum parameters in experimental group are similar to changes in serum of patients with non-alcoholic fatty liver disease. We have shown that diabetes mellitus influenced peroxisomal enzymes by the different way. Despite of well-known induction of peroxisomal beta-oxidation, the activities of catalase, aminoacid oxidase and NADH-cytochrome b(5) reductase were not significantly changed and the activities of glycolate oxidase and NADP-isocitrate dehydrogenase were significantly decreased. The effect of diabetes on liver peroxisomes is probably due to the increased supply of fatty acids to liver in diabetic state and also due to increased oxidative stress. The changes of metabolic activity of peroxisomal compartment may participate on the development of diabetic hepatopathy.

  16. Numerical and Experimental Validation of a New Damage Initiation Criterion

    Science.gov (United States)

    Sadhinoch, M.; Atzema, E. H.; Perdahcioglu, E. S.; van den Boogaard, A. H.

    2017-09-01

    Most commercial finite element software packages, like Abaqus, have a built-in coupled damage model where a damage evolution needs to be defined in terms of a single fracture energy value for all stress states. The Johnson-Cook criterion has been modified to be Lode parameter dependent and this Modified Johnson-Cook (MJC) criterion is used as a Damage Initiation Surface (DIS) in combination with the built-in Abaqus ductile damage model. An exponential damage evolution law has been used with a single fracture energy value. Ultimately, the simulated force-displacement curves are compared with experiments to validate the MJC criterion. 7 out of 9 fracture experiments were predicted accurately. The limitations and accuracy of the failure predictions of the newly developed damage initiation criterion will be discussed shortly.

  17. Criterion of damage beginning: experimental identification for laminate composite

    International Nuclear Information System (INIS)

    Thiebaud, F.; Perreux, D.; Varchon, D.; Lebras, J.

    1996-01-01

    The aim of this study is to propose a criterion of damage beginning for laminate composite. The materials is a glass-epoxy laminate [+55 deg.,-55 deg.[ n performed by winding filament process. First of all a description of the damage is performed and allows to define a damage variable. Thanks to the potential of free energy, an associated variable is defined. The damage criterion is written by using this last one. The parameter of the criterion is identified using mechanical and acoustical methods. The result is compared and exhibit a good agreement. (authors). 13 refs., 5 figs

  18. Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Oliveira C.P.M.S.

    2006-01-01

    Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

  19. Experimental modified orthotopic piggy-back liver autotransplantation

    International Nuclear Information System (INIS)

    Roveda, L.; Zonta, A.; Staffieri, F.; Timurian, D.; DiVenere, B.; Bakeine, G.J.; Crovace, A.; Prati, U.

    2009-01-01

    The classical orthotopic liver autotransplantation is a very challenging and time wasting technique; it includes the division of major hepatic vessels and choledocus, and subsequent reconnection by end to end anastomoses. The caval end to end anastomoses are the most difficult to be performed and the interposition of a prosthesis can be required. We adopted the classical orthotopic liver autotransplantation technique in 2 patients affected with diffused liver metastases from colorectal cancer, for extracorporeal neutron capture therapy (BNCT). The procedure required very long operating times and the extracorporeal circulation (ECC) set up; furthermore the vena cava reconstruction was performed by the interposition of a goretex-prosthesis. We propose a 'modified orthotopic piggy-back technique' to simplify liver reconnection and shorten the operating time. Materials and methods: The technique was developed in the swine (25 kg body weight), under general anaesthesia. We performed the resection of the retro-hepatic vena cava with preservation of the caval flow during the anhepatic phase, by interposing a goretex-prosthesis. The reconstruction of the vena cava was then performed by a side-to-side cava-prosthesis anastomosis with lateral clamping of the prosthesis. The procedure was then completed according to the classical technique of liver transplantation. Results: The mean time for VC reconstruction was 56 (±10) min. and the mean time for side-to-side VC-prosthesis anastomosis was 13 (±4) min. Conclusions: The 'modified orthotopic piggy-back technique' can simplify the reimplant of the liver during autotransplantation and shorten the operating time. Furthermore also the time of total extracorporeal circulation is reduced, as during the anhepatic phase and during the side-to-side cava-prosthesis anastomosis the flow in the inferior vena cava is uninterrupted.

  20. Experimental modified orthotopic piggy-back liver autotransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Roveda, L. [Oncologic Surgery, Cancer Center of Excellence Fond. ' T.Campanella' , Europa Avenue, Catanzaro CZ-88100 (Italy)], E-mail: roveda.l@libero.it; Zonta, A. [Department of Surgery, University of Pavia, PV 27100 (Italy); Staffieri, F. [Veterinary Surgery Unit, Department of Emergencies and Organs Transplantation, Faculty of Veterinary Medicine, SP per Casamassima km 3, Valenzano, BA 70010 (Italy); Timurian, D.; DiVenere, B. [Surgery ' Madonna delle Grazie' Hospital, Contrada Cattedra Ambulante, Matera, MT 75100 (Italy); Bakeine, G.J. [Laboratorio Nazionale di Tecnologie Avanzate e Nanoscienza (TASC), Basovizza, TR (Italy); Crovace, A. [Veterinary Surgery Unit, Department of Emergencies and Organs Transplantation, Faculty of Veterinary Medicine, SP per Casamassima km 3, Valenzano, BA 70010 (Italy); Prati, U. [Oncologic Surgery, Cancer Center of Excellence Fond. ' T.Campanella' , Europa Avenue, Catanzaro CZ-88100 (Italy)

    2009-07-15

    The classical orthotopic liver autotransplantation is a very challenging and time wasting technique; it includes the division of major hepatic vessels and choledocus, and subsequent reconnection by end to end anastomoses. The caval end to end anastomoses are the most difficult to be performed and the interposition of a prosthesis can be required. We adopted the classical orthotopic liver autotransplantation technique in 2 patients affected with diffused liver metastases from colorectal cancer, for extracorporeal neutron capture therapy (BNCT). The procedure required very long operating times and the extracorporeal circulation (ECC) set up; furthermore the vena cava reconstruction was performed by the interposition of a goretex-prosthesis. We propose a 'modified orthotopic piggy-back technique' to simplify liver reconnection and shorten the operating time. Materials and methods: The technique was developed in the swine (25 kg body weight), under general anaesthesia. We performed the resection of the retro-hepatic vena cava with preservation of the caval flow during the anhepatic phase, by interposing a goretex-prosthesis. The reconstruction of the vena cava was then performed by a side-to-side cava-prosthesis anastomosis with lateral clamping of the prosthesis. The procedure was then completed according to the classical technique of liver transplantation. Results: The mean time for VC reconstruction was 56 ({+-}10) min. and the mean time for side-to-side VC-prosthesis anastomosis was 13 ({+-}4) min. Conclusions: The 'modified orthotopic piggy-back technique' can simplify the reimplant of the liver during autotransplantation and shorten the operating time. Furthermore also the time of total extracorporeal circulation is reduced, as during the anhepatic phase and during the side-to-side cava-prosthesis anastomosis the flow in the inferior vena cava is uninterrupted.

  1. Numerical and Experimental Validation of a New Damage Initiation Criterion

    NARCIS (Netherlands)

    Sadhinoch, M.; Atzema, E.H.; Perdahcioglu, E.S.; Van Den Boogaard, A.H.

    2017-01-01

    Most commercial finite element software packages, like Abaqus, have a built-in coupled damage model where a damage evolution needs to be defined in terms of a single fracture energy value for all stress states. The Johnson-Cook criterion has been modified to be Lode parameter dependent and this

  2. Rat Liver Enzyme Release Depends on Blood Flow-Bearing Physical Forces Acting in Endothelium Glycocalyx rather than on Liver Damage

    Directory of Open Access Journals (Sweden)

    Julieta A. Díaz-Juárez

    2017-01-01

    Full Text Available We have found selective elevation of serum enzyme activities in rats subjected to partial hepatectomy (PH, apparently controlled by hemodynamic flow-bearing physical forces. Here, we assess the involvement of stretch-sensitive calcium channels and calcium mobilization in isolated livers, after chemical modifications of the endothelial glycocalyx and changing perfusion directionality. Inhibiting in vivo protein synthesis, we found that liver enzyme release is influenced by de novo synthesis of endothelial glycocalyx components, and released enzymes are confined into a liver “pool.” Moreover, liver enzyme release depended on extracellular calcium entry possibly mediated by stretch-sensitive calcium channels, and this endothelial-mediated mechanotransduction in liver enzyme release was also evidenced by modifying the glycocalyx carbohydrate components, directionality of perfusing flow rate, and the participation of nitric oxide (NO and malondialdehyde (MDA, leading to modifications in the intracellular distribution of these enzymes mainly as nuclear enrichment of “mitochondrial” enzymes. In conclusion, the flow-induced shear stress may provide fine-tuned control of released hepatic enzymes through mediation by the endothelium glycocalyx, which provides evidence of a biological role of the enzyme release rather to be merely a biomarker for evaluating hepatotoxicity and liver damage, actually positively influencing progression of liver regeneration in mammals.

  3. Experimental study on quantitative evaluation of fatty liver by computed tomography

    International Nuclear Information System (INIS)

    Kunieda, Tokuro; Kawata, Ryo; Hayashi, Koki; Nishiwaki, Tsutomu; Kunieda, Katsuyuki; Saji, Shigetoyo; Sakata, Kazuki

    1984-01-01

    Biochemical, histological and CT examinations of the liver were perfiormed in 32 rabbits on significance of measuring CT values in the diagnosis of fatty liver. In 2 groups of rabbits, in which 2g/kg/day and 4g/kg/day of fat emulsion were adminstered intravenously for 4 weeks respectively, post-treatment reduction in CT value of light dergree was observed. In a group, in which 8g/kg/day were given, there was a sufficient reduction in CT value for giving diagnosis of fatty liver of moderate degree. Significant correlation was found between changes in CT value of the liver on the one hand and contents of triglyceride, total cholesterol and cholesterol ester in the liver on the other hand, while there was no significant correlation between changes in CT value and contents of phospholipid, protein and water. Significcant correlation was found between changes in CT value of the liver and degress of histological fat accumulation in the liver cells. It has been evidenced experimentally that prolonged administration of fat emulsion may cause fatty liver, and that measurement of CT values of the liver is a non-aggressive method of diagnosing fatty liver. (author)

  4. Developmental stages in experimental liver metastases: relation to invasiveness

    NARCIS (Netherlands)

    Dingemans, K. P.; van den Bergh Weerman, M. A.; Keep, R. F.; Das, P. K.

    1994-01-01

    We have previously reported that an invasive morphotype can be evoked in a rat colon carcinoma by transplanting it into pre-induced subcutaneous granulation tissue. We have now studied the interaction of the same tumor with liver tissue, which is extremely poor in connective tissue in comparison

  5. Honey can repairing damage of liver tissue due to protein energy malnutrition through induction of endogenous stem cells

    Directory of Open Access Journals (Sweden)

    R. Heru Prasetyo

    2017-06-01

    Full Text Available Aim: This study was to evaluate effect of honey in repairing damage of liver tissue due to energy protein malnutrition and in mobilization of endogenous stem cells. Materials and Methods: Male mice model of degenerative liver was obtained through food fasting but still have drinking water for 5 days. It caused energy protein malnutrition and damage of liver tissue. The administration of 50% (v/v honey was performed for 10 consecutive days, while the positive control group was fasted and not given honey and the negative control not fasted and without honey. Observations of regeneration the liver tissue based on histologically examination, observation of Hsp70 expression, and homing signal based on vascular endothelial growth factor-1 (VEGF-1 expression using immunohistochemistry technique. Observation on expression of CD34 and CD45 as the marker of auto mobilization of hematopoietic stem cells using flow cytometry technique. Results: There is regeneration of the liver tissue due to protein energy malnutrition, decrease of Hsp70 expression, increase of VEGF-1 expression, and high expression of CD34 and CD45. Conclusion: Honey can improve the liver tissue based on: (1 Mobilization of endogenous stem cells (CD34 and CD45; (2 Hsp70 and VEGF-1 expressions as regeneration marker of improvement, and (3 regeneration histologically of liver tissue.

  6. Honey can repairing damage of liver tissue due to protein energy malnutrition through induction of endogenous stem cells.

    Science.gov (United States)

    Prasetyo, R Heru; Hestianah, Eka Pramyrtha

    2017-06-01

    This study was to evaluate effect of honey in repairing damage of liver tissue due to energy protein malnutrition and in mobilization of endogenous stem cells. Male mice model of degenerative liver was obtained through food fasting but still have drinking water for 5 days. It caused energy protein malnutrition and damage of liver tissue. The administration of 50% (v/v) honey was performed for 10 consecutive days, while the positive control group was fasted and not given honey and the negative control not fasted and without honey. Observations of regeneration the liver tissue based on histologically examination, observation of Hsp70 expression, and homing signal based on vascular endothelial growth factor-1 (VEGF-1) expression using immunohistochemistry technique. Observation on expression of CD34 and CD45 as the marker of auto mobilization of hematopoietic stem cells using flow cytometry technique. There is regeneration of the liver tissue due to protein energy malnutrition, decrease of Hsp70 expression, increase of VEGF-1 expression, and high expression of CD34 and CD45. Honey can improve the liver tissue based on: (1) Mobilization of endogenous stem cells (CD34 and CD45); (2) Hsp70 and VEGF-1 expressions as regeneration marker of improvement, and (3) regeneration histologically of liver tissue.

  7. Effect of the aqueous extract of Psidium guajava on erythromycin-induced liver damage in rats.

    Science.gov (United States)

    Sambo, N; Garba, S H; Timothy, H

    2009-12-01

    The effect of Psidium guajava extract on erythromycin-induced liver damage in albino rats was investigated using 30 normal rats grouped into six. Group I and II served as the normal and treatment controls that were administered with normal saline and 100 mg/kg body weight of erythromycin stearate daily for 14 days respectively. Rats in group III were administered 450 mg/kg body weight of Psidium guajava only for 7 days while rats in groups IV, V and VI were administered Psidium guajava extract for 7 days and 100mg/kg body weight of erythromycin for 14 days. Histopathological investigation of the liver tissues revealed striking oedema and mild periportal mononuclear cell infiltration of hepatic cords in the liver of rats administered 100 mg/kg of erythromycin stearate and 300/450 mg/kg of Psidium guajava extract. Pretreatment with 150 mg/kg of Psidium guajava extract showed a slight degree of protection against the induced hepatic injury caused by 100 mg/kg of erythromycin stearate. Biochemical analysis of the serum obtained revealed a significant increase in serum levels of hepatic enzymes measured in the groups administered with 100 mg/kg of erythromycin stearate and 300/450 mg/kg of Psidium guajava extract compared to the control groups and those pretreated with 150 mg/kg of Psidium guajava extract. This study has shown that the aqueous extract of psidium guajava leaf possesses hepatoprotective property at lower dose and a hepatotoxic property at higher dose but further studies with prolonged duration is recommended.

  8. Persistent and heritable structural damage induced in heterochromatic DNA from rat liver by N-nitrosodimethylamine

    International Nuclear Information System (INIS)

    Ward, E.J.; Stewart, B.W.

    1987-01-01

    Analysis, by benzoylated DEAE-cellulose chromatography, has been made of structural change in eu- and heterochromatic DNA from rat liver following administration of the carcinogen N-nitrosodimethylamine. Either hepatic DNA was prelabeled with [ 3 H]thymidine administered 2-3 weeks before injection of the carcinogen or the labeled precursor was given during regenerative hyperplasia in rats treated earlier with N-nitrosodimethylamine. Following phenol extraction of either whole liver homogenate or nuclease-fractionated eu- and heterochromatin, carcinogen-modified DNA was examined by stepwise or caffeine gradient elution from benzoylated DEAE-cellulose. In whole DNA, nitrosamine-induced single-stranded character was maximal 4-24 h after treatment, declining rapidly thereafter; gradient elution of these DNA preparations also provided short-term evidence of structural change. Caffeine gradient chromatography suggested short-term nitrosamine-induced structural change in euchromatic DNA, while increased binding of heterochromatic DNA was evident for up to 3 months after carcinogen treatment. Preparations of newly synthesized heterochromatic DNA from animals subjected to hepatectomy up to 2 months after carcinogen treatment provided evidence of heritable structural damage. Carcinogen-induced binding of heterochromatic DNA to benzoylated DEAE-cellulose was indicative of specific structural lesions whose affinity equalled that of single-stranded DNA up to 1.0 kilobase in length. The data suggest that structural lesions in heterochromatin, which may be a consequence of incomplete repair, are preferentially degraded by endogenous nuclease(s)

  9. An Innovative Hyperbaric Hypothermic Machine Perfusion Protects the Liver from Experimental Preservation Injury

    Directory of Open Access Journals (Sweden)

    Ferdinando A. Giannone

    2012-01-01

    Full Text Available Purpose. Hypothermic machine perfusion systems seem more effective than the current static storage to prevent cold ischemic liver injury. Thus, we test an innovative hyperbaric hypothermic machine perfusion (HHMP, which combines hyperbaric oxygenation of the preservation solution and continuous perfusion of the graft. Methods. Rat livers were preserved with Celsior solution according to 4 different modalities: normobaric static preservation; hyperbaric static preservation at 2 atmosphere absolute (ATA; normobaric dynamic preservation, with continuous perfusion; hyperbaric dynamic preservation, with continuous perfusion at 2 ATA. After 24 h cold preservation, we assessed different parameters. Results. Compared to baseline, livers preserved with the current static storage showed severe ultrastructural damage, glycogen depletion and an increased oxidative stress. Normobaric perfused livers showed improved hepatocyte ultrastructure and ameliorated glycogen stores, but they still suffered a significant oxidative damage. The addition of hyperbaric oxygen produces an extra benefit by improving oxidative injury and by inducing endothelial NO synthase (eNOS gene expression. Conclusions. Preservation by means of the present innovative HHMP reduced the liver injury occurring after the current static cold storage by lowering glycogen depletion and oxidative damage. Interestingly, only the use of hyperbaric oxygen was associated to a blunted oxidative stress and an increased eNOS gene expression.

  10. Visualization of acute liver damage induced by cycloheximide in rats using PET with [(18F]FEDAC, a radiotracer for translocator protein (18 kDa.

    Directory of Open Access Journals (Sweden)

    Akiko Hatori

    Full Text Available Liver damage induced by drug toxicity is an important concern for both medical doctors and patients. The aim of this study was to noninvasively visualize acute liver damage using positron emission tomography (PET with N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[(18F]fluoroethyl-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ([(18F]FEDAC, a radiotracer specific for translocator protein (18 kDa, TSPO as a biomarker for inflammation, and to determine cellular sources enriching TSPO expression in the liver. A mild acute liver damage model was prepared by a single intraperitoneal injection of cycloheximide (CHX into rats. Treatment with CHX induced apoptosis and necrotic changes in hepatocytes with slight neutrophil infiltration. The uptake of radioactivity in the rat livers was measured with PET after injection of [(18F]FEDAC. The uptake of [(18F]FEDAC increased in livers damaged from treatment with CHX compared to the controls. Presence of TSPO was examined in the liver tissue using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical assays. mRNA expression of TSPO was elevated in the damaged livers compared to the controls, and the level was correlated with the [(18F]FEDAC uptake and severity of damage. TSPO expression in the damaged liver sections was mainly found in macrophages (Kupffer cells and neutrophils, but not in hepatocytes. The elevation of TSPO mRNA expression was derived from the increase of the number of macrophages with TSPO and neutrophils with TSPO in damaged livers. From this study we considered that PET imaging with [(18F]FEDAC represented the mild liver damage through the enhanced TSPO signal in inflammatory cells. We conclude that this method may be a useful tool for diagnosis in early stage of acute liver damage.

  11. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    International Nuclear Information System (INIS)

    Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

    2012-01-01

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p 4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl 4 , reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ► After 30-day chronic CCl 4 intoxication mitochondria displayed considerable changes. ► The functional parameters of mitochondria were similar to the control values. ► Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ► The above complex enhanced regenerative processes in the liver.

  12. Experimental Study of Damage Evolution in Circular Stirrup-Confined Concrete.

    Science.gov (United States)

    Li, Zuohua; Peng, Zhihan; Teng, Jun; Wang, Ying

    2016-04-08

    This paper presents an experimental study on circular stirrup-confined concrete specimens under uniaxial and monotonic load. The effects of stirrup volume ratio, stirrup yield strength and concrete strength on damage evolution of stirrup-confined concrete were investigated. The experimental results showed that the strength and ductility of concrete are improved by appropriate arrangement of the stirrup confinement. Firstly, the concrete damage evolution can be relatively restrained with the increase of the stirrup volume ratio. Secondly, higher stirrup yield strength usually causes larger confining pressures and slower concrete damage evolution. In contrast, higher concrete strength leads to higher brittleness, which accelerates the concrete damage evolution. A plastic strain expression is obtained through curve fitting, and a damage evolution equation for circular stirrup-confined concrete is proposed by introducing a confinement factor ( C ) based on the experimental data. The comparison results demonstrate that the proposed damage evolution model can accurately describe the experimental results.

  13. Experimental Study of Damage Evolution in Circular Stirrup-Confined Concrete

    Science.gov (United States)

    Li, Zuohua; Peng, Zhihan; Teng, Jun; Wang, Ying

    2016-01-01

    This paper presents an experimental study on circular stirrup-confined concrete specimens under uniaxial and monotonic load. The effects of stirrup volume ratio, stirrup yield strength and concrete strength on damage evolution of stirrup-confined concrete were investigated. The experimental results showed that the strength and ductility of concrete are improved by appropriate arrangement of the stirrup confinement. Firstly, the concrete damage evolution can be relatively restrained with the increase of the stirrup volume ratio. Secondly, higher stirrup yield strength usually causes larger confining pressures and slower concrete damage evolution. In contrast, higher concrete strength leads to higher brittleness, which accelerates the concrete damage evolution. A plastic strain expression is obtained through curve fitting, and a damage evolution equation for circular stirrup-confined concrete is proposed by introducing a confinement factor (C) based on the experimental data. The comparison results demonstrate that the proposed damage evolution model can accurately describe the experimental results. PMID:28773402

  14. Detection of damage in welded structure using experimental modal data

    Energy Technology Data Exchange (ETDEWEB)

    Abu Husain, N [Transportation Research Alliance, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor (Malaysia); Ouyang, H, E-mail: nurul@fkm.utm.my, E-mail: h.ouyang@liv.ac.uk [Department of Engineering, Harrison-Hughes Building, University of Liverpool, Brownlow Hill, Liverpool L69 3GH (United Kingdom)

    2011-07-19

    A typical automotive structure could contain thousands of spot weld joints that contribute significantly to the vehicle's structural stiffness and dynamic characteristics. However, some of these joints may be imperfect or even absent during the manufacturing process and they are also highly susceptible to damage due to operational and environmental conditions during the vehicle lifetime. Therefore, early detection and estimation of damage are important so necessary actions can be taken to avoid further problems. Changes in physical parameters due to existence of damage in a structure often leads to alteration of vibration modes; thus demonstrating the dependency between the vibration characteristics and the physical properties of structures. A sensitivity-based model updating method, performed using a combination of MATLAB and NASTRAN, has been selected for the purpose of this work. The updating procedure is regarded as parameter identification which aims to bring the numerical prediction to be as closely as possible to the measured natural frequencies and mode shapes data of the damaged structure in order to identify the damage parameters (characterised by the reductions in the Young's modulus of the weld patches to indicate the loss of material/stiffness at the damage region).

  15. Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats

    International Nuclear Information System (INIS)

    Balaha, Mohamed; Kandeel, Samah; Barakat, Waleed

    2016-01-01

    Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1 ml/kg 10% CCL 4 in olive oil three times/week (every other day) for 12 weeks to induce hepatic cirrhosis. Carvedilol (10 mg/kg/day suspended in 0.5% CMC orally), silymarin (50 mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL 4 induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries. - Highlights: • Chronic liver damage ends into hepatocellular carcinoma in 5% of patients. • Persistent elevation of IL-6 induces hepatocarcinogenesis in chronic

  16. Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats

    Energy Technology Data Exchange (ETDEWEB)

    Balaha, Mohamed, E-mail: Mohamed.Balaha@Med.Tanta.Edu.Eg [Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt); Kandeel, Samah [Histology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt); Barakat, Waleed [Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt)

    2016-11-15

    Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1 ml/kg 10% CCL{sub 4} in olive oil three times/week (every other day) for 12 weeks to induce hepatic cirrhosis. Carvedilol (10 mg/kg/day suspended in 0.5% CMC orally), silymarin (50 mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL{sub 4} induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries. - Highlights: • Chronic liver damage ends into hepatocellular carcinoma in 5% of patients. • Persistent elevation of IL-6 induces hepatocarcinogenesis

  17. A comparative study on the hepatoprotective action of bear bile and Coptidis Rhizoma aqueous extract on experimental liver fibrosis in rats.

    Science.gov (United States)

    Wang, Ning; Feng, Yibin; Cheung, Fan; Chow, Oi-Yee; Wang, Xuanbin; Su, Weiwei; Tong, Yao

    2012-11-29

    Bear bile and Coptidis Rhizoma have been used in Chinese medicine with a long tradition in treating heat-diseases. Both bear bile and Coptidis Rhizoma are used to treat liver diseases in clinical practice of Chinese Medicine. Since bears are currently endangered, it raises the question whether the use of bear bile is ethical. To look for substitute for bear bile, the aim of this study is to compare the anti-fibrotic effects of Coptidis Rhizoma and its major component berberine with the actions of bear bile and its major compound tauroursodeoxycholic acid on experimental liver fibrosis in rats. Quality assessment was conducted with high performance liquid chromatography. The experimental liver fibrosis in rats was induced by carbon tetrachloride, alcohol, and bile duct ligation respectively. The biochemical criteria in the blood and tissue samples were measured to evaluate the anti-fibrotic properties and underlying mechanisms of the drugs. Coptidis Rhizoma Aqueous Extract (CRAE), berberine, and bear bile exerted anti-fibrotic properties on various liver fibrosis models in rats. CRAE and berberine significantly reduced the peroxidative stress in liver through increasing the superoxide dismutase enzyme activity. CRAE and berberine were able to excrete bilirubin products from the liver and protect hepatocytes from cholestatic damage. The effect of CRAE and berberine are comparable to that of bear bile. Instead of using bear bile, CRAE and berberine can be potential substitutes in treating liver fibrosis.

  18. Resveratrol Ameliorates Experimental Alcoholic Liver Disease by Modulating Oxidative Stress

    Directory of Open Access Journals (Sweden)

    He Peiyuan

    2017-01-01

    Full Text Available The aim of this study was to investigate the hepatoprotective effects of resveratrol in alcoholic liver disease (ALD. Alcohol was administered to healthy female rats starting from 6% (v/v and gradually increased to 20% (v/v by the fifth week. After 16 weeks of intervention, liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] were analyzed using a chemistry analyzer, while hepatic antioxidant enzymes, oxidative stress markers, and caspase 3 activity were assessed using ELISA kits. Furthermore, hepatic CYP2E1 protein levels and mRNA levels of antioxidant and inflammation-related genes were determined using western blotting and RT-PCR, respectively. The results showed that resveratrol significantly attenuated alcohol-induced elevation of liver enzymes and improved hepatic antioxidant enzymes. Resveratrol also attenuated alcohol-induced CYP2E1 increase, oxidative stress, and apoptosis (caspase 3 activity. Moreover, genes associated with oxidative stress and inflammation were regulated by resveratrol supplementation. Taken together, the results suggested that resveratrol alleviated ALD through regulation of oxidative stress, apoptosis, and inflammation, which was mediated at the transcriptional level. The data suggests that resveratrol is a promising natural therapeutic agent against chronic ALD.

  19. Ketamine-associated CT findings of damage in liver and gall and urinary system

    International Nuclear Information System (INIS)

    Zhang Keyun; Wang Lijuan; Wang Jiajun; Cheng Kuishan; Chen Aidi; Xu Dasheng

    2011-01-01

    Objective: To investigate the image signs of damage e in urinary system and liver and gall system and diagnostic value of CT findings in abuse of ketamine. Methods: With ethics committee approval, a retrospective analysis of 10 patients with a history of taking K powder (1 to 10 years) was done with abdominal CT scan and enhanced scan data to analysis the imaging findings of ketamine-related abdominal organ damage. Results: CT images of the 10 patients showed different degrees of reduced bladder capacity, bladder wall thickening range of 3∼14 mm. Of which the wall were thickened on both sides with the waist-shaped in 5 patients. Bilateral hydronephrosis and hydroureterosis was found in 3 cases with uniform wall thickening of both ureters. 4 cases of renal multi-lesion papillary necrosis was found, of which 2 patients showed multi-lesion ischemic changes in renal parenchyma in both kidneys. Expansion of the common bile duct appeared in 3 cases, of which 2 cases with merger intrahepatic bile duct dilation. Conclusion: CT findings of ketamine associated abdominal organ injuries in the bladder and renal may have certain characteristics. It is helpful to make diagnosis with the combination of favorable clinical data and medical history. (authors)

  20. Experimental study on liver accumulation of N-isopropyl-p-iodoamphetamine

    Energy Technology Data Exchange (ETDEWEB)

    Kosuda, Shigeru (Tokyo Metropolitan Komagome Hospital (Japan)); Kawahara, Shunji; Ishibashi, Akihiko; Tamura, Kohei; Kubo, Atsushi; Hashimoto, Shozo

    1990-06-01

    In order to clarify the mechanism of N-isopropyl-p-iodoamphetamine (IMP) liver accumulation, liver dynamic study by the portal injection of {sup 123}I-IMP and liver microautoradiography by {sup 125}I-IMP were performed using 5, 2 male rats, respectively. The initial uptake of {sup 123}I-IMP in the liver was very high and thereafter {sup 123}I-IMP showed relatively rapid wash-out (count ratio of lung to liver at 10 min after the injection was 0.12, 0.15). On the other hand, the addition of 5 mg, 8 mg ketamine hydrochloride decreased the initial {sup 123}I-IMP liver uptake and its lung accumulation was noted immediately after the injection (count ratio of lung to liver at 10 min was 0.20). Microautoradiography of the liver using {sup 125}I-IMP showed grain density in the central vein and sinusoids, but not in the liver parenchymal cell. These results suggest that non-specific amine receptor (binding site) may exist in the endothelial cell in the central vein, although the number of experimental rats in this series was small for conclusion. (author).

  1. Damage of rat liver tissue caused by repeated and sustained +Gz exposure and the mechanism thereof

    Directory of Open Access Journals (Sweden)

    Wen-bing LI

    2014-03-01

    Full Text Available Objective  To explore the mechanisms of positive acceleration (+Gz on the damage of rat liver tissue and the effect of +Gz on the expression of JNK/c-Jun in liver cells. Methods  Twenty four male Wistar rats were randomly divided into 4 groups (n=6: control, +2Gz, +6Gz and +10Gz group. With prone position, the rats in control group were fixed to the turning arm of centrifuge with head towards the axis for 5 minutes. The fixation method in +2Gz, +6Gz and +10Gz group was the same as in the control group. The increase rate of acceleration was 1G/s with a peak-time of 3 minutes, and each +Gz exposure repeated 5 times with an interval of 30 minutes. HE staining was used to observe the morphological changes of liver tissue, fluorescence real-time quantitative PCR to detect the expression of hepatic c-Jun mRNA, and Western blotting to detect the hepatic protein expression of p-c-Jun, c-Jun, p-JNK and JNK. Plasma aspartate aminotransferase (AST and alanine aminotransferase (ALT were determined. Results  The levels of serum ALT and AST increased significantly in +6Gz and, especially, the +10Gz group than in control group and +2Gz group (P<0.05. The same situation also existed in the increase of c-Jun mRNA expression (P<0.05. Hepatic c-jun and p-c-Jun (c-Jun activated form protein expression increased with the increase of G value. Compared with control group, no change was found in JNK protein expression in the other three groups, but the expression of p-JNK (activated form of JNK increased in +6Gz and +10Gz groups (P<0.05. HE staining showed the disorganized liver cells with irregular shapes, the unclear cell gap and the vacuolar changes in +6Gz and +10Gz groups. Conclusions  Repeated and sustained +Gz may cause enhanced expression of c-Jun/ p-c-Jun and p-JNK in hepatic cells. JNK/c-Jun signaling pathway may play an important role in the process of hepatic stress injury. DOI: 10.11855/j.issn.0577-7402.2014.03.15

  2. Effect of aqueous extract of Capparis spinosa on biochemical and histological changes in paracetamol–induced liver damage in rats

    Directory of Open Access Journals (Sweden)

    R. J. M. Alnuaimy

    2012-01-01

    Full Text Available This study showed that paracetamol administration to male rats at 1 g /kg of body weight for 21 days resulted in significant increase in activities of serum alanine amino transferase and aspartate amino transferase. There was an increase in the total bilirubin and creatinine levels. Paracetamol caused hepatic damage in appearance characterized with degeneration, necrosis and fatty changes in liver, as well as central vein congestion. Treatment of the damaged liver rats with 25, 50, 100, 200 mg/kg of body weight with aqueous extract of Capparis spinosa for 7, 14, 21 days led to a decrease in alanine amino transferase, aspartate amino transferase activity, total bilirubin and creatinine levels, as well as an improve in the damaged liver tissues with increasing extract concentration. The results showed that treatment of the damaged liver rats with 100, 200 mg/kg of body weight of aqueous extract of Capparis spinosa for 14, 21 days gave protection against harmful effects of paracetamol.The protective effects of this extract determined by the rebound of the enzymes and biochemical variable levels to the pretreatment levels. High doses of this extract gave a decrease in harmful effects which resulted from the paracetamol in hepatic tissues.

  3. Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo.

    Science.gov (United States)

    Zahr, Natalie M; Sullivan, Edith V; Rohlfing, Torsten; Mayer, Dirk; Collins, Amy M; Luong, Richard; Pfefferbaum, Adolf

    2016-07-01

    Serious neurological concomitants of alcoholism include Wernicke's encephalopathy (WE), Korsakoff's syndrome (KS), and hepatic encephalopathy (HE). This study was conducted in animal models to determine neuroradiological signatures associated with liver damage caused by carbon tetrachloride (CCl4), thiamine deficiency caused by pyrithiamine treatment, and nonspecific nutritional deficiency caused by food deprivation. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were used to evaluate brains of wild-type Wistar rats at baseline and following treatment. Similar to observations in ethanol (EtOH) exposure models, thiamine deficiency caused enlargement of the lateral ventricles. Liver damage was not associated with effects on cerebrospinal fluid volumes, whereas food deprivation caused modest enlargement of the cisterns. In contrast to what has repeatedly been shown in EtOH exposure models, in which levels of choline-containing compounds (Cho) measured by MRS are elevated, Cho levels in treated animals in all three experiments (i.e., liver damage, thiamine deficiency, and food deprivation) were lower than those in baseline or controls. These results add to the growing body of literature suggesting that MRS-detectable Cho is labile and can depend on a number of variables that are not often considered in human experiments. These results also suggest that reductions in Cho observed in humans with alcohol use disorder (AUD) may well be due to mild manifestations of concomitants of AUD such as liver damage or nutritional deficiencies and not necessarily to alcohol consumption per se.

  4. YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population

    DEFF Research Database (Denmark)

    Kjaergaard, Alisa D; Bojesen, Stig E; Nordestgaard, Børge G

    2014-01-01

    BACKGROUND: We tested the hypothesis that observationally and genetically increased YKL-40 concentrations are associated with alcoholic liver and pancreas damage and disease. METHODS: We performed cohort and mendelian randomization in 86,258 individuals from the Danish general population......, with measured concentrations of plasma YKL-40 (n = 21 646) and CHI3L1 rs4950928 genotype (n = 84 738). RESULTS: Increased YKL-40 was associated with increased alanine aminotransferase, bilirubin, alkaline phosphatase, γ-glutamyl transferase, erythrocyte mean corpuscular volume, C-reactive protein...... alcoholic liver disease, 4.1 (1.7-10) for alcoholic pancreatitis, and 3.4 (1.9-6.1) for any pancreatitis. CHI3L1 rs4950928 genotype explained 14% of the variation in plasma YKL-40 concentrations but was not associated with alcoholic liver and pancreas damage or disease. A doubling in YKL-40 concentrations...

  5. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease

    Science.gov (United States)

    Gentile, Christopher L.; Nivala, Angela M.; Gonzales, Jon C.; Pfaffenbach, Kyle T.; Wang, Dong; Wei, Yuren; Jiang, Hua; Orlicky, David J.; Petersen, Dennis R.; Maclean, Kenneth N.

    2011-01-01

    The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD. PMID:21957160

  6. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    Energy Technology Data Exchange (ETDEWEB)

    Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  7. Protective Effects of Pinus halepensis L. Essential Oil on Aspirin-induced Acute Liver and Kidney Damage in Female Wistar Albino Rats.

    Science.gov (United States)

    Bouzenna, Hafsia; Samout, Noura; Amani, Etaya; Mbarki, Sakhria; Tlili, Zied; Rjeibi, Ilhem; Elfeki, Abdelfattah; Talarmin, Hélène; Hfaiedh, Najla

    2016-08-01

    Aromatic and medicinal plants are sources of natural antioxidants thanks to their secondary metabolites. Administration of Pinus halepensis L. (Pinaceae family) in previous studies was found to alleviate deleterious effects of aspirin-induced damage on liver and kidney. The present study, carried out on female rats, evaluates the effects of P. halepensis L. essential oil (EOP) on aspirin (A)-induced damage to liver and kidney. The animals used in this study were rats (n=28) divided into 4 groups of 7 each: (1) a control group (C); (2) a group given NaCl for 56 days then treated with (A) (600 mg/kg) for 4 days (A); (3) a group fed with (EOP) for 56 days then (A) for 4 days; and a group fed with only (EOP) for 56 days and given NaCl for 4 days. Estimations of biochemical parameters in blood were determined using kit methods (Spinreact). Lipid peroxidation levels (TBARS), superoxide dismutase (SOD) and catalase (CAT), glutathione peroxidase (GPx) activities were determined. Histopathological study was done by immersing pieces of both organs in a fixative solution followed by paraffin embeddeding and hematoxylin-eosin staining. Under our experimental conditions, Aspirin at dose 600 mg/kg body weight induced an increase of serum biochemical parameters as well as an oxidative stress in both organs. An increase occurred in TBARS by 108% and 55%, a decrease in SOD by 78% and 53%, CAT by 53% and 78%, and GPx by 78% and 51% in liver and kidney, respectively, compared to control. Administration of EOP given to rats enabled correction in these parameters. It could be concluded that the treatment with P. halepensis L. essential oil inhibited aspirin-induced liver and kidney damage.

  8. Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats.

    Science.gov (United States)

    Karimi-Khouzani, Omid; Heidarian, Esfandiar; Amini, Sayed Asadollah

    2017-08-01

    Fluoxetine-induced liver damage is a cause of chronic liver disease. In the present study the hepatoprotective effects of gallic acid against fluoxetine-induced liver damage were examined. Forty-eight male rats were divided into six groups as follow: group 1, the control group; group 2, rats receiving fluoxetine (24mg/kg bw daily, po) without treatment; group 3, rats receiving 24mg/kg bw fluoxetine, treated with 50mg/kg bw silymarin and groups 4, 5, and 6 in which gallic acid (50, 100, and 200mg/kg bw, po, respectively) was prescribed after the consumption of fluoxetine. The histopathological changes of hepatic tissues were checked out. Fluoxetine caused a significant increase in the levels of serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT), lipid profiles, urea, fasting blood sugar (FBS), creatinine (Cr), protein carbonyl (PC) content, malondialdehyde (MDA), and liver TNF-α as an inflammatory element. Also, the obtained results of group 2 revealed a significant decline in ferric reducing ability of plasma (FRAP), liver catalase (CAT), superoxide dismutase (SOD), and vitamin C levels. The treatment with gallic acid showed significant ameliorations in abnormalities of fluoxetine-induced liver injury as represented by the improvement of hepatic CAT, SOD activities, vitamin C levels, serum biochemical parameters, and histopathological changes, in addition to the recovery of antioxidant defense system status. Gallic acid has inhibitory effects on fluoxetine-induced liver damage. The effect of gallic acid is derived from free radical scavenging properties and the anti-inflammatory effect related to TNF-α. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  9. Protective effects of total glucosides of paeony and the underlying mechanisms in carbon tetrachloride-induced experimental liver injury

    Science.gov (United States)

    Qin, Ying; Tian, Ya-ping

    2011-01-01

    Introduction We explored the protective effects of total glucosides of paeony (TGP) and the underlying mechanisms in carbon tetrachloride (CCl4)-induced experimental liver injury in mice. Material and methods Chronic liver damage was induced by intraperitoneal injection of CCl4 (0.5 µl/g) three times per week for 8 weeks. Mice also received 25, 50 or 100 mg/kg TGP. Liver sections were stained with haematoxylin/eosin. Serum amino transferases, lipid peroxidation and tumour necrosis factor-α (TNF-α) levels were determined using commercial assays. Quantitative real-time polymerase chain reaction was used to determine the changes in hepatic TNF-α, COX-2, iNOS and HO-1 expression. Protein levels of nitric oxide synthase, cyclooxygenase-2, haem oxygenase-1 and cytochrome P450 2E1 were determined by western blotting. Results Histological results showed that TGP improved the CCl4-induced changes in liver structure and alleviated lobular necrosis. The increases in serum protein and hepatic mRNA expression of TNF-α induced by CCl4 treatment were suppressed by TGP. Total glucosides of paeony also attenuated the increase the expression in iNOS and CYP2E1 but augmented the increase in HO-1.The mRNA and protein expression levels of inducible HO-1 increased significantly after CCl4 treatment. Conclusions Total glucosides of paeony protects hepatocytes from oxidative damage induced by CCl4. Total glucosides of paeony may achieve these effects by enhancing HO-1 expression and inhibiting the expression of proinflammatory mediators. PMID:22291795

  10. 6-Gingerol-Rich Fraction from Zingiber officinale Prevents Hematotoxicity and Oxidative Damage in Kidney and Liver of Rats Exposed to Carbendazim.

    Science.gov (United States)

    Salihu, Mariama; Ajayi, Babajide O; Adedara, Isaac A; Farombi, Ebenezer O

    2016-01-01

    Ginger (Zingiber officinale) is a globally marketed flavoring agent and cooking spice with a long history of human health benefits. The fungicide carbendazim (CBZ) is often detected in fruits and vegetables for human nutrition and has been reported to elicit toxic effects in different experimental animal models. The present study investigated the protective effects of 6-Gingerol-rich fraction (6-GRF) from ginger on hematotoxicity and hepatorenal damage in rats exposed to CBZ. CBZ was administered at a dose of 50 mg/kg alone or simultaneously administered with 6-GRF at 50, 100, and 200 mg/kg, whereas control rats received corn oil alone at 2 mL/kg for 14 days. Hematological examination showed that CBZ-mediated toxicity to the total white blood cell (WBC), neutrophils, lymphocytes, and platelets counts were normalized to the control values in rats cotreated with 6-GRF. Moreover, administration of CBZ significantly decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase as well as glutathione level in the livers and kidneys of rats compared with control. However, the levels of hydrogen peroxide (H2O2) and malondialdehyde were markedly elevated in kidneys and livers of CBZ-treated rats compared with control. The significant elevation in the plasma indices of renal and hepatic dysfunction in CBZ-treated rats was confirmed by light microscopy. Coadministration of 6-GRF exhibited chemoprotection against CBZ-mediated hematotoxicity, augmented antioxidant status, and prevented oxidative damage in the kidney and liver of rats.

  11. Hepatoprotective effect of collagen peptides from cod skin against liver oxidative damage in vitro and in vivo.

    Science.gov (United States)

    Han, Yantao; Xie, Jing; Gao, Hui; Xia, Yunqiu; Chen, Xuehong; Wang, Chunbo

    2015-03-01

    The objective of this study was to investigate the hepatoprotective effect of cod skin collagen peptides (CSCP), isolated from fishing industrial by-products, in vitro and in vivo. Effect of CSCP on cell proliferation of normal and H2O2-damaged Chang liver cells was determined by MTT assay in vitro. Two animal models, CCl4-induced and acetaminophenum-induced acute hepatotoxicity, were established to assess the hepatoprotective effect of CSCP. Liver weight index, serum ALT and AST, antioxidant enzymes, and lipid peroxidation product were used as the markers of liver toxicity. The cell viability in the H2O2-treated Chang liver cells was remarkably increased when pretreated with CSCP from 100 to 1,000 µg/ml in a dose-dependent manner. CSCP pretreatment also alleviated the CCL4-induced liver index loss, while no marked changes were found in acetaminophenum-treated mice. Furthermore, CSCP pulled down serum ALT and AST level, increased the activities of SOD and CAT, and decreased MDA in both murine models of acute liver toxicity. Pretreatment with CSCP protected liver tissue against oxidative injure in vivo and in vitro. The underlying mechanism might involve enhancement in the activities of antioxidant enzymes and reduction in the lipid peroxidation.

  12. Moisture damage susceptibility of asphalt mixtures: Experimental characterization and modelling

    OpenAIRE

    Varveri, A.

    2017-01-01

    A well-functioning, long-lasting and safe highway infrastructure network ensures the mobility of people and facilitates the transport of goods, promoting thus environmental, economic, and social sustainability. The development of sustainable highway infrastructure requires, among other activities, the construction of pavement systems with enhanced durability. Moisture damage in asphalt pavements is associated with inferior performance, unexpected failures and reduced service life. All of thes...

  13. Photodynamic therapy induced vascular damage: an overview of experimental PDT

    International Nuclear Information System (INIS)

    Wang, W; Moriyama, L T; Bagnato, V S

    2013-01-01

    Photodynamic therapy (PDT) has been developed as one of the most important therapeutic options in the treatment of cancer and other diseases. By resorting to the photosensitizer and light, which convert oxygen into cytotoxic reactive oxygen species (ROS), PDT will induce vascular damage and direct tumor cell killing. Another consequence of PDT is the microvascular stasis, which results in hypoxia and further produces tumor regression. To improve the treatment with PDT, three promising strategies are currently attracting much interest: (1) the combination of PDT and anti-angiogenesis agents, which more effectively prevent the proliferation of endothelial cells and the formation of new blood vessels; (2) the nanoparticle-assisted delivery of photosensitizer, which makes the photosensitizer more localized in tumor sites and thus renders minimal damage to the normal tissues; (3) the application of intravascular PDT, which can avoid the loss of energy during the transmission and expose the target area directly. Here we aim to review the important findings on vascular damage by PDT on mice. The combination of PDT with other approaches as well as its effect on cancer photomedicine are also reviewed. (review)

  14. Experimental evaluation on the damages of different drilling modes to tight sandstone reservoirs

    Directory of Open Access Journals (Sweden)

    Gao Li

    2017-07-01

    Full Text Available The damages of different drilling modes to reservoirs are different in types and degrees. In this paper, the geologic characteristics and types of such damages were analyzed. Then, based on the relationship between reservoir pressure and bottom hole flowing pressure corresponding to different drilling modes, the experimental procedures on reservoir damages in three drilling modes (e.g. gas drilling, liquid-based underbalanced drilling and overbalanced drilling were designed. Finally, damage simulation experiments were conducted on the tight sandstone reservoir cores of the Jurassic Ahe Fm in the Tarim Basin and Triassic Xujiahe Fm in the central Sichuan Basin. It is shown that the underbalanced drilling is beneficial to reservoir protection because of its less damage on reservoir permeability, but it is, to some extent, sensitive to the stress and the empirical formula of stress sensitivity coefficient is obtained; and that the overbalanced drilling has more reservoir damages due to the invasion of solid and liquid phases. After the water saturation of cores rises to the irreducible water saturation, the decline of gas logging permeability speeds up and the damage degree of water lock increases. It is concluded that the laboratory experiment results of reservoir damage are accordant with the reservoir damage characteristics in actual drilling conditions. Therefore, this method reflects accurately the reservoir damage characteristics and can be used as a new experimental evaluation method on reservoir damage in different drilling modes.

  15. Effects of seaweed-restructured pork diets enriched or not with cholesterol on rat cholesterolaemia and liver damage.

    Science.gov (United States)

    Schultz Moreira, Adriana R; García-Fernández, Rosa A; Bocanegra, Aranzazu; Méndez, M Teresa; Bastida, Sara; Benedí, Juana; Sánchez-Reus, M Isabel; Sánchez-Muniz, Francisco J

    2013-06-01

    Seaweed enriched-restructured pork (RP) is a potential functional food. However, indications of adverse effects associated with herbal medications, which include among others liver failure, toxic hepatitis, and death have been reported. Cholesterol feeding produces hepatomegalia and fat liver infiltration. The effect of seaweed-RP diet, cholesterol-enriched or not, on plasma cholesterol, liver damage markers, structure, and cytochrome CYP4A-1 were evaluated after 5 wk. Eight rat groups were fed a mix of 85% AIN-93M rodent-diet plus 15% RP. The Cholesterol-control (CC), Cholesterol-Wakame (CW), Cholesterol-Nori (CN) and Cholesterol-Sea Spaghetti (CS) groups respectively consumed similar diets to control (C), Wakame (W), Nori (N), and Sea Spaghetti (S) but as part of hypercholesterolaemic diets. CN and CS significantly blocked the hypercholesterolaemic effect observed in CC group. After 5-wk, N and S diets increased the CYP4A-1 expression. However, seaweed-RPs were unable to reduce the histological liver alterations observed in CC group. Larger and more abundant hepatocellular alterations were found in CS and CN rats suggesting that the hypocholesterolaemic effects of these seaweed-RPs seem to be a two-edged sword as they increased liver damage. Future studies are needed to understand the involved mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Protective Efficacy of Alpha-lipoic Acid against AflatoxinB1-induced Oxidative Damage in the Liver

    Directory of Open Access Journals (Sweden)

    Y. Li

    2014-06-01

    Full Text Available Alpha-lipoic acid (α-LA is not only involved in energy metabolism, but is also a powerful antioxidant that can protect against hepatic oxidative stress induced by some drugs, toxins, or under various physiological and pathophysiological conditions. Here, we investigated the effect of α-LA against liver oxidative damage in broilers exposed to aflatoxin B1 (AFB1. Birds were randomly divided into four groups and assigned different diets: basal diet, 300 mg/kg α-LA supplementation in basal diet, diet containing 74 μg/kg AFB1, and 300 mg/kg α-LA supplementation in diet containing 74 μg/kg AFB1, for 3 weeks. The results revealed that the addition of 300 mg/kg α-LA protected against the liver function damage of broilers induced by chronic low dose of AFB1 as estimated by a significant (p<0.05 change in levels of plasma total protein, albumin, alkaline phosphatase and the activities of liver glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. The histopathological analysis also showed that liver tissues were injured in the AFB1 diet, but this effect was alleviated by the addition of 300 mg/kg α-LA. Additionally, AFB1 induced a profound elevation of oxidative stress in birds, as indicated by an increase in malondialdehyde level, a decrease in glutathione peroxidase activity and a depletion of the glutathione content in the liver. All of these negative effects were inhibited by treatment with α-LA. Our results suggest that the inhibition of AFB1-induced excess production of lipid peroxides and the maintenance of intracellular antioxidant status may play important roles in the protective effects of α-LA against AFB1-induced oxidative damage in the liver.

  17. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  18. Halothane anaesthesia and liver damage A review of the literature on this and associated hazards

    CERN Document Server

    Spoor, N L

    1977-01-01

    In radiological protection the decision to use bronchopulmonary lavage, or not to use it, will occasionally rest on a comparison of risks: on the one hand the long-term radiological risk and, on the other, the short-term risks from the operation itself (after several repetitions) and from multiple exposure to the anaesthetic agents, thiopentone (or other barbiturate) and halothane. The purpose of this review was to find a numerical estimate for the risk of irreversible liver damage from multiple exposure to halothane in a healthy male aged between 20 and 60 years. The many reports which have appeared since 1970 have shown that halothane hepatitis is probably a specific, but rare, pathological condition and that the risks from halothane exposure are no greater than those from other anaesthetics. The facts suggest that there is an increased risk associated with multiple exposure. If for the average patient the mortality risk from one anaesthetic exposure to halothane is 1 in 10 sup 5 , the risk from two further...

  19. Halothane anaesthesia and liver damage: A review of the literature on this and associated hazards

    Energy Technology Data Exchange (ETDEWEB)

    Spoor, N L

    1977-09-01

    In radiological protection the decision to use bronchopulmonary lavage, or not to use it, will occasionally rest on a comparison of risks: on the one hand the long-term radiological risk and, on the other, the short-term risks from the operation itself (after several repetitions) and from multiple exposure to the anaesthetic agents, thiopentone (or other barbiturate) and halothane. The purpose of this review was to find a numerical estimate for the risk of irreversible liver damage from multiple exposure to halothane in a healthy male aged between 20 and 60 years. The many reports which have appeared since 1970 have shown that halothane hepatitis is probably a specific, but rare, pathological condition and that the risks from halothane exposure are no greater than those from other anaesthetics. The facts suggest that there is an increased risk associated with multiple exposure. If for the average patient the mortality risk from one anaesthetic exposure to halothane is 1 in 10{sup 5}, the risk from two further exposures within the following 4 weeks is nearer 1 in 10{sup 4}. Other risks associated with surgical operations have not been ignored; errors in the administration of thiopentone, for example, which increase the overall risk to a level nearer 5 in 10{sup 4}, and errors of operational diagnosis or judgement. (author)

  20. Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

    Directory of Open Access Journals (Sweden)

    Pei-Rong Wang

    2015-03-01

    Full Text Available Background/Aims: Immunologically and hemodynamically mediated the destruction of glomerular architecture is thought to be the major causes of end-stage renal failure. The purpose of this study is to evaluate the effect of glomerular hypertension on glomerular injury and the progression of glomerular sclerosis after Thy-1 nephritis was induced. Method: Thy-1 nephritis was induced in the stroke-prone spontaneously hypertensive rat strain (SHR-SP (group SP and in age-matched Wistar-Kyoto (WKY (group WKY rats, following unilateral nephrectomy (UNX, and a vehicle was injected alone in UNX SHR-SP as control (group SC. Result: The degree of glomerular damage in response to a single dose of anti-thy-1 antibody, and its functional consequences (eg. proteinuria, diminished GFR are more pronounced in group SP than normotensive group WKY and hypertensive group SC without mesangial cell injury. While normotensive group WKY rats recovered completely from mesangial cell injury on day 28-42, glomeruli in group SP kept on persistent macrophage infiltration, α-SMA expression on day 42-56. In addition, glomerular capillary repair with the GECs was rarely seen in pronouncedly proliferative and sclerostic areas. The incidence of glomerular sclerosis and the level of proteinuria were markedly increased by day 56 in the group SP. Conclusions: Our results demonstrate that glomerular hypertension aggravate glomerular damage and glomerulosclerosis in this model of Thy 1 nephritis.

  1. Brain Aquaporin-4 in Experimental Acute Liver Failure

    Science.gov (United States)

    Rama Rao, Kakulavarapu V.; Jayakumar, Arumugam R.; Tong, Xiaoying; Curtis, Kevin M.; Norenberg, Michael D.

    2016-01-01

    Intracranial hypertension due to brain edema and associated astrocyte swelling is a potentially lethal complication of acute liver failure (ALF). Mechanisms of edema formation are not well understood but elevated levels of blood and brain ammonia and its byproduct glutamine have been implicated in this process. We examined mRNA and protein expression of the water channel protein aquaporin-4 (AQP4) in cerebral cortex in a rat model of ALF induced by the hepatotoxin thioacetamide. Rats with ALF showed increased AQP4 protein in the plasma membrane (PM). Total tissue levels of AQP4 protein and mRNA levels were not altered indicating that increased AQP4 is not transcriptionally mediated but is likely due to a conformational change in the protein, i.e. a more stable anchoring of AQP4 to the PM and/or interference with its degradation. By immunohistochemistry there was an increase in AQP4 immunoreactivity in the PM of perivascular astrocytes in ALF. Rats with ALF showed increased levels of α-syntrophin, a protein involved in the anchoring of AQP4 to perivascular astrocytic end-feet. Increased AQP4 and α-syntrophin levels were inhibited by L-histidine, an inhibitor of glutamine transport into mitochondria, suggesting a role for glutamine in the increase of PM levels of AQP4. These results indicate that increased AQP4 PM levels in perivascular astrocytic end-feet are likely critical to the development of brain edema in ALF. PMID:20720509

  2. Experimental validation of a structural damage detection method based on marginal Hilbert spectrum

    Science.gov (United States)

    Banerji, Srishti; Roy, Timir B.; Sabamehr, Ardalan; Bagchi, Ashutosh

    2017-04-01

    Structural Health Monitoring (SHM) using dynamic characteristics of structures is crucial for early damage detection. Damage detection can be performed by capturing and assessing structural responses. Instrumented structures are monitored by analyzing the responses recorded by deployed sensors in the form of signals. Signal processing is an important tool for the processing of the collected data to diagnose anomalies in structural behavior. The vibration signature of the structure varies with damage. In order to attain effective damage detection, preservation of non-linear and non-stationary features of real structural responses is important. Decomposition of the signals into Intrinsic Mode Functions (IMF) by Empirical Mode Decomposition (EMD) and application of Hilbert-Huang Transform (HHT) addresses the time-varying instantaneous properties of the structural response. The energy distribution among different vibration modes of the intact and damaged structure depicted by Marginal Hilbert Spectrum (MHS) detects location and severity of the damage. The present work investigates damage detection analytically and experimentally by employing MHS. The testing of this methodology for different damage scenarios of a frame structure resulted in its accurate damage identification. The sensitivity of Hilbert Spectral Analysis (HSA) is assessed with varying frequencies and damage locations by means of calculating Damage Indices (DI) from the Hilbert spectrum curves of the undamaged and damaged structures.

  3. An experimental study on damage detection of structures using a timber beam

    International Nuclear Information System (INIS)

    Choi, Fook Choon; Li, Jianchun; Samali, Bijan; Crews, Keith

    2007-01-01

    Using vibration methods for the damage detection and structural health monitoring in bridge structures is rapidly developing. However, very little work has so far been reported on timber bridges. This paper intends to address such shortcomings by experimental investigation on a timber beam using a vibration based method to detect damage. A promising damage detection algorithm based on modal strain energy was adopted and modified to locate/evaluate damage. A laboratory investigation was conducted on a timber beam inflicted with various damage scenarios using modal tests. The modal parameters obtained from the undamaged and damaged state of the test beam were used in the computation of damage index, were then applied using a damage detection algorithm utilising modal strain energy and a statistical approach to detect location of damage. A mode shape reconstruction technique was used to enhance the capability of the damage detection algorithm with limited number of sensors. The test results and analysis show that location of damage can be accurately identified with limited sensors. The modified method is less dependent on the number of modes selected and can detect damage with a higher degree of confidence

  4. FRF-based structural damage detection of controlled buildings with podium structures: Experimental investigation

    Science.gov (United States)

    Xu, Y. L.; Huang, Q.; Zhan, S.; Su, Z. Q.; Liu, H. J.

    2014-06-01

    How to use control devices to enhance system identification and damage detection in relation to a structure that requires both vibration control and structural health monitoring is an interesting yet practical topic. In this study, the possibility of using the added stiffness provided by control devices and frequency response functions (FRFs) to detect damage in a building complex was explored experimentally. Scale models of a 12-storey main building and a 3-storey podium structure were built to represent a building complex. Given that the connection between the main building and the podium structure is most susceptible to damage, damage to the building complex was experimentally simulated by changing the connection stiffness. To simulate the added stiffness provided by a semi-active friction damper, a steel circular ring was designed and used to add the related stiffness to the building complex. By varying the connection stiffness using an eccentric wheel excitation system and by adding or not adding the circular ring, eight cases were investigated and eight sets of FRFs were measured. The experimental results were used to detect damage (changes in connection stiffness) using a recently proposed FRF-based damage detection method. The experimental results showed that the FRF-based damage detection method could satisfactorily locate and quantify damage.

  5. Experimental observation of dynamic ductile damage development under various triaxiality conditions - description of the principle

    Directory of Open Access Journals (Sweden)

    Pillon L.

    2012-08-01

    Full Text Available The Gurson model has been extended by Perrin to describe damage evolution in ductile viscoplastic materials. The so-called Gurson-Perrin model allows representing damage development with respect to strain-rate conditions. In order to fill a lack in current experimental procedures, we propose an experimental project able to test and validate the Gurson-Perrin model under various dynamic conditions and for different stress triaxiality levels.

  6. Risk of obstructive sleep apnea with daytime sleepiness is associated with liver damage in non-morbidly obese patients with nonalcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Edoardo Alessandro Pulixi

    Full Text Available BACKGROUND: A high prevalence of obstructive sleep apnea syndrome (OSAS has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD, but few studies have evaluated OSAS in non-morbidly obese NAFLD patients. AIMS: To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage. METHODS: We considered 159 consecutive patients with histological NAFLD and body mass index (BMI 1; 9/13, 69% vs. 39/146, 27%; p = 0.003. At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7-51, p = 0.005 and OR 14.0, 95% c.i. 3.5-70, p = 0.0002, respectively. CONCLUSIONS: A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.

  7. Carvacrol attenuates N-nitrosodiethylamine induced liver injury in experimental Wistar rats

    Directory of Open Access Journals (Sweden)

    Balan Rajan

    2015-06-01

    Full Text Available Carvacrol is a main constituent in the essential oils of countless aromatic plants including Origanum Vulgare and Thymus vulgari, which has been assessed for substantial pharmacological properties. In recent years, notable research has been embarked on to establish the biological actions of Carvacrol for its promising use in clinical applications. The present study is an attempt to reveal the protective role of Carvacrol against N-Nitrosodiethylamine (DEN induced hepatic injury in male Wistar albino rats. DEN is an egregious toxin, present in numerous environmental factors, which enhances chemical driven liver damage by inducing oxidative stress and cellular injury. Administration of DEN (200 mg/kg bodyweight, I.P to rats results in elevated marker enzymes (in both serum and tissue. Carvacrol (15 mg/kg body weight suppressed the elevation of marker enzymes (in both serum and tissue and augmented the antioxidants levels. The hoisted activities of Phase I enzymes and inferior activities of Phase II enzymes were observed in DEN-administered animals, whereas Carvacrol treated animals showed improved near normal activity. Histological observations also support the protective role of Carvacrol against DEN induced liver damage. Final outcome from our findings intimate that Carvacrol might be beneficial in attenuating toxin induced liver damage.

  8. Gallstone disease is associated with more severe liver damage in patients with non-alcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Anna Ludovica Fracanzani

    Full Text Available BACKGROUND: Nonalcoholic fatty liver disease (NAFLD and gallstone disease (GD are both highly prevalent in the general population and associated with obesity and insulin resistance. We aimed to evaluate the prevalence of GD in a cross sectional study of NAFLD patients and to define whether the presence of GD is associated with diabetes and predicts more severe liver disease. METHODOLOGY/PRINCIPAL FINDINGS: We merged databases of four Liver Units, comprising 524 consecutive biopsy-proven NAFLD (373 males observed between January 2003 and June 2010. GD was diagnosed in 108 (20%, and 313 cases (60% were classified by liver biopsy as nonalcoholic steatohepatitis (NASH. The GD subgroup was characterized by a significantly higher prevalence of females, prediabetes/diabetes, abdominal obesity and metabolic syndrome, older age, higher BMI, fasting glucose, HOMA-IR and lower ALT. The prevalence of GD progressively increased with advancing fibrosis and with the severity of necroinflammatory activity (p for trend  = 0.0001 and  = 0.01, respectively, without differences in the severity of steatosis. At multivariate analysis GD was associated with female gender (OR 1.37, 95% CI 1.04-1.8, age (OR 1.027, 95% CI1.003-1.05, fasting glucose (OR 1.21, 95% CI 1.10-1.33 and NASH (OR 1.40,95% CI 1.06-1.89, whereas ALT levels were associated with a lower GD risk (OR 0.98, 95% CI 0.97-0.99. When subjects with cirrhosis were excluded from analysis, the association between GD and fasting glucose, female gender, and NASH was maintained. CONCLUSION: Patients with NAFLD have a high prevalence of GD, which characterizes subjects with altered glucose regulation and more advanced liver disease.

  9. Loss of c-Met signaling sensitizes hepatocytes to lipotoxicity and induces cholestatic liver damage by aggravating oxidative stress

    International Nuclear Information System (INIS)

    Gomez-Quiroz, Luis E.; Seo, Daekwan; Lee, Yun-Han; Kitade, Mitsuteru; Gaiser, Timo; Gillen, Matthew; Lee, Seung-Bum; Gutierrez-Ruiz, Ma Concepcion; Conner, Elizabeth A.; Factor, Valentina M; Thorgeirsson, Snorri S.; Marquardt, Jens U.

    2016-01-01

    Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting. Loss of c-Met signaling amplified the extent of liver injury in MetKO mice fed with high-cholesterol diet for 30 days as evidenced by upregulation of liver enzymes and increased synthesis of total bile acids, aggravated inflammatory response and enhanced intrahepatic lipid deposition. Global transcriptomic changes confirmed the enrichment of networks involved in steatosis and cholestasis. In addition, signaling pathways related to glutathione and lipid metabolism, oxidative stress and mitochondria dysfunction were significantly affected by the loss of c-Met function. Mechanistically, exacerbation of oxidative stress in MetKO livers was corroborated by increased lipid and protein oxidation. Western blot analysis further revealed suppression of Erk, NF-kB and Nrf2 survival pathways and downstream target genes (e.g. cyclin D1, SOD1, gamma-GCS), as well as up-regulation of proapoptotic signaling (e.g. p53, caspase 3). Consistent with the observed steatotic and cholestatic phenotype, nuclear receptors RAR, RXR showed increased activation while expression levels of CAR, FXR and PPAR-alpha were decreased in MetKO. Collectively, our data provide evidence for the critical involvement of c-Met signaling in cholesterol and bile acids toxicity.

  10. Time-Dependent Damage Investigation of Rock Mass in an In Situ Experimental Tunnel

    Science.gov (United States)

    Jiang, Quan; Cui, Jie; Chen, Jing

    2012-01-01

    In underground tunnels or caverns, time-dependent deformation or failure of rock mass, such as extending cracks, gradual rock falls, etc., are a costly irritant and a major safety concern if the time-dependent damage of surrounding rock is serious. To understand the damage evolution of rock mass in underground engineering, an in situ experimental testing was carried out in a large belowground tunnel with a scale of 28.5 m in width, 21 m in height and 352 m in length. The time-dependent damage of rock mass was detected in succession by an ultrasonic wave test after excavation. The testing results showed that the time-dependent damage of rock mass could last a long time, i.e., nearly 30 days. Regression analysis of damage factors defined by wave velocity, resulted in the time-dependent evolutional damage equation of rock mass, which corresponded with logarithmic format. A damage viscoelastic-plastic model was developed to describe the exposed time-dependent deterioration of rock mass by field test, such as convergence of time-dependent damage, deterioration of elastic modules and logarithmic format of damage factor. Furthermore, the remedial measures for damaged surrounding rock were discussed based on the measured results and the conception of damage compensation, which provides new clues for underground engineering design.

  11. Quantification of complex DNA damage by ionising radiation. An experimental and theoretical approach

    International Nuclear Information System (INIS)

    Fulford, J.

    2000-05-01

    Ionising radiation potentially produces a broad spectrum of damage in DNA including single and double strand breaks (ssb and dsb) and base damages. It has been hypothesised that sites of complex damage within cellular DNA have particular biological significance due to an associated decreased efficiency in repair. The aim of this study is to gain further understanding of the formation of complex DNA damage. Irradiations of plasmid DNA illustrate that an increase in ionising density of the radiation results in a decrease in ssb yields/Gy but an increase in dsb per ssb, indicative of an increase in the number of complex damage sites per simple isolated damage site. As the mechanism for damage formation shifts from purely indirect at low scavenging capacities to a significant proportion of direct at higher scavenging capacities the proportion of complex damage increases. Comparisons with the yields of ssb and dsb simulated by Monte-Carlo calculations for Al K USX and α-particles also indicate this correspondence. The ionisation density of low energy, secondary electrons produced by photons was assessed experimentally from the dependence of the yield of OH radicals escaping intra-track recombination on photon energy. As energy decreases the OH radical yield initially decreases reflecting an increased ionisation density. However, with further decrease in photon energy the yield of OH radicals increases in line with theoretical calculations. Base damage yields were determined for low and high ionising density radiation over a range of scavenging capacities. As scavenging capacity increases the base damage: ssb ratios increases implying a contribution from electrons to base damage. It is proposed that base damage contributes to DNA damage complexity. Complex damage analysis reveals that at cell mimetic scavenging capacities, 23% and 72% of ssb have an additional spatially close damage site following γ-ray and α-particle irradiation respectively. (author)

  12. Experimental Determination of Damage Threshold Characteristics of IR Compatible Optical Materials

    International Nuclear Information System (INIS)

    Soong, Ken

    2011-01-01

    The accelerating gradient in a laser-driven dielectric accelerating structure is often limited by the laser damage threshold of the structure. For a given laser-driven dielectric accelerator design, we can maximize the accelerating gradient by choosing the best combination of the accelerator's constituent material and operating wavelength. We present here a model of the damage mechanism from ultrafast infrared pulses and compare that model with experimental measurements of the damage threshold of bulk silicon. Additionally, we present experimental measurements of a variety of candidate materials, thin films, and nanofabricated accelerating structures.

  13. Experimental study on quantitative analysis of fatty liver by computed tomography in rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Park, Choong Ki; Hahm, Chang Kok; Kim, Chung Jin [Hanyang University College of Medicine, Seoul (Korea, Republic of); Yoon, Jong Sup [Hallym College, Seoul (Korea, Republic of)

    1985-10-15

    For the study of correlation of CT number and fatty contact of the liver, total 35 rabbit were used. The rabbits were divided into one control and three experimental groups according to the amount of carbon tetrachloride, administered 1 ml, 2 ml, and 3 ml per kg of body weight respectively. The carbon tetrachloride was administered via intragastric route. CT was performed 72 hours following administration of carbon tetrachloride, and immediately prior to CT scan each rabbit was anesthetized by means of IM injection of ketamine and IV injection of succinylcholine to stop motion and respiration. CT numbers were measured and histological study for the deposition of fat in the liver tissue was done. Also biochemical analysis of lipid in the blood and in the extraction of liver tissue was performed. Comparison of CT number with biochemical and histological data was done. The result was as follows: 1. In each experimental group, the degree of accumulation of fat in the liver was proportional to the amount of carbon tetrachloride. 2. Degree of decreasing CT number was correlated with the increase in the accumulation of fat in the liver. 3. In the control and experimental (1, 2, 3) groups, when the amount of carbon tetrachloride increased, the amount of total lipid, cholesterol and triglyceride on biochemical analysis of the liver increased. Also increase in the amount of plasma lipids on biochemical analysis and great degree of increase in accumulation of fat in the liver on histological examination were seen. But no changes in the amount of phospholipid and protein on biochemical analysis of the liver were noticed. 4. Increase in the amount of total lipid could make a change in the CT number of the liver remarkably (r=-0.63). As the amount of cholesterol and triglyceride increased, the CT number of the liver decreased (r=-0.61 and r=-0.76 respectively). But there was no significant correlation between the amount of protein and phospholipid and the degree of decrease in

  14. Experimental study on quantitative analysis of fatty liver by computed tomography in rabbit

    International Nuclear Information System (INIS)

    Park, Choong Ki; Hahm, Chang Kok; Kim, Chung Jin; Yoon, Jong Sup

    1985-01-01

    For the study of correlation of CT number and fatty contact of the liver, total 35 rabbit were used. The rabbits were divided into one control and three experimental groups according to the amount of carbon tetrachloride, administered 1 ml, 2 ml, and 3 ml per kg of body weight respectively. The carbon tetrachloride was administered via intragastric route. CT was performed 72 hours following administration of carbon tetrachloride, and immediately prior to CT scan each rabbit was anesthetized by means of IM injection of ketamine and IV injection of succinylcholine to stop motion and respiration. CT numbers were measured and histological study for the deposition of fat in the liver tissue was done. Also biochemical analysis of lipid in the blood and in the extraction of liver tissue was performed. Comparison of CT number with biochemical and histological data was done. The result was as follows: 1. In each experimental group, the degree of accumulation of fat in the liver was proportional to the amount of carbon tetrachloride. 2. Degree of decreasing CT number was correlated with the increase in the accumulation of fat in the liver. 3. In the control and experimental (1, 2, 3) groups, when the amount of carbon tetrachloride increased, the amount of total lipid, cholesterol and triglyceride on biochemical analysis of the liver increased. Also increase in the amount of plasma lipids on biochemical analysis and great degree of increase in accumulation of fat in the liver on histological examination were seen. But no changes in the amount of phospholipid and protein on biochemical analysis of the liver were noticed. 4. Increase in the amount of total lipid could make a change in the CT number of the liver remarkably (r=-0.63). As the amount of cholesterol and triglyceride increased, the CT number of the liver decreased (r=-0.61 and r=-0.76 respectively). But there was no significant correlation between the amount of protein and phospholipid and the degree of decrease in

  15. Experimental investigations on chronic irradiation damage of the heart

    International Nuclear Information System (INIS)

    Lauk, S.

    1984-02-01

    Irradiation of rat hearts induced the following clinical phenomena: increasingly severe dyspnea, associated flank respiration and deterioration of the general condition bordering on a prefinal syndrome. Dissection of the sick animals and thoracal x-rays taken regularly revealed extensive pesicardial and pleural effusions. The tissue of the pericardium was thickened and edematous. The most striking histological finding consisted in a focal degeneration and destruction of the myocardium without an increase in collagenous fibres. This damage to the heart muscle was quite severe and seen in all dose groups from 15 to 40 Gy. At the same time there was a reduction of the capillary density as a function of the radiation dose. Clinical symptoms were also observed in animals irradiated with 10 Gy only. All animals irradiated with at least 20 Gy, attained a state where death was imminent. Consequently, the LD-50 must be lower than 20 Gy. The latency period was over a year at 15 Gy but decreased considerably as the dose increased. (orig.) [de

  16. Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

    Science.gov (United States)

    Zweckberger, K; Hackenberg, K; Jung, C S; Hertle, D N; Kiening, K L; Unterberg, A W; Sakowitz, O W

    2014-07-11

    Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); pbeam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in the treatment of TBI. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Cohesive Laws and Progressive Damage Analysis of Composite Bonded Joints, a Combined Numerical/Experimental Approach

    Science.gov (United States)

    Girolamo, Donato; Davila, Carlos G.; Leone, Frank A.; Lin, Shih-Yung

    2015-01-01

    The results of an experimental/numerical campaign aimed to develop progressive damage analysis (PDA) tools for predicting the strength of a composite bonded joint under tensile loads are presented. The PDA is based on continuum damage mechanics (CDM) to account for intralaminar damage, and cohesive laws to account for interlaminar and adhesive damage. The adhesive response is characterized using standard fracture specimens and digital image correlation (DIC). The displacement fields measured by DIC are used to calculate the J-integrals, from which the associated cohesive laws of the structural adhesive can be derived. A finite element model of a sandwich conventional splice joint (CSJ) under tensile loads was developed. The simulations, in agreement with experimental tests, indicate that the model is capable of predicting the interactions of damage modes that lead to the failure of the joint.

  18. Effect of Hibiscus sabdariffa extract on high fat diet–induced obesity and liver damage in hamsters

    Directory of Open Access Journals (Sweden)

    To-Wei Huang

    2015-10-01

    Full Text Available Background: Obesity is a chronic metabolic disorder associated with an increase in adipogenesis and often accompanied with fatty liver disease. Objective: In this study, we investigated the anti-obesity effects of Hibiscus sabdariffa water extract (HSE in vivo. Method: Eight-weeks-old male mice were divided into six groups (n=8 per group and were fed either normal feed, a high fat diet (HFD, HFD supplemented with different concentrations of HSE, or HFD supplemented with anthocyanin. After 10 weeks of feeding, all the blood and livers were collected for further analysis. Results: Mesocricetus auratus hamster fed with a high-fat diet developed symptoms of obesity, as determined from their body weight change and from their plasma lipid levels. Meanwhile, HSE treatment reduced fat accumulation in the livers of hamsters fed with HFD in a concentration-dependent manner. Administration of HSE reduced the levels of liver cholesterol and triglycerides, which were elevated by HFD. Analysis of the effect of HSE on paraoxonase 1, an antioxidant liver enzyme, revealed that HSE potentially regulates lipid peroxides and protects organs from oxidation-associated damage. The markers of liver damage such as serum alanine aminotransferase and aspartate aminotransferase levels that were elevated by HFD were also reduced on HSE treatment. The effects of HSE were as effective as treatment with anthocyanin; therefore the anthocyanins present in the HSE may play a crucial role in the protection established against HFD-induced obesity. Conclusions: In conclusion HSE administration constitutes an effective and viable treatment strategy against the development and consequences of obesity.

  19. Effect of Hibiscus sabdariffa extract on high fat diet–induced obesity and liver damage in hamsters

    Science.gov (United States)

    Huang, To-Wei; Chang, Chia-Ling; Kao, Erl-Shyh; Lin, Jenq-Horng

    2015-01-01

    Background Obesity is a chronic metabolic disorder associated with an increase in adipogenesis and often accompanied with fatty liver disease. Objective In this study, we investigated the anti-obesity effects of Hibiscus sabdariffa water extract (HSE) in vivo. Method Eight-weeks-old male mice were divided into six groups (n=8 per group) and were fed either normal feed, a high fat diet (HFD), HFD supplemented with different concentrations of HSE, or HFD supplemented with anthocyanin. After 10 weeks of feeding, all the blood and livers were collected for further analysis. Results Mesocricetus auratus hamster fed with a high-fat diet developed symptoms of obesity, as determined from their body weight change and from their plasma lipid levels. Meanwhile, HSE treatment reduced fat accumulation in the livers of hamsters fed with HFD in a concentration-dependent manner. Administration of HSE reduced the levels of liver cholesterol and triglycerides, which were elevated by HFD. Analysis of the effect of HSE on paraoxonase 1, an antioxidant liver enzyme, revealed that HSE potentially regulates lipid peroxides and protects organs from oxidation-associated damage. The markers of liver damage such as serum alanine aminotransferase and aspartate aminotransferase levels that were elevated by HFD were also reduced on HSE treatment. The effects of HSE were as effective as treatment with anthocyanin; therefore the anthocyanins present in the HSE may play a crucial role in the protection established against HFD-induced obesity. Conclusions In conclusion HSE administration constitutes an effective and viable treatment strategy against the development and consequences of obesity. PMID:26475512

  20. Possible role of Arthrospira platensis in reversing oxidative stress-mediated liver damage in rats exposed to lead.

    Science.gov (United States)

    Khalil, Samah R; Elhady, Walaa M; Elewa, Yaser H A; Abd El-Hameed, Noura E; Ali, Sozan A

    2018-01-01

    Environmental pollutants, particularly metallic elements, mobilized and released into the environment, eventually accumulate in the food chain and thus pose a serious threat to human and animal health. In the present study, the role of Arthrospira (Spirulina platensis; SP) as a protector against oxidative stress-mediated liver damage induced by an exposure to lead acetate (LA; as a metallic pollutant) was assessed. To achieve this aim, rats were orally administered with 300 mg/kg bw SP for 15 days, before and concurrently with an intraperitoneal injection of 50 mg/kg bw LA (6 injections throughout 15 days). As a result, co-administration of SP with LA reduced the amount of lead that accumulated in both blood and liver tissue of the exposed rats and minimized the increased levels of lipid peroxidation, protein oxidation, DNA oxidative damage, and liver enzyme endpoints. In addition, because of SP administration, the levels of depleted biomarkers of antioxidant status and total antioxidant capacity in LA-exposed rats improved. Moreover, SP protected the liver tissue against the changes caused by LA exposure and also decreased the reactivity of HSP70 in the cytoplasm of hepatocytes. Collectively, our data suggest that SP has a potential use as a food supplement in the regions highly polluted with heavy metals such as lead. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

    Science.gov (United States)

    2013-01-01

    Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 2013. These rules will create an urgent need for optimized standard operating procedures regarding animal experimentation and improved international communication in the liver fibrosis community. This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation. We discuss potential complications in experimental liver fibrosis and provide examples of how the findings of studies in which these models are used can be translated to human disease and therapy. In this review, we want to motivate the international community to design more standardized animal models which might help to address the legally requested replacement, refinement and reduction of animals in fibrosis research. PMID:24274743

  2. The protective effect of Moringa oleifera leaf extract on liver damage in mice infected with Plasmodium berghei ANKA

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    Kittiyaporn Dondee

    2016-09-01

    Full Text Available Objective: To investigate the protective effect of Moringa oleifera leaf extract on liver damage in mice infected with Plasmodium berghei ANKA (P. berghei Methods: For extraction of Moringa oleifera (M. oleifera leaves, microwave with hot water method was used and acute toxicity study was then be done. Standard Peters’ test was carried out to test the efficacy of M. oleifera extract in vivo. The ICR mice were inoculated with 1 × 107 red blood cells infected with P. berghei strain by intraperitoneal injection. They were subsequently given with 100, 500 and 1000 mg/kg of this extract by intragastric route once a day for 4 consecutive days. Parasitemia was estimated using microscopy and levels of aspartate aminotransferase, alanine aminotransferase and albumin were also measured. Results: The M. oleifera leaf extract showed the protective activity on liver damage in mice infected with P. berghei in a dose-dependent fashion. It can be indicated by normal levels of aspartate aminotransferase, alanine aminotransferase and albumin in mice treated with extract. The 1000 mg/kg of extract was observed to present the highest activity. Interestingly, the dosedependent antimalarial activity was also found in the mice treated with extract. Conclusions: The M. oleifera leaf extract presented protective effect on liver damage in mice infected with P. berghei.

  3. Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease.

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    Salvatore Petta

    Full Text Available We assessed whether obstructive sleep apnea (OSA and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes.Consecutive patients (n = 126 with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50, OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defined as a focal thickening >1.3 mm.Prevalence of high OSA risk was similar in patients refusing or accepting PG (76% vs 68%, p = 0.17. Among those accepting PG, overall OSA prevalence was significantly higher in patients with F2-F4 fibrosis compared to those without (72% vs 44%; p = 0.04. Significant fibrosis was independently associated with mean nocturnal oxygen saturation (SaO21 (OR 6.30, 95%C.I. 1.02-12.3; p = 0.01.In NAFLD patients with chronically elevated ALT at low prevalence of morbid obesity, OSA was highly prevalent and indexes of SaO2 resulted independently associated with severity of liver fibrosis and carotid atherosclerosis. These data suggest to consider sleep disordered breathing as a potential additional therapeutic target in severe NAFLD patients.

  4. Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Petta, Salvatore; Marrone, Oreste; Torres, Daniele; Buttacavoli, Maria; Cammà, Calogero; Di Marco, Vito; Licata, Anna; Lo Bue, Anna; Parrinello, Gaspare; Pinto, Antonio; Salvaggio, Adriana; Tuttolomondo, Antonino; Craxì, Antonio; Bonsignore, Maria Rosaria

    2015-01-01

    We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes. Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defined as a focal thickening >1.3 mm. Prevalence of high OSA risk was similar in patients refusing or accepting PG (76% vs 68%, p = 0.17). Among those accepting PG, overall OSA prevalence was significantly higher in patients with F2-F4 fibrosis compared to those without (72% vs 44%; p = 0.04). Significant fibrosis was independently associated with mean nocturnal oxygen saturation (SaO2)1 (OR 6.30, 95%C.I. 1.02-12.3; p = 0.01). In NAFLD patients with chronically elevated ALT at low prevalence of morbid obesity, OSA was highly prevalent and indexes of SaO2 resulted independently associated with severity of liver fibrosis and carotid atherosclerosis. These data suggest to consider sleep disordered breathing as a potential additional therapeutic target in severe NAFLD patients.

  5. Influence of experimental conditions on data variability in the liver comet assay.

    Science.gov (United States)

    Guérard, M; Marchand, C; Plappert-Helbig, U

    2014-03-01

    The in vivo comet assay has increasingly been used for regulatory genotoxicity testing in recent years. While it has been demonstrated that the experimental execution of the assay, for example, electrophoresis or scoring, can have a strong impact on the results; little is known on how initial steps, that is, from tissue sampling during necropsy up to slide preparation, can influence the comet assay results. Therefore, we investigated which of the multitude of steps in processing the liver for the comet assay are most critical. All together eight parameters were assessed by using liver samples of untreated animals. In addition, two of those parameters (temperature and storage time of liver before embedding into agarose) were further investigated in animals given a single oral dose of ethyl methanesulfonate at dose levels of 50, 100, and 200 mg/kg, 3 hr prior to necropsy. The results showed that sample cooling emerged as the predominant influence factor, whereas variations in other elements of the procedure (e.g., size of the liver piece sampled, time needed to process the liver tissue post-mortem, agarose temperature, or time of lysis) seem to be of little relevance. Storing of liver samples of up to 6 hr under cooled conditions did not cause an increase in tail intensity. In contrast, storing the tissue at room temperature, resulted in a considerable time-dependent increase in comet parameters. Copyright © 2013 Wiley Periodicals, Inc.

  6. Selective segmental sclerotherapy of the liver by transportal absolute ethanol injection: an animal experimental study

    International Nuclear Information System (INIS)

    Pan Jie; Yang Ning; Zhang Zhongzhong; Hu Libin; Chen Jie; Wu Wei; Jin Zhengyu; Liu Wei

    2003-01-01

    Objective: To evaluate the safety and efficacy of selective segmental sclerotherapy (SSS) of the liver by transportal absolute ethanol injection with an animal experimental study, and to discuss several technical points involved in this method. Methods: Thirty dogs received SSS of the liver by transportal absolute ethanol injection with the injection dose of 0.2-1.0 ml/kg, repeated examinations of blood ethanol level, WBC, and liver functions were done, and CT and pathological examinations of the liver were performed. Results: All dogs treated with SSS survived during the study. The maximum elevation of blood ethanol values occurred in group F. Its average value was (1.603 ± 0.083) mg/ml, which was much lower than that of death level. Transient elevations of blood WBC and ALT were seen. The average values of WBC and ALT were (46.36 ± 7.28) x 10 9 and (827.36 ± 147.25) U/L, respectively. CT and pathological examinations proved that the dogs given SSS by transportal absolute ethanol injection with the injection dose of 0.3-1.0 ml/kg had a complete wedge-shaped necrosis in the liver. Conclusion: Selective segmental sclerotherapy of the liver by transportal ethanol injection was quite safe and effective if the proper dose of ethanol was injected. SSS may be useful in the treatment of HCC

  7. Angiotensin converting enzyme (ACE) gene expression in experimentally induced liver cirrhosis in rats.

    Science.gov (United States)

    Shahid, Syed Muhammad; Fatima, Syeda Nuzhat; Mahboob, Tabassum

    2013-09-01

    Angiotensin converting enzyme (ACE) is a key player of Renin Angiotensin System (RAS), involved in conversion of active product, angiotensin-II. Alterations in RAS have been implicated in the pathophysiology of various diseases involving heart, kidney, lung and liver. This study is designed to investigate the association of ACE gene expression in induction of liver cirrhosis in rats. Total 12 male albino Wistar rats were selected and divided in two groups. Control group received 0.9% NaCl, where as Test group received thioacidamide (TAA), dissolved in 0.9%NaCl, injected intraperitoneally at a dosage of 200mg/Kg of body weight, twice a week for 12 weeks. The rats were decapitated and blood sample was collected at the end of experimental period and used for liver functions, enzyme activity, antioxidant enzymes and lipid peroxidation estimations. Genomic DNA was isolated from excised tissue determine the ACE genotypes using specific primers. The ACE gene expression in liver tissue was assessed using the quantitative RT-PCR method. The activity of ALT, total and direct bilirubin, SOD and CAT levels were significantly high (pACE gene expression after 12 weeks TAA treatment in cirrhotic rats was significantly increased (pACE gene expression. The finding of major up-regulation of ACE in the experimental rat liver provides further insight into the complexities of the RAS and its regulation in liver injury. The development of specific modulators of ACE activity and function, in future, will help determine the role of ACE and its genetic variants in the pathophysiology of liver disease.

  8. The inverse relationship between bladder and liver in 4-aminobiphenyl-induced DNA damage

    Science.gov (United States)

    Stablewski, Aimee B.; Vouros, Paul; Zhang, Yuesheng

    2015-01-01

    Bladder cancer risk is significantly higher in men than in women. 4-Aminobiphenyl (ABP) is a major human bladder carcinogen from tobacco smoke and other sources. In mice, male bladder is more susceptible to ABP-induced carcinogenesis than female bladder, but ABP is more carcinogenic in the livers of female mice than of male mice. Here, we show that castration causes male mice to acquire female phenotype regarding susceptibility of bladder and liver to ABP. However, spaying has little impact on organ susceptibility to ABP. Liver UDP-glucuronosyltransferases (UGTs) are believed to protect liver against but sensitize bladder to ABP, as glucuronidation of ABP and its metabolites generally reduces their toxicity and promotes their elimination via urine, but the metabolites are labile in urine, delivering carcinogenic species to the bladder. Indeed, liver expression of ABP-metabolizing human UGT1A3 transgene in mice increases bladder susceptibility to ABP. However, ABP-specific liver UGT activity is significantly higher in wild-type female mice than in their male counterparts, and castration also significantly increases ABP-specific UGT activity in the liver. Taken together, our data suggest that androgen increases bladder susceptibility to ABP via liver, likely by modulating an ABP-metabolizing liver enzyme, but exclude UGT as an important mediator. PMID:25596734

  9. Improved clinicopathologic assessments of acute liver damage due to trauma in Indian ring-necked parakeets (Psittacula krameri manillensis).

    Science.gov (United States)

    Williams, Susan M; Holthaus, Lisa; Barron, Heather Wilson; Divers, Stephen J; McBride, Michael; Almy, Frederic; Bush, Sharon; Latimer, Kenneth S

    2012-06-01

    Increased activities of certain biochemical enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], alkaline phosphatase [ALP]) have been associated with blunt liver injury in many species. To evaluate changes in plasma hepatic biochemical parameters in acute avian liver disease caused by trauma and to compare biochemical changes with histologic lesions in hepatic parenchyma, 30 healthy fasted Indian ring-necked parakeets (Psittacula krameri manillensis) were divided into 2 groups, and traumatic liver injury was caused by endoscopic liver biopsy (group 1) or by liver biopsy and crushing injury to the hepatic parenchyma with endoscopic forceps (group 2) in anesthetized birds. Blood samples were collected at baseline and at 12, 24, 36, 48, 60, 72, 84, 96, 108, and 120 hours in alternate groups to compare analyte values after injury with those at baseline. Results showed consistently decreased plasma ALP activity (excluding 1 time point) throughout the study, which was thought to be associated with isoflurane administration. Plasma glutamate dehydrogenase activity initially increased but rapidly declined thereafter and was attributed to acute focal hepatocellular injury. In both groups, increases in plasma AST, ALT, and LDH activities was most likely caused by muscle injury because creatine kinase activity was concurrently increased. Compared with baseline values, bile acid concentration and y-glutamyl transferase activity were not affected by liver biopsy or crush injury. Plasma sorbitol dehydrogenase activity was the most specific indicator of liver injury in both groups. Histologic changes correlated poorly with biochemical results, possibly because the small area of hepatic parenchyma that was damaged did not affect enzyme values substantially.

  10. Biochemically Investigation of the Effects of Nettle Seed Herbal Mixture on Alcohol Damaged Liver

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    A. ÇELİK

    2014-06-01

    Full Text Available It was experimentally investigated in this research how protective Nettle Seed Herbal Mixture is against ethanol which causes oxidative stress in rats and causes toxic effects in the liver with chronic use. 20 4-month-old female Wistar male rats were used in the study. All rats in the study were fed with normal pellet Mouse food during the experiment. 10 week application was done by dividing the rats into four equal groups. Application method is orally drinking method. First group is the control group. The second group is the alcohol group. This group was given 30% ethanol in order to cause chronic alcoholisms. The third group was the alcohol+ Nettle Seed Herbal Mixture group and the rats in this group were given liquid, which was 30% ethanol,+ Nettle Seed Herbal Mixture extract. Fourth group was Nettle Seed Herbal Mixture extract group and the rats in this group were given liquid, which was Nettle Seed Herbal Mixture extract. At the end of ten weeks, within the first 24 hours, blood species were obtained from the animals under anesthesia using appropriate techniques. Serum ALT and AST values of the obtained blood samples were studied by enzymatic methods in "Roche Cobas 6000" device.. Biochemically ALT and AST enzyme values and statistical analysis with SPSS programe were done. No significant difference was found between these four groups at the end of the analysis because p value was bigger than 0,005.

  11. Experimental verifications of a structural damage identification technique using reduced order finite-element model

    Science.gov (United States)

    Li, Rui; Zhou, Li; Yang, Jann N.

    2010-04-01

    An objective of the structural health monitoring system is to identify the state of the structure and to detect the damage when it occurs. Analysis techniques for the damage identification of structures, based on vibration data measured from sensors, have received considerable attention. Recently, a new damage tracking technique, referred to as the adaptive quadratic sum-square error (AQSSE) technique, has been proposed, and simulation studies demonstrated that the AQSSE technique is quite effective in identifying structural damages. In this paper, the adaptive quadratic sumsquare error (AQSSE) along with the reduced-order finite-element method is proposed to identify the damages of complex structures. Experimental tests were conducted to verify the capability of the proposed damage detection approach. A series of experimental tests were performed using a scaled cantilever beam subject to the white noise and sinusoidal excitations. The capability of the proposed reduced-order finite-element based adaptive quadratic sum-square error (AQSSE) method in detecting the structural damage is demonstrated by the experimental results.

  12. Protective effect of lycopene on whole body irradiation induced liver damage of Swiss albino mice: pathological evaluation

    International Nuclear Information System (INIS)

    Marimuthu, Srinivasan; Menon, Venugopal Padmanabhan

    2013-01-01

    The present study was aimed to evaluate the radioprotective efficacy of lycopene, a naturally occurring dietary carotenoid on whole body radiation-induced liver damage of Swiss albino mice. The first phase of the study was carried out to fix the effective concentration of Iycopene by performing a 30 days survival studies using different graded doses (10, 20, 40 and 80 mg/kg body weight) of lycopene administered orally to mice via intragastric intubations for seven consecutive days prior to exposure of whole body radiation (10 Gy). Based on the results of survival studies, the effective dose of Iycopene was fixed which was then administered to mice orally via intragastric intubations for seven consecutive days prior to exposure of whole body radiation (4 Gy) to evaluate its radioprotective efficacy by performing various biochemical assays in the liver of Swiss albino mice. The results indicated that radiation-induced decrease in the activities of endogenous antioxidant enzymes and increase in lipid peroxidative index, DNA damage and comet assays were altered by pre-administration with the effective dose of Iycopene (20 mg/kg body weight) which restored the antioxidant status to near normal and decreased the levels of lipid peroxidative index, DNA damage and comet assays.These results were further confirmed by histopathological examinations which indicated that pre-administration with the effective dose of Iycopene reduced the hepatic damage induced by radiation. (author)

  13. Daño hepático y enfermedad celíaca Liver damage and celiac disease

    Directory of Open Access Journals (Sweden)

    M. D. Cantarero Vallejo

    2007-11-01

    Full Text Available La enfermedad celiaca (EC es una causa importante de elevación de transaminasas: entre un 5 y un 10% de los pacientes con elevación crónica, criptogénica, de las transaminasas presentan EC y, al contrario, la EC puede estar asociada a diferentes enfermedades hepáticas. En efecto, un amplio abanico de patología hepática puede asociarse a EC, tanto en niños como en adultos, que pueden resumirse en: a daño hepático mínimo caracterizado por la ausencia de síntomas o signos clínicos asociables a una enfermedad hepática crónica y con cambios histológicos no específicos que desaparecen después de la introducción de una dieta sin gluten; b hepatopatías de etiología autoinmune, incluyendo la hepatitis autoinmune, la colangitis esclerosante primaria y la cirrosis biliar primaria, en las que la respectiva evolución no está influenciada por la introducción de dieta sin gluten; y c insuficiencia hepática grave y cirrosis hepática criptogénica descompensada, potencialmente tratables con la dieta sin gluten. Todas estas patologías están condicionadas por diferentes factores individuales y por una predisposición genética. La progresión y la reversibilidad del daño hepático en los diferentes cuadros patológicos, pueden estar condicionadas por la exposición al gluten y la edad, precoz o tardía, en la cual ha sido introducido en la dieta. Hay suficiente evidencia clínica para recomendar un atento cribado cruzado tanto para el diagnóstico del daño hepático asintomático en los pacientes con EC como para el diagnóstico de la EC en los pacientes con daño hepático criptogénico.Celiac disease (CD is an important cause of serum aminotransferase elevation: between 5 and 10% of patients with persistent and cryptogenetic transaminase elevation may have CD. In fact, a wide spectrum of liver injuries in children and adults may be related to CD, particularly: a mild parenchymal damage characterized by absence of any clinical signs

  14. Liver Damage Risk Assessment Study in Workers Occupationally Exposed to E-waste in Benin City, South-South Nigeria

    Directory of Open Access Journals (Sweden)

    Osaretin God Igaro Igaro

    2015-07-01

    Full Text Available    Large volumes of mostly irreparable electronic waste (e-waste are shipped to Africa on a monthly basis, of which Nigeria receives the largest share. E-waste management practices in Nigeria have remained completely primitive until date; and e-waste workers have little or no occupational safety knowledge and devices. The thousands of chemicals in e-waste have been reported to be toxic to human health in any degree of exposure. The present study has assessed the risk of liver damage in workers occupationally exposed to e-waste in Benin City, South-south Nigeria in 2014. Serum activities of liver enzymes [alanine aminotransferase (ALT, aspartate aminotransferase (AST, gamma glutamyltransferase (GGT and alkaline phosphatase (ALP]; and levels albumin (ALB, total bilirubin (T/Bil and conjugated bilirubin (C/Bil were determined using standard colorimetric methods. Serum Alpha fetoprotein (AFP was determined using ELISA in Nigerian e-waste workers (n=63 and in age-matched unexposed participants (n=41 in Benin City. The results showed significantly raised activities of enzymatic biomarkers of liver damage (ALT, AST, ALP and GGT in the e-waste group compared with the unexposed participants. There was no significant difference in the levels of ALB, T/Bil and C/Bil between exposed and unexposed participants. AFP levels in e-waste workers (3.56 ± 0.34 ng/mL were significantly different compared with the unexposed group (2.14 ± 0.80 ng/mL (P< 0.045. The significantly elevated cancer risk biomarker (AFP and the enzymatic biomarkers of liver damage observed in the Nigerian e-waste workers studied may be associated with occupational exposure to known carcinogens and hepatotoxic metals in e-waste. 

  15. Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage

    NARCIS (Netherlands)

    Gonzalez Ponce, Herson Antonio; Consolacion Martinez-Saldana, Maria; Rosa Rincon-Sanchez, Ana; Teresa Sumaya-Martinez, Maria; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han; Jaramillo-Juarez, Fernando

    2016-01-01

    Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-L-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients

  16. Experimental and Modelling Investigations of the Coupled Elastoplastic Damage of a Quasi-brittle Rock

    Science.gov (United States)

    Zhang, Jiu-Chang

    2018-02-01

    Triaxial compression tests are conducted on a quasi-brittle rock, limestone. The analyses show that elastoplastic deformation is coupled with damage. Based on the experimental investigation, a coupled elastoplastic damage model is developed within the framework of irreversible thermodynamics. The coupling effects between the plastic and damage dissipations are described by introducing an isotropic damage variable into the elastic stiffness and yield criterion. The novelty of the model is in the description of the thermodynamic force associated with damage, which is formulated as a state function of both elastic and plastic strain energies. The latter gives a full consideration on the comprehensive effects of plastic strain and stress changing processes in rock material on the development of damage. The damage criterion and potential are constructed to determine the onset and evolution of damage variable. The return mapping algorithms of the coupled model are deduced for three different inelastic corrections. Comparisons between test data and numerical simulations show that the coupled elastoplastic damage model is capable of describing the main mechanical behaviours of the quasi-brittle rock.

  17. Peroxynitrite and Peroxiredoxin in the Pathogenesis of Experimental Amebic Liver Abscess

    Directory of Open Access Journals (Sweden)

    Judith Pacheco-Yepez

    2014-01-01

    Full Text Available The molecular mechanisms by which Entamoeba histolytica causes amebic liver abscess (ALA are still not fully understood. Amebic mechanisms of adherence and cytotoxic activity are pivotal for amebic survival but apparently do not directly cause liver abscess. Abundant evidence indicates that chronic inflammation (resulting from an inadequate immune response is probably the main cause of ALA. Reports referring to inflammatory mechanisms of liver damage mention a repertoire of toxic molecules by the immune response (especially nitric oxide and reactive oxygen intermediates and cytotoxic substances released by neutrophils and macrophages after being lysed by amoebas (e.g., defensins, complement, and proteases. Nevertheless, recent evidence downplays these mechanisms in abscess formation and emphasizes the importance of peroxynitrite (ONOO−. It seems that the defense mechanism of amoebas against ONOO−, namely, the amebic thioredoxin system (including peroxiredoxin, is superior to that of mammals. The aim of the present text is to define the importance of ONOO− as the main agent of liver abscess formation during amebic invasion, and to explain the superior capacity of amoebas to defend themselves against this toxic agent through the peroxiredoxin and thioredoxin system.

  18. Proof-of-concept experimental study of damage detection of concrete piles using embedded piezoceramic transducers

    International Nuclear Information System (INIS)

    Wang, R L; Gu, H; Song, G; Mo, Y L

    2013-01-01

    This paper presents a proof-of-concept experimental study of an innovative active-sensing approach for damage detection of concrete piles by using embedded piezoceramic transducers. In the proposed active-sensing approach, one piezoceramic transducer is used as an actuator to generate a stress wave to propagate through the concrete pile and the other distributed piezoceramic transducers are used as sensors to detect the wave response. Cracks or damage inside the concrete structure act as stress relief in the wave propagation path. The amplitude of the wave and the transmission energy will decrease due to the existence of cracks or damage. Experiments were performed on two bored piles instrumented with embedded piezoceramic transducers. The experimental results demonstrate the effectiveness of the proposed approach for pile damage detection. (fast track communication)

  19. Isolated Liver Perfusion Using Percutaneous Methods:[ql An Experimental Study in the Pig

    International Nuclear Information System (INIS)

    Harnek, Jan; Cwikiel, Wojciech; Bergqvist, Lennart; Persson, Bo; Stridbeck, Hans

    1996-01-01

    Purpose: To develop a method for isolated perfusion of the liver using radiological methods. Methods: Twenty-one pigs, weighing about 20 kg, were divided into three groups. By transjugular and transfemoral approaches two occlusion balloons were placed in the inferior vena cava cranial and caudal, respectively, to the origin of the hepatic veins. One occlusion balloon was placed transfemorally in the common hepatic artery. Another occlusion balloon was inserted in the main branch of the portal vein via the transjugular-transhepatic approach in 11 pigs (groups 1 and 2), and in 10 pigs (group 3) by a percutaneous transhepatic route. After inflation of the balloons, patency of the isolated liver circulation was evaluated by recirculation of 99 Tc m -labelled human albumin during 30 min. Blood tests were obtained after 1, 3, 5, 10, 15, and 30 min to evaluate leakage from the liver to the systemic circulation. Results: Increasing leakage to the systemic circulation from the isolated liver circulation was observed in groups 1 and 2. In the third group the leakage was less than 10%. Conclusion: In an experimental animal model, isolated perfusion of the liver with minor leakage to the systemic circulation may be achieved using radiological methods

  20. Laser-induced damage in dielectrics with nanosecond to subpicosecond pulses. I. Experimental. Part 1

    International Nuclear Information System (INIS)

    Stuart, B.C.; Herman, S.; Perry, M.D.

    1994-12-01

    The authors report extensive laser-induced damage threshold measurements on pure and multilayer dielectrics at 1053 and 526 mm for pulse durations, τ, ranging from 140 fs to 1 ns. Qualitative differences in the morphology of damage and a departure from the diffusion-dominated τ 1/2 scaling indicate that damage results from plasma formation and ablation for τ≤10 ps and from conventional melting and boiling for τ>50 ps. A theoretical model based on electron production via multiphoton ionization, Joule heating, and collisional (avalanche) ionization is in good agreement with both the pulsewidth and wavelength scaling of experimental results

  1. Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway

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    Miao Long

    2016-10-01

    Full Text Available Lead is harmful for human health and animals. Proanthocyanidins (PCs, a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER stress-related genes and protein (GRP78 and CHOP. Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress

  2. Full experimental modelling of a liver tissue mimicking phantom for medical ultrasound studies employing different hydrogels.

    Science.gov (United States)

    Casciaro, Sergio; Conversano, Francesco; Musio, Stefano; Casciaro, Ernesto; Demitri, Christian; Sannino, Alessandro

    2009-04-01

    Tissue mimicking phantoms have been widely reported to be an important tool for development, optimisation and performance testing of ultrasound-based diagnostic techniques. In particular, modern applications of tissue mimicking phantoms often include characterisation of the nonlinear behaviour of experimental ultrasound contrast agents. In such cases, the tissue-mimicking materials should be chosen not only based on the values of their density, speed of sound and attenuation coefficient, but also considering their effect on the appearance of "native harmonics" due to nonlinear distortion of ultrasound signal during propagation. In a previous paper it was demonstrated that a cellulose-based hydrogel is suitable to simulate nonlinear acoustical behaviour of liver tissue for thicknesses up to 8 cm. In this paper we present the experimental characterisation of the nonlinear acoustical behaviour of a different polyethylene glycol diacrylate (PEGDA)-based hydrogel, in order to assess whether and how it can improve the performances and overcome some limitations of the cellulose-based hydrogel as liver tissue-mimicking material. Samples of pig liver tissue, cellulose-based hydrogel and PEGDA-based hydrogel were insonified in a through-transmission set-up, employing 2.25-MHz pulses with different mechanical index (MI) values. Second harmonic and first harmonic amplitudes were extracted from the spectra of received signals and their difference was then used to compare sample behaviours. Obtained results show how a new more accurate and combined experimental model of linear and nonlinear acoustical behaviour of liver tissue is feasible. In fact, a further confirmation of the cellulose-based hydrogel effectiveness to precisely simulate the liver tissue for penetration depths up to 8 cm was provided, and it was also shown that the employment of the PEGDA-based hydrogel can extend the range of useful tissue-mimicking material thicknesses up to 11 cm, moreover allowing a

  3. Liver and Cardiovascular Damage in Patients With Lean Nonalcoholic Fatty Liver Disease, and Association With Visceral Obesity.

    Science.gov (United States)

    Fracanzani, Anna Ludovica; Petta, Salvatore; Lombardi, Rosa; Pisano, Giuseppina; Russello, Maurizio; Consonni, Dario; Di Marco, Vito; Cammà, Calogero; Mensi, Laura; Dongiovanni, Paola; Valenti, Luca; Craxì, Antonio; Fargion, Silvia

    2017-10-01

    Lean nonalcoholic fatty liver disease (NAFLD) is defined as NAFLD that develops in patients with a body mass index (BMI) less than 25 kg/m 2 . We investigated the differences between lean NAFLD and NAFLD in overweight and obese persons, factors associated with the severity of liver and cardiovascular disease, and the effects of visceral obesity. We performed a retrospective cohort study of 669 consecutive patients with biopsy-proven NAFLD seen at 3 liver centers in Italy. We collected anthropometric, clinical, and biochemical data, as well as information on carotid atherosclerosis (artery intima-media thickness and plaque), liver histology (nonalcoholic steatohepatitis [NASH] and fibrosis), insulin resistance, and diabetes. Overweight was defined as a BMI of 25 to 29.9 kg/m 2 , and obese was defined as a BMI of 30 kg/m 2 or greater. Patients were assigned to groups based on waist circumference, a marker of visceral obesity (low: men, 102 cm, women >88 cm). DNA samples were analyzed for the rs738409 C>G (I148M in PNPLA3), the rs58542926 C>T (E167K in TM6SF2), and single-nucleotide polymorphisms. Variables in men and women were analyzed using chi-squared analysis and the Mann-Whitney or Kruskal-Wallis tests. Multiple linear or logistic regression analyses were adjusted for all the variables of clinical relevance or statistically significant at univariate analyses. The primary outcome was the difference in liver and cardiovascular disease between lean NAFLD and NAFLD in overweight and obese persons. Secondary outcomes were effects of visceral obesity, based on waist circumference, on hepatic, vascular, and metabolic features. Significantly lower proportions of patients with lean NAFLD (143 patients; 43 women; mean age, 46 ± 13 y) had hypertension (P = .001), diabetes (P = .0001), and metabolic syndrome (P = .0001) than overweight or obese patients with NAFLD (526 patients; 149 women; mean age, 49 ± 12 y). Significantly lower proportions of patients with lean

  4. Chondroitin Sulfate-Rich Extract of Skate Cartilage Attenuates Lipopolysaccharide-Induced Liver Damage in Mice.

    Science.gov (United States)

    Song, Yeong Ok; Kim, Mijeong; Woo, Minji; Baek, Jang-Mi; Kang, Keon-Hee; Kim, Sang-Ho; Roh, Seong-Soo; Park, Chan Hum; Jeong, Kap-Seop; Noh, Jeong-Sook

    2017-06-15

    The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body weight (BW) of CS or 400 mg/kg BW of CSE for 3 consecutive days, followed by a one-time intraperitoneal injection of LPS (20 mg/kg BW). The experimental groups were vehicle treatment without LPS injection (NC group), vehicle treatment with LPS injection (LPS group), CS pretreatment with LPS injection (CS group), and CSE pretreatment with LPS injection (CSE group). Hepatic antioxidant enzyme expression levels in the CS and CSE groups were increased relative to those in the LPS group. In LPS-insulted hepatic tissue, inflammatory factors were augmented relative to those in the NC group, but were significantly suppressed by pretreatment with CS or CSE. Moreover, CS and CSE alleviated the LPS-induced apoptotic factors and mitogen-activated protein kinase (MAPK). In addition, CS and CSE effectively decreased the serum lipid concentrations and downregulated hepatic sterol regulatory element-binding proteins expression. In conclusion, the skate CSE could protect against LPS-induced hepatic dyslipidemia, oxidative stress, inflammation, and apoptosis, probably through the regulation of MAPK signaling.

  5. Voluntary Ingestion of Natural Cocoa Extenuated Hepatic Damage in Rats with Experimentally Induced Chronic Alcoholic Toxicity

    Directory of Open Access Journals (Sweden)

    Godwin Sokpor

    2012-05-01

    Full Text Available Background: Chronic ethanol ingestion causes hepatic damage imputable to an increasedoxidative stress engendered by alcoholic toxicity. Polyphenols in cocoa have antioxidant properties, and natural cocoa powder (NCP contains the highest levels of total antioxidant capacity when compared to all other kinds of edible cocoa products. This study tested the hypothesis that dietary supplementation with NCP mitigates hepatic injury resulting from chronic ethanol consumption. Three groups of eight randomized Sprague-Dawley rats were fed standardrat food and treated daily for 12 weeks as follows: (i the Ethanol-water group was given unrestricted access to 40% (v/v ethanol for 12 hours (at night followed by water for the remaining 12 hours (daytime, (ii the Ethanol-cocoa group had similarly unrestricted access to 40% ethanol for 12 hours followed by 2% (w/v NCP for 12 hours, and (iii the control group was not given alcohol and had unrestricted access to only water which was synchronously replenished every 12 hours as it was for the ethanol treated animals.Results: Qualitative structural liver damage evidenced by hepatocyte cytoplasmic fatty accumulation, nuclear alterations, and disruption of general liver micro-architecture, was severe in the ethanol-water group when compared with the ethanol-cocoa group of rats. Design-based stereologic assessment yielded a significantly greater volume (Tukey’s HSD, p = 0.0005 ofundamaged hepatocytes (9.61 ml, SD 2.18 ml in the ethanol-cocoa group as opposed to theethanol-water group of rats (2.34 ml, SD 1.21 ml. Control rats had 10.34 ml (SD 1.47 ml of undamaged hepatocytes, and that was not significantly greater (Tukey’s HSD, p=0.659 than the value for the ethanol-cocoa group of rats. Relative to controls, therefore, histomorphometryFunctional Foods in Health and Disease 2012, 2(5:166- 187 showed 93% hepatocyte preservation from alcoholic injury in rats that voluntarily imbibed NCP suspension compared with 23% in

  6. Protective effect of treatment with thiamine or benfotiamine on liver oxidative damage in rat model of acute ethanol intoxication.

    Science.gov (United States)

    Portari, Guilherme Vannucchi; Ovidio, Paula Payão; Deminice, Rafael; Jordão, Alceu Afonso

    2016-10-01

    The aim of this study was to evaluate possible beneficial effects of treatment with thiamine or benfotiamine in an animal model of acute ethanol intoxication. Thirty male Wistar rats were separated at random into three groups of 10 animals each: Ethanol (E), Ethanol treated with thiamine (T) and Ethanol treated with benfotiamine (BE). Rats were gavaged with single dose of ethanol (5g/kg, 40% v:v). After 30min of ethanol gavage the animals were treated with thiamine or benfotiamine. Six hours after first gavage, the animals were euthanized and blood and liver samples were collected for ethanol and oxidative stress biomarkers quantification. Serum ethanol levels were higher in animals treated with thiamine or benfotiamine while hepatic alcohol levels were higher in animals of the group treated with benfotiamine comparing to controls or thiamine treated groups. The lipid peroxidation biomarkers were diminished for the groups treated with thiamine or benfotiamine comparing to E animals. Concerning protein oxidative damage parameters, they were enhanced for animals treated with benfotiamine in relation to other groups. In conclusion, the treatment with thiamine or benfotiamine even 30min after the massive dose of ethanol has proven to be beneficial against liver damage. Improved results were obtained with benfotiamine in relation to oxidative damage from aqueous compartments. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Liver

    International Nuclear Information System (INIS)

    Bernardino, M.E.; Sones, P.J. Jr.; Barton Price, R.; Berkman, W.A.

    1984-01-01

    Evaluation of the liver for focal lesions is extremely important because the liver is one of the most common sites for metastatic disease. Most patients with metastatic deposits to the liver have a survival rate of about 6 months. Thus, metastatic disease to the liver has an extremely grave prognosis. In the past patients with hepatic lesions had no therapeutic recourse. However, with recent aggressive surgical advances (such as partial hepatectomies) and hepatic artery embolization, survival of patients with hepatic metastases has increased. Thus it is important for noninvasive imaging not only to detect lesions early in their course, but also to give their true hepatic involvement and the extent of the neoplastic process elsewhere in the body. Recent advances in imaging have been rapidly changing over the past 5 years. These changes have been more rapid in computed tomography (CT) and ultrasound than in radionuclide imaging. Thus, the question addressed in this chapter is: What is the relationship of hepatic ultrasound to the other current diagnostic modalities in detecting metastatic liver disease and other focal liver lesions? Also, what is its possible future relationship to nuclear magnetic resonance?

  8. (PNPLA3) I148M polymorphism and liver damage in chronic

    African Journals Online (AJOL)

    Amal M.H. Mackawy

    2015-06-23

    Jun 23, 2015 ... index (BMI) and lipid levels, but the presence of G allele is associated with higher liver ..... Ishak classification classified the patients according to the ..... [2] Roskams T, Desmet VJ, Verslype C. Development, structure and.

  9. [ACTION OF L-CARNITINE, CORVITIN AND THEIR COMBINATION ON FUNCTIONAL STATE OF LIVER IN EXPERIMENTAL MODEL OF REYE SYNDROME IN RATS].

    Science.gov (United States)

    Ghonghadze, M; Antelava, N; Liluashvili, K; Okujava, M; Pachkoria, K

    2017-02-01

    Administration of Aacetylsalicylic acid in children with viral infections (influence B, chickenpox) can be related with development of Reye syndrome - severe encephalopathy and liver insufficiency with mortality in 50% of cases. During Reye syndrome most important is deficiency of carnitine and hepatocyte damage. Decreased amount of carnitine impairs the energy function of mitochondria and gluconeogenesis as well as production of urea. As a result develops toxic encephalopathy and liver insufficiency. The goal of the research was assessment of efficacy of L-Carnitine, Corvitin and their combination on functional state of liver in experimental model of Reye Syndrome in rats. The study was performed on mature white male Wistar rates with body mass 150-180g. 50 rats were randomly divided into 5 groups (10 rats in each group). The model of Reye syndrome was induced in accordance with A.Vengersky's method. Intraperitoneal administration of 4-pentenoic acid was performed once daily during seven days, the used dosage was 20mg/kg. The treatment of toxic hepatitis was carried with intraperitoneal administration of L-Carnitine 300mg/kg, Corvitine 100mg/kg and concurrent administration of these drugs. Monotherapy with Corvitin and L-Carnitin successfully improved liver function and equally decreased indicators of hepatocyte's cytolyses and increased levels of glucose and urea. The markers of cholestasis was slightly more improved during use of L-Carnitine. Simultaneous use of both drugs was effective in rats with Reye syndrome, indicators of liver damage normalized and herewith, no mortality outcome was observed. The most pronounced hepatoprotective effect of concurrent administration of L-Carnitine and Corvitin may be due to synergic action of these drugs and such regime can be recommended for correction of liver function during Reye syndrome.

  10. Effect of juice and fermented vinegar from Hovenia dulcis peduncles on chronically alcohol-induced liver damage in mice.

    Science.gov (United States)

    Xiang, Jinle; Zhu, Wenxue; Li, Zhixi; Ling, Shengbao

    2012-06-01

    The protective effects of juice and fermented vinegar from Hovenia dulcis peduncles on chronically ethanol-induced biochemical changes in male mice were investigated. Administration of ethanol (50%, v/v, 10 mL kg⁻¹) to mice for 6 weeks induced liver damage with a significant increase (P vinegar from Hovenia dulcis peduncles (10 mL kg⁻¹ bw) along with alcohol significantly (P vinegar from Hovenia dulcis peduncles showed better profiles of the antioxidant systems with relatively higher glutathione (GSH) content, total superoxide dismutase (T-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities. All these results were accompanied by histological observations in liver. The results demonstrate that both of the juice and fermented vinegar from Hovenia dulcis peduncles have beneficial effects in reducing the adverse effect of alcohol.

  11. Hepatoprotective effect of Opuntia dillenii seed oil on CCl4 induced acute liver damage in rat

    Directory of Open Access Journals (Sweden)

    Mohamed Bouhrim

    2018-01-01

    Full Text Available Objective: To investigate the hepatoprotective effect of Opuntia dillenii seed oil (ODSO on CCl4 provoked liver injury in rat. Methods: Animals were treated orally with ODSO at a concentration of 2 mL/kg, once daily for one week before the first intraperitoneal injection of CCl4, and thereafter the administration of the oil was continued for 7 days until the introduction of the second injection of CCl4. Fourteen hours after the last dose of CCl4, rats were sacrificed, and the relative liver weight, weight gain, alkaline phosphatase, aspartate amino transferase, alanine aminotransferase, direct bilirubin, total bilirubin, triglycerides, total cholesterol, very low density lipoprotein, low density lipoprotein, high density lipoprotein, plasmatic glucose, urea, creatinine, acid uric and malondialdehyde were determined. Results: The significant increase was found in relative liver weight and plasma levels of alanine aminotransferase, aspartate amino transferase, alkaline phosphatase, total bilirubin, direct bilirubin, triglycerides, very low-density lipoprotein, urea, uric acid and malondialdehyde. Likewise, the significant decrease was indicated in the weight gain and the level of glucose plasmatic, and high-density lipoprotein levels in CCl4 produced liver injury in rats were re-established to normal levels when treated with ODSO. While, no change was observed in the total cholesterol, low-density lipoprotein and creatinine in all animals. Conclusions: We conclude that the ODSO has a protective effect on CCl4-mediated liver injury. Hence, we suggest its inclusion as a preventive control of liver disorders.

  12. Experimental verification of a progressive damage model for composite laminates based on continuum damage mechanics. M.S. Thesis Final Report

    Science.gov (United States)

    Coats, Timothy William

    1994-01-01

    Progressive failure is a crucial concern when using laminated composites in structural design. Therefore the ability to model damage and predict the life of laminated composites is vital. The purpose of this research was to experimentally verify the application of the continuum damage model, a progressive failure theory utilizing continuum damage mechanics, to a toughened material system. Damage due to tension-tension fatigue was documented for the IM7/5260 composite laminates. Crack density and delamination surface area were used to calculate matrix cracking and delamination internal state variables, respectively, to predict stiffness loss. A damage dependent finite element code qualitatively predicted trends in transverse matrix cracking, axial splits and local stress-strain distributions for notched quasi-isotropic laminates. The predictions were similar to the experimental data and it was concluded that the continuum damage model provided a good prediction of stiffness loss while qualitatively predicting damage growth in notched laminates.

  13. Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats

    Directory of Open Access Journals (Sweden)

    Campos de Carvalho Antonio

    2010-01-01

    Full Text Available Abstract Background Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results Forty Wistar rats (30 treated, 10 controls were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%. One third of cirrhotic rats presented with ascites. Conclusion The use of ultrasound imaging in the follow-up of murine diffuse liver disease

  14. Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats

    Science.gov (United States)

    2010-01-01

    Background Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results Forty Wistar rats (30 treated, 10 controls) were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD) and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%). One third of cirrhotic rats presented with ascites. Conclusion The use of ultrasound imaging in the follow-up of murine diffuse liver disease models is feasible and

  15. 915 MHz microwave ablation with implanted internal cooled-shaft antenna: Initial experimental study in in vivo porcine livers

    International Nuclear Information System (INIS)

    Cheng Zhigang; Xiao Qiujin; Wang Yang; Sun Yuanyuan; Lu Tong; Liang Ping

    2011-01-01

    Purpose: To explore a preferred power output for further clinical application based on the ablated lesions induced by the four power outputs of 915 MHz microwave in experimental study of in vivo porcine livers. Materials and methods: A KY2000-915 microwave ablation system with an implanted 915 MHz internal cooled-shaft antenna was used in this study. A total of 24 ablations were performed in eight in vivo porcine livers. The energy was applied for 10 min at microwave output powers of 50 W, 60 W, 70 W, and 80 W. Long-axis and short-axis diameters of the coagulation zone were measured on all gross specimens. Results: The shapes of the 915 MHz microwave ablation lesions were elliptical commonly. As the power increased, the long-axis and short-axis diameters of the coagulation zone had a tendency to rise. But the long-axis diameter of the ablated lesion at 50 W was not significantly smaller than that of the ablated lesion at 60 W (P > 0.05) and there were no statistical differences in short-axis diameters of the ablated lesion among the three power outputs of 60 W, 70 W and 80 W (P > 0.05). After 10 min irradiation of 60 W, the long-axis and short-axis diameters of the coagulation zone were 5.02 ± 0.60 cm and 3.65 ± 0.46 cm, respectively. Conclusions: For decreasing the undesired damages of liver tissues along the shaft and the number of antenna in further clinically percutaneous microwave ablation treatment, the power of 60 W may be a preferred setting among the four power outputs used in present study.

  16. Oxidized low-density-lipoprotein accumulation is associated with liver fibrosis in experimental cholestasis

    Directory of Open Access Journals (Sweden)

    Güldeniz Karadeniz

    2008-01-01

    Full Text Available OBJECTIVE: The aim of the present study was to examine the probable relationship between the accumulation of oxLDL and hepatic fibrogenesis in cholestatic rats. INTRODUCTION: There is growing evidence to support the current theories on how oxidative stress that results in lipid peroxidation is involved in the pathogenesis of cholestatic liver injury and fibrogenesis. One of the major and early lipid peroxidation products, OxLDL, is thought to play complex roles in various immuno-inflammatory mechanisms. METHODS: A prolonged (21-day experimental bile duct ligation was performed on Wistar-albino rats. Biochemical analysis of blood, histopathologic evaluation of liver, measurement of the concentration of malondialdehyde (MDA and superoxide-dismutase (SOD in liver tissue homogenates, and immunofluorescent staining for oxLDL in liver tissue was conducted in bile-duct ligated (n = 8 and sham-operated rats (n = 8. RESULTS: Significantly higher levels of MDA and lower concentrations of SOD were detected in jaundiced rats than in the sham-operated rats. Positive oxLDL staining was also observed in liver tissue sections of jaundiced rats. Histopathological examination demonstrated that neither fibrosis nor other indications of hepatocellular injury were found in the sham-operated group, while features of severe hepatocellular injury, particularly fibrosis, were found in jaundiced rats. CONCLUSION: Our results support the finding that either oxLDLs are produced as an intermediate agent during exacerbated oxidative stress or they otherwise contribute to the various pathomechanisms underlying the process of liver fibrosis. Whatever the mechanism, it is clear that an association exists between elevated oxLDL levels and hepatocellular injury, particularly with fibrosis. Further studies are needed to evaluate the potential effects of oxLDLs on the progression of secondary biliary cirrhosis.

  17. Caffeine demethylation measured by breath analysis in experimental liver injury in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Schaad, H.J.; Renner, E.L.; Wietholtz, H.; Preisig, R. [University of Berne, Department of Clinical Pharmaceology, Berne (Switzerland); Arnaud, M.J. [Nestle Research Center, Nestec Ltd., Vevey (Switzerland)

    1995-01-01

    To assess the effect of experimental liver injury on caffeine metabolism, 1 {mu}{sup C}i/kg b.w. of [3-methyl{sup 14}C]-caffeine (together with 5 mg/kg b.w. of the cold compound) was injected i.p. to four different experimental groups and respective controls of unanesthetized male Sprague-Dawley rats. Exhaled {sup 14}CO{sub 2} was completely collected during 4 h and peak exhalation rate and fraction of dose recovered were calculated. 1/3 hepatectomy affected {sup 14}CO{sub 2} exhalation to a limited extent, decreasing solely peak exhalation rate (p<0.05 compared to sham-operated control). 2/3 hepatectomy, on the other hand, resulted in significant reduction (p<0.01) in both peak exhalation rate (by 59%) and fraction of dose recovered (by 47%), that were proportionate to the loss of liver mass (50%). End-to-side portocaval shunt led to the well-documented hepatic `atrophy`, liver weight being diminished on average to 50% within 2 weeks of surgery; however, reductions in peak exhalation rate (by 75%) and fraction of dose recovered (by 64%) were even more pronounced. Finally, 48 h bile duct ligation was equivalent to `functional 2/3 hepatectomy`, peak exhalation rate (by 65%) and fraction of dose recovered (by 56%) being markedly diminished despite increased liver weight. These results indicate that {sup 14}CO{sub 2} exhalation curves following administration of specifically labelled caffeine are quantitative indicators of acute or chronic loss of functioning liver mass. In addition, the 3-demethylation pathway appears to be particularly sensitive to the inhibitory effects of cholestasis on microsomal function. (au) (30 refs.).

  18. In vitro study of (1-14C)-acetate incorporation into lipids of liver slices in experimental diabetes

    International Nuclear Information System (INIS)

    Greco, A.V.; Mingrone, G.; Peruzzi, E.; Orlando, P.

    1981-01-01

    The effect of insulin deficiency on lipid synthesis in the liver of normal rats, diabetic rats by alloxan and pancreatectomized rats was studied in vitro using (1- 14 C)-acetate as lipid precursor. Insulin deficiency induces an increased incorporation of (1- 14 C)-acetate into triglycerides in rat liver. This is particularly evident in pancreatectomized rats with respect to alloxan diabetic rats. It is concluded that in experimental diabetes an atherogenous metabolic pattern is elaborated by the liver. (author)

  19. In vitro study of (1-/sup 14/C)-acetate incorporation into lipids of liver slices in experimental diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Greco, A V; Mingrone, G; Peruzzi, E [Universita Cattolica S. Cuore, Roma (Italy). Ist. di Patologia Medica; Orlando, P [Universita Cattolica S. Cuore, Roma (Italy). Centre Radioisotopi

    1981-01-01

    The effect of insulin deficiency on lipid synthesis in the liver of normal rats, diabetic rats by alloxan and pancreatectomized rats was studied in vitro using (1-/sup 14/C)-acetate as lipid precursor. Insulin deficiency induces an increased incorporation of (1-/sup 14/C)-acetate into triglycerides in rat liver. This is particularly evident in pancreatectomized rats with respect to alloxan diabetic rats. It is concluded that in experimental diabetes an atherogenous metabolic pattern is elaborated by the liver.

  20. Low-velocity impact damage of woven fabric composites: Finite element simulation and experimental verification

    International Nuclear Information System (INIS)

    Hassan, M.A.; Naderi, S.; Bushroa, A.R.

    2014-01-01

    Highlights: • Low-velocity impact test on GFRP with different energy levels and thicknesses. • Using force–deflection curve to determine critical energy for penetration threshold. • Reflection of damage processes to different type of diagrams. • Significant influence of Initial energy and thickness on dynamic response of plates. • Good agreements between experimental and FEM models for the force history data. - Abstract: This paper addresses the response of Glass Fiber Reinforced Plastic laminates (GFRPs) under low-velocity impact. Experimental tests were performed according to ASTM: D5628 for different initial impact energy levels ranging from 9.8 J to 29.4 J and specimen thicknesses of 2, 3 and 4 mm. The impact damage process and contact stiffness were studied incrementally until a perforation phase of the layered compounds occurred, in line with a force–deflection diagram and imaging of impacted laminates. The influence that impact parameters such as velocity and initial energy had on deflection and damage of the test specimens was investigated. Finite Element Simulation (FES) was done using MSC. MARC® was additionally carried out to understand the impact mechanism and correlation between these parameters and the induced damage. The simulation and experimental results reached good accord regarding maximum contact force and contact time with insignificant amount of damage

  1. Experimental and Numerical Analysis of Damage in Woven GFRP Composites Under Large-deflection Bending

    Science.gov (United States)

    Ullah, Himayat; Harland, Andy R.; Silberschmidt, Vadim V.

    2012-10-01

    Textile-reinforced composites such as glass fibre-reinforced polymer (GFRP) used in sports products can be exposed to different in-service conditions such as large bending deformation and multiple impacts. Such loading conditions cause high local stresses and strains, which result in multiple modes of damage and fracture in composite laminates due to their inherent heterogeneity and non-trivial microstructure. In this paper, various damage modes in GFRP laminates are studied using experimental material characterisation, non-destructive micro-structural damage evaluation and numerical simulations. Experimental tests are carried out to characterise the behaviour of these materials under large-deflection bending. To obtain in-plane shear properties of laminates, tensile tests are performed using a full-field strain-measurement digital image correlation technique. X-ray micro computed tomography (Micro CT) is used to investigate internal material damage modes - delamination and cracking. Two-dimensional finite element (FE) models are implemented in the commercial code Abaqus to study the deformation behaviour and damage in GFRP. In these models, multiple layers of bilinear cohesive-zone elements are employed to study the onset and progression of inter-ply delamination and intra-ply fabric fracture of composite laminate, based on the X-ray Micro CT study. The developed numerical models are capable to simulate these features with their mechanisms as well as subsequent mode coupling observed in tests and Micro CT scanning. The obtained results of simulations are in agreement with experimental data.

  2. Blockade of Thrombopoietin Reduces Organ Damage in Experimental Endotoxemia and Polymicrobial Sepsis.

    Science.gov (United States)

    Cuccurullo, Alessandra; Greco, Elisabetta; Lupia, Enrico; De Giuli, Paolo; Bosco, Ornella; Martin-Conte, Erica; Spatola, Tiziana; Turco, Emilia; Montrucchio, Giuseppe

    2016-01-01

    Thrombopoietin (TPO), a growth factor primarily involved in thrombopoiesis may also have a role in the pathophysiology of sepsis. In patients with sepsis, indeed, TPO levels are markedly increased, with disease severity being the major independent determinant of TPO concentrations. Moreover, TPO increases and correlates with ex vivo indices of platelet activation in patients with burn injury upon sepsis development, and may contribute to depress cardiac contractility in septic shock. Still, the role of TPO in sepsis pathophysiology remains controversial, given the protective role of TPO in other experimental disease models, for instance in doxorubicin-induced cardiotoxicity and myocardial ischemia/reperfusion injury. The aim of our study was to define the contribution of TPO in the development of organ damage induced by endotoxemia or sepsis, and to investigate the effects of inhibiting TPO in these conditions. We synthesized a chimeric protein able to inhibit TPO, mTPOR-MBP, and studied its effect in two murine experimental models, acute endotoxemia and cecal ligation and puncture (CLP) model. In both models, TPO levels markedly increased, from 289.80±27.87 pg/mL to 465.60±45.92 pg/mL at 3 hours in the LPS model (P<0.01), and from 265.00±26.02 pg/mL to 373.70±26.20 pg/mL in the CLP model (P<0.05), respectively. Paralleling TPO levels, also platelet-monocyte aggregates increased, from 32.86±2.48% to 46.13±1.39% at 3 hours in the LPS model (P<0.01), and from 43.68±1.69% to 56.52±4.66% in the CLP model (P<0.05). Blockade of TPO by mTPOR-MBP administration reduced histological damage in target organs, namely lung, liver, and gut. In particular, neutrophil infiltration and lung septal thickening were reduced from a score of 1.86±0.34 to 0.60±0.27 (P<0.01) and from 1.43±0.37 to 0.40±0.16 (P<0.05), respectively, in the LPS model at 3 hours, and from a score of 1.75±0.37 to 0.38±0.18 (P<0.01) and from 1.25±0.31 to 0.13±0.13 (P<0.001), respectively, in the

  3. Blockade of Thrombopoietin Reduces Organ Damage in Experimental Endotoxemia and Polymicrobial Sepsis.

    Directory of Open Access Journals (Sweden)

    Alessandra Cuccurullo

    Full Text Available Thrombopoietin (TPO, a growth factor primarily involved in thrombopoiesis may also have a role in the pathophysiology of sepsis. In patients with sepsis, indeed, TPO levels are markedly increased, with disease severity being the major independent determinant of TPO concentrations. Moreover, TPO increases and correlates with ex vivo indices of platelet activation in patients with burn injury upon sepsis development, and may contribute to depress cardiac contractility in septic shock. Still, the role of TPO in sepsis pathophysiology remains controversial, given the protective role of TPO in other experimental disease models, for instance in doxorubicin-induced cardiotoxicity and myocardial ischemia/reperfusion injury. The aim of our study was to define the contribution of TPO in the development of organ damage induced by endotoxemia or sepsis, and to investigate the effects of inhibiting TPO in these conditions.We synthesized a chimeric protein able to inhibit TPO, mTPOR-MBP, and studied its effect in two murine experimental models, acute endotoxemia and cecal ligation and puncture (CLP model.In both models, TPO levels markedly increased, from 289.80±27.87 pg/mL to 465.60±45.92 pg/mL at 3 hours in the LPS model (P<0.01, and from 265.00±26.02 pg/mL to 373.70±26.20 pg/mL in the CLP model (P<0.05, respectively. Paralleling TPO levels, also platelet-monocyte aggregates increased, from 32.86±2.48% to 46.13±1.39% at 3 hours in the LPS model (P<0.01, and from 43.68±1.69% to 56.52±4.66% in the CLP model (P<0.05. Blockade of TPO by mTPOR-MBP administration reduced histological damage in target organs, namely lung, liver, and gut. In particular, neutrophil infiltration and lung septal thickening were reduced from a score of 1.86±0.34 to 0.60±0.27 (P<0.01 and from 1.43±0.37 to 0.40±0.16 (P<0.05, respectively, in the LPS model at 3 hours, and from a score of 1.75±0.37 to 0.38±0.18 (P<0.01 and from 1.25±0.31 to 0.13±0.13 (P<0.001, respectively

  4. Protective effect of genetic deletion of pannexin1 in experimental mouse models of acute and chronic liver disease.

    Science.gov (United States)

    Willebrords, Joost; Maes, Michaël; Pereira, Isabel Veloso Alves; da Silva, Tereza Cristina; Govoni, Veronica Mollica; Lopes, Valéria Veras; Crespo Yanguas, Sara; Shestopalov, Valery I; Nogueira, Marina Sayuri; de Castro, Inar Alves; Farhood, Anwar; Mannaerts, Inge; van Grunsven, Leo; Akakpo, Jephte; Lebofsky, Margitta; Jaeschke, Hartmut; Cogliati, Bruno; Vinken, Mathieu

    2018-03-01

    Pannexins are transmembrane proteins that form communication channels connecting the cytosol of an individual cell with its extracellular environment. A number of studies have documented the presence of pannexin1 in liver as well as its involvement in inflammatory responses. In this study, it was investigated whether pannexin1 plays a role in acute liver failure and non-alcoholic steatohepatitis, being prototypical acute and chronic liver pathologies, respectively, both featured by liver damage, oxidative stress and inflammation. To this end, wild-type and pannexin1 -/- mice were overdosed with acetaminophen for 1, 6, 24 or 48h or were fed a choline-deficient high-fat diet for 8weeks. Evaluation of the effects of genetic pannexin1 deletion was based on a number of clinically relevant read-outs, including markers of liver damage, histopathological analysis, lipid accumulation, protein adduct formation, oxidative stress and inflammation. In parallel, in order to elucidate molecular pathways affected by pannexin1 deletion as well as to mechanistically anchor the clinical observations, whole transcriptome analysis of liver tissue was performed. The results of this study show that pannexin1 -/- diseased mice present less liver damage and oxidative stress, while inflammation was only decreased in pannexin1 -/- mice in which non-alcoholic steatohepatitis was induced. A multitude of genes related to inflammation, oxidative stress and xenobiotic metabolism were differentially modulated in both liver disease models in wild-type and in pannexin1 -/- mice. Overall, the results of this study suggest that pannexin1 may play a role in the pathogenesis of liver disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Ethylenediaminetetraacetic acid induces antioxidant and anti-inflammatory activities in experimental liver fibrosis.

    Science.gov (United States)

    González-Cuevas, J; Navarro-Partida, J; Marquez-Aguirre, A L; Bueno-Topete, M R; Beas-Zarate, C; Armendáriz-Borunda, J

    2011-01-01

    Experimental liver fibrosis induced by carbon tetrachloride (CCl(4)) is associated with oxidative stress, lipid peroxidation, and inflammation. This work was focused on elucidating the anti-inflammatory and antioxidant effects of ethylenediaminetetraacetic acid (EDTA) in this model of hepatotoxicity. Wistar male rats were treated with CCl(4) and EDTA (60, 120, or 240 mg/kg). Morphometric analyses were carried out in Masson's stained liver sections to determine fibrosis index. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) were also determined. Gene expression for transforming growth factor beta (TGF-beta1), alpha1(I) procollagen gene (alpha1 Col I), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and superoxide dismutase (SOD) was monitored by real-time PCR. Antioxidant effect of EDTA was measured by its effects on lipid peroxidation; biological activity of ceruloplasmin (Cp), SOD, and catalase (Cat) were analyzed by zymography assays. Animals with CCl(4)-hepatic injury that received EDTA showed a decrement in fibrosis (20%) and lipid peroxidation (22%). The mRNA expression for TNF-alpha (55%), TGF-beta1 (50%), IL-6 (52%), and alpha1 Col I (60%) was also decreased. This group of animals showed increased Cp (62%) and SOD (25%) biological activities. Coagulation blood tests, Cat activity, and gene expression for SOD were not modified by EDTA treatment. This study demonstrates that EDTA treatment induces the activity of antioxidant enzymes, decreases lipid peroxidation, hepatic inflammation, and fibrosis in experimental liver fibrosis induced by CCl(4).

  6. Long-term study of liver damage following subcutaneous injection of airborne particle extracts and polycyclic aromatic hydrocarbon fractions

    Energy Technology Data Exchange (ETDEWEB)

    Meiss, R.; Heinrich, U.; Offermann, M.; Themann, H.

    1982-02-01

    Female NMRI mice aged 9-12 weeks were each given a single subcutaneous injection of 0.5 ml of a suspension containing either the total extracts or the polycyclic aromatic hydrocarbon (PAH) fraction of airborne particles. Both the total extracts and PAH fractions contain 3 microgram benzopyrene. After about 15 months the livers were removed from the animals, which had by that time developed tumors at the injection site, and were subjected to electron-microscopical study. The essential alterations were observed in the nucleoli and the cell nuclei, which had greatly proliferated and exhibited irregular nuclear membranes. Advanced fibrosis was observed in central liver specimens of all groups. Marked alterations were also observed in the mitochondria and the mitochondrial cristae as well as in the bile canaliculi, Intracytoplasmic glycogen usually occurred densely clustered along the periphery of the cell. It may be concluded from the observations that both the total extract of atmospheric suspended particulate matter and the PAH fraction cause hematogenic damage to the liver following subcutaneous injection, a finding which cannot be interpreted as metastatic carcinoma.

  7. Long-term study of liver damage following subcutaneous injection of airborne particle extracts and polycyclic aromatic hydrocarbon fractions

    Energy Technology Data Exchange (ETDEWEB)

    Meiss, R.; Heinrich, U.; Offermann, M.; Themann, H.

    1982-02-01

    Female NMRI mice aged 9-12 weeks were each given a single subcutaneous injection of 0.5 ml of a suspension containing either the total extracts or the polycyclic aromatic hydrocarbon (PAH) fraction of airborne particles. Both the total extracts and PAH fractions contain 3 ..mu..g benzopyrene. After about 15 months the livers were removed from the animals, which had by that time developed tumors at the injection site, and were subjected to electron-microscopical study. The essential alterations were observed in the nucleoli and the cell nuclei, which had greatly proliferated and exhibited irregular nuclear membranes. Advanced fibrosis was observed in central liver specimens of all groups. Marked alterations were also observed in the mitochondria and the mitochondrial cristae as well as in the bile canaliculi. Intracytoplasmic glycogen usually occurred densely clustered along the periphery of the cell. It may be concluded from the observations that both the total extract of atmospheric suspended particulate matter and the PAH fraction cause hematogenic damage to the liver following subcutaneous injection, a finding which cannot be interpreted as metastatic carcinoma.

  8. Dicranostiga leptopodu (Maxim.) Fedde extracts attenuated CCl4-induced acute liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function.

    Science.gov (United States)

    Tang, Deping; Wang, Fang; Tang, Jinzhou; Mao, Aihong; Liao, Shiqi; Wang, Qin

    2017-01-01

    Dicranostiga Leptodu (Maxim.) fedde (DLF), a poppy plant, has been reported have many benefits and medicinal properties, including free radicals scavenging and detoxifying. However, the protective effect of DLF extracts against carbon tetrachloride (CCl 4 )-induced damage in mice liver has not been elucidated. Here, we demonstrated that DLF extracts attenuated CCl 4 -induced liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function. In this study, the mice liver damage evoked by CCl 4 was marked by morphology changes, significant rise in lipid peroxidation, as well as alterations of mitochondrial respiratory function. Interestingly, pretreatment with DLF extracts attenuated CCl 4 -induced morphological damage and increasing of lipid peroxidation in mice liver. Additionally, DLF extracts improved mitochondrial function by preventing the disruption of respiratory chain and suppression of mitochondrial Na + K + -ATPase and Ca 2+ -ATPase activity. Furthermore, administration with DLF extracts elevated superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels and maintained the balance of redox status. This results showed that toxic protection effect of DLF extracts on mice liver is mediated by improving mitochondrial respiratory function and keeping the balance of redox status, which suggesting that DLF extracts could be used as potential toxic protection agent for the liver against hepatotoxic agent. Copyright © 2016. Published by Elsevier Masson SAS.

  9. Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

    Directory of Open Access Journals (Sweden)

    Mikael Bjursell

    Full Text Available Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1, the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

  10. Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

    Science.gov (United States)

    Bjursell, Mikael; Wedin, Marianne; Admyre, Therése; Hermansson, Majlis; Böttcher, Gerhard; Göransson, Melker; Lindén, Daniel; Bamberg, Krister; Oscarsson, Jan; Bohlooly-Y, Mohammad

    2013-01-01

    Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR) is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH) and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

  11. Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage

    Directory of Open Access Journals (Sweden)

    Herson Antonio González-Ponce

    2016-10-01

    Full Text Available Acetaminophen (APAP-induced acute liver failure (ALF is a serious health problem in developed countries. N-acetyl-L-cysteine (NAC, the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800mg/kg/day, orally were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally. Rat hepatocyte cultures were exposed to 20mmol/LAPAP, and necrosis was assessed by LDH leakage. Opuntia robusta had significantly higher levels of antioxidants than Opuntia streptacantha. Both extracts significantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts significantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF.

  12. Rheological-dynamical continuum damage model for concrete under uniaxial compression and its experimental verification

    Directory of Open Access Journals (Sweden)

    Milašinović Dragan D.

    2015-01-01

    Full Text Available A new analytical model for the prediction of concrete response under uniaxial compression and its experimental verification is presented in this paper. The proposed approach, referred to as the rheological-dynamical continuum damage model, combines rheological-dynamical analogy and damage mechanics. Within the framework of this approach the key continuum parameters such as the creep coefficient, Poisson’s ratio and damage variable are functionally related. The critical values of the creep coefficient and damage variable under peak stress are used to describe the failure mode of the concrete cylinder. The ultimate strain is determined in the post-peak regime only, using the secant stress-strain relation from damage mechanics. The post-peak branch is used for the energy analysis. Experimental data for five concrete compositions were obtained during the examination presented herein. The principal difference between compressive failure and tensile fracture is that there is a residual stress in the specimens, which is a consequence of uniformly accelerated motion of load during the examination of compressive strength. The critical interpenetration displacements and crushing energy are obtained theoretically based on the concept of global failure analysis. [Projekat Ministarstva nauke Republike Srbije, br. ON 174027: Computational Mechanics in Structural Engineering i br. TR 36017: Utilization of by-products and recycled waste materials in concrete composites for sustainable construction development in Serbia: Investigation and environmental assessment of possible applications

  13. Protective effects of rosmarinic acid on sepsis-induced DNA damage in the liver of Wistar albino rats

    Directory of Open Access Journals (Sweden)

    Hatice Gul Goktas

    2015-06-01

    Full Text Available Sepsis is an imbalance between pro and anti-inflammatory responses. Sepsis induced multiple organ failure that is associated with mortality is characterized by liver, renal, cardiovascular and pulmonary dysfunction and reactive oxygen species (ROS are believed to be involved in the development of sepsis. Plant polyphenols may act as antioxidants by different mechanisms such as free radical scavenging, metal chelation and protein binding. Data indicates possible beneficial effects of plant derived phenolic compounds against sepsis. Rosmarinic acid (RA (α-O-caffeoyl-3,4-dihydroxyphenyllactic acid is a phenolic compound commonly found in various plants such as Rosmarinus officinalis (rosemary, Origanum vulgare (oregano, Thymus vulgaris (thyme, Mentha spicata (spearmint, Perilla frutescens (perilla, Ocimum basilicum (sweet basil and several other medicinal plants. It has been shown that RA has many biological activities including antioxidant, anti-inflammatory, antiallergic, anticancer and actimicrobial and is widely used in cosmetic and food industry. In the present study, we aimed to determine the protective effects of RA against the oxidative DNA damage induced by sepsis in Wistar albino rats. The rats were divided into four groups; sham, sepsis induced, RA-treated, RA treated and sepsis induced groups. Wistar rats were subjected to sepsis by cecal ligation puncture. The liver tissues were carefully dissected from their attachments and totally excised. The concentrations of the hepatic tissue cells were adjusted to approximately 2 x 106 cells/ml. Standard and formamidopyrimidine-DNA glycosylase (Fpg modified comet assay described by Singh et al were used. There were no statistically significant differences in terms of tail length, tail intensity and tail moment between the sham group and the RA-treated groups (p>0.05. The DNA damage was found significantly higher in the sepsis-induced group compared to the sham group (p0.05, and the DNA damage

  14. Protective role of lycopene against damage induced in liver, lung and vertebrae of gamma irradiated rat fetus

    International Nuclear Information System (INIS)

    Ismail, N.H.; Ramadan, F.L.

    2007-01-01

    The present study was designed to investigate the protective effects of lycopene (0.9 mg/100 g/day) orally given pre and post gamma irradiation on the histological changes in the liver, lung and vertebrae of fetuses. Four groups of pregnant female rats were irradiated as follows: first group represented control (C), second group treated with lycopene (L), third group exposed to radiation (R) and fourth group exposed to radiation and treated with lycopene (R+L). Pregnant female rats of group 3 and 4 were exposed to gamma irradiation at a dose level of 1.5 Gy at day 5 and 1.5 Gy at day 10 of gestation. All groups were sacrificed on day 20 of gestation. Histological results showed serious injury in the liver after exposure to gamma irradiation, where hemo siderosis was noted surrounding the dilated central vein and hepatocytes were atrophied with depression in the hemopoiesis process. Lung sections of fetuses maternally subjected to 1.5 Gy at day 5 and at day 10 of gestation and inspected on day 20 of gestation exhibited dilated and atrophied air alveoli with flattened lining epithelium. Vertebrae of these fetuses showed reductions in number of mitoses and disorderly maturation followed by the asymptomatic degeneration and necrosis of less mature element and bleeding in the periosteum of vertebra. Oral administration of lycopene pre and post gamma irradiation markedly reduced the radiation injury and showed marked protection against the liver and lung damaging effects of irradiation. On the other hand, the vertebrae sections showed no protective role of lycopene from the irradiation damage. Therefore, it may be suggested that lycopene, a potent antioxidant, can attenuate radiation injuries in certain organ

  15. An experimental study on tissue damage following subcutaneous injection of water soluble contrast media

    International Nuclear Information System (INIS)

    Kim, Seung Hyup; Park, Jae Hyung; Kang, Heung Sik; Kim, Chu Wan; Han, Man Chung; Kim, Yong Il

    1989-01-01

    The water soluble contrast media cause tissue necrosis infrequently by extravasation during intravenous injection in various radiological examinations. However, it has not been well documented that what kind and what concentration of contrast media can cause tissue necrosis. And also, the mechanism of tissue necrosis by extravasated contrast media has not been well known. The purpose of this experimental study was to evaluate the frequency and severity of tissue damage following subcutaneous injection of various water soluble contrast media to investigate the characteristics of the contrast media acting on the tissue damage, and to provide the basic data for the clinical application. Meglumine ioxithalamate,sodium and meglumine ioxithalamate, iopromide, iopamidol, ioxaglate,meglumine diatrizoate and sodium diatrizoate of various iodine content and osmolality were injected into subcutaneous tissue of the dorsum of 970 feet of 485 rats. The tissue reaction of injection sites were grossly examined with period from 1 day to 8 weeks after the injection. Representative gross changes were correlated with histologic findings. The results were as follows; 1. The basic tissue damage by extravasated contrast media was acute and chronic inflammatory reaction of the soft tissue with subsequent progress into the hemorrhagic and necrotizing lesion. 2. Lager volume of contrast media caused more severe tissue damage. 3. Contrast media of higher osmolality caused more severe tissue damage. 4. At same osmolality, contrast media of higher iodine content caused more severe tissue damage

  16. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  17. Anti-hepatotoxic activities of Hibiscus sabdariffa L. in animal model of streptozotocin diabetes-induced liver damage.

    Science.gov (United States)

    Adeyemi, David O; Ukwenya, Victor O; Obuotor, Efere M; Adewole, Stephen O

    2014-07-30

    Flavonoid-rich aqueous fraction of methanolic extract of Hibiscus sabdariffa calyx was evaluated for its anti-hepatotoxic activities in streptozotocin-induced diabetic Wistar rats. Diabetes Mellitus was induced in Wistar rats by a single i.p injection of 80 mg/kg b.w. streptozotocin (STZ) dissolved in 0.1 M citrate buffer (pH 6.3). The ameliorative effects of the extract on STZ-diabetes induced liver damage was evident from the histopathological analysis and the biochemical parameters evaluated in the serum and liver homogenates. Reduced levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (3.76 ± 0.38 μM, 0.42 ± 0.04 U/L, 41.08 ± 3.04 U/ml, 0.82 ± 0.04 U/L respectively) in the liver of diabetic rats were restored to a near normal level in the Hibiscus sabdariffa-treated rats (6.87 ± 0.51 μM, 0.72 ± 0.06 U/L, 87.92 ± 5.26 U/ml, 1.37 ± 0.06 U/L respectively). Elevated levels of aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) in the serum of diabetic rats were also restored in Hibiscus sabdariffa -treated rats. Examination of stained liver sections revealed hepatic fibrosis and excessive glycogen deposition in the diabetic rats. These pathological changes were ameliorated in the extract-treated rats. The anti-hepatotoxic activity of Hibiscus sabdariffa extract in STZ diabetic rats could be partly related to its antioxidant activity and the presence of flavonnoids.

  18. Lipid droplet-associated proteins in alcoholic liver disease: a potential linkage with hepatocellular damage

    OpenAIRE

    Ikura, Yoshihiro; Caldwell, Stephen H

    2015-01-01

    Steatosis is a characteristic morphological change of alcoholic liver disease, but its pathologic significance is still obscure. Regardless of cell types, intracellular lipid droplets are coated with a phospholipid monolayer, on which many kinds of lipid droplet-associated proteins are present. These proteins, such as the perilipin family of proteins and the cell death inducing DNA fragmentation factor (DFF) 45-like effectors, are recognized to play important roles in lipid metabolism in the ...

  19. An experimental study on developing seismic damage indicator appearing OBE exceedance

    International Nuclear Information System (INIS)

    Park, D. S.; Kwon, K. J.; Lee, J. L.

    2000-01-01

    Immediate measurement should be taken depending on the level of seismic damage to nuclear power plants when an earthquake exceeds Operating Base Earthquake by NRC regulatory guide. An earthquake at nuclear plant site is felt with seismic instrument and analyzed by seismic monitoring systems. However, if operators of insufficient knowledge to earthquake can recognize the intensity of the earthquake with a subsidiary indicating model, more immediate response can be conducted. This subsidiary indicating model is called seismic damage indicator. In this regard, an experimental study using shaking table was conducted to develop the seismic damage indicator by CAV and OBE compatible with NRC standard response spectrum. In this test result, stacked acrylic cylinders were manufactured to behave consistently for each direction of seismic load. If the developed SDI is installed in nuclear power plants, it is seemed to be useful in easily determining OBE exceedance easily, and counteracting by plant operator along with the existing seismic monitoring systems

  20. Experimental setup and first measurement of DNA damage induced along and around an antiproton beam

    DEFF Research Database (Denmark)

    Kavanagh, J. N.; Currell, F. J.; Timson, D. J.

    2010-01-01

    a further enhancement due to their annihilation at the end of the path. The work presented here aimed to establish and validate an experimental procedure for the quantification of plasmid and genomic DNA damage resulting from antiproton exposure. Immunocytochemistry was used to assess DNA damage in directly......Radiotherapy employs ionizing radiation to induce lethal DNA lesions in cancer cells while minimizing damage to healthy tissues. Due to their pattern of energy deposition, better therapeutic outcomes can, in theory, be achieved with ions compared to photons. Antiprotons have been proposed to offer...... and indirectly exposed human fibroblasts irradiated in both plateau and Bragg peak regions of a 126 MeV antiproton beam at CERN. Cells were stained post irradiation with an anti-γ-H2AX antibody. Quantification of the γ-H2AX foci-dose relationship is consistent with a linear increase in the Bragg peak region...

  1. Experimental Study on Damage Detection in Timber Specimens Based on an Electromechanical Impedance Technique and RMSD-Based Mahalanobis Distance

    Directory of Open Access Journals (Sweden)

    Dansheng Wang

    2016-10-01

    Full Text Available In the electromechanical impedance (EMI method, the PZT patch performs the functions of both sensor and exciter. Due to the high frequency actuation and non-model based characteristics, the EMI method can be utilized to detect incipient structural damage. In recent years EMI techniques have been widely applied to monitor the health status of concrete and steel materials, however, studies on application to timber are limited. This paper will explore the feasibility of using the EMI technique for damage detection in timber specimens. In addition, the conventional damage index, namely root mean square deviation (RMSD is employed to evaluate the level of damage. On that basis, a new damage index, Mahalanobis distance based on RMSD, is proposed to evaluate the damage severity of timber specimens. Experimental studies are implemented to detect notch and hole damage in the timber specimens. Experimental results verify the availability and robustness of the proposed damage index and its superiority over the RMSD indexes.

  2. Effects of a Brussels sprouts extract on oxidative DNA damage and metabolising enzymes in rat liver

    DEFF Research Database (Denmark)

    Sørensen, Mette; Jensen, B.R.; Poulsen, Henrik E.

    2001-01-01

    and catalase activity was also assessed in the kidneys. In order to examine a possible effect of the Brussels sprouts related to oxidative stress, we measured oxidative DNA damage in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) and lipid peroxidation in terms of malondialdehyde (MDA) formation...... on MDA levels were found. The present results support the data obtained in several studies that consumption of cruciferous vegetables is capable of inducing various phase II enzyme systems. However, the observed increase in oxidative DNA damage raises the question of whether greatly increased ingestion...

  3. Experimental Investigation into Vibration Characteristics for Damage Minimization in a Lapping Process

    Directory of Open Access Journals (Sweden)

    J. Suwatthikul

    2016-01-01

    Full Text Available Lapping machines are used in a hard disk rough lapping process where a workpiece (a wafer row bar is locked with a robot arm and rubbed on a lap plate. In this process, the lap plate’s condition and lifetime are among important concerned factors. The lifetime can be too short due to the plate being accidentally scratched by the workpiece during lapping. This problem leads to undesired consequences such as machine downtime and excessive plate material usage. This paper presents an experimental investigation into vibration characteristics of passed and failed lapping scenarios and discusses a potential solution to minimize the serious damage so-called “plate scratch” which intermittently occurs in such process. The experimental results show that, by in situ monitoring vibration and utilizing artificial intelligence, damage minimization can be possible.

  4. Time course of gene expression profiling in the liver of experimental mice infected with Echinococcus multilocularis.

    Directory of Open Access Journals (Sweden)

    Renyong Lin

    Full Text Available BACKGROUND: Alveolar echinococcosis (AE is a severe chronic parasitic disease which behaves like a slow-growing liver cancer. Clinical observations suggest that the parasite, Echinococcus multilocularis (E. multilocularis influences liver homeostasis and hepatic cell metabolism. However, this has never been analyzed during the time course of infection in the common model of secondary echinococcosis in experimental mice. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles were assessed using DNA microarray analysis, 1, 2, 3 and 6 months after injection of E. multilocularis metacestode in the liver of susceptible mice. Data were collected at different time points to monitor the dynamic behavior of gene expression. 557 differentially expressed genes were identified at one or more time points, including 351 up-regulated and 228 down-regulated genes. Time-course analysis indicated, at the initial stage of E. multilocularis infection (month 1-2, that most of up-regulated pathways were related to immune processes and cell trafficking such as chemokine-, mitogen-activated protein kinase (MAPK signaling, and down-regulated pathways were related to xenobiotic metabolism; at the middle stage (month 3, MAPK signaling pathway was maintained and peroxisome proliferator-activated receptor (PPAR signaling pathway emerged; at the late stage (month 6, most of up-regulated pathways were related to PPAR signaling pathway, complement and coagulation cascades, while down-regulated pathways were related to metabolism of xenobiotics by cytochrome P450. Quantitative RT-PCR analysis of a random selection of 19 genes confirmed the reliability of the microarray data. Immunohistochemistry analysis showed that proliferating cell nuclear antigen (PCNA was increased in the liver of E. multilocularis infected mice from 2 months to 6 months. CONCLUSIONS: E. multilocularis metacestode definitely exerts a deep influence on liver homeostasis, by modifying a number of gene

  5. An Experimental Study to Measure the Mechanical Properties of the Human Liver.

    Science.gov (United States)

    Karimi, Alireza; Shojaei, Ahmad

    2018-01-01

    Since the liver is one of the most important organs of the body that can be injured during trauma, that is, during accidents like car crashes, understanding its mechanical properties is of great interest. Experimental data is needed to address the mechanical properties of the liver to be used for a variety of applications, such as the numerical simulations for medical purposes, including the virtual reality simulators, trauma research, diagnosis objectives, as well as injury biomechanics. However, the data on the mechanical properties of the liver capsule is limited to the animal models or confined to the tensile/compressive loading under single direction. Therefore, this study was aimed at experimentally measuring the axial and transversal mechanical properties of the human liver capsule under both the tensile and compressive loadings. To do that, 20 human cadavers were autopsied and their liver capsules were excised and histologically analyzed to extract the mean angle of a large fibers population (bundle of the fine collagen fibers). Thereafter, the samples were cut and subjected to a series of axial and transversal tensile/compressive loadings. The results revealed the tensile elastic modulus of 12.16 ± 1.20 (mean ± SD) and 7.17 ± 0.85 kPa under the axial and transversal loadings respectively. Correspondingly, the compressive elastic modulus of 196.54 ± 13.15 and 112.41 ± 8.98 kPa were observed under the axial and transversal loadings respectively. The compressive axial and transversal maximum/failure stress of the capsule were 32.54 and 37.30 times higher than that of the tensile ones respectively. The capsule showed a stiffer behavior under the compressive load compared to the tensile one. In addition, the axial elastic modulus of the capsule was found to be higher than that of the transversal one. The findings of the current study have implications not only for understanding the mechanical properties of the human capsule tissue under tensile

  6. New experimental model for single liver lobe hyperthermia in small animals using non-directional microwaves.

    Directory of Open Access Journals (Sweden)

    Ionuț Tudorancea

    Full Text Available Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control.A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250-270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected.In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R2 = 0.9551, while the increment is lower it the next two intervals (40-42°C and 42-44°C with 0.291°C/ s (R2 = 0.9337 and 0.136°C/ s (R2 = 0.7894 respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments.We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia.

  7. Experimental Estimation of Journal Bearing Stiffness for Damage Detection in Large Hydrogenerators

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    Geraldo Carvalho Brito

    2017-01-01

    Full Text Available Based on experimental pieces of evidence collected in a set of twenty healthy large hydrogenerators, this article shows that the operating conditions of the tilting pad journal bearings of these machines may have unpredictable and significant changes. This behavior prevents the theoretical determination of bearing stiffness and damping coefficients with an adequate accuracy and makes damage detection difficult. Considering that dynamic coefficients have similar sensitivity to damage and considering that it is easier to monitor bearing stiffness than bearing damping, this article discusses a method to estimate experimentally the effective stiffness coefficients of hydrogenerators journal bearings, using only the usually monitored vibrations, with damage detection purposes. Validated using vibration signals synthesized by a simplified mathematical model that simulates the dynamic behavior of large hydrogenerators, the method was applied to a journal bearing of a 700 MW hydrogenerator, using two different excitations, the generator rotor unbalance and the vortices formed in the turbine rotor when this machine operates at partial loads. The experimental bearing stiffnesses obtained using both excitations were similar, but they were also much lower than the theoretical predictions. The article briefly discusses the causes of these discrepancies, the method’s uncertainties, and the possible improvements in its application.

  8. DNA damage in mouse and rat liver by caprolactam and benzoin, evaluated with three different methods.

    Science.gov (United States)

    Parodi, S; Abelmoschi, M L; Balbi, C; De Angeli, M T; Pala, M; Russo, P; Taningher, M; Santi, L

    1989-11-01

    Benzoin and caprolactam were examined for their capability of inducing alkaline DNA fragmentation in mouse and rat liver DNA after treatment in vivo. Three different methods were used. With the alkaline elution technique we measured an effect presumably related to the conformation of the DNA coil. With a viscometric and a fluorometric unwinding method we measured an effect presumably related to the number of unwinding points in DNA. For both compounds only the alkaline elution technique was clearly positive. The results suggest that both caprolactam and benzoin can induce an important change in the conformation of the DNA coil without inducing true breaks in DNA.

  9. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases necroinflammation and hepatic stellate cell activation but does not exacerbate experimental liver fibrosis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Lamb, Cheri L.; Cholico, Giovan N. [Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725 (United States); Pu, Xinzhu [Biomolecular Research Center, Boise State University, Boise, ID 83725 (United States); Hagler, Gerald D. [Department of Biological Sciences, Boise State University, Boise, ID 83725 (United States); Cornell, Kenneth A. [Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725 (United States); Biomolecular Research Center, Boise State University, Boise, ID 83725 (United States); Department of Chemistry and Biochemistry, Boise State University, Boise, ID 83725 (United States); Mitchell, Kristen A., E-mail: kristenmitchell@boisestate.edu [Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725 (United States); Department of Biological Sciences, Boise State University, Boise, ID 83725 (United States)

    2016-11-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant and high-affinity ligand for the aryl hydrocarbon receptor (AhR). Increasing evidence indicates that AhR signaling contributes to wound healing, which involves the coordinated deposition and remodeling of the extracellular matrix. In the liver, wound healing is attributed to the activation of hepatic stellate cells (HSCs), which mediate fibrogenesis through the production of soluble mediators and collagen type I. We recently reported that TCDD treatment increases the activation of human HSCs in vitro. The goal of this study was to determine how TCDD impacts HSC activation in vivo using a mouse model of experimental liver fibrosis. To elicit fibrosis, C57BL6/male mice were treated twice weekly for 8 weeks with 0.5 ml/kg carbon tetrachloride (CCl{sub 4}). TCDD (20 μg/kg) or peanut oil (vehicle) was administered once a week during the last 2 weeks. Results indicate that TCDD increased liver-body-weight ratios, serum alanine aminotransferase activity, and hepatic necroinflammation in CCl{sub 4}-treated mice. Likewise, TCDD treatment increased mRNA expression of HSC activation and fibrogenesis genes, namely α-smooth muscle actin, desmin, delta-like homolog-1, TGF-β1, and collagen type I. However, TCDD treatment did not exacerbate fibrosis, nor did it increase the collagen content of the liver. Instead, TCDD increased hepatic collagenase activity and increased expression of matrix metalloproteinase (MMP)-13 and the matrix regulatory proteins, TIMP-1 and PAI-1. These results support the conclusion that TCDD increases CCl{sub 4}-induced liver damage and exacerbates HSC activation, yet collagen deposition and the development of fibrosis may be limited by TCDD-mediated changes in extracellular matrix remodeling. - Highlights: • TCDD increased liver damage and inflammation in mice treated with CCl{sub 4}. • TCDD treatment enhanced markers of hepatic stellate cell activation and

  10. Acetaminophen-induced liver damage in mice is associated with gender-specific adduction of peroxiredoxin-6

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    Isaac Mohar

    2014-01-01

    Full Text Available The mechanism by which acetaminophen (APAP causes liver damage evokes many aspects drug metabolism, oxidative chemistry, and genetic-predisposition. In this study, we leverage the relative resistance of female C57BL/6 mice to APAP-induced liver damage (AILD compared to male C57BL/6 mice in order to identify the cause(s of sensitivity. Furthermore, we use mice that are either heterozygous (HZ or null (KO for glutamate cysteine ligase modifier subunit (Gclm, in order to titrate the toxicity relative to wild-type (WT mice. Gclm is important for efficient de novo synthesis of glutathione (GSH. APAP (300 mg/kg, ip or saline was administered and mice were collected at 0, 0.5, 1, 2, 6, 12, and 24 h. Male mice showed marked elevation in serum alanine aminotransferase by 6 h. In contrast, female WT and HZ mice showed minimal toxicity at all time points. Female KO mice, however, showed AILD comparable to male mice. Genotype-matched male and female mice showed comparable APAP–protein adducts, with Gclm KO mice sustaining significantly greater adducts. ATP was depleted in mice showing toxicity, suggesting impaired mitochondria function. Indeed, peroxiredoxin-6, a GSH-dependent peroxiredoxin, was preferentially adducted by APAP in mitochondria of male mice but rarely adducted in female mice. These results support parallel mechanisms of toxicity where APAP adduction of peroxiredoxin-6 and sustained GSH depletion results in the collapse of mitochondria function and hepatocyte death. We conclude that adduction of peroxiredoxin-6 sensitizes male C57BL/6 mice to toxicity by acetaminophen.

  11. Comparison of various structural damage tracking techniques with unknown excitations based on experimental data

    Science.gov (United States)

    Huang, Hongwei; Yang, Jann N.; Zhou, Li

    2009-03-01

    An early detection of structural damages is critical for the decision making of repair and replacement maintenance in order to guarantee a specified structural reliability. Consequently, the structural damage detection, based on vibration data measured from the structural health monitoring (SHM) system, has received considerable attention recently. The traditional time-domain analysis techniques, such as the least square estimation (LSE) method and the extended Kalman filter (EKF) approach, require that all the external excitations (inputs) be available, which may not be the case for some SHM systems. Recently, these two approaches have been extended to cover the general case where some of the external excitations (inputs) are not measured, referred to as the LSE with unknown inputs (LSE-UI) and the EKF with unknown inputs (EKF-UI). Also, new analysis methods, referred to as the sequential non-linear least-square estimation with unknown inputs and unknown outputs (SNLSE-UI-UO) and the quadratic sum-square error with unknown inputs (QSSE-UI), have been proposed for the damage tracking of structures when some of the acceleration responses are not measured and the external excitations are not available. In this paper, these newly proposed analysis methods will be compared in terms of accuracy, convergence and efficiency, for damage identification of structures based on experimental data obtained through a series of experimental tests using a small-scale 3-story building model with white noise excitation. The capability of the LSE-UI, EKF-UI, SNLSE-UI-UO and QSSE-UI approaches in tracking the structural damages will be demonstrated.

  12. Sweet potato Ipomoea Batatas Modulates Radiation-induced Oxidative damage in Liver and kidney of Male Albino Rats

    International Nuclear Information System (INIS)

    Darwish, M. M.; Farag, M. F. S.; Osman, N. N.

    2010-01-01

    Sweet potato Ipomoea Batatas, one of the major vegetable crops consumed worldwide, is rich in phytochemicals, which displayed antioxidant activities. This work aims at assessing the radio-protective properties of sweet potato tubers on liver and kidney tissues. Male albino rats were whole body exposed to 0.5 Gy day after day for a period of 20 days. Animal received orally prepared aqueous extract of sweet potato tubers (100 mg kg/body weight), one week before irradiation and during the period of radiation exposure. The results demonstrated that irradiation of rats induced a significant increase in lipid peroxides level measured as thiobarbituric acid reactive substances (TBARS) concomitant with a significant decrease in superoxide dismutase (SOD), and catalase (CAT) activity and glutathione (GSH) content in liver and kidney tissues. Administration of a freshly prepared aqueous extract of sweet potato tubers to rats, one week pre-irradiation and during the period of radiation exposure has significantly of ameliorated the oxidative stress in both tissues. The significant amelioration in oxidative stress was substantiated by improvement of liver and kidney enzymes Treatment of rats with sweet potato has significantly reduced the increase in serum alanine amino transferase (ALT), aspartate amino transferase (AST) and lactate dehydrogenase (LDH) activity, serum creatinine and urea levels. Furthermore, hyperglycemia and alteration in lipid profile manifested by a significant increase in triglycerides (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C), and a significant decrease in high density lipoprotein cholesterol (HDL-C), were improved in sweet potato-treated irradiated rats compared to those only irradiated. According to the results obtained in the present study, it could be concluded that sweet potato through its antioxidant activities could protect cellular membrane from radiation induced oxidative damage in animals and preserve the

  13. The organ specificity in pathological damage of chronic intermittent hypoxia: an experimental study on rat with high-fat diet.

    Science.gov (United States)

    Wang, Hui; Tian, Jian-li; Feng, Shu-zhi; Sun, Ning; Chen, Bao-yuan; Zhang, Yun

    2013-09-01

    It is known today that sleep apnea hypopnea syndrome and its characteristic chronic intermittent hypoxia can cause damages to multiple organs, including the cardiovascular system, urinary system, and liver. It is still unclear, however, whether the damage caused by sleep apnea hypopnea syndrome and the severity of the damage are organ-specific. This research observed the pathological effects of chronic intermittent hypoxia on rat's thoracic aorta, myocardium, liver, and kidney, under the condition of lipid metabolism disturbance, through establishing the rat model of chronic intermittent hypoxia with high-fat diet by imitating the features of human sleep apnea hypopnea syndrome. In this model, 24 male Wistar rats were randomly divided into three groups: a control group fed by regular diet, a high-fat group fed by high-fat diet, and a high-fat plus intermittent hypoxia group fed by high-fat diet and treated with intermittent hypoxia 7 h a day. At the end of the ninth week, the pathological changes of rat's organs, including the thoracic aorta, myocardium, liver, and kidney are observed (under both optical microscopy and transmission electron microscopy). As the result of the experiment shows, while there was no abnormal effect observed on any organs of the control group, slight pathological changes were found in the organs of the high-fat group. For the high-fat plus intermittent hypoxia group, however, remarkably severer damages were found on all the organs. It also showed that the severity of the damage varies by organ in the high-fat plus intermittent hypoxia group, with the thoracic aorta being the worst, followed by the liver and myocardium, and the kidney being the slightest. Chronic intermittent hypoxia can lead to multiple-organ damage to rat with high-fat diet. Different organs appear to have different sensitivity to chronic intermittent hypoxia.

  14. Systemic agonistic anti-CD40 treatment of tumor bearing mice modulates hepatic myeloid suppressive cells and causes immune-mediated liver damage

    Science.gov (United States)

    Medina-Echeverz, José; Ma, Chi; Duffy, Austin; Eggert, Tobias; Hawk, Nga; Kleiner, David E.; Korangy, Firouzeh; Greten, Tim F.

    2015-01-01

    Immune stimulatory monoclonal antibodies are currently evaluated as anti tumor agents. Although overall toxicity appears to be moderate, liver toxicities have been reported and are not completely understood. We studied the effect of systemic CD40 antibody treatment on myeloid cells in spleen and liver. Naïve and tumor-bearing mice were treated systemically with agonistic anti-CD40 antibody. Immune cell subsets in liver and spleen, serum transaminases and liver histologies were analyzed after antibody administration. Nox2−/−, Cd40−/− as well as bone marrow chimeric mice were used to study the mechanism by which agonistic anti-CD40 mediates its effects in vivo. Suppressor function of murine and human tumor-induced myeloid derived suppressive cells was studied upon CD40 ligation. Agonistic CD40 antibody caused liver damage within 24 hours after injection in two unrelated tumor models and mice strains. Using bone marrow chimeras we demonstrated that CD40 antibody-induced hepatitis in tumor-bearing mice was dependent on the presence of CD40-expressing hematopoietic cells. Agonistic CD40 ligation-dependent liver damage was induced by the generation of reactive oxygen species. Furthermore, agonistic CD40 antibody resulted in increased CD80 and CD40 positive liver CD11b+Gr-1+ immature myeloid cells. CD40 ligation on tumor-induced murine and human CD14+HLA-DRlow PBMC from cancer patients reduced their immune suppressor function. Collectively, agonistic CD40 antibody treatment activated tumor-induced, myeloid cells, caused myeloid dependent hepatotoxicity and ameliorated the suppressor function of murine and human MDSC. Collectively, our data suggests that CD40 may mature immunosuppressive myeloid cells and thereby cause liver damage in mice with an accumulation of tumor-induced hepatic MDSC. PMID:25637366

  15. Administration of high doses of copper to capuchin monkeys does not cause liver damage but induces transcriptional activation of hepatic proliferative responses.

    Science.gov (United States)

    Araya, Magdalena; Núñez, Héctor; Pavez, Leonardo; Arredondo, Miguel; Méndez, Marco; Cisternas, Felipe; Pizarro, Fernando; Sierralta, Walter; Uauy, Ricardo; González, Mauricio

    2012-02-01

    Liver cells respond to copper loading upregulating protective mechanisms. However, to date, except for liver content, there are no good indicators that identify individuals with excess liver copper. We hypothesized that administering high doses of copper to young (5.5 mg Cu · kg⁻¹ . d⁻¹) and adult (7.5 mg Cu · kg⁻¹ . d⁻¹) capuchin monkeys would induce detectable liver damage. Study groups included adult monkeys (2 females, 2 males) 3-3.5 y old at enrollment treated with copper for 36 mo (ACu); age-matched controls (1 female, 3 males) that did not receive additional copper (AC); young monkeys (2 female, 2 males) treated from birth with copper for 36 mo (YCu); and young age-matched controls (2 female, 2 males) that did not receive additional copper (YC). We periodically assessed clinical, blood biochemical, and liver histological indicators and at 36 mo the hepatic mRNA abundance of MT2a, APP, DMT1, CTR1, HGF, TGFβ, and NFκΒ only in adult monkeys. After 36 mo, the liver copper concentration was 4-5 times greater in treated monkeys relative to controls. All monkeys remained healthy with normal routine serum biochemical indices and there was no evidence of liver tissue damage. Relative mRNA abundance of HGF, TGFβ and NFκB was significantly greater in ACu than in AC monkeys. In conclusion, capuchin monkeys exposed to copper at doses up to 50 times the current upper level enhanced expression of genes related to inflammation and injury without clinical, blood biochemical, or histological evidence of liver damage.

  16. Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease.

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    Davide Povero

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy.Choline Deficient L-Amino Acid (CDAA and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens.We observed statistically significant differences in the level of extracellular vesicles (EVs in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05, fibrosis (r2 = 0.66, p<0.05 and pathological angiogenesis (r2 = 0.71, p<0.05. Extensive characterization of blood EVs identified both microparticles (MPs and exosomes (EXO present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192--two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver.These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD.

  17. Prophylactic effects of pomegranate (Punica granatum) juice on sodium fluoride induced oxidative damage in liver and erythrocytes of rats.

    Science.gov (United States)

    Bouasla, Asma; Bouasla, Ihcène; Boumendjel, Amel; Abdennour, Cherif; El Feki, Abdelfattah; Messarah, Mahfoud

    2016-07-01

    The objective of this study was to investigate the protective effects of pomegranate (Punica granatum) juice (PGJ) on oxidative damages in liver tissue and erythrocytes of rats intoxicated by sodium fluoride (NaF). Rats were randomly divided into two groups: group I received standard diet and group II received orally 1 mL of PGJ. After 5 weeks of pretreatment, each group was divided again into two subgroups and treated for another 3 weeks as follows: group I was subdivided into a control group and a group that was treated with 100 ppm of NaF (in drinking water); group II was subdivided into one group that was treated daily with both 100 ppm NaF and PGJ (1 mL orally) and one that received daily 1 mL of pomegranate juice. Exposure to NaF decreased hematological parameters, changed the total protein, albumin, bilirubin levels, and increased the activities of hepatic marker enzymes. We also noted an increase in lipid peroxidation contents, accompanied by a decrease of reduced glutathione levels. Antioxidant enzyme activities in both tissues were modified in the NaF group compared with the control group. However, the administration of PGJ juice caused an amelioration of the previous parameters. Our results indicated the potential effects of NaF to induce oxidative damage in tissues and the ability of PGJ to attenuate NaF-induced oxidative injury.

  18. The role of zinc supplementation in the inhibition of tissue damage caused by exposure to electromagnetic field in rat lung and liver tissues.

    Science.gov (United States)

    Baltaci, A K; Mogulkoc, R; Salbacak, A; Celik, I; Sivrikaya, A

    2012-01-01

    The objective of the present study was to examine the effects of zinc supplementation on the oxidant damage in lung and liver tissues in rats exposed to a 50-Hz frequency magnetic field for 5 minutes every other day over a period of 6 months. The study included 24 adult male Sprague-Dawley rats, which were divided into the three groups in equal numbers: Group 1, the control group (G1); Group 2, the group exposed to an electromagnetic field (G2); and Group 3, the group, which was exposed to an EMF and supplemented with zinc (G3). At the end of the 6-month procedures, the animals were decapitated to collect lung and liver tissue samples, in which MDA was analyzed using the "TBARS method (nmol/g/protein)", GSH by the "biuret method (mg/g/protein)" and zinc levels by atomic emission (µg/dl). MDA levels in lung and liver tissues in G2 were higher than those in G1 and G3, and the levels in G3 were higher than those in G1 (pelectromagnetic field caused cellular damage in lung and liver tissues and zinc supplementation inhibited the inflicted cellular damage. Another important result of this study that needs emphasis was that exposure to an electromagnetic field led to a significant decrease in zinc levels in lung and liver tissues (Tab. 3, Ref. 23).

  19. Plasma clearance of sup(99m)Tc-N/2,4-dimethyl-acetanilido/iminodiacetate complex as a measure of parenchymal liver damage

    International Nuclear Information System (INIS)

    Studniarek, M.; Durski, K.; Liniecki, J.; Akademia Medyczna, Lodz

    1983-01-01

    Fifty-two patients were studied with various diseases affecting liver parenchyma. Any disorders of bile transport were excluded on the basis of dynamic liver scintigraphy using intravenously injected N/2,4-dimethyl acetanilid/iminodiacetate sup(99m)Tc complex (HEPIDA). The activity concentration of sup(99m)Tc-HEPIDA in plasma was measured from 5 through 60 min post injection. Clearance of the substance (Clsub(B)) was calculated from blood plasma disappearance curves and compared with results of 13 laboratory tests used conventionally for assessment of damage of the liver and its functional capacity; age and body weight was also included in the analysis. Statistical relations were studied using linear regression analysis of two variables, multiple regression analysis as well as multidimensional analysis of variance. It was demonstrated that sup(99m)Tc-HEPIDA clearance is a simple, accurate and repeatable measure of liver parenchyma damage. In males, values of Clsub(B) above 245 ml min - 1 /1.73 m 2 exclude hepatic damage with high probability; values below 195 ml min - 1 /1.73 m 2 indicate evident impairment of liver parenchyma function. (orig.) [de

  20. Detection of xenobiotic-induced DNA damage by the comet assay applied to human and rat precision-cut liver slices

    NARCIS (Netherlands)

    Plazar, Janja; Hrejac, Irena; Pirih, Primoz; Filipic, Metka; Groothuis, Geny M. M.

    The comet assay is a simple and sensitive method for measuring DNA damage at the level of individual cells and is extensively used in genotoxicity studies. It is commonly applied to cultured cells. The aim of this study was to apply the comet assay for use in fresh liver tissue, where metabolic

  1. Experimental study on ablating goat liver tissue with ultrasound imaging guided percutaneous irreversible electroporation

    Directory of Open Access Journals (Sweden)

    Ying LIU

    2011-03-01

    Full Text Available Objective To investigate the proper method of percutaneous irreversible electroporation(IRE to ablate goat liver tissue under ultrasonic guidance,and observe the features of ultrasound imaging and histological changes.Methods The pulse electric fields(PEFs with permanent duration(100 μs,frequency(1Hz,voltage(2000V and pulses(120 pieces were applied to the electrodes,and the electrodes were placed into goats’ liver under ultrasound guidance through the animal skin to the target area.The treated area was observed by real-time ultrasound scanning,and the histopathological changes were assessed by hematoxylin and eosin(HE staining under light microscope at the time of 0h and 24h after IRE ablation.The circumscribed ablated area was compared with that of finite element modeling(FEM calculation method.Results Ultrasound imaging guidance was accurate in focusing on the target area.Imaging captured by the ultrasound after IRE procedure was quite different from that of the normal liver imaging.Complete hepatic cell death with a sharp demarcation between the ablated zone and the non-ablated zone was well visualized 24 hours after the procedure.Necrospy-based measurement demonstrated a high consistence with FEM-anticipated ablation zones.Conclusion With real-time monitoring by ultrasonography and well-controlled ablation of the target tissue,percutaneous IRE can provide a novel and unique ablative method for cancer treatment.The present paper provides a fundamental experimental work for future studies on clinical application of IRE.

  2. Fagraea racemosa leaf extract inhibits oxidative stress-induced liver damage in Wistar rats

    Directory of Open Access Journals (Sweden)

    Eva Rachmi

    2012-07-01

    Full Text Available Latar belakang: Kemampuan hati mengatasi stres oksidatif dapat ditingkatkan dengan konsumsi antioksidan eksogen yang berasal dari alam. Penelitian ini ditujukan untuk mempelajari kemampuan hepatoprotektif dari ekstrak metanol  daun  Fagraea racemosa, dengan menggunakan CCL4 sebagai model sumber radikal bebas. Metode: Tiga kelompok perlakuan tikus Wistar  (enam ekor per  kelompok, masing-masing diberi dosis ekstrak berturut-turut 50, 100, 200 mg/kg bb per oral, sekali perhari selama 30 hari. CCl4 diinjeksikan intraperitoneal kepada ketiga kelompok , dua kali per minggu (1,5 ml/kg bb.  Sebagai pembanding, digunakan dua kelompok kontrol, yaitu kontrol normal dan kontrol CCl4.  Pada hari ke-30, tikus dibunuh dan hati diwarnai dengan hematoksilin-eosin. Perubahan histopatologi ditentukan berdasar derajat steatosis, degenerasi hidropik, dan inflamasi. Data dianalisis dengan Anova dan uji post hoc LSD (p≤0.05 menggunakan SPSS versi 13.0 Hasil: Hasil menunjukkan perbaikan derajat degenerasi hidropik dan inflamasi (p≤0,05 pada ketiga kelompok perlakuan bila dibanding dengan kelompok kontrol CCl4. Tetapi, derajat steatosis meningkat pada kelompok perlakuan dosis  50 dan 100 mg/kg bb, dan kemudian menurun secara bermakna pada perlakuan 200 mg/kg bb. Kesimpulan : Ekstrak methanol daun Fagraea racemosa  mampu melindungi hati dari radikal bebas yang dihasilkan dari CCl4. Hasil ini mengindikasikan bahwa Fagraea racemosa menjanjikan untuk dikembangkan sebagai suplemen antioksidan. (Health Science Indones 2011;2:46-51   Abstract Background: The ability of the liver in dealing with oxidative stress can be enhanced by consumption of exogenous antioxidants derived from nature. This study aimed to explore the hepatoprotective ability of Fagraea racemosa leaves methanolic extract against CCl4 exposure as a model of free radicals source. Methods: Three different doses (50, 100, 200 mg/kg bw were administered orally to three treatment groups of Wistar rats

  3. Grapefruit juice intake does not enhance but rather protects against aflatoxin B1-induced liver DNA damage through a reduction in hepatic CYP3A activity.

    Science.gov (United States)

    Miyata, Masaaki; Takano, Hiroki; Guo, Lian Q; Nagata, Kiyoshi; Yamazoe, Yasushi

    2004-02-01

    Influence of grapefruit juice intake on aflatoxin B1 (AFB1)-induced liver DNA damage was examined using a Comet assay in F344 rats given 5 mg/kg AFB1 by gavage. Rats allowed free access to grapefruit juice for 5 days prior to AFB1 administration resulted in clearly reduced DNA damage in liver, to 65% of the level in rats that did not receive grapefruit juice. Furthermore, rats treated with grapefruit juice extract (100 mg/kg per os) for 5 days prior to AFB1 treatment also reduced the DNA damage to 74% of the level in rats that did not receive grapefruit juice. No significant differences in the portal blood and liver concentrations of AFB1 were observed between grapefruit juice intake rats and the controls. In an Ames assay with AFB1 using Salmonella typhimurium TA98, lower numbers of revertant colonies were detected with hepatic microsomes prepared from rats administered grapefruit juice, compared with those from control rats. Microsomal testosterone 6beta-hydroxylation was also lower with rats given grapefruit juice than with control rats. Immunoblot analyses showed a significant decrease in hepatic CYP3A content, but not CYP1A and CYP2C content, in microsomes of grapefruit juice-treated rats than in non-treated rats. No significant difference in hepatic glutathione S-transferase (GST) activity and glutathione content was observed in the two groups. GSTA5 protein was not detected in hepatic cytosol of the two groups. In microsomal systems, grapefruit juice extract inhibited AFB1-induced mutagenesis in the presence of a microsomal activation system from livers of humans as well as rats. These results suggest that grapefruit juice intake suppresses AFB1-induced liver DNA damage through inactivation of the metabolic activation potency for AFB1 in rat liver.

  4. Experimental study of surface quality and damage when drilling unidirectional CFRP composites

    Directory of Open Access Journals (Sweden)

    Eshetu D. Eneyew

    2014-10-01

    Full Text Available In this study, an experimental investigation on the drilling of unidirectional carbon fiber reinforced plastic (UD-CFRP composite was conducted using polycrystalline diamond (PCD tipped eight facet drill. The quality of the drilled hole surface was examined through surface roughness measurements and surface damage by scanning electron microscopy (SEM. It was found that fiber pullout occurred in two specific sectors relative to the angle between the cutting direction and the fiber orientation. The thrust force was highly influenced by the feed rate than the cutting speed and it shows a significant variation throughout the rotation of the drill.

  5. 1,25-(OH)2-vitamin D3 prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4−/− model

    International Nuclear Information System (INIS)

    Reiter, Florian P.; Hohenester, Simon; Nagel, Jutta M.; Wimmer, Ralf; Artmann, Renate; Wottke, Lena; Makeschin, Marie-Christine; Mayr, Doris; Rust, Christian; Trauner, Michael; Denk, Gerald U.

    2015-01-01

    Background/Purpose of the study: Vitamin D 3 -deficiency is common in patients with chronic liver-disease and may promote disease progression. Vitamin D 3 -administration has thus been proposed as a therapeutic approach. Vitamin D 3 has immunomodulatory effects and may modulate autoimmune liver-disease such as primary sclerosing cholangitis. Although various mechanisms of action have been proposed, experimental evidence is limited. Here we test the hypothesis that active 1,25-(OH) 2 -vitamin D 3 inhibits activation of hepatic stellate cells (HSC) in vitro and modulates liver-injury in vivo. Methods: Proliferation and activation of primary murine HSC were assessed by BrdU- and PicoGreen ® -assays, immunoblotting, immunofluorescence-microscopy, quantitative-PCR, and zymography following calcitriol-treatment. Wild-type and ATP-binding cassette transporter b4 −/− (Abcb4 −/− )-mice received calcitriol for 4 weeks. Liver-damage, inflammation, and fibrosis were assessed by serum liver-tests, Sirius-red staining, quantitative-PCR, immunoblotting, immunohistochemistry and hydroxyproline quantification. Results: In vitro, calcitriol inhibited activation and proliferation of murine HSC as shown by reduced α-smooth muscle actin and platelet-derived growth factor-receptor-β-protein-levels, BrdU and PicoGreen®-assays. Furthermore, mRNA-levels and activity of matrix metalloproteinase 13 were profoundly increased. In vivo, calcitriol ameliorated inflammatory liver-injury reflected by reduced levels of alanine aminotransferase in Abcb4 −/− -mice. In accordance, their livers had lower mRNA-levels of F4/80, tumor necrosis factor-receptor 1 and a lower count of portal CD11b positive cells. In contrast, no effect on overall fibrosis was observed. Conclusion: Calcitriol inhibits activation and proliferation of HSCs in vitro. In Abcb4 −/− -mice, administration of calcitriol ameliorates inflammatory liver-damage but has no effect on biliary fibrosis after 4 weeks

  6. 1,25-(OH){sub 2}-vitamin D{sub 3} prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4{sup −/−} model

    Energy Technology Data Exchange (ETDEWEB)

    Reiter, Florian P., E-mail: florian.reiter@med.uni-muenchen.de [Department of Medicine II, Liver Center Munich, University of Munich, Marchioninistr. 15, D-81377 Munich (Germany); Hohenester, Simon; Nagel, Jutta M.; Wimmer, Ralf; Artmann, Renate; Wottke, Lena [Department of Medicine II, Liver Center Munich, University of Munich, Marchioninistr. 15, D-81377 Munich (Germany); Makeschin, Marie-Christine; Mayr, Doris [Institute of Pathology, University of Munich, Thalkirchner Str. 36, D-80337 Munich (Germany); Rust, Christian [Department of Medicine I, Krankenhaus Barmherzige Brüder, Romanstr. 93, D-80639 Munich (Germany); Trauner, Michael [Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna (Austria); Denk, Gerald U. [Department of Medicine II, Liver Center Munich, University of Munich, Marchioninistr. 15, D-81377 Munich (Germany)

    2015-04-03

    Background/Purpose of the study: Vitamin D{sub 3}-deficiency is common in patients with chronic liver-disease and may promote disease progression. Vitamin D{sub 3}-administration has thus been proposed as a therapeutic approach. Vitamin D{sub 3} has immunomodulatory effects and may modulate autoimmune liver-disease such as primary sclerosing cholangitis. Although various mechanisms of action have been proposed, experimental evidence is limited. Here we test the hypothesis that active 1,25-(OH){sub 2}-vitamin D{sub 3} inhibits activation of hepatic stellate cells (HSC) in vitro and modulates liver-injury in vivo. Methods: Proliferation and activation of primary murine HSC were assessed by BrdU- and PicoGreen{sup ®}-assays, immunoblotting, immunofluorescence-microscopy, quantitative-PCR, and zymography following calcitriol-treatment. Wild-type and ATP-binding cassette transporter b4{sup −/−} (Abcb4{sup −/−})-mice received calcitriol for 4 weeks. Liver-damage, inflammation, and fibrosis were assessed by serum liver-tests, Sirius-red staining, quantitative-PCR, immunoblotting, immunohistochemistry and hydroxyproline quantification. Results: In vitro, calcitriol inhibited activation and proliferation of murine HSC as shown by reduced α-smooth muscle actin and platelet-derived growth factor-receptor-β-protein-levels, BrdU and PicoGreen®-assays. Furthermore, mRNA-levels and activity of matrix metalloproteinase 13 were profoundly increased. In vivo, calcitriol ameliorated inflammatory liver-injury reflected by reduced levels of alanine aminotransferase in Abcb4{sup −/−}-mice. In accordance, their livers had lower mRNA-levels of F4/80, tumor necrosis factor-receptor 1 and a lower count of portal CD11b positive cells. In contrast, no effect on overall fibrosis was observed. Conclusion: Calcitriol inhibits activation and proliferation of HSCs in vitro. In Abcb4{sup −/−}-mice, administration of calcitriol ameliorates inflammatory liver-damage but has

  7. Simultaneous Administration of ADSCs-Based Therapy and Gene Therapy Using Ad-huPA Reduces Experimental Liver Fibrosis.

    Science.gov (United States)

    Meza-Ríos, Alejandra; García-Benavides, Leonel; García-Bañuelos, Jesus; Salazar-Montes, Adriana; Armendáriz-Borunda, Juan; Sandoval-Rodríguez, Ana

    2016-01-01

    hADSCs transplantation in cirrhosis models improves liver function and reduces fibrosis. In addition, Ad-huPA gene therapy diminished fibrosis and increased hepatocyte regeneration. In this study, we evaluate the combination of these therapies in an advanced liver fibrosis experimental model. hADSCs were expanded and characterized before transplantation. Ad-huPA was simultaneously administrated via the ileac vein. Animals were immunosuppressed by CsA 24 h before treatment and until sacrifice at 10 days post-treatment. huPA liver expression and hADSCs biodistribution were evaluated, as well as the percentage of fibrotic tissue, hepatic mRNA levels of Col-αI, TGF-β1, CTGF, α-SMA, PAI-I, MMP2 and serum levels of ALT, AST and albumin. hADSCs homed mainly in liver, whereas huPA expression was similar in Ad-huPA and hADSCs/Ad-huPA groups. hADSCs, Ad-huPA and hADSCs/Ad-huPA treatment improves albumin levels, reduces liver fibrosis and diminishes Collagen α1, CTGF and α-SMA mRNA liver levels. ALT and AST serum levels showed a significant decrease exclusively in the hADSCs group. These results showed that combinatorial effect of cell and gene-therapy does not improve the antifibrogenic effects of individual treatments, whereas hADSCs transplantation seems to reduce liver fibrosis in a greater proportion.

  8. Experimental setup and first measurement of DNA damage induced along and around an antiproton beam

    International Nuclear Information System (INIS)

    Kavanagh, J.N.; Currell, F.J.; Prise, K.M.; Schettino, G.; Currell, F.J.; Timson, D.J.; Holzscheiter, M.H.; Bassler, N.; Herrmann, R.

    2010-01-01

    Radiotherapy employs ionizing radiation to induce lethal DNA lesions in cancer cells while minimizing damage to healthy tissues. Due to their pattern of energy deposition, better therapeutic outcomes can, in theory, be achieved with ions compared to photons. Antiprotons have been proposed to offer a further enhancement due to their annihilation at the end of the path. The work presented here aimed to establish and validate an experimental procedure for the quantification of plasmid and genomic DNA damage resulting from antiproton exposure. Immunocytochemistry was used to assess DNA damage in directly and indirectly exposed human fibroblasts irradiated in both plateau and Bragg peak regions of a 126 MeV antiproton beam at CERN. Cells were stained post irradiation with an anti-γ-H2AX antibody. Quantification of the γ-H2AX foci-dose relationship is consistent with a linear increase in the Bragg peak region. A qualitative analysis of the foci detected in the Bragg peak and plateau region indicates significant differences highlighting the different severity of DNA lesions produced along the particle path. Irradiation of desalted plasmid DNA with 5 Gy antiprotons at the Bragg peak resulted in a significant portion of linear plasmid in the resultant solution. (authors)

  9. Hepatoprotective and nephroprotective effects of Cnidoscolus aconitifolius in protein energy malnutrition induced liver and kidney damage.

    Science.gov (United States)

    Oyagbemi, Ademola A; Odetola, Adebimpe A

    2013-10-01

    This study was designed to evaluate the ameliorative and hypocholesterolemic effects of dietary supplementation of Cnidoscolus aconitifolius leaf meal (CALM) on hepatic injury and kidney injury associated with protein energy malnutrition (PEM). In this study, PEM was induced in weaning male Wistar albino rats by feeding them with low protein diet for 2 weeks. The effects of several recovery diets containing 20% soya protein or 20% C. aconitifolius in place of soya protein or 10% soya proteins with 10% C. aconitifolius or commercial rat feed were assessed in PEM rats. Plasma biochemical parameters were assessed as well. After the induction of PEM, results obtained showed significant increase in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total proteins (T.P), total bilirubin (T.Bil), triglycerides, total cholesterol, low density lipoproteins (LDL), blood urea nitrogen (BUN), and creatinine with significant reduction in plasma high density lipoproteins (HDL), albumin, sodium (Na(+)), potassium (K(+)), chloride (Cl(-)), bicarbonate (HC03(-)), and phosphate (P04(2-)) in PEM rats. Upon introduction of recovery diets containing 20% soya protein or 20% C. aconitifolius in place of soya protein or 10% soya proteins with 10% C. aconitifolius or commercial rat feed for 4 weeks caused significant (P protein deficient diets has a protective role against hepatic injury and renal damage associated with PEM.

  10. Protective effects of extracts of Vernonia amygdalina, Hibiscus sabdariffa and vitamin C against radiation-induced liver damage in rats

    International Nuclear Information System (INIS)

    Adaramoye, Oluwatosin; Ogungbenro, Bayo; Anyaegbu, Oluchi; Fafunso, Michael

    2008-01-01

    The radioprotective efficacy of methanolic extracts of leaves of Vernonia amygdalina (VA) and Hibiscus sabdariffa (HS), and vitamin C (VIT C) against gamma radiation (4 Gy) induced liver damage was studied in male Wistar albino rats. VIT C was administered at a dose of 250 mg/kg body weight, while VA and HS were administered at doses; 200, 400 and 800-mg/kg body weight, orally for 4 weeks prior to radiation and 5 weeks after irradiation. The rats were sacrificed at 24 hours and 5 weeks after irradiation. Treatment with VIT C and VA (800 mg/kg) significantly (p<0.05) decreased the gamma radiation-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at 24 hours after irradiation, whereas, HS (400 mg/kg) significantly (p<0.05) decreased the serum ALT activity only. Similarly, treatment with VIT C and VA (800 mg/kg) significantly (p<0.05) decreased the serum conjugated bilirubin levels by 56% and 29%, respectively at 24 hours. Furthermore, VIT C, VA and HS significantly (p<0.05) decreased the levels of serum lipid peroxidation (LPO) and increased the hepatic superoxide dismutase (SOD) activities at 24 hours. Treatment for 5 weeks after irradiation with VIT C, VA and HS significantly (p<0.05) decreased the levels of unconjugated bilirubin, while VIT C and VA alone decreased the levels of conjugated bilirubin. Furthermore, treatment with VA (400 and 800 mg/kg) decreased the serum ALT activities by 25% and 34%, respectively, at 5 weeks after irradiation. Similarly, alkaline phosphatase and lipid peroxidation (LPO) levels were significantly (p<0.05) attenuated following treatment with VIT C and VA (400 and 800 mg/kg) at 5 weeks after irradiation. In addition, treatment with VIT C, VA (800 mg/kg) and HS (400 and 800 mg/kg) significantly (p<0.05) elevated the levels of reduced glutathione (GSH) by 61%, 56%, 41% and 44%, respectively, at 5 weeks. Similar elevation of antioxidant enzymes; SOD, glutathione-s-transferase and

  11. Various irrigation fluids affect postoperative brain edema and cellular damage during experimental neurosurgery in rats.

    Science.gov (United States)

    Doi, Kazuhisa; Kawano, Takeshi; Morioka, Yujiro; Fujita, Yasutaka; Nishimura, Masuhiro

    2006-12-01

    This study was conducted to investigate how various irrigation fluids used during neurosurgical procedures affect the degree of postoperative brain edema and cellular damage during experimental neurosurgery in rats. The cerebral cortex was exposed and incised crosswise with a surgical knife under irrigation with an artificial CSF, lactated Ringer's solution, or normal saline. Four hours after injury, irrigation was stopped and brain tissue samples were obtained from injured and uninjured sites. Specific gravity, cerebrovascular permeability, and TTC staining of the samples were evaluated. Incision and irrigation of the brain were not performed on the control group. At the injured site, specific gravities of the samples in the normal saline group and the lactated Ringer's solution group were significantly lower than the specific gravity in the artificial CSF group. The EB concentration was significantly higher in the lactated Ringer's solution group and relatively high in the normal saline group as compared with the artificial CSF group. TTC staining did not differ significantly between the artificial CSF group and the control group. It was significantly lower in the lactated Ringer's solution group and the normal saline group than in the control group and the artificial CSF group. As compared with normal saline and lactated Ringer's solution, artificial CSF reduced postoperative brain edema, cerebrovascular permeability, and cellular damage in sites injured by experimental neurosurgery in rats.

  12. A Theoretical and Experimental Investigation of Mechanical Damage to Rodent Sperm Generated by Microscale Ice Formation.

    Science.gov (United States)

    Han, X; Critser, J K

      BACKGROUND: Rodent sperm cryopreservation is of critical importance for the maintenance of lines or strains of genetically engineered mice and rats. However, rodent sperm are extremely mechanically sensitive due to their unusual morphology, and are severely damaged using current methods of cryopreservation. Those methods result in poor post thaw motility (PTM) for mouse. To investigate the mechanism of mechanical damage introduced to rodent sperm during freezing, a micro-mechanical model was established to analyze the sperm radial and axial thermal stresses generated by microscale extracellular ice formation. PTM of mouse sperm cryopreserved in capillaries of different radii (100, 200, 344, 526, 775µm) was measured using a standard computer-assisted sperm analysis system. The model predicts that when one of the inner dimensions of the containers (the inner diameter of plastic straws or straw capillaries) is on the same order of magnitude of sperm length, axial stress is significantly increased. The experimental results showed that the value of PTM was decreased from 38 ± 8 % in the larger (775µm) capillaries to 0 ± 0 % in the smaller (100 µm) ones. Theoretical analysis based on the established model were experimentally validated and can be used to guide the design of novel devices to improve the efficiency of rodent sperm cryopreservation.

  13. Laser shocks: A tool for experimental simulation of damage into materials

    Energy Technology Data Exchange (ETDEWEB)

    Boustie, M.; Cuq Lelandais, J. P.; Berthe, L.; Ecault, R. [Institut PPRIME, Departement Physique et Mecanique des Materiaux, CNRS-ENSMA-Universite de Poitiers, 1 av Clement Ader, 86961 FUTUROSCOPE Cedex (France); CEA-DAM Valduc, 21120 Is-sur-Tille (France); Laboratoire Procedes et Ingenierie en Mecanique et Materiaux (CNRS), Arts et Metiers ParisTech, 151 bd de l' Hopital, 75013 PARIS (France); Institut PPRIME, Departement Physique et Mecanique des Materiaux, CNRS-ENSMA-Universite de Poitiers, 1 av Clement Ader, 86961 FUTUROSCOPE Cedex (France)

    2012-07-30

    High power laser irradiation of solids results in a strong shock wave propagation, driving very high amplitude pressure loadings with very short durations. These particular characteristics offer the possibility to study the behaviour of matter under extreme dynamic conditions in continuity with what is possible with the conventional generators of shock (launchers of projectiles, explosives). An advantage of laser shocks is a possible recovery of the shocked samples presenting the metallurgical effects of the shock in most cases. We introduce the principle of the laser shock generation, the characterization of these shocks, the principal mechanisms and effects associated with their propagation in the solids. We show how laser shocks can be a laboratory tool for simulating shock effects at ultra high strain rate, providing a high in information experimental layout for validation of damage modelling on an extended strain rate range compared to conventional shock generators. New data have been obtained with ultra short femtosecond range irradiation. Experimental data gathered through post mortem observation, time resolved velocity measurement are shown along with numerical associated simulations, showing the possibility to predict the damage behaviour of metallic targets under extreme strain rate up to 10{sup 8} s{sup -1}.

  14. Ameliorating reactive oxygen species-induced in vitro lipid peroxidation in brain, liver, mitochondria and DNA damage by Zingiber officinale Roscoe.

    Science.gov (United States)

    Ajith, T A

    2010-01-01

    Iron is an essential nutrient for a number of cellular activities. However, excess cellular iron can be toxic by producing reactive oxygen species (ROS) such as superoxide anion (O(2) (-)) and hydroxyl radical (HO(·)) that damage proteins, lipids and DNA. Mutagenic and genotoxic end products of lipid peroxidation can induce the decline of mitochondrial respiration and are associated with various human ailments including aging, neurodegenerative disorders, cancer etc. Zingiber officinale Roscoe (ginger) is a widely used spice around the world. The protective effect of aqueous ethanol extract of Z. officinale against ROS-induced in vitro lipid peroxidation and DNA damage was evaluated in this study. The lipid peroxidation was induced by hydroxyl radical generated from Fenton's reaction in rat liver and brain homogenates and mitochondrial fraction (isolated from rat liver). The DNA protection was evaluated using H(2)O(2)-induced changes in pBR-322 plasmid and Fenton reaction-induced DNA fragmentation in rat liver. The results indicated that Z. officinale significantly (Pofficinale in the liver homogenate was 94 %. However, the extract could partially alleviate the DNA damage. The protective mechanism can be correlated to the radical scavenging property of Z. officinale. The results of the study suggest the possible nutraceutical role of Z. officinale against the oxidative stress induced human ailments.

  15. Fucoidan from Fucus vesiculosus Protects against Alcohol-Induced Liver Damage by Modulating Inflammatory Mediators in Mice and HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Jung Dae Lim

    2015-02-01

    Full Text Available Fucoidan is an l-fucose-enriched sulfated polysaccharide isolated from brown algae and marine invertebrates. In this study, we investigated the protective effect of fucoidan from Fucus vesiculosus on alcohol-induced murine liver damage. Liver injury was induced by oral administration of 25% alcohol with or without fucoidan (30 mg/kg or 60 mg/kg for seven days. Alcohol administration increased serum aspartate aminotransferase and alanine aminotransferase levels, but these increases were suppressed by the treatment of fucoidan. Transforming growth factor beta 1 (TGF-β1, a liver fibrosis-inducing factor, was highly expressed in the alcohol-fed group and human hepatoma HepG2 cell; however, the increase in TGF-β1 expression was reduced following fucoidan administration. Treatment with fucoidan was also found to significantly reduce the production of inflammation-promoting cyclooygenase-2 and nitric oxide, while markedly increasing the expression of the hepatoprotective enzyme, hemeoxygenase-1, on murine liver and HepG2 cells. Taken together, the antifibrotic and anti-inflammatory effects of fucoidan on alcohol-induced liver damage may provide valuable insights into developing new therapeutics or interventions.

  16. Experimental studies on local damage of reinforced concrete structures by the impact of deformable missiles-Part 1

    International Nuclear Information System (INIS)

    Muto, K.; Tachikawa, H.; Sugano, T.; Tsubota, H.; Kobayshi, H.; Kasai, Y.; Koshika, N.; Tsujimoto, T.

    1989-01-01

    Structural damage induced by an accidental aircraft crash into a reinforced concrete structure includes local damage caused by the engine, the rigid portion of the aircraft, and the global elasto-plastic structural response caused by the entire aircraft. Local damage consists of spalling of concrete from the front face of the target together with missile penetration into the target, scabbing of concrete from the rear face of the target and perforation of the missile through the target. The engine is a soft missile that deforms during impact. An experimental research program has been planned and executed to establish a rational evaluation method of the local damage by the deformable engine missiles

  17. Effects of curcumin on antioxidative activities and cytokine production in Jian carp (Cyprinus carpio var. Jian) with CCl4-induced liver damage.

    Science.gov (United States)

    Cao, Liping; Ding, Weidong; Du, Jingliang; Jia, Rui; Liu, Yingjuan; Zhao, Caiyuan; Shen, Yujin; Yin, Guojun

    2015-03-01

    We investigated the protective effects of curcumin on liver-damaged Cyprinus carpio var. Jian (Jian carp). The carp were fed 0.1%, 0.5%, or 1.0% curcumin for 60 days, then injected intraperitoneally with 30% carbon tetrachloride solution. Liver and blood samples were collected to measure the liver index, serum- and liver-associated enzymes, liver histology, nuclear factor-κB (NF-κB)/c-Rel, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-12 mRNA expression, and the level of NF-κB/c-Rel protein in the liver, and for a comet assay. We found that 0.5% and 1.0% curcumin significantly reduced the CCl(4)-induced increase in the liver index. The comet assay showed that the tail moment, olive tail moment, tail length, and tail DNA% improved in fish pretreated with 0.5 or 1.0% curcumin. CCl(4)-induced histological changes, including extensive hepatocyte degeneration, indistinct cell borders, nuclear condensation, and karyolysis were clearly reduced after treatment with 0.5% and 1.0% curcumin. Moreover, 0.5% and 1.0% curcumin significantly inhibited the CCl(4)-induced increase in serum glutamic oxaloacetic transaminase and promoted the restoration of superoxide dismutase in the liver; 1.0% curcumin significantly reduced serum glutamic pyruvic transaminase and lactate dehydrogenase and hepatic malondialdehyde, but significantly increased the total antioxidant capacity and glutathione levels in the liver. The CCl(4)-induced upregulation of NF-κB/c-Rel, IL-1β, and TNF-α mRNAs and NF-κB/c-Rel protein levels was inhibited by 0.5% and 1.0% curcumin, and IL-12 mRNA was reduced by all three doses of curcumin. The effects of curcumin on the liver index, enzymes, histological changes, and cytokines were dose-dependent. Our results indicate that curcumin reduces CCl(4)-induced liver damage in Jian carp by upregulating antioxidative activities and inhibiting NF-κB, IL-1β, TNF-α, and IL-12 expression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Effect of Ganfukang on liver function and serum hepatic fibrosis markers levels in SD rats with experimental hepatic fibrosis

    International Nuclear Information System (INIS)

    Che Ying; Wang Shanju; Xu Tingting; Jiang Miaona; Jia Yujie

    2004-01-01

    Objective: To observe the effect of Ganfukang on liver function and serum hepatic fibrosis markers levels in SD rats with experimental hepatic fibrosis. Methods: SD rat models of liver fibrosis was induced by CCl 4 (n=57). Liver function (GPT, GOT) and serum hepatic fibrosis markers levels (HA, LN, C-IV, PC-III, with RIA) were tested in these models and 10 control rats. Eleven model rats were left untreated, the others were treated with Ganfukang of different concentrations and the above hepatic parameters were again determined after completion of treatment. Results: Lever function was much deteriorated and serum markers levels significantly increased in the model rats (vs controls, P<0.01). After treatment with Ganfukang, the improvement was significant (vs untreated models, P<0.01). Conclusion: Ganfukang is of definite therapeutic value for experimental hepatic fibrosis in rat models. (authors)

  19. MRT of experimental liver abscesses - comparison of a new blood pool contrast agent with gadolinium-DTPA

    International Nuclear Information System (INIS)

    Dick, A.; Adam, G.; Spuentrup, E.; Prescher, A.; Muehler, A.; Guenther, R.W.

    1996-01-01

    Purpose: In an experimental pyogenic liver abscess model, the signal intensities were compared intraindividually and interindividually after the application of a new blood pool contrast agent, 24-gadolinium-DTPA (diethylenetriamine-pentaacetic acid) cascade polymer, and after the application of gadopentetate dimeglumine. Methods: In 20 rabbits with experimentally induced liver abscesses, the relative signal intensities of the liver, abscess centre, abscess wall and portal vein were assessed before and between 30 seconds and 60 minutes after injection of a 25 μmol/kg dose of gadolinium polymer and of 100 μmol/kg of gadolinium-DTPA, respectively. Measurements were performed at 1.5 Tesla, using a head coil and a Flash-2-D sequence. Results: The interindividual comparison (unpaired T-test, p [de

  20. Studies on the distribution of manganese (54Mn) in broilers with experimental fatty liver degeneration

    International Nuclear Information System (INIS)

    Nowosad, R.; Simoni, J.

    1979-01-01

    The studies were performed on 30 broilers, at the age of 6 weeks, crossbred DWC chi WR, with an experimental fatty liver degeneration caused by subcutaneous injection of carbon tetrachloride at a dose of 2.5 ml per 1 kg of body weight for 2 weeks. In the second week each bird was injected subcutaneously in subpectorial region 2rCi of 54 Mn per one kg of body weight. Radioactivity of parenchymatous organs, digestive tract and its content, trachea, lungs, ovaries, bones, muscles, skin, feathers, gall, cloth, blood serum was measured on scintillograph USB - 2 cooperating with electronic computer PT - 72. After an appropriate correction the results were presented in a form of the percentage of the applied dose in one g of a specimen, multiplied by 10 2 . It was found that the level of manganese 54 was lower in the experimental birds in comparison to control ones. One exception was the content of rectum, serum and cloth. In these cases the observed differences were statistically insignificant. (author)

  1. Damage threshold of lithium niobate crystal under single and multiple femtosecond laser pulses: theoretical and experimental study

    International Nuclear Information System (INIS)

    Meng, Qinglong; Zhang, Bin; Zhong, Sencheng; Zhu, Liguo

    2016-01-01

    The damage threshold of lithium niobate crystal under single and multiple femtosecond laser pulses has been studied theoretically and experimentally. Firstly, the model for the damage threshold prediction of crystal materials based on the improved rate equation has been proposed. Then, the experimental measure method of the damage threshold of crystal materials has been given in detail. On the basis, the variation of the damage threshold of lithium niobate crystal with the pulse duration has also been analyzed quantitatively. Finally, the damage threshold of lithium niobate crystal under multiple laser pulses has been measured and compared to the theoretical results. The results show that the transmittance of lithium niobate crystal is almost a constant when the laser pulse fluence is relative low, whereas it decreases linearly with the increase in the laser pulse fluence below the damage threshold. The damage threshold of lithium niobate crystal increases with the increase in the duration of the femtosecond laser pulse. And the damage threshold of lithium niobate crystal under multiple laser pulses is obviously lower than that irradiated by a single laser pulse. The theoretical data fall in good agreement with the experimental results. (orig.)

  2. Diet - liver disease

    Science.gov (United States)

    Proteins normally help the body repair tissue. They also prevent fatty buildup and damage to the liver cells. In people with badly damaged livers, proteins are not properly processed. Waste products may build up and affect the brain. Dietary ...

  3. Evaluation of the risk of liver damage from the use of 5-aminolevulinic acid for intra-operative identification and resection in patients with malignant gliomas

    DEFF Research Database (Denmark)

    Offersen, Cecilie Mørck; Skjoeth-Rasmussen, Jane

    2017-01-01

    BACKGROUND: The clinical efficacy of 5-aminolevulinic acid (5-ALA) for fluorescence-guided surgery of malignant gliomas is evident from several studies; however, as post-operative elevations of liver enzymes have been seen, there is a potential risk of liver damage upon administration. The aim...... (September 2012-September 2014) at the University Hospital of Copenhagen, Rigshospitalet, was conducted. All patients received a pre-operative dose of 20 mg/kg bodyweight 5-ALA. The pre- and post-operative enzyme levels of alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase...

  4. Supplementation of T3 Recovers Hypothyroid Rat Liver Cells from Oxidatively Damaged Inner Mitochondrial Membrane Leading to Apoptosis

    Directory of Open Access Journals (Sweden)

    Sutapa Mukherjee

    2014-01-01

    Full Text Available Hypothyroidism is a growing medical concern. There are conflicting reports regarding the mechanism of oxidative stress in hypothyroidism. Mitochondrial oxidative stress is pivotal to thyroid dysfunction. The present study aimed to delineate the effects of hepatic inner mitochondrial membrane dysfunction as a consequence of 6-n-propyl-2-thiouracil-induced hypothyroidism in rats. Increased oxidative stress predominance in the submitochondrial particles (SMP and altered antioxidant defenses in the mitochondrial matrix fraction correlated with hepatocyte apoptosis. In order to check whether the effects caused by hypothyroidism are reversed by T3, the above parameters were evaluated in a subset of T3-treated hypothyroid rats. Complex I activity was inhibited in hypothyroid SMP, whereas T3 supplementation upregulated electron transport chain complexes. Higher mitochondrial H2O2 levels in hypothyroidism due to reduced matrix GPx activity culminated in severe oxidative damage to membrane lipids. SMP and matrix proteins were stabilised in hypothyroidism but exhibited increased carbonylation after T3 administration. Glutathione content was higher in both. Hepatocyte apoptosis was evident in hypothyroid liver sections; T3 administration, on the other hand, exerted antiapoptotic and proproliferative effects. Hence, thyroid hormone level critically regulates functional integrity of hepatic mitochondria; hypothyroidism injures mitochondrial membrane lipids leading to hepatocyte apoptosis, which is substantially recovered upon T3 supplementation.

  5. Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor

    Directory of Open Access Journals (Sweden)

    Kezhen Shen

    2017-01-01

    Full Text Available Experimental cholestatic liver fibrosis was performed by bile duct ligation (BDL in mice, and significant liver injury was observed in 15 days. Administration of baicalin in mice significantly ameliorates liver fibrosis. Experimental cholestatic liver fibrosis was associated with induced gene expression of fibrotic markers such as collagen I, fibronectin, alpha smooth muscle actin (SMA, and connective tissue growth factor (CTGF; increased inflammatory cytokines (TNFα, MIP1α, IL1β, and MIP2; increased oxidative stress and reactive oxygen species- (ROS- inducing enzymes (NOX2 and iNOS; dysfunctional mitochondrial electron chain complexes; and apoptotic/necrotic cell death markers (DNA fragmentation, caspase 3 activity, and PARP activity. Baicalin administration on alternate day reduced fibrosis along with profibrotic gene expression, proinflammatory cytokines, oxidative stress, and cell death whereas improving the function of mitochondrial electron transport chain. We observed baicalin enhanced NRF2 activation by nuclear translocation and induced its target genes HO-1 and GCLM, thus enhancing antioxidant defense. Interplay of oxidative stress/inflammation and NRF2 were key players for baicalin-mediated protection. Stellate cell activation is crucial for initiation of fibrosis. Baicalin alleviated stellate cell activation and modulated TIMP1, SMA, collagen 1, and fibronectin in vitro. This study indicates that baicalin might be beneficial for reducing inflammation and fibrosis in liver injury models.

  6. Experimental Studies on Damage Detection in Frame Structures Using Vibration Measurements

    Directory of Open Access Journals (Sweden)

    Giancarlo Fraraccio

    2010-01-01

    Full Text Available This paper presents an experimental study of frequency and time domain identification algorithms and discusses their effectiveness in structural health monitoring of frame structures using acceleration input and response data. Three algorithms were considered: 1 a frequency domain decomposition algorithm (FDD, 2 a time domain Observer Kalman IDentification algorithm (OKID, and 3 a subsequent physical parameter identification algorithm (MLK. Through experimental testing of a four-story steel frame model on a uniaxial shake table, the inherent complications of physical instrumentation and testing are explored. Primarily, this study aims to provide a dependable first-order and second-order identification of said test structure in a fully instrumented state. Once the characteristics (i.e. the stiffness matrix for a benchmark structure have been determined, structural damage can be detected by a change in the identified structural stiffness matrix. This work also analyzes the stability of the identified structural stiffness matrix with respect to fluctuations of input excitation magnitude and frequency content in an experimental setting.

  7. Experimental investigation and analysis of damage evolution in concrete under high-cyclic fatigue loadings

    International Nuclear Information System (INIS)

    Thiele, Marc

    2016-01-01

    The main objective of this thesis is the fatigue behavior of concrete under high-cycle compressive loadings. Current knowledge about fatigue behavior of concrete is still incomplete. This concerns especially the process of fatigue which is preceding the fatigue failure. The leak of knowledge about fatigue behavior is opposed to the steady growing importance of this topic within the practice in civil engineering. Therefore, within this thesis a systematic and comprehensive investigation of the process of fatigue itself was done. This contributes to the better understanding of the progression of damage and the corresponding processes within the material. The experimental investigation consisted mainly of experiments with constant amplitude loadings in compression with cylindrical specimen made of normal strength concrete. Two differed load levels were used which resulted in numbers of cycles to failure of 10 6 and 10 7 as well as 10 3 and 10 4 . The experiments were done in combination with different types of nondestructive and destructive testing methods like strain measuring, deformation of surface, ultrasonic signals, acoustic emissions, optical microscopy and also scattering electron microscopy. To access some parameters of influence in relation to the fatigue behavior additional creep tests and also several tests with different scales of specimen were done. The fatigue process of concrete is determined as an evolution of damage that starts from the beginning of the loading process. This evolution has manifold and different influences on the different material properties of concrete. In this relation a major finding was that fatigue related damage leads to a transformation of the complete stress-strain-relationship. This relationship is also subjected to an evolution process. Due to the authors observations it could not be determined that the investigated changes in macroscopic material behavior are caused by a development of micro cracks within the material

  8. Development of experimental fibrotic liver diseases animal model by Carbon Tetracholoride.

    Science.gov (United States)

    Gitiara, Atoosa; Tokhanbigli, Samaneh; Mazhari, Sogol; Baghaei, Kaveh; Hatami, Behzad; Hashemi, Seyed Mahmoud; Asadi Rad, Ali; Moradi, Afshin; Nasiri, Meyam; Zarrabi Ahrabi, Nakisa; Zali, Mohammad Reza

    2017-01-01

    This study is presenting an effective method of inducing liver fibrosis by CCL4 as a toxin in two different breeds of rat models. Liver fibrosis is a result of inflammation and liver injury caused by wound healing responses which ultimately lead to liver failure. Consequently, after liver fibrosis, the progression will be continued to liver cirrhosis and at the end stage hepatocellular carcinoma (HCC). Many studies have demonstrated that one of the most important causes of liver fibrosis is Non-alcoholic steatohepatitis (NASH). Fibrotic Liver is affected by an excessive accumulation of extracellular matrix (ECM) proteins like collagen and α-SMA. In two different experiments, male Vistar, and Sprague Dawley Rat models ranging from 200±60, corresponding to an age of approximately 10 weeks were utilized in order to induce CCL4 treated liver fibrosis. After 6 weeks of CCL4 injection, different tests have been carried out to verify the liver fibrosis including serum markers such as Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT), molecular tests containing, laminin and α-SMA and also pathological observation by Hematoxylin and eosin staining in both fibrosis and control group. The results of Pathology and Real-time PCR showed that fibrosis was induced much more effectively in Sprague Dawley rat model compared with Wistar rats.

  9. The effects of diet-induced obesity on hepatocyte insulin signaling pathways and induction of non-alcoholic liver damage

    Directory of Open Access Journals (Sweden)

    Sameer Fatani

    2011-03-01

    Full Text Available Sameer Fatani1, Imose Itua2, Paul Clark3, Christopher Wong3, Ebrahim K Naderali21Obesity Biology Unit, School of Clinical Sciences, University of Liverpool, Liverpool, UK; 2Department of Health and Applied Social Sciences, Liverpool Hope University, Hope Park, Liverpool UK; 3Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool, UKAbstract: The prevalence of diet-induced obesity is increasing amongst adults and children worldwide, predisposing millions of people to an array of health problems that include metabolic syndrome, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. In this study we used experimental animals to investigate the effects of dietary obesity on markers of hepatic insulin signaling as well as structural changes in hepatocytes. Adult male Wistar rats were randomized and assigned to either a control group or a test group. Controls were fed standard laboratory pelleted diet (chow-fed, while the test group had free access to a highly-palatable diet (HPD. After eight weeks, the HPD-fed animals were subdivided into three subgroups and their diets altered as follows: HPD-to-chow, HPD with the addition of fenofibrate given by oral gavage for a further seven weeks, or HPD with vehicle (1% carboxymethylcellulose at 1 mL/kg body weight given by oral gavage for a further seven weeks, respectively. Untreated diet-fed animals had significantly higher body weight, liver weight, and all measured metabolic profiles compared with chow-fed and treated diet-fed groups. Expression of kinases IRβ, IRS-1, AKt, eNOS, Shc and ERK1/2 were unaffected by obesity, while IRS-2 and P I3 kinase levels were significantly reduced in untreated HPD animals. Compared with chow-fed animals, steatosis and steatohepatitis were almost doubled in animals from untreated HPD, while removal of HPD and fenofibrate-treatment reduced steatosis by 40% and 80% respectively. These data suggest that diet-induced obesity affects

  10. Radiation Damage in Nuclear Fuel for Advanced Burner Reactors: Modeling and Experimental Validation

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Niels Gronbech; Asta, Mark; Ozolins, Nigel Browning' Vidvuds; de Walle, Axel van; Wolverton, Christopher

    2011-12-29

    The consortium has completed its existence and we are here highlighting work and accomplishments. As outlined in the proposal, the objective of the work was to advance the theoretical understanding of advanced nuclear fuel materials (oxides) toward a comprehensive modeling strategy that incorporates the different relevant scales involved in radiation damage in oxide fuels. Approaching this we set out to investigate and develop a set of directions: 1) Fission fragment and ion trajectory studies through advanced molecular dynamics methods that allow for statistical multi-scale simulations. This work also includes an investigation of appropriate interatomic force fields useful for the energetic multi-scale phenomena of high energy collisions; 2) Studies of defect and gas bubble formation through electronic structure and Monte Carlo simulations; and 3) an experimental component for the characterization of materials such that comparisons can be obtained between theory and experiment.

  11. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy.

    Science.gov (United States)

    Hammes, Hans-Peter; Du, Xueliang; Edelstein, Diane; Taguchi, Tetsuya; Matsumura, Takeshi; Ju, Qida; Lin, Jihong; Bierhaus, Angelika; Nawroth, Peter; Hannak, Dieter; Neumaier, Michael; Bergfeld, Regine; Giardino, Ida; Brownlee, Michael

    2003-03-01

    Three of the major biochemical pathways implicated in the pathogenesis of hyperglycemia induced vascular damage (the hexosamine pathway, the advanced glycation end product (AGE) formation pathway and the diacylglycerol (DAG)-protein kinase C (PKC) pathway) are activated by increased availability of the glycolytic metabolites glyceraldehyde-3-phosphate and fructose-6-phosphate. We have discovered that the lipid-soluble thiamine derivative benfotiamine can inhibit these three pathways, as well as hyperglycemia-associated NF-kappaB activation, by activating the pentose phosphate pathway enzyme transketolase, which converts glyceraldehyde-3-phosphate and fructose-6-phosphate into pentose-5-phosphates and other sugars. In retinas of diabetic animals, benfotiamine treatment inhibited these three pathways and NF-kappaB activation by activating transketolase, and also prevented experimental diabetic retinopathy. The ability of benfotiamine to inhibit three major pathways simultaneously might be clinically useful in preventing the development and progression of diabetic complications.

  12. Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Martínez-Cáceres, E M

    2003-01-01

    Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells......, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue...... repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain....

  13. Different DNA damage response of cis and trans isomers of commonly used UV filter after the exposure on adult human liver stem cells and human lymphoblastoid cells.

    Science.gov (United States)

    Sharma, Anežka; Bányiová, Katarína; Babica, Pavel; El Yamani, Naouale; Collins, Andrew Richard; Čupr, Pavel

    2017-09-01

    2-ethylhexyl 4-methoxycinnamate (EHMC), used in many categories of personal care products (PCPs), is one of the most discussed ultraviolet filters because of its endocrine-disrupting effects. EHMC is unstable in sunlight and can be transformed from trans-EHMC to emergent cis-EHMC. Toxicological studies are focusing only on trans-EHMC; thus the toxicological data for cis-EHMC are missing. In this study, the in vitro genotoxic effects of trans- and cis-EHMC on adult human liver stem cells HL1-hT1 and human-derived lymphoblastoid cells TK-6 using a high-throughput comet assay were studied. TK-6 cells treated with cis-EHMC showed a high level of DNA damage when compared to untreated cells in concentrations 1.56 to 25μgmL -1 . trans-EHMC showed genotoxicity after exposure to the two highest concentrations 12.5 and 25μgmL -1 . The increase in DNA damage on HL1-hT1 cells induced by cis-EHMC and trans-EHMC was detected at the concentration 25μgmL -1 . The No observed adverse effect level (NOAEL, mg kg -1 bwday -1 ) was determined using a Quantitative in vitro to in vivo extrapolation (QIVIVE) approach: NOAEL trans-EHMC =3.07, NOAEL cis-EHMC =0.30 for TK-6 and NOAEL trans-EHMC =26.46, NOAEL cis-EHMC =20.36 for HL1-hT1. The hazard index (HI) was evaluated by comparing the reference dose (RfD, mgkg -1 bwday -1 ) obtained from our experimental data with the chronic daily intake (CDI) of the female population. Using comet assay experimental data with the more sensitive TK-6 cells, HI cis-EHMC was 7 times higher than HI trans-EHMC . In terms of CDI, relative contributions were; dermal exposure route>oral>inhalation. According to our results we recommend the RfD trans-EHMC =0.20 and RfD cis-EHMC =0.02 for trans-EHMC and cis-EHMC, respectively, to use for human health risk assessment. The significant difference in trans-EHMC and cis-EHMC response points to the need for toxicological reevaluation and application reassessment of both isomers in PCPs. Copyright © 2017 Elsevier B

  14. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    International Nuclear Information System (INIS)

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki

    2013-01-01

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA

  15. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp

    2013-11-15

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA.

  16. Surgical management and outcome of blunt major liver injuries: experience of damage control laparotomy with perihepatic packing in one trauma centre.

    Science.gov (United States)

    Lin, Being-Chuan; Fang, Jen-Feng; Chen, Ray-Jade; Wong, Yon-Cheong; Hsu, Yu-Pao

    2014-01-01

    This retrospective study aimed to assess the clinical experience and outcome of damage control laparotomy with perihepatic packing in the management of blunt major liver injuries. From January 1998 to December 2006, 58 patients of blunt major liver injury, American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS) equal or greater than III, were operated with perihepatic packing at our institute. Demographic data, intra-operative findings, operative procedures, adjunctive managements and outcome were reviewed. To determine whether there was statistical difference between the survivor and non-survivor groups, data were compared by using Mann-Whitney U test for continuous variables, either Pearson's chi-square test or with Yates continuity correction for contingency tables, and results were considered statistically significant if phepatic artery ligation (n=11) and 7 patients required post-laparotomy hepatic transarterial embolization. Of the 58 patients, 28 survived and 30 died with a 52% mortality rate. Of the 30 deaths, uncontrolled liver bleeding in 24-h caused 25 deaths and delayed sepsis caused residual 5 deaths. The mortality rate versus OIS was grade III: 30% (6/20), grade IV: 54% (13/24), and grade V: 79% (11/14), respectively. On univariate analysis, the significant predictors of mortality were OIS grade (p=0.019), prolonged initial prothrombin time (PT) (p=0.004), active partial thromboplastin time (APTT) (p<0.0001) and decreased platelet count (p=0.005). The mortality rate of surgical blunt major liver injuries remains high even with perihepatic packing. Since prolonged initial PT, APTT and decreased platelet count were associated with high risk of mortality, we advocate combination of damage control resuscitation with damage control laparotomy in these major liver injuries. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Hepatocyte growth factor gene-modified adipose-derived mesenchymal stem cells ameliorate radiation induced liver damage in a rat model.

    Directory of Open Access Journals (Sweden)

    Jiamin Zhang

    Full Text Available Liver damage caused by radiotherapy is associated with a high mortality rate, but no established treatment exists. Adipose-derived mesenchymal stem cells (ADSCs are capable of migration to injured tissue sites, where they aid in the repair of the damage. Hepatocyte growth factor (HGF is critical for damage repair due to its anti-apoptotic, anti-fibrotic and cell regeneration-promoting effects. This study was performed to investigate the therapeutic effects of HGF-overexpressing ADSCs on radiation-induced liver damage (RILD. ADSCs were infected with a lentivirus encoding HGF and HGF-shRNA. Sprague-Dawley (SD rats received 60Gy of irradiation to induce liver injury and were immediately given either saline, ADSCs, ADSCs + HGF or ADSCs + shHGF. Two days after irradiation, a significant reduction in apoptosis was observed in the HGF-overexpressing ADSC group compared with the RILD group, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining. Scanning electron microscopy showed chromatin condensation after irradiation, which was ameliorated in the group that received ADSCs and was reversed in the group that received HGF-overexpressing ADSCs. HGF-overexpressing ADSCs ameliorated radiation- induced liver fibrosis through down regulation of α-SMA and fibronectin. Hepatocyte regeneration was significantly improved in rats treated with ADSCs compared with rats from the RILD group, as assessed by Ki-67 immunohistochemistry. Rats that received HGF-overexpressing ADSCs showed an even greater level of hepatocyte regeneration. HGF-overexpressing ADSCs completely blocked the radiation-induced increase in the enzymes ALT and AST. The effect of mitigating RILD was compromised in the ADSC + shHGF group compared with the ADSC group. Altogether, these results suggest that HGF-overexpressing ADSCs can significantly improve RILD in a rat model, which may serve as a valuable therapeutic alternative.

  18. Polydatin attenuates d-galactose-induced liver and brain damage through its anti-oxidative, anti-inflammatory and anti-apoptotic effects in mice.

    Science.gov (United States)

    Xu, Lie-Qiang; Xie, You-Liang; Gui, Shu-Hua; Zhang, Xie; Mo, Zhi-Zhun; Sun, Chao-Yue; Li, Cai-Lan; Luo, Dan-Dan; Zhang, Zhen-Biao; Su, Zi-Ren; Xie, Jian-Hui

    2016-11-09

    Accumulating evidence has shown that chronic injection of d-galactose (d-gal) can mimic natural aging, with accompanying liver and brain injury. Oxidative stress and apoptosis play a vital role in the aging process. In this study, the antioxidant ability of polydatin (PD) was investigated using four established in vitro systems. An in vivo study was also conducted to investigate the possible protective effect of PD on d-gal-induced liver and brain damage. The results showed that PD had remarkable in vitro free radical scavenging activity on 2,2-diphenyl-1-picryl-hydrazyl (DPPH˙), 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) (ABTS + ˙) radical ions, and hydroxyl and superoxide anions. Results in vivo indicated that, in a group treated with d-gal plus PD, PD remarkably decreased the depression of body weight and organ indexes, reduced the levels of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and alleviated alterations in liver and brain histopathology. PD also significantly decreased the level of MDA and elevated SOD, GSH-Px, CAT activity and T-AOC levels in the liver and brain. In addition, the levels of inflammatory mediators, such as TNF-α, IL-1β and IL-6 in serum were markedly reduced after PD treatment. Western blotting results revealed that PD treatment noticeably attenuated the d-gal-induced elevation of Bcl-2/Bax ratio and caspase-3 protein expression in liver and brain. Overall, our findings indicate that PD treatment could effectively attenuate d-gal-induced liver and brain damage, and the mechanism might be associated with decreasing the oxidative stress, inflammation and apoptosis caused by d-gal. PD holds good potential for further development into a promising pharmaceutical candidate for the treatment of age-associated diseases.

  19. Effects of Freshwater Clam Extract Supplementation on Time to Exhaustion, Muscle Damage, Pro/Anti-Inflammatory Cytokines, and Liver Injury in Rats after Exhaustive Exercise

    Directory of Open Access Journals (Sweden)

    Kuang-Wen Liao

    2013-03-01

    Full Text Available The potent anti-inflammatory activities and tissue-protective effects of freshwater clams (Corbicula fluminea have been well reported. The aim of this study was to determine the effects of freshwater clam extract (FCE supplementation on time to exhaustion, muscle damage, pro- and anti-inflammatory cytokines, and liver injury in rats after exhaustive exercise. Thirty-two rats were divided into four groups: sedentary control (SC; SC group with FCE supplementation (SC+FCE; exhaustive exercise (E; and E group with FCE supplementation (E+FCE. The SC+FCE and E+FCE groups were treated with gavage administration of 20 mg/kg for seven consecutive days. Blood samples were collected for the evaluation of biochemical parameters. The cytokine levels of TNF-α and IL-10 were also examined. Twenty-four hours after exhaustive exercise, the rat livers were removed for H & E staining. The FCE supplementation could extend the time to exhaustion in exercised rats. The levels of CPK, LDH, AST, ALT, lactate, TNF-α and H & E stains of the liver injury were significantly decreased in the E+FCE group, but the blood glucose and IL-10 were significantly higher in comparison with the E group. This study suggests that FCE supplementation may improve endurance performance and reduce exercise-induced muscle damage, inflammatory stress and liver injury.

  20. Disruption of erythrocyte antioxidant defense system, hematological parameters, induction of pro-inflammatory cytokines and DNA damage in liver of co-exposed rats to aluminium and acrylamide.

    Science.gov (United States)

    Ghorbel, Imen; Maktouf, Sameh; Kallel, Choumous; Ellouze Chaabouni, Semia; Boudawara, Tahia; Zeghal, Najiba

    2015-07-05

    The individual toxic effects of aluminium and acrylamide are well known but there are no data on their combined effects. The present study was undertaken to determine (i) hematological parameters during individual and combined chronic exposure to aluminium and acrylamide (ii) correlation of oxidative stress in erythrocytes with pro-inflammatory cytokines expression, DNA damage and histopathological changes in the liver. Rats were exposed to aluminium (50 mg/kg body weight) in drinking water and acrylamide (20 mg/kg body weight) by gavage, either individually or in combination for 3 weeks. Exposure rats to AlCl3 or/and ACR provoked an increase in MDA, AOPP, H2O2 and a decrease in GSH and NPSH levels in erythrocytes. Activities of catalase, glutathione peroxidase and superoxide dismutase were decreased in all treated rats. Our results showed that all treatments induced an increase in WBC, erythrocyte osmotic fragility and a decrease in RBC, Hb and Ht. While MCV, MCH, MCHC remained unchanged. Hepatic pro-inflammatory cytokines expression including tumor necrosis factor-α, interleukin-6, interleukin-1β was increased suggesting leucocytes infiltration in the liver. A random DNA degradation was observed on agarose gel only in the liver of co-exposed rats to AlCl3 and ACR treatment. Interestingly, co-exposure to these toxicants exhibited synergism based on physical and biochemical variables in erythrocytes, pro-inflammatory cytokines and DNA damage in liver. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Lassa virus infection in experimentally infected marmosets: liver pathology and immunophenotypic alterations in target tissues.

    Science.gov (United States)

    Carrion, Ricardo; Brasky, Kathleen; Mansfield, Keith; Johnson, Curtis; Gonzales, Monica; Ticer, Anysha; Lukashevich, Igor; Tardif, Suzette; Patterson, Jean

    2007-06-01

    Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.

  2. A study on the Regenerative Effect of Platelets Rich Plasma on Experimentally Induced Hepatic Damage In Albino Rats.

    Science.gov (United States)

    Shoeib, Heba Mamdoh; Keshk, Walaa Arafa; Foda, Abdallah Mahmoud; Abo El Noeman, Saad El-Deen Abd Elfatah

    2018-02-14

    Hepatic fibrosis is a worldwide health problem with significant morbidity and mortality. Currently, there is no effective therapy for hepatic fibrosis. So that the present study was aimed to evaluate the possible regenerative effect of Platelet-rich plasma (PRP) against thioacetamide (TAA) induced hepatic damage. Eighty albino rats were included; 40 were used for PRP preparation and 40 were randomly divided into four groups. Group I (control group); group II (PRP control); group III (TAA- intoxicated in a dose of 200 mg ∕ kg body weight/twice weekly for 7 weeks, intra-peritoneal and group IV (TAA-intoxicated+ PRP treated). Macrophage inflammatory protein-1α (MIP-1α) and cyclic adenosine monophosphate (cAMP) were immunoassayed in addition to peroxinitrite level, NADPH-quinine oxido-reductase-1 (NQO1) enzyme activity and liver function. PRP treatment showed significant improvement in hepatic function, decreased MIP-1α and peroxinitrite level. Meanwhile, significant increase in NQO1 enzyme activity and cAMP level were observed. The histopathological results confirmed the laboratory results with improvement of hepatic architecture except for some inflammatory cellular infiltrates. PRP has the ability to protect against TAA-induced liver damage possibly by improving redox status, liver histopathological architecture, disruption of the inflammatory and fibrotic response induced by TAA.

  3. Avoiding thermal striping damage: Experimentally-based design procedures for high-cycle thermal fatigue

    International Nuclear Information System (INIS)

    Betts, C.; Judd, A.M.; Lewis, M.W.J.

    1994-01-01

    In the coolant circuits of a liquid metal cooled reactor (LMR), where there is turbulent mixing of coolant streams at different temperatures, there are temperature fluctuations in the fluid. If an item of the reactor structure is immersed in this fluid it will, because of the good heat transfer from the flowing liquid metal, experience surface temperature fluctuations which will induce dynamic surface strains. It is necessary to design the reactor so that these temperature fluctuations do not, over the life of the plant, cause damage. The purpose of this paper is to describe design procedures to prevent damage of this type. Two such procedures are given, one to prevent the initiation of defects in a nominally defect-free structure or to allow initiation only at the end of the component life, and the other to prevent significant growth of undetectable pre-existing defects of the order of 0.2 to 0.4 mm in depth. Experimental validation of these procedures is described, and the way they can be applied in practice is indicated. To set the scene the paper starts with a brief summary of cases in which damage of this type, or the need to avoid such damage, have had important effects on reactor operation. Structural damage caused by high-cycle thermal fatigue has had a significant adverse influence on the operation of LMRs on several occasions. It is necessary to eliminate the risk of such damage at the design stage. In the absence of detailed knowledge of the temperature history to which it will be subject, an LMR structure can be designed so that, if it is initially free of defects more than 0.1 mm deep, no such defects will be initiated by high-cycle fatigue. This can be done by ensuring that the maximum source temperature difference in the liquid metal is less than a limiting value, which depends on temperature. The limit is very low, however, and likely to be restrictive. This method, by virtue of its safety margin, takes into account pre-existing surface crack

  4. Hepatoprotective and antioxidant properties of the aqueous extract of Olea europaea leaves against Diclofenac-induced liver damages in mice.

    Science.gov (United States)

    Soussi, Rawya; Hfaiedh, Najla; Guesmi, Fatma; Sakly, Mohsen; Ben Rhouma, Khémais

    2018-04-20

    Historically, olive tree "Olea europaea" is one of the most important fruit trees in Mediterranean countries. Several studies suggest that olive leaf is a significant source of bioactive phenolic compounds compared to olive oil and fruits. This study was undertaken to investigate, the protective effect of the aqueous extract of « Chemlali » olive leaves against diclofenac-induced damages in liver and haematological alterations in swiss albinos mice. For this, twenty-eight mice were divided into four groups: a control group, a diclofenac-treated group (2.37 mg/kg) for 5 consecutive days, a group orally gavaged with aqueous extract of olive leaves, (3.3g/kg) during 28 days, and a group pre-treated with aqueous extract of olive leaves during 23 days then injected with diclofenac for 5 days. Results obtained from this study revealed that administration of diclofenac alone led to disturbance of some haematological parameters including red and white blood cells (RBC), (WBC) haemoglobin (Hb) and platelets content (PLT). However, diclofenac-treated mice group showed a increasing in the levels of cholesterol, triglyceride, glucose, creatinine, urea, aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT). Additionally we noted a state of oxidative stress in hepatic tissue indicated by the increasing of lipid peroxidation level (TBARS) and decreasing of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Interstingly, pre-treatment with olive leaves extract improved the haematological parameters and minimised the adverse effect on the hepatic function markers induced by diclofenac. The beneficial effect of olive leaves could be attributed to its antioxidant components as confirmed by phytochemical analysis.

  5. The effects of sulforaphane on the liver and remote organ damage in hepatic ischemia-reperfusion model formed with pringle maneuver in rats.

    Science.gov (United States)

    Oguz, Abdullah; Kapan, Murat; Kaplan, Ibrahim; Alabalik, Ulas; Ulger, Burak Veli; Uslukaya, Omer; Turkoglu, Ahmet; Polat, Yilmaz

    2015-06-01

    The purpose of this study was to investigate the effect of Sulforaphane on ischemia/ reperfusion (IR) injury of the liver and distant organs resulting from liver blood flow arrest. Fourty Wistar rats were assigned into four groups, each included 10 rats were used. Group I as only laparatomy, Group II laparatomy and Sulforaphane application, Group III hepatic IR; and Group IV as hepatic IR and Sulforaphane application group. Animals were subjected to liver ischemia for 30 min and then reperfusion is started. 5 mg/kg Sulforaphane was applied via oral lavage 15 minutes before initiating the experimental study. Blood samples were taken from the animals for biochemical analysis at 60th minutes of the experiment in the first and second groups; 30 minutes after beginning reperfusion in the third and forth groups. Simultaneously, liver, lung and kidney tissues were sampled for biochemical and histopathological examinations. The administration of sulforaphane significantly reduced the serum TOA and liver TOA levels, increased the serum TAC and liver TAC levels and also decreased The OSI and liver OSI levels. In the histopathologic examination, the injury was reduced by the administration of sulforaphane. Administration of sulforaphane did not lead to any significant changes in any parameter including histopathological parameters in both the kidney and the lung. Sulforaphane reduced the liver oxidative stress from I/R injury. A histological injury in liver was reduced by sulforaphane administration. However, there were no significant effects of sulforaphane on the remote organ injuries induced by IR. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  6. Radiation damage to the normal monkey brain. Experimental study induced by interstitial irradiation

    International Nuclear Information System (INIS)

    Mishima, Nobuya; Tamiya, Takashi; Matsumoto, Kengo; Furuta, Tomohisa; Ohmoto, Takashi

    2003-01-01

    Radiation damage to normal brain tissue induced by interstitial irradiation with iridium-192 seeds was sequentially evaluated by computed tomography (CT), magnetic resonance imaging (MRI), and histological examination. This study was carried out in 14 mature Japanese monkeys. The experimental area received more than 200-260 Gy of irradiation developed coagulative necrosis. Infiltration of macrophages to the periphery of the necrotic area was seen. In addition, neovascularization, hyalinization of vascular walls, and gliosis were found in the periphery of the area invaded by the macrophages. All sites at which the vascular walls were found to have acute stage fibrinoid necrosis eventually developed coagulative necrosis. The focus of necrosis was detected by MRI starting 1 week after the end of radiation treatment, and the size of the necrotic area did not change for 6 months. The peripheral areas showed clear ring enhancement with contrast material. Edema surrounding the lesions was the most significant 1 week after radiation and was reduced to a minimum level 1 month later. However, the edema then expanded once again and was sustained for as long as 6 months. CT did not provide as clear of a presentation as MRI, but it did reveal similar findings for the most part, and depicted calcification in the necrotic area. This experimental model is considered useful for conducting basic research on brachytherapy, as well as for achieving a better understanding of delayed radiation necrosis. (author)

  7. Evaluation of liver function in carbon tetrachloride-damaged rabbits by dynamic SPECT. Comparison of 99mTc-GSA and 99mTc-Sn colloid

    International Nuclear Information System (INIS)

    Kiuchi, Takaaki; Kawasaki, Yukiko; Hino, Ichirou; Kojima, Kanji; Ohkawa, Motoomi; Tanabe, Masatada; Tamai, Toyosato.

    1994-01-01

    Technetium-99m-DTPA-galactosyl human serum albumin ( 99m Tc-GSA) is a new ligand that binds specifically to asialoglycoprotein receptors in hepatocytes. We performed liver dynamic SPECT using 99m Tc-GSA and 99m Tc-Sn colloid in nine normal control rabbits and 17 chronically CCl 4 -damaged rabbits (total 29 examinations), and also performed liver function tests (ICGR 15 , Alb, etc). Using the obtained dynamic SPECT data, we analyzed the liver kinetics of 99m Tc-Sn colloid using a one-compartment model (hepatic blood flow [K]) and 99m Tc-GSA using a two-compartment model (hepatic blood flow and receptor binding [K 1 ], catabolism [K 2 ]). As the CCl 4 -treated period increased, K 1 decreased most significantly. K 1 showed the most statistically significant correlation with the results of liver function tests, ICGR 15 (p 1 showed a correlation with the hepatic fibrosis of the HAI score. From the present results, liver dynamic SPECT using 99m Tc-GSA may be said to provide a novel method for the evaluation of hepatic functional reserve. (author)

  8. BL153 Partially Prevents High-Fat Diet Induced Liver Damage Probably via Inhibition of Lipid Accumulation, Inflammation, and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Jian Wang

    2014-01-01

    Full Text Available The present study was to investigate whether a magnolia extract, named BL153, can prevent obesity-induced liver damage and identify the possible protective mechanism. To this end, obese mice were induced by feeding with high fat diet (HFD, 60% kcal as fat and the age-matched control mice were fed with control diet (10% kcal as fat for 6 months. Simultaneously these mice were treated with or without BL153 daily at 3 dose levels (2.5, 5, and 10 mg/kg by gavage. HFD feeding significantly increased the body weight and the liver weight. Administration of BL153 significantly reduced the liver weight but without effects on body weight. As a critical step of the development of NAFLD, hepatic fibrosis was induced in the mice fed with HFD, shown by upregulating the expression of connective tissue growth factor and transforming growth factor beta 1, which were significantly attenuated by BL153 in a dose-dependent manner. Mechanism study revealed that BL153 significantly suppressed HFD induced hepatic lipid accumulation and oxidative stress and slightly prevented liver inflammation. These results suggest that HFD induced fibrosis in the liver can be prevented partially by BL153, probably due to reduction of hepatic lipid accumulation, inflammation and oxidative stress.

  9. Niemann-Pick type C2 protein supplementation in experimental non-alcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Christensen, Claus Uhrenholt; Glavind, Emilie; Thomsen, Karen Louise

    2018-01-01

    the last two weeks or the entire four weeks. End-points were liver/body- and spleen/body weight ratios, histopathological NASH scores, fibrosis, serum liver enzymes, cholesterol, lipoproteins, cytokines, and quantitative polymerase chain reaction derived hepatic gene expression related to cholesterol...... metabolism, inflammation, and fibrosis. RESULTS: HFHC rats developed hepatomegaly, non-fibrotic NASH histopathology, elevated liver enzymes, serum cholesterol, and pro-inflammatory cytokines. Their sterol regulatory element binding factor 2 (SREBF2) and low-density lipoprotein receptor (LDL-R) mRNAs were...... down-regulated compared with rats on standard chow. NPC2 did not improve liver weight, histopathology, levels of serum liver enzymes or pro-inflammatory tumor necrosis factor-α (TNFα), Interleukin (IL)-6, or IL-1β in HFHC rats. Two weeks of NPC2 treatment lowered hepatic TNFα and COL1A1 mRNA expression...

  10. Determination of ultra-short laser induced damage threshold of KH2PO4 crystal: Numerical calculation and experimental verification

    Directory of Open Access Journals (Sweden)

    Jian Cheng

    2016-03-01

    Full Text Available Rapid growth and ultra-precision machining of large-size KDP (KH2PO4 crystals with high laser damage resistance are tough challenges in the development of large laser systems. It is of high interest and practical significance to have theoretical models for scientists and manufacturers to determine the laser-induced damage threshold (LIDT of actually prepared KDP optics. Here, we numerically and experimentally investigate the laser-induced damage on KDP crystals in ultra-short pulse laser regime. On basis of the rate equation for free electron generation, a model dedicated to predicting the LIDT is developed by considering the synergistic effect of photoionization, impact ionization and decay of electrons. Laser damage tests are performed to measure the single-pulse LIDT with several testing protocols. The testing results combined with previously reported experimental data agree well with those calculated by the model. By taking the light intensification into consideration, the model is successfully applied to quantitatively evaluate the effect of surface flaws inevitably introduced in the preparation processes on the laser damage resistance of KDP crystals. This work can not only contribute to further understanding of the laser damage mechanisms of optical materials, but also provide available models for evaluating the laser damage resistance of exquisitely prepared optical components used in high power laser systems.

  11. Hepatoprotective effect of Solanum xanthocarpum fruit extract against CCl4 induced acute liver toxicity in experimental animals.

    Science.gov (United States)

    Gupta, Ramesh K; Hussain, Talib; Panigrahi, G; Das, Avik; Singh, Gireesh Narayan; Sweety, K; Faiyazuddin, Md; Rao, Chandana Venkateswara

    2011-12-01

    To investigate the hepatoprotective potential of Solanum xanthocarpum (Solanaceae) (S. xanthocarpum) in experimental rats to validate its traditional claim. 50% ethanolic fruit extract of S. xanthocarpum (SXE, 100, 200 or 400 mg/kg body weight) was administered daily for 14 days in experimental animals. Liver injury was induced chemically, by CCl(4) administration (1 mL/kg i. p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), Serum alkaline phosphatise (SALP) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were screened along with histopathological studies. Obtained results demonstrated that the treatment with SXE significantly (P<0.05-<0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore, SXE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed that SXE attenuated the hepatocellular necrosis and led to reduction of inflammatory cells inflltration. The results of this study strongly indicate the protective effect of SXE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  12. Enlarged Liver

    Science.gov (United States)

    ... of liver damage. Medicinal herbs. Certain herbs, including comfrey, ma huang and mistletoe, can increase your risk ... herbs to avoid include germander, chaparral, senna, mistletoe, comfrey, ma huang, valerian root, kava, celandine and green ...

  13. Experimental Study of Damage Indicators for a 2-Bay, 6-Storey RC-Frame

    DEFF Research Database (Denmark)

    Skjærbæk, P. S.; Nielsen, Søren R. K.; Kirkegaard, Poul Henning

    index, Park and Ang's index, the normalized cumulative dissipated energy, various ductility ratios, a low-cycle fatigue model formulated by Stephens, the flexural damage ratios, interstorey drift based damage ratios and a newly proposed local maximum softening damage index are used. Like the maximum...

  14. Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation.

    Science.gov (United States)

    Afrin, Rejina; Arumugam, Somasundaram; Rahman, Azizur; Wahed, Mir Imam Ibne; Karuppagounder, Vengadeshprabhu; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Suzuki, Kenji; Yoneyama, Hiroyuki; Ueno, Kazuyuki; Watanabe, Kenichi

    2017-03-01

    Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding. We found that curcumin improved the histopathological changes of the NASH liver via reducing the level of steatosis, fibrosis associated with decreasing serum aminotransferases. In addition, curcumin treatment markedly reduced the hepatic protein expression of oxidative stress, pro-inflammatory cytokines, and chemokines including interferon (IFN) γ, interleukin-1β and IFNγ-inducible protein 10, in NASH mice. Furthermore, curcumin treatment significantly reduced the cytoplasmic translocation of high mobility group box 1 (HMGB1) and the protein expression of toll like receptor 4. Nuclear translocation of nuclear factor kappa B (NF-κB) was also dramatically attenuated by the curcumin in NASH liver. Curcumin treatment effectively reduced the progression of NASH to HCC by suppressing the protein expression of glypican-3, vascular endothelial growth factor, and prothrombin in the NASH liver. Our data suggest that curcumin reduces the progression of NASH and liver damage, which may act via inhibiting HMGB1-NF-κB translocation. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Avidin chase can reduce myelotoxicity associated with radioimmunotherapy of experimental liver micrometastases in mice

    International Nuclear Information System (INIS)

    Sato, Noriko; Saga, Tsuneo; Sakahara, Harumi; Nakamoto, Yuji; Zhao, Songji; Iida, Yasuhiko; Konishi, Junji; Kuroki, Masahide; Endo, Keigo

    2000-01-01

    Myelotoxicity is the main factor which decides the maximum tolerated dose (MTD) in radioimmunotherapy (RIT). Since bone marrow is mostly irradiated from blood radioactivity, enhancing the clearance of unbound circulating radiolabeled antibody is important to reduce myelotoxicity and to increase the MTD. We applied the avidin chase method, which was devised to obtain high tumor-to-background ratios in tumor-targeting, to RIT of experimental liver micrometastases and evaluated its influence on the side effects and therapeutic outcome. Seven days after intrasplenic injection of human colon cancer LS174T cells, nude mice were intravenously injected with biotinylated 131 I-labeled anti-CEA monoclonal antibody (MAb) (24-38 μg, 11.1 MBq). Mice of the chase group then received an intravenous injection of avidin twice (24 and 30 h, 72-115 μg each). Biodistribution, side effects (white blood cell counts and body weight change), and short- and long-term therapeutic effects were determined. Avidin chase markedly accelerated the clearance of radiolabeled MAb from the blood (P<0.0001) and normal tissues, resulting in milder leukocytopenia and body weight loss, both of which recovered earlier than in the non-chase group (P<0.01). The tumor uptake of radiolabeled MAb was also decreased by avidin chase, but the metastases-to-background ratios were increased. Avidin chase gave the therapeutic gain ratio of 1.89. Treated groups with and without avidin chase showed significant therapeutic effects compared to the non-treated group. There was no significant difference in the therapeutic effects between the two treated groups. Avidin chase effectively reduced the side effects of RIT and should increase the MTD. (author)

  16. Liver hypertrophy in winter flounder following exposure to experimentally oiled sediments

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, G L; King, M J; Kiceniuk, J W; Addison, R F

    1982-01-01

    1. Male winter flounder were exposed to sediments contaminated with Venezuelan crude oil in 3 laboratory experiments of 4-5 months duration. 2. Oil exposure resulted in significant increases in liver weight. This was particularly evident in fish weighing less than 400 g. 3. The enlarged livers of the oil-exposed flounder had reduced concentrations of DNA, protein, Na/sup +/ and Zn2/sup +/, and increased concentrations of lipid and phospholipid. 4. The reduced DNA and Na/sup +/ concentrations suggested liver hypertrophy rather than hyperplasia. 5. The increased phospholipid concentrations suggested growth of membrane structures such as endoplasmic reticulum.

  17. Liver Disease

    Science.gov (United States)

    ... and ridding your body of toxic substances. Liver disease can be inherited (genetic) or caused by a variety of factors that damage the ... that you can't stay still. Causes Liver disease has many ... or semen, contaminated food or water, or close contact with a person who is ...

  18. Lack of association between peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms and progressive liver damage in patients with non-alcoholic fatty liver disease: a case control study

    Directory of Open Access Journals (Sweden)

    Dongiovanni Paola

    2010-09-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptors (PPARs play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD. Aim to assess the effect of functional single nucleotide polymorphisms (SNPs of PPARα and PPARγ2, previously associated with insulin resistance and dyslipidemia, on liver damage in NAFLD, whose progression is influenced by metabolic abnormalities and inherited factors. Methods The Leu162Val PPARα and Pro12Ala PPARγ2 SNPs were evaluated by restriction analysis. We considered 202 Italian patients with biopsy-proven NAFLD. Results The frequency of the evaluated SNPs did not differ between patients and 346 healthy controls. The presence of the PPARα 162Val allele (prevalence 57%, but not of the PPARγ2 12Ala allele (prevalence 18%, was associated with higher insulin resistance (HOMA-IR index 4.71 ± 3.8 vs. 3.58 ± 2.7, p = 0.026, but not with hyperglycemia. The PPARα 162Val and PPARγ2 12Ala alleles were not associated with the severity of steatosis, necroinflammation, or fibrosis. Conclusions The presence of the PPARα 162Val allele was associated with insulin resistance, but not with liver damage in NAFLD. Because of the limited power of the present sample, larger studies are needed to exclude a minor effect of the PPARγ2 12Ala allele on necroinflammation/fibrosis in NAFLD.

  19. Ursodeoxycholic acid inhibits hepatic cystogenesis in experimental models of polycystic liver disease

    NARCIS (Netherlands)

    Munoz-Garrido, Patricia; Marin, José J. G.; Perugorria, María J.; Urribarri, Aura D.; Erice, Oihane; Sáez, Elena; Úriz, Miriam; Sarvide, Sarai; Portu, Ainhoa; Concepcion, Axel R.; Romero, Marta R.; Monte, María J.; Santos-Laso, Álvaro; Hijona, Elizabeth; Jimenez-Agüero, Raúl; Marzioni, Marco; Beuers, Ulrich; Masyuk, Tatyana V.; LaRusso, Nicholas F.; Prieto, Jesús; Bujanda, Luis; Drenth, Joost P. H.; Banales, Jesús M.

    2015-01-01

    Background & Aims: Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive biliary cystogenesis. Current therapies show short-term and/or modest beneficial effects. Cystic cholangiocytes hyperproliferate as a consequence of diminished intracellular calcium levels

  20. Experimental hypothyroidism modulates the expression of the low density lipoprotein receptor by the liver

    International Nuclear Information System (INIS)

    Scarabottolo, Lia; Trezzi, Ermanno; Roma, Paola; Catapano, A.L.

    1986-01-01

    The effect of exprimental hypothyroidism of the catabolism of plasma lipoproteins and on the expression of low density lipoprotein receptors by the liver was investigated in rats made hypothyroid by surgery. The animals developed mild hypercholesterolemia, mainly due to an increase of plasma low density lipoprotein, while other lipoprotein classes were only marginally affected. Kinetic studies using ( 125 I)LDL indicated that a decreased fractional catabolic rate of the lipoprotein was responsible for this finding in agreement with the in vitro observation of a reduced binding of lipoproteins to liver membranes from hyperthyroid rats and with the demonstrations, by ligand blotting analysis, of a decreasd expression of lipoprotein receptors in liver membranes. These data suggest that hypothyroidism affects lipoprotein distribution also by decreasing the catabolism of low density lipoproteins by the liver (author)

  1. Microscale experimental investigation of deformation and damage of argillaceous rocks under cyclic hydric and mechanical loads

    International Nuclear Information System (INIS)

    Wang, Linlin; Yang, Diansen; Heripre, Eva; Chanchole, Serge; Bornert, Michel; Pouya, Ahmad; Halphen, Bernard

    2012-01-01

    Document available in abstract form only. Argillaceous rocks are possible host rocks for underground nuclear waste repositories. They exhibit complex coupled thermo-hydro-chemo-mechanical behavior, the description of which would strongly benefit from an improved experimental insight on their deformation and damage mechanisms at microscale. We present some recent observations of the evolution of these rocks at the scale of their composite microstructure, essentially made of a clay matrix with embedded carbonates and quartz particles with sizes ranging from a few to several tens of micrometers, when they are subjected to cyclic variations of relative humidity and mechanical loading. They are based on the combination of high definition and high resolution imaging in an environmental scanning electron microscope (ESEM), in situ hydro-mechanical loading of the samples, and digital image correlation techniques. Samples, several millimeters in diameter, are held at a constant temperature of 2 deg. Celsius while the vapor pressure in the ESEM chamber is varied from a few to several hundreds of Pascals, generating a relative humidity ranging from about 10% up to 90%. Results show a strongly heterogeneous deformation field at microscale, which is the result of complex hydro-mechanical interactions. In particular, it can be shown that local swelling incompatibilities can generate irreversible deformations in the clay matrix, even if the overall hydric deformations seem reversible. In addition, local damage can be generated, in the form of a network of microcracks, located in the bulk of the clay matrix and/or at the interface between clay and other mineral particles. The morphology of this network, described in terms of crack length, orientation and preferred location, has been observed to be dependent on the speed of the variation of the relative humidity, and is different in a saturation or desaturation process. Besides studying the deformation and damage under hydric

  2. Experimental investigation of strain, damage and failure of hydrided zircaloy-4 with various hydride orientations

    International Nuclear Information System (INIS)

    Racine, A; Catherine, C.S.; Cappelaere, C.; Bornert, M.; Caldemaison, D.

    2005-01-01

    This experimental investigation is devoted to the influence of the orientation of hydrides on the mechanical response of Zircaloy-4. Ring tensile tests are performed on unirradiated CWSR Zircaloy-4, charged with about 200 or 500wppm hydrogen. Hydrides are oriented either parallel ('tangential'), or perpendicular ('radial') to the circumferential tensile direction. Tangential hydrides are usually observed in cladding tubes, however, hydrides can be reoriented after cooling under stress to become radial and then trigger brittle behavior. In this investigation, we perform, 'macroscopic' or SEM in-situ tensile tests on smooth rings, at room temperature. We get the mechanical response of the material as a function of hydride orientation and hydrogen content and we investigate the deformation, damage and failure mechanisms. In both cases, digital image correlation techniques are used to estimate local and global strain distributions. The results lead to the following conclusions: neither the tensile stress-strain response nor the strain modes are affected by hydrogen content or hydride orientation, but the failure modes are. Indeed, only 200wppm radial hydrides embrittle Zy-4: sample fails in the elastic domain at about 350 MPa before strain bands could develop; whereas in other cases samples reach at least 750 MPa before failure, with ductile or brittle mode. (authors)

  3. Experimental study on the expression of CD44 and CD54 in liver metastasis of colorectal carcinoma

    International Nuclear Information System (INIS)

    Ma Chen; Mao Dabeng; Wang Chengzhong; Guo Yu

    2004-01-01

    Objective: To study the significance of CD44 and CD54 expression in animal models with liver metastasis of colorectal cancer and try to find a stable biological marker for the early diagnosis of liver metastasis of colorectal cancer. Methods: Fourth two nude mice of 4-6 wks were adopted in the study. Thirty-six were used to establish animal models with liver metastasis of colorectal cancer, the rest 6 mice were used as the controls. 36 mice of the experimental group were divided into 6 subgroups, each containing 6 mice, in which low grade colorectal adenocarcinoma cells were injected in the subcapsule of the spleen. On the day 10th, 15th, 20th, 25th, 30th day and at the time of the brink of death, animas in each subgroup were sacrificed by eyeball removal and blood letting. Serum CD44, CD54 and CEA levels of the nude mice were measured by ELISA and the sizes and number of liver metastatic loci were observed and noted. the 6 mice for control were raised in the same cages and were killed on the 30th day, and were compared with that in the experimental group. Results: Through the measurement at different phrases, authors found with the development progression and metastasis of cancer, CD44 and CD54 levels in the animal serum tend to increase gradually and were correlated positively with the growth time, size, and extent metastasis of the cancer. Conclusion: CD44 and CD54 may be early tumor markers for liver metastasis of colorectal cancer

  4. Damage to Liver and Skeletal Muscles in Marathon Runners During a 100 km Run With Regard to Age and Running Speed

    Directory of Open Access Journals (Sweden)

    Jastrzębski Zbigniew

    2015-03-01

    Full Text Available The purpose of this study was to determine: (1 whether damage to liver and skeletal muscles occurs during a 100 km run; (2 whether the metabolic response to extreme exertion is related to the age or running speed of the participant; (3 whether it is possible to determine the optimal running speed and distance for long-distance runners’ health by examining biochemical parameters in venous blood. Fourteen experienced male amateur ultra-marathon runners, divided into two age groups, took part in a 100 km run. Blood samples for liver and skeletal muscle damage indexes were collected from the ulnar vein just before the run, after 25, 50, 75 and 100 km, and 24 hours after termination of the run. A considerable increase in alanine aminotransferase (ALT and aspartate aminotransferase (AST was observed with the distance covered (p < 0.05, which continued during recovery. An increase in the mean values of lactate dehydrogenase (LDH, creatine kinase (CK and C-reactive protein (CRP (p < 0.05 was observed with each sequential course. The biggest differences between the age groups were found for the activity of liver enzymes and LDH after completing 75 km as well as after 24 hours of recovery. It can be concluded that the response to extreme exertion deteriorates with age in terms of the active movement apparatus.

  5. Perfusion device for liver preservation ex vivo before transplantation: first experimental study

    Directory of Open Access Journals (Sweden)

    O. N. Reznik

    2017-01-01

    Full Text Available Introduction. Successful liver transplantation including from donors with a sudden irreversible cardiac arrest requires the use of modern hardware and technical support to maintain, select and sustain organ viability for the period from harvesting to transplantation to the recipient.Materials and methods. Hardware-software system (HSS developed by the Russian State Scientific Center for Robotics and Technical Cybernetics (RTC was used for testing of normothermic perfusion of donor’s liver ex vivo. The experiment was conducted on the isolated pig liver (Duroc breed in accordance with the ethical principles.Result. During perfusion spontaneous recovery of bile outflow through the cannula installed in the common bile duct (volume of bile released – 240 ml was observed, and the color and uniformity of the perfused liver did not differ from the normal parameters. Biochemical indicators were stabilized at the physiological values after 40 minutes of perfusion procedure.Conclusion. Isolated liver transplant was completely restored after 30 minutes of warm ischemia and was functioning well due to ex vivo perfusion procedure on the new perfusion device. The first case of the new device usage for normothermic liver ex vivo demonstrated hopeful results to be further investigated.

  6. Effect of Vaccination with Irradiated Tachyzoites on Histopathological Changes and DNA Damage in Hepatocytes of Experimental Toxoplasmosis

    International Nuclear Information System (INIS)

    Amin, M.M.; Hafez, E.N.

    2015-01-01

    Current strategies for the control of toxoplasmosis are based on chemotherapy, however successful vaccine has also been demonstrated. The present study aims to assess the effect of the vaccination with radiation-attenuated tachyzoites in challenged mice regarding histopathological alteration and DNA damage of hepatocytes. Sixty mice were equally divided as follow: Group I left as a normal control group II was infected with 2x10 3 RH virulent tachyzoite s (infected control). Groups III and IV were subdivided into two subgroups a and b where subgroups III a and IV a were vaccinate d with 2.47 mw-min/cm 2 UV and 0.3 KGy gamma radiation – attenuate d tachyzoites respectively without challenge (as vaccine control). Subgroups III b and IV b were vaccinate d with UV and gamma radiation - attenuated tachyzoites and challenged after three weeks with 2x10 3 RH virulent tachyzoites. Livers were examined for histopathological changes and DNA comet assay. It was observed that acute infection with Toxoplasma tachyzoites produced toxic effects which lead to severe damage in liver tissues and DNA of hepatocytes. Meanwhile, the protective effect of UV or gamma radiation-attenuated tachyzoites vaccine resulted in the maintenance of normal histopathological characteristics and DNA of hepatocyte s and UV irradiation is better in its protective capacity

  7. Hepatic regeneration and functional recovery following partial liver resection in an experimental model of hepatic steatosis treated with omega-3 fatty acids

    NARCIS (Netherlands)

    Marsman, H. A.; de Graaf, W.; Heger, M.; van Golen, R. F.; ten Kate, F. J. W.; Bennink, R.; van Gulik, T. M.

    2013-01-01

    Omega-3 fatty acids (FAs) have been shown to reduce experimental hepatic steatosis and protect the liver from ischaemia-reperfusion injury. The aim of this study was to examine the effects of omega-3 FAs on regeneration of steatotic liver. Steatosis was induced in rats by a 3-week

  8. Biodistribution of Boron compounds in an experimental model of liver metastases for Boron Neutron Capture (BNCT) Studies

    International Nuclear Information System (INIS)

    Garabalino, Marcela A.; Monti Hughes, Andrea; Molinari, Ana J.; Heber, Elisa M.; Pozzi, Emiliano C.C.; Itoiz, Maria E.; Trivillin, Veronica A.; Schwint, Amanda E.; Nievas, Susana; Aromando, Romina F.

    2009-01-01

    Boron Neutron Capture Therapy (BNCT) is a binary treatment modality that involves the selective accumulation of 10 B carriers in tumors followed by irradiation with thermal or epithermal neutrons. The high linear energy transfer alpha particles and recoiling 7 Li nuclei emitted during the capture of a thermal neutron by a 10 B nucleus have a short range and a high biological effectiveness. Thus, BNCT would potentially target neoplastic tissue selectively. In previous studies we demonstrated the therapeutic efficacy of different BNCT protocols in an experimental model of oral cancer. More recently we performed experimental studies in normal rat liver that evidenced the feasibility of treating liver metastases employing a novel BNCT protocol proposed by JEC based on ex-situ treatment and partial liver auto-transplant. The aim of the present study was to perform biodistribution studies with different boron compounds and different administration protocols to determine the protocols that would be therapeutically useful in 'in vivo' BNCT studies at the RA-3 Nuclear Reactor in an experimental model of liver metastases in rats. Materials and Methods. A total of 70 BDIX rats (Charles River Lab., MA, USA) were inoculated in the liver with syngeneic colon cancer cells DH/DK12/TRb (ECACC, UK) to induce the development of subcapsular metastatic nodules. 15 days post-inoculation the animals were used for biodistribution studies. A total of 11 protocols were evaluated employing the boron compounds boronophenylalanine (BPA) and GB-10 (Na 2 10 B 1 -0H 10 ), alone or combined employing different doses and administration routes. Tumor, normal tissue and blood samples were processed for boron measurement by ICP-OES. Results. Several protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue, i.e. BPA 15.5 mg 10 B/kg iv + GB-10 50 mg 10 B/kg iv; BPA 46.5 mg 10 B/kg ip; BPA 46.5 mg 10 B/kg ip

  9. Hydrodynamic rupture of liver in combat patient: a case of successful application of "damage control" tactic in area of the hybrid war in East Ukraine.

    Science.gov (United States)

    Khomenko, Igor; Shapovalov, Vitalii; Tsema, Ievgen; Makarov, Georgii; Palytsia, Roman; Zavodovskyi, Ievgen; Ishchenko, Ivan; Dinets, Andrii; Mishalov, Vladimir

    2017-08-15

    The hybrid war of Russia against Ukraine has been started in certain districts of Donetsk and Luhansk oblasts within the Donbas area in 2014. We report a clinical case of a combat patient who was injured after the multiple launcher rocket system "Grad" shelling, diagnosed with hydrodynamic liver rupture followed by medical management with application of damage control (DC) tactic in conditions of hybrid war. The patient underwent relaparatomy, liver resection, endoscopic papillosphincterotomy, endoscopic retrograde cholecystopancreatography, stenting of the common bile duct, and VAC-therapy. Applied treatment modalities were effective; the patient was discharged on the 49th day after injury. To our best knowledge, this is the first report describing a successful application of DC tactic in the hybrid war in East Ukraine. From this case, we suggest that application of DC tactic at all levels of combat medical care could save more lives.

  10. Liver changes under the influence of chronic experimental intoxication with nitrogen oxides

    Energy Technology Data Exchange (ETDEWEB)

    Kosmider, S; Misiewicz, A

    1973-01-01

    Male guinea pigs were divided into three groups: a control group; a group of animals breathing air containing 1 ppM nitrogen oxides during 6 months, 8 hr/day; and third group exposed to products of reactions between nitrogen oxide and gaseous ammonia. The animals lived through the 6 mo with no increase in mortality. The body weight of the animals exposed to nitrogen oxides increased during the 6 mo by 62 g on the average, while in the control group the body weight increased by 395 g on the average. In homogenates of the livers of the animals exposed to nitrogen oxides, the activities of aldolase, lactic dehydrogenase, acid, and alkaline phosphatase increased, and the activities of cholinesterase, ceruloplasmin, and aminotransferases (aspartic and alanine) decreased. Neutralization of NO/sub x/ by gaseous ammonia restored the disorders in enzyme activities in the liver of the animals exposed to nitrogen oxides to their normal values. The study was statistically analyzed. The livers of the animals exposed to nitrogen oxides contained small foci of necrosis, and hemorrhages could be observed. In some animals, fatty degeneration of the liver could be observed. The changes in the liver can also be associated with inhibited protein synthesis, enhanced catabolic processes, and hypovitaminosis.

  11. Experimental investigation of a new iodinated lipid emulsion for computed tomography of the liver

    International Nuclear Information System (INIS)

    Ivancev, K.; Lunderquist, A.; McCuskey, R.; McCuskey, P.; Wretlind, A.; Arizona Univ., Tucson, AZ; Veterans Administration Medical Center, Tucson, AZ

    1989-01-01

    We have tested a new iodinated lipid emulsion, Intraiodol. The size and surface properties of the particles of this emulsion are similar to those of Intralipid which in turn closely resemble the naturally occurring chylomicrons. Using computed tomography (CT) of the rabbit liver as well as vital microscopy and electron microscopy of the rat liver we found that Intraiodol has low efficiency as a liver-specific contrast medium because its particles are predominantly taken up by the hepatocytes and to a less extent by the Kupffer cells, as is Intralipid. The low efficiency of Intraiodol could be fully compensated by an increase in dosage without any significant effect on sinusoidal blood flow. This in turn suggests that the likelihood of release of toxic mediators (and thereby related adverse reactions from activated macrophages) is reduced. We believe that this new way of delivering iodinated lipid particles to the liver represents an important advance in the search for a non-toxic lipid emulsion for CT of the liver. (orig./MG)

  12. Hepatitis B virus induces IL-23 production in antigen presenting cells and causes liver damage via the IL-23/IL-17 axis.

    Directory of Open Access Journals (Sweden)

    Qinghong Wang

    Full Text Available IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated. In vivo observations also indicated that the main sources of IL-23 were myeloid dendritic cells (mDCs and macrophages. Analysis of in vitro differentiated immature DCs and macrophages isolated from healthy donors revealed that the HBV surface antigen (HBsAg efficiently induces IL-23 secretion in a mannose receptor (MR-dependent manner. Culture with an endosomal acidification inhibitor and the dynamin inhibitor showed that, upon binding to the MR, the HBsAg is taken up by mDCs and macrophages through an endocytosis mechanism. In contrast, although the HBV core antigen (HBcAg can also stimulate IL-23 secretion from mDCs, the process was MR- and endocytosis-independent. In addition, IL-23 was shown to be indispensible for HBsAg-stimulated differentiation of naïve CD4(+ T cells into Th17 cells, which were determined to be the primary source of IL-17 in HBV-infected livers. The cognate receptor, IL-17R, was found to exist on the hepatic stellate cells and mDCs, both of which might represent the potential target cells of IL-17 in hepatitis B disease. These data provide novel insights into a yet unrecognized mechanism of HBV-induced hepatitis, by which increases in IL-23 expression, through an MR/endocytosis-dependent or -independent manner, produce liver damage through the IL-23/IL-17 axis.

  13. Patients with HBV-related acute-on-chronic liver failure have increased concentrations of extracellular histones aggravating cellular damage and systemic inflammation.

    Science.gov (United States)

    Li, X; Gou, C; Yao, L; Lei, Z; Gu, T; Ren, F; Wen, T

    2017-01-01

    Acute-on-chronic liver failure (ACLF) is the most common type of liver failure and associated with grave consequences. Systemic inflammation has been linked to its pathogenesis and outcome, but the identifiable triggers are absent. Recently, extracellular histones, especially H4, have been recognized as important mediators of cell damage in various inflammatory conditions. This study aimed to investigate whether extracellular histones have clinical implications in patients with hepatitis B virus (HBV)-related ACLF. One hundred and twelve patients with HBV-related ACLF, 90 patients with chronic hepatitis B, 88 patients with HBV-related liver cirrhosis and 40 healthy volunteers were entered into this study. Plasma histone H4 levels, cytokine profile and clinical data were obtained. Besides, patient's sera were incubated overnight with human L02 hepatocytes or monocytic U937 cells in the presence or absence of antihistone H4 antibody, and cellular damage and cytokine production were evaluated. We found that plasma histone H4 levels were greatly increased in patients with ACLF as compared with chronic hepatitis B, liver cirrhosis and healthy control subjects and were significantly associated with disease severity, systemic inflammation and outcome. Notably, ACLF patients' sera incubation decreased cultured L02 cell integrity and induced profound cytokine production in the supernatant of U937 cells. Antihistone H4 antibody treatment abrogated these adverse effects, thus confirming a cause-effect relationship between extracellular histones and organ injury/dysfunction. The data support the hypothesis that the increased extracellular histone levels in ACLF patients may aggravate disease severity by inducing cellular injury and systemic inflammation. Histone-targeted therapies may have potentially interventional value in clinical practice. © 2016 John Wiley & Sons Ltd.

  14. The therapeutic effect of nano-encapsulated and nano-emulsion forms of carvacrol on experimental liver fibrosis.

    Science.gov (United States)

    Hussein, Jihan; El-Banna, Mona; Mahmoud, Khaled F; Morsy, Safaa; Abdel Latif, Yasmin; Medhat, Dalia; Refaat, Eman; Farrag, Abdel Razik; El-Daly, Sherien M

    2017-06-01

    The present study aimed to compare the therapeutic efficiency of nano-encapsulated and nano-emulsion carvacrol administration on liver injury in thioacetamide (TAA) treated rats. To fulfill our target, we used sixty male albino rats classified into six groups as follow: control, nano-encapsulated carvacrol, nano-emulsion carvacrol, thioacetamide, treated nano-encapsulated carvacrol and treated nano-emulsion carvacrol groups. Blood samples were collected from all groups and the separated serum was used for analysis of the following biochemical parameters; aspartate aminotransferase (AST), alanine aminotransferase (ALT), S100 B protein, alpha fetoprotein (AFP) and caspase-3. The levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), monocyte chemoattractant protein-1(MCP-1) and hydroxyproline content were all evaluated in liver tissue homogenate. Histopathological examinations for liver tissues were also performed. Thioacetamide induced hepatic damage in rats as revealed by the significant increase in the levels of serum ALT, AST and produced oxidative stress as displayed by the significant elevation in the levels of hepatic MDA and NO concomitant with a significant decrease in GSH. In addition, thioacetamide significantly increased serum S100B protein, alpha fetoprotein and caspase-3 along with hepatic MCP-1 and hydroxyproline; these results were confirmed by the histopathological investigation. In contrast, nano-encapsulated and nano-emulsion carvacrol were able to ameliorate these negative changes in the thioacetamide injected rats. However, the effect of the nano-encapsulated form of carvacrol was more prominent than the nano-emulsion form. Nano-encapsulated and nano-emulsion carvacrol can ameliorate thioacetamide induced liver injury. These results could be attributed to the potential anti-inflammatory, antioxidant, and anti-apoptotic activities of carvacrol in addition to the effectiveness of the encapsulation technique that can protect

  15. Gamma Amino Butyric Acid Attenuates Liver and Kidney Damage Associated with Insulin Alteration in γ-Irradiated and Streptozotocin-Treated Rats

    International Nuclear Information System (INIS)

    Saada, H.N.; Eltahawy, N.A.; Hammad, A.S.; Morcos, N.Y.S.

    2016-01-01

    Gamma aminobutyric acid (GABA) is one of the inhibitory neurotransmitters that may have the ability to relive the intensity of stress. The aim of the current study was to evaluate the role of γ-amino butyric acid (GABA) in modulating insulin disturbance associated with liver and kidney damage in γ-irradiated and streptozotocin-treated rats. Irradiation was performed by whole body exposure to 6 Gy from a Cs-137 source. Streptozotocin (STZ) was administered in a single intraperitoneal dose (60 mg/kg body weight). GABA (200 mg/Kg body weight/day) was administered daily via gavages during 3 weeks to γ-irradiated and STZ-treated-rats. The results obtained showed that γ-irradiation induced hyperglycemia, hyperinsulinaemia and insulin resistance (similar to type 2 Diabetes), while STZ-treatment produced hyperglycemia, insulin deficiency with no insulin resistance detected (similar to type 1 Diabetes). In both cases, significant increases of alanine amino transferase (ALT) and aspartate amino transferase (AST) activities, urea and creatinine levels were recorded in the serum. These changes were associated with oxidative damage to the liver and kidney tissues notified by significant decreases of superoxide dismutase (SOD ), catalase and glutathione peroxidase ( GSH-Px) activities in parallel to significant increases of malondialdehyde (MDA) and advanced oxidation protein products ( AOPP) levels. The administration of GABA to irradiated as well as STZ-treated rats regulated insulin and glucose levels, minimized oxidative stress and reduced the severity of liver and kidney damage. It could be concluded that GABA could be a useful adjunct to reduce some metabolic complications associated with insulin deficiency and insulin resistance

  16. Tumor control induced by Boron Neutron Capture Therapy (BNCT) as a function of dose in an experimental model of liver metastases at 5 weeks follow-up

    International Nuclear Information System (INIS)

    Pozzi, E C C; Trivillin, V A; Colombo, L L; Monti Hughes, A; Thorp, S; Cardoso, J E; Garabalino, M A; Molinari, A J; Heber, E M; Curotto, Paula; Miller, M; Itoiz, M E; Aromando, R F; Nigg, D W; Schwint, A E

    2012-01-01

    BNCT has been proposed for the treatment of multifocal, non-resectable, bilobar colorectal liver metastases that do not respond to chemotherapy. We recently reported that BNCT mediated by boronophenylalanine (BPA) induced significant remission of experimental colorectal tumor nodules in rat liver at 3 weeks follow-up with no contributory liver toxicity (Pozzi et al.,2012). The aim of the present study was to evaluate tumor control and potential liver toxicity of BPA-BNCT at 5 weeks follow-up. Prescribed dose was retrospectively evaluated based on blood boron values, allowing for assessment of response over a range of delivered dose values (author)

  17. Experimental increase in baseline corticosterone level reduces oxidative damage and enhances innate immune response.

    Directory of Open Access Journals (Sweden)

    Csongor I Vágási

    Full Text Available Glucocorticoid (GC hormones are significant regulators of homeostasis. The physiological effects of GCs critically depend on the time of exposure (short vs. long as well as on their circulating levels (baseline vs. stress-induced. Previous experiments, in which chronic and high elevation of GC levels was induced, indicate that GCs impair both the activity of the immune system and the oxidative balance. Nonetheless, our knowledge on how mildly elevated GC levels, a situation much more common in nature, might influence homeostasis is limited. Therefore, we studied whether an increase in GC level within the baseline range suppresses or enhances condition (body mass, hematocrit and coccidian infestation and physiological state (humoral innate immune system activity and oxidative balance. We implanted captive house sparrows Passer domesticus with either 60 days release corticosterone (CORT or control pellets. CORT-treated birds had elevated baseline CORT levels one week after the implantation, but following this CORT returned to its pre-treatment level and the experimental groups had similar CORT levels one and two months following the implantation. The mass of tail feathers grown during the initial phase of treatment was smaller in treated than in control birds. CORT implantation had a transient negative effect on body mass and hematocrit, but both of these traits resumed the pre-treatment values by one month post-treatment. CORT treatment lowered oxidative damage to lipids (malondialdehyde and enhanced constitutive innate immunity at one week and one month post-implantation. Our findings suggest that a relatively short-term (i.e. few days elevation of baseline CORT might have a positive and stimulatory effect on animal physiology.

  18. Micromechanical experimental analysis and modelling of elastic and damageable behaviour of unidirectional SiC/SiC composites

    International Nuclear Information System (INIS)

    Chateau, C.

    2011-01-01

    Because of their potential use as a cladding material in future nuclear reactors, the complex mechanical behavior of SiC/SiC composites, which combines damage and anisotropy, must be understood and predictable. As part of a multi-scale approach, this work focuses on the first scale change: from the elementary constituents to the tow. Micromechanical approaches are implemented to describe the macroscopic behavior of the tow taking into account its microstructure heterogeneity and damage mechanisms occurring at the local scale. A representative virtual microstructure is generated based on a detailed microstructural investigation of the tow and its elastic response is studied by numerical homogenization. In addition to addressing the mechanical RVE issue, this study highlights the significant effects of residual porosity on the transverse behavior of the tow, due to the matrix infiltration process. The longitudinal damage is being studied through mini-composites, for which the evolution of microscopic damage mechanisms (matrix cracks and fiber breaks) is experimentally analyzed (in-situ SEM and tomography tensile tests). The identification of interfacial parameters of a 1D statistical damage model is based on the experimental characterization. Conventional assumptions of such models can adequately describe matrix cracking at macro and micro scale. However it is necessary to change them to get a proper prediction of ultimate failure. (author) [fr

  19. Double-Balloon Catheter for Isolated Liver Perfusion: An Experimental Study

    International Nuclear Information System (INIS)

    Cwikiel, Wojciech; Bergqvist, Lennart; Harnek, Jan

    2001-01-01

    Purpose: Further development of a previously described interventional method for isolated liver perfusion (ILP) with a new double-lumen balloon catheter, and evaluation of the side-effects of such isolation.Methods: In six pigs a double-balloon occlusion catheter was placed via the transjugular approach with its tip in the portal vein. One of the balloons was positioned in the inferior vena cava (IVC), cranial to the origin of the hepatic veins and the other balloon in the portal vein. By the transfemoral approach, a single-balloon occlusion catheter was placed in the IVC caudal to the origin of the hepatic veins. A third catheter was placed by the transfemoral route with the occlusion balloon in the proper hepatic artery. After inflation of all balloons 99 Tc m -labelled human serum albumin was recirculated through the liver. The isolation was evaluated by repeated measurement of radioactivity levels in peripheral blood. Laboratory tests of liver and pancreas function, and hemoglobin, were taken before, at the end of, and 3 days after the procedure. Blood gases were tested at the beginning and end of the procedure.Results: One pig died during the procedure due to technical failure and was excluded from the study. In the other pigs leakage from the isolated liver to the systemic circulation increased slowly, up to 9.7% (mean) during 30 min of recirculation of the perfusate through the liver. Laboratory tests were normal in all pigs except insignificant acidosis directly after the procedure and the slight elevation of s-ALAT after 3 days.Conclusions: Only minor leakage from the liver to the systemic circulation was noted during ILP performed with a new, double-balloon catheter. There were no serious side effects

  20. Ursodeoxycholic acid inhibits hepatic cystogenesis in experimental models of polycystic liver disease.

    Science.gov (United States)

    Munoz-Garrido, Patricia; Marin, José J G; Perugorria, María J; Urribarri, Aura D; Erice, Oihane; Sáez, Elena; Úriz, Miriam; Sarvide, Sarai; Portu, Ainhoa; Concepcion, Axel R; Romero, Marta R; Monte, María J; Santos-Laso, Álvaro; Hijona, Elizabeth; Jimenez-Agüero, Raúl; Marzioni, Marco; Beuers, Ulrich; Masyuk, Tatyana V; LaRusso, Nicholas F; Prieto, Jesús; Bujanda, Luis; Drenth, Joost P H; Banales, Jesús M

    2015-10-01

    Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive biliary cystogenesis. Current therapies show short-term and/or modest beneficial effects. Cystic cholangiocytes hyperproliferate as a consequence of diminished intracellular calcium levels ([Ca(2+)]i). Here, the therapeutic value of ursodeoxycholic acid (UDCA) was investigated. Effect of UDCA was examined in vitro and in polycystic (PCK) rats. Hepatic cystogenesis and fibrosis, and the bile acid (BA) content were evaluated from the liver, bile, serum, and kidneys by HPLC-MS/MS. Chronic treatment of PCK rats with UDCA inhibits hepatic cystogenesis and fibrosis, and improves their motor behaviour. As compared to wild-type animals, PCK rats show increased BA concentration ([BA]) in liver, similar hepatic Cyp7a1 mRNA levels, and diminished [BA] in bile. Likewise, [BA] is increased in cystic fluid of PLD patients compared to their matched serum levels. In PCK rats, UDCA decreases the intrahepatic accumulation of cytotoxic BA, normalizes their diminished [BA] in bile, increases the BA secretion in bile and diminishes the increased [BA] in kidneys. In vitro, UDCA inhibits the hyperproliferation of polycystic human cholangiocytes via a PI3K/AKT/MEK/ERK1/2-dependent mechanism without affecting apoptosis. Finally, the presence of glycodeoxycholic acid promotes the proliferation of polycystic human cholangiocytes, which is inhibited by both UDCA and tauro-UDCA. UDCA was able to halt the liver disease of a rat model of PLD through inhibiting cystic cholangiocyte hyperproliferation and decreasing the levels of cytotoxic BA species in the liver, which suggests the use of UDCA as a potential therapeutic tool for PLD patients. Copyright © 2015 European Association for the Study of the Liver. All rights reserved.

  1. Experimental and analytical investigation on metal damage suffered from simulated lightning currents

    Science.gov (United States)

    Yakun, LIU; Zhengcai, FU; Quanzhen, LIU; Baoquan, LIU; Anirban, GUHA

    2017-12-01

    The damage of two typical metal materials, Al alloy 3003 and steel alloy Q235B, subjected to four representative lightning current components are investigated by laboratory and analytical studies to provide fundamental data for lightning protection. The four lightning components simulating the natural lightning consist of the first return stroke, the continuing current of interval stroke, the long continuing current, and the subsequent stroke, with amplitudes 200 kA, 8 kA, 400 A, and 100 kA, respectively. The damage depth and area suffered from different lightning components are measured by the ultrasonic scanning system. And the temperature rise is measured by the thermal imaging camera. The results show that, for both Al 3003 and steel Q235B, the first return stroke component results in the largest damage area with damage depth 0.02 mm uttermost. The long continuing current component leads to the deepest damage depth of 3.3 mm for Al 3003 and much higher temperature rise than other components. The correlation analysis between damage results and lightning parameters indicates that the damage depth has a positive correlation with charge transfer. The damage area is mainly determined by the current amplitude and the temperature rise increases linearly with the charge transfer larger.

  2. Experimental Investigations on Effect of Damage on Vibration Characteristics of a Reinforced Concrete Beam

    Science.gov (United States)

    Srinivas, V.; Jeyasehar, C. Antony; Ramanjaneyulu, K.; Sasmal, Saptarshi

    2012-02-01

    Need for developing efficient non-destructive damage assessment procedures for civil engineering structures is growing rapidly towards structural health assessment and management of existing structures. Damage assessment of structures by monitoring changes in the dynamic properties or response of the structure has received considerable attention in recent years. In the present study, damage assessment studies have been carried out on a reinforced concrete beam by evaluating the changes in vibration characteristics with the changes in damage levels. Structural damage is introduced by static load applied through a hydraulic jack. After each stage of damage, vibration testing is performed and system parameters were evaluated from the measured acceleration and displacement responses. Reduction in fundamental frequencies in first three modes is observed for different levels of damage. It is found that a consistent decrease in fundamental frequency with increase in damage magnitude is noted. The beam is numerically simulated and found that the vibration characteristics obtained from the measured data are in close agreement with the numerical data.

  3. Hepatic vessel segmentation for 3D planning of liver surgery experimental evaluation of a new fully automatic algorithm.

    Science.gov (United States)

    Conversano, Francesco; Franchini, Roberto; Demitri, Christian; Massoptier, Laurent; Montagna, Francesco; Maffezzoli, Alfonso; Malvasi, Antonio; Casciaro, Sergio

    2011-04-01

    The aim of this study was to identify the optimal parameter configuration of a new algorithm for fully automatic segmentation of hepatic vessels, evaluating its accuracy in view of its use in a computer system for three-dimensional (3D) planning of liver surgery. A phantom reproduction of a human liver with vessels up to the fourth subsegment order, corresponding to a minimum diameter of 0.2 mm, was realized through stereolithography, exploiting a 3D model derived from a real human computed tomographic data set. Algorithm parameter configuration was experimentally optimized, and the maximum achievable segmentation accuracy was quantified for both single two-dimensional slices and 3D reconstruction of the vessel network, through an analytic comparison of the automatic segmentation performed on contrast-enhanced computed tomographic phantom images with actual model features. The optimal algorithm configuration resulted in a vessel detection sensitivity of 100% for vessels > 1 mm in diameter, 50% in the range 0.5 to 1 mm, and 14% in the range 0.2 to 0.5 mm. An average area overlap of 94.9% was obtained between automatically and manually segmented vessel sections, with an average difference of 0.06 mm(2). The average values of corresponding false-positive and false-negative ratios were 7.7% and 2.3%, respectively. A robust and accurate algorithm for automatic extraction of the hepatic vessel tree from contrast-enhanced computed tomographic volume images was proposed and experimentally assessed on a liver model, showing unprecedented sensitivity in vessel delineation. This automatic segmentation algorithm is promising for supporting liver surgery planning and for guiding intraoperative resections. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

  4. Boron Neutron Capture Therapy (BCNT) for the Treatment of Liver Metastases: Biodistribution Studies of Boron Compounds in an Experimental Model

    Energy Technology Data Exchange (ETDEWEB)

    Marcela A. Garabalino; Andrea Monti Hughes; Ana J. Molinari; Elisa M. Heber; Emiliano C. C. Pozzi; Maria E. Itoiz; Veronica A. Trivillin; Amanda E. Schwint; Jorge E. Cardoso; Lucas L. Colombo; Susana Nievas; David W. Nigg; Romina F. Aromando

    2011-03-01

    Abstract We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of 10B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B10H10), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.

  5. Hearing loss and cochlear damage in experimental pneumococcal meningitis, with special reference to the role of neutrophil granulytes

    DEFF Research Database (Denmark)

    Brandt, CT; Caye-Thomsen, P; Lund, SP

    2006-01-01

    of an augmented neutrophil response on the development of hearing loss and cochlear damage in a model of experimental pneumococcal meningitis in rats. Hearing loss and cochlear damage were assessed by distortion product oto-acoustic emissions (DPOAE), auditory brainstem response (ABR) and histopathology in rats...... infection. Pretreatment with G-CSF increased hearing loss 24 h after infection and on day 8 compared to untreated rats (Mann-Whitney, P = 0.012 and P = 0.013 respectively). The increased sensorineural hearing loss at day 8 was associated with significantly decreased spiral ganglion cell counts (P = 0...

  6. Proceedings of the workshop. Recognition of DNA damage as onset of successful repair. Computational and experimental approaches

    International Nuclear Information System (INIS)

    Pinak, Miroslav

    2002-03-01

    This was held at The Tokai Research Establishment, Japan Atomic Energy Research Institute, on the 18th and 19th of December 2001. The Laboratory of Radiation Risk Analysis of JAERI organized the workshop. The main subject of the workshop was the DNA damage and its repair. Presented works described the leading experimental as well computational approaches, focusing mainly on the formation of DNA damage, its proliferation, enzymatic recognition and repair, and finally imaging and detection of lesions on a DNA molecule. The 19 of the presented papers are indexed individually. (J.P.N.)

  7. Liver Immunology

    Science.gov (United States)

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

  8. The experimental study of radiation injury on bile duct and liver tissue

    International Nuclear Information System (INIS)

    Cao Guiwen; Wang Bin; Sun Yequan; Shao Xueye; Ning Houfa; Sui Shouguang; Wang Xiuchun; Bai Xuming

    2007-01-01

    Objective: To investigate the safety, acceptance and the effective extent of 192 Ir-internal irradiation, providing theoretical guidelines for HC. Methods: Sixteen male healthy hybrid dogs enrolled in the experiment were divided into 4 groups of 4 each. The brachytherapy applicator was introduced from gall bladder into the convergence of cystic duct with common hepatic duct during the operation and a small chip of 1 cm 3 liver tissue was cut off and taken for control later on. The animals in group A-D were irradiated by 192 Ir-internal irradiation with 30 Gy, 40 Gy, 50 Gy arid 60 Gy at the correlative dose points respectively. Animals were put to death after 10 days subsequently, with sampling specimens obtained from radiation cystic duct and the in between liver tissue with the distant cystic duct. The radiation injury of the cystic duct and liver tissue near bile ducts were observed and studied by light microscope and transmission election microscope. Results: By the limit of the safest endurance dose(50 Gy) of Bile duct, unreversed injury of the nuclei of liver cells occurred at 0 to 15 mm from bile duct revealed by transmission electron microscope and light microscope. The whole biliary duct wall would be undergone necrosis with irradiation dose over 60 Gy. Conclusions: Normal bile duct possesses good endurance to 192 Ir-internal irradiation. Within the safest endurance limit of 50 Gy the effective irradiation field could reach 15 mm from the involved bile duct. (authors)

  9. An experimental microangiographic study on injured liver acinus by ligation of common bile duct

    International Nuclear Information System (INIS)

    Park, Jong Yeon; Kim, Yoon Gyu; Moon, Ki Ho; Lee, Suek Hong; Kim, Byung Soo; Han, Gun Taik

    1994-01-01

    The purpose of this study was to evaluate the morphologic changes of the injured hepatic acini following ligation of common bile duct and to investigate the pathophysiologic process of hepatic failure and biliary liver cirrhosis in the extrahepatic cholestasis. The common bile ducts of 18 rabbits were ligated partially. The rabbits were killed and selective microangiography was carried out with infusion of barium suspensio via portal vein 4 to 24 weeks after ligation. Selective microangiography was also carried out in two normal rabbits. The microangiographic findings were evaluated and correlated with histopathologic features. The sinusoids of the liver acinus showed distortion, varying degrees of luminal widening, and irregularities in architecture. Terminal branches of the portal vein (TPV) showed increased number of branches, luminal narrowing, tortuosity, distortion, and beaded appearance. Peribiliary plexi were found as thin curvilinear, barium-filled structures along the wall of the dilated bile duct. The microangiographic findings were well correlated with histopathologic findings. The grades of microangiographic and histopathologic findings were poorly correlated with the duration of the ligation of CBD. Changes in microvasculature of the liver scinus following partial ligation of common bile duct were demonstrated by microangiography. Although the microvascular changes were evoked secondary to the injury, they might have some active roles in the pathophysiologic process in the liver

  10. Effect of obeticholic acid on liver regeneration following portal vein embolization in an experimental model

    NARCIS (Netherlands)

    Olthof, P. B.; Huisman, F.; Schaap, F. G.; van Lienden, K. P.; Bennink, R. J.; van Golen, R. F.; Heger, M.; Verheij, J.; Jansen, P. L.; Olde Damink, S. W.; van Gulik, T. M.

    2017-01-01

    The bile salt-activated transcription factor farnesoid X receptor (FXR) is a key mediator of proliferative bile salt signalling, which is assumed to play a role in the early phase of compensatory liver growth. The aim of this study was to evaluate the effect of a potent FXR agonist (obeticholic

  11. Protective Effect of Cymbopogon citratus Essential Oil in Experimental Model of Acetaminophen-Induced Liver Injury.

    Science.gov (United States)

    Uchida, Nancy Sayuri; Silva-Filho, Saulo Euclides; Aguiar, Rafael Pazinatto; Wiirzler, Luiz Alexandre Marques; Cardia, Gabriel Fernando Esteves; Cavalcante, Heitor Augusto Otaviano; Silva-Comar, Francielli Maria de Souza; Becker, Tânia Cristina Alexandrino; Silva, Expedito Leite; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

    2017-01-01

    To investigate the hepatoprotective effect of Cymbopogon citratus or lemongrass essential oil (LGO), it was used in an animal model of acute liver injury induced by acetaminophen (APAP). Swiss mice were pretreated with LGO (125, 250 and 500[Formula: see text]mg/kg) and SLM (standard drug, 200[Formula: see text]mg/kg) for a duration of seven days, followed by the induction of hepatotoxicity of APAP (single dose, 250[Formula: see text]mg/kg). The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase were determined to evaluate the hepatoprotective effects of the LGO. The livers were used to determine myeloperoxidase (MPO) activity, nitric oxide (NO) production and histological analysis. The effect of LGO on leukocyte migration was evaluated in vitro. Anti-oxidant activity was performed by assessing the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro. LGO pretreatment decreased significantly the levels of ALT, AST and ALP compared with APAP group. MPO activity and NO production were decreased. The histopathological analysis showed an improved of hepatic lesions in mice after LGO pretreatment. LGO inhibited neutrophil migration and exhibited anti-oxidant activity. Our results suggest that LGO has protective activity against liver toxicity induced by paracetamol.

  12. The protective effects of pomegranate on liver and remote organs caused by experimental obstructive jaundice model.

    Science.gov (United States)

    Yilmaz, E E; Arikanoğlu, Z; Turkoğlu, A; Kiliç, E; Yüksel, H; Gümüş, M

    2016-01-01

    We aimed to investigate the protective potential of pomegranate extract on the liver and remote organs in rats with obstructive jaundice. The rats were split into 4 groups. In Group 1 (G1) (sham group) rats, the common bile duct was mobilized without any ligation. Group 2 (G2) received a combination of the sham operation and synchronous treatment with pomegranate. Group 3 (G3) received common bile duct ligation (CBDL). Group 4 (G4) were subjected to CBDL and treatment with pomegranate. After 8 days, we measured total oxidative status (TOS) and antioxidant capacity in the rats' liver tissue and remote organs, and evaluated blood levels of malondialdehyde and total antioxidant capacity (TAC). G3 rats showed significantly raised malondialdehyde level as compared to G1 rats (p pomegranate therapy, a decrease in malondialdehyde was observed (p = 0.015). TAC levels were significantly raised in the G3 rats compared to the G1 rats (p = 0.004). TAC levels dropped after pomegranate therapy (p = 0.011). CBDL caused elevated TOS levels in the liver and remote organs, with a statistically significant increase in the lung tissue (p = 0.002). TOS levels in the CBDL groups decreased after pomegranate treatment (p pomegranate on the liver and remote organs in obstructive jaundice.

  13. The experimental study on liver VX-2 tumor by using MR diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Yuan Youhong; Xiao Enhua; Jin Ke; Yan Ronghua; He Zhong; Shang Quanliang; Hu Weizhou; Yuan Shiwen; Xiang Jun; Tang Keli; Yi Shijian; Yin Qiang

    2005-01-01

    Objective: To study the imaging characteristics of rabbit's liver VX-2 tumor on MR diffusion-weighted imaging. Methods: Of the 35 New Zealand rabbits, 14 were implanted under the skin while 6 were implanted in liver with VX-2 tumor in preparing experiment, and 12 were implanted in liver and 3 as controls in formal experiment. Before and after the implantation, MR diffusion-weighted imaging (DWI), T 1 -weighted and T 2 -weighted images were performed respectively and periodically in 15 tumors including 12 liver tumor implantations in formal experiment. DWI parameters including apparent diffusion coefficient (ADC) value were acquired and statistically analyzed by SPSS 10.0. Results: (1) The successful rate of implantation was 29% (4/14) under the skin and 33% (2/6) in the liver in preparing experiment. And the successful rate of formal experiment was 83% (10/12). (2) DWI signal of VX-2 tumor was high and the signal became lower and lower with b value increased step by step. The signal of VX-2 tumor on ADC map was low. The ADC value of normal group was (2.57 ± 0.26) mm 2 /s (b=100 s/mm 2 ) and (1.73 ± 0.31) mm 2 /s (b=300 s/mm 2 ), and ADC value of VX-2 tumor group was (1.87 ± 0.25) mm 2 /s (b=100 s/mm 2 ) and (1.57 ± 0.23) mm 2 /s (b=300 s/mm 2 ), respectively.The F value of analysis of variance was 43.26 (P<0.001). The distinction of tumor ADC value in different b values was significant (P<0.05), and the distinction of ADC value between VX-2 tumor and normal liver was also significant (P<0.01). (3) VX-2 tumor developed quickly and metastasized early to all parts of the body, especially to the lung, the liver, the lymph nodes of mediastinum and so on. Conclusion: DWI signal of VX-2 tumor has its characteristic and DWI has important value in reflecting the movement of water molecules, discovering the VX-2 tumor, and tracking its progress. (authors)

  14. Effects of transcutaneous electrical stimulation of lower limb muscles on experimental fatty liver.

    Science.gov (United States)

    El-Kafoury, Bataa M; Seif, Ansam A; El-Aziz Abd El-Hady, Enas A; El-Sebaiee, Ahmed E

    2016-03-01

    Although the beneficial effects of exercise on fatty liver have been described, a previous study conducted at our department showed that transcutaneous electrical muscle stimulation (TEMS) of lower abdominal muscles aggravated fatty liver. The present study aims to evaluate the ability of TEMS of the lower limb muscles to improve fatty liver infiltration. Thirty male Wistar rats were randomly allocated into three groups: control; fructose-fed (F), fed fructose-enriched diet for 6weeks; and fructose-fed with transcutaneous electrical muscle stimulation (F+TEMS), fed fructose-enriched diet for 6weeks and lower limb muscles subjected to TEMS during the last 3weeks of feeding, five sessions/week. Body weight, length, body mass index (BMI), and abdominal and lower limb circumferences were all recorded. Fasting blood glucose, serum insulin, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, serum albumin, high density lipoprotein cholesterol (HDL-C), triglyceride (TG), and total cholesterol (TC) levels were measured. LDL cholesterol (LDL-C) and the atherogenic index (AI) were calculated. Absolute and relative hepatic weights as well as histological examination of the liver were assessed. Final body weight, abdominal and lower limb circumferences, absolute liver weight, homoeostasis model assessment (HOMA) score, and TG, LDL-C, AI, serum ALT, and AST levels were all significantly reduced in the (F+TEMS) group compared to the (F) group. There was a significant increase in GPx and HDL-C levels, HDL/LDL ratio, and total protein and serum albumin content in (F+TEMS) rats compared to (F) rats. Histologically, hepatic tissue from (F+TEMS) rats had minimal steatotic changes that were restricted to zone 1 and less marked inflammatory cell infiltration compared to (F) rats. TEMS was able to reverse steatosis, hyperglycaemia, insulin resistance, dyslipidaemia, and fatty liver caused by fructose feeding. The study confirmed that the variation in

  15. Sequential projection pursuit for optimised vibration-based damage detection in an experimental wind turbine blade

    Science.gov (United States)

    Hoell, Simon; Omenzetter, Piotr

    2018-02-01

    To advance the concept of smart structures in large systems, such as wind turbines (WTs), it is desirable to be able to detect structural damage early while using minimal instrumentation. Data-driven vibration-based damage detection methods can be competitive in that respect because global vibrational responses encompass the entire structure. Multivariate damage sensitive features (DSFs) extracted from acceleration responses enable to detect changes in a structure via statistical methods. However, even though such DSFs contain information about the structural state, they may not be optimised for the damage detection task. This paper addresses the shortcoming by exploring a DSF projection technique specialised for statistical structural damage detection. High dimensional initial DSFs are projected onto a low-dimensional space for improved damage detection performance and simultaneous computational burden reduction. The technique is based on sequential projection pursuit where the projection vectors are optimised one by one using an advanced evolutionary strategy. The approach is applied to laboratory experiments with a small-scale WT blade under wind-like excitations. Autocorrelation function coefficients calculated from acceleration signals are employed as DSFs. The optimal numbers of projection vectors are identified with the help of a fast forward selection procedure. To benchmark the proposed method, selections of original DSFs as well as principal component analysis scores from these features are additionally investigated. The optimised DSFs are tested for damage detection on previously unseen data from the healthy state and a wide range of damage scenarios. It is demonstrated that using selected subsets of the initial and transformed DSFs improves damage detectability compared to the full set of features. Furthermore, superior results can be achieved by projecting autocorrelation coefficients onto just a single optimised projection vector.

  16. Experimental detection of iron overload in liver through neutron stimulated emission spectroscopy

    International Nuclear Information System (INIS)

    Kapadia, A J; Tourassi, G D; Sharma, A C; Crowell, A S; Kiser, M R; Howell, C R

    2008-01-01

    Iron overload disorders have been the focus of several quantification studies involving non-invasive imaging modalities. Neutron spectroscopic techniques have demonstrated great potential in detecting iron concentrations within biological tissue. We are developing a neutron spectroscopic technique called neutron stimulated emission computed tomography (NSECT), which has the potential to diagnose iron overload in the liver at clinically acceptable patient dose levels through a non-invasive scan. The technique uses inelastic scatter interactions between atomic nuclei in the sample and incoming fast neutrons to non-invasively determine the concentration of elements in the sample. This paper discusses a non-tomographic application of NSECT investigating the feasibility of detecting elevated iron concentrations in the liver. A model of iron overload in the human body was created using bovine liver tissue housed inside a human torso phantom and was scanned with a 5 MeV pulsed beam using single-position spectroscopy. Spectra were reconstructed and analyzed with algorithms designed specifically for NSECT. Results from spectroscopic quantification indicate that NSECT can currently detect liver iron concentrations of 6 mg g -1 or higher and has the potential to detect lower concentrations by optimizing the acquisition geometry to scan a larger volume of tissue. The experiment described in this paper has two important outcomes: (i) it demonstrates that NSECT has the potential to detect clinically relevant concentrations of iron in the human body through a non-invasive scan and (ii) it provides a comparative standard to guide the design of iron overload phantoms for future NSECT liver iron quantification studies

  17. Experimental and numerical characterization of anisotropic damage evolution of forged Al6061-T6 alloy

    International Nuclear Information System (INIS)

    Shen, Y.; Garnier, J.; Allais, L.; Crepin, J.; Ancelet, O.; Hiver, J.M.

    2011-01-01

    Aluminum alloy 6061-T6 (Al-Mg-Si) has been selected as the material of the vessel for the construction of Jules-Horowitz material testing reactor. Fracture mechanism of this alloy has been investigated using mechanical testing of smooth and notched tensile specimens loaded in different directions. A strong anisotropic fracture behavior has been observed. Microstructural studies using tomography and image analysis have shown a presence of anisotropic distributed coarse precipitates which is the key microstructural feature affecting the damage evolution. These observations were complemented by investigations on fractured tensile samples. A damage scenario of anisotropic growth and coalescence of voids is proposed to explain the fracture behavior associated with the distribution of precipitates. A GTN (Gurson-Tvergaard-Needleman) damage model is used to simulate this scenario and to predict damage evolution. (authors)

  18. Correlation of experimental damage data for the development of the UT-MARLOWE Monte Carlo ion implant simulator

    International Nuclear Information System (INIS)

    Morris, M. F.; Tian, S.; Chen, Y.; Tasch, A.; Baumann, S.; Kirchhoff, J. F.; Hummel, R.; Prussin, S.; Kamenitsa, D.; Jackson, J.

    1999-01-01

    The Monte Carlo ion implant simulator UT-MARLOWE has usually been verified using a large array of Secondary Ion Mass Spectroscopy (SIMS) data (∼200 profiles per ion species)(1). A model has recently been developed (1) to explicitly simulate defect production, diffusion, and their interactions during the picosecond 'defect production stage' of ion implantation. In order to thoroughly validate this model, both SIMS and various damage measurements were obtained (primarily channeling-Rutherford Backscattering Spectroscopy, Differential Reflectometry and Tapered Groove Profilometry, but supported with SEM and XTEM data). In general, the data from the various experimental techniques was consistent, and the Kinetic Accumulation Damage Model (KADM) was developed and validated using this data. This paper discusses the gathering of damage data in conjunction with SIMS in support of the development of an ion implantation simulator

  19. Filtered air plastic chamber as an experimental facility to prove visible damage of crops due to air pollution

    Energy Technology Data Exchange (ETDEWEB)

    Matsuoka, Y; Yoda, H; Omichi, S; Shiratori, K

    1975-01-01

    An experimental filtered air chamber was constructed to prove the visible damage of crops due to air pollution. The chamber was provided with another room into which non-filtered ambient air was introduced. The purified air was prepared by filtering ambient air with activated carbon. The average content of air pollutants in the purified air chamber was less than 10 to 20% of the ozone and 20% of the sulfur oxides in the ambient air. However, cultivated vegetables such as tobacco and spinach, which are susceptible to oxidant, showed no visible damage in the filtered air chamber, and showed the same damage in the nonfiltered air chamber as was seen in fields at the same time.

  20. Experimental Analysis and Discussion on the Damage Variable of Frozen Loess

    Directory of Open Access Journals (Sweden)

    Cong Cai

    2017-01-01

    Full Text Available The damage variable is very important to study damage evolution of material. Taking frozen loess as an example, a series of triaxial compression and triaxial loading-unloading tests are performed under five strain rates of 5.0 × 10−6–1.3 × 10−2/s at a temperature of −6°C. A damage criterion of frozen loess is defined and a damage factor Dc is introduced to satisfy the requirements of the engineering application. The damage variable of frozen loess is investigated using the following four methods: the stiffness degradation method, the deformation increase method, the dissipated energy increase method, and the constitutive model deducing method during deformation process. In addition, the advantages and disadvantages of the four methods are discussed when they are used for frozen loess material. According to the discussion, the plastic strain may be the most appropriate variable to characterize the damage evolution of frozen loess during the deformation process based on the material properties and the nature of the material service.

  1. Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep

    Directory of Open Access Journals (Sweden)

    Wolfgang Härtig

    2017-08-01

    Full Text Available As part of the extracellular matrix (ECM, perineuronal nets (PNs are polyanionic, chondroitin sulfate proteoglycan (CSPG-rich coatings of certain neurons, known to be affected in various neural diseases. Although these structures are considered as important parts of the neurovascular unit (NVU, their role during evolution of acute ischemic stroke and subsequent tissue damage is poorly understood and only a few preclinical studies analyzed PNs after acute ischemic stroke. By employing three models of experimental focal cerebral ischemia, this study was focused on histopathological alterations of PNs and concomitant vascular, glial and neuronal changes according to the NVU concept. We analyzed brain tissues obtained 1 day after ischemia onset from: (a mice after filament-based permanent middle cerebral artery occlusion (pMCAO; (b rats subjected to thromboembolic MACO; and (c sheep at 14 days after electrosurgically induced focal cerebral ischemia. Multiple fluorescence labeling was applied to explore simultaneous alterations of NVU and ECM. Serial mouse sections labeled with the net marker Wisteria floribunda agglutinin (WFA displayed largely decomposed and nearly erased PNs in infarcted neocortical areas that were demarcated by up-regulated immunoreactivity for vascular collagen IV (Coll IV. Subsequent semi-quantitative analyses in mice confirmed significantly decreased WFA-staining along the ischemic border zone and a relative decrease in the directly ischemia-affected neocortex. Triple fluorescence labeling throughout the three animal models revealed up-regulated Coll IV and decomposed PNs accompanied by activated astroglia and altered immunoreactivity for parvalbumin, a calcium-binding protein in fast-firing GABAergic neurons which are predominantly surrounded by neocortical PNs. Furthermore, ischemic neocortical areas in rodents simultaneously displayed less intense staining of WFA, aggrecan, the net components neurocan, versican and the

  2. Effect of radiotherapy on experimental liver regenerative capacities following partial hepatectomy in rats

    International Nuclear Information System (INIS)

    Du Shisuo; Zeng Zhaochong; Tang Zhaoyou; Zhang Zhenyu; Wu Zheng; Shi Liusheng

    2008-01-01

    Objective: To investigate the regenerative capacities and proliferation related cytokines expression of normal and irradiated livers following 70% partial hepatectomy in rats. Methods: 90 male Sprague-Dawley rats were divided into 3 groups. The control group was only received 70% partial hepatectomy. The two irradiated groups were performed a single dose of 4 Gy and 8 Gy photon irradiation respectively followed 70% partial hepatectomy. The remanent liver were excised at 0.5,1.0,2.0,3.0,7.0 and 10.0 d after hepatectomy, and liver regeneration capacities in normal and irradiated rats were evaluated through remanent liver weigh, BrdU incorporation, PCNA labeling, and mitotic indices. The proliferation related cytokines expression were also compared. Results: After radiotherapy and hepatectomy 1 rats died of infection in control group, and two rats in 8 Gy group died of radiation induced enteritis. The original liver weigh is regained within 12 days in control and 4 Gy group, and proliferative speed was lower in 4 Gy group than control group. The weigh of remanent liver in 8 Gy group was significantly lower than the two groups all time points from 2d. The apex of PCNA labeling index was 80.2 ± 7.6%, 71.2 ± 6.5% and 55.3 ± 4.7% in control, 4 Gy and 8 Gy groups respectively at 2d, and 44.2 ± 5.4%, 35.3 ± 5.72% and 5.3 ± 6.9% with BrdU incorporation index. HGF mRNA expression peak of 4 Gy group was significantly lower than in control at 1 d, but no apparent peak value in 8 Gy group. TGF-β1 and TGF-β RII level of radiation groups was apparently higher than the control group at different time points. Meanwhile the p53 protein tend to increase at 1 d then decline with high expression in irradiated groups. Conclusion: Whole radiation can significantly inhibit the regenerative capacities following partial hepatectomy in rats with dose dependent. (authors)

  3. Altered hepatic mRNA expression of immune response-associated DNA damage in mice liver induced by potassium bromate: Protective role of vanillin.

    Science.gov (United States)

    Ben Saad, Hajer; Driss, Dorra; Ben Amara, Ibtissem; Boudawara, Ons; Boudawara, Tahia; Ellouz Chaabouni, Samia; Mounir Zeghal, Khaled; Hakim, Ahmed

    2016-12-01

    Chronic exposure to potassium bromate (KBrO 3 ), a toxic halogen existing widely in the environment, environment through contaminated drinking water, has become a global problem of public health. The present study investigates the protective role of vanillin against KBrO 3 induced oxidative stress, distruption in inflammatory cytokines expression, DNA damage, and histopathological changes. Adult mice were exposed orally to KBrO 3 (2g/L of drinking water) for 2 weeks The co-administration of vanillin to the KBrO 3 -treated mice significantly prevented the plasma transaminases increase in. Furthermore, it inhibited hepatic lipid peroxidation (malondialdehyde), advanced oxidation protein product (AOPP) and protein carbonyl (PCO) formation and attenuated the KBrO 3 -mediated depletion of enzymatic and non enzymatic antioxidants catalase, superoxide dismutase, and glutathione peroxidase activities and glutathione level in the liver. In addition, vanillin markedly attenuated the expression levels of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and COX2 and prevented KBrO 3 -induced hepatic cell alteration and necrosis, as indicated by histopathological data. DNA damage, as assessed by the alkaline comet assay, was also found to be low in the co-treated group. Thus, these findings show that vanillin acts as potent chemopreventive agent against KBrO 3 -mediated liver oxidative stress and genotoxicity through its antioxidant properties. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1796-1807, 2016. © 2015 Wiley Periodicals, Inc.

  4. Heat Damage Zones Created by Different Energy Sources Used in the Treatment of Benign Prostatic Hyperplasia in a Pig Liver Model.

    Science.gov (United States)

    Kan, Chi Fai; Chan, Alexander Chak Lam; Pun, Chung Ting; Ho, Lap Yin; Chan, Steve Wai-Hee; Au, Wing Hang

    2015-06-01

    There are different types of transurethral prostatic surgeries and the complication profiles are different. This study aims to compare the heat damage zones (HDZ) created by five different technologies in a pig liver model. Monopolar resection, bipolar resection, electrovaporization, and Greenlight™ lasers of 120 and 180 W were used to remove fresh pig liver tissue in a simulated model. Each procedure was repeated in five specimens. Two blocks were selected from each specimen to measure the three deepest HDZ. The mean of HDZ was 295, 234, 192, 673, and 567 μm, respectively, for monopolar resection, bipolar resection, electrovaporization, Greenlight laser 120 W, and Greenlight laser 180 W, respectively. The Greenlight laser produced one to three times deeper HDZ than the other energy sources (p=0.000). Both 120 and 180 W Greenlight lasers produced deeper HDZ than the other energy sources. Urologists need to be aware of HDZ that cause tissue damage outside the operative field.

  5. Antioxidant and hepatoprotective effects of Capparis spinosa L. fractions and Quercetin on tert-butyl hydroperoxide- induced acute liver damage in mice

    Directory of Open Access Journals (Sweden)

    Heibatullah Kalantari

    2018-01-01

    Full Text Available The present study investigates the antioxidant and hepatoprotective effects of Capparis spinosa L. and Quercetin in tert-butyl hydroperoxide (t-BHP induced acute liver damage. Different fractions of C. spinosa were examined for total phenolic content and antioxidant property. Among these fractions, hydroalcoholic extract was used to assess the hepatoprotective effect in tert-butyl hydroperoxide (t-BHP induced hepatotoxicity model by determining serum biochemical markers, sleeping time and antioxidant assay such as reduced glutathione (GSH as well as histopathological examination of liver tissues. The total phenolic and Quercetin contents of hydroalcoholic fraction were significantly higher than other fractions. It also showed high antioxidant activity. Pretreatment with hydroalcoholic fraction at the dose of 400 mg/kg and Quercetin at the dose of 20 mg/kg showed liver protection against t-BHP induced hepatic injury, as it was evident by a significant decrease in serum enzymes marker, sleeping time and MDA and an increase in the GSH, SOD and CAT activities confirmed by pathology tests. The final results ascertained the hepatoprotective and antioxidant effects of C. spinosa and Quercetin in a dose-dependent manner. Moreover, this study suggests that possible mechanism of this protection may be associated with its property of scavenging free radicals which may be due to the presence of phenolic compounds.

  6. Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

    Directory of Open Access Journals (Sweden)

    Zeba Farooqui

    Full Text Available Cisplatin (CP is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p. respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism. Keywords: Cisplatin, Nigella sativa oil, Carbohydrate metabolism, Antioxidant

  7. Halloysite nanotubes-induced Al accumulation and oxidative damage in liver of mice after 30-day repeated oral administration.

    Science.gov (United States)

    Wang, Xue; Gong, Jiachun; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

    2018-06-01

    Halloysite (Al 2 Si 2 O 5 (OH) 4 ·nH 2 O) nanotubes (HNTs) are natural clay materials and widely applied in many fields due to their natural hollow tubular structures. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility, however the in vivo toxicity of HNTs remains unclear. The objective of this study was to assess the hepatic toxicity of the purified HNTs in mice via oral route. The purified HNTs were orally administered to mice at 5, 50, and 300 mg/kg body weight (BW) every day for 30 days. Oral administration of HNTs stimulated the growth of the mice at the low dose (5 mg/kg BW) with no liver toxicity, but inhibited the growth of the mice at the middle (50 mg/kg BW) and high (300 mg/kg BW) doses. In addition, oral administration of HNTs at the high dose caused Al accumulation in the liver but had no marked effect on the Si content in the organ. The Al accumulation caused significant oxidative stress in the liver, which induced hepatic dysfunction and histopathologic changes. These findings demonstrated that Al accumulation-induced oxidative stress played an important role in the oral HNTs-caused liver injury. © 2018 Wiley Periodicals, Inc.

  8. Protective role of ginkgo Biloba extract against gamma radiation and alcohol induced liver damage in albino rats

    International Nuclear Information System (INIS)

    Fahmy, N. M.; Mohamed, E.T.; Mansour, H.H; Hafez, H.F.

    2007-01-01

    Ginkgo biloba extract (EGb 761) is a standardized extract of Ginkgo biloba leaves that promotes vasodilatation and improves blood flow through arteries, veins and capillaries and has antioxidant properties as a tree radical scavenger. This study was designed to evaluate the protective efficacy of EGb 761 against gamma radiation and/ or alcohol induced disorders in the liver of male albino rats. EGb 761 was given orally at a dose level of 100 mg/ kg body wt for 4 days, absolute alcohol was administered orally at a dose level of 1ml/ rat for 4 days and the dose of gamma radiation was 6.5 Gy. All animals were subjected to the following investigations: nitric oxide (NO), superoxide dismutase (SOD), malonaldehyde (MDA). reduced glutathion (GSH) and glutathione peroxidase (GSHPx) in the liver tissue. In irradiated and/ or alcoholic animal groups, there was a highly significant decrease in liver NO and GSH content and in the activities of GSHPx and SOD. On the other hand, significant increase in MDA content was observed. Treatment with EGb 761 before irradiation and/or alcohol causes significant increase in NO and GSH content and in the activities of GSHPx and SOD and significant decrease in MDA content compared to the irradiated and/ or alcoholic groups. Based on these observations, one could conclude that pre-treatment of rats with EGb 761 could partly protect liver from gamma rays and/ or absolute alcohol injurious and this protection may be induced, at least partly, through antioxidant mechanisms

  9. New therapeutic aspect for carvedilol: Antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage

    International Nuclear Information System (INIS)

    Hamdy, Nadia; El-Demerdash, Ebtehal

    2012-01-01

    Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10 mg/kg, orally) daily for 6 weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-κB). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-κB expression and finally HSC activation. -- Highlights: ► Carvedilol is a beta blocker with antioxidant and antifibrotic

  10. Erythrocytes Membrane Alterations Reflecting Liver Damage in CCl₄-Induced Cirrhotic Rats: The Ameliorative Effect of Naltrexone

    Directory of Open Access Journals (Sweden)

    Fatemeh Sarhadi Kholari

    2016-11-01

    Full Text Available Cirrhosis is the consequence of chronic liver disease. Deleterious effects of oxidative stress on hepatocytes may be reflected in the erythrocyte membrane. Naltrexone (NTX has been shown to attenuate hepatocellular injury in fibrotic animal models. The aim of this study was to investigate the progressive effect of CCl4 on the liver and whether the improvement of liver cirrhosis can be monitored through alterations in the erythrocyte membrane. In this study, 84 male Wistar rats were divided into 4 groups and received reagents (i.p. as follows: 1- CCl₄, 2- NTX + CCl₄, 3- Mineral Oil (M, and 4- NTX + M. After 2, 6 and 8 weeks, the blood and liver tissue samples were collected. Plasma enzyme activities, the content of erythrocyte GSH and some membrane compositions, including protein carbonyl, protein sulfhydryl, and malondialdehyde were assessed. After 6 and 8 weeks, plasma enzyme activities and the content of protein carbonyl were higher in CCl4 group significantly, as compared to other groups (P<0.001. NTX significantly diminished protein carbonyl and plasma enzyme activities (P<0.001. GSH did not change until the 6th week. However, CCl4+NTX increased it significantly as compared to CCl₄ group (P<0.05. Protein sulfhydryl showed changes in NTX+CCl₄ group which indicated a significant increase in protein sulfhydryl content in a 6th week compared to CCl4 group (P<0.05. MDA did not show any significant alteration. CCl₄-induced cirrhosis is accompanied by increased content of oxidative stress markers, especially protein carbonyl of RBC membrane and plasma enzyme activities. This study shows that the progression of liver cirrhosis and the ameliorative effect of NTX can be followed through alterations of these markers.

  11. New therapeutic aspect for carvedilol: Antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage

    Energy Technology Data Exchange (ETDEWEB)

    Hamdy, Nadia [Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); El-Demerdash, Ebtehal, E-mail: ebtehal_dm@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2012-06-15

    Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10 mg/kg, orally) daily for 6 weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-κB). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-κB expression and finally HSC activation. -- Highlights: ► Carvedilol is a beta blocker with antioxidant and antifibrotic

  12. The effect of experimental diabetes on phenylalanine metabolism in isolated liver cells.

    OpenAIRE

    Santana, M A; Fisher, M J; Bate, A J; Pogson, C I

    1985-01-01

    Chronic (10-day) diabetes was associated with increased metabolic flux through phenylalanine hydroxylase in isolated liver cells. This flux was stimulated by 0.1 microM-glucagon, but not by 10 microM-noradrenaline; 0.1 microM-insulin affected neither basal nor glucagon-stimulated flux. The increased rate of phenylalanine hydroxylation in diabetes was accompanied by parallel increases in enzyme activity (as measured with artificial cofactor) and immunoreactive-enzyme-protein content. In contra...

  13. Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination.

    Science.gov (United States)

    Schultz, Verena; van der Meer, Franziska; Wrzos, Claudia; Scheidt, Uta; Bahn, Erik; Stadelmann, Christine; Brück, Wolfgang; Junker, Andreas

    2017-08-01

    Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP- and SMI32- positive damaged axons and the density of SMI31-positive and silver impregnated preserved axons. Early de- and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  14. Optimal statistical damage detection and classification in an experimental wind turbine blade using minimum instrumentation

    Science.gov (United States)

    Hoell, Simon; Omenzetter, Piotr

    2017-04-01

    The increasing demand for carbon neutral energy in a challenging economic environment is a driving factor for erecting ever larger wind turbines in harsh environments using novel wind turbine blade (WTBs) designs characterized by high flexibilities and lower buckling capacities. To counteract resulting increasing of operation and maintenance costs, efficient structural health monitoring systems can be employed to prevent dramatic failures and to schedule maintenance actions according to the true structural state. This paper presents a novel methodology for classifying structural damages using vibrational responses from a single sensor. The method is based on statistical classification using Bayes' theorem and an advanced statistic, which allows controlling the performance by varying the number of samples which represent the current state. This is done for multivariate damage sensitive features defined as partial autocorrelation coefficients (PACCs) estimated from vibrational responses and principal component analysis scores from PACCs. Additionally, optimal DSFs are composed not only for damage classification but also for damage detection based on binary statistical hypothesis testing, where features selections are found with a fast forward procedure. The method is applied to laboratory experiments with a small scale WTB with wind-like excitation and non-destructive damage scenarios. The obtained results demonstrate the advantages of the proposed procedure and are promising for future applications of vibration-based structural health monitoring in WTBs.

  15. The Protective Effect of Cell Wall and Cytoplasmic Fraction of Selenium Enriched Yeast on 1, 2-Dimethylhydrazine-induced Damage in Liver

    Directory of Open Access Journals (Sweden)

    Mitra Dadrass

    2014-02-01

    administration of cell wall and cytoplasmic fraction prepared from Se-enriched S. cerevisiae could reduce the tissue damages in the livers DMH-injected rats. This beneficial effect would warrant further study on the clinical application of Se-enriched yeast.

  16. An animal experimental model for evaluating endothelial damage caused by various angiographic contrast media

    International Nuclear Information System (INIS)

    Gottlob, R.

    1981-01-01

    The endothelial damage caused by X-ray contrast media is tested on en face preparations of the rat aorta after silver staining. Hypertonic contrast media cause dehydration of the vessels so that solutions of silver nitrate penetrate into the media during the phase of rehydration whereby medial transverse lines are stained. These artifacts can be avoided by 3 minute rehydration of the vessels by Ringer solution prior to silver staining. In addition it is recommended to add highly diluted silver nitrate to the fixing media in order to intensify the pattern of the endothelial silver lines. Modern contrast media may cause very little endothelial damage, however, significant differences can be detected when in addition to the evaluation of larger foci damages of single endothelial cells ( brown cells with sparing of the nuclei and pseudonuclei ) are evaluated as well. No significant differences were found between the endothelial toxicity of meglumin diatrizoate and meglumin iothalamate. (orig.) [de

  17. Proposed Pharmacological Countermeasures Against Apoptotic Cell Death in Experimental Models Mimicking Space Environment Damage

    Science.gov (United States)

    Lulli, Matteo; Papucci, Laura; Witort, Ewa; Donnini, Martino; Lapucci, Andrea; Lazzarano, Stefano; Mazzoni, Tiziano; Simoncini, Madine; Falciani, Piergiuseppe; Capaccioli, Sergio

    2008-06-01

    Several damaging agents have been suggested to affect human vision during long term space travels. Recently, apoptosis induced by DNA-damaging agents has emerged as frequent pathogenetic mechanism of ophthalmologic pathologies. Here, we propose two countermeasures: coenzyme Q10 and bcl-2 downregulation preventing antisense oligoribonucleotides (ORNs), aimed to inhibit cellular apoptotic death. Our studies have been carried out on retina and neuronal cultured cells treated with the following apoptotic stimuli mimicking space environment: a several-day exposure to either 3H-labeled tymidine or to the genotoxic drug doxorubicin, UV irradiation, hypoxia and glucose/growth factor starvation (Locke medium). The preliminary results clearly indicate that CoQ10, as well as bcl-2 down-regulation preventing ORNs, significantly counteract apoptosis in response to different DNA damaging agents in cultured eye and in neuronal cells. This supports the possibility that both could be optimal countermeasures against ophthalmologic lesions during space explorations.

  18. Effect of interventional treatment with p53 on the invasion and metastasis of VX2 liver tumor in experimental rabbits

    International Nuclear Information System (INIS)

    Li Caixia; Feng Yan; Gu Tao; Li Chunmei

    2010-01-01

    Objective: To investigate the effect of interventional treatment with p53 on the invasion and metastasis of VX2 liver tumor in experimental rabbits. Methods: VX2 carcinoma cells were surgically implanted into the left hepatic lobe in 48 New Zealand white rabbits, and the rabbit hepatic carcinoma models were thus established. The rabbits were randomly divided into 4 groups with 12 rabbits in each group. After hepatic arterial catheterization was completed physiological saline (control group), Lipiodol (Group A), Ad-p53 (Group B) and Lipiodol+Ad-p53 (Group C) were respectively infused into the rabbits of four groups via common hepatic artery. One week after the procedure the rabbits were sacrificed and the livers were removed for the determination of matrix metalloprotein-2 (MMP-2), proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) of the tumor with immunohistochemistry technique. Results: The tumor growth in study groups (group A, B and C) was markedly suppressed, which was significantly different in comparison with that in control group (P 0.05). The positive rates of MMP-2, PCNA and VEGF in group B and C were significantly lower than those in control group (P < 0.05). The positive rates of MMP-2, PCNA and VEGF of the rabbits with metastasis were markedly higher than those without metastasis(P < 0.05). MMP-2 bore a certain relationship with VEGF and PCNA (P < 0.05). Conclusion: The increase of the positive rates of MMP-2, PCNA and VEGF indicates that the tumor possesses higher possibility for developing metastasis, proliferation and vascular formation. The interventional treatment with Adp53 or Lipiodol+Ad-p53 can inhibit the growth, metastasis and vascular formation of VX2 liver tumor in experimental rabbits. (J Intervent Radiol, 2010, 19 : 800-804) (authors)

  19. Evaluation of the Hepatoprotective Effects of Lantadene A, a Pentacyclic Triterpenoid of Lantana Plants against Acetaminophen-induced Liver Damage

    Directory of Open Access Journals (Sweden)

    Sreenivasan Sasidharan

    2012-11-01

    Full Text Available The aim of the present study was to evaluate the hepatoprotective activity of lantadene A against acetaminophen-induced liver toxicity in mice was studied. Activity was measured by monitoring the levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP and bilirubin, along with histo-pathological analysis. Silymarin was used as positive control. A bimodal pattern of behavioural toxicity was exhibited by the lantadene A-treated group at the beginning of the treatment. However, treatment with lantadene A and silymarin resulted in an increase in the liver weight compared with the acetaminophen treated group. The results of the acetaminophen-induced liver toxicity experiments showed that mice treated with lantadene A (500 mg/kg showed a significant decrease in the activity of ALT, AST and ALP and the level of bilirubin, which were all elevated in the acetaminophen treated group (p < 0.05. Histological studies supported the biochemical findings and a maximum improvement in the histoarchitecture was seen. The lantadene A-treated group showed remarkable protective effects against histopathological alterations, with comparable results to the silymarin treated group. The current study confirmed the hepatoprotective effects of lantadene A against the model hepatotoxicant acetaminophen, which is likely related to its potent antioxidative activity.

  20. Effects of grape seed polyphenols on oxidative damage in liver tissue of acutely and chronically exercised rats.

    Science.gov (United States)

    Belviranlı, Muaz; Gökbel, Hakkı; Okudan, Nilsel; Büyükbaş, Sadık

    2013-05-01

    The objective of the present study was to investigate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant defense markers in liver tissue of acutely and chronically exercised rats. Rats were randomly assigned to six groups: Control (C), Control Chronic Exercise (CE), Control Acute Exercise (AE), GSE-supplemented Control (GC), GSE-supplemented Chronic Exercise(GCE) and GSE-supplemented Acute Exercise (GAE). Rats in the chronic exercise groups were subjected to a six-week treadmill running and in the acute exercise groups performed an exhaustive running. Rats in the GSE supplemented groups received GSE (100 mg.kg(-1) .day(-1) ) in drinking water for 6 weeks. Liver tissues of the rats were taken for the analysis of malondialdehyde (MDA), nitric oxide (NO) levels and total antioxidant activity (AOA) and xanthine oxidase (XO) activities. MDA levels decreased with GSE supplementation in control groups but increased in acute and chronic exercise groups compared to their non-supplemented control. NO levels increased with GSE supplementation. XO activities were higher in AE group compared to the CE group. AOA decreased with GSE supplementation. In conclusion, while acute exercise triggers oxidative stress, chronic exercise has protective role against oxidative stress. GSE has a limited antioxidant effect on exercise-induced oxidative stress in liver tissue.

  1. Full-scale experimental validation of decentralized damage identification using wireless smart sensors

    International Nuclear Information System (INIS)

    Jang, Shinae; Sim, Sung-Han; Jo, Hongki; Spencer Jr, Billie F

    2012-01-01

    Wireless smart sensor networks (WSSN) facilitate a new paradigm for structural health monitoring (SHM) of civil infrastructure. Conventionally, SHM systems employing wired sensors and centralized data acquisition have been used to characterize the state of a structure; however, widespread implementation has been limited due to high costs and difficulties in installation. WSSN offer a unique opportunity to overcome such difficulties. Recent developments have realized low-cost, smart sensors with on-board computation and wireless communication capabilities, making deployment of a dense array of sensors on large civil structures both economical and feasible. Wireless smart sensors (WSS) have shown their tremendous potential for SHM in recent full-scale bridge monitoring examples. However, structural damage identification using on-board computation capability in a WSSN, a primary objective of SHM, has yet to reach its full potential. This paper presents full-scale validation of a damage identification strategy using a decentralized network of Imote2 nodes on a historic steel truss bridge. A total of 24 WSS nodes with 144 sensor channels are deployed on the bridge to validate the developed damage identification software. The performance of this decentralized damage identification strategy is demonstrated on the WSSN by comparing its results with those from the traditional centralized approach, as well as visual inspection. (paper)

  2. The effect of resveratrol on experimental non-alcoholic fatty liver disease depends on severity of pathology and timing of treatment

    DEFF Research Database (Denmark)

    Heebøll, Sara; El-Houri, Rime Bahij; Hellberg, Ylva Erika Kristina

    2016-01-01

    BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. RSV prevents the development of steatosis in a number of experimental fatty liver (NAFL) models but the preventive or therapeutic effects on experimental NASH.......01), while there was no effect on biochemical, histopathological, or transcriptional NASH changes. Further, RSV had no therapeutic effect on established NASH. We found RSV metabolites but no parent RSV in serum or liver tissue, confirming low bioavailability. CONCLUSIONS: These experimental findings suggest...... are not yet clarified, and clinical results on NAFLD are ambiguous. Thus, we aimed to compare the RSV-mediated preventive and therapeutic effects on experimental NAFL and NASH. METHODS: We used a high-fat (HF) diet to generate a rat NAFL model and a high-fat, high-cholesterol (HFC) diet to generate a rat NASH...

  3. Bipolar Radiofrequency Ablation Using Dual Internally Cooled Wet Electrodes: Experimental Study in Ex Vivo Bovine Liver

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Joon; Byun, Jae Young [Dept. of Radiology, Seoul St. Mary' s Hospital, The Catholic University of Korea, College of Medicine, Seoul (Korea, Republic of)

    2012-11-15

    To determine the optimized protocol for bipolar radiofrequency ablation (RFA), using dual internally cooled wet (ICW) electrodes in the ex vivo bovine liver. RFA was applied to the explanted bovine liver, using two 3 cm active tip electrodes with 3.5 cm spacing. A total of 25 ablation zones were created by five groups; group A: 70 W-20 minute (min), group B: 70 W-25 min, group C: 90 W-15 min, group D: 90 W-20 min, and group E: 90 W-25 min. We measured the total energy and size of ablation zones with a color of grey or pink. Statistical analysis was done using Kruskal Wallis test and Mann Whitney U-test. The mean energy, mean volume of ablation zone with grey and pink color of groups A to E were 16.7, 23.9, 16.7, 21.8, 29.2 kcal, 25.7, 34.3, 29.5, 36.2, 45.2 cm{sup 3}, and 60.0, 88.0, 71.5, 87.4, 104.5 cm{sup 3}, respectively. Those were significantly different (p < 0.05). The volume of ablation zone of group E with grey color was larger than groups A, B and C (p < 0.05). Bipolar RFA, using dual ICW electrodes, can produce a large ablation zone with the protocol of 90 W-25 min.

  4. Bipolar Radiofrequency Ablation Using Dual Internally Cooled Wet Electrodes: Experimental Study in Ex Vivo Bovine Liver

    International Nuclear Information System (INIS)

    Lee, Young Joon; Byun, Jae Young

    2012-01-01

    To determine the optimized protocol for bipolar radiofrequency ablation (RFA), using dual internally cooled wet (ICW) electrodes in the ex vivo bovine liver. RFA was applied to the explanted bovine liver, using two 3 cm active tip electrodes with 3.5 cm spacing. A total of 25 ablation zones were created by five groups; group A: 70 W-20 minute (min), group B: 70 W-25 min, group C: 90 W-15 min, group D: 90 W-20 min, and group E: 90 W-25 min. We measured the total energy and size of ablation zones with a color of grey or pink. Statistical analysis was done using Kruskal Wallis test and Mann Whitney U-test. The mean energy, mean volume of ablation zone with grey and pink color of groups A to E were 16.7, 23.9, 16.7, 21.8, 29.2 kcal, 25.7, 34.3, 29.5, 36.2, 45.2 cm 3 , and 60.0, 88.0, 71.5, 87.4, 104.5 cm 3 , respectively. Those were significantly different (p < 0.05). The volume of ablation zone of group E with grey color was larger than groups A, B and C (p < 0.05). Bipolar RFA, using dual ICW electrodes, can produce a large ablation zone with the protocol of 90 W-25 min.

  5. Posthemorrhage glycogen and lactate metabolism in the liver: an experimental study with postprandial rats

    International Nuclear Information System (INIS)

    Boija, P.O.; Nylander, G.; Suhaili, A.; Ware, J.

    1988-01-01

    Glycogen and lactate metabolism was studied in livers from three groups of postprandial rats sustaining 70 mm Hg hemorrhagic hypotension for variable periods, 60 min (60H group), 120 min (120H group), and nonbled controls. The donor livers were investigated after completed hemorrhage using an in vitro perfusion system with L-lactate as substrate, together with U- 14 C-lactate. The residual glycogen stores were determined after perfusions. The incorporation of labelled lactate to glucose was increased in the 120H group by 66.7% and 116.8% compared to the 60H group and controls (p less than 0.01), but glycogenolysis was still the main source of glucose released in the 120H group. Glycogen formation from labelled lactate was 46.6% higher in the 120H group compared to controls (p less than 0.05) and lactate oxidation was decreased by 67.5% (p less than 0.05). The data suggest that hepatocytes are capable of rapid change from glycolysis to gluconeogenesis during hemorrhagic hypovolemia. However, energy-sparing glycogen breakdown is given priority over gluconeogenesis as long as glycogen remains available

  6. TRANEXAMIC ACID ACTION ON LIVER REGENERATION AFTER PARTIAL HEPATECTOMY: EXPERIMENTAL MODEL IN RATS.

    Science.gov (United States)

    Sobral, Felipe Antonio; Daga, Henrique; Rasera, Henrique Nogueira; Pinheiro, Matheus da Rocha; Cella, Igor Furlan; Morais, Igor Henrique; Marques, Luciana de Oliveira; Collaço, Luiz Martins

    2016-01-01

    Different lesions may affect the liver resulting in harmful stimuli. Some therapeutic procedures to treat those injuries depend on liver regeneration to increase functional capacity of this organ. Evaluate the effects of tranexamic acid on liver regeneration after partial hepatectomy in rats. 40 rats (Rattus norvegicus albinus, Rodentia mammalia) of Wistar-UP lineage were randomly divided into two groups named control (CT) and tranexamic acid (ATX), with 20 rats in each. Both groups were subdivided, according to liver regeneration time of 32 h or seven days after the rats had been operated. The organ regeneration was evaluated through weight and histology, stained with HE and PCNA. The average animal weight of ATX and CT 7 days groups before surgery were 411.2 g and 432.7 g, and 371.3 g and 392.9 g after the regeneration time, respectively. The average number of mitotic cells stained with HE for the ATX and CT 7 days groups were 33.7 and 32.6 mitosis, and 14.5 and 14.9 for the ATX and CT 32 h groups, respectively. When stained with proliferating cell nuclear antigen, the numbers of mitotic cells counted were 849.7 for the ATX 7 days, 301.8 for the CT 7 days groups, 814.2 for the ATX 32 hand 848.1 for the CT 32 h groups. Tranexamic acid was effective in liver regeneration, but in longer period after partial hepatectomy. Muitas são as injúrias que acometem o fígado e levam a estímulo lesivo. Alguns procedimentos terapêuticos para tratamento dessas lesões dependem da regeneração hepática para aumentar a sua capacidade funcional. Avaliar o efeito do ácido tranexâmico na regeneração hepática após hepatectomia parcial em ratos. Foram utilizados 40 ratos (Rattus norvegicus albinus, Rodentia mammalia) convencionais da linhagem Wistar-UP. Foram divididos aleatoriamente em dois grupos de 20: grupo controle (CT) e grupo ácido tranexâmico (ATX). Cada um deles foi divido em dois subgrupos para avaliar a regeneração hepática no tempo de 32 h e 7 dias do p

  7. A New Experimental Approach to Evaluate Plasma-induced Damage in Microcantilever

    Directory of Open Access Journals (Sweden)

    Yuki Nishimori

    2013-09-01

    Full Text Available Plasma  etching,  during  micro-fabrication  processing  is  indispensable  for  fabricating  MEMS  structures.  During  the plasma  processes,  two  major matters,  charged  ions  and  vacuum–ultraviolet  (VUV  irradiation  damage,  take  charge  of reliability  degradation.  The  charged  ions  induce  unwanted  sidewall  etching,  generally  called  as  “notching”,  which causes  degradation  in  brittle  strength.  Furthermore,  the  VUV  irradiation  gives  rise  to  crystal  defects  on  the  etching surface.  To overcome  the  problem,  neutral  beam  etching  (NBE,  which  use  neutral  particles  without  the  VUV irradiation,  has  been  developed.  In  order  to  evaluate  the  effect  of  the  NBE  quantitatively,  we  measured  the  resonance property of a micro-cantilever before and after NBE treatment. The thickness of damage layer (δ times the imaginary part  of  the  complex Young's  modulus  (Eds  were  then  compared,  which  is  a  parameter  of  surface  damage.  Although plasma processes  make the initial surface of cantilevers damaged during their fabrication, the removal of that damage by NBE was confirmed as the reduction in δEds. NBE will realize a damage-free surface for microstructures.

  8. Fetal brain damage following maternal carbon monoxide intoxication: an experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Ginsberg, M D; Myers, R E

    1974-01-01

    Techniques of fetal monitoring, including fetal blood sampling in utero, were employed to study the physiological effects of acute maternal carbon monoxide intoxication on nine term-pregnant female rhesus monkeys exposed to 0.1 to 0.3% inspired carbon monoxide over 1 to 3 hr. The mothers tolerated carboxyhemoglobin levels exceeding 60% without clinical sequelae, whereas the fetuses promptly developed profound hypoxia upon exposure of the mothers to CO. The fetal COHb levels rose only gradually over 1 to 3 hr, and thus contributed only slightly to the development of early fetal hypoxia. The fetal hypoxia was associated with bradycardia, hypotension, and metabolic and respiratory acidosis. Severity of intrauterine hypoxia was closely correlated with the appearance of brain damage. Brain swelling associated with hemorrhagic necrosis of the cerebral hemispheres (severe brain damage) appeared only in fetuses whose arterial oxygen content was reduced below 1.0 ml/100 ml for at least 45 min during the maternal CO intoxication.

  9. Evaluation of hepatoprotective effect of methanolic extract of Clitoria ternatea (Linn. flower against acetaminophen-induced liver damage

    Directory of Open Access Journals (Sweden)

    Kuppan Nithianantham

    2013-08-01

    Full Text Available Objective: To evaluate the hepatoprotective and antioxidant activity of Clitoria ternatea (C. ternatea flower extract against acetaminophen-induced liver toxicity. Methods: The antioxidant property of C. ternatea flower extract was investigated by employing established in vitro antioxidant assay. The C. ternatea flower extract was studied in this work for its hepatoprotective effect against acetaminophen-induced liver toxicity in mice. Activity was measured by monitoring the levels of aspartate aminotransferase, alanine aminotransferase, billirubin and glutathione with histopathological analysis. Results: The amount of total phenolics and flavonoids were estimated to be 105.40依2.47 mg/g gallic acid equivalent and 72.21依0.05 mg/g catechin equivalent respectively. The antioxidant activity of C. ternatea flower extract was 68.9% at a concentration of 1 mg/mL and was also concentration dependant, with an IC 50 value of 327.00 µg/mL. The results of acetaminophen-induced liver toxicity experiment showed that mice treated with the extract (200 mg/kg showed a significant decrease in alanine aminotransferase, aspartate aminotransferase, and bilirubin levels, which were all elevated in the paracetamol group (P<0.05. Meanwhile, the level of glutathione was found to be restored in extract treated animals compared to the groups treated with acetaminophen alone (P<0.05. Therapy of extract also showed its protective effect on histopathological alterations and supported the biochemical finding. Conclusion: The present work confirmed the hepatoprotective effect of C. ternatea flower against model hepatotoxicant acetaminophen.

  10. Effectiveness of Melatonin, as a Radiation Damage-Mitigating Drug in Modulating Liver Biochemical disorders in γ-Irradiated Rats

    International Nuclear Information System (INIS)

    El-Fatih, N.M.; Elshamy, E.

    2011-01-01

    Melatonin has an anti per oxidative effect on several tissues as well as a scavenger effect on reactive oxygen species (ROS). Whilst radiation-hazards due to free radical generation, present enormous challenges for biological and medical safety. Therefore, rats were classified into four groups; control (n= 8), (received 0.5 ml of alcoholic saline as a vehicle for 5 days). Melatonin-treated rats received 10 mg/ kg body wt, for 5 days (given to the animals in the morning via stomach tube). gamma-irradiated rats received 0.5 ml of the melatonin vehicle followed by one shot dose of 3 Gy gamma-rays. Each of these groups was compared with a further group, which-received melatonin for 5 days after 3 Gy gamma-irradiation exposure. The results revealed that all considered biochemical parameters were not changed significantly in melatonin-treated group as compared with control one. In the liver tissue of the gamma-irradiated animals (3 Gy), the oxidative stress markers malondialdehyde (MDA) and protein carbonyl (PC) were significantly increased, while a marked decrease occurred in the contents of deoxy- and ribo-nucleic acids (DNA and RNA) and glutathione (GSH) as well as activity of glutathione-S-transferase (GST). In addition, catalase (CAT) and myeloperoxidase (MPO) activities were increased. Activities of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) were significantly increased in sera of the irradiated rats. Treatment with melatonin for 5 days after gamma-rays exposure significantly modulated the radiation-induced elevations in MDA and PC levels in the liver tissue and significantly restored hepatic GSH content, GST, CAT and MPO activities. Post-irradiation treatment with melatonin showed significant higher hepatic DNA and RNA contents than irradiated rats. The activities of AST, ALP, and GGT in serum were significantly ameliorated when melatonin was administrated after irradiation. Conclusion: Melatonin has effective

  11. Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice

    Directory of Open Access Journals (Sweden)

    Isabela Finamor

    2017-04-01

    Full Text Available No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC. Chronic administration of aspartame increased plasma alanine aminotransferase (ALT and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH, oxidized glutathione (GSSG, γ-glutamylcysteine ​​(γ-GC, and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM, and S-adenosylhomocysteine ​​(SAH. Aspartame also triggered a decrease in mRNA and protein levels of the catalytic subunit of glutamate cysteine ligase (GCLc and cystathionine γ-lyase, and in protein levels of methionine adenosyltransferase 1A and 2A. N-acetylcysteine prevented the aspartame-induced liver injury and the increase in plasma ALT activity as well as the decrease in GSH, γ-GC, cysteine, SAM and SAH levels and GCLc protein levels. In conclusion, chronic administration of aspartame caused marked hepatic GSH depletion, which should be ascribed to GCLc down-regulation and decreased cysteine levels. Aspartame triggered blockade of the trans-sulphuration pathway at two steps, cystathionine γ-lyase and methionine adenosyltransferases. NAC restored glutathione levels as well as the impairment of the trans-sulphuration pathway.

  12. Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice.

    Science.gov (United States)

    Finamor, Isabela; Pérez, Salvador; Bressan, Caroline A; Brenner, Carlos E; Rius-Pérez, Sergio; Brittes, Patricia C; Cheiran, Gabriele; Rocha, Maria I; da Veiga, Marcelo; Sastre, Juan; Pavanato, Maria A

    2017-04-01

    No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC). Chronic administration of aspartame increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH), oxidized glutathione (GSSG), γ-glutamylcysteine ​​(γ-GC), and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine ​​(SAH). Aspartame also triggered a decrease in mRNA and protein levels of the catalytic subunit of glutamate cysteine ligase (GCLc) and cystathionine γ-lyase, and in protein levels of methionine adenosyltransferase 1A and 2A. N-acetylcysteine prevented the aspartame-induced liver injury and the increase in plasma ALT activity as well as the decrease in GSH, γ-GC, cysteine, SAM and SAH levels and GCLc protein levels. In conclusion, chronic administration of aspartame caused marked hepatic GSH depletion, which should be ascribed to GCLc down-regulation and decreased cysteine levels. Aspartame triggered blockade of the trans-sulphuration pathway at two steps, cystathionine γ-lyase and methionine adenosyltransferases. NAC restored glutathione levels as well as the impairment of the trans-sulphuration pathway. Copyright © 2017. Published by Elsevier B.V.

  13. Benchmark Theoretical and Experimental Study on N-15 NMR Shifts of Oxidatively Damaged Guanine

    Czech Academy of Sciences Publication Activity Database

    Dračínský, Martin; Šála, Michal; Klepetářová, Blanka; Šebera, Jakub; Fukal, Jiří; Holečková, Veronika; Tanaka, Y.; Nencka, Radim; Sychrovský, Vladimír

    2016-01-01

    Roč. 120, č. 5 (2016), s. 915-925 ISSN 1520-6106 R&D Projects: GA ČR GA13-27676S; GA ČR GA15-11223S Institutional support: RVO:61388963 Keywords : NMR spectroscopy * DFT calculations * oxidatively damaged guanine * hOGG1 Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.177, year: 2016

  14. Piezosurgery prevents brain tissue damage: an experimental study on a new rat model

    Czech Academy of Sciences Publication Activity Database

    Pavlíková, G.; Foltán, R.; Burian, M.; Horká, E.; Adámek, S.; Hejčl, Aleš; Hanzelka, T.; Šedý, Jiří

    2011-01-01

    Roč. 40, č. 8 (2011), s. 840-844 ISSN 0901-5027 R&D Projects: GA MŠk(CZ) LC554; GA ČR GAP304/10/0320 Grant - others:GA MŠk(CZ) 1M0538 Program:1M Institutional research plan: CEZ:AV0Z50390703 Keywords : piezosurgery * brain * tissue damage Subject RIV: FJ - Surgery incl. Transplants; FH - Neurology (UEM-P) Impact factor: 1.506, year: 2011

  15. New radiofrequency device to reduce bleeding after core needle biopsy: Experimental study in a porcine liver model

    International Nuclear Information System (INIS)

    Lim, Sang Hyeok; Rhim, Hyun Chul; Lee, Min Woo; Song, Kyoung Doo; Kang, Tae Wook; Kim, Young Sun; Lim, Hyo Keun

    2017-01-01

    To evaluate the in vivo efficiency of the biopsy tract radiofrequency ablation for hemostasis after core biopsy of the liver in a porcine liver model, including situations with bleeding tendency and a larger (16-gauge) core needle. A preliminary study was performed using one pig to determine optimal ablation parameters. For the main experiment, four pigs were assigned to different groups according to heparinization use and biopsy needle caliber. In each pig, 14 control (without tract ablation) and 14 experimental (tract ablation) ultrasound-guided core biopsies were performed using either an 18- or 16-gauge needle. Post-biopsy bleeding amounts were measured by soaking up the blood for five minutes. The results were compared using the Mann-Whitney U test. The optimal parameters for biopsy tract ablation were determined as a 2-cm active tip electrode set at 40-watt with a tip temperature of 70–80℃. The bleeding amounts in all experimental groups were smaller than those in the controls; however they were significant in the non-heparinized pig biopsied with an 18-gauge needle and in two heparinized pigs (p < 0.001). In the heparinized pigs, the mean blood loss in the experimental group was 3.5% and 13.5% of the controls biopsied with an 18- and 16-gauge needle, respectively. Radiofrequency ablation of hepatic core biopsy tract ablation may reduce post-biopsy bleeding even under bleeding tendency and using a larger core needle, according to the result from in vivo porcine model experiments

  16. New radiofrequency device to reduce bleeding after core needle biopsy: Experimental study in a porcine liver model

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Hyeok; Rhim, Hyun Chul; Lee, Min Woo; Song, Kyoung Doo; Kang, Tae Wook; Kim, Young Sun; Lim, Hyo Keun [Dept. of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2017-01-15

    To evaluate the in vivo efficiency of the biopsy tract radiofrequency ablation for hemostasis after core biopsy of the liver in a porcine liver model, including situations with bleeding tendency and a larger (16-gauge) core needle. A preliminary study was performed using one pig to determine optimal ablation parameters. For the main experiment, four pigs were assigned to different groups according to heparinization use and biopsy needle caliber. In each pig, 14 control (without tract ablation) and 14 experimental (tract ablation) ultrasound-guided core biopsies were performed using either an 18- or 16-gauge needle. Post-biopsy bleeding amounts were measured by soaking up the blood for five minutes. The results were compared using the Mann-Whitney U test. The optimal parameters for biopsy tract ablation were determined as a 2-cm active tip electrode set at 40-watt with a tip temperature of 70–80℃. The bleeding amounts in all experimental groups were smaller than those in the controls; however they were significant in the non-heparinized pig biopsied with an 18-gauge needle and in two heparinized pigs (p < 0.001). In the heparinized pigs, the mean blood loss in the experimental group was 3.5% and 13.5% of the controls biopsied with an 18- and 16-gauge needle, respectively. Radiofrequency ablation of hepatic core biopsy tract ablation may reduce post-biopsy bleeding even under bleeding tendency and using a larger core needle, according to the result from in vivo porcine model experiments.

  17. Extract of Bauhinia vahlii Shows Antihyperglycemic Activity, Reverses Oxidative Stress, and Protects against Liver Damage in Streptozotocin-induced Diabetic Rats

    Science.gov (United States)

    Elbanna, Ahmed H.; Nooh, Mohammed M.; Mahrous, Engy A.; Khaleel, Amal E.; Elalfy, Taha S.

    2017-01-01

    Background: Several studies have affirmed the effectiveness of some Bauhinia plants as antihyperglycemic agents. Objective: We investigated the possible effect of Bauhinia vahlii leaves extract in reducing hyperglycemia and reversing signs of organ damage associated with diabetes in streptozotocin (STZ) rat model. Materials and Methods: Both polar fraction of the B. vahlii leaves (defatted ethanolic extract [DEE]) and nonpolar fraction (n-hexane extract) were evaluated in vitro for α-glucosidase inhibition and 2,2-diphenyl-1-picrylhydrazyl radical scavenging potential. DEE was selected for further in vivo studies and was administered at two doses, i.e., 150 or 300 mg/kg to STZ-diabetic rats for 4 weeks. Results: Only DEE exhibited in vitro antioxidant and antihyperglycemic activities and its oral administration at both dose levels resulted in significant reduction in fasting blood glucose and glycated hemoglobin. Furthermore, signs of oxidative stress as indicated by hepatic reduced glutathione, nitric oxide, and malondialdehyde levels were completely reversed. In addition, histopathological examination and measurement of serum aspartate transaminase and alanine transaminase levels showed that DEE protected the liver from signs of liver pathogenesis when compared to diabetic untreated animals and those treated with metformin. Phytochemical analysis of DEE showed high flavonoids content with quercitrin as the major constituent along with other quercetin glycosides. Conclusion: This study strongly highlights the possible beneficial effect of B. vahlii leaves extract in relieving hyperglycemia and liver damage in STZ-diabetic rats and recommends further investigation of the value of quercetin derivatives in controlling diabetes and ameliorating liver damage associated with it. SUMMARY The polar fraction of the Bauhinia vahlii leaves (defatted ethanolic extract [DEE]) exhibited both in vitro antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenging assay and

  18. Metformin increases liver accumulation of vitamin B12 - An experimental study in rats

    DEFF Research Database (Denmark)

    Greibe, E; Miller, J W; Foutouhi, S H

    2013-01-01

    AIMS/HYPOTHESIS: Patients treated with metformin exhibit low levels of plasma vitamin B(12) (B(12)), and are considered at risk for developing B(12) deficiency. In this study, we investigated the effect of metformin treatment on B(12) uptake and distribution in rats. METHODS: Sprague Dawley rats (n...... that metformin has no decreasing effect on the B(12) absorption. CONCLUSIONS/INTERPRETATION: These results show that metformin treatment increases liver accumulation of B(12), thereby resulting in decreases in circulating B(12) and kidney accumulation of the vitamin. Our data questions whether the low plasma B......(12) observed in patients treated with metformin reflects impaired B(12) status, and rather suggests altered tissue distribution and metabolism of the vitamin....

  19. Ultrastructural changes in the liver following chronic experimental intoxication with benzine and ethyline vapor

    Energy Technology Data Exchange (ETDEWEB)

    Jonek, J.; Przybylowski, J.; Gryzbek, H.; Podolecki, A.; Pacholek, A.

    1978-01-01

    The livers of two groups of rabbits exposed to longer lasting intoxidation, one with benzine vapors and the other one with ethyline vapors, were subjected to examination in an electron microscope twice; immediately after the completion of intoxication and then 3 months later. In both groups there were found: dilatation of the perinuclear spaces, a symptom of nucleolus segregation, dilation of the ergastoplasm, features of cristolysis of mitochondria and the absence of glycogen. These changes were more intensive in the animals intoxicated with ethyline. 3 months after the completion of the process of petrol intoxication the following was observed: persistence of the majority of the changes as well as accumulation of glycogen and hypertrophy of the smooth endoplasmatic reticulum. These changes were more intensified in animals intoxicated with ethyline.

  20. Interaction of 1.319 μm laser with skin: an optical-thermal-damage model and experimental validation

    Science.gov (United States)

    Jiao, Luguang; Yang, Zaifu; Wang, Jiarui

    2014-09-01

    With the widespread use of high-power laser systems operating within the wavelength region of approximately 1.3 to 1.4 μm, it becomes very necessary to refine the laser safety guidelines setting the exposure limits for the eye and skin. In this paper, an optical-thermal-damage model was developed to simulate laser propagation, energy deposition, heat transfer and thermal damage in the skin for 1.319 μm laser irradiation. Meanwhile, an experiment was also conducted in vitro to measure the tempreture history of a porcine skin specimen irradiated by a 1.319 μm laser. Predictions from the model included light distribution in the skin, temperature response and thermal damge level of the tissue. It was shown that the light distribution region was much larger than that of the incident laser at the wavelength of 1.319 μm, and the maximum value of the fluence rate located on the interior region of the skin, not on the surface. By comparing the calculated temperature curve with the experimentally recorded temperautre data, good agreement was shown betweeen them, which validated the numerical model. The model also indicated that the damage integral changed little when the temperature of skin tissue was lower than about 55 °C, after that, the integral increased rapidly and denatunation of the tissue would occur. Based on this model, we can further explore the damage mechanisms and trends for the skin and eye within the wavelength region of 1.3 μm to 1.4 μm, incorporating with in vivo experimental investigations.

  1. The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney.

    Science.gov (United States)

    Gholampour, Firouzeh; Behzadi Ghiasabadi, Fatemeh; Owji, Seyed Mohammad; Vatanparast, Jaafar

    2017-01-01

    Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger ( Zingiber officinale ) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. The rats were divided into four groups (n=7): Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected. Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p<0.001). This was accompanied by increased malondialdehyde levels and histological damages (p<0.001). In the FS + G.E, ginger extract significantly (p<0.01) reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides and cholesterol and decreased bilirubin concentration in the blood. All these changes were corroborated by histological observations of liver and kidney. In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron.

  2. Comparison of the Hepatoprotective Effects of Four Endemic Cirsium Species Extracts from Taiwan on CCl4-Induced Acute Liver Damage in C57BL/6 Mice

    Directory of Open Access Journals (Sweden)

    Zi-Wei Zhao

    2018-04-01

    Full Text Available Species of Cirsium (Asteraceae family have been used in folk hepatoprotective medicine in Taiwan. We collected four Cirsium species—including the aerial part of Cirsium arisanense (CAH, the aerial part of Cirsium kawakamii (CKH, the flower part of Cirsium japonicum DC. var. australe (CJF, and Cirsii Herba (CH—and then made extractions from them with 70% methanol. We compared the antioxidant contents and activities of these four Cirsium species extracts by a spectrophotometric method and high-performance liquid chromatography–photodiode array detector (HPLC-DAD. We further evaluated the hepatoprotective effects of these extracts on CCl4-induced acute liver damage in C57BL/6 mice. The present study found CAH possesses the highest antioxidant activity among the four Cirsium species, and these antioxidant activities are closely related to phenylpropanoid glycoside (PPG contents. The extracts decreased serum ALT and AST levels elevated by injection with 0.2% CCl4. However, only CJF and CH decreased hepatic necrosis. Silibinin decreased serum alanine aminotransferase (ALT and aspartate aminotransferase (AST levels and hepatic necrosis caused by CCl4. CJF and CH restored the activities of hepatic antioxidant enzymes and decreased hepatic malondialdehyde (MDA levels. CJF further restored the expression of hepatic antioxidant enzymes including Cu/Zn-superoxide dismutase (Cu/Zn-SOD, Mn-superoxide dismutase (Mn-SOD, and glutathione S-transferase (GST proteins. HPLC chromatogram indicated that CKH, CJF, and CH contained silibinin diastereomers (α and β. Only CJF contained diosmetin. Hence, the hepatoprotective mechanism of CJF against CCl4-induced acute liver damage might be involved in restoring the activities and protein expression of the hepatic antioxidant defense system and inhibiting hepatic inflammation, and these hepatoprotective effects are related to the contents of silibinin diastereomers and diosmetin.

  3. Downregulation of Lung Toll-Like Receptor 4 Could Effectively Attenuate Liver Transplantation-Induced Pulmonary Damage at the Early Stage of Reperfusion

    Directory of Open Access Journals (Sweden)

    Xinjin Chi

    2015-01-01

    Full Text Available Acute lung injury (ALI is a severe complication of orthotopic liver transplantation (OLT with unclear underline mechanism. Toll-like receptor 4 (TLR4 has been identified as a key receptor mediating inflammation. We hypothesized that TLR4-mediated pulmonary inflammation may contribute to development of ALI during OLT. Patients with or without ALI were observed for serum cytokines and expression of TLR4 on peripheral blood polymorphonuclear leukocytes (PMNs. Next, rats which underwent orthotopic autologous liver transplantation (OALT were divided into sham and model groups. Pulmonary function and the level of TLR4 expression and cytokines were analyzed. Furthermore, the role of TLR4 in OALT-mediated ALI was assessed in rats treated with TLR4-siRNA before OALT. The PMNs TLR4 expression and the serum TNF-α and IL-β level were higher in patients with ALI than those with non-ALI. Interestingly, lung TLR4 expression was significantly increased after 8 hours of OALT with increased levels of TNF-α and IL-β, which lead to lung pathological damage and an increase of lung myeloperoxidase content. Moreover, knockdown of TLR4 reduced lung cytokines release and reversed the above pathologic changes after OALT and finally improved rats’ survival rate. In conclusion, TLR4 overexpression, potentially by stimulating proinflammatory cytokine overproduction, contributes to the development of ALI after OLT.

  4. Effects of anti-cocaine vaccine and viral gene transfer of cocaine hydrolase in mice on cocaine toxicity including motor strength and liver damage.

    Science.gov (United States)

    Gao, Yang; Geng, Liyi; Orson, Frank; Kinsey, Berma; Kosten, Thomas R; Shen, Xiaoyun; Brimijoin, Stephen

    2013-03-25

    In developing an vivo drug-interception therapy to treat cocaine abuse and hinder relapse into drug seeking provoked by re-encounter with cocaine, two promising agents are: (1) a cocaine hydrolase enzyme (CocH) derived from human butyrylcholinesterase and delivered by gene transfer; (2) an anti-cocaine antibody elicited by vaccination. Recent behavioral experiments showed that antibody and enzyme work in a complementary fashion to reduce cocaine-stimulated locomotor activity in rats and mice. Our present goal was to test protection against liver damage and muscle weakness in mice challenged with massive doses of cocaine at or near the LD50 level (100-120 mg/kg, i.p.). We found that, when the interceptor proteins were combined at doses that were only modestly protective in isolation (enzyme, 1mg/kg; antibody, 8 mg/kg), they provided complete protection of liver tissue and motor function. When the enzyme levels were ~400-fold higher, after in vivo transduction by adeno-associated viral vector, similar protection was observed from CocH alone. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Experimental analysis of the evolution of thermal shock damage using transit time measurement of ultrasonic waves

    NARCIS (Netherlands)

    Damhof, F.; Brekelmans, W.A.M.; Geers, M.G.D.

    2009-01-01

    Thermal shock is a principal cause of catastrophic wear of the refractory lining of high temperature installations in metal making processes. To investigate thermal shock experimentally with realistic and reproducible heat transfer conditions, chamotte and corund refractory samples of ambient

  6. Transplant of Hepatocytes, Undifferentiated Mesenchymal Stem Cells, and In Vitro Hepatocyte-Differentiated Mesenchymal Stem Cells in a Chronic Liver Failure Experimental Model: A Comparative Study.

    Science.gov (United States)

    El Baz, Hanan; Demerdash, Zeinab; Kamel, Manal; Atta, Shimaa; Salah, Faten; Hassan, Salwa; Hammam, Olfat; Khalil, Heba; Meshaal, Safa; Raafat, Inas

    2018-02-01

    Liver transplant is the cornerstone line of treatment for chronic liver diseases; however, the long list of complications and obstacles stand against this operation. Searching for new modalities for treatment of chronic liver illness is a must. In the present research, we aimed to compare the effects of transplant of undifferentiated human mesenchymal stem cells, in vitro differentiated mesenchymal stem cells, and adult hepatocytes in an experimental model of chronic liver failure. Undifferentiated human cord blood mesenchymal stem cells were isolated, pro-pagated, and characterized by morphology, gene expression analysis, and flow cytometry of surface markers and in vitro differentiated into hepatocyte-like cells. Rat hepatocytes were isolated by double perfusion technique. An animal model of chronic liver failure was developed, and undifferentiated human cord blood mesenchymal stem cells, in vitro hepato-genically differentiated mesenchymal stem cells, or freshly isolated rat hepatocytes were transplanted into a CCL4 cirrhotic experimental model. Animals were killed 3 months after transplant, and liver functions and histopathology were assessed. Compared with the cirrhotic control group, the 3 cell-treated groups showed improved alanine aminotransferase, aspartate aminotransferase, albumin, and bilirubin levels, with best results shown in the hepatocyte-treated group. Histopathologic examination of the treated groups showed improved fibrosis, with best results obtained in the undifferentiated mesenchymal stem cell-treated group. Both adult hepatocytes and cord blood mesenchymal stem cells proved to be promising candidates for cell-based therapy in liver regeneration on an experimental level. Improved liver function was evident in the hepatocyte-treated group, and fibrosis control was more evident in the undifferentiated mesenchymal stem cell-treated group.

  7. Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

    Science.gov (United States)

    Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

    2012-01-01

    Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

  8. Compressive damage mechanism of GFRP composites under off-axis loading: Experimental and numerical investigations

    DEFF Research Database (Denmark)

    Zhou, H.W.; Li, H.Y.; Gui, L.L.

    2013-01-01

    the angle between the fiber direction and the loading vector goes from 0° to 45° (by 2.3–2.6 times), and then slightly increases (when the angle approaches 80–90°). At the low angles between the fiber and the loading vector, fiber buckling and kinking are the main mechanisms of fiber failure....... With increasing the angle between the fiber and applied loading, failure of glass fibers is mainly controlled by shear cracking. For the computational analysis of the damage mechanisms, 3D multifiber unit cell models of GFRP composites and X-FEM approach to the fracture modeling were used. The computational...

  9. Experimental investigation of slamming impact acted on flat bottom bodies and cumulative damage

    Directory of Open Access Journals (Sweden)

    Hyunkyoung Shin

    2018-05-01

    Full Text Available Most offshore structures including offshore wind turbines, ships, etc. suffer from the impulsive pressure loads due to slamming phenomena in rough waves. The effects of elasticity & plasticity on such slamming loads are investigated through wet free drop test results of several steel unstiffened flat bottom bodies in the rectangular water tank. Also, their cumulative deformations by consecutively repetitive free drops from 1000 mm to 2000 mm in height are measured. Keywords: Slamming phenomena, Impulsive pressure load, Wet free drop test, Flat bottom body, Cumulative damage

  10. Treatment with metallothionein prevents demyelination and axonal damage and increases oligodendrocyte precursors and tissue repair during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, Milena; Hidalgo, Juan

    2003-01-01

    Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human demyelinating disease multiple sclerosis (MS). EAE and MS are characterized by significant inflammation, demyelination, neuroglial damage, and cell death. Metallothionein-I and -II (MT-I + II) are antiinflammatory an......)beta, neurotrophin-3 (NT-3), NT-4/5, and nerve growth factor (NGF). These beneficial effects of Zn-MT-II treatment could not be attributable to its zinc content per se. The present results support further the use of Zn-MT-II as a safe and successful therapy for multiple sclerosis....

  11. Pathological and MRI study on experimental heroin-induced brain damage in rats

    International Nuclear Information System (INIS)

    Long Yu; Kong Xiangquan; Xu Haibo; Liu Dingxi; Yuan Ren; Yu Qun; Xiong Yin; Deng Xianbo

    2005-01-01

    Objective: To study the pathological characteristics of the heroin-induced brain damage in rats, and to assess the diagnostic value of MRI. Methods: A total of 40 adult Wistar rats were studied, 32 rats were used for injecting heroin as heroin group and 8 were used for injecting saline as control group. The heroin dependent rat model was established by administering heroin (ip) in the ascending dosage schedule (0.5 mg/kg), three times a day (at 8:00, 12:00, and 18:00). The control group was established by the same way by injection with saline. The withdrawal scores were evaluated with imp roved criterion in order to estimate the degree of addiction after administering naloxone. Based on the rat model of heroin dependence, the rat model of heroin-induced brain damage was established by the same way with increasing heroin dosage everyday. Two groups were examined by using MRI, light microscope, and electron microscope, respectively in different heroin accumulated dosage (918, 1580, 2686, 3064, 4336, and 4336 mg/kg withdrawal after 2 weeks). Results: There was statistically significant difference (t=9.737, P<0.01) of the withdrawal scores between the heroin dependent group and the saline group (23.0 ± 4.4 and 1.4 ± 0.5, respectively). It suggested that the heroin dependent rat model be established successfully. In different accumulated dosage ( from 1580 mg/kg to 4336 mg/kg), there were degeneration and death of nerve cells in cerebrum and cerebellum of heroin intoxicated rats, and it suggested that the rat model of heroin-induced brain damage was established successfully. The light microscope and electron microscope features of heroin-induced brain damage in rats included: (1) The nerve cells of cerebral cortex degenerated and died. According to the heroin accumulated dosage, there were statistically significant difference of the nerve cell deaths between 4336 mg/kg group and 1580 mg/kg group or control group (P=0.024 and P=0.032, respectively); (2) The main

  12. Calculated and experimental research of WWER-1000 assembly vibration and fretting damage

    International Nuclear Information System (INIS)

    Drozdov, Y.; Afanasyev, A.; Makarov, V.; Tutnov, A.; Tutnov, A.; Alekseev, E.

    2008-01-01

    The report covers the methods and results of the latest analytical and experimental studies of fretting corrosion and natural vibrations of a WWER-1000 reactor fuel assemblies (FA). The process of fretting-corrosion was investigated using a multi-specimen facility that simulated fragments of fuel rod-to-spacer grid and lower support grid mating units. A computational model was developed for vibrations in the mechanical system of a fuel rod fragment and a spacer grid fragment. A calculational and experimental modal analysis of a FA was performed. Natural frequencies, modes and decrements of FA vibrations were determined and a satisfactory coincidence of analytical and experimental results was obtained. The assessment of fretting-corrosion process dynamics was made and its dependences on operational factors were obtained. (authors)

  13. Experimental investigation and numerical description of the damage evolution in a duplex stainless steel subjected to VHCF-loading

    Energy Technology Data Exchange (ETDEWEB)

    Dönges, B., E-mail: benjamin.doenges@uni-siegen.de [Institut für Werkstofftechnik, Universität Siegen, D-57068 Siegen (Germany); Institut für Mechanik und Regelungstechnik – Mechatronik, Universität Siegen, D-57068 Siegen (Germany); Istomin, K. [Festkörperphysik, Universität Siegen, D-57068 Siegen (Germany); Söker, M. [Fakultät für Ingenieurwissenschaften und Informatik, Hochschule Osnabrück, D-49009 Osnabrück (Germany); Schell, N. [Helmholtz-Zentrum Geesthacht, Zentrum für Material- und Küstenforschung, D-21502 Geesthacht (Germany); Krupp, U. [Fakultät für Ingenieurwissenschaften und Informatik, Hochschule Osnabrück, D-49009 Osnabrück (Germany); Pietsch, U. [Festkörperphysik, Universität Siegen, D-57068 Siegen (Germany); Fritzen, C.-P. [Institut für Mechanik und Regelungstechnik – Mechatronik, Universität Siegen, D-57068 Siegen (Germany); Christ, H.-J. [Institut für Werkstofftechnik, Universität Siegen, D-57068 Siegen (Germany)

    2015-10-14

    The present study documents how the irreversible fraction of cyclic plastic strain, induced by loading amplitudes close to the durability limit, causes fatigue damage such as (i) slip band development, (ii) fatigue crack initiation and (iii) short fatigue crack propagation. The damage evolution of the austenitic–ferritic duplex stainless steel X2CrNiMoN22-5-3 (318 LN) was investigated up to one billion load cycles by means of high resolution electron microscopy (HR-SEM, TEM), focused ion beam (FIB) cutting, confocal laser scanning microscopy (CLSM), in-situ far field microscopy and high-energy (87.1 keV) X-ray diffraction (XRD) experiments. The experimentally identified damage mechanisms were implemented into three-dimensional finite element simulations, which consider crystal plasticity. These simulations enable fatigue life predictions of real microstructures obtained for instance by means of, e.g. automated electron back scatter diffraction (EBSD) analysis. The simulations allow for determining whether microcracks (i) initiate in a microstructure, (ii) arrest in the midst of the first grain, (iii) are permanently, (iv) temporary or (v) not at all blocked by grain or phase boundaries. Moreover, this concept is capable to contribute to the concept of tailored microstructures for improved cyclic-loading behavior.

  14. Experimental strain modal analysis for beam-like structure by using distributed fiber optics and its damage detection

    Science.gov (United States)

    Cheng, Liangliang; Busca, Giorgio; Cigada, Alfredo

    2017-07-01

    Modal analysis is commonly considered as an effective tool to obtain the intrinsic characteristics of structures including natural frequencies, modal damping ratios, and mode shapes, which are significant indicators for monitoring the health status of engineering structures. The complex mode indicator function (CMIF) can be regarded as an effective numerical tool to perform modal analysis. In this paper, experimental strain modal analysis based on the CMIF has been introduced. Moreover, a distributed fiber-optic sensor, as a dense measuring device, has been applied to acquire strain data along a beam surface. Thanks to the dense spatial resolution of the distributed fiber optics, more detailed mode shapes could be obtained. In order to test the effectiveness of the method, a mass lump—considered as a linear damage component—has been attached to the surface of the beam, and damage detection based on strain mode shape has been carried out. The results manifest that strain modal parameters can be estimated effectively by utilizing the CMIF based on the corresponding simulations and experiments. Furthermore, damage detection based on strain mode shapes benefits from the accuracy of strain mode shape recognition and the excellent performance of the distributed fiber optics.

  15. Effects of a 6-wk intraduodenal supplementation with quercetin on energy metabolism and indicators of liver damage in periparturient dairy cows.

    Science.gov (United States)

    Stoldt, Ann-Kathrin; Derno, Michael; Nürnberg, Gerd; Weitzel, Joachim M; Otten, Winfried; Starke, Alexander; Wolffram, Siegfried; Metges, Cornelia C

    2015-07-01

    conclusion, supplementation with Q resulted in lower pp plasma aminotransferase and glutamate dehydrogenase, which indicated reduced liver damage. However, the direct effects of Q on the liver and the implications for animal performance remain to be investigated. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Experimental techniques for the study of radiation damage in metals and alloys

    International Nuclear Information System (INIS)

    Novion, C.H. de.

    1983-06-01

    In this review, one presents the main experimental techniques used to study point defects and defect clusters introduced by irradiation in metals and alloys; emphasis will be put on some recent techniques. In particular, the studies allowing to analyse the very small agglomerates of point defects (Huang and small angle scattering, positron annihilation, electron microscopy) will be compared [fr

  17. An Experimental Study of the Local Parameters of a Damaged Cantilever

    DEFF Research Database (Denmark)

    Rytter, A.; Brincker, Rune; Kirkegaard, Poul Henning

    of results from experimental tests with six hollow section steel cantilevers containing a fatigue crack introduced from a narrow laser cut slot. The modal parameters have been identified for different size and location of a crack. The modal parameters have been estimated by mean of frequency domain and time...

  18. An Experimental Study of the Modal Parameters of a Damaged Cantilever

    DEFF Research Database (Denmark)

    Rytter, A.; Brincker, Rune; Kirkegaard, Poul Henning

    of results from experimental tests with six hollow section steel cantilevers containing a fatigue crack introduced from a narrow laser cut slot. The modal parameters have been identified for different size and location of a crack. The modal parameters have been estimated by mean of frequency domain and time...

  19. Experimental Study of the Lead Tungstate Scintillator Proton-Induced Damage and Recovery

    CERN Document Server

    Auffray, Etiennette; Singovski , A

    2011-01-01

    Lead tungstate (PbWO4, or PWO) scintillating crystals are used by two of the four experiments at the Large Hadron Collider (LHC): 75848 in CMS and 17920 in ALICE. For the CMS electromagnetic calorimeter, one of the most important crystal properties is its radiation hardness. With the increase of luminosity, the radiation level will increase drastically, particularly in the high pseudorapidity regions of the calorimeter. Beside the effects of color-centre formation caused by gamma-radiation, additional measurable effect originated by hadron irradiation could appear, which will further deteriorate the optical transmission of the crystals and therefore their efficiency. In this paper, we will present results of the proton-induced damage in PWO and a study of optical transmission recovery at different temperatures and under different light-induced "bleaching" conditions for proton-irradiated crystals.

  20. Subthreshold transpupillary thermotherapy reduces experimental choroidal neovascularization in the mouse without collateral damage to the neural retina.

    Science.gov (United States)

    Ming, Yue; Algvere, Peep V; Odergren, Anne; Berglin, Lennart; van der Ploeg, Ingeborg; Seregard, Stefan; Kvanta, Anders

    2004-06-01

    Transpupillary thermotherapy (TTT) is currently being evaluated for treatment of choroidal neovascularization (CNV) in age-related macular degeneration. To optimize TTT for CNV, the effect was analyzed of invisible (subthreshold) or visible (threshold) doses of TTT on the normal mouse retina and on experimental CNV. TTT was delivered to the normal retina of 42 mice with a diode laser at increasing power settings (50, 60, 70, or 80 mW), to obtain thermal lesions ranging from invisible (subthreshold) to visible (threshold) burns. CNV was induced in 53 mice by krypton laser photocoagulation of the fundus, after which the CNV lesions were treated with TTT (50, 60, or 80 mW). Eyes were enucleated 7 days after TTT and prepared for histology, and the CNV complex was evaluated on hematoxylin-eosin stained serial sections by measuring the maximum height of the CNV lesions. Ultrastructural changes were examined by transmission electron microscopy. Increasing the TTT laser power yielded gradually more visible effects. At 50 mW, which induced subthreshold burns, no damage was seen in the neural retina, retinal pigment epithelium (RPE), or choroid at any time point. By contrast, eyes treated with higher power exhibited progressively more damage to the neural retina, including a complete disruption of the outer nuclear layer. When TTT was applied to the laser-induced CNV lesions, the height of lesions was significantly reduced (P response to all three power settings at 7 days after treatment. The mean relative thickness of the CNV lesion was 3.29 +/- 0.89 in untreated mice, whereas in TTT-treated mice it was 1.69 +/- 0.35, 1.69 +/- 0.41 and 1.70 +/- 0.17 at power settings of 50, 60, and 80 mW, respectively. The overlying neural retina showed no apparent damage with the 50- or 60-mW settings, whereas outer nuclear layer disruption occurred with a power of 80 mW. Electron microscopy confirmed the presence of vascular occlusion at 1 day and a fibrotic scar at 7 days after TTT

  1. Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

    International Nuclear Information System (INIS)

    Yu, Ge; Wan, Rong; Hu, Yanling; Ni, Jianbo; Yin, Guojian; Xing, Miao; Shen, Jie; Tang, Maochun; Chen, Congying; Fan, Yuting; Xiao, Wenqin; Zhao, Yan; Wang, Xingpeng

    2014-01-01

    Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway

  2. Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Ge [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Wan, Rong [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Hu, Yanling [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Ni, Jianbo [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Yin, Guojian; Xing, Miao [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Shen, Jie [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Tang, Maochun [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Chen, Congying [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Fan, Yuting; Xiao, Wenqin; Zhao, Yan [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Wang, Xingpeng, E-mail: wangxingpeng@hotmail.com [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); and others

    2014-01-31

    Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.

  3. Aquaporin-4 deletion in mice reduces encephalopathy and brain edema in experimental acute liver failure.

    Science.gov (United States)

    Rama Rao, Kakulavarapu V; Verkman, A S; Curtis, Kevin M; Norenberg, Michael D

    2014-03-01

    Brain edema and associated astrocyte swelling leading to increased intracranial pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain levels of ammonia have been implicated in the development of brain edema in ALF. Cultured astrocytes treated with ammonia have been shown to undergo cell swelling and such swelling was associated with an increase in the plasma membrane expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here, we examined the evolution of brain edema in AQP4-null mice and their wild type counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly increased brain water content in WT mice (by 1.6% ± 0.3 and 2.3 ± 0.4%, respectively). AQP4 protein was significantly increased in brain plasma membranes of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain water content did not increase in AQP4-null mice. Additionally, AQP4-null mice treated with either TAA or APAP showed a remarkably lesser degree of neurological deficits as compared to WT mice; the latter displayed an inability to maintain proper gait, and demonstrated a markedly reduced exploratory behavior, with the mice remaining in one corner of the cage with its head tilted downwards. These results support a central role of AQP4 in the brain edema associated with ALF. Published by Elsevier Inc.

  4. Virgin coconut oil protects against liver damage in albino rats challenged with the anti-folate combination, trimethoprim-sulfamethoxazole.

    Science.gov (United States)

    Otuechere, Chiagoziem A; Madarikan, Gbemisola; Simisola, Tinuala; Bankole, Olubukola; Osho, Adeleke

    2014-05-01

    Trimethoprim-sulfamethoxazole (TMP-SMX) is a broad-spectrum antibiotic. However, its use is associated with toxic reactions. Virgin coconut oil (VCO), derived from coconut, has been widely used throughout history for its medicinal value. The aim of this study was to investigate the beneficial actions of VCO against TMP-SMX-induced alterations in serum biochemical end points. Twenty rats were divided into four groups. Group 1 (control) received no drug, whereas group 2 received TMP-SMX (8/40 mg/kg) twice daily for 7 days. Group 3 was administered coconut oil at a dose of 600 mg/kg body weight per day. The last group was treated with TMP-SMX (8/40 mg/kg) and coconut oil (600 mg/kg) simultaneously. Blood samples were collected from all groups on the 8th day of the experiment for measurement of serum biochemical parameters. Organ weights and coefficients were also evaluated. TMP-SMX caused a significant (p0.05) in the activities of serum aminotransferases, total acid phosphatase, γ-glutamyl transferase, uric acid, cholesterol, albumin, and urea levels. Supplementation of VCO ameliorated TMP-SMX-induced effects by restoring the levels of total bilirubin, alkaline phospahatase, and lactate dehydrogenase. The results of this study demonstrate that the active components of coconut oil had protective effects against the toxic effects induced by TMP-SMX administration, especially in the liver of rats.

  5. Dehydroepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage.

    Science.gov (United States)

    Kuebler, J F; Jarrar, D; Wang, P; Bland, K I; Chaudry, I H

    2001-05-15

    Recent studies have shown that administration of the sex steroid dehydroepiandrosterone (DHEA) in males following trauma-hemorrhagic shock has salutary effects on the depressed cardiovascular and immunological functions under those conditions. Since the effects of sex steroids are gender specific, we examined whether administration of DHEA has any beneficial effects on hepatocellular function in female rats with low estrogen levels following trauma-hemorrhage. Ovariectomy was performed in female Sprague-Dawley rats 14 days prior to the experiments. The animals then underwent a 5-cm midline laparotomy and were subjected to hemorrhagic shock (40 mm Hg for 90 min). This was followed by fluid resuscitation (Ringer's lactate over 60 min) and administration of DHEA (30 mg/kg BW) or vehicle subcutaneously at the end of resuscitation. At 24 h after resuscitation hepatocellular function, i.e., clearance of indocyanine green (ICG), and hepatocyte damage (serum alanine aminotransferase) were measured. Plasma levels of DHEA and 17beta-estradiol were also assayed. Vehicle-treated rats had significantly reduced hepatocellular function, increased ALT activity, and decreased levels of 17beta-estradiol following trauma-hemorrhage compared to sham-operated animals (P trauma-hemorrhage, hepatocellular function and ALT activity were similar to those of shams. However, administration of DHEA did not influence the plasma levels of 17beta-estradiol. Administration of DHEA following trauma-hemorrhage restored hepatocellular function and reduced hepatic damage that was observed in ovariectomized female rats under such conditions. This salutary effect of DHEA did not appear to be due to elevated levels of plasma 17beta-estradiol. We therefore propose that DHEA should be considered a novel, safe, and useful adjunct in the treatment of trauma-induced hepatocellular dysfunction in ovariectomized and postmenopausal females. Copyright 2001 Academic Press.

  6. An experimental study of radioprotective effect of ginseng alkaloid fraction on cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seong Yul; Cho, Chul Koo; Kim, Mi Sook; Yoo, Hyung Jun; Kim, Seong Ho; Kim, Tae Hwan [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1997-09-01

    This paper is to assess the effect of Adaptagen as a radioprotector in which main component is alkaloid fraction of ginseng. Evaluation was made in vitro and in vivo study with NIGP(S) mouse by the measurement of regeneration of jejunal crypt cell and micronucleus assay to analyze radioprotective effect of ginseng alkaloid fraction in comparison with that of water fraction after whole body irradiation. The results were as follows, 1. The degree of radiation damage of mouse jejunal crypt cell was diminished in both of alkaloid and water fraction groups compared to control group but more in alkaloid fraction group than water fraction group. 2. Regeneration of mouse jejunal crypt cell was higher both in alkaloid and water fraction groups than control group. 3. In vitro study, frequency of micronucleus was diminished in tendency for the treated groups than control group but statistically insignificant. 4. In vitro study, frequency of micronucleus was diminished in both alkaloid and water fraction groups compared to control group but more in alkaloid fraction group than water fraction group.

  7. An experimental study on renal damage induced by ionic contrast media in relation to iodine concentration

    International Nuclear Information System (INIS)

    Sung, Dong Wook; Yoon, Yup; Lim, Jae Hoon; Yang, Moon Ho

    1990-01-01

    Renal injury caused by iodinated contrast media has been widely known, but there has been few papers regarding the pathological change. A series of kidneys after injection of iodinated contrast media was examined to document pathological change. A total of 80 rats was divided into two groups; those given Urografin-60% by 5ml/kg; those given Urografin-76% by 5ml/kg. The kidneys were removed out 1, 2, 3, 5, 7, 10, 14 and 21 days after injection of contrast media and microscopically examined. The resulted were as follows: 1. Pathological changes induced by ionic contrast media were deposition of proteinaceous materials in the proximal convoluted tubules, congestion of interstitial vessels, and vasa rectae, and epithelial degeneration of collecting ducts. There was no detectable pathological changes in the glomerulus, loop of Henle, and distal convoluted tubules. 2. All pathological changes were severe, as the concentration of contrast media increased. 3. These pathologic changes appeared 1 day after injection of contrast media and persisted at least 3 weeks without improvement. Author concludes that the renal damage induced by ionic contrast media becomes severe with increase in concentration, and pathologic changes are not influence with time interval

  8. [Experimental research in vitro of TK/GCV system for osteosarcoma MG-63 cell damage].

    Science.gov (United States)

    Zhang, Hua-Dong; Lu, Zhi; Feng, Yi; Liu, Xiao-Li; Hou, Hui-Ming

    2014-03-01

    To study the killing effects of the liposome-mediated thymidine kinase (TK)/ganciclovir (GCV) system on MG-63 osteosarcoma (OS) cells and its bystander effects. Liposome-mediated TK gene transfected into MG-63 OS cells, the efficiency of transfection was analyzed by flow cytometry and observed under inverted fluorescence microscope. Non-transfected osteosarcoma MG-63 cells were divided into three groups,in the experimental group 1 transfected TK/GCV cells cultured in solutiona liquid mixture by supernatant by 1/10,1/7,1/5,1/2 ratio to original broth; in the experimental group 2 transfected cells cultured in solutiona liquid mixture of supernatant filtered through 0.22 microm filter by 1/10,1/7, 1/5, 1/2 ratio to original broth, in control group the transfection cells cultured in original culture solution. Cell growth inhibition rate and osteosarcoma cell sensitivity to TK/GCV system were measured by MTT assay in each group. The TK gene was transfected into MG-63 OS cells successfully by liposome-mediated, flow cytometry instrument detection TK gene transfection cell transfection efficiency can reach 75.5%. Six days later the MTT assay showed that in the experimental group 1 inhibition rate of all concentration ratio of the mixed culture fluid were statistically significant as compared with the control group (P culture medium was not statistically significant as compared with the control group (P > 0.05). TK gene transfected MG-63 cells increased with the the GCV concentration,the cell apoptosis rate increased. The experiment demonstrated that the MG-63 OS cells are sensitive to the liposome-mediated TK/GCV system and bystander effects are significant.

  9. Numerical and experimental study of long term creep damage in austenitic stainless steels

    International Nuclear Information System (INIS)

    Cui, Yiting

    2015-01-01

    The creep fracture of 316L(N) austenitic stainless steels has been studied both experimentally and theoretically for temperatures from 525 C up to 700 C and lifetimes up to nineteen years. For short term creep, failure is due to necking. Experimental lifetimes are bounded by the lower and upper bound predictions provided by a necking model and taking into account scatter in input parameters. This model leads to fair predictions of lifetimes up to a few thousand hours at very high temperature. Based on FEG-SEM observations, the transition observed in the failure curves is due to intergranular cavitation. The Riedel modeling of cavity growth by vacancy diffusion along grain boundaries coupled with continuous nucleation is carried out. Lifetimes are predicted fairly well using this model for long term creep failure whatever the considered austenitic stainless steel (316L(N), 304H, 316H, 321H) and the applied temperature (525 C - 700 C). Taking into account low and high stress regimes of Norton-power law, the Riedel model allows us to predict the creep lifetimes up to 25 years which differ from experimental data by less than a factor 3. The effect of the heterogeneity of the microstructure on grain boundary stress concentrations and cavity nucleation is simulated by the finite element method (Cast3M software). It aims to determine the distribution of grain boundary normal stress fields around precipitates depending on time and temperature. The features of the precipitates and the creep behavior of the austenitic matrix are both taking into account. (author) [fr

  10. Experimental Study of Plasma-Surface Interaction and Material Damage Relevant to ITER Type I Elms

    International Nuclear Information System (INIS)

    Makhlai, V.A.; Bandura, A.N.; Byrka, O.V. and others; Landman, I.; Neklyudov, I.M.

    2006-01-01

    The paper presents experimental investigations of main features of plasma surface interaction and energy transfer to the material surface in dependence on plasma heat loads. The experiments were performed with QSPA repetitive plasma pulses of the duration of 0.25 ms and the energy density up to 2.5 MJ/m 2 . Surface morphology of the targets exposed to QSPA plasma screams is analyzed. Relative contribution of the Lorentz force and plasma pressure gradient to the resulting surface profile is discussed. development of cracking on the tungsten surface and swelling of the surface are found to be in strong dependence on initial temperature of the target

  11. Solanum torvum Swartz. fruit attenuates cadmium-induced liver and kidney damage through modulation of oxidative stress and glycosylation.

    Science.gov (United States)

    Ramamurthy, C H; Subastri, A; Suyavaran, A; Subbaiah, K C V; Valluru, L; Thirunavukkarasu, C

    2016-04-01

    Increased levels of environmental pollutants are linked to almost all human disorders; the efficient method to manage the human health is through naturally available dietary molecule. Solanum torvum (ST) Swartz (Solanaceae) commonly called Turkey Berry is found in Africa, Asia, and South America. Its fruit, part of traditional Indian cuisine, is a widely consumed nutritious herb, acclaimed for its medicinal value. ST aqueous extract (STAe) (250, 500, and 1000 mg/kg b.w., 6 days; oral) against acute Cadmium (Cd) (6.3 mg/kg b.w., single dose; oral) toxicity was evaluated in rats. Protective effect was assessed using serum markers, tissue antioxidants, oxidant derivatives, glycoprotein, and histopathological studies. The activities of serum marker enzymes were increased (40-60 %); antioxidant enzymes such as SOD and CAT, GSH, and its metabolic enzyme activities were decreased (50-80 %) in the liver and kidney upon Cd intoxication. During STAe pre-treatment, at doses of 250 and 500 mg/kg b.w., the above changes were brought to near normal (25-63 %). Tissue 4-hydroxynonenal, 3-nitrotyrosine, and protein carbonyls were increased (8-15 fold) in Cd-alone-treated rats, whereas pre-supplementation of STAe significantly decreased their levels and inhibited the protein glycosylation effectively. The pharmacological effect of STAe was confirmed by histopathological observations. Based on previous literature and present investigation, we conclude that ST may serve as a potential functional food against environmental contaminant such as heavy metal-induced oxidative stress.

  12. Efficacy of Royal Jelly in Modulating Radiation-Induced Liver Damage in Rats Subjected to Low Level of Gamma Radiation

    International Nuclear Information System (INIS)

    Ibrahim, N.K.

    2010-01-01

    Royal Jelly (RJ) is bee product, rich in proteins, vitamins, enzymes, minerals, hormones (trace elements of testosterone), lipids, glucides, niacin, pantothenic acid, biotin, inositol and folic acid, which may be beneficial in neutralizing the free oxygen radicals. The present study was carried out evaluate the radio-protective effect of Royal Jelly exposure of male Swiss albino rats to 1 Gy for 5 times day post day. Royal jelly was supplemented by gavage to rats at a dose of 150 mg/ kg body wt/ day for successive 10 days through exposure to gamma radiation 1 Gy x 5 time day post day. The dose of royal jelly is equivalent to daily human nutritional supplementation quantity. The result revealed that whole body gamma-irradiation of rats produced significant decrease in plasma total protein, albumin and globulin contents and significant increase in plasma alanine transaminase (ALT) and aspartate transaminase (AST) activity. However, plasma testosterone significantly decrease and follicle-stimulating hormone (FSH) and luteinising hormone (LH) significantly increased. Cholesterol (TC), triacyleglycerol (TAC), superoxide dismutase (SOD) and glutathione per oxidise (GSHPx) decreased whereas, malondialdehde (MDA) increased. Oral administration of the RJ exerted a noticeable amelioration of the radiation induced hormonal and biochemical changes according to the results of the present study. It could be concluded that RJ possess anti-oxidative potential that may protect the liver against ?-radiation induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the limitation of culprit free radicals and the amelioration of oxidative stress and also due to the synergistic relationship between the natural components found in RJ

  13. Protective effect of Ganoderma lucidum polysaccharide against carbon tetrachloride-induced hepatic damage in precision-cut carp liver slices.

    Science.gov (United States)

    Liu, Yingjuan; Zhang, Chunyun; Du, Jinliang; Jia, Rui; Cao, Liping; Jeney, Galina; Teraoka, Hiroki; Xu, Pao; Yin, Guojun

    2017-10-01

    The aim of the present study was to investigate the protective effects of Ganoderma lucidum polysaccharide (GLPS) against carbon tetrachloride (CCl 4 )-induced hepatotoxicity in vitro in common carp. Precision-cut liver slices (PCLSs), which closely resemble the organ from which they are derived, were employed as an in vitro model system. GLPS (0.1, 0.3, and 0.6 mg/ml) was added to PCLS culture system before the exposure to 12 mM CCl 4 . The supernatants and slices were collected to detect molecular and biochemical responses to CCl 4 and PCLS treatments. The levels of CYP1A, CYP3A, and CYP2E1 were measured by ELISA; the mRNA expressions of TNF-α, IL-1β, IL-6, and iNOS were determined by RT-PCR; and the relative protein expressions of c-Rel and p65 were analyzed by western blotting. Results showed that GLPS inhibited the elevations of the marker enzymes (GOT, GPT, LDH) and MDA induced by CCl 4 ; it also enhanced the suppressed activity of antioxidant enzymes (SOD, CAT, GSH-Px, T-AOC). The treatment with GLPS resulted in significant downregulation of NF-κB and inflammatory cytokine mRNA levels and significant decreases in the hepatic protein levels of CYP1A, CYP3A, and CYP2E1. These results suggest that GLPS can protect CCl 4 -induced PCLS injury through inhibiting lipid peroxidation, elevating antioxidant enzyme activity, and suppressing immune inflammatory response.

  14. Neural Damage in Experimental Trypanosoma brucei gambiense Infection: Hypothalamic Peptidergic Sleep and Wake-Regulatory Neurons

    Directory of Open Access Journals (Sweden)

    Claudia Laperchia

    2018-02-01

    Full Text Available Neuron populations of the lateral hypothalamus which synthesize the orexin (OX/hypocretin or melanin-concentrating hormone (MCH peptides play crucial, reciprocal roles in regulating wake stability and sleep. The disease human African trypanosomiasis (HAT, also called sleeping sickness, caused by extracellular Trypanosoma brucei (T. b. parasites, leads to characteristic sleep-wake cycle disruption and narcoleptic-like alterations of the sleep structure. Previous studies have revealed damage of OX and MCH neurons during systemic infection of laboratory rodents with the non-human pathogenic T. b. brucei subspecies. No information is available, however, on these peptidergic neurons after systemic infection with T. b. gambiense, the etiological agent of 97% of HAT cases. The present study was aimed at the investigation of immunohistochemically characterized OX and MCH neurons after T. b. gambiense or T. b. brucei infection of a susceptible rodent, the multimammate mouse, Mastomysnatalensis. Cell counts and evaluation of OX fiber density were performed at 4 and 8 weeks post-infection, when parasites had entered the brain parenchyma from the periphery. A significant decrease of OX neurons (about 44% reduction and MCH neurons (about 54% reduction was found in the lateral hypothalamus and perifornical area at 8 weeks in T. b. gambiense-infected M. natalensis. A moderate decrease (21% and 24% reduction, respectively, which did not reach statistical significance, was found after T. b. brucei infection. In two key targets of diencephalic orexinergic innervation, the peri-suprachiasmatic nucleus (SCN region and the thalamic paraventricular nucleus (PVT, densitometric analyses showed a significant progressive decrease in the density of orexinergic fibers in both infection paradigms, and especially during T. b. gambiense infection. Altogether the findings provide novel information showing that OX and MCH neurons are highly vulnerable to chronic

  15. Neural Damage in Experimental Trypanosoma brucei gambiense Infection: The Suprachiasmatic Nucleus

    Directory of Open Access Journals (Sweden)

    Chiara Tesoriero

    2018-02-01

    , which have the capacity to cause permanent partial damage of this structure.

  16. Increase of infiltrating monocytes in the livers of patients with chronic liver diseases.

    Science.gov (United States)

    Huang, Rui; Wu, Hongyan; Liu, Yong; Yang, Chenchen; Pan, Zhiyun; Xia, Juan; Xiong, Yali; Wang, Guiyang; Sun, Zhenhua; Chen, Jun; Yan, Xiaomin; Zhang, Zhaoping; Wu, Chao

    2016-01-01

    Infiltrating monocytes have been demonstrated to contribute to tissue damage in experimental models of liver injury and fibrosis. However, less is known about monocyte infiltration in the livers of patients with chronic liver diseases (CLD). In the present study, we demonstrated that CD68+ hepatic macrophages and MAC387+ infiltrating monocytes were significantly increased in the livers of CLD patients with different etiologies as compared with normal liver tissue. In addition, CLD patients with higher inflammatory grading scores had more CD68+ macrophages and MAC387+ monocytes infiltration in their livers compared to those with lower scores. Significantly more MAC387+ infiltrating monocytes were found in the liver tissue of CLD patients with higher fibrotic staging scores compared to those with lower scores. Monocyte chemoattractant protein-1 (MCP-1) expression was significantly increased in the livers of CLD patients with different etiologies. MCP-1 staining scores were significantly positively associated with the numbers of MAC387+ infiltrating monocytes in CLD patients. Taken together, our results demonstrate that infiltrating monocytes may play a pathological role in exacerbating chronic liver inflammation and fibrosis in CLD. MCP-1 may be involved in the monocyte infiltration and progression of liver inflammation and fibrosis in CLD.

  17. Experimentally nonylphenol-polluted diet induces the expression of silent genes VTG and ER{alpha} in the liver of male lizard Podarcis sicula

    Energy Technology Data Exchange (ETDEWEB)

    Verderame, Mariailaria; Prisco, Marina; Andreuccetti, Piero [Department of Biological Sciences, Evolutionary and Comparative Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy); Aniello, Francesco [Department of Biological Sciences, Genetic and Molecular Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy); Limatola, Ermelinda, E-mail: limatola@unina.it [Department of Biological Sciences, Evolutionary and Comparative Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy)

    2011-05-15

    Endocrine Disruptor Chemicals (EDCs) with estrogen-like properties i.e nonylphenol (NP) induce vitellogenin (VTG) synthesis in males of aquatic and semi-aquatic specie. In the oviparous species VTG is a female-specific oestrogen dependent protein. Males are unable to synthesize VTG except after E{sub 2} treatment. This study aimed to verify if NP, administered via food and water, is able to induce the expression of VTG even in males of vertebrates with a terrestrial habitat such as the lizard Podarcis. By means of ICC, ISH, W/B and ELISA we demonstrated that NP induces the presence of VTG in the plasma and its expression in the liver. VTG, undetectable in untreated males, reaches the value of 4.34 {mu}g/{mu}l in the experimental ones. Expression analysis and ISH in the liver showed that an NP-polluted diet also elicits the expression of ER{alpha} in the liver which is known to be related to VTG synthesis in Podarcis. - Highlights: > Nonylphenol (NP) polluted diet induces VTG synthesis in a terrestrial vertebrate. > VTG and ER{alpha} genes are unexpressed in the liver of untreated male lizards Podarcis. > In the liver cells of NP-treated males the expression of both VTG and ER{alpha} occurs. > In treated males VTG synthesis is coupled with ER{alpha} expression as in breeding females. - NP-polluted diet induces the expression of ER{alpha} and VTG in the liver.

  18. Experimentally nonylphenol-polluted diet induces the expression of silent genes VTG and ERα in the liver of male lizard Podarcis sicula

    International Nuclear Information System (INIS)

    Verderame, Mariailaria; Prisco, Marina; Andreuccetti, Piero; Aniello, Francesco; Limatola, Ermelinda

    2011-01-01

    Endocrine Disruptor Chemicals (EDCs) with estrogen-like properties i.e nonylphenol (NP) induce vitellogenin (VTG) synthesis in males of aquatic and semi-aquatic specie. In the oviparous species VTG is a female-specific oestrogen dependent protein. Males are unable to synthesize VTG except after E 2 treatment. This study aimed to verify if NP, administered via food and water, is able to induce the expression of VTG even in males of vertebrates with a terrestrial habitat such as the lizard Podarcis. By means of ICC, ISH, W/B and ELISA we demonstrated that NP induces the presence of VTG in the plasma and its expression in the liver. VTG, undetectable in untreated males, reaches the value of 4.34 μg/μl in the experimental ones. Expression analysis and ISH in the liver showed that an NP-polluted diet also elicits the expression of ERα in the liver which is known to be related to VTG synthesis in Podarcis. - Highlights: → Nonylphenol (NP) polluted diet induces VTG synthesis in a terrestrial vertebrate. → VTG and ERα genes are unexpressed in the liver of untreated male lizards Podarcis. → In the liver cells of NP-treated males the expression of both VTG and ERα occurs. → In treated males VTG synthesis is coupled with ERα expression as in breeding females. - NP-polluted diet induces the expression of ERα and VTG in the liver.

  19. Intestinal Endotoxins as Co-Factors of Liver Injury in Obstructive Jaundice

    OpenAIRE

    Menteş, B. Bülent; Tatlicioğlu, Ertan; Akyol, Gülen; Uluoğlu, Ömer; Sultan, Nedim; Yilmaz, Erdal; Çelebi, Murat; Taneri, Ferit; Ferahköşe, Zafer

    1996-01-01

    The concept of endotoxin-mediated rather than direct liver injury in biliary obsruction was investigated using the experimental rat model of bile duct ligation (BDL) and small bowel bacterial overgrowth (SBBO). Small identical doses of intravenous endotoxin (bacterial LPS) caused a significantly more severe liver injury in rats with BDL, compared with sham-operated rats, suggesting the possible contribution of LPS in this type of liver damage. BDL was then combined with surgica...

  20. Liver and biliary damages following transarterial chemoembolization of hepatocellular carcinoma: comparison between drug-eluting beads and lipiodol emulsion

    Energy Technology Data Exchange (ETDEWEB)

    Monier, Arnaud; Duran, Rafael; Bize, Pierre; Dunet, Vincent; Denys, Alban [Lausanne University Hospital, Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland); Guiu, Boris [Lausanne University Hospital, Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland); Montpellier University Hospital, Department of Diagnostic and Interventional Radiology, Montpellier (France); Aho, Serge [University Hospital, Department of Epidemiology, Dijon (France); Deltenre, Pierre [Lausanne University Hospital, Department of Gastroenterology, Lausanne (Switzerland)

    2017-04-15

    To compare transarterial chemoembolization (TACE)-related hepatic toxicities of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with intermediate-stage hepatocellular carcinoma. In this retrospective study, 151 consecutive patients undergoing cTACE or DEB-TACE and MRI 3-6 weeks before and after therapy were included. Toxicity was assessed on imaging (global hepatic damages (GHD), overall biliary injuries, biliary cast, bile duct dilatation, intrahepatic biloma, portal thrombosis), and clinico-biological follow-ups. Tumour response, time to progression (TTP), and overall survival were assessed. Factors influencing complication rate were identified by generalized equation logistic regression model. Biliary injuries and intrahepatic biloma incidence were significantly higher following DEB-TACE (p < 0.001). DEB-TACE showed a significant increased risk of GHD (OR: 3.13 [1.74-5.63], p < 0.001) and biliary injuries (OR: 4.53 [2.37-8.67], p < 0.001). A significant relationship was found between baseline prothrombin value and GHD, biliary injuries and intrahepatic biloma (all p < 0.01), and between the dose of chemotherapy and intrahepatic biloma (p = 0.001). Only TTP was significantly shorter following DEB-TACE compared to cTACE (p = 0.025). DEB-TACE was associated with increased hepatic toxicities compared to cTACE. GHD, biliary injuries, and intrahepatic biloma were more frequently observed with high baseline prothrombin value, suggesting that cTACE might be more appropriate than DEB-TACE in patients with less advanced cirrhosis. (orig.)

  1. Increased Parenchymal Damage and Steatohepatitis in Caucasian Nonalcoholic Fatty Liver Disease Patients with Common IL1B and IL6 Polymorphisms

    Science.gov (United States)

    Nelson, James E.; Handa, Priya; Aouizerat, Bradley; Wilson, Laura; Vemulakonda, L Akhila; Yeh, Matthew M.; Kowdley, Kris V.

    2016-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in nonalcoholic steatohepatitis (NASH). The goal of this study was to investigate the relationship between IL1B and IL6 gene polymorphisms and histologic features of NAFLD in the NASH CRN cohort. Methods 604 adult (≥18 yrs) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. Results The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. Conclusions These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1β and IL-6 suppression. PMID:27730688

  2. Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms.

    Science.gov (United States)

    Nelson, J E; Handa, P; Aouizerat, B; Wilson, L; Vemulakonda, L A; Yeh, M M; Kowdley, K V

    2016-12-01

    Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort. A total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with not only increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1β and IL-6 suppression. © 2016 John Wiley & Sons Ltd.

  3. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  4. Piezosurgery prevents brain tissue damage: an experimental study on a new rat model.

    Science.gov (United States)

    Pavlíková, G; Foltán, R; Burian, M; Horká, E; Adámek, S; Hejčl, A; Hanzelka, T; Sedý, J

    2011-08-01

    Piezosurgery is a promising meticulous system for bone cutting, based on ultrasound microvibrations. It is thought that the imp