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Sample records for non-reproductive liver tissues

  1. Research progress in liver tissue engineering.

    Science.gov (United States)

    Zhang, Lei; Guan, Zheng; Ye, Jun-Song; Yin, Yan-Feng; Stoltz, Jean-François; de Isla, Natalia

    2017-01-01

    Liver transplantation is the definitive treatment for patients with end-stage liver diseases (ESLD). However, it is hampered by shortage of liver donor. Liver tissue engineering, aiming at fabricating new livers in vitro, provides a potential resolution for donor shortage. Three elements need to be considered in liver tissue engineering: seeding cell resources, scaffolds and bioreactors. Studies have shown potential cell sources as hepatocytes, hepatic cell line, mesenchymal stem cells and others. They need scaffolds with perfect biocompatiblity, suitable micro-structure and appropriate degradation rate, which are essential charateristics for cell attachment, proliferation and secretion in forming extracellular matrix. The most promising scaffolds in research include decellularized whole liver, collagens and biocompatible plastic. The development and function of cells in scaffold need a microenvironment which can provide them with oxygen, nutrition, growth factors, et al. Bioreactor is expected to fulfill these requirements by mimicking the living condition in vivo. Although there is great progress in these three domains, a large gap stays still between their researches and applications. Herein, we summarized the recent development in these three major fields which are indispensable in liver tissue engineering.

  2. Tissue Remodelling following Resection of Porcine Liver

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    Ingvild Engdal Nygård

    2015-01-01

    Full Text Available Aim. To study genes regulating the extracellular matrix (ECM and investigate the tissue remodelling following liver resection in porcine. Methods. Four pigs with 60% partial hepatectomy- (PHx- induced liver regeneration were studied over six weeks. Four pigs underwent sham surgery and another four pigs were used as controls of the normal liver growth. Liver biopsies were taken upon laparotomy, after three and six weeks. Gene expression profiles were obtained using porcine-specific oligonucleotide microarrays. Immunohistochemical staining was performed and a proliferative index was assessed. Results. More differentially expressed genes were associated with the regulation of ECM in the resection group compared to the sham and control groups. Secreted protein acidic and rich in cysteine (SPARC and collagen 1, alpha 2 (COL1A2 were both upregulated in the early phase of liver regeneration, validated by immunopositive cells during the remodelling phase of liver regeneration. A broadened connective tissue was demonstrated by Masson’s Trichrome staining, and an immunohistochemical staining against pan-Cytokeratin (pan-CK demonstrated a distinct pattern of migrating cells, followed by proliferating cell nuclear antigen (PCNA positive nuclei. Conclusions. The present study demonstrates both a distinct pattern of PCNA positive nuclei and a deposition of ECM proteins in the remodelling phase of liver regeneration.

  3. Gene expression profiles in liver cancer and normal liver tissues

    Institute of Scientific and Technical Information of China (English)

    Lian Xin Liu; Hong Chi Jiang; An Long Zhu; Jin Zhou; Xiu Qin Wang; Min Wu

    2000-01-01

    AIM To describe a liver cancer = specific gene expression profile and to identify genes that showed alteredexpression between liver cancer tissues and their adjacent nearly normal tissues.METHODS The cDNA probes which were labeled with a-32P dATP were synthesized from total RNA ofliver cancer and adjacent normal tissues and hybridized separately to two identical Atlas human cancer eDNAexpression array membranes containing 588 known genes.RESULTS Autoradiographic results were analyzed by specific Atlas ImageTM (version 1. 0) software.Among the 588 genes analyzed, 18 genes were found up-regulated in cancer, including TFDP2, Aktl, E2F-3etc, and 25 genes were down-regulated in cancer, including TDGF1, BAK, LAR, etc. Expression levels ofgenes that associated with the regulation of cell proliferation, apoptosis, differentiation, cell-cellinteraction, invasion regulators and eytokines altered mostly.CONCLUSION The result obtained from Atlas microarray provides a comprehensive liver cancer-specificexpression profile. The results can lead to the identification of liver cancer-specific biomarkers and may behelpful in early diagnosis and dentifiction of target genes for designing rational therapeutic strategies.

  4. Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver Tumors

    OpenAIRE

    Ibarra, R.; Dazard, J-E.; Y. Sandlers; Rehman, F; Abbas, R.; Kombu, R.; Zhang, G-F; Brunengraber, H; Sanabria, J.

    2014-01-01

    Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+...

  5. Adipose tissue-liver axis in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Alcoholic liver disease (ALD) remains an important healthproblem worldwide. The disease spectrum is featuredby early steatosis, steatohepatitis (steatosis with inflammatorycells infiltration and necrosis), with someindividuals ultimately progressing to fibrosis/cirrhosis.Although the disease progression is well characterized,no effective therapies are currently available for thetreatment in humans. The mechanisms underlying theinitiation and progression of ALD are multifactorial andcomplex. Emerging evidence supports that adiposetissue dysfunction contributes to the pathogenesis ofALD. In the first part of this review, we discuss themechanisms whereby chronic alcohol exposure contributedto adipose tissue dysfunction, including cell death,inflammation and insulin resistance. It has been longknown that aberrant hepatic methionine metabolismis a major metabolic abnormality induced by chronicalcohol exposure and plays an etiological role in thepathogenesis of ALD. The recent studies in our groupdocumented the similar metabolic effect of chronicalcohol drinking on methionine in adipose tissue. Inthe second part of this review, we also briefly discussthe recent research progress in the field with a focuson how abnormal methionine metabolism in adiposetissue contributes to adipose tissue dysfunction and liverdamage.

  6. Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms

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    Wan Nurlina Wan Yahya

    2014-07-01

    Full Text Available Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration.

  7. Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms

    Science.gov (United States)

    Yahya, Wan Nurlina Wan; Kadri, Nahrizul Adib; Ibrahim, Fatimah

    2014-01-01

    Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP) force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration. PMID:24991941

  8. 3D liver models in tissue engineering and toxicology

    NARCIS (Netherlands)

    Starokozhko, Viktoriia

    2016-01-01

    In her thesis, Viktoriia Starokozhko developed new and improved existing liver models for the use in tissue engineering and toxicology. One of the models she described and used are liver slices (PCLS), a mini-organ model for the liver. PCLS are used already for many years in various fields of pharma

  9. Correlation between the mechanical and histological properties of liver tissue

    OpenAIRE

    Başdoğan, Çağatay; Yarpuzlu, Berkay; Ayyıldız, Mehmet; Tok, Olgu Enis; Aktaş, Ranan Gülhan

    2014-01-01

    In order to gain further insight into the mechanisms of tissue damage during the progression of liver diseases as well as the liver preservation for transplantation, an improved understanding of the relation between the mechanical and histological properties of liver is necessary. We suggest that this relation can only be established truly if the changes in the states of those properties are investigated dynamically as a function of post mortem time. In this regard, we first perform mechanica...

  10. Synchrotron refractive-index microradiography of human liver cancer tissue

    Institute of Scientific and Technical Information of China (English)

    TONG Yongpeng; ZHANG Guilin; LI Yan; HWU Yeukuang; TSAI Wenli; JE Jung Ho; Margaritondo G.; YUAN Dong

    2005-01-01

    Three human liver tissue samples (~5 mm × 40 mm × 20 mm) were excised from a cancer patient's liver during surgery. The microradiology analysis was performed with a non-standard approach on a synchrotron. High-resolution refractive-index edge-enhanced microradiographs that cover a larger volume of the liver tissue sample were obtained. The cancer tissue and normal tissue could be clearly identified and distinguished based on their different textures. Furthermore, new blood vessel hyperplasia was found near the cancer area. Blood vessels with a diameter smaller than 20 μm could be identified. These findings were fully consistent with the histopathological examination of the same area. Microradiographs of the newly formed blood vessels at different angles were also obtained. This result shows that it is possible to further develop this approach into a technique of microradiographic imaging for clinic diagnosis of liver cancer at the early stage.

  11. VEGF in hepatocellular carcinoma and surrounding cirrhotic liver tissues

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Francois Labrousse; Yves Denizot

    2006-01-01

    @@ TO THE EDITOR We read with a great interest the recent work of Deli and colleagues.[1] in the World Journal of Gastroenterology reporting vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) and cirrhotic liver tissues.

  12. Effects of different mitogens on intrasplenic liver tissue transplants in comparison to orthotopic liver.

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    Lupp, Amelie; Lucas, Norma; Tralls, Manuela; Fuchs, Udo; Danz, Manfred

    2003-06-01

    Ectopic liver cell transplants, when compared to orthotopic liver, can serve as a tool to study topic influences on liver cell differentiation, multiplication, function and responsiveness to xenobiotics. The aim of the present study was to evaluate, if characteristic effects of mitogens are exerted in both liver and intrasplenic liver cell transplants in a similar manner. Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic rats. Four months later, transplant recipients and controls were treated with fluorene (FEN), fluorenone (FON), 2-acetylaminofluorene (AAF), N-nitrosodibenzylamine (NDBA) or the solvent 48 hours before sacrifice. The following parameters were assessed within livers and spleens: mitotic activity of hepatocytes, glycogen content, cytochrome P450 (P450) isoforms expression, P450 mediated monooxygenase functions, tissue content of lipid peroxides (LPO) and of reduced and oxidized glutathione (GSH; GSSG). In both orthotopic livers and intrasplenic transplants FEN, FON or NDBA administration increased the mitotic activity of the hepatocytes. Treatment with the mitogens caused a distinct and characteristic induction of the P450 isoforms expression and of the respective monooxygenase functions in the livers and (with certain differences) also in the transplants. FEN and FON slightly increased, AAF and NDBA reduced liver glycogen content. The latter effect was also seen in the transplants. NDBA administration caused a slight increase in tissue LPO content in livers, but not in spleens. Additionally, AAF or NDBA treatment led to an elevation of liver (but not of spleen) GSH and GSSG concentrations. The results of the present investigation show that characteristic effects of mitogens on orthotopic liver occur with certain differences also in ectopic liver cell transplants.

  13. Liver transplantation in the mouse: Insights into liver immunobiology, tissue injury, and allograft tolerance.

    Science.gov (United States)

    Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A; Thomson, Angus W

    2016-04-01

    The surgically demanding mouse orthotopic liver transplant model was first described in 1991. It has proved to be a powerful research tool for the investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction, and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, because the mouse genome is well characterized and there is much greater availability of both genetically modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice have provided valuable mechanistic insights into the immunobiology and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in the regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/immune-mediated events in the hepatic environment and systemically. In conclusion, orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology, and allograft tolerance that may result in therapeutic innovation in the liver and in the treatment of other diseases.

  14. Fetal and adult liver stem cells for liver regeneration and tissue engineering.

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    Fiegel, H C; Lange, Claudia; Kneser, U; Lambrecht, W; Zander, A R; Rogiers, X; Kluth, D

    2006-01-01

    For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches.

  15. Hyperplasia vs hypertrophy in tissue regeneration after extensive liver resection.

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    Marongiu, Fabio; Marongiu, Michela; Contini, Antonella; Serra, Monica; Cadoni, Erika; Murgia, Riccardo; Laconi, Ezio

    2017-03-14

    To address to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. The ability of the liver to regenerate is remarkable on both clinical and biological grounds. Basic mechanisms underlying this process have been intensively investigated. However, it is still debated to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. We addressed this issue using a genetically tagged system. We were able to follow the fate of single transplanted hepatocytes during the regenerative response elicited by 2/3 partial surgical hepatectomy (PH) in rats. Clusters of transplanted cells were 3D reconstructed and their size distribution was evaluated over time after PH. Liver size and liver DNA content were largely recovered 10 d post-PH, as expected (e.g., total DNA/liver/100 g b.w. was 6.37 ± 0.21 before PH and returned to 6.10 ± 0.36 10 d after PH). Data indicated that about 2/3 of the original residual hepatocytes entered S-phase in response to PH. Analysis of cluster size distribution at 24, 48, 96 h and 10 d after PH revealed that about half of the remnant hepatocytes completed at least 2 cell cycles. Average size of hepatocytes increased at 24 h (248.50 μm(2) ± 7.82 μm(2), P = 0.0015), but returned to control values throughout the regenerative process (up to 10 d post-PH, 197.9 μm(2) ± 6.44 μm(2), P = 0.11). A sizeable fraction of the remnant hepatocyte population does not participate actively in tissue mass restoration. Hyperplasia stands as the major mechanism contributing to liver mass restoration after PH, with hypertrophy playing a transient role in the process.

  16. Ultrasonic characterization of porcine liver tissue at frequency between 25 to 55 MHz

    Institute of Scientific and Technical Information of China (English)

    Xiao-Zhou Liu; Xiu-Fen Gong; Dong Zhang; Shi-Gong Ye; Bing Rui

    2006-01-01

    AIM: To study the relation between acoustic parameters and histological structure of biological tissue and to provide the basis for high-resolution image of biological tissues and quantitative ultrasonic diagnosis of liver disease.METHODS: Ultrasonic imaging and tissue characterization of four normal porcine liver and five cirrhotic liver tissue samples were performed using a high frequency imaging system.RESULTS: The acoustic parameters of cirrhotic liver tissue were larger than those of normal liver tissue. The sound velocity was 1577 m/s in normal liver tissue and 1631 m/s in cirrhotic liver tissue. At 35 MHz, the attenuation coefficient was 3.0 dB/mm in normal liver tissue and 4.1 dB/mm in cirrhotic liver tissue. The backscatter coefficient was 0.00431 dB/Srmm in cirrhotic liver tissue and 0.00303 dB/Srmm in normal liver tissue. The backscatter coefficient increased with the frequency. The high frequency images coincided with their histological features.CONCLUSION: The acoustic parameters, especially the sound backscatter coefficient, are sensitive to the changes of liver tissues and can be used to differentiate between the normal and pathological liver tissues.High frequency image system is a useful device for high-resolution image and tissue characterization.

  17. Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Mendoza, Michael; Caltharp, Shelley; Song, Ming; Collin, Lindsay; Konomi, Juna V; McClain, Craig J; Vos, Miriam B

    2017-07-01

    Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P < 0.001). Copper levels were not associated with degree of fibrosis, lobular inflammation, portal inflammation, or balloon degeneration. In this cohort of pediatric subjects with NAFLD, we observed decreased tissue copper levels in subjects with NAFLD when compared with non-NAFLD subjects. In addition, tissue copper levels were lower in subjects with nonalcoholic steatohepatitis, a more severe form of the disease, when compared with steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.

  18. Cold-induced changes in gene expression in brown adipose tissue, white adipose tissue and liver.

    Directory of Open Access Journals (Sweden)

    Andrew M Shore

    Full Text Available Cold exposure imposes a metabolic challenge to mammals that is met by a coordinated response in different tissues to prevent hypothermia. This study reports a transcriptomic analysis in brown adipose tissue (BAT, white adipose (WAT and liver of mice in response to 24 h cold exposure at 8°C. Expression of 1895 genes were significantly (P<0.05 up- or down-regulated more than two fold by cold exposure in all tissues but only 5 of these genes were shared by all three tissues, and only 19, 14 and 134 genes were common between WAT and BAT, WAT and liver, and BAT and liver, respectively. We confirmed using qRT-PCR, the increased expression of a number of characteristic BAT genes during cold exposure. In both BAT and the liver, the most common direction of change in gene expression was suppression (496 genes in BAT and 590 genes in liver. Gene ontology analysis revealed for the first time significant (P<0.05 down regulation in response to cold, of genes involved in oxidoreductase activity, lipid metabolic processes and protease inhibitor activity, in both BAT and liver, but not WAT. The results reveal an unexpected importance of down regulation of cytochrome P450 gene expression and apolipoprotein, in both BAT and liver, but not WAT, in response to cold exposure. Pathway analysis suggests a model in which down regulation of the nuclear transcription factors HNF4α and PPARα in both BAT and liver may orchestrate the down regulation of genes involved in lipoprotein and steroid metabolism as well as Phase I enzymes belonging to the cytochrome P450 group in response to cold stress in mice. We propose that the response to cold stress involves decreased gene expression in a range of cellular processes in order to maximise pathways involved in heat production.

  19. Mathematical modelling of cell aggregation in liver tissue engineering

    OpenAIRE

    Green, John Edward E.

    2006-01-01

    A promising method for growing functional liver tissue in vitro involves culturing hepatocytes as spheroidal cell aggregates. In this thesis, we develop mathematical models of cell aggregation, and use them to determine how hepatocytes' interactions with the extracellular matrix (ECM) on which they are seeded, and with stellate cells, affect the process. Chapters 2-4 focus on the effect that cell-ECM coupling has on the aggregation process. We use a novel formulation that couples a mechani...

  20. Tissue classification of liver pathological tissue specimens image using spectral features

    Science.gov (United States)

    Hashimoto, Emi; Ishikawa, Masahiro; Shinoda, Kazuma; Hasegawa, Madoka; Komagata, Hideki; Kobayashi, Naoki; Mochidome, Naoki; Oda, Yoshinao; Iwamoto, Chika; Ohuchida, Kenoki; Hashizume, Makoto

    2017-03-01

    In digital pathology diagnosis, accurate recognition and quantification of the tissue structure is an important factor for computer-aided diagnosis. However, the classification accuracy of cytoplasm is low in Hematoxylin and eosin (HE) stained liver pathology specimens because the RGB color values of cytoplasm are almost similar to that of fibers. In this paper, we propose a new tissue classification method for HE stained liver pathology specimens by using hyperspectral image. At first we select valid spectra from the image to make a clear distinction between fibers and cytoplasm, and then classify five types of tissue based on the bag of features (BoF). The average classification accuracy for all tissues was improved by 11% in the case of using BoF of RGB and selected spectra bands in comparison with using only RGB. In particular, the improvement reached to 24% for fibers and 5% for cytoplasm.

  1. Nano scaffolds and stem cell therapy in liver tissue engineering

    Science.gov (United States)

    Montaser, Laila M.; Fawzy, Sherin M.

    2015-08-01

    Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

  2. Analysis of Expressed Sequence Tags from Liver Tissue in Swine

    Institute of Scientific and Technical Information of China (English)

    LI Ning; ZHAO Zhi-hui; LIU Zhao-liang; ZHAO Xing-bo; LIAN Zhen-xing; WU Chang-xin

    2002-01-01

    In order to study the expression of function gene and its effect on metabolic control and other physiological function in liver, 438 expressed sequence tags (ESTs) were determined, which were from a cDNA library of porcine liver tissue. The results showed that the nucleotide sequences of 186 ESTs have already presented in GenBank database, and 37 ESTs could be found the homology with human and other species,while the others were not identified. 45 full length insertion of the clones randomly isolated from cDNA library were also completely sequenced with different size, and the results showed that 19 of them were functionknown genes, 11 had no open reading frame ( ORF )at all and 15 had ORF but the function were not elucidated yet.

  3. A multiscale model for bioimpedance dispersion of liver tissue.

    Science.gov (United States)

    Huang, W H; Chui, C K; Teoh, S H; Chang, S K Y

    2012-06-01

    Radio-frequency ablation (RFA) has been used in liver surgery to minimize blood loss during tissue division. However, the current RFA tissue division method lacks an effective way of determining the stoppage of blood flow. There is limitation on the current state-of-the-art laser Doppler flow sensor due to its small sensing area. A new technique was proposed to use bioimpedance for blood flow sensing. This paper discusses a new geometrical multiscale model of the liver bioimpedance incorporating blood flow impedance. This model establishes correlation between the physical tissue structure and bioimpedance measurement. The basic Debye structure within a multilevel framework is used in the model to account for bioimpedance dispersion. This dispersion is often explained by the Cole-Cole model that includes a constant phase element without physical explanation. Our model is able to account for reduced blood flow in its output with changes in permittivity in gamma dispersion that is mainly due to the polarization of water molecules. This study demonstrates the potential of a multiscale model in determining the stoppage of blood flow during surgery.

  4. High intensity interval training improves liver and adipose tissue insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Katarina Marcinko

    2015-12-01

    Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

  5. Con A affinity glycoproteomics of normal human liver tissue

    Institute of Scientific and Technical Information of China (English)

    SUN QiangLing; LU HaoJie; LIU YinKun; LU WenJing; CHENG Gang; ZHOU HaiJun; ZHOU XinWen; WEI LiMing; DAI Zhi; GUO Kun

    2007-01-01

    In order to establish the novel high throughput, high efficiency and Iow cost technological platform for the research of N-glycoproteomics, to resolve the significance of characteristic expression profile of glycoprotein and to find the proteins with biological functional importance, the glycoproteins with high-mannose core and the two antennary types were purified and enriched by the Con A affinity chromatography. Con A affinity protein expression profiles of normal human liver tissue were generated by using SDS-PAGE, two-dimensional electrophoresis (2-DE) followed by fast fluorescence staining based on multiplexed proteomics (MP) technology. 301 visible protein spots on the gel were detected and 85 of glycoproteins were further successfully identified via peptide mass fingerprinting (PMF) by a matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS/MS) and annotated to IPI databases. Identified glycoproteins definitely take part in the regulation of cell cycle and metabolic processes. The glycosylation sites were predicted with NetNGlyc 1.0 and NetOGlyc 3.1 software, meanwhile they were classified according to the geneontology methods. The construction of Con A affinity glycoprotein database of normal human liver tissue would contribute to the subsequent research.

  6. Con A affinity glycoproteomics of normal human liver tissue

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In order to establish the novel high throughput, high efficiency and low cost technological platform for the research of N-glycoproteomics, to resolve the significance of characteristic expression profile of glycoprotein and to find the proteins with biological functional importance, the glycoproteins with high-mannose core and the two antennary types were purified and enriched by the Con A affinity chromatography. Con A affinity protein expression profiles of normal human liver tissue were gener- ated by using SDS-PAGE, two-dimensional electrophoresis (2-DE) followed by fast fluorescence stain- ing based on multiplexed proteomics (MP) technology. 301 visible protein spots on the gel were de- tected and 85 of glycoproteins were further successfully identified via peptide mass fingerprinting (PMF) by a matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF- MS/MS) and annotated to IPI databases. Identified glycoproteins definitely take part in the regulation of cell cycle and metabolic processes. The glycosylation sites were predicted with NetNGlyc 1.0 and NetOGlyc 3.1 software, meanwhile they were classified according to the geneontology methods. The construction of Con A affinity glycoprotein database of normal human liver tissue would contribute to the subsequent research.

  7. Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

    Directory of Open Access Journals (Sweden)

    RINI PUSPITANINGRUM

    2010-09-01

    Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxiatolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

  8. Superoxide Dismutase (SOD Enzyme Activity Assay in Fasciola spp. Para-sites and Liver Tissue Extract

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    M Assady

    2011-09-01

    Full Text Available Background: The purpose of this comparative study was to detect superoxide dismutase (SOD activities in Fasciola hepatica, F. gigantica parasites, infected and healthy liver tissues in order to determine of species effects and liver infection on SODs activity level.Methods: Fasciola spp. parasites and sheep liver tissues (healthy and infected liver tissues, 10 samples for each, were collected, homogenized and investigated for protein measurement, protein detection and SOD enzyme activity assay. Protein concentration was measured by Bradford method and SODs band protein was detected on SDS-PAGE. SODs activity was determined by iodonitrotetrazolium chloride, INT, and xanthine substrates. Independent samples t-test was conducted for analysis of SODs activities difference.Results: Protein concentration means were detected for F. hepatica 1.3 mg/ ml, F. gigantica 2.9 mg/ml, healthy liver tissue 5.5 mg/ml and infected liver tissue 1.6 mg/ml (with similar weight sample mass. Specific enzyme activities in the samples were obtained 0.58, 0.57, 0.51, 1.43 U/mg for F. hepatica, F. gigantica, healthy liver and infected liver respectively. Gel electrophoresis of Fasciola spp. and sheep liver tissue extracts revealed a band protein with MW of 60 kDa. The statistical analysis revealed significant difference between SOD activities of Fasciola species and also between SOD activity of liver tissues (P<.05.Conclusion: Fasciola species and liver infection are effective causes on SOD enzyme activity level.

  9. Comparing differential tissue harmonic imaging with tissue harmonic and fundamental gray scale imaging of the liver.

    Science.gov (United States)

    Chiou, See-Ying; Forsberg, Flemming; Fox, Traci B; Needleman, Laurence

    2007-11-01

    The purpose of this study was to compare fundamental gray scale sonography, tissue harmonic imaging (THI), and differential tissue harmonic imaging (DTHI) for depicting normal and abnormal livers. The in vitro lateral resolution of DTHI, THI, and sonography was assessed in a phantom. Sagittal and transverse images of right and left hepatic lobes of 5 volunteers and 20 patients and images of 27 liver lesions were also acquired. Three independent blinded readers scored all randomized images for noise, detail resolution, image quality, and margin (for lesions) on a 7-point scale. Next, images from the same location obtained with all 3 modes were compared blindly side by side and rated by all readers. Contrast-to-noise ratios were calculated for the lesions, and the depth of penetration (centimeters) was determined for all images. In vitro, the lateral resolution of DTHI was significantly better than fundamental sonography (P = .009) and showed a trend toward significance versus THI (P = .06). In the far field, DTHI performed better than both modes (P images were scored, and for all parameters, DTHI and THI did better than sonography (P tissue harmonic imaging scored significantly higher than THI with regard to detail resolution and image quality (P Tissue harmonic imaging and DTHI do better than fundamental sonography for hepatic imaging, with DTHI being rated the best of the 3 techniques.

  10. TLR4-dependent immune response promotes radiation-induced liver disease by changing the liver tissue interstitial microenvironment during liver cancer radiotherapy.

    Science.gov (United States)

    Zhi-Feng, Wu; Le-Yuan, Zhou; Xiao-Hui, Zhou; Ya-Bo, Gao; Jian-Ying, Zhang; Yong, Hu; Zhao-Chong, Zeng

    2014-12-01

    Liver tissue interstitial fluid (TIF) a special microenvironment around liver cells, which may play a vital role in cell communication during liver injury. Moreover, toll-like receptor 4 (TLR4) is an important trigger of the immune response that may also play a role in liver injuries, including radiation-induced liver disease (RILD). Therefore, the purpose of this study was to identify the roles of the TLR4-dependent immune response and TIFs in RILD after radiation therapy (RT) for liver cancer. This study consisted of two phases, and in the primary phase, the livers of TLR4 mutant (TLR4(-)) and normal (TLR4(+)) mice were irradiated with 30 Gy. TIF was then obtained from mouse livers and assessed by cytokine array analysis 20 days after irradiation, and cytokines in the TIFs, TLR4 and RILD were analyzed. In the second or validation phase, hepatocytes were isolated from TLR4(+) or TLR4(-) mice irradiated with 8 Gy and were co-cultured with TIFs from mouse livers, apoptosis of the hepatocytes was then measured using flow cytometry. We found that severe RILD was accompanied by higher expression of granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor receptor 2(VEGFR-2) in liver TIFs, from in TLR4(+) mice compared with TLR4(-) mice (P livers irradiated, compared with TIFs from TLR4(-) mice that had their livers irradiated or TIFs from unirradiated mice (P liver TIFs.

  11. Iron in spleen and liver: Some cases of normal tissues and tissues from patients with hematological malignancies

    Science.gov (United States)

    Alenkina, Irina V.; Oshtrakh, Michael I.; Felner, Israel; Vinogradov, Alexander V.; Konstantinova, Tatiana S.; Semionkin, Vladimir A.

    2016-10-01

    Iron deposits in spleen and liver tissues obtained from several healthy people and patients with mantle cell lymphoma, acute myeloid leukemia and primary myelofibrosis were studied using Mössbauer spectroscopy and magnetization measurements. The results obtained demonstrated differences in the iron content in tissues as well as some variations in the ferrihydrite-like iron core structure in the iron storage proteins in these tissues. The presence of tiny amount of magnetite and paramagnetic component in spleen and liver tissue was also detected in different quantities in the studied tissues.

  12. Telomerase activity (TMA) in tumour and peritumoural tissues in a rat liver cancer model.

    Science.gov (United States)

    Zhang, Huo-Jun; Yang, Ji-Jin; Tian, Jian-Ming; Wang, Pei-Jun; Shao, Cheng-Wei; Zuo, Chang-Jing; Zhang, Shun-Min; Gupta, Sanjay

    2009-02-01

    To study the levels of telomerase activity (TMA) in tumour and peritumoural tissues in a liver cancer model in rats, and to study the change in TMA expression over time. Using the telomeric repeated amplification protocol (TRAP), TMA was measured in tumour tissue, peritumoural tissue and normal liver tissue of Walker-256 tumour-bearing rats at 4, 6 and 8 days after tumour implantation. TMA at day 4, 6 and 8 was 0.767+/-0.117, 0.768+/-0.118 and 0.774+/-0.111 in tumour tissue, 0.389+/-0.263, 0.492+/-0.253 and 0.584+/-0.239 in peritumoural tissue, and 0.231+/-0.022, 0.229+/-0.022 and 0.233+/-0.021 in normal liver tissue, respectively. TMA in tumour tissue was higher than that in peri-tumour and normal liver tissues at all time points of measurement (P TMA levels in tumour tissue and normal liver tissue did not show any change over time. TMA level in the peritumoural tissue increased with time; TMA level in animals sacrificed at day 8 was higher than that seen in animals sacrificed at day 4 (P TMA in walker-256 tumour-bearing rats was higher than that in normal and peritumoural tissues. TMA level in the peritumoural tissue increased with time suggesting that TMA activation in peritumoural tissue may be an important factor promoting tumour growth.

  13. CXCL16 participates in pathogenesis of immunological liver injury by regulating T lymphocyte infiltration in liver tissue

    Institute of Scientific and Technical Information of China (English)

    Huan-Bin Xu; Yan-Ping Gong; Jin Cheng; Yi-Wei Chu; Si-Dong Xiong

    2005-01-01

    AIM: To investigate the role of CXCL16 in the pathogenesis of immunological liver injury and to explore the possible mechanism of T lymphocyte infiltration requlated by CXCL16.METHODS: Immunological liver injury in murine model was induced by Bacille Calmette-Guerin and lipopolysaccharide.Expression pattem and distribution of CXCL16 were examined by real-time quantitative RT-PCR and immunohistochemical analysis. Anti-CXCL16 antibody was administrated in vivo to investigate its effect on T-cell recruitment and acute hepatic necrosis. The survival of murine model was also evaluated.RESULTS: The murine immunological liver injury model was successfully established. CXCL16 expression increased and predominantly distributed in periportal areas and vascular endothelia in injured liver tissues. Administration of anti-CXCL16 Ab protected the mice from death and acute liver damage. Approximately 70% of the mice survived for 72 h in the anti-CXCL16 Ab treatment group, whereas 80% died within 72 h in control Ab group. The number of liver-infiltrating T lymphocytes was significantly reduced from 1.01×L07 to 3.52x 106/liver, compared with control Ab treatment.CONCLUSION: CXCL16 is involved in immunological liver injury by regulating T lymphocyte infiltration in liver tissue.

  14. Hepatic tissue engineering: from transplantation to customized cell-based liver directed therapies from the laboratory.

    Science.gov (United States)

    Fiegel, Henning C; Kaufmann, Peter M; Bruns, Helge; Kluth, Dietrich; Horch, Raymund E; Vacanti, Joseph P; Kneser, Ulrich

    2008-01-01

    Today, liver transplantation is still the only curative treatment for liver failure due to end-stages liver diseases. Donor organ shortage, high cost and the need of immunosuppressive medications are still the major limitations in the field of liver transplantation. Thus, alternative innovative cell-based liver directed therapies, e.g. liver tissue engineering, are under investigation with the aim, that in future an artificial liver tissue could be created and be used for the replacement of the liver function in patients. Using cells instead of organs in this setting should permit (i) expansion of cells in an in vitro phase, (ii) genetic or immunological manipulation of cells for transplantation, (iii) tissue typing and cryopreservation in a cell bank, and (iv) the ex vivo genetic modification of patient's own cells prior re-implantation. Function and differentiation of liver cells are influenced by the three-dimensional organ architecture. The use of polymeric matrices permits the three dimensional formation of a neo-tissue and specific stimulation by adequate modification of the matrix-surface which might be essential for appropriate differentiation of transplanted cells. Additionally, culturing hepatocytes on three dimensional matrices permits culture in a flow bioreactor system with increased function and survival of the cultured cells. Based on bioreactor technology, bioartificial liver devices (BAL) are developed for extracorporeal liver support. Although BALs improved clinical and metabolic conditions, increased patient survival rates have not been proven yet. For intra-corporeal liver replacement, a concept which combines Tissue Engineering using three-dimensional, highly porous matrices with cell transplantation could be useful. In such a concept, whole liver mass transplantation, long term engraftment and function as well as correction of a metabolic defect in animal models could be achieved with a principally reversible procedure. Future studies have to

  15. Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post Radioembolization 90Y PET

    Directory of Open Access Journals (Sweden)

    Shyam Mohan Srinivas

    2014-10-01

    Full Text Available Background: Radioembolization with Yttrium-90 (90Y microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC. Using post-treatment 90Y PET/CT scans,the distribution of microspheres within the liver can be determined and quantitatively assessesed . We studied the radiation dose of 90Y delivered to liver and treated tumors.Methods: This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres® to the frequency of complications with mRECIST. 90Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL to an absorbed dose (Gy.Results: The 98 studied tumors received a mean dose of 169 Gy (mode 90-120 Gy;range 0-570 Gy. Tumor response by mRECIST criteria was performed for 48 tumors that had follow up scans. There were 21 responders (mean dose 215 Gy and 27 nonresponders (mean dose 167 Gy. The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p=0.099. Normal liver tissue received a mean dose of 67 Gy (mode 60-70 Gy; range 10-120 Gy. There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p=0.036.Conclusion: Our cohort of patients showed a possible dose response trend for the tumors. Collateral dose to normal liver is nontrivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the dose which the tumor or normal liver received.

  16. Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Kamran Qureshi; Gary A Abrams

    2007-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver-related morbidity and mortality.It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome (hypertension, dyslipidemia, diabetes). This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome (adipokines, cytokines, free fatty acids and other lipid moieties) of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance (IR). IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR,metabolic syndrome and NAFLD.

  17. Synergistic ablation of liver tissue and liver cancer cells with high-intensity focused ultrasound and ethanol.

    Science.gov (United States)

    Hoang, Nguyen H; Murad, Hakm Y; Ratnayaka, Sithira H; Chen, Chong; Khismatullin, Damir B

    2014-08-01

    We investigated the combined effect of ethanol and high-intensity focused ultrasound (HIFU), first, on heating and cavitation bubble activity in tissue-mimicking phantoms and porcine liver tissues and, second, on the viability of HepG2 liver cancer cells. Phantoms or porcine tissues were injected with ethanol and then subjected to HIFU at acoustic power ranging from 1.2 to 20.5 W (HIFU levels 1-7). Cavitation events and the temperature around the focal zone were measured with a passive cavitation detector and embedded type K thermocouples, respectively. HepG2 cells were subjected to 4% ethanol solution in growth medium (v/v) just before the cells were exposed to HIFU at 2.7, 8.7 or 12.0 W for 30 s. Cell viability was measured 2, 24 and 72 h post-treatment. The results indicate that ethanol and HIFU have a synergistic effect on liver cancer ablation as manifested by greater temperature rise and lesion volume in liver tissues and reduced viability of liver cancer cells. This effect is likely caused by reduction of the cavitation threshold in the presence of ethanol and the increased rate of ethanol diffusion through the cell membrane caused by HIFU-induced streaming, sonoporation and heating.

  18. Expression of SOCS-1 in the liver tissues of chronic hepatitis B and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Zhi-Xin Zhao; Qing-Xian Cai; Xiao-Mou Peng; Yu-Tian Chong; Zhi-Liang Gao

    2008-01-01

    AIM: To study the expression of suppressor of cytokine signaling-1 (SOCS-1) in the liver tissues of chronic hepatitis B (CHB) and the clinical significance of this expression.METHODS: The expression of SOCS-1 in liver tissues of 45 cases of CHB was investigated by immunohistochemical staining, and its correlations with inflammation grades and fibrosis stage were analyzed by SPSS statistics software.RESULTS: The result showed SOCS-1 expressing could be observed in the liver tissue of CHB. The expression of SOCS-1 was mainly distributed near the portal area in the liver tissue of mild inflammation CHB group, and was diffusely distributed in the liver tissue of moderate and severe inflammation groups. SOCS-1 positive stains mainly appear in the hepatocytes, only a few of liver interstitial cells were involved. Inside the hepatocyte, SOCS-1 positive stains are mainly distributed in the plasma. Some of the staining was observed on the membrane. The inclusion bodies in the plasma of hepatocytes were observed occasionally. There were both obvious correlations between the expression of SOCS-1 and the inflammatory grade, and that between the expression of SOCS-1 and the fibrosis stage.CONCLUSION: The distribution of SOCS-1 in the liver tissue of CHB is variable. This expression was correlated with the inflammation grade and fibrosis stage.

  19. Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

    Science.gov (United States)

    Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

    2014-05-01

    Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group).

  20. The analysis of γ-glutamyl transpeptidase gene in different type liver tissues

    Institute of Scientific and Technical Information of China (English)

    Guo-Qing Han; Cheng-Yong Qin; Rong-Hua Shu

    2003-01-01

    AIM: To probe the value of γ-glutamyl transpeptidase (GGT)messenger RNA in monitoring canceration of liver cells andfor early diagnosis of hepatocellular carcinoma (HCC), byresearching the types of GGT messenger RNA (GGTmRNA)in liver tissues and peripheral blood of different hepatopathy.METHODS: The three types of GGTmRNA (A, B, C) in livertissues and peripheral blood from the patients with HCC,noncancerous hepatopathy, hepatic benign tumor, secondarycarcinoma of liver, and healthy persons were detected byreverse-transcription polymerase chain reaction (RT-PCR).RESULTS: (1) In normal liver tissues, type A waspredominantly found (100.00 %), type B was not found,type C was found occasionally (25.00 %). (2) The distributionof types of GGTmRNA in liver tissues with acute hepatitis,chronic hepatitis, cirrhosis, alcoholic hepatopathy was similaras in normal liver tissues (P>0.05), but type B was found in3 of 18 patients with chronic hepatitis (16.67 %), and alsoin 3 of 11 patients with cirrhosis (27.27 %). (3) There wasno significant difference of types of GGTmRNA between livertissues with hepatic benign tumor, secondary carcinoma ofliver and normal liver tissues (P>0.05). (4) Type B waspredominant in cancerous tissues with HCC (87.5 %), theprevalence of type B in cancerous tissues was significantlyhigher than that in normal liver tissues (0/12) (P<0.05), butthe prevalence of type A in cancerous tissues (46.88 %)was significantly lower than that in normal liver tissues(100.00 %) (P<0.05), and the prevalence of type C (6.25 %)in cancerous was the same as that in normal liver tissues(25.00 %) (P>0.05). In noncancerous tissues of livers withHCC, the main types were type A and type B, the prevalenceof type A (85.71%, 90.48 %) and type C (14.29 %, 9.52 %)in noncancerous tissues of liver with HCC was similar asthat in normal liver tissues (A: 100.00 %; C: 25.00 %)(P>0.05), but the prevalence of type B (80.95 %, 76.19 %)in noncancerous tissues of livers with HCC

  1. Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland

    DEFF Research Database (Denmark)

    Dewailly, Éric; Mulvad, Gert; Pedersen, Henning S.

    1999-01-01

    report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high...

  2. Effects of cefodizime on chemokines of liver tissues in mice with immunological hepatic injury

    Institute of Scientific and Technical Information of China (English)

    WANG Peng; KAN Quan-cheng; YU Zu-jiang; LI Ling; PAN Xue

    2011-01-01

    Background Chronic hepatic inflammation is characterized by the accumulation of lymphocytes as a consequence of increased recruitment from the blood and retention within the tissue at sites of infection. CXC chemokine ligand 16 (CXCL16) mRNA has been detected in both inflamed and normal liver tissues and is strongly upregulated in the injured liver tissues in a murine model. The aim of this study was to investigate the effect of cefodizime on CXCL16 mRNA of liver tissues in mice with immunological hepatic injury.Methods The murine model of immunological hepatic injury was induced by Bacillus Calmette Guerin and Lipoposaccharide. The mice with immunological hepatic injury were randomly assigned to the model group, the cefodizime group and the ceftriaxone group. The three groups were continuously given agents for seven days and CXCL16 mRNA of liver tissue was determined and contrasted with the control group treated by normal saline. Reverse transcription-polymerase chain reaction was used to assay CXCL16 mRNA levels in liver tissues.Results The expressions of CXCL16 mRNA were significantly higher in the model group and the ceftriaxone group than in the control group and the cefodizime group (P <0.05), indicating the mice in the model group and the ceftriaxone group were immunodeficient. There was no statistical difference in the expressions of CXCL16 mRNA between the control group and the cefodizime group. Similarly, no statistical difference in the expressions of CXCL16 mRNA between the model group and the ceftriaxone group was detected (P >0.05).Conclusion Cefodizime effectively reduces the infiltration of lymphocytes into liver tissues and alleviates the liver damage by decreasing CXCL16 mRNA in liver tissues in mice with immunological hepatic injury.

  3. The nanomechanical signature of liver cancer tissues and its molecular origin

    Science.gov (United States)

    Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong

    2015-07-01

    Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus

  4. Activin A-Smad Signaling Mediates Connective Tissue Growth Factor Synthesis in Liver Progenitor Cells.

    Science.gov (United States)

    Ding, Ze-Yang; Jin, Guan-Nan; Wang, Wei; Sun, Yi-Min; Chen, Wei-Xun; Chen, Lin; Liang, Hui-Fang; Datta, Pran K; Zhang, Ming-Zhi; Zhang, Bixiang; Chen, Xiao-Ping

    2016-03-22

    Liver progenitor cells (LPCs) are activated in chronic liver damage and may contribute to liver fibrosis. Our previous investigation reported that LPCs produced connective tissue growth factor (CTGF/CCN2), an inducer of liver fibrosis, yet the regulatory mechanism of the production of CTGF/CCN2 in LPCs remains elusive. In this study, we report that Activin A is an inducer of CTGF/CCN2 in LPCs. Here we show that expression of both Activin A and CTGF/CCN2 were upregulated in the cirrhotic liver, and the expression of Activin A positively correlates with that of CTGF/CCN2 in liver tissues. We go on to show that Activin A induced de novo synthesis of CTGF/CCN2 in LPC cell lines LE/6 and WB-F344. Furthermore, Activin A contributed to autonomous production of CTGF/CCN2 in liver progenitor cells (LPCs) via activation of the Smad signaling pathway. Smad2, 3 and 4 were all required for this induction. Collectively, these results provide evidence for the fibrotic role of LPCs in the liver and suggest that the Activin A-Smad-CTGF/CCN2 signaling in LPCs may be a therapeutic target of liver fibrosis.

  5. Self-assembling functionalized nanopeptides for immediate hemostasis and accelerative liver tissue regeneration

    Science.gov (United States)

    Cheng, Tzu-Yun; Wu, Hsi-Chin; Huang, Ming-Yuan; Chang, Wen-Han; Lee, Chao-Hsiung; Wang, Tzu-Wei

    2013-03-01

    Traumatic injury or surgery may trigger extensive bleeding. However, conventional hemostatic methods have limited efficacy and may cause surrounding tissue damage. In this study, we use self-assembling peptides (SAPs) and specifically extend fragments of functional motifs derived from fibronectin and laminin to evaluate the capability of these functionalized SAPs in the effect of hemostasis and liver tissue regeneration. From the results, these peptides can self-assemble into nanofibrous network structure and gelate into hydrogel with pH adjustment. In animal studies, the efficacy of hemostasis is achieved immediately within seconds in a rat liver model. The histological analyses by hematoxylin-eosin stain and immunohistochemistry reveal that SAPs with these functionalized motifs significantly enhance liver tissue regeneration. In brief, these SAPs may have potential as pharmacological tools to extensively advance clinical therapeutic applications in hemostasis and tissue regeneration in the field of regenerative medicine.Traumatic injury or surgery may trigger extensive bleeding. However, conventional hemostatic methods have limited efficacy and may cause surrounding tissue damage. In this study, we use self-assembling peptides (SAPs) and specifically extend fragments of functional motifs derived from fibronectin and laminin to evaluate the capability of these functionalized SAPs in the effect of hemostasis and liver tissue regeneration. From the results, these peptides can self-assemble into nanofibrous network structure and gelate into hydrogel with pH adjustment. In animal studies, the efficacy of hemostasis is achieved immediately within seconds in a rat liver model. The histological analyses by hematoxylin-eosin stain and immunohistochemistry reveal that SAPs with these functionalized motifs significantly enhance liver tissue regeneration. In brief, these SAPs may have potential as pharmacological tools to extensively advance clinical therapeutic applications

  6. Expression and significance of SOCS3 in liver tissue of rats with severe acute pancreatitis complicated by liver injury

    Directory of Open Access Journals (Sweden)

    Bin WANG

    2012-11-01

    Full Text Available Objective  To investigate the expression and mechanism of action of suppressor of cytokine signaling 3 (SOCS3 in liver tissue of rats with experimental severe acute pancreatitis (SAP concurring with liver injury. Methods  The rat model of SAP was reproduced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct. Thirty-two male SD rats were randomly assigned into 4 groups (8 each: normal control group (NC, SAP 6h, 12h, and 18h groups. The levels of serum amylase (AMY, alanine aminotransferase (ALT and aspartate aminotransferase (AST were measured dynamically. The concentrations of IL -6 and IL -18 were determined by ELISA. The localization and expression of SOCS3 protein in liver were determined by immunohistochemical staining and Western blotting. Results  Compared with NC group, the serum levels of AMY, ALT and AST increased significantly in SAP groups (P < 0.05, and there was significant difference among SAP groups. The serum concentrations of IL-6 and IL-18 increased significantly in the SAP groups than in NC group (P < 0.05, and there was significant difference among SAP groups. Compared with NC group, the concentration of SOCS3 protein increased significantly in SAP groups, and increased gradually along with the increased duration of pancreatitis (P < 0.05. A minor expression of SOCS3 protein was found in NC group. The change in SOCS3 protein concentration was consistent with the severity of liver injury as well as the serum concentrations of IL-6 and IL-18. Conclusions  The inflammatory action induced by SAP concurring with liver injury may induce the expression of SOCS3 in liver tissue, and it may increase in intensity along with the severity of liver injury and inflammatory reaction. The mechanism may be attributed to a negative feedback regulation of the inflammatory action mediated by JAK/STAT pathway.

  7. The nanomechanical signature of liver cancer tissues and its molecular origin.

    Science.gov (United States)

    Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong

    2015-08-14

    Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the "gold standard" in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.

  8. Gene expression of hepatocyte growth factor and its receptor in HCC and nontumorous liver tissues

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To study the changes of gene expression of hepatocyte growth factor (HGF) and hepatocyte growth factor receptor (HGFr) in hepatocellular carcinoma (HCC) tissue and nontumorous liver tissue and the relationship between these changes and the biological behavior of the tumor.METHODS Gene expression of HGF and HGFr in 26 cases of HCC tissue and their adjacent nontumorous liver tissues was determined with digoxigenin-labeled DNA probes.RESULTS Positive expression of HGF in HCC tissue was similar to that in the adjacent nontumorous liver tissue, but positive rate of HGF expression was lower than HGFr gene expression. However, HGFr expression was higher in the metastatic cases than in those without metastasis. It was found that HGFr was overexpressed in HCC tissue as well as in the adjacent nontumorous liver tissue.CONCLUSION There seems to be a close relationship between overexpression of HGFr gene and tumor metastasis, and the HGF and HGFr system plays an important role in regulating tumor growth and metastasis.

  9. Collagen immunostains can distinguish capsular fibrous tissue from septal fibrosis and may help stage liver fibrosis.

    Science.gov (United States)

    Chen, Wei; Rock, Jonathan B; Yearsley, Martha M; Hanje, A James; Frankel, Wendy L

    2014-01-01

    Core-needle biopsy remains essential for diagnosis of cirrhosis; however, evaluation of fibrosis in such biopsies is often challenging due to the fragmented nature of cirrhotic liver specimens. It is also common to see portions of liver capsules present in the biopsy which adds to the diagnostic challenge. The distinction between capsular/subcapsular fibrous tissue and septal fibrosis is critical to avoid potential overstaging of liver fibrosis. We compared the differential immunostaining in liver capsular and septal areas for collagens III, IV, V, VI, vitronectin, laminin, Orcein, and Trichrome in 15 whole sections of explanted cirrhotic livers and 5 simulated liver biopsies. Collagens III, IV, V, VI, Trichrome, and Orcein show distinct staining patterns in capsular fibrous tissue and septal fibrosis. Collagen IV shows strong diffuse septal staining and consistently weak to negative capsular staining. Collagens III and VI stain similar to IV for septal fibrosis, whereas collagen V, Trichrome, and Orcein show strong staining in both areas. Collagen IV, possibly with III or VI in addition to the routine Trichrome and hematoxylin and eosin stain, is useful in differentiating capsular fibrous tissue from septal fibrosis on challenging and fragmented liver biopsies.

  10. Significance of hepatic arterial responsiveness for adequate tissue oxygenation upon portal vein occlusion in cirrhotic livers.

    Science.gov (United States)

    Mücke, I; Richter, S; Menger, M D; Vollmar, B

    2000-11-01

    We investigated sinusoidal blood flow and hepatic tissue oxygenation during portal vein occlusion in cirrhotic rat livers to examine the effect of cirrhosis on the properties of hepatic microvascular blood flow regulation. After 8 weeks of CCl4/phenobarbital sodium treatment to induce cirrhosis Sprague-Dawley rats were prepared surgically to allow assessment of portal venous and hepatic arterial inflow using miniaturized flow probes with simultaneous analysis of hepatic microcirculation and tissue oxygenation by fluorescence microscopy and polarographic oxymetry. Age-matched noncirrhotic animals served as controls. Upon portal vein occlusion in cirrhotic livers (flow reduction to portal vein occlusion did not cause a deterioration in hepatic tissue pO2 (11 +/- 3 vs. 10 +/- 3 mmHg at baseline). Sinusoidal diameters were found unchanged, disproving a major role of the sinusoidal tone in the regulation of HABR. Microvascular response of cirrhotic livers did not generally differ from that in noncirrhotic livers upon portal inflow restriction. We conclude that HABR in cirrhotic livers operates sufficiently to meet the liver tissue oxygen demand, most probably by an increased relative contribution of arterial perfusion of hepatic sinusoids.

  11. Simulation research of “heat conduction effect” of liver tissue during radiofrequency ablation

    Directory of Open Access Journals (Sweden)

    Kai JIANG

    2013-05-01

    Full Text Available Objective  To explore the heat conduction effect (HCE and effective extent in liver tissue produced by radiofrequency ablation (RFA. Methods  To simulate the HCE produced by RFA, isolated swine livers were heated to different temperature for a range of different heating time with RFA. The temperature of liver in different distance away from the center and the changes in color and morphology of liver tissue after radiofrequency treatment were recorded to explore the attenuation pattern of different heating center temperature and duration of treatment. Results  When the temperature of heating center reached 70℃, 5mm in radius of liver tissue was ablated in 10min. To expand the range to 10mm, central temperature should be maintained above 80℃ or 90℃, and the heating time should be maintained for 40min and 25min, respectively. Conclusion  To complete ablation of an area of liver tissue with 10mm in diameter with HCE, the temperature of heating center should be maintained at higher than 8090℃ and the ablation time should be maintained for 25-40min.

  12. Liver-adipose tissue crosstalk: A key player in the pathogenesis of glucolipid metabolic disease.

    Science.gov (United States)

    Ye, De-Wei; Rong, Xiang-Lu; Xu, Ai-Min; Guo, Jiao

    2017-06-01

    Glucolipid metabolic disease (GLMD), a complex of interrelated disorders in glucose and lipid metabolism, has become one of the leading chronic diseases causing public and clinical problem worldwide. As the metabolism of lipid and glucose is a highly coordinated process under both physiological and diseased conditions, the impairment in the signals corresponding to the metabolism of either lipid or glucose represents the common mechanism underlying the pathogenesis of GLMD. The liver and adipose tissue are the major metabolic organs responsible for energy utilization and storage, respectively. This review article aims to summarize the current advances in the investigation of the functional roles and the underling mechanisms of the interplay between the liver and adipose tissue in the modulation of GLMD development. Fibroblast growth factor 21 (FGF21) and adiponectin represent the two major hormones secreted from the liver and adipose tissues, respectively. FGF21 exerts pleiotropic effects on regulating glucose and lipid homeostasis majorly through inducing the expression and secretion of adiponectin. Therefore, FGF21-adiponectin axis functions as the key mediator for the crosstalk between the liver and adipose tissue to exert the beneficial effects on the maintenance of the homeostasis of energy consumption. The liver- and adipose tissue-derived factors with pleiotropic effects on regulating of lipid and glucose metabolism function as the key mediator for the crosstalk between these two highly active metabolic organs, thereby coordinating the initiation and development of GLMD.

  13. Development of a 3D cell printed construct considering angiogenesis for liver tissue engineering.

    Science.gov (United States)

    Lee, Jin Woo; Choi, Yeong-Jin; Yong, Woon-Jae; Pati, Falguni; Shim, Jin-Hyung; Kang, Kyung Shin; Kang, In-Hye; Park, Jaesung; Cho, Dong-Woo

    2016-01-12

    Several studies have focused on the regeneration of liver tissue in a two-dimensional (2D) planar environment, whereas actual liver tissue is three-dimensional (3D). Cell printing technology has been successfully utilized for building 3D structures; however, the poor mechanical properties of cell-laden hydrogels are a major concern. Here, we demonstrate the printing of a 3D cell-laden construct and its application to liver tissue engineering using 3D cell printing technology through a multi-head tissue/organ building system. Polycaprolactone (PCL) was used as a framework material because of its excellent mechanical properties. Collagen bioink containing three different types of cells-hepatocytes (HCs), human umbilical vein endothelial cells , and human lung fibroblasts--was infused into the canals of a PCL framework to induce the formation of capillary--like networks and liver cell growth. A co-cultured 3D microenvironment of the three types of cells was successfully established and maintained. The vascular formation and functional abilities of HCs (i.e., albumin secretion and urea synthesis) demonstrated that the heterotypic interaction among HCs and nonparenchymal cells increased the survivability and functionality of HCs within the collagen gel. Therefore, our results demonstrate the prospect of using cell printing technology for the creation of heterotypic cellular interaction within a structure for liver tissue engineering.

  14. Correlation of HIFs/PPAR signaling pathway activation degree and lipid metabolism in liver tissue of alcoholic fatty liver rat model

    Institute of Scientific and Technical Information of China (English)

    Li-Ying Guo; Ya-Min Li; Qing-Chun Li

    2015-01-01

    Objective:To study the correlation of HIFs/PPAR signaling pathway activation degree and lipid metabolism in liver tissue of alcoholic fatty liver rat model.Methods:Adult SD rats were selected and alcoholic fatty liver rat models were established by alcohol administration and high-fat diet feeding. Liver tissue was collected and contents of HIF-1α, PPARγ and lipid metabolism-related enzymes were detected; serum was collected and contents of lipid metabolism indexes and liver cell damage indexes were detected.Results:(1) one week, two weeks, three weeks and four weeks after models were established, HIF-1αα in livers of the model group showed an increasing trend and PPARγ showed a decreasing trend; HIF-1α content was higher than that of the control group and PPARγ content was lower than that of the control group; (2) contents of apoCII, apoCIII,α-GST and GLDH in serum as well as levels of FAT, FABP1, FAS, ACC and ACAT-2 in liver tissue of the model group all significantly increased, and were positively correlated with HIF-1α and negatively correlated with PPARγ.Conclusion:Transcription factor HIF-1α content abnormally increases and PPARγ content abnormally decreases in liver tissue of alcoholic fatty liver rat models; it results in abnormal lipid metabolism and liver cell damage through increasing the expression of lipid metabolism-related enzymes in the liver.

  15. Age and diet affect gene expression profiles in canine liver tissue.

    Directory of Open Access Journals (Sweden)

    Dong Yong Kil

    Full Text Available BACKGROUND: The liver plays a central role in nutrient and xenobiotic metabolism, but its functionality declines with age. Senior dogs suffer from many of the chronic hepatic diseases as elderly humans, with age-related alterations in liver function influenced by diet. However, a large-scale molecular analysis of the liver tissue as affected by age and diet has not been reported in dogs. METHODOLOGY/PRINCIPAL FINDINGS: Liver tissue samples were collected from six senior (12-year old and six young adult (1-year old female beagles fed an animal protein-based diet (APB or a plant protein-based diet (PPB for 12 months. Total RNA in the liver tissue was extracted and hybridized to Affymetrix GeneChip® Canine Genome Arrays. Using a 2.0-fold cutoff and false discovery rate <0.10, our results indicated that expression of 234 genes was altered by age, while 137 genes were differentially expressed by diet. Based on functional classification, genes affected by age and/or diet were involved in cellular development, nutrient metabolism, and signal transduction. In general, gene expression suggested that senior dogs had an increased risk of the progression of liver disease and dysfunction, as observed in aged humans and rodents. In particular for aged liver, genes related to inflammation, oxidative stress, and glycolysis were up-regulated, whereas genes related to regeneration, xenobiotic metabolism, and cholesterol trafficking were down-regulated. Diet-associated changes in gene expression were more common in young adult dogs (33 genes as compared to senior dogs (3 genes. CONCLUSION: Our results provide molecular insight pertaining to the aged canine liver and its predisposition to disease and abnormalities. Therefore, our data may aid in future research pertaining to age-associated alterations in hepatic function or identification of potential targets for nutritional management as a means to decrease incidence of age-dependent liver dysfunction.

  16. Doping with anabolic androgenic steroids (AAS): Adverse effects on non-reproductive organs and functions.

    Science.gov (United States)

    Nieschlag, Eberhard; Vorona, Elena

    2015-09-01

    Since the 1970s anabolic androgenic steroids (AAS) have been abused at ever increasing rates in competitive athletics, in recreational sports and in bodybuilding. Exceedingly high doses are often consumed over long periods, in particular by bodybuilders, causing acute or chronic adverse side effects frequently complicated by additional polypharmacy. This review summarizes side effects on non-reproductive organs and functions; effects on male and female reproduction have been recently reviewed in a parallel paper. Among the most striking AAS side effects are increases in haematocrit and coagulation causing thromboembolism, intracardiac thrombosis and stroke as well as other cardiac disturbances including arrhythmias, cardiomyopathies and possibly sudden death. 17α-alkylated AAS are liver toxic leading to cholestasis, peliosis, adenomas and carcinomas. Hyperbilirubinaemia can cause cholemic nephrosis and kidney failure. AAS abuse may induce exaggerated self-confidence, reckless behavior, aggressiveness and psychotic symptoms. AAS withdrawal may be accompanied by depression and suicidal intentions. Since AAS abuse is not or only reluctantly admitted physicians should be aware of the multitude of serious side effects when confronted with unclear symptoms.

  17. In vitro measurements of temperature-dependent specific heat of liver tissue.

    Science.gov (United States)

    Haemmerich, Dieter; dos Santos, Icaro; Schutt, David J; Webster, John G; Mahvi, David M

    2006-03-01

    We measured the specific heat of liver tissue in vitro by uniformly heating liver samples between two electrodes. We insulated the samples by expanded polystyrene, and corrected for heat loss and water loss. The specific heat of the liver is temperature-dependent, and increases by 17% at 83.5 degrees C (p specific heat was 3411 J kg(-1)K(-1) at 25 degrees C, and 4187 J kg(-1)K(-1) at 83.5 degrees C. Water loss from the samples was significant above 70 degrees C, with approximately 20% of reduction in sample mass at 90 degrees C.

  18. The expression of HIF-1 α in liver tissues in the rat model of paraquat poisoning

    Institute of Scientific and Technical Information of China (English)

    熊莺

    2014-01-01

    Objective To observe the levels of HIF-αand TGF-βin the liver tissue,change of serum transaminase in different phases after paraquat(PQ)toxicity and liver histopathology change in PQ-induced liver toxicity of rat models in order to analyze the relationship between HIF-αand hepatic toxicity induced by PQ.Methods A total of 48 healthy SD rats were randomly(random number)assigned into 2 groups:PQ poisoning group(n=42,

  19. Antioxidant enzyme activities in hepatic tissue from children with chronic cholestatic liver disease

    Directory of Open Access Journals (Sweden)

    Ismail Nagwa

    2010-01-01

    Full Text Available Background/Aim: To study the oxidative stress status in children with cholestatic chronic liver disease by determining activities of glutathione peroxidase (GPx, superoxide dismutase (SOD and catalase (CAT in liver tissue. Materials and Methods: A total of 34 children suffering from cholestatic chronic liver disease were studied. They were selected from the Hepatology Clinic, Cairo University, and compared with seven children who happened to have incidental normal liver biopsy. The patients were divided into three groups: extrahepatic biliary atresia (n=13, neonatal hepatitis (n=15 and paucity of intrahepatic bile ducts (n=6; GPx, SOD and CAT levels were measured in fresh liver tissue using ELISA . Results: In the cholestatic patients, a significant increase was found in mean levels of SOD, GPx and CAT in hepatic tissue compared to control children. The three enzymes significantly increased in the extrahepatic biliary atresia group, whereas in the groups of neonatal hepatitis and paucity of intrahepatic bile ducts, only GPx and CAT enzymes were significantly increased. Conclusion: Oxidative stress could play a role in the pathogenesis of cholestatic chronic liver diseases. These preliminary results are encouraging to conduct more extensive clinical studies using adjuvant antioxidant therapy.

  20. The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function.

    Science.gov (United States)

    Conroy, Melissa J; Fitzgerald, Vivienne; Doyle, Suzanne L; Channon, Shauna; Useckaite, Zivile; Gilmartin, Niamh; O'Farrelly, Cliona; Ravi, Narayanasamy; Reynolds, John V; Lysaght, Joanne

    2016-12-01

    The role of NK cells in visceral adipose tissue (VAT) and liver inflammation in obesity is not fully understood. This study investigated the frequency, cytokine expression, chemokine receptor, and cytotoxicity receptor profile of NK cells in the blood, omentum, and liver of patients with the obesity-associated cancer, oesophageal adenocarcinoma (OAC). The effect of chronically inflamed tissue microenvironments on NK cell viability and function was also examined. We identified significantly lower NK cell frequencies in the liver of OAC patients compared with healthy controls and within the omentum and liver of OAC patients compared with blood, whereas IL-10-producing populations were significantly higher. Interestingly, our data suggest that reduced frequencies of NK cells in omentum and liver of OAC patients are not a result of impaired NK cell chemotaxis to these tissues. In fact, our functional data revealed that secreted factors from omentum and liver of OAC patients induce significant levels of NK cell death and lead to reduced percentages of TNF-α(+) and NKP46(+) NK cells and higher frequencies of IL-10-producing NK cells. Together, these data suggest that the omental and hepatic microenvironments of OAC patients alter the NK cell phenotype to a more anti-inflammatory homeostatic role. © Society for Leukocyte Biology.

  1. Total mercury in liver and muscle tissue of two coastal sharks from the northwest of Mexico.

    Science.gov (United States)

    Hurtado-Banda, Rocío; Gomez-Alvarez, Agustín; Márquez-Farías, J Fernando; Cordoba-Figueroa, Marcial; Navarro-García, Gerardo; Medina-Juárez, Luis Angel

    2012-06-01

    Total mercury (THg) in liver and muscle of three costal sharks from Mexico were evaluated. The highest concentrations of THg in muscle tissue of juveniles were found in Sphyrna lewini (0.82 ± 0.33 mg kg(-1) wet basis). Rhizoprionodon longurio adults had the highest concentrations (0.92 ± 1.03 mg kg(-1)). THg concentrations in liver were low compared to those found in muscle tissue; higher levels were found in liver of juvenile S. lewini (0.250 ± 0.07 mg kg(-1)). Results showed that 35 % of muscle tissue samples are above the precautionary limit (0.50 mg kg(-1) of THg) and a 7 % exceeded the maximum limit for human consumption (1 mg kg(-1)).

  2. Histopathology effects of nickel nanoparticles on lungs, liver, and spleen tissues in male mice

    Science.gov (United States)

    Ajdari, Marziyeh; Ziaee Ghahnavieh, Marziyeh

    2014-09-01

    Because of the classification of the nickel compounds as carcinogenic substances, there is a need for in vivo tests to nickel nanoparticles (NiNPs) for observing their effects on health experimentally. Spherical NiNPs with 10 nm in diameter and 75 ppm concentration were applied for investigating their toxicities within male albino mice as an in vivo model. We randomly made sham group, control group, and 75 ppm group (with five animals in each group). Then, the nanoparticles were injected into mice intraperitonealy for 7 days and after that their lungs, liver, and spleen were removed for histopathological observations. At the end of the test, section microscopic observations of liver, spleen, and lung in sham and control groups showed normal tissues but these tissues underwent significant abnormal effects in 75 ppm group. NiNPs can cause undesirable effects in lungs, liver, and spleen tissues with same condition of this study.

  3. A Case of Hemorrhagic Necrosis of Ectopic Liver Tissue within the Gallbladder Wall.

    LENUS (Irish Health Repository)

    Nagar, Sapna

    2012-02-01

    Ectopic liver tissue is a rare clinical entity that is mostly asymptomatic and found incidentally. In certain situations, however, patients may present with symptoms of abdominal pain secondary to torsion, compression, obstruction of adjacent organs, or rupture secondary to malignant transformation. Herein, we report a case of a 25-year-old female that presented with acute onset of epigastric pain found to have ectopic liver tissue near the gallbladder complicated by acute hemorrhage necessitating operative intervention in the way of laparoscopic excision and cholecystectomy. The patient\\'s postoperative course was uneventful. Gross pathology demonstrated a 1.2 x 2.8 x 4.5 cm firm purple ovoid structure that histologically revealed extensive hemorrhagic necrosis of benign ectopic liver tissue.

  4. Functional link between ETB receptors and eNOS maintain tissue oxygenation in the normal liver.

    Science.gov (United States)

    Paxian, Markus; Keller, Steve A; Baveja, Rajiv; Korneszczuk, Katarzyna; Huynh, Toan T; Clemens, Mark G

    2004-01-01

    Endothelins and their receptors play a crucial role in regulating liver microcirculation in pathophysiological conditions. The authors investigated the functional significance of the coupling of ET(B) receptors and eNOS in maintaining regional perfusion and tissue oxygenation in the normal liver. The effect of endothelin-1 or the ET(B) agonist IRL1620 on oxygen consumption was determined in isolated perfused liver and isolated hepatocytes. Oxygen delivery to the liver tissue was determined in vivo. Following eNOS or iNOS blockade, either ET-1 or IRL1620 was infused via the portal vein. Hepatic tissue oxygenation, redox state, and microcirculation were investigated by intravital microscopy. Injury was estimated by serum LDH. Although IRL1620 and endothelin-1 increased oxygen consumption in isolated hepatocytes, in intact liver, endothelin decreased oxygen consumption while IRL1620 produced no change. In vivo, ET(B) stimulation modestly altered hepatic tissue P(O(2)), redox potential, and microcirculation. eNOS inhibition and ET(B) activation dramatically reduced microcirculatory blood flow, oxygen supply, and increased LDH release. Inhibition of iNOS resulted in small but not significant changes in these parameters. Concomitant ET(A)/ET(B) receptor activation increased microcirculatory failure and decreased tissue oxygen even without NOS inhibition. In contrast, hepatocellular injury was significantly increased following eNOS inhibition. Coupling between ET(B) receptor stimulation and eNOS activation decreases sinusoidal constriction and plays a functionally important role in maintaining microcirculation and tissue oxygenation in the normal liver.

  5. Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

    DEFF Research Database (Denmark)

    Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard;

    2013-01-01

    of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...

  6. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs

    DEFF Research Database (Denmark)

    Tous, Nuria; Theil, Peter Kappel; Lauridsen, Charlotte

    2012-01-01

    in these tissues, except for SM intermuscular fat. Dietary CLA increased PPARγ in LT muscle (P fat. Transcription of genes related to FA synthesis was reduced by CLA in SM muscle and liver (SREBP1......, both P muscle and reduced (P increased (P muscle and intermuscular fat. Saturated FA were increased in all studied tissues (P ... (LPL), delta-6-desaturase (D6D), and stearoyl CoA desaturase (SCD) were determined by real-time PCR in longissimus thoracis (LT) and semimembranosus (SM) muscles, LT subcutaneous and SM intermuscular fat, and in the liver. Fatty acid (FA) composition was analyzed using gas chromatography...

  7. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused 3D Porous Polymer Scaffold for Liver Tissue Engineering

    DEFF Research Database (Denmark)

    Hemmingsen, Mette; Muhammad, Haseena Bashir; Mohanty, Soumyaranjan

    A huge shortage of liver organs for transplantation has motivated the research field of tissue engineering to develop bioartificial liver tissue and even a whole liver. The goal of NanoBio4Trans is to create a vascularized bioartificial liver tissue, initially as a liver-support system. Due...... to limitations of primary hepatocytes regarding availability and maintenance of functionality, stem cells and especially human induced pluripotent stem cells (hIPS cells) are an attractive cell source for liver tissue engineering. The aim of this part of NanoBio4Trans is to optimize culture and hepatic...... differentiation of hIPS-derived definitive endoderm (DE) cells in a 3D porous polymer scaffold built-in a perfusable bioreactor. The use of a microfluidic bioreactor array enables the culture of 16 independent tissues in one experimental run and thereby an optimization study to be performed....

  8. Method for Processing Liver Spheroids Using an Automatic Tissue Processor

    Science.gov (United States)

    2016-05-01

    of any commercial products. This report may not be cited for purposes of advertisement . This report has been approved for public release... alcohol dehydration and hot liquid wax infiltration. After the water in the tissue is replaced with wax and cooled, it then becomes possible to cut...series of alcohol solutions, a final exchange with xylene, and paraffin embedding. The embedded sample was then sectioned to enable subsequent staining

  9. Liver regeneration - The best kept secret: A model of tissue injury response

    Directory of Open Access Journals (Sweden)

    Javier A. Cienfuegos

    2014-03-01

    Full Text Available Liver regeneration (LR is one of the most amazing tissue injury response. Given its therapeutic significance has been deeply studied in the last decades. LR is an extraordinary complex process, strictly regulated, which accomplishes the characteristics of the most evolutionary biologic systems (robustness and explains the difficulties of reshaping it with therapeutic goals. TH reproduces the physiological tissue damage response pattern, with a first phase of priming of the hepatocytes -cell-cycle transition G0-G1-, and a second phase of proliferation -cell-cycle S/M phases- which ends with the liver mass recovering. This process has been related with the tissue injury response regulators as: complement system, platelets, inflammatory cytokines (TNF-α, IL-1β, IL-6, growth factors (HGF, EGF, VGF and anti-inflammatory factors (IL-10, TGF-β. Given its complexity and strict regulation, illustrates the unique alternative to liver failure is liver transplantation. The recent induced pluripotential cells (iPS description and the mesenchymal stem cell (CD133+ plastic capability have aroused new prospects in the cellular therapy field. Those works have assured the cooperation between mesenchymal and epithelial cells. Herein, we review the physiologic mechanisms of liver regeneration.

  10. Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats.

    Science.gov (United States)

    Yüce, Abdurrauf; Ateşşahin, Ahmet; Ceribaşi, Ali Osman; Aksakal, Mesut

    2007-11-01

    Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity, and several studies suggest that supplemental antioxidants can reduce cisplatin-induced hepatotoxicity. The present study was designed to determine the effects on the liver and heart oxidant/antioxidant system and the possible protective effects of ellagic acid on liver and heart toxicity induced by cisplatin. The control group received 0.9% saline; animals in the ellagic acid group received only ellagic acid (10 mg/kg); animals in the cisplatin group received only cisplatin (7 mg/kg); animals in cisplatin + ellagic acid group received ellagic acid for 10 days after cisplatin. The rats were killed at the end of the treatment period. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione-peroxidase (GSH-Px) and catalase (CAT) activities were determined in liver and heart tissue. While administration of cisplatin increased the MDA levels in liver and heart tissues, it decreased the GSH, GSH-Px and CAT in these samples when compared to the control group. The administration of ellagic acid to cisplatin-treated rats decreased the MDA levels, and increased GSH, GSH-Px and CAT in these samples. Cisplatin caused marked damages in the histopathological status of liver and heart tissues. These damages were ameliorated by ellagic acid administration. In conclusion, ellagic acid may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters.

  11. Detection of Helicobacter species in liver and stomach tissues of patients with chronic liver diseases using polymerase chain reaction-denaturing gradient gel electrophoresis and immunohistochemistry.

    Science.gov (United States)

    Stalke, Piotr; Al-Soud, Waleed Abu; Bielawski, Krzysztof P; Bakowska, Alicja; Trocha, Hanna; Stepinski, Jan; Wadström, Torkel

    2005-09-01

    Helicobacter DNA has been detected in the hepatobiliary tree of patients with chronic liver diseases (CLD). The presence of H. pylori in the stomach compared with in the liver of the same patients with CLD has not been studied, therefore to the aim of this study was to investigate the presence of Helicobacter DNA and antigens in the liver and stomach of Polish patients with chronic liver diseases using molecular and immunological methods. Gastric mucosa and liver tissue samples and sera were collected from 97 Polish patients with CLD. Anti-H. pylori antibodies were detected by enzyme immunoassay (EIA), and H. pylori-like antigens detected by immunohistochemistry. Helicobacter DNA was detected in stomach and liver samples using a semi-nested Helicobacter genus-specific polymerase chain reaction (PCR) assay, and Helicobacter species identified by denaturing gradient gel electrophoresis (DGGE) and sequencing analysis of amplified PCR products. H. pylori was identified by DGGE and sequence analysis in 60/62 (97%) and 25/25 (100%) of the gastric and liver Helicobacter genus-positive samples, respectively, whereas DNA of H. heilmannii was detected in 2/62 (3%) of the Helicobacter genus-positive gastric samples. H. pylori cagA gene was detected in 23/62 (36%) and 3/25 (12%) gastric and liver tissue samples, respectively. H. pylori-like antigens were detected in 61/97 (63%) gastric mucosa and in 40/97 (41%) liver tissue samples. H. pylori-like organisms appeared to dominate the gastric mucosa and liver tissue of Polish patients with CLD. The prevalence of the cagA gene was higher in stomach compared with liver samples, which suggests a possible role of cagA negative H. pylori-like organisms in CLD. On the other hand, no significant correlation was found between the presence of H. pylori-like DNA and antigens in the liver and liver function tests.

  12. Optical spectroscopy for differentiation of liver tissue under distinct stages of fibrosis: an ex vivo study

    Science.gov (United States)

    Fabila, D. A.; Hernández, L. F.; de la Rosa, J.; Stolik, S.; Arroyo-Camarena, U. D.; López-Vancell, M. D.; Escobedo, G.

    2013-11-01

    Liver fibrosis is the decisive step towards the development of cirrhosis; its early detection affects crucially the diagnosis of liver disease, its prognosis and therapeutic decision making. Nowadays, several techniques are employed to this task. However, they have the limitation in estimating different stages of the pathology. In this paper we present a preliminary study to evaluate if optical spectroscopy can be employed as an auxiliary tool of diagnosis of biopsies of human liver tissue to differentiate the fibrosis stages. Ex vivo fluorescence and diffuse reflectance spectra were acquired from biopsies using a portable fiber-optic system. Empirical discrimination algorithms based on fluorescence intensity ratio at 500 nm and 680 nm as well as diffuse reflectance intensity at 650 nm were developed. Sensitivity and specificity of around 80% and 85% were respectively achieved. The obtained results show that combined use of fluorescence and diffuse reflectance spectroscopy could represent a novel and useful tool in the early evaluation of liver fibrosis.

  13. Exposure to industrial wideband noise increases connective tissue in the rat liver

    Directory of Open Access Journals (Sweden)

    Maria João R Oliveira

    2012-01-01

    Full Text Available Rats were daily exposed (eight hours/day for a period of four weeks to the same high-intensity wideband noise that was recorded before in a large textile plant. Histologic observation of liver sections of the rats was used to perform quantitative comparison of hepatic connective tissue (dyed by Masson trichromic staining between the noise-exposed and control animals. For that, we have photographed at random centrolobular areas of stained rat liver sections. We found that noise exposure resulted in significant enhancement in the area of collagen-rich connective tissue present in the centrolobular domain of the rat liver. Our data strengthen previous evidence showing that fibrotic transformation is a systemic effect of chronic exposure of rodents and humans to industrial wideband noise.

  14. Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury

    Directory of Open Access Journals (Sweden)

    Eva Koellensperger

    2013-01-01

    Full Text Available In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20. Injection of cell culture medium performed in group 2 (n = 20 served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017, total protein (P < 0.031, glutamic oxaloacetic transaminase (P < 0.001, and lactate dehydrogenase (P < 0.04 levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

  15. The alterations in the extracellular matrix composition guide the repair of damaged liver tissue.

    Science.gov (United States)

    Klaas, Mariliis; Kangur, Triin; Viil, Janeli; Mäemets-Allas, Kristina; Minajeva, Ave; Vadi, Krista; Antsov, Mikk; Lapidus, Natalia; Järvekülg, Martin; Jaks, Viljar

    2016-06-06

    While the cellular mechanisms of liver regeneration have been thoroughly studied, the role of extracellular matrix (ECM) in liver regeneration is still poorly understood. We utilized a proteomics-based approach to identify the shifts in ECM composition after CCl4 or DDC treatment and studied their effect on the proliferation of liver cells by combining biophysical and cell culture methods. We identified notable alterations in the ECM structural components (eg collagens I, IV, V, fibronectin, elastin) as well as in non-structural proteins (eg olfactomedin-4, thrombospondin-4, armadillo repeat-containing x-linked protein 2 (Armcx2)). Comparable alterations in ECM composition were seen in damaged human livers. The increase in collagen content and decrease in elastic fibers resulted in rearrangement and increased stiffness of damaged liver ECM. Interestingly, the alterations in ECM components were nonhomogenous and differed between periportal and pericentral areas and thus our experiments demonstrated the differential ability of selected ECM components to regulate the proliferation of hepatocytes and biliary cells. We define for the first time the alterations in the ECM composition of livers recovering from damage and present functional evidence for a coordinated ECM remodelling that ensures an efficient restoration of liver tissue.

  16. Effects of octenidine HCl on liver tissue: could it be an alternative scolicidal for Hidatid disease?

    Science.gov (United States)

    Arikan, Yüksel; Akbulut, Gökhan; Sahin, Dursun Ali; Dilek, Fatma Hüsniye; Saykol, Volkan; Dilek, Osman Nuri

    2007-06-01

    Octenidine HCl is new topical antiseptic solution for wounds and abdominal washing that has been found to be highly effective for inactivating scolices in an in vitro study. However, the effects of octenidine HCl on the liver are not yet known. The aim of this study was to determine if there are any histopathologic changes after injecting octenidine HCl into the liver. A group of 50 male Sprague-Dawley rats were included in the study and randomly divided into five groups of 10 rats each, as follows: sham group; 0.09% NaCl group; 20% NaCl group; undiluted octenidine HCl group; 1% octenidine HCl group. The scolicidal agents (0.3 ml) were directly injected into the left lobe of the liver (except in the sham group). At 3 and 7 days after the injection, the rats were sacrificed, and the left lobe of the liver was harvested. Liver tissue was scored for degree of necrosis and the diameter of the necrosis examined under light microscopy. The highest scores were found in the undiluted octenidine HCl group, although a similar effect was observed in the 20% NaCl group. There was no necrosis in the sham group, the 0.09% NaCl group, or the 1% octenidine HCl group. All of the injury was coagulation-type necrosis. No mortality was observed throughout the study. The 1% octenidine HCl solution could thus be used as a scolicidal agent in liver tissue, whereas the undiluted form of octenidine and 20% NaCl solutions were shown to cause necrosis when directly injected into liver tissue in our animal model.

  17. Micronucleus test in rodent tissues other than liver or erythrocytes: Report of the IWGT working group.

    Science.gov (United States)

    Uno, Yoshifumi; Morita, Takeshi; Luijten, Mirjam; Beevers, Carol; Hamada, Shuichi; Itoh, Satoru; Ohyama, Wakako; Takasawa, Hironao

    2015-05-01

    At the 6th International Workshop on Genotoxicity Testing, the liver micronucleus test (MNT) working group briefly discussed the MNT using tissues other than liver/erythrocytes. Many tissues other than liver/erythrocytes have been studied, primarily for research purposes. They have included the colon and intestinal epithelium, skin, spleen, lung, stomach, bladder, buccal mucosa, vagina, and fetal/neonatal tissues. These tissues were chosen because they were target sites of carcinogens, and/or relevant to a specific route of exposure. Recently, there has been particular focus on the gastrointestinal (GI) tract as it is a contact site associated with high exposure following oral gavage. Furthermore GI tumors are observed with high frequency in human populations. A collaborative study of the rat glandular stomach and colon MNT was conducted in conjunction with a collaborative study of the repeated-dose liver MNT. Based on limited data currently available, the rodent MNT using the glandular stomach and/or colon seems to detect genotoxic carcinogens with GI tract target-organ specificity. The working group concluded that the GI tract MNT would be a promising method to examine clastogenicity or aneugenicity of test chemicals in the stomach and/or colon. Further data will be needed to fully establish the methods, and to identify the sensitivity and specificity of the GI tract MNT.

  18. Polychlorinated biphenyls in adipose tissue, liver, and brain from nine stillborns of varying gestational ages

    NARCIS (Netherlands)

    Huisman, M; Muskiet, FAJ; Van Der Paauw, CG; Essed, CE; Boersma, ER

    1998-01-01

    We analyzed polychlorinated biphenyls (PCBs) in s.c. adipose tissue, liver, and brain of nine fetuses who died in utero. Their median (range) gestational ages and birth weights were 34 (17-40) wk and 2050 (162-3225) g. Three fetuses were small for gestational age. The levels of PCB congener nos. 118

  19. Predominant expression of Th1-type cytokines in primary hepatic cancer and adjacent liver tissues

    Institute of Scientific and Technical Information of China (English)

    Fa-Bo Qiu; Li-Qun Wu; Yun Lu; Shun Zhang; Bing-Yuan Zhang

    2007-01-01

    BACKGROUND: Research has revealed a shift towards Th2 in many types of malignant tumor, but the state of Th1/Th2 is not clear in patients with primary hepatic cancer (PHC). This study was designed to determine the expression of Th1-versus Th2-type cytokines in primary hepatic cancer and the adjacent liver tissue in order to provide evidence for treatment of the Th1/Th2 shift. METHODS:Samples were collected from 11 patients with PHC. The gene expression of Th1/Th2 cytokines was detected by reverse transcriptase polymerase chain reaction (RT-PCR) using IFN-γ and IL-2 as Th1-type cytokine genes, and IL-4 and IL-10 as Th2-type cytokine genes. RESULTS: Th1-type cytokines were expressed in 7/11 PHCs and 9/11 adjacent liver tissues, while Th0 type cytokines occurred in 4/11 PHCs and 2/11 adjacent liver tissues. CONCLUSION: Th1-type cytokines are expressed predominantly in primary hepatic cancer and the adjacent liver tissue.

  20. In vivo quantification of motion in liver parenchyma and its application in shistosomiasis tissue characterization

    Science.gov (United States)

    Badawi, Ahmed M.; Hashem, Ahmed M.; Youssef, Abou-Bakr M.; Abdel-Wahab, Mohamed F.

    1995-03-01

    Schistosomiasis is a major problem in Egypt, despite an active control program it is estimated to exist in about 1/3 of the population. Deposition of less functioning fibrous tissues in the liver is the major contributory factor to the hepatic pathology. Fibrous tissues consist of a complex array of connective matrix material and a variety of collagen isotopes. As a result of an increased stromal density (collagen content), the parenchyma became more ectogenic and less elastic (hard). In this study we investigated the effect of cardiac mechanical impulses from the heart and aorta on the kinetics of the liver parenchyma. Under conditions of controlled patient movements and suspended respiration, a 30 frame per second of 588 X 512 ultrasound images (cineloop, 32 pels per cm) are captured from an aTL ultrasound machine then digitized. The image acquisition is triggered by the R wave of the ECG of the patient. The motion that has a forced oscillation form in the liver parenchyma is quantified by tracking of small box (20 - 30 pels) in 16 directions for all the successive 30 frames. The tracking was done using block matching techniques (the max correlation between boxes in time, frequency domains, and the minimum SAD (sum absolute difference) between boxes). The motion is quantified for many regions at different positions within the liver parenchyma for 80 cases of variable degrees of schisto., cirrhotic livers, and for normal livers. The velocity of the tissue is calculated from the displacement (quantified motion), time between frames, and the scan time for the ultrasound scanner. We found that the motion in liver parenchyma is small in the order of very few millimeters, and the attenuation of the mechanical wave for one ECG cycle is higher in the schisto. and cirrhotic livers than in the normal ones. Finally quantification of motion in liver parenchyma due to cardiac impulses under controlled limb movement and respiration may be of value in the characterization of

  1. Finite element modeling of cooled-tip probe radiofrequency ablation processes in liver tissue.

    Science.gov (United States)

    Barauskas, Rimantas; Gulbinas, Antanas; Vanagas, Tomas; Barauskas, Giedrius

    2008-06-01

    Finite element model of radiofrequency ablation (RFA) with cooled-tip probe in liver has been developed by employing COMSOL Multiphysics software. It describes coupled electric, thermal and sodium chloride solution infiltration flow phenomena taking place during ablation processes. Features of hydraulic capacity, saturation of the tissue by infiltration, and dependency of electrical conductivity on the damage integral of the tissue have been supplied to the model. RFA experiments have validated the model. Physical parameters describing hydraulic capacity and hydraulic conductivity in the tissue, as well as, the relation of electrical conductivity against the value of damage integral have been determined.

  2. Histopathological changes in the gill and liver tissues of freshwater fish, Cirrhinus mrigala exposed to dichlorvos

    Directory of Open Access Journals (Sweden)

    Babu Velmurugan

    2009-10-01

    Full Text Available The histopathological effects of dichlorvos, an organophosphate pesticide, on the gill and liver tissues in Cirrhinus mrigala were determined by light microscopy. The fishes were exposed to sublethal concentrations (0.91 and 1.82 ppm of dichlorvos for 10 days with parallel untreated control. No histopathological effects were observed in control group. Hyperplasia, desquamation, and necrosis of epithelial, epithelial lifting, oedema, lamellar fusion, collapsed secondary lamellae, curling of secondary lamellae and aneurism in the secondary lamellae were observed in gill tissues exposed to dichlorvos. Hepatic lesions in the liver tissues of fishes exposed to dichlorvos were characterized by cloudy swelling of hepatocytes, congestion, vacuolar degeneration, karyolysis, karyohexis, dilation of sinusoids and nuclear hypertrophy.

  3. Ductular proliferation in liver tissues with severe chronic hepatitis B: An immunohistochemical study

    Institute of Scientific and Technical Information of China (English)

    Yao-Kai Chen; Xu-Xia Zhao; Jun-Gang Li; Song Lang; Yu-Ming Wang

    2006-01-01

    AIM: To clarify the pathogenesis of ductular proliferation and its possible association with oval cell activation and hepatocyte regeneration.METHODS: Immunohistochemical staining and image analysis of the ductular structures in the liver tissues from 11 patients with severe chronic hepatitis B and 2healthy individuals were performed. The liver specimens were sectioned serially, and then cytokeratin 8 (CK8),CK19, OV6, proliferating cell nuclear antigens (PCNA),glutathione-S-transferase (GST), o-fetal protein (AFP)and albumin were stained immunohistochemically.RESULTS: Typical and atypical types of ductular proliferation were observed in the portal tracts of the liver tissues in all 11 patients. The proliferating ductular cells were positive for CK8, CK19, OV6 and PCNA staining.Some atypical ductular cells displayed the morphological and immunohistochemical characteristics of hepatic oval cells. Some small hepatocyte-like cells were between hepatic oval cells and mature hepatocytes morphometrically and immunohistochemically.CONCLUSION: The proliferating ductules in the liver of patients with severe chronic liver disease may have different origins. Some atypical ductular cells are actually activated hepatic oval cells. Atypical ductular proliferation is related to hepatocyte regeneration and small hepatocyte-like cells may be intermediate transient cells between hepatic oval cells and mature hepatocytes.

  4. Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

    Energy Technology Data Exchange (ETDEWEB)

    Lanza-Jacoby, S.; Tabares, A. (Jefferson Medical College, Philadelphia, PA (USA))

    1990-04-01

    The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of (2-3H)glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.

  5. Comparison of Different Double Immunostaining Protocols for Paraffin Embedded Liver Tissue

    Directory of Open Access Journals (Sweden)

    Alexander Schütz

    1999-01-01

    Full Text Available Most of the double immunostaining protocols that have been introduced so far have been developed for application on fresh frozen material or based on different species antibodies. In liver tissue, general problems of double immunostaining techniques are further complicated by tissue‐specific difficulties, such as necrosis or high intracellular protein content. To assess a reliable double immunostaining protocol for archived, paraffin embedded liver tissue, different protocols based on the use of same species primary antibodies were evaluated in terms of sensitivity, specificity and non‐specific background staining in pathological liver specimens. We compared peroxidase–anti‐peroxidase, alkaline phosphatase–anti‐alkaline phosphatase (PAP/APAP, labelled‐avidin–biotin (LAB/LAB and digoxigenin–anti‐digoxigenin (dig–a‐dig/PAP techniques using different cytokeratin antibodies and an antibody against PCNA. Comparison of the double immunostaining techniques revealed a high sensitivity and specificity in all procedures. Sections, which were stained employing PAP/APAP‐technique, displayed a higher background staining compared to sections which were treated with the LAB/LAB or dig–a‐dig/PAP protocol. In contrast to the dig–a‐dig/PAP protocol, the LAB/LAB technique provides a better time/cost relationship. Therefore, we would like to recommend a modified LAB/LAB protocol for simultaneous detection of different antigens in archived liver tissue.

  6. TISSUE HARMONIC IMAGING IN DIFFERENTIATING HEPATOCELLULAR CARCINOMA, LIVER METASTASIS AND HEMANGIOMA

    Institute of Scientific and Technical Information of China (English)

    赵玉珍; 翟栋材; 纪晓惠

    2003-01-01

    To explore the role of tissue harmonic imaging(THI) in differentiating hepatocellular carcinoma (HCC), liver metastasis and hemangioma.Methods TOSHIBA SSA-370A ultrasonic system with a 3-to 6-MHz convex transducer (PMV-375AT) was utilized for the study.68 patients(30 cases of HCC, 14 liver metastasis, 24 cases of hemangioma) were examined with fundamental imaging(FI) and tissue harmonic imaging ( THI). Signal-to-noise ratio (SNR), tissue structure parameter:coefficient of variation(CTV) and specific coefficient of variation(CTVs) were calculated, then the tendency of each parameter in every group was evaluated.Results CTV and CTVs within group had no difference, but those between the groups had significant difference(P<0. 05). As a good parameter, CTVs could correctly discriminate HCC, liver metastasis and hemangioma in three groups. It showed that the value of SNR was the highest in hemangioma and the lowest in liver metastasis, and it showed the tendency of increment of the value with a decreased frequ

  7. Expression of tissue inhibitor of matrix metalloproteinase-1 in aging of transgenic mouse liver

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is related to the aging of many organs, but few data are available on the change of TIMP-1 in liver aging. The purpose of this study was to investigate the expression and role of TIMP-1, matrix metalloproteinase-2 (MMP-2) and MMP-9 in the process of natural aging in the livers of normal and transgenic mice, and to detect the effects of TIMP-1 on oxidative level and anti-oxidative ability of the livers of transgenic young mice.Methods Normal and transgenic mice were divided into 3 groups according to their age: 3-month-old group (n=5), 12-month-old group (n=5) and 24-month-old group (n=5). Histopathological changes of the liver were observed after HE and Masson staining. The messenger RNA (mRNA) levels of TIMP-1, MMP-2 and MMP-9 were determined by semi-quantitative reverse transcriptional polymerase chain reaction; protein expression was measured by Western blot in the livers of normal and transgenic mice of various ages. Changes in levels of superoxide dismutase (SOD), monoamine oxidase (MAO), malondialdehyde (MDA) as well as oxidative and anti-oxidative ability were measured.Results Histologically, more fatty degeneration and collagen deposition were found in the aging livers of transgenic mice than in those of the normal mice as their age of months increased. The mRNA and protein expressions of TIMP-1 were significantly high in the oldest animals. The histopathological changes, mRNA and protein expressions of TIMP-1 increased significantly in the liver of transgenic mice as compared with normal mice. The expression of MMP-2 and MMP-9 showed a minor change in the process of aging. Liver change and collagen deposition were not observed in young mice, but the activity of SOD decreased (P<0.05), and the activity of MAO (P<0.01) and the content of MDA increased in the liver of transgenic mice (P<0.01).Conclusions The expression of TIMP-1 is significantly high in the liver of transgenic mouse in the

  8. Obstructive jaundice leads to accumulation of oxidized low density lipoprotein in human liver tissue

    Institute of Scientific and Technical Information of China (English)

    Mustafa Comert; Yucel Ustundag; Ishak Ozel Tekin; Banu Dogan Gun; Figen Barut

    2006-01-01

    Oxidized low density lipoprotein (ox-LDL) molecule is one of the most important modified lipoproteins produced during the oxidative stress. Modified lipoproteins have been defined as being part of the immune inflammatory mechanisms in association with oxidant stress. We have reported the accumulation of ox-LDL in Balb/c mice liver after bile duct ligation previously. Here, we investigated this finding in human beings with obstructive jaundice.Our study demonstrates that obstructive jaundice results in tremendous accumulation of ox-LDL in the liver tissue of patients.

  9. Effects of mild calorie restriction on lipid metabolism and inflammation in liver and adipose tissue.

    Science.gov (United States)

    Park, Chan Yoon; Park, Soyoung; Kim, Min Soo; Kim, Hye-Kyeong; Han, Sung Nim

    2017-08-26

    Calorie restriction (CR) has been reported to improve lipid metabolism and to decrease inflammatory diseases. However, most existing CR models use 30-50% calorie reduction, which is hard to achieve in humans. We investigated the effects of mild CR on lipid metabolism and inflammatory responses. Male C57BL/6 mice were fed control diet (10% kcal fat, Control) or high fat diet (60% kcal fat, HFD) ad libitum or reduced amount of control diet to achieve 15% CR for 16 wks. Body weights, white adipose tissue weights, liver triacylglycerol levels, and serum fetuin-A levels were lower in CR than in the Control. Serum adiponectin levels were higher in CR and lower in HFD compared with the Control. Liver and adipose tissue Mcp-1 mRNA levels were significantly lower in CR compared with the Control. Adipose tissue mRNA levels of Mcp-1, Il-6, Tnf-α and Socs3 were significantly higher in HFD than in the Control and CR, and levels of these negatively correlated with serum adiponectin levels. CR group had the lowest leptin levels and the highest liver Lepr expression, and Lepr mRNA levels positively correlated with liver Socs3 mRNA levels. Our findings showed that mild CR lowered adiposity which resulted in higher adiponectin and lower fetuin-A levels, and might have contributed to alleviation of inflammatory status in the liver and adipose tissue. Furthermore, mild CR might have affected leptin sensitivity by up-regulating Lepr expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Evaluation of 2-year-old intrasplenic fetal liver tissue transplants in rats.

    Science.gov (United States)

    Lupp, Amelie; Danz, Manfred; Müller, Dieter

    2003-01-01

    Liver cell transplantation into host organs like the spleen may possibly provide a temporary relief after extensive liver resection or severe liver disease or may enable treatment of an enzyme deficiency. With time, however, dedifferentiation or malignant transformation of the ectopically transplanted cells may be possible. Thus, in the present study syngenic fetal liver tissue suspensions were transplanted into the spleen of adult male rats and evaluated 2 years thereafter in comparison to orthotopic livers for histopathological changes and (as markers for preneoplastic transformation) for cytochrome P450 (P450) and glutathione S-transferase (GST) isoform expression. Because inducibility of P450 and GST isoforms may be changed in preneoplastic foci, prior to sacrifice animals were additionally treated either with beta-naphthoflavone, phenobarbital, dexamethasone, or the respective solvent. In the 2-year-old grafts more than 70% of the spleen mass was occupied by the transplant. The transplanted hepatocytes were arranged in cord-like structures. Also few bile ducts were present. Morphologically, no signs of malignancy were visible. With all rats, transplant recipients as well as controls, however, discrete nodular structures were seen in the livers. Due to age, both livers and transplants displayed only a low P450 2B1 and 3A2 and GST class alpha and mu isoform expression. No immunostaining for P450 1A1 was visible. At both sites, beta-naphthoflavone, phenobarbital, or dexamethasone treatment enhanced P450 1A1, P450 2B1 and 3A2, or P450 3A2 expression, respectively. No immunostaining for GST class pi isoforms was seen in the transplants. The livers of both transplant recipients and control rats, however, displayed GST pi-positive foci, corresponding to the nodular structures seen histomorphologically. Compared to the surrounding tissue, these foci also exhibited a more pronounced staining for GST class alpha and mu isoforms and a stronger inducibility of the P450 1A

  11. Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics.

    Science.gov (United States)

    Perepelyuk, Maryna; Chin, LiKang; Cao, Xuan; van Oosten, Anne; Shenoy, Vivek B; Janmey, Paul A; Wells, Rebecca G

    2016-01-01

    Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G' and G" and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver.

  12. Molecular characterization, tissue expression, and polymorphism analysis of liver-type fatty acid binding protein in Landes geese.

    Science.gov (United States)

    Song, Z; Shao, D; Sun, X X; Niu, J W; Gong, D Q

    2015-01-01

    Liver weight is an important economic trait in the fatty goose liver industry. Liver-type fatty acid binding protein (L-FABP) is involved in the formation and metabolism of fatty acids. Thus, we hypothesized that sequence polymorphisms in L-FABP were associated with fatty liver weight in goose. We first isolated, sequenced, and characterized the goose L-FABP gene, which had not been previously reported. The goose L-FABP gene was 2490 bp and included 4 exons coding for a 126-amino acid protein. Analysis of expression levels of the goose L-FABP gene in different tissues showed that the expression level in the liver tissue was higher than in other tissues, and was significantly higher in the liver tissue of overfed geese than in control geese. Moreover, a single nucleotide polymorphism located at 774 bp in the gene was identified in a Landes goose population. To test whether this single nucleotide polymorphism was associated with fatty liver production, liver weight and the ratio of liver to carcass weights were determined for the 3 genotypes with this single nucleotide polymorphism (TT, TG, GG) in overfed Landes geese. Our data indicate that individuals with the GG genotype had higher values for the variables measured than those with the other 2 genotypes, suggesting that L-FABP can be a selection marker for the trait of fatty liver production in goose.

  13. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs.

    Science.gov (United States)

    Tous, N; Theil, P K; Lauridsen, C; Lizardo, R; Vilà, B; Esteve-Garcia, E

    2012-12-01

    The aim of this study was to investigate underlying mechanisms of dietary conjugated linoleic acid (CLA) on lipid metabolism in various tissues of pigs. Sixteen gilts (73 ± 3 kg) were fed a control (containing sunflower oil) or an experimental diet in which 4% of sunflower oil was replaced by CLA, and slaughtered at an average BW of 117 ± 4.9 kg. Transcription of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), sterol regulatory element binding protein (SREBP1), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), delta-6-desaturase (D6D), and stearoyl CoA desaturase (SCD) were determined by real-time PCR in longissimus thoracis (LT) and semimembranosus (SM) muscles, LT subcutaneous and SM intermuscular fat, and in the liver. Fatty acid (FA) composition was analyzed using gas chromatography in these tissues, except for SM intermuscular fat. Dietary CLA increased PPARγ in LT muscle (P tissues studied (P muscle and liver (SREBP1, both P muscle and reduced (P muscle and intermuscular fat. Saturated FA were increased in all studied tissues (P tissue-specific way by CLA. It was concluded that dietary CLA affected transcription of genes and fat metabolism in a tissue-specific manner.

  14. Glutathione protects liver and kidney tissue from cadmium- and lead-provoked lipid peroxidation

    Directory of Open Access Journals (Sweden)

    Jovanović Jasmina M.

    2013-01-01

    Full Text Available Cd and Pb represent a serious ecological problem due to their soluble nature, their mobility and ability to accumulate in the soil. The exposure to these heavy metals can originate from different sources (drinking water, food, air, and they can make their way into the human body through the respiratory and digestive system. We investigated the effects of glutathione on Cd and Pb accumulation and lipid peroxidation effects in the liver and kidneys of heavy metal intoxicated rats. The content of the marker of lipid peroxidation - malondialdehyde was increased several fold the in tissues of exposed animals, the effects being more pronounced in liver. The treatment of intoxicated animals with glutathione drastically suppressed lipid peroxidation. Our results imply that the application of glutathione may have protective role in heavy metal intoxication by inhibiting lipid peroxidation. However, precaution should be made when it comes to Cd, since it seems that glutathione promoted Cd accumulation in the liver.

  15. A rare condition: Ectopic liver tissue with its unique blood supply encountered during laparoscopic cholecystectomy

    Science.gov (United States)

    Bal, Ahmet; Yilmaz, Sezgin; Yavas, Betul Demirciler; Ozdemir, Cigdem; Ozsoy, Mustafa; Akici, Murat; Kalkan, Mustafa; Ersen, Ogun; Saripinar, Baris; Arikan, Yuksel

    2015-01-01

    Introduction Developmental abnormalities of liver including ectopic liver tissue (ELT) are rare conditions. Few cases presenting ELT have been reported in literature till now. Even though the most common area seen is gallbladder, it is detected both abdominal and thoracic sites. There is a relationship between HCC and ectopic liver that necessitates the removal. Presentation of case A 51-year-old female was hospitalized because of abdominal pain. Gallstone and bile duct dilatation were determined during ultrasonographic (USG) evaluation. The patient was operated for cholecystectomy following a successful endoscopic retrograde cholangiopancreatography (ERCP). During operation, a mass located on gallbladder with its unique vascular support was identified and resected together with gallbladder. The mass had a separate vascular stalk arising from liver parenchyma substance and it was clipped with laparoscopic staples. The histopathological examination revealed that the mass adherent to gallbladder was ectopic liver confirming the intraoperative observation. The postoperative course of patient was uneventfull and she was discharged at the second day after the operation. Discussion Ectopic liver tissue is incidentally found both in abdominal and thoracic cavity. ELT can rarely be diagnosed before surgical procedures or autopsies. It can be overlooked easily by radiological techniques. Although it does not usually produce any symptom clinically, it can rarely result in serious complications such as bleeding, pyloric and portal vein obstruction. ELT also has the capacity of malignant transformation to hepatocellular carcinoma that makes it essential to be removed. Conclusion Although ELT is rarely seen, it should be removed when recognized in order to prevent the complications and malignant transformation. PMID:25723748

  16. Histological Changes in the Lung and Liver Tissues in Mice Exposed to Pyrethroid Inhalation

    Directory of Open Access Journals (Sweden)

    Nadeem SHEIKH

    2013-12-01

    Full Text Available Cypermethrin, a type II pyrethroid, is one of the most widely used insecticides in Pakistan. It is considered to be a safe pesticide; however, the possible health hazards of this pyrethroid have been ignored. Cypermethrin may become an air pollutant and adversely affect the health of non-target organisms, leading to acute or chronic disorders. The present work aims to investigate the effects of cypermethrin on lung and liver tissues due to inhalation exposure. The study is performed on 16 mature Swiss albino mice, including controls. The animals are divided into 4 groups (4 mice each and exposed to 0.5 % dilution of cypermethrin in an inhalation chamber (40×35×25 cm3 for different time periods, whereas control animals are not exposed to any insecticide. The histopathological changes in lungs and liver tissues reveal that cypermethrin exposure induces time dependent changes in the liver and in the lungs. It damages the normal organization of liver tissues, causing liver injury due to necrosis, significant decrease in number of cells, and widening of sinusoids and fibrosis. Inhalation exposure of cypermethrin results in significant hyperplasia, clumping of cells and necrosis in the lungs. It also induces pulmonary edema, alveolitis, and pulmonary fibrosis by the deposition of collagen. Taking these findings together, it may be concluded that cypermethrin and other pyrethroids cause hazardous effects in non-target organisms through inhalation exposure. Serious efforts and awareness are required to monitor and reduce the insecticide induced health hazards in third world countries.doi:10.14456/WJST.2014.67

  17. Adipose tissue supports normalization of macrophage and liver lipid handling in obesity reversal.

    Science.gov (United States)

    Vatarescu, Maayan; Bechor, Sapir; Haim, Yulia; Pecht, Tal; Tarnovscki, Tanya; Slutsky, Noa; Nov, Ori; Shapiro, Hagit; Shemesh, Avishai; Porgador, Angel; Bashan, Nava; Rudich, Assaf

    2017-06-01

    Adipose tissue inflammation and dysfunction are considered central in the pathogenesis of obesity-related dysmetabolism, but their role in the rapid metabolic recovery upon obesity reversal is less well defined. We hypothesized that changes in adipose tissue endocrine and paracrine mechanisms may support the rapid improvement of obesity-induced impairment in cellular lipid handling. C57Bl-6J mice were fed ad libitum either normal chow (NC) or high-fat diet (HFF) for 10 weeks. A dietary obesity reversal group was fed HFF for 8 weeks and then switched to NC for 2 weeks (HFF→NC). Whole-body glucose homeostasis rapidly nearly normalized in the HFF→NC mice (fasting glucose and insulin fully normalized, glucose and insulin tolerance tests reversed 82% to the NC group levels). During 2 weeks of the dietary reversal, the liver was significantly cleared from ectopic fat, and functionally, glucose production from pyruvate, alanine or fructose was normalized. In contrast, adipose tissue inflammation (macrophage infiltration and polarization) largely remained as in HFF, though obesity-induced adipose tissue macrophage lipid accumulation decreased by ~50%, and adipose tissue MAP kinase hyperactivation was reversed. Ex vivo, mild changes in adipose tissue adipocytokine secretion profile were noted. These corresponded to partial or full reversal of the excess cellular lipid droplet accumulation induced by HFF adipose tissue conditioned media in hepatoma or macrophage cells, respectively. We propose that early after initiating reversal of nutritional obesity, rapid metabolic normalization largely precedes resolution of adipose tissue inflammation. Nevertheless, we demonstrate a hitherto unrecognized contribution of adipose tissue to the rapid improvement in lipid handling by the liver and by macrophages. © 2017 The authors.

  18. Protective effects of erdosteine on rotenone-induced oxidant injury in liver tissue.

    Science.gov (United States)

    Terzi, Alpaslan; Iraz, Mustafa; Sahin, Semsettin; Ilhan, Atilla; Idiz, Nuri; Fadillioglu, Ersin

    2004-09-01

    Rotenone, an insecticide of botanical origin, causes toxicity through inhibition of complex I of the respiratory chain in mitochondria. This study was undertaken to determine whether rotenone-induced liver oxidant injury is prevented by erdosteine, a mucolytic agent showing antioxidant properties. There were four groups of Male Wistar Albino rats: group one was untreated as control; the other groups were treated with erdosteine (50 mg/kg per day, orally), rotenone (2.5 mg/mL once and 1 mL/kg per day for 60 days, i.p.) or rotenone plus erdosteine, respectively. Rotenone treatment without erdosteine increased xanthine oxidase (XO) enzyme activity and also increased lipid peroxidation in liver tissue (P erdosteine produced a significant decrease in lipid peroxidation and XO activities in comparison with rotenone group (P Erdosteine treatment with rotenone led to an increase in catalase (CAT) and superoxide dismutase (SOD) activities in comparison with the rotenone group (P erdosteine group, there was a negative correlation between XO activity and NO level in liver tissue (r = -0.833, P erdosteine may be a protective agent for rotenone-induced liver oxidative injury in rats.

  19. Skeletal Muscle Derived IL-6 in Liver and Adipose Tissue Metabolism

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet

    Summary Physical activity can lead to metabolic disease and treatment of several metabolic diseases include exercise training. Skeletal muscle has, due to its central role in glucose and fat metabolism at rest and during exercise been studied in detail with regard to exercise training. The role...... and adipose tissue metabolism is unknown. It has been suggested that myokines, such as IL-6, released from skeletal muscle affects liver and adipose tissue and are involved in the regulation of exercise training adaptations. Thus, the aim of this thesis was to investigate the role of skeletal muscle derived...... indicate that during 1h of exercise the liver utilizes carbohydrates for oxidation rather than gluconeogenesis and that gluconeogenic activity during 1h of exercise is not regulated through increases in protein content. The aim of study III was to investigate the role of skeletal muscle derived IL-6...

  20. Cadmium accumulation in gill, liver, kidney and muscle tissues of common carp, Cyprinus carpio, and Nile tilapia, Oreochromis niloticus.

    Science.gov (United States)

    Yeşilbudak, Burcu; Erdem, Cahit

    2014-05-01

    Accumulation of cadmium in gill, liver, muscle and kidney tissues of Cyprinus carpio and Oreochromis niloticus were investigated in fish exposed to 0.5 ppm cadmium over 1, 15 and 30 days under controlled laboratory conditions. Tissue accumulation of the metal was measured using Atomic Absorption Spectrophotometric techniques. Cadmium accumulation in gill, liver, kidney and muscle, tissues of C. carpio and O. niloticus exposed to metal for 1, 15 and 30 days increased significantly compared with the control group (p muscle tissue of O. niloticus. A general increase was observed in Cd accumulation with increasing exposure periods. Highest metal accumulation was observed in kidney followed by liver, gill and muscle tissues in both species. Liver accumulation of Cd was higher in C. carpio than O. niloticus, whereas kidney accumulation of the metal was higher in O. niloticus than C. carpio.

  1. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues.

    Science.gov (United States)

    Wang, Ye; He, Honghui; Chang, Jintao; He, Chao; Liu, Shaoxiong; Li, Migao; Zeng, Nan; Wu, Jian; Ma, Hui

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health.Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper,we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameter scan provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  2. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues

    Science.gov (United States)

    Wang, Ye; He, Honghui; Chang, Jintao; He, Chao; Liu, Shaoxiong; Li, Migao; Zeng, Nan; Wu, Jian; Ma, Hui

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health. Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper, we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameters can provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  3. Transcriptome difference and potential crosstalk between liver and mammary tissue in mid-lactation primiparous dairy cows

    Science.gov (United States)

    Bu, Dengpan; Bionaz, Massimo; Wang, Mengzhi; Nan, Xuemei; Ma, Lu; Wang, Jiaqi

    2017-01-01

    Liver and mammary gland are among the most important organs during lactation in dairy cows. With the purpose of understanding both the different and the complementary roles and the crosstalk of those two organs during lactation, a transcriptome analysis was performed on liver and mammary tissues of 10 primiparous dairy cows in mid-lactation. The analysis was performed using a 4×44K Bovine Agilent microarray chip. The transcriptome difference between the two tissues was analyzed using SAS JMP Genomics using ANOVA with a false discovery rate correction (FDR). The analysis uncovered >9,000 genes differentially expressed (DEG) between the two tissues with a FDR<0.001. The functional analysis of the DEG uncovered a larger metabolic (especially related to lipid) and inflammatory response capacity in liver compared with mammary tissue while the mammary tissue had a larger protein synthesis and secretion, proliferation/differentiation, signaling, and innate immune system capacity compared with the liver. A plethora of endogenous compounds, cytokines, and transcription factors were estimated to control the DEG between the two tissues. Compared with mammary tissue, the liver transcriptome appeared to be under control of a large array of ligand-dependent nuclear receptors and, among endogenous chemical, fatty acids and bacteria-derived compounds. Compared with liver, the transcriptome of the mammary tissue was potentially under control of a large number of growth factors and miRNA. The in silico crosstalk analysis between the two tissues revealed an overall large communication with a reciprocal control of lipid metabolism, innate immune system adaptation, and proliferation/differentiation. In summary the transcriptome analysis confirmed prior known differences between liver and mammary tissue, especially considering the indication of a larger metabolic activity in liver compared with the mammary tissue and the larger protein synthesis, communication, and proliferative

  4. Rare entity: Ectopic liver tissue in the wall of the gallbladder - A case report

    OpenAIRE

    Arslan, Yusuf; Altintoprak, Fatih; Serin, Kursat R; Kivilcim, Taner; Yalkin, Omer; Ozkan, Orhan V; Celebi, Fehmi

    2014-01-01

    Ectopic liver tissue (ELT) is a rare condition, which is usually not diagnosed preoperatively, but coincidentally during abdominal surgery. While the location of ELT can vary, it is usually localized on the gallbladder wall or in close proximity. ELT is associated with various complications, a major complication being extrahepatic hepatocellular carcinoma. A 59-year-old female underwent elective surgery for chronic cholecystitis with stones. During laparoscopic exploration, a 2-cm-diameter EL...

  5. GATA Transcription Factors in Tissue Homeostasis and Pathology of the Gastrointestinal Tract and Liver

    OpenAIRE

    Haveri, Hanna

    2008-01-01

    Mammalian gastrointestinal tract and liver are self-renewing organs that are able to sustain themselves due to stem cells present in their tissues. In constant, inflammation-related epithelial damage, vigorous activation of stem cells may lead to their uncontrolled proliferation, and further, to cancer. GATA-4, GATA-5, and GATA-6 regulate cell proliferation and differentiation in many mammalian organs. Lack of GATA-4 or GATA-6 leads to defective endodermal development and cell differentiation...

  6. [Effect of lipiodol emulsion and local hyperthermia on hepatic tissue blood flow in rabbits with VX-2 liver tumor].

    Science.gov (United States)

    Suzuki, K; Tada, I; Okada, K; Kim, Y I; Kobayashi, M

    1988-08-01

    The effect of intra-arterial infusion of lipiodol-emulsion and local hyperthermia on tissue blood flow was examined in experimental hepatic tumor and normal liver of rabbits. VX-2 tumor was implanted in liver of rabbit. The tissue blood flow was estimated by hydrogen gas clearance method when the tumor grew to about 2 cm. Tissue blood flow in tumor (64.5 ml/min/100 g) was significantly less than in normal liver (90.8 ml/min/100 g) (p less than 0.005). The intra-arterial infusion of lipiodol-emulsion did not alter the flow in either tissue. However, the addition of hyperthermia induced a substantial rise of tissue blood flow in normal liver (35% increase, from 93.8 to 127 ml/min/100 g) when compared with in VX-2 tumor (8.9% increase, from 65.1 to 71.8 ml/min/100 g). These were accompanied by a selective heating of liver tumor; the tumor temperature rose to 43 degrees C, although that of normal liver remained at 38 degrees C. Our results suggested that a specific temperature rise of liver tumor after infusion of lipiodol-emulsion and local heating might be related to a different response of microcirculation in tumor and normal liver to the hyperthermia.

  7. Elevated levels of G-quadruplex formation in human stomach and liver cancer tissues.

    Science.gov (United States)

    Biffi, Giulia; Tannahill, David; Miller, Jodi; Howat, William J; Balasubramanian, Shankar

    2014-01-01

    Four-stranded G-quadruplex DNA secondary structures have recently been visualized in the nuclei of human cultured cells. Here, we show that BG4, a G-quadruplex-specific antibody, can be used to stain DNA G-quadruplex structures in patient-derived tissues using immunohistochemistry. We observe a significantly elevated number of G-quadruplex-positive nuclei in human cancers of the liver and stomach as compared to background non-neoplastic tissue. Our results suggest that G-quadruplex formation can be detected and measured in patient-derived material and that elevated G-quadruplex formation may be a characteristic of some cancers.

  8. Postpartal subclinical endometritis alters transcriptome profiles in liver and adipose tissue of dairy cows.

    Science.gov (United States)

    Akbar, Haji; Cardoso, Felipe C; Meier, Susanne; Burke, Christopher; McDougall, Scott; Mitchell, Murray; Walker, Caroline; Rodriguez-Zas, Sandra L; Everts, Robin E; Lewin, Harris A; Roche, John R; Loor, Juan J

    2014-01-01

    Transcriptome alterations in liver and adipose tissue of cows with subclinical endometritis (SCE) at 29 d postpartum were evaluated. Bioinformatics analysis was performed using the Dynamic Impact Approach by means of KEGG and DAVID databases. Milk production, blood metabolites (non-esterified fatty acids, magnesium), and disease biomarkers (albumin, aspartate aminotransferase) did not differ greatly between healthy and SCE cows. In liver tissue of cows with SCE, alterations in gene expression revealed an activation of complement and coagulation cascade, steroid hormone biosynthesis, apoptosis, inflammation, oxidative stress, MAPK signaling, and the formation of fibrinogen complex. Bioinformatics analysis also revealed an inhibition of vitamin B3 and B6 metabolism with SCE. In adipose, the most activated pathways by SCE were nicotinate and nicotinamide metabolism, long-chain fatty acid transport, oxidative phosphorylation, inflammation, T cell and B cell receptor signaling, and mTOR signaling. Results indicate that SCE in dairy cattle during early lactation induces molecular alterations in liver and adipose tissue indicative of immune activation and cellular stress.

  9. Effects of Loud Noise on Oxidation and Lipid peroxidation Variations of Liver Tissue of Rabbit

    Directory of Open Access Journals (Sweden)

    Mirzaei Ramazan

    2009-06-01

    Full Text Available Background: In today's world, noise is one of the major physical pollutants. The exact mechanism leading to tissue damage in loud noise is not clear. There are increasing evidences that show damage to cochlear tissue by noise is linked to cell injury induced by free radical species. The aim of this study was to investigate the relationship between change in liver tissue glutathione (anti- oxidant and malondialdehyde (one metabolite of lipid oxidation levels that occur in rabbits which were exposed to continuous loud noise.Materials and Methods: This experimental study was performed on 12 white Newzeland male rabbits in Tarbiat Modarres University in 2004. The rabbits were assigned to the following two groups: control, and exposed to continuous loud noise for 96 hours (8 h/day for 12 days, SPL=110dBA and 250Hz to 20 KHz. The concentration of malondialdehyde (MDA and glutathione (GSH in liver tissue samples were measured in rabbits after exposure to noise. Thiobarbituric acid reacting substance, Ellman's reagent and spectrophotometry techniques were used for this measurement. The data were statically analyzed by SPSS software and 2 groups were compared by t-test. Differences at the level of P<0.05 were considered statistically significant.Results: Comparison of the biochemical parameters of GSH and MDA measured in treated group with control indicated that antioxidant and lipid peroxidants parameters were suppressed in treated group compared to control group (p<0.05.Conclusion: Possible similarities between rabbit and human biological system indicate the possible role of noise in causation of oxidative stress in context with liver tissue impairm

  10. Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver.

    Science.gov (United States)

    Ferreira, Andréa G K; da Cunha, Aline A; Machado, Fernanda R; Pederzolli, Carolina D; Dalazen, Giovana R; de Assis, Adriano M; Lamers, Marcelo L; dos Santos, Marinilce F; Dutra-Filho, Carlos S; Wyse, Angela T S

    2012-01-01

    The present study investigated the effects of chronic hyperprolinemia on oxidative and metabolic status in liver and serum of rats. Wistar rats received daily subcutaneous injections of proline from their 6th to 28th day of life. Twelve hours after the last injection the rats were sacrificed and liver and serum were collected. Results showed that hyperprolinemia induced a significant reduction in total antioxidant potential and thiobarbituric acid-reactive substances. The activities of the antioxidant enzymes catalase and superoxide dismutase were significantly increased after chronic proline administration, while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH, sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the liver revealed that proline treatment induced changes of the hepatic microarchitecture and increased the number of inflammatory cells and the glycogen content. Biochemical determination also demonstrated an increase in glycogen concentration, as well as a higher synthesis of glycogen in liver of hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an increase on glucose oxidation and a decrease on lipid synthesis from glucose. However, hepatic lipid content and serum glucose levels were not changed. Proline administration did not alter the aminotransferases activities and serum markers of hepatic injury. Our findings suggest that hyperprolinemia alters the liver homeostasis possibly by induction of a mild degree of oxidative stress and metabolic changes. The hepatic alterations caused by proline probably do not implicate in substantial hepatic tissue damage, but rather demonstrate a process of adaptation of this tissue to oxidative stress. However, the biological significance of these findings requires additional investigation. Copyright © 2011 Wiley Periodicals, Inc.

  11. [The role of pro- and antioxidant processes in the liver tissue of guinea pigs in pathogenesis of allergic alveolitis].

    Science.gov (United States)

    Shchepans'kyĭ, F I; Reheda, M S

    2005-01-01

    It was shown that allergic alveolitis development is accompanied by increase of superoxyddismutase and catalase activity as well as an increase of dien conjugates and malonic dialdehyde content in Guinea pig liver. The administration of alfa-tokoferol acetate, an antioxidant resulted in decrease of these indices in the liver tissue that testifies its correcting influence upon PLO and antioxidant system processes.

  12. Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse.

    Science.gov (United States)

    Kelly, Daniel M; Akhtar, Samia; Sellers, Donna J; Muraleedharan, Vakkat; Channer, Kevin S; Jones, T Hugh

    2016-11-01

    Testosterone deficiency is commonly associated with obesity, metabolic syndrome, type 2 diabetes and their clinical consequences-hepatic steatosis and atherosclerosis. The testicular feminised mouse (non-functional androgen receptor and low testosterone) develops fatty liver and aortic lipid streaks on a high-fat diet, whereas androgen-replete XY littermate controls do not. Testosterone treatment ameliorates these effects, although the underlying mechanisms remain unknown. We compared the influence of testosterone on the expression of regulatory targets of glucose, cholesterol and lipid metabolism in muscle, liver, abdominal subcutaneous and visceral adipose tissue. Testicular feminised mice displayed significantly reduced GLUT4 in muscle and glycolytic enzymes in muscle, liver and abdominal subcutaneous but not visceral adipose tissue. Lipoprotein lipase required for fatty acid uptake was only reduced in subcutaneous adipose tissue; enzymes of fatty acid synthesis were increased in liver and subcutaneous tissue. Stearoyl-CoA desaturase-1 that catalyses oleic acid synthesis and is associated with insulin resistance was increased in visceral adipose tissue and cholesterol efflux components (ABCA1, apoE) were decreased in subcutaneous and liver tissue. Master regulator nuclear receptors involved in metabolism-Liver X receptor expression was suppressed in all tissues except visceral adipose tissue, whereas PPARγ was lower in abdominal subcutaneous and visceral adipose tissue and PPARα only in abdominal subcutaneous. Testosterone treatment improved the expression (androgen receptor independent) of some targets but not all. These exploratory data suggest that androgen deficiency may reduce the buffering capability for glucose uptake and utilisation in abdominal subcutaneous and muscle and fatty acids in abdominal subcutaneous. This would lead to an overspill and uptake of excess glucose and triglycerides into visceral adipose tissue, liver and arterial walls.

  13. Stem cells for liver tissue repair:Current knowledge and perspectives

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Stem cells from extra- or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated.Therefore,they are being increasingly considered for future applications in liver cell therapy.In that field,liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation,while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures.However,the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype,both in vitro and in vivo.Furthermore,the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures.The present review focuses on the current knowledge of the stern cell potential for liver therapy.We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo.We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated.

  14. The Effects of Pollen on Serum Parameters, and Liver and Kidney Tissues on Rats

    Directory of Open Access Journals (Sweden)

    Güldeniz Selmanoğlu

    2007-01-01

    Full Text Available The objective of this study was to investigate any positive effects or possible side effects of the use of pollen. Mature male rats were fed pollen of three different plant sources (Trifolium spp., Raphanus spp. and Cistus spp. at the rate of 60 mg/animal/day over a periodof 30 days. After treatment, biochemical parameters and serum enzyme activities were analysed and weights of liver and kidney measured. Liver and kidney tissues of rats were examined by light microscope.Serum cholesterol and HDL levels decreased in rats fed on pollen of Trifolium spp. and Cistus spp. Serum glucose levels increased in rats given pollen of Trifolium spp. and Raphanus spp. There was no change in serum enzyme levels in rats of any pollen group.While absolute liver weights of rats fed on pollen of Trifolium spp. and Cistus spp. increased, no change at all in absolute kidney weight and relative weight (organ weight/body weight of liver and kidney of rats was found in any pollen group. Histopathological changes in theliver and kidney of rats given pollen were not observed. Although serum cholesterol and HDL levels decreased, we cannot suggest that pollen caused either adverse or beneficial effects because of the short tretment period of 30 days.

  15. Liver-targeting of interferon-alpha with tissue-specific domain antibodies.

    Science.gov (United States)

    Coulstock, Edward; Sosabowski, Jane; Ovečka, Milan; Prince, Rob; Goodall, Laura; Mudd, Clare; Sepp, Armin; Davies, Marie; Foster, Julie; Burnet, Jerome; Dunlevy, Gráinne; Walker, Adam

    2013-01-01

    Interferon alpha (IFNα) is used for the treatment of hepatitis C infection and whilst efficacious it is associated with multiple adverse events including reduced leukocyte, erythrocyte, and platelet counts, fatigue, and depression. These events are most likely caused by systemic exposure to interferon. We therefore hypothesise that targeting the therapeutic directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. We genetically fused IFN to a domain antibody (dAb) specific to a hepatocyte restricted antigen, asialoglycoprotein receptor (ASGPR). Our results show that the murine IFNα2 homolog (mIFNα2) fused to an ASGPR specific dAb, termed DOM26h-196-61, could be expressed in mammalian tissue culture systems and retains the desirable biophysical properties and activity of both fusion partners when measured in vitro. Furthermore a clear increase in in vivo targeting of the liver by mIFNα2-ASGPR dAb fusion protein, compared to that observed with either unfused mIFNα2 or mIFNα2 fused to an isotype control dAb VHD2 (which does not bind ASGPR) was demonstrated using microSPECT imaging. We suggest that these findings may be applicable in the development of a liver-targeted human IFN molecule with improved safety and patient compliance in comparison to the current standard of care, which could ultimately be used as a treatment for human hepatitis virus infections.

  16. A High Linoleic Acid Diet does not Induce Inflammation in Mouse Liver or Adipose Tissue.

    Science.gov (United States)

    Vaughan, Roger A; Garrison, Richard L; Stamatikos, Alexis D; Kang, Minsung; Cooper, Jamie A; Paton, Chad M

    2015-11-01

    Recently, the pro-inflammatory effects of linoleic acid (LNA) have been re-examined. It is now becoming clear that relatively few studies have adequately assessed the effects of LNA, independent of obesity. The purpose of this work was to compare the effects of several fat-enriched but non-obesigenic diets on inflammation to provide a more accurate assessment of LNA's ability to induce inflammation. Specifically, 8-week-old male C57Bl/6 mice were fed either saturated (SFA), monounsaturated (MUFA), LNA, or alpha-linolenic acid enriched diets (50 % Kcal from fat, 22 % wt/wt) for 4 weeks. Chow and high-fat, hyper-caloric diets were used as negative and positive controls, respectively. Expression of pro-inflammatory and pro-coagulant markers from epididymal fat, liver, and plasma were measured along with food intake and body weights. Mice fed the high SFA, MUFA, and high-fat diets exhibited increased pro-inflammatory markers in liver and adipose tissue; however, mice fed LNA for four weeks did not display significant changes in pro-inflammatory or pro-coagulant markers in epididymal fat, liver, or plasma. The present study demonstrates that LNA alone is insufficient to induce inflammation. Instead, it is more likely that hyper-caloric diets are responsible for diet-induced inflammation possibly due to adipose tissue remodeling.

  17. Inflammation inhibits the expression of phosphoenolpyruvate carboxykinase in liver and adipose tissue.

    Science.gov (United States)

    Feingold, Kenneth R; Moser, Arthur; Shigenaga, Judy K; Grunfeld, Carl

    2012-04-01

    Inhibition of adipocyte triglyceride biosynthesis is required for fatty acid mobilization during inflammation. Triglyceride biosynthesis requires glycerol 3-phosphate and phosphoenolpyruvate carboxykinase (PEPCK) plays a key role. We demonstrate that LPS, zymosan, and TNF-α decrease PEPCK in liver and fat. Turpentine decreases PEPCK in liver, but not in fat. The LPS-induced decrease in PEPCK does not occur in TLR4 deficient animals, indicating that this receptor is required. The LPS-induced decrease in hepatic PEPCK does not occur in TNF receptor/IL-1 receptor knockout mice, but occurs in fat, indicating that TNF-α/IL-1 is essential for the decrease in liver but not fat. In 3T3-L1 adipocytes TNF-α, IL-1, IL-6, and IFNγ inhibit PEPCK indicating that there are multiple pathways by which PEPCK is decreased in adipocytes. The binding of PPARγ and RXRα to the PPARγ response element in the PEPCK promoter is markedly decreased in adipose tissue nuclear extracts from LPS treated animals. Lipopolysaccharide and zymosan reduce PPARγ and RXRα expression in fat, suggesting that a decrease in PPARγ and RXRα accounts for the decrease in PEPCK. Thus, there are multiple cytokine pathways by which inflammation inhibits PEPCK expression in adipose tissue which could contribute to the increased mobilization of fatty acids during inflammation.

  18. Validation of a mathematical model for laser-induced thermotherapy in liver tissue.

    Science.gov (United States)

    Hübner, F; Leithäuser, C; Bazrafshan, B; Siedow, N; Vogl, T J

    2017-08-01

    The purpose of the study was to develop a simulation approach for laser-induced thermotherapy (LITT) that is based on mathematical models for radiation transport, heat transport, and tissue damage. The LITT ablation was applied to ex vivo pig liver tissue. Experiments were repeated with different laser powers, i.e., 22-34 W, and flow rates of the cooling water in the applicator system, i.e., 47-92 ml/min. During the procedure, the temperature was measured in the liver sample at different distances to the applicator as well as in the cooling circuit using a fiber optic thermometer. For validation, the simulation results were compared with the results of the laser ablation experiments in the ex vivo pig liver samples. The simulated and measured temperature curves presented a relatively good agreement. The Bland-Altman plot showed an average of temperature differences of -0.13 (∘)C and 95%-limits-of-agreement of ±7.11 (∘)C. The standard deviation amounted to ±3.63 (∘)C. The accuracy of the developed simulation is comparable with the accuracy of the MR thermometry reported in other clinical studies. The simulation showed a significant potential for the application in treatment planning.

  19. Liver fibrosis and tissue architectural change measurement using fractal-rectified metrics and Hurst's exponent

    Institute of Scientific and Technical Information of China (English)

    Nicola Dioguardi; Fabio Grizzi; Barbara Franceschini; Paola Bossi; Carlo Russo

    2006-01-01

    AIM: To provide the accurate alternative metrical means of monitoring the effects of new antiviral drugs on the reversal of newly formed collagen.METHODS: Digitized histological biopsy sections taken from 209 patients with chronic C virus hepatitis with different grade of fibrosis or cirrhosis, were measured by means of a new, rapid, user-friendly, fully computeraided method based on the international system meter rectified using fractal principles.RESULTS: The following were described: geometric perimeter, area and wrinkledness of fibrosis; the collation of the Knodell, Sheuer, Ishak and METAVIR scores with fractal-rectified metric measurements; the meaning of the physical composition of fibrosis in relation to the magnitude of collagen islets; the intra- and inter-biopsy sample variability of these parameters; the "staging"of biopsy sections indicating the pathway covered by fibrosis formation towards its maximum known value;the quantitative liver tissue architectural changes with the Hurst exponent.CONCLUSION: Our model provides the first metrical evaluations of the geometric properties of fibrosis and the quantitative architectural changes of the liver tissue.The representativeness of histological sections of the whole liver is also discussed in the light of the results obtained with the Hurst coefficient.

  20. Acute effect of nano-copper on liver tissue and function in rat

    Directory of Open Access Journals (Sweden)

    Miron Doudi

    2014-10-01

    Full Text Available Objective(s: This paper reports on the toxicity of CuO NPs on hepatic enzymes and liver and lung histology. Materials and Methods: To assess the toxicity of copper nanoparticles (10-15 nm in vivo, pathological examinations and blood biochemical indexes including serum glutamate oxaloacetate transaminase (SGOT and serum glutamate pyruvate transaminase (SGPT at various time points (2, 7 and 14 dayswere studied. Thirty two Wistar rats were randomly divided into four groups. Treatment groups (group 1, 2, 3 received CuO NP solution containing 5, 10 and 100 mg/kg, respectively. Control group received 0.5 mL of normal saline via ip injection for 7 consecutive days. After 14 days, the tissue of liver and lung were collected and investigated for their histological problems. Results:The histology of the hepatic tissues showed vasculature in central veins and portal triad vessels in all three treatment groups. Histology of lungs showed air sac wall thickening and increased fibrous tissue in all three groups. Biochemical results of the hepatic enzymes showed that the SGOT levels in groups 1 and 2 were significantly higher than the control group two days after the intervention. Conclusion: Results of this study indicated that all concentration of copper nanoparticles [with 10-15 nm diameters, spherical shape, purity of 99.9%, mineral in nature, and wet synthesis method in liquid phase (alternation] induce toxicity and changes of histo-pathological changes in liver and lung tissues of rats. It is evident that these nanoparticles cannot be used for human purposes because of their toxicity.

  1. Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland

    DEFF Research Database (Denmark)

    Dewailly, Éric; Mulvad, Gert; Pedersen, Henning S.

    1999-01-01

    Organochlorines are persistent lipophilic compounds that accumulate in Inuit people living in circumpolar countries. Organochlorines accumulate as a result of the Inuits' large consumption of sea mammal fat; however, available data are limited to blood lipids, milk fat, and adipose tissue. We...... report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high......-resolution gas chromatography with electron capture detection. Mean concentrations of polychlorinated biphenyls, 2, 2'-bis(4-chlorophenyl)-1,1-dichloroethylene, ss-hexachlorocyclohexane, hexachlorobenzene, mirex, trans-nonachlor, and oxychlordane in adipose tissue samples from Greenlanders were 3-34-fold higher...

  2. Adipose Tissue, Metabolic Syndrome, and Non-Alcoholic Fatty Liver Disease – A Short Review

    Directory of Open Access Journals (Sweden)

    Panayiotis Kouis

    2014-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common chronic liver disease globally, and it is expected to rise even further as a result of the increase in obesity and related risk factors. This short review summarises current evidence on the role of adipose tissue and insulin resistance in NAFLD and the interrelationship between NAFLD and the metabolic syndrome (MetS, considering central adiposity is a major feature of both the MetS and NAFLD, and that NAFLD has been previously described as the hepatic manifestation of the MetS. In addition, genetic studies of NAFLD with relation to adiposity and insulin resistance are reviewed, and up-to-date diagnostic and therapeutic tools are also discussed.

  3. A conserved non-reproductive GnRH system in chordates.

    Directory of Open Access Journals (Sweden)

    Takehiro G Kusakabe

    Full Text Available Gonadotropin-releasing hormone (GnRH is a neuroendocrine peptide that plays a central role in the vertebrate hypothalamo-pituitary axis. The roles of GnRH in the control of vertebrate reproductive functions have been established, while its non-reproductive function has been suggested but less well understood. Here we show that the tunicate Ciona intestinalis has in its non-reproductive larval stage a prominent GnRH system spanning the entire length of the nervous system. Tunicate GnRH receptors are phylogenetically closest to vertebrate GnRH receptors, yet functional analysis of the receptors revealed that these simple chordates have evolved a unique GnRH system with multiple ligands and receptor heterodimerization enabling complex regulation. One of the gnrh genes is conspicuously expressed in the motor ganglion and nerve cord, which are homologous structures to the hindbrain and spinal cord of vertebrates. Correspondingly, GnRH receptor genes were found to be expressed in the tail muscle and notochord of embryos, both of which are phylotypic axial structures along the nerve cord. Our findings suggest a novel non-reproductive role of GnRH in tunicates. Furthermore, we present evidence that GnRH-producing cells are present in the hindbrain and spinal cord of the medaka, Oryzias latipes, thereby suggesting the deep evolutionary origin of a non-reproductive GnRH system in chordates.

  4. Prolonged Ischemia Triggers Necrotic Depletion of Tissue-Resident Macrophages To Facilitate Inflammatory Immune Activation in Liver Ischemia Reperfusion Injury.

    Science.gov (United States)

    Yue, Shi; Zhou, Haoming; Wang, Xuehao; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Zhai, Yuan

    2017-05-01

    Although mechanisms of immune activation against liver ischemia reperfusion (IR) injury (IRI) have been studied extensively, questions regarding liver-resident macrophages, that is, Kupffer cells (KCs), remain controversial. Recent progress in the biology of tissue-resident macrophages implicates homeostatic functions of KCs. This study aims to dissect responses and functions of KCs in liver IRI. In a murine liver partial warm ischemia model, we analyzed liver-resident versus infiltrating macrophages by FACS and immunofluorescence staining. Our data showed that liver immune activation by IR was associated with not only infiltrations/activations of peripheral macrophages, but also necrotic depletion of KCs. Inhibition of receptor-interacting protein 1 (RIP1) by necrostatin-1s protected KCs from ischemia-induced depletion, resulting in the reduction of macrophage infiltration, suppression of proinflammatory immune activation, and protection of livers from IRI. The depletion of KCs by clodronate liposomes abrogated the effect of necrostatin-1s. Additionally, liver reconstitutions with KCs postischemia exerted anti-inflammatory/cytoprotective effects against IRI. These results reveal a unique response of KCs against liver IR, that is, RIP1-dependent necrosis, which constitutes a novel mechanism of liver inflammatory immune activation in the pathogenesis of liver IRI. Copyright © 2017 by The American Association of Immunologists, Inc.

  5. Complex responses to Si quantum dots accumulation in carp liver tissue: Beyond oxidative stress.

    Science.gov (United States)

    Serban, Andreea Iren; Stanca, Loredana; Sima, Cornelia; Staicu, Andrea Cristina; Zarnescu, Otilia; Dinischiotu, Anca

    2015-09-05

    The use of quantum dots (QDs) in biomedical applications is limited due to their inherent toxicity caused by the heavy metal core of the particles. Consequently, silicon-based QDs are expected to display diminished toxicity. We investigated the in vivo effects induced by Si/SiO2 QDs intraperitoneally injected in crucian carp liver. The QDs contained a crystalline Si core encased in a SiO2 shell, with a size between 2.75 and 11.25nm and possess intrinsic fluorescence (Ex 325nm/Em ∼690nm). Tissue fluorescence microscopy analysis revealed the presence of QDs in the liver for at least 2weeks after injection. Although protein and lipid oxidative stress markers showed the onset of oxidative stress, the hepatic tissue exhibited significant antioxidant adaptations (increase of antioxidant enzymes, recovery of glutathione levels), sustained by the activation of Hsp30 and Hsp70 chaperoning proteins. The increased activity of cyclooxigenase-2 (COX-2) and matrix metalloproteinases (MMPs) support the idea that Si/SiO2 QDs have a potential to induce inflammatory response, a scenario also indicated by the profile of Hsp60 and Hsp90 heat shock proteins. MMPs profile and the recovery of oxidative stress markers suggested a tissue remodelation phase after 3weeks from QDs administration.

  6. Methodologies of tissue preservation and analysis of the glycogen content of the broiler chick liver.

    Science.gov (United States)

    Bennett, L W; Keirs, R W; Peebles, E D; Gerard, P D

    2007-12-01

    The current study was performed to develop convenient, rapid, reliable, and pragmatic methodologies by which to harvest and preserve liver tissue glycogen and to analyze its levels within reasonable limits of quantification and with extended chromophore stability. Absorbance values decreased by 2 h and again by 24 h after preparation of the iodine-potassium iodide chromophore, whereas absorbance values of the phenol-sulfuric acid chromophore remained constant over the same time period. These absorbance trends for each chromophore followed full color development within 5 min after combining the analyte with the respective chromophore reagent. Use of the phenol-sulfuric acid reagent allowed for a 10-fold reduction in assay limits of detection and quantification when compared with the iodine-potassium iodide reagent. Furthermore, glycogen concentration-absorbance relationships were affected by the source (i.e., rabbit liver vs. bovine liver) of glycogen standards when the iodine-potassium iodide chromophore was used, but the source of the standards had no influence when the phenol-sulfuric acid chromophore was used. The indifference of the phenol-sulfuric acid method to the glycogen source, as exhibited by similar linear regressions of absorbance, may be attributed to actual determination of glucose subunit concentrations after complete glycogen hydrolysis by sulfuric acid. This is in contrast to the actual measurement of whole glycogen, which may exhibit source- or time-related molecular structural differences. The iodine-potassium iodide methodology is a test of whole glycogen concentrations; therefore, it may be influenced by glycogen structural differences. Liver tissue sample weight (between 0.16 and 0.36 g) and processing, which included mincing, immediate freezing, or refrigeration in 10% perchloric acid for 1 wk prior to tissue grinding, had no effect on glycogen concentrations that were analyzed by using the phenol-sulfuric acid reagent. These results

  7. Effect of preservation period on the viscoelastic material properties of soft tissues with implications for liver transplantation.

    Science.gov (United States)

    Ocal, Sina; Ozcan, M Umut; Basdogan, Ipek; Basdogan, Cagatay

    2010-10-01

    The liver harvested from a donor must be preserved and transported to a suitable recipient immediately for a successful liver transplantation. In this process, the preservation period is the most critical, since it is the longest and most tissue damage occurs during this period due to the reduced blood supply to the harvested liver and the change in its temperature. We investigate the effect of preservation period on the dynamic material properties of bovine liver using a viscoelastic model derived from both impact and ramp and hold experiments. First, we measure the storage and loss moduli of bovine liver as a function of excitation frequency using an impact hammer. Second, its time-dependent relaxation modulus is measured separately through ramp and hold experiments performed by a compression device. Third, a Maxwell solid model that successfully imitates the frequency- and time-dependent dynamic responses of bovine liver is developed to estimate the optimum viscoelastic material coefficients by minimizing the error between the experimental data and the corresponding values generated by the model. Finally, the variation in the viscoelastic material coefficients of bovine liver are investigated as a function of preservation period for the liver samples tested 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 36 h, and 48 h after harvesting. The results of our experiments performed with three animals show that the liver tissue becomes stiffer and more viscous as it spends more time in the preservation cycle.

  8. The apoptotic effect of a high dose of toluene on liver tissue during the acute phase: an experimental study.

    Science.gov (United States)

    Ayan, Murat; Tas, Ufuk; Sogut, Erkan; Kuloglu, Tuncay; Cayli, Sevil; Kocaman, Nevin; Karaca, Zafer Ismail; Sahin, Mehmet

    2013-09-01

    The aim of this study is to investigate the acute toxic effects of high-dose toluene and its mechanisms on the liver tissue of toluene-treated rats. In this study, 16 adult male Wistar albino rats (200-220 g) were divided into two equal groups. Group I was used as a control group, while group II was exposed to high dose of toluene, 5200 mg/kg (6 ml/kg per gavage). After the 3-hour experimental period, blood samples and liver tissues were taken from the euthanized animals. Serum aspartate and alanine aminotransferase levels were assayed. Liver tissues were fixed in 10% neutral formalin, then embedded in paraffin and sectioned (5 μm thickness). Sections were stained with hematoxylin and eosin for histopathological examination. A terminal transferase dUTP nick end labeling assay was also done for the determination of apoptosis in liver tissues. For the determination of Bax and caspase-3 immunoreactivity, the sections were stained using avidin-biotin-peroxidase immunohistochemical method. The level of plasma transaminase was found to be increased in toluene administered rats. Additionally, slight degeneration of hepatocyte and mononuclear cell infiltration was observed in the liver tissue sections and a high (+++) immunoreactivity for Bax and caspase-3 protein was observed in the toluene group. This study showed that the high dose of toluene triggers apoptosis in the liver of rats via the mitochondrial pathway in acute period.

  9. Rare entity: Ectopic liver tissue in the wall of the gallbladder - A case report.

    Science.gov (United States)

    Arslan, Yusuf; Altintoprak, Fatih; Serin, Kursat R; Kivilcim, Taner; Yalkin, Omer; Ozkan, Orhan V; Celebi, Fehmi

    2014-12-16

    Ectopic liver tissue (ELT) is a rare condition, which is usually not diagnosed preoperatively, but coincidentally during abdominal surgery. While the location of ELT can vary, it is usually localized on the gallbladder wall or in close proximity. ELT is associated with various complications, a major complication being extrahepatic hepatocellular carcinoma. A 59-year-old female underwent elective surgery for chronic cholecystitis with stones. During laparoscopic exploration, a 2-cm-diameter ELT was detected in the anterior gallbladder wall and a laparoscopic cholecystectomy was performed. The case is presented due to the rare nature of ELT and as a reminder of ELT-related complications.

  10. Selective protection of human liver tissue in TNF-targeting of cancers of the liver by transient depletion of adenosine triphosphate.

    Directory of Open Access Journals (Sweden)

    Timo Weiland

    Full Text Available BACKGROUND: Tumor necrosis factor alpha (TNF is able to kill cancer cells via receptor-mediated cell death requiring adenosine triphosphate (ATP. Clinical usage of TNF so far is largely limited by its profound hepatotoxicity. Recently, it was found in the murine system that specific protection of hepatocytes against TNF's detrimental effects can be achieved by fructose-mediated ATP depletion therein. Before employing this quite attractive selection principle in a first clinical trial, we here comprehensively investigated the interdependence between ATP depletion and TNF hepatotoxicity in both in vitro and ex vivo experiments based on usage of primary patient tissue materials. METHODS: Primary human hepatocytes, and both non-tumorous and tumorous patient-derived primary liver tissue slices were used to elucidate fructose-induced ATP depletion and TNF-induced cytotoxicity. RESULTS: PHH as well as tissue slices prepared from non-malignant human liver specimen undergoing a fructose-mediated ATP depletion were both demonstrated to be protected against TNF-induced cell death. In contrast, due to tumor-specific overexpression of hexokinase II, which imposes a profound bypass on hepatocytic-specific fructose catabolism, this was not the case for human tumorous liver tissues. CONCLUSION: Normal human liver tissues can be protected transiently against TNF-induced cell death by systemic pretreatment with fructose used in non-toxic/physiologic concentrations. Selective TNF-targeting of primary and secondary tumors of the liver by transient and specific depletion of hepatocytic ATP opens up a new clinical avenue for the TNF-based treatment of liver cancers.

  11. The role of visceral and subcutaneous adipose tissue fatty acid composition in liver pathophysiology associated with NAFLD.

    Science.gov (United States)

    Gentile, C L; Weir, T L; Cox-York, K A; Wei, Y; Wang, D; Reese, L; Moran, G; Estrada, A; Mulligan, C; Pagliassotti, M J; Foster, M T

    2015-01-01

    Visceral adiposity is associated with type-2-diabetes, inflammation, dyslipidemia and non-alcoholic fatty liver disease (NAFLD), whereas subcutaneous adiposity is not. We hypothesized that the link between visceral adiposity and liver pathophysiology involves inherent or diet-derived differences between visceral and subcutaneous adipose tissue to store and mobilize saturated fatty acids. The goal of the present study was to characterize the fatty acid composition of adipose tissue triglyceride and portal vein fatty acids in relation to indices of liver dysregulation. For 8 weeks rats had free access to control (CON; 12.9% corn/safflower oil; 3.6 Kcal/g), high saturated fat (SAT; 45.2% cocoa butter; 4.5 Kcal/g) or high polyunsaturated fat (PUFA; 45.2% safflower oil; 4.5 Kcal/g) diets. Outcome measures included glucose tolerance, visceral and subcutaneous adipose tissue triglyceride, liver phospholipids and plasma (portal and systemic) free fatty acid composition, indices of inflammation and endoplasmic reticulum stress in the liver and adipose tissue depots and circulating adipo/cytokines. Hepatic triglycerides were significantly increased in both high fat diet groups compared to control and were significantly higher in PUFA compared to SAT. Although glucose tolerance was not different among diet groups, SAT increased markers of inflammation and ER stress in the liver and both adipose tissue depots. Fatty acid composition did not differ among adipose depots or portal blood in any dietary group. Overall, these data suggest that diets enriched in saturated fatty acids are associated with liver inflammation, ER stress and injury, but that any link between visceral adipose tissue and these liver indices does not involve selective changes to fatty acid composition in this depot or the portal vein.

  12. Fatty Acid Composition of Muscle, Adipose Tissue and Liver from Muskoxen (Ovibos moschatus) Living in West Greenland.

    Science.gov (United States)

    Alves, Susana P; Raundrup, Katrine; Cabo, Ângelo; Bessa, Rui J B; Almeida, André M

    2015-01-01

    Information about lipid content and fatty acid (FA) composition of muskoxen (Ovibos moschatos) edible tissues is very limited in comparison to other meat sources. Thus, this work aims to present the first in-depth characterization of the FA profile of meat, subcutaneous adipose tissue and liver of muskoxen living in West Greenland. Furthermore, we aim to evaluate the effect of sex in the FA composition of these edible tissues. Samples from muscle (Longissimus dorsi), subcutaneous adipose tissue and liver were collected from female and male muskoxen, which were delivered at the butchery in Kangerlussuaq (West Greenland) during the winter hunting season. The lipid content of muscle, adipose tissue and liver averaged 284, 846 and 173 mg/g of dry tissue, respectively. This large lipid contents confirms that in late winter, when forage availability is scarce, muskoxen from West Greenland still have high fat reserves, demonstrating that they are well adapted to seasonal feed restriction. A detailed characterization of FA and dimethylacetal composition of muskoxen muscle, subcutaneous adipose tissue and liver showed that there are little differences on FA composition between sexes. Nevertheless, the 18:1cis-9 was the most abundant FA in muscle and adipose tissue, reaching 43% of total FA in muscle. The high content of 18:1cis-9 suggests that it can be selectively stored in muskoxen tissues. Regarding the nutritional composition of muskoxen edible tissues, they are not a good source of polyunsaturated FA; however, they may contribute to a higher fat intake. Information about the FA composition of muskoxen meat and liver is scarce, so this work can contribute to the characterization of the nutritional fat properties of muskoxen edible tissues and can be also useful to update food composition databases.

  13. Expression of Innate Immune Response Genes in Liver and Three Types of Adipose Tissue in Cloned Pigs

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard; Skovgaard, Kerstin; Stagsted, Jan;

    2012-01-01

    remain unaffected by the cloning process. We investigated the expression of 40 innate immune factors by high-throughput quantitative real-time PCR in samples from liver, abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and neck SAT in cloned pigs compared to normal outbred pigs...

  14. Determination of nifursol metabolites in poultry muscle and liver tissue. Development and validation of a confirmatory method

    NARCIS (Netherlands)

    Mulder, P.P.J.; Zuidema, T.; Keestra, N.G.M.; Kooij, P.J.F.; Elbers, I.J.W.; Rhijn, J.A. van

    2005-01-01

    A method is described for the identification and quantitative determination of 3,5-dinitrosalicylic acid hydrazide (DSH), the marker residue of nifursol metabolites in poultry (turkey, broiler) muscle and liver tissue. The method is based on the acid-catalysed hydrolysis of tissue-bound metabolites

  15. Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury.

    Science.gov (United States)

    Esch, Mandy B; Mahler, Gretchen J; Stokol, Tracy; Shuler, Michael L

    2014-08-21

    The use of nanoparticles in medical applications is highly anticipated, and at the same time little is known about how these nanoparticles affect human tissues. Here we have simulated the oral uptake of 50 nm carboxylated polystyrene nanoparticles with a microscale body-on-a-chip system (also referred to as multi-tissue microphysiological system or micro Cell Culture Analog). Using the 'GI tract-liver-other tissues' system allowed us to observe compounding effects and detect liver tissue injury at lower nanoparticle concentrations than was expected from experiments with single tissues. To construct this system, we combined in vitro models of the human intestinal epithelium, represented by a co-culture of enterocytes (Caco-2) and mucin-producing cells (TH29-MTX), and the liver, represented by HepG2/C3A cells, within one microfluidic device. The device also contained chambers that together represented the liquid portions of all other organs of the human body. Measuring the transport of 50 nm carboxylated polystyrene nanoparticles across the Caco-2/HT29-MTX co-culture, we found that this multi-cell layer presents an effective barrier to 90.5 ± 2.9% of the nanoparticles. Further, our simulation suggests that a larger fraction of the 9.5 ± 2.9% nanoparticles that travelled across the Caco-2/HT29-MTX cell layer were not large nanoparticle aggregates, but primarily single nanoparticles and small aggregates. After crossing the GI tract epithelium, nanoparticles that were administered in high doses estimated in terms of possible daily human consumption (240 and 480 × 10(11) nanoparticles mL(-1)) induced the release of aspartate aminotransferase (AST), an intracellular enzyme of the liver that indicates liver cell injury. Our results indicate that body-on-a-chip devices are highly relevant in vitro models for evaluating nanoparticle interactions with human tissues.

  16. Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas

    Science.gov (United States)

    Kakehashi, Anna; Stefanov, Vasily E.; Ishii, Naomi; Okuno, Takahiro; Fujii, Hideki; Kawai, Kazuaki; Kawada, Norifumi; Wanibuchi, Hideki

    2017-01-01

    To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV+ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed. Similar changes in the proteome spectrum such as overexpression of enzymes involved in lipid, cholesterol and bile acid biosynthesis and examples associated with suppression of fatty acid oxidation and catabolism, alcohol metabolism, mitochondrial function as well as low expression levels of cytokeratins 8 and 18 were observed in both human NASH biopsies and NASH HCCs, but not HCV+ HCCs. Alterations in downstream protein expression pointed to significant activation of transforming growth factor β, SMAD family member 3, β-catenin, Nrf2, SREBP-LXRα and nuclear receptor-interacting protein 1 (NRIP1), and inhibition of PPARs and p53 in human NASH biopsies and/or HCCs, suggesting their involvement in accumulation of lipids, development of fibrosis, oxidative stress, cell proliferation and suppression of apoptosis in NASH hepatocarcinogenesis. In STAM mice, PPARs inhibition was not obvious, while expression of cytokeratins 8 and 18 was elevated, indicative of essential differences between human and mouse NASH pathogenesis. PMID:28218651

  17. Expression and localization of augmenter of liver regeneration in human muscle tissue.

    Science.gov (United States)

    Polimeno, Lorenzo; Pesetti, Barbara; Giorgio, Floriana; Moretti, Biagio; Resta, Leonardo; Rossi, Roberta; Annoscia, Emanuele; Patella, Vittorio; Notarnicola, Angela; Mallamaci, Rosanna; Francavilla, Antonio

    2009-08-01

    Mitochondrial DNA (mt-DNA) disorders and abnormal regulation of nuclear-derived proteins devoted to the cross-talk between the two cellular genomes have recently interested researchers in the field of neuromuscular diseases. We have identified, isolated and sequenced a new gene, augmenter of liver regeneration (ALR) that stimulates in vivo hepatocyte proliferation and up-regulates mt-DNA expression and ATP production. ALR protein (Alrp) is mainly located, in rat, in the mitochondrial inter-membrane space and its mRNA is particularly abundant in brain, muscle, testis and liver, tissues whose activity is mostly dependent on mitochondrial metabolism. Studies on rat Alrp sequence revealed the presence of homologous amino-acid sections into proteins derived from mouse, human, Drosophyla, plants and even DNA viruses. In this article, we evaluated ALR expression in normal human muscular tissues, both as protein and as mRNA. The data, obtained by molecular biology, immunohistochemistry and electron microscopy, demonstrated that: (i) Alrp and ALR mRNA are present in human muscular tissue; (ii) Alrp is particularly expressed in muscular fibres rich in mitochondria; (iii) Alrp is localized in the mitochondrial inter-membrane space or associated to mitochondrial cristae; and (iv) in subjects younger then 35 years of age, ALR mRNA expression is different between male and female subjects. In conclusion, the present data set Alrp, as a factor associated with mitochondria also in human tissue, call for future studies aimed at establishing Alrp as an important factor involved in the molecular events that trigger neuromuscular diseases.

  18. Influence of recipient gender on intrasplenic fetal liver tissue transplants in rats: cytochrome P450-mediated monooxygenase functions.

    Science.gov (United States)

    Lupp, Amelie; Hugenschmidt, Sabine; Rost, Michael; Müller, Dieter

    2004-05-01

    Rat livers display a sex-specific cytochrome P450 (P450) isoforms expression pattern with consecutive differences in P450-mediated monooxygenase activities, which have been shown to be due to a differential profile of growth hormone (GH) secretion. Parallel to previous investigations on P450 isoforms expression, the aim of the present study was to elucidate the influence of recipient gender on P450-mediated monooxygenase activities in intrasplenic liver tissue transplants in comparison to orthotopic liver. Fetal liver tissue suspensions of mixed gender were transplanted into the spleen of adult male or female syngenic recipients. Four months after grafting transplant-recipients and age-matched controls were treated with beta-naphthoflavone (BNF), phenobarbital (PB), dexamethasone (DEX) or the vehicles and sacrificed 24 or 48 h thereafter. P450-dependent monooxygenase activities were assessed by a series of model reactions for different P450 subtypes in liver and spleen 9000 g supernatants. In spleens of male and female control rats only very low monooxygenase activities were detectable, whereas with most model reactions distinct activities were observed in transplant-containing organs. Livers and transplant-containing spleens from male rats displayed higher basal ethoxycoumarin O-deethylase and testosterone 2alpha-, 2beta-, 6beta-, 14alpha-, 15alpha-, 15beta-, 16alpha-, 16beta- and 17-hydroxylase activities than those from females. On the other hand, like the respective livers, spleens from female transplant-recipients demonstrated more pronounced p-nitrophenol- and testosterone 6alpha- and 7alpha-hydroxylase activities than those from male hosts. With nearly all model reactions gender-specific differences in inducibility by BNF, PB or DEX could be demonstrated in livers as well as in transplant-containing spleens. These results further confirm that the P450 system of intrasplenic liver tissue transplants and the respective orthotopic livers is similarly influenced

  19. Structural effects of simvastatin on liver rate tissue: Fourier transform infrared and Raman microspectroscopic studies

    Science.gov (United States)

    Garip, Sebnem; Bayari, Sevgi Haman; Severcan, Mete; Abbas, Sherif; Lednev, Igor K.; Severcan, Feride

    2016-02-01

    Simvastatin is one of the most frequently prescribed statins because of its efficacy in the treatment of hypercholesterolemia, reducing cardiovascular risk and related mortality. Determination of its side effects on different tissues is mandatory to improve safe use of this drug. In the present study, the effects of simvastatin on molecular composition and structure of healthy rat livers were investigated by Fourier transform infrared and Raman imaging. Simvastatin-treated groups received 50 mg/kg/day simvastatin for 30 days. The ratio of the area and/or intensity of the bands assigned to lipids, proteins, and nucleic acids were calculated to get information about the drug-induced changes in tissues. Loss of unsaturation, accumulation of end products of lipid peroxidation, and alterations in lipid-to-protein ratio were observed in the treated group. Protein secondary structure studies revealed significant decrease in α-helix and increase in random coil, while native β-sheet decreases and aggregated β-sheet increases in treated group implying simvastatin-induced protein denaturation. Moreover, groups were successfully discriminated using principal component analysis. Consequently, high-dose simvastatin treatment induces hepatic lipid peroxidation and changes in molecular content and protein secondary structure, implying the risk of liver disorders in drug therapy.

  20. Diagnostic value of real-time tissue elastography for liver fibrosis in patients with chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    ZHANG Guosheng

    2014-07-01

    Full Text Available ObjectiveTo investigate the diagnostic value of real-time tissue elastography (RTE in evaluating liver fibrosis in patients with chronic hepatitis B (CHB. MethodsEighty-six patients with CHB, who visited Beijing Tiantan Hospital and Beijing You′an Hospital from March to August, 2013, were grouped according to the pathological stages of liver fibrosis. They were examined by RTE, biochemical tests, and liver biopsy. Then, liver fibrosis index (LFI and aspartate aminotransferase-to-platelet ratio index (APRI were calculated. Comparison between groups was made by one-way analysis of variance, followed by LSD t-test for multiple comparisons. The correlation between LFI and pathological stage of liver fibrosis was analyzed by Spearman correlation test. The sensitivity and specificity of LFI for the diagnosis of liver fibrosis were calculated. Regarding S≥2 (significant liver fibrosis and S≥4 (early liver cirrhosis as the positive standards, the receiver operating characteristic (ROC curve was drawn and compared with APRI. ResultsLFI differed significantly across the groups (P=0.000, except the comparison between S0 and S1 (P=0.298. LFI was significantly correlated with pathological stage (r=0.831, P<0.001. The areas under the ROC curve of LFI in diagnosing significant liver fibrosis and early liver cirrhosis were 0873 (P<0.001 and 0.923 (P=0002, respectively; the diagnostic thresholds were 2.74 and 3.61, respectively; the sensitivity and specificity were 0.766/0.872 and 0.833/0.878, respectively. LFI was significantly superior to APRI. ConclusionRTE has high diagnostic values for significant liver fibrosis and early liver cirrhosis and is an important noninvasive diagnostic method for liver fibrosis in patients with CHB.

  1. Gene network activity in cultivated primary hepatocytes is highly similar to diseased mammalian liver tissue.

    Science.gov (United States)

    Godoy, Patricio; Widera, Agata; Schmidt-Heck, Wolfgang; Campos, Gisela; Meyer, Christoph; Cadenas, Cristina; Reif, Raymond; Stöber, Regina; Hammad, Seddik; Pütter, Larissa; Gianmoena, Kathrin; Marchan, Rosemarie; Ghallab, Ahmed; Edlund, Karolina; Nüssler, Andreas; Thasler, Wolfgang E; Damm, Georg; Seehofer, Daniel; Weiss, Thomas S; Dirsch, Olaf; Dahmen, Uta; Gebhardt, Rolf; Chaudhari, Umesh; Meganathan, Kesavan; Sachinidis, Agapios; Kelm, Jens; Hofmann, Ute; Zahedi, René P; Guthke, Reinhard; Blüthgen, Nils; Dooley, Steven; Hengstler, Jan G

    2016-10-01

    It is well known that isolation and cultivation of primary hepatocytes cause major gene expression alterations. In the present genome-wide, time-resolved study of cultivated human and mouse hepatocytes, we made the observation that expression changes in culture strongly resemble alterations in liver diseases. Hepatocytes of both species were cultivated in collagen sandwich and in monolayer conditions. Genome-wide data were also obtained from human NAFLD, cirrhosis, HCC and hepatitis B virus-infected tissue as well as mouse livers after partial hepatectomy, CCl4 intoxication, obesity, HCC and LPS. A strong similarity between cultivation and disease-induced expression alterations was observed. For example, expression changes in hepatocytes induced by 1-day cultivation and 1-day CCl4 exposure in vivo correlated with R = 0.615 (p < 0.001). Interspecies comparison identified predominantly similar responses in human and mouse hepatocytes but also a set of genes that responded differently. Unsupervised clustering of altered genes identified three main clusters: (1) downregulated genes corresponding to mature liver functions, (2) upregulation of an inflammation/RNA processing cluster and (3) upregulated migration/cell cycle-associated genes. Gene regulatory network analysis highlights overrepresented and deregulated HNF4 and CAR (Cluster 1), Krüppel-like factors MafF and ELK1 (Cluster 2) as well as ETF (Cluster 3) among the interspecies conserved key regulators of expression changes. Interventions ameliorating but not abrogating cultivation-induced responses include removal of non-parenchymal cells, generation of the hepatocytes' own matrix in spheroids, supplementation with bile salts and siRNA-mediated suppression of key transcription factors. In conclusion, this study shows that gene regulatory network alterations of cultivated hepatocytes resemble those of inflammatory liver diseases and should therefore be considered and exploited as disease models.

  2. Liver-targeting of interferon-alpha with tissue-specific domain antibodies.

    Directory of Open Access Journals (Sweden)

    Edward Coulstock

    Full Text Available Interferon alpha (IFNα is used for the treatment of hepatitis C infection and whilst efficacious it is associated with multiple adverse events including reduced leukocyte, erythrocyte, and platelet counts, fatigue, and depression. These events are most likely caused by systemic exposure to interferon. We therefore hypothesise that targeting the therapeutic directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. We genetically fused IFN to a domain antibody (dAb specific to a hepatocyte restricted antigen, asialoglycoprotein receptor (ASGPR. Our results show that the murine IFNα2 homolog (mIFNα2 fused to an ASGPR specific dAb, termed DOM26h-196-61, could be expressed in mammalian tissue culture systems and retains the desirable biophysical properties and activity of both fusion partners when measured in vitro. Furthermore a clear increase in in vivo targeting of the liver by mIFNα2-ASGPR dAb fusion protein, compared to that observed with either unfused mIFNα2 or mIFNα2 fused to an isotype control dAb VHD2 (which does not bind ASGPR was demonstrated using microSPECT imaging. We suggest that these findings may be applicable in the development of a liver-targeted human IFN molecule with improved safety and patient compliance in comparison to the current standard of care, which could ultimately be used as a treatment for human hepatitis virus infections.

  3. Long-term stability of RNA in post-mortem bovine skeletal muscle, liver and subcutaneous adipose tissues

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    Schmidt Olaf

    2007-11-01

    Full Text Available Abstract Background Recovering high quality intact RNA from post-mortem tissue is of major concern for gene expression studies in animals and humans. Since the availability of post-mortem tissue is often associated with substantial delay, it is important that we understand the temporal variation in the stability of total RNA and of individual gene transcripts so as to be able to appropriately interpret the data generated from such studies. Hence, the objective of this experiment was to qualitatively and quantitatively assess the integrity of total and messenger RNA extracted from bovine skeletal muscle, subcutaneous adipose tissue and liver stored at 4°C at a range of time points up to 22 days post-mortem. These conditions were designed to mimic the environment prevailing during the transport of beef from the abattoir to retail outlets. Results The 28S and 18S rRNA molecules of total RNA were intact for up to 24 h post-mortem in liver and adipose tissues and up to 8 days post-mortem in skeletal muscle. The mRNA of housekeeping genes (GAPDH and ACTB and two diet-related genes (RBP5 and SCD were detectable up to 22 days post-mortem in skeletal muscle. While the mRNA stability of the two housekeeping genes was different in skeletal muscle and liver, they were similar to each other in adipose tissue. After 22 days post-mortem, the relative abundance of RBP5 gene was increased in skeletal muscle and in adipose tissue and decreased in liver. During this period, the relative abundance of SCD gene also increased in skeletal muscle whereas it decreased in both adipose tissue and liver. Conclusion Stability of RNA in three tissues (skeletal muscle, subcutaneous adipose tissue and liver subjected to long-term post-mortem storage at refrigeration temperature indicated that skeletal muscle can be a suitable tissue for recovering biologically useful RNA for gene expression studies even if the tissue is subjected to post-mortem storage for weeks, whereas

  4. Evaluation of liver tissue by polymerase chain reaction for hepatitis B virus in patients with negative viremia

    Institute of Scientific and Technical Information of China (English)

    Fouad Thakeb; Magdy El-Serafy; Soheir Zakaria; Bahaa Monir; Sahar Lashin; Raghda Marzaban; Mostafa El-Awady

    2005-01-01

    AIM: To assess the clinical significance of Hepatitis B virus (HBV) DNA localization in the liver tissue of patients with positive HBsAg and negative viremia.METHODS: HBV virological parameters of 33 HBsAg positive chronic hepatitis patients, including seromarkers and HBV DNA amplification in both sera and liver biopsies, were evaluated.RESULTS: Ten patients had negative viremia and positive HBV DNA in their liver biopsies. Most of them had HBeAg-negative/HBeAb-positive chronic hepatitis.Their liver biochemical and histopathological profiles were different from the viremic patients. Their disease pattern was designated as "hepatitis B in situ".CONCLUSION: Hepatitis B in situ is a consequential entity which can be missed in clinical practice. It is a new clinical pattern of chronic HBV infection that considers HBV in liver biopsy and adds a new indication for antiviral therapy.

  5. Reproduction is associated with a tissue-dependent reduction of oxidative stress in eusocial female Damaraland mole-rats (Fukomys damarensis.

    Directory of Open Access Journals (Sweden)

    Christina M Schmidt

    Full Text Available Oxidative stress has been implicated as both a physiological cost of reproduction and a driving force on an animal's lifespan. Since increased reproductive effort is generally linked with a reduction in survival, it has been proposed that oxidative stress may influence this relationship. Support for this hypothesis is inconsistent, but this may, in part, be due to the type of tissues that have been analyzed. In Damaraland mole-rats the sole reproducing female in the colony is also the longest lived. Therefore, if oxidative stress does impact the trade-off between reproduction and survival in general, this species may possess some form of enhanced defense. We assessed this relationship by comparing markers of oxidative damage (malondialdehyde, MDA; protein carbonyls, PC and antioxidants (total antioxidant capacity, TAC; superoxide dismutase, SOD in various tissues including plasma, erythrocytes, heart, liver, kidney and skeletal muscle between wild-caught reproductive and non-reproductive female Damaraland mole-rats. Reproductive females exhibited significantly lower levels of PC across all tissues, and lower levels of MDA in heart, kidney and liver relative to non-reproductive females. Levels of TAC and SOD did not differ significantly according to reproductive state. The reduction in oxidative damage in breeding females may be attributable to the unusual social structure of this species, as similar relationships have been observed between reproductive and non-reproductive eusocial insects.

  6. Developmental changes in glutathione S-transferase isoforms expression and activity in intrasplenic fetal liver tissue transplants in rats.

    Science.gov (United States)

    Lupp, Amelie; Anschütz, Tino; Lindström-Seppä, Pirjo; Müller, Dieter

    2003-09-01

    The aim of the present study was to characterise developmental changes in glutathione S-transferase (GST) isoforms expression and in glutathione conjugation capacity in intrasplenic liver tissue transplants. For this purpose, syngenic fetal liver tissue suspensions were transplanted into the spleens of adult male Fischer 344 rats. Three days, 1, 2, 4 weeks, 2, 4, 6 months and 1 year later, transplant-recipients and control animals were sacrificed and class alpha, mu and pi GST isoforms expression and GST activities using the substrates o-dinitrobenzene and 1-chloro-2,4-dinitrobenzene were assessed in livers and spleens. In the hepatocytes of the adult livers no class pi, but a distinct class alpha and mu GST expression was seen. The bile duct epithelia were class pi GST positive. Fetal livers displayed almost no class alpha and mu, but a slight class pi GST expression. The same pattern was seen in 3-day-old intrasplenic liver tissue transplants. Up to 2 weeks after surgery the class alpha and mu GST expression increased in the hepatocytes of the transplants, whereas the immunostaining for class pi GST disappeared. No remarkable changes were seen thereafter. Normal conjugation capacities were observed with the livers of both groups of rats. Control spleens displayed only low GST activities. From 2 months after transplantation on activities were significantly higher in transplant-containing spleens than in respective control organs with a further increase up to one year after grafting. These results show that intrasplenically transplanted fetal liver cells proliferate and differentiate into mature cells displaying a GST expression pattern with respective enzyme activities similar to adult liver.

  7. Reduction in the desaturation capacity of the liver in mice subjected to high fat diet: Relation to LCPUFA depletion in liver and extrahepatic tissues.

    Science.gov (United States)

    Valenzuela, Rodrigo; Barrera, Cynthia; Espinosa, Alejandra; Llanos, Paola; Orellana, Paula; Videla, Luis A

    2015-07-01

    α-Linolenic (ALA) and linoleic (LA) acids are precursors of long chain polyunsaturated fatty acids (LCPUFAs), FAs with important biochemical and physiological functions. In this process, desaturation reactions catalyzed by Δ5- and Δ6-desaturase play a major role, enzymes that are subjected to hormonal and dietary regulation. The aim of this study was to assess the influence of a high fat diet (HFD) on activity of liver Δ5 and Δ6 desaturases, in relation to LCPUFA composition in liver and extrahepatic tissues. Male C57BL/6J mice received control diet (CD) (10% fat, 20% protein and 70% carbohydrate) or high fat diet (HFD) (60% fat, 20% protein, and 20% carbohydrate) for 12 weeks. After this time, blood and liver samples were taken for metabolic, morphologic, inflammatory, oxidative stress and desaturase activity assessment, besides FA phospholipid analysis in erythrocytes, heart, adipose tissue and brain. HFD significantly increased hepatic total fat, triacylglycerides and free FA content with macrovesicular steatosis and oxidative stress enhancement, concomitantly with higher fasting serum glucose and insulin levels, HOMA, and serum cholesterol, triacylglycerols, TNF-α, and IL-6. Diminution in liver Δ5- and Δ6-desaturase activities and LCPUFA depletion were induced by HFD, the later finding being also observed in extrahepatic tissues. In conclusion, HFD-induced reduction in the bioavailability of liver LCPUFA is associated with defective desaturation of ALA and LA, with Δ5- and Δ6-desaturase activities being correlated with insulin resistance development. Data analyzed point to the liver as a major organ responsible for extrahepatic LCPUFA homeostasis, which is markedly deranged by HFD.

  8. Extreme Learning Machine Framework for Risk Stratification of Fatty Liver Disease Using Ultrasound Tissue Characterization.

    Science.gov (United States)

    Kuppili, Venkatanareshbabu; Biswas, Mainak; Sreekumar, Aswini; Suri, Harman S; Saba, Luca; Edla, Damodar Reddy; Marinhoe, Rui Tato; Sanches, J Miguel; Suri, Jasjit S

    2017-08-23

    Fatty Liver Disease (FLD) is caused by the deposition of fat in liver cells and leads to deadly diseases such as liver cancer. Several FLD detection and characterization systems using machine learning (ML) based on Support Vector Machines (SVM) have been applied. These ML systems utilize large number of ultrasonic grayscale features, pooling strategy for selecting the best features and several combinations of training/testing. As result, they are computationally intensive, slow and do not guarantee high performance due to mismatch between grayscale features and classifier type. This study proposes a reliable and fast Extreme Learning Machine (ELM)-based tissue characterization system (a class of Symtosis) for risk stratification of ultrasound liver images. ELM is used to train single layer feed forward neural network (SLFFNN). The input-to-hidden layer weights are randomly generated reducing computational cost. The only weights to be trained are hidden-to-output layer which is done in a single pass (without any iteration) making ELM faster than conventional ML methods. Adapting four types of K-fold cross-validation (K = 2, 3, 5 and 10) protocols on three kinds of data sizes: S0-original, S4-four splits, S8-sixty four splits (a total of 12 cases) and 46 types of grayscale features, we stratify the FLD US images using ELM and benchmark against SVM. Using the US liver database of 63 patients (27 normal/36 abnormal), our results demonstrate superior performance of ELM compared to SVM, for all cross-validation protocols (K2, K3, K5 and K10) and all types of US data sets (S0, S4, and S8) in terms of sensitivity, specificity, accuracy and area under the curve (AUC). Using the K10 cross-validation protocol on S8 data set, ELM showed an accuracy of 96.75% compared to 89.01% for SVM, and correspondingly, the AUC: 0.97 and 0.91, respectively. Further experiments also showed the mean reliability of 99% for ELM classifier, along with the mean speed improvement of 40% using

  9. Detection of serum tumor marker contents of liver cancer patients and itscorrelation with JAK-STAT pathway in tumor tissue

    Institute of Scientific and Technical Information of China (English)

    Zhi-Gang Dong; Li-Li Ma; Ya-Juan Li; Zhan-Hong Zhang

    2015-01-01

    Objective: To study the serum tumor marker contents of liver cancer patients and its correlation with HAK-STAT pathway in tumor tissue. Methods: 50 cases of primary liver cancer patients diagnosed in our hospital from August 2013 to November 2014 were enrolled in liver cancer group; 50 cases of healthy persons received physical examination in our hospital during the same period were enrolled in healthy group. Then serum was collected and Livin, Xiap, Pim-1, ICAM-1, VCAM-1, CD44v6, DNMT1, DNMT2, DNMT3A, DNMT3B, HDAC1 and HDAC5 were detected; liver tissue was collected and JAK1, JAK2, STAT1, STAT3 and STAT5 were detected. Results: (1) Proliferation and adhesion molecules: compared with serum proliferation and adhesion molecule contents of the healthy group, serum Livin, Xiap, Pim-1, ICAM-1, VCAM-1 and CD44v6 contents of liver cancer group were higher; (2) Methyltransferase and histone deacetylase: compared with serum methyltransferase and histone deacetylase contents of healthy group, serum mRNA contents of DNMT1, DNMT2, DNMT3A, DNMT3B, HDAC1 and HDAC5 of liver cancer group were higher; (3) Signal molecules: compared with JAK-STAT signal molecule contents in adjacent normal liver tissue, mRNA contents of JAK1, JAK2, STAT1, STAT3 and STAT5 in hepatocellular carcinoma tissue were higher. Conclusion: Contents of serum proliferation and adhesion molecules, methyltransferase and histone deacetylase abnormally increase, which is closely related to the abnormal activation of JAK-STAT pathway in tumor tissue.

  10. Effect of Butanol Extract of Maturated Mahkota Dewa (Phaleria macrocarpa Fruit on Liver Tissue of Mice (Mus musculus

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    ARIF SOEKSMANTO

    2006-10-01

    Full Text Available Mahkota dewa (Phaleria macrocarpa [Scheff.] Boerl. is a poisonous plant, but almost all parts of the plants can be used as a traditional medicine. Consuming the plant directly can cause swollen, sprue, numb at tongue, fever, even unconscious. Although the plant can conquere various diseases, from diabetes mellitus, hemorrhoid, impotency to cancer, but research on the plant is still limited. A research was conducted to find out effect of subchronic dosage of butanol extract of maturated mahkota dewa fruit. Observation was carried out on liver tissue which is main organ detoxifying poison in the body. Dosage of butanol extract of 0; 42,5; 85 and 170 mg/kg body weight was administered intra peritoneally to mice. The result showed that butanol extract of maturated mahkota dewa fruit did not affect liver tissue, although at dosage 170 mg/kg body weight, a vacuolization on liver's tissue, was occurred.

  11. Effect of extracellular vesicles of human adipose tissue on insulin signaling in liver and muscle cells.

    Science.gov (United States)

    Kranendonk, Mariëtte E G; Visseren, Frank L J; van Herwaarden, Joost A; Nolte-'t Hoen, Esther N M; de Jager, Wilco; Wauben, Marca H M; Kalkhoven, Eric

    2014-10-01

    Insulin resistance (IR) is a key mechanism in obesity-induced cardiovascular disease. To unravel mechanisms whereby human adipose tissue (AT) contributes to systemic IR, the effect of human AT-extracellular vesicles (EVs) on insulin signaling in liver and muscle cells was determined. EVs released from human subcutaneous (SAT) and omental AT (OAT)-explants ex vivo were used for stimulation of hepatocytes and myotubes in vitro. Subsequently, insulin-induced Akt phosphorylation and expression of gluconeogenic genes (G6P, PEPCK) was determined. AT-EV adipokine levels were measured by multiplex immunoassay, and AT-EVs were quantified by high-resolution flow cytometry. In hepatocytes, AT-EVs from the majority of patients inhibited insulin-induced Akt phosphorylation, while EVs from some patients stimulated insulin-induced Akt phosphorylation. In myotubes AT-EVs exerted an ambiguous effect on insulin signaling. Hepatic Akt phosphorylation related negatively to G6P-expression by both SAT-EVs (r = -0.60, P = 0.01) and OAT-EVs (r = -0.74, P = 0.001). MCP-1, IL-6, and MIF concentrations were higher in OAT-EVs compared to SAT-EVs and differently related to lower Akt phosphorylation in hepatocytes. Finally, the number of OAT-EVs correlated positively with liver enzymes indicative for liver dysfunction. Human AT-EVs can stimulate or inhibit insulin signaling in hepatocytes- possibly depending on their adipokine content- and may thereby contribute to systemic IR. Copyright © 2014 The Obesity Society.

  12. Adipose tissue-derived stem cells promote the reversion of non-alcoholic fatty liver disease: An in vivo study.

    Science.gov (United States)

    Liao, Naishun; Pan, Fan; Wang, Yingchao; Zheng, Youshi; Xu, Bo; Chen, Wenwei; Gao, Yunzhen; Cai, Zhixiong; Liu, Xiaolong; Liu, Jingfeng

    2016-05-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver injury and seriously affects human health. In the present study, we aimed to investigate whether adipose tissue-derived stem cell (ADSC) transplantation in combination with dietary modification was capable of reversing the progression of NAFLD. After establishing a rat model of NAFLD by feeding them a high-fat diet (HFD), ADSCs were transplanted via the portal vein into rats with HFD-induced NAFLD, and simultaneously fed a modified diet. Thereafter, gross liver morphology, the hepatosomatic (HSI) index and indicators of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were evaluated. Subsequently, the serum levels of total cholesterol (TC), triglycerides (TGs) and fatty acids (FAs) were also assayed. Furthermore, H&E and oil red O staining were used to confirm the pathological effects of NAFLD in the rat livers. Although dietary modification alone caused liver function to recover, ADSC transplantation in combination with dietary modification further decreased the HSI index, the serum levels of ALT, TBIL, TC, TGs, FAs, reduced lipid accumulation to normal levels, and reversed the hepatic pathological changes in the rat livers. Taken together, these findings suggest that ADSC transplantation assists in the reversion of NAFLD by improving liver function and promoting lipid metabolism, thereby exerting hepatoprotective effects. Thus, we suggest that ADSC transplantation is a promising, potential therapeutic strategy for NAFLD treatment.

  13. Optimizing EUS-guided liver biopsy sampling: comprehensive assessment of needle types and tissue acquisition techniques.

    Science.gov (United States)

    Schulman, Allison R; Thompson, Christopher C; Odze, Robert; Chan, Walter W; Ryou, Marvin

    2017-02-01

    EUS-guided liver biopsy sampling using FNA and, more recently, fine-needle biopsy (FNB) needles has been reported with discrepant diagnostic accuracy, in part due to differences in methodology. We aimed to compare liver histologic yields of 4 EUS-based needles and 2 percutaneous needles to identify optimal number of needle passes and suction. Six needle types were tested on human cadaveric tissue: one 19G FNA needle, one existing 19G FNB needle, one novel 19G FNB needle, one 22G FNB needle, and two 18G percutaneous needles (18G1 and 18G2). Two needle excursion patterns (1 vs 3 fanning passes) were performed on all EUS needles. Primary outcome was number of portal tracts. Secondary outcomes were degree of fragmentation and specimen adequacy. Pairwise comparisons were performed using t tests, with a 2-sided P samplings (48 per needle type) were performed. The novel 19G FNB needle had significantly increased mean portal tracts compared with all needle types. The 22G FNB needle had significantly increased portal tracts compared with the 18G1 needle (3.8 vs 2.5, P sampling. Investigations are underway to determine whether these results can be replicated in a clinical setting. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  14. Peripheral effects of the endocannabinoid system in energy homeostasis: adipose tissue, liver and skeletal muscle.

    Science.gov (United States)

    Silvestri, Cristoforo; Ligresti, Alessia; Di Marzo, Vincenzo

    2011-09-01

    The endocannabinoid system (ECS) is composed of lipid signalling ligands, their G-protein coupled receptors and the enzymes involved in ligand generation and metabolism. Increasingly, the ECS is emerging as a critical agent of energy metabolism regulation through its ability to modulate caloric intake centrally as well as nutrient transport, cellular metabolism and energy storage peripherally. Visceral obesity has been associated with an upregulation of ECS activity in several systems and inhibition of the ECS, either pharmacologically or genetically, results in decreased energy intake and increased metabolic output. This review aims to summarize the recent advances that have been made regarding our understanding of the role the ECS plays in crucial peripheral systems pertaining to energy homeostasis: adipose tissues, the liver and skeletal muscle.

  15. Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro

    Science.gov (United States)

    Funk, Juergen; Robbins, Justin B.; Crogan-Grundy, Candace; Presnell, Sharon C.; Singer, Thomas; Roth, Adrian B.

    2016-01-01

    Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI). This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (≤ 4uM). Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level. PMID:27387377

  16. Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro.

    Directory of Open Access Journals (Sweden)

    Deborah G Nguyen

    Full Text Available Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI. This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (≤ 4uM. Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level.

  17. Coordinated gene expression in adipose tissue and liver differs between cows with high or low NEFA concentrations in early lactation.

    Science.gov (United States)

    van Dorland, H A; Sadri, H; Morel, I; Bruckmaier, R M

    2012-02-01

    Dairy cows with high and low plasma non-esterified fatty acid (NEFA) concentrations in early lactation were compared for plasma parameters and mRNA expression of genes in liver and subcutaneous adipose tissue. The study involved 16 multiparous dairy cows with a plasma NEFA concentration of >500 μmol/l [n = 8, high NEFA (HNEFA)] and Subcutaneous adipose and liver tissues were analysed for mRNA abundance by real-time qRT-PCR encoding parameters related to lipid metabolism. Results showed that mean daily milk yield and milk fat quantity were higher in HNEFA than in LNEFA cows (p carnitine palmitoyltransferase 2 and very long chain acyl-coenzyme A dehydrogenase) and ketogenesis (3-hydroxy-3-methylglutaryl-coenzyme A synthase 2) were lower in HNEFA than in LNEFA cows. No differences between the two groups were observed for mRNA expression of genes in adipose tissue. The number of calculated significant correlation coefficients (moderately strong) between parameters in the liver and in adipose tissue was nearly similar on +1d, and higher for HNEFA compared with LNEFA cows in +3wk. In conclusion, dairy cows with high compared with low plasma NEFA concentrations in early lactation show differentially synchronized mRNA expression of genes in adipose tissue and liver in +3wk that suggests a different orchestrated homeorhetic regulation of lipid metabolism.

  18. 工程化肝组织肝表面片状植入新方法%New method of liver mrface sheet implantation with engineering Liver tissue

    Institute of Scientific and Technical Information of China (English)

    刘巨超; 周海洋; 孙慧伟; 丁毅; 徐迎新

    2012-01-01

    Objective To explore the feasibility of orthotopic.ally implanting larger-size,sheet-likeengineered liver tissue on the surface of liver to facilitate the establishment of blood supply.MethodsHepatocytes and microvessel endothelial cells isolated from newborn rats using enzymatic dissociation withtypsin and by tissue adherence method,respectively,were combined with sheet-like collagen scaffold andvascular endothelial growth factor (VEGF,10 g/L) to generate bepatocytes/endotheliocytes/VEGF/colla-gen constructs.The constructs were then implanted onto the surface of 15 rats' livers through the adherencemethod of sheet-like engineered liver tissue.Gross and histological observation was taken four weeks afterimplantation.Results The viability of both hepatocytes and endotheliocytes was over 90%.Sheet engi-neering liver tissue can fit closely with the orthotopic liver by the liver surface pasting method,and formhepatocyte-like tissue which was larger than 1 cm3.Hematoxylin and eosin (HE) staining showed that thehepatocytes were in good condition and distributed evenly in the implants,and angiogenesis could also beseen.We didn' t find cell degeneration and death.Conclusion The liver surface pasting method is sim-ple and safe,which can be used to build larger size of the engineering liver tissue,and also expected toreach the purpose of repairing damaged liver in situ.%目的 探索较大尺度工程化肝组织原位肝表面贴覆片状植入、尽快建立血供的可行性.方法 将采用胰酶冷消化法分离的新生大鼠肝细胞(1×1010个/L)、肺组织块贴壁法分离的大鼠微血管内皮细胞(1 ×1010个/L),与片状胶原支架、血管内皮生长因子(VEGF,10g/L)复合构建肝细胞/内皮细胞/血管生长因子/胶原支架复合的片状工程化肝组织.将其在15只大鼠肝表面贴覆植入,4周后取样进行大体观察及组织切片苏木素-伊红(HE)染色.结果 分离的肝细胞及内皮细胞活率均为90%以上.片状工

  19. Difference in hepatic tissue oxygenation between total vascular exclusion and inflow occlusion of the liver and the possible role of hepatic venous blood under liver ischemia.

    Science.gov (United States)

    Sato, T; Asanuma, Y; Kusano, T; Sasaki, N; Shindo, Y; Koyama, K

    1998-01-01

    The difference between total vascular exclusion (TVE) and inflow occlusion (IO) of the liver was assessed by the extent of DNA injury in rats and by hepatic tissue oxygen saturation (SahtO2) in pigs. Moreover, the role of hepatic venous blood under liver ischemia was discussed. Seventy percent of the rat livers were exposed to complete IO (hepatic artery + portal vein) or to TVE (IO + hepatic vein) for 30 or 60 min. DNA strand breaks following blood flow interception were measured using the in situ nick translation technique as an indicator of liver damage. IO/TVE were performed on pigs as well under portosystemic bypass, and the oxygen saturation of the hepatic venous blood (SahvO2) was altered by changing the fraction of inspiratory oxygen or by oxygenating the inferior caval blood using an extracorporeal membrane oxygenator. The changes in SahtO2 were measured sequentially using near-infrared spectroscopy. The results were as follows: (1) DNA injury occurred more severely under TVE than under IO of the rat liver at the end of ischemia, as well as 30 min after revascularization. (2) SahtO2 during TVE was significantly lower than that during IO. (3) The increase in SahvO2 by oxygenation of the inferior caval blood resulted in the elevation of SahtO2 under IO. In conclusion, TVE could cause greater damage to the liver than IO due to the lack of the hepatic venous blood. Hepatic venous blood might play an important role in hepatic tissue oxygenation in the case of hepatic blood flow interception.

  20. Plasmodium falciparum liver stage antigen-1 is cross-linked by tissue transglutaminase

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    Doerig Christian

    2011-01-01

    Full Text Available Abstract Background Plasmodium falciparum sporozoites injected by mosquitoes into the blood rapidly enter liver hepatocytes and undergo pre-erythrocytic developmental schizogony forming tens of thousands of merozoites per hepatocyte. Shortly after hepatocyte invasion, the parasite starts to produce Liver Stage Antigen-1 (LSA-1, which accumulates within the parasitophorous vacuole surrounding the mass of developing merozoites. The LSA-1 protein has been described as a flocculent mass, but its role in parasite development has not been determined. Methods Recombinant N-terminal, C-terminal or a construct containing both the N- and C- terminal regions flanking two 17 amino acid residue central repeat sequences (LSA-NRC were subjected to in vitro modification by tissue transglutaminase-2 (TG2 to determine if cross-linking occurred. In addition, tissue sections of P. falciparum-infected human hepatocytes were probed with monoclonal antibodies to the isopeptide ε-(γ-glutamyllysine cross-bridge formed by TG2 enzymatic activity to determine if these antibodies co-localized with antibodies to LSA-1 in the growing liver schizonts. Results This study identified a substrate motif for (TG2 and a putative casein kinase 2 phosphorylation site within the central repeat region of LSA-1. The function of TG2 is the post-translational modification of proteins by the formation of a unique isopeptide ε-(γ-glutamyllysine cross-bridge between glutamine and lysine residues. When recombinant LSA-1 protein was crosslinked in vitro by purified TG2 in a calcium dependent reaction, a flocculent mass of protein was formed that was highly resistant to degradation. The cross-linking was not detectably affected by phosphorylation with plasmodial CK2 in vitro. Monoclonal antibodies specific to the very unique TG2 catalyzed ε- lysine cross-bridge co-localized with antibodies to LSA-1 in infected human hepatocytes providing visual evidence that LSA-1 was cross-linked in vivo

  1. Nonlinear microscopy of lipid storage and fibrosis in muscle and liver tissues of mice fed high-fat diets

    Science.gov (United States)

    Brackmann, Christian; Gabrielsson, Britt; Svedberg, Fredrik; Holmäng, Agneta; Sandberg, Ann-Sofie; Enejder, Annika

    2010-11-01

    Hallmarks of high-fat Western diet intake, such as excessive lipid accumulation in skeletal muscle and liver as well as liver fibrosis, are investigated in tissues from mice using nonlinear microscopy, second harmonic generation (SHG), and coherent anti-Stokes Raman scattering (CARS), supported by conventional analysis methods. Two aspects are presented; intake of standard chow versus Western diet, and a comparison between two high-fat Western diets of different polyunsaturated lipid content. CARS microscopy images of intramyocellular lipid droplets in muscle tissue show an increased amount for Western diet compared to standard diet samples. Even stronger diet impact is found for liver samples, where combined CARS and SHG microscopy visualize clear differences in lipid content and collagen fiber development, the latter indicating nonalcoholic fatty liver disease (NAFLD) and steatohepatitis induced at a relatively early stage for Western diet. Characteristic for NAFLD, the fibrous tissue-containing lipids accumulate in larger structures. This is also observed in CARS images of liver samples from two Western-type diets of different polyunsaturated lipid contents. In summary, nonlinear microscopy has strong potential (further promoted by technical advances toward clinical use) for detection and characterization of steatohepatitis already in its early stages.

  2. Comparative Proteomic Analysis of Human Liver Tissue and Isolated Hepatocytes with a Focus on Proteins Determining Drug Exposure.

    Science.gov (United States)

    Vildhede, Anna; Wiśniewski, Jacek R; Norén, Agneta; Karlgren, Maria; Artursson, Per

    2015-08-07

    Freshly isolated human hepatocytes are considered the gold standard for in vitro studies of liver functions, including drug transport, metabolism, and toxicity. For accurate predictions of the in vivo outcome, the isolated hepatocytes should reflect the phenotype of their in vivo counterpart, i.e., hepatocytes in human liver tissue. Here, we quantified and compared the membrane proteomes of freshly isolated hepatocytes and human liver tissue using a label-free shotgun proteomics approach. A total of 5144 unique proteins were identified, spanning over 6 orders of magnitude in abundance. There was a good global correlation in protein abundance. However, the expression of many plasma membrane proteins was lower in the isolated hepatocytes than in the liver tissue. This included transport proteins that determine hepatocyte exposure to many drugs and endogenous compounds. Pathway analysis of the differentially expressed proteins confirmed that hepatocytes are exposed to oxidative stress during isolation and suggested that plasma membrane proteins were degraded via the protein ubiquitination pathway. Finally, using pitavastatin as an example, we show how protein quantifications can improve in vitro predictions of in vivo liver clearance. We tentatively conclude that our data set will be a useful resource for improved hepatocyte predictions of the in vivo outcome.

  3. Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering.

    Science.gov (United States)

    Jiang, Wei-Cheng; Cheng, Yu-Hao; Yen, Meng-Hua; Chang, Yin; Yang, Vincent W; Lee, Oscar K

    2014-04-01

    Liver transplantation is the ultimate treatment for severe hepatic failure to date. However, the limited supply of donor organs has severely hampered this treatment. So far, great potentials of using mesenchymal stem cells (MSCs) to replenish the hepatic cell population have been shown; nevertheless, there still is a lack of an optimal three-dimensional scaffold for generation of well-transplantable hepatic tissues. In this study, we utilized a cryo-chemical decellularization method which combines physical and chemical approach to generate acellular liver scaffolds (ALS) from the whole liver. The produced ALS provides a biomimetic three-dimensional environment to support hepatic differentiation of MSCs, evidenced by expression of hepatic-associated genes and marker protein, glycogen storage, albumin secretion, and urea production. It is also found that hepatic differentiation of MSCs within the ALS is much more efficient than two-dimensional culture in vitro. Importantly, the hepatic-like tissues (HLT) generated by repopulating ALS with MSCs are able to act as functional grafts and rescue lethal hepatic failure after transplantation in vivo. In summary, the cryo-chemical method used in this study is suitable for decellularization of liver and create acellular scaffolds that can support hepatic differentiation of MSCs and be used to fabricate functional tissue-engineered liver constructs.

  4. Visible to near-infrared refractive properties of freshly-excised human-liver tissues: marking hepatic malignancies

    Science.gov (United States)

    Giannios, Panagiotis; Toutouzas, Konstantinos G.; Matiatou, Maria; Stasinos, Konstantinos; Konstadoulakis, Manousos M.; Zografos, George C.; Moutzouris, Konstantinos

    2016-01-01

    The refractive index is an optical constant that plays a significant role in the description of light-matter interactions. When it comes to biological media, refraction is understudied despite recent advances in the field of bio-optics. In the present article, we report on the measurement of the refractive properties of freshly excised healthy and cancerous human liver samples, by use of a prism-coupling technique covering the visible and near-infrared spectral range. Novel data on the wavelength-dependent complex refractive index of human liver tissues are presented. The magnitude of the real and imaginary part of the refractive index is correlated with hepatic pathology. Notably, the real index contrast is pointed out as a marker of discrimination between normal liver tissue and hepatic metastases. In view of the current progress in optical biosensor technologies, our findings may be exploited for the development of novel surgical and endoscopic tools. PMID:27297034

  5. The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues.

    Science.gov (United States)

    Altinoz, E; Turkoz, Y; Vardi, N

    2015-01-01

    The aim of this study was to investigate the protective effects of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues in rats.The rats were divided into four groups. Acrylamide administration increased MDA levels in all tissues significantly (p acrylamide+NAC administration decreased MDA levels significantly as compared to the acrylamide group, and lowered it to a level close to the control group values (p acrylamide group (p acrylamide+NAC administration increased GSH levels significantly in all tissues. Whereas GST activity decreased significantly in the acrylamide group in liver and small intestine tissues as compared to the other groups (p acrylamide+NAC group in all tissues as compared to the acrylamide group (p acrylamide group. Small intestine histopathology showed that the intestinal villous epithelial cells were damaged significantly in the acrylamide group.Our results indicate that a high level of acrylamide causes oxidative damage in liver and small and large intestine tissues, while N-acetylcysteine administration in a pharmacological dose shows to have an antioxidant effect in preventing this damage (Tab. 2, Fig. 2, Ref. 66).

  6. Liver fat content is linked to inflammatory changes in subcutaneous adipose tissue in type 2 diabetes patients.

    NARCIS (Netherlands)

    Jansen, H.J.; Vervoort, G.M.; Graaf, van der M.; Stienstra, R.; Tack, C.J.

    2013-01-01

    Background Patients with type 2 diabetes mellitus (T2DM) are typically overweight and have an increased liver fat content (LFAT). High LFAT may be explained by an increased efflux of free fatty acids from the adipose tissue, which is partly instigated by inflammatory changes. This would imply an

  7. Weak mitochondrial targeting sequence determines tissue-specific subcellular localization of glutamine synthetase in liver and brain cells.

    NARCIS (Netherlands)

    Matthews, G.D.; Gur, N.; Koopman, W.J.H.; Pines, O.; Vardimon, L.

    2010-01-01

    Evolution of the uricotelic system for ammonia detoxification required a mechanism for tissue-specific subcellular localization of glutamine synthetase (GS). In uricotelic vertebrates, GS is mitochondrial in liver cells and cytoplasmic in brain. Because these species contain a single copy of the GS

  8. Molecular constituents of the extracellular matrix in rat liver mounting a hepatic progenitor cell response for tissue repair

    DEFF Research Database (Denmark)

    Vestentoft, Peter Siig; Jelnes, Peter; Andersen, Jesper Bøje

    2013-01-01

    Tissue repair in the adult mammalian liver occurs in two distinct processes, referred to as the first and second tiers of defense. We undertook to characterize the changes in molecular constituents of the extracellular matrix when hepatic progenitor cells (HPCs) respond in a second tier of defense...

  9. Liver fat content is linked to inflammatory changes in subcutaneous adipose tissue in type 2 diabetes patients

    NARCIS (Netherlands)

    Jansen, H.J.; Vervoort, G.M.M.; Graaf, M. van der; Stienstra, R.; Tack, C.J.J.

    2013-01-01

    BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are typically overweight and have an increased liver fat content (LFAT). High LFAT may be explained by an increased efflux of free fatty acids from the adipose tissue, which is partly instigated by inflammatory changes. This would imply an

  10. STUDY ON GLUTATHIONE S-TRANSFERASE INHIBITION ASSAY BY TRICLABENDAZOLE. III: NEMATODIRUS PARASITE AND SHEEP LIVER TISSUE

    Directory of Open Access Journals (Sweden)

    A. Farahnak

    2007-09-01

    Full Text Available The most important and widely prevalent nematodes of sheep are the trichostrongyle group parasites, including nematodirus parasite. Accidental infection of man by nematodirus has been reported in Iran. Glutathione S-Transferase enzymes (GSTs are detoxification enzymes in parasites such as nematodirus. Therefore, GST enzymes of these parasites could be a target for evaluation of drugs effect as triclabendazole (C14H9CL3N2OS. For this reason, GST enzymes were purified from nematodirus parasite and sheep liver tissue by glutathione affinity chromatography and prepared their SDS-PAGE banding pattern for GST fraction separation. GST enzymes specific activity levels are also assayed in the whole extract and purified solutions with reduced glutathione (GSH and 1-chloro-2, 4-dinitrobenzen (CDNB secondary substrate. Finally, GST inhibition assay was investigated in the solutions by powder and bolus forms of triclabendazole. The level of GST specific activity in purified solutions was detected 9.86 µmol / min/ mg protein for nematodirus parasite and 37.84 µmol/ min/ mg protein for liver tissue. Comparison of the effect of powder and bolus of tricla¬bendazole on solutions revealed inhibition concentration (IC50 5.54 and 6.01 µg/ml for nematodirus GST and 8.65 and 9.70 µg/ml for liver tissue GST, respectively. These findings revealed the possibility of isolation and inhibition of nematodirus GST by triclabendazole, and more tolerance of liver tissue than parasite against this drug in vitro situation.

  11. Normal tissue tolerance to external beam radiation therapy: Liver; Dose de tolerance a l'irradiation des tissus sains: le foie

    Energy Technology Data Exchange (ETDEWEB)

    De Bari, B.; Mornex, F. [Departement de radiotherapie-oncologie, centre hospitalier Lyon-Sud, Universite Claude-Bernard Lyon 1 et EA3738, 69 - Pierre-Benite (France); Pointreau, Y. [Service de radiotherapie, hopital Bretonneau, CHU de Tours, centre regional universitaire de cancerologie Henry-S.-Kaplan, 37 - Tours (France); Rio, E. [Service de radiotherapie, centre regional de lutte contre le cancer Nantes-Atlantique, 44 - Saint-Herblain (France); Mirabel, X. [Centre Oscar-Lambret, 59 - Lille (France)

    2010-07-15

    The liver is a large abdominal organ in the right hypondrium. Because of its anatomical situation, it is near many abdominal PTVs as well as some lower thoracic PVTs. The liver could also be at the same time the target (for irradiation of liver metastases or primary liver tumours) and organ at risk (OAR). Radiation-induced liver disease (RILD) is radio-biologically the normal tissue complication probability (NTCP), i.e., the clinical event limiting the total dose that could be delivered. This review describes radiobiological criteria justifying the NTCP data, and recommendations for conformal 3D radiotherapy and stereotactic liver irradiation. (authors)

  12. Gestational age dependent changes of the fetal brain, liver and adipose tissue fatty acid compositions in a population with high fish intakes

    NARCIS (Netherlands)

    Kuipers, Remko S.; Luxwolda, Martine F.; Offringa, Pieter J.; Boersma, E. Rudy; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    2012-01-01

    Introduction: There are no data on the intrauterine fatty acid (FA) compositions of brain, liver and adipose tissue of infants born to women with high fish intakes. Subjects and methods: We analyzed the brain (n = 18), liver (n = 14) and adipose tissue (n = 11) FA compositions of 20 stillborn infant

  13. High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice

    NARCIS (Netherlands)

    van der Heijden, Roel A.; Sheedfar, Fareeba; Morrison, Martine C.; Hommelberg, Pascal P. H.; Kor, Danny; Kloosterhuis, Niels J.; Gruben, Nanda; Youssef, Sameh A.; de Bruin, Alain; Hofker, Marten H.; Kleemann, Robert; Koonen, Debby P. Y.; Heeringa, Peter

    2015-01-01

    Metabolic inflammation in adipose tissue and the liver is frequently observed as a result of diet-induced obesity in human and rodent studies. Although the adipose tissue and the liver are both prone to become chronically inflamed with prolonged obesity, their individual contribution to the developm

  14. High-fat diet induced obesity primes inflammation in adipose tissues prior to liver in C57BL/6j mice

    NARCIS (Netherlands)

    Heijden, R.A. van der; Fareeba Sheedfar, F.; Morrison, M.C.; Hommelberg, P.P.H.; Kor1, D.; Kloosterhuis, N.J.; Gruben, N.; Youssef, S.A.; Bruin, A. de; Hofker, M.H.; Kleemann, R.; Koonen, D.P.Y.; Heeringa1, P.

    2015-01-01

    Metabolic inflammation in adipose tissue and the liver is frequently observed as a result of diet-induced obesity in human and rodent studies. Although the adipose tissue and the liver are both prone to become chronically inflamed with prolonged obesity, their individual contribution to the

  15. High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice

    NARCIS (Netherlands)

    van der Heijden, Roel A; Sheedfar, Fareeba; Morrison, Martine C; Hommelberg, Pascal H; Kor, Danny; Kloosterhuis, Niels J; Gruben, Nanda; Youssef, Sameh A; de Bruin, Alain|info:eu-repo/dai/nl/304837261; Hofker, Marten H; Kleemann, Robert; Koonen, Debby Y; Heeringa, Peter

    Metabolic inflammation in adipose tissue and the liver is frequently observed as a result of diet-induced obesity in human and rodent studies. Although the adipose tissue and the liver are both prone to become chronically inflamed with prolonged obesity, their individual contribution to the

  16. Gestational age dependent changes of the fetal brain, liver and adipose tissue fatty acid compositions in a population with high fish intakes

    NARCIS (Netherlands)

    Kuipers, Remko S.; Luxwolda, Martine F.; Offringa, Pieter J.; Boersma, E. Rudy; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    2012-01-01

    Introduction: There are no data on the intrauterine fatty acid (FA) compositions of brain, liver and adipose tissue of infants born to women with high fish intakes. Subjects and methods: We analyzed the brain (n = 18), liver (n = 14) and adipose tissue (n = 11) FA compositions of 20 stillborn

  17. Tissue-specific bioaccumulation of human and veterinary antibiotics in bile, plasma, liver and muscle tissues of wild fish from a highly urbanized region.

    Science.gov (United States)

    Zhao, Jian-Liang; Liu, You-Sheng; Liu, Wang-Rong; Jiang, Yu-Xia; Su, Hao-Chang; Zhang, Qian-Qian; Chen, Xiao-Wen; Yang, Yuan-Yuan; Chen, Jun; Liu, Shuang-Shuang; Pan, Chang-Gui; Huang, Guo-Yong; Ying, Guang-Guo

    2015-03-01

    We investigated the bioaccumulation of antibiotics in bile, plasma, liver and muscle tissues of wild fish from four rivers in the Pearl River Delta region. In total, 12 antibiotics were present in at least one type of fish tissues from nine wild fish species in the four rivers. The mean values of log bioaccumulation factors (log BAFs) for the detected antibiotics in fish bile, plasma, liver, and muscle tissues were at the range of 2.06-4.08, 1.85-3.47, 1.41-3.51, and 0.48-2.70, respectively. As the digestion tissues, fish bile, plasma, and liver showed strong bioaccumulation ability for some antibiotics, indicating a different bioaccumulation pattern from hydrophobic organic contaminants. Human health risk assessment based on potential fish consumption indicates that these antibiotics do not appear to pose an appreciable risk to human health. To the best of our knowledge, this is first report of bioaccumulation patterns of antibiotics in wild fish bile and plasma.

  18. Insulin Signaling in Liver and Adipose Tissues in Periparturient Dairy Cows Supplemented with Dietary Nicotinic Acid.

    Science.gov (United States)

    Kinoshita, Asako; Kenéz, Ákos; Locher, Lena; Meyer, Ulrich; Dänicke, Sven; Rehage, Jürgen; Huber, Korinna

    2016-01-01

    The glucose homeostasis in dairy cattle is very well controlled, in line with the metabolic adaptation during the periparturient period. Former studies showed that nicotinic acid (NA) lowered plasma non-esterified fatty acids (NEFA) concentrations and increased insulin sensitivity in dairy cows. Thus, the purpose of this study was to investigate whether the expression of proteins involved in hepatic and adipose insulin signaling and protein expression of hepatic glucose transporter 2 (GLUT2) were affected by dietary NA and dietary concentrate intake in periparturient dairy cows. Twenty pluriparous German Holstein cows were fed with the same diet from about 21 days before the expected calving date (d-21) to calving. After calving, cows were randomly assigned in 4 groups and fed with diets different in concentrate proportion ("HC" with 60:40% or "LC" with 30:70% concentrate-to-roughage ratio) and supplemented with NA (24 g/day) (NA) or without (CON) until d21. Biopsy samples were taken from the liver, subcutaneous (SCAT) and retroperitoneal (RPAT) adipose tissues at d-21 and d21. Protein expression of insulin signaling molecules (insulin receptor (INSR), phosphatidylinositol-3-kinase (PI3K), protein kinase Cζ (PKCζ)) and hepatic GLUT2 was measured by Western Blotting. The ratio of protein expression at d21/at d-21 was calculated and statistically evaluated for the effects of time and diet. Cows in HC had significantly higher dietary energy intake than cows in LC. In RPAT a decrease in PI3K and PKCζ expression was found in all groups, irrespectively of diet. In the liver, the GLUT2 expression was significantly lower in cows in NA compared with cows in CON. In conclusion, insulin signaling might be decreased in RPAT over time without any effect of diet. NA was able to modulate hepatic GLUT2 expression, but its physiological role is unclear.

  19. Sorafenib metabolism is significantly altered in the liver tumor tissue of hepatocellular carcinoma patient.

    Directory of Open Access Journals (Sweden)

    Ling Ye

    Full Text Available BACKGROUND: Sorafenib, the drug used as first line treatment for hepatocellular carcinoma (HCC, is metabolized by cytochrome P450 (CYP 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT 1A9-mediated glucuronidation. Liver diseases are associated with reduced CYP and UGT activities, which can considerably affect drug metabolism, leading to drug toxicity. Thus, understanding the metabolism of therapeutic compounds in patients with liver diseases is necessary. However, the metabolism characteristic of sorafenib has not been systematically determined in HCC patients. METHODS: Sorafenib metabolism was tested in the pooled and individual tumor hepatic microsomes (THLMs and adjacent normal hepatic microsomes (NHLMs of HCC patients (n = 18. Commercial hepatic microsomes (CHLMs were used as a control. In addition, CYP3A4 and UGT1A9 protein expression in different tissues were measured by Western blotting. RESULTS: The mean rates of oxidation and glucuronidation of sorafenib were significantly decreased in the pooled THLMs compared with those in NHLMs and CHLMs. The maximal velocity (Vmax of sorafenib oxidation and glucuronidation were approximately 25-fold and 2-fold decreased in the pooled THLMs, respectively, with unchanged Km values. The oxidation of sorafenib in individual THLMs sample was significantly decreased (ranging from 7 to 67-fold than that in corresponding NHLMs sample. The reduction of glucuronidation in THLMs was observed in 15 out of 18 patients' samples. Additionally, the level of CYP3A4 and UGT1A9 expression were both notably decreased in the pooled THLMs. CONCLUSIONS: Sorafenib metabolism was remarkably decreased in THLMs. This result was associated with the down regulation of the protein expression of CYP3A4 and UGT1A9.

  20. Tissue contaminants and associated transcriptional response in trout liver from high elevation lakes of Washington

    Science.gov (United States)

    Moran, P.W.; Aluru, N.; Black, R.W.; Vijayan, M.M.

    2007-01-01

    The consistent cold temperatures and large amount of precipitation in the Olympic and Cascade ranges of Washington State are thought to enhance atmospheric deposition of contaminants. However, little is known about contaminant levels in organisms residing in these remote high elevation lakes. We measured total mercury and 28 organochlorine compounds in trout collected from 14 remote lakes in the Olympic, Mt. Rainer, and North Cascades National Parks. Mercury was detected in trout from all lakes sampled (15 to 262 ??g/kg ww), while two organochlorines, total polychlorinated biphenyls (tPCB) and dichlorodiphenyldichloroethylene (DDE), were also detected in these fish tissues (<25 ??g/kg ww). In sediments, organochlorine levels were below detection, while median total and methyl mercury were 30.4 and 0.34 ??g/ kg dry weight (ww), respectively. Using fish from two lakes, representing different contaminant loading levels (Wilcox lake: high; Skymo lake: low), we examined transcriptional response in the liver using a custom-made low-density targeted rainbow trout cDNA microarray. We detected significant differences in liver transcriptional response, including significant changes in metabolic, endocrine, and immune-related genes, in fish collected from Wilcox Lake compared to Skymo Lake. Overall, our results suggest that local urban areas contribute to the observed contaminant patterns in these high elevation lakes, while the transcriptional changes point to a biological response associated with exposure to these contaminants in fish. Specifically, the gene expression pattern leads us to hypothesize a role for mercury in disrupting the metabolic and reproductive pathways in fish from high elevation lakes in western Washington. ?? 2007 American Chemical Society.

  1. Investigation of liver tissue and biochemical parameters of adult wistar rats treated with Arctium lappa L.

    Directory of Open Access Journals (Sweden)

    Fabrícia Souza Predes

    2009-04-01

    Full Text Available This study was carried out to evaluate the effects of Arctium lappa L. (burdock on the liver of adult male Wistar rats as measured by light microscopy and biochemical parameters. The rats received the extract in water bottles at doses of 10 or 20 g/L daily for 40 days. There were no significant changes in the plasma levels of albumin, aspartate transaminase (AST, alanine transaminase (ALT, gamma glutamyl transferase (GGT, total protein, total cholesterol, urea, uric acid, triacylglycerol, calcium, phosphorus, chlorine and direct bilirubin. The morphological analysis did not reveal histopathological alterations in liver tissue. Both biochemical and morphological data did not indicate A. lappa toxicity.A bardana (Arctium lappa L é uma planta trazida do Japão e aclimatada no Brasil, e é extensamente utilizada na medicina popular em todo mundo. Este estudo foi realizado para avaliar os possíveis efeitos da A. lappa no fígado e nos parâmetros bioquímicos plasmáticos em ratos Wistar adultos. Estes receberam a infusão de bardana nas doses de 10 ou 20 g de folhas secas /L de água, por 40 dias. Não houve alteração significativa nos níveis plasmáticos de albumina, aspartato transaminase (AST, alanina transaminase (ALT, gamma glutamil transferase (GGT, proteínas totais, colesterol total, uréia, ácido úrico, triglicérides, cálcio, fósforo, bilirrubina direta e cloro. A análise morfológica não revelou alterações histopatológicas no fígado. Os dados bioquímicos e morfológicos não indicaram a toxicidade da bardana.

  2. Tissue inhibitor of matrix metalloproteinase-1 expression in colorectal cancer liver metastases is associated with vascular structures.

    Science.gov (United States)

    Illemann, Martin; Eefsen, Rikke Helene Løvendahl; Bird, Nigel Charles; Majeed, Ali; Osterlind, Kell; Laerum, Ole Didrik; Alpízar-Alpízar, Warner; Lund, Ida Katrine; Høyer-Hansen, Gunilla

    2016-02-01

    Metastatic growth by colorectal cancer cells in the liver requires the ability of the cancer cells to interact with the new microenvironment. This interaction results in three histological growth patterns of liver metastases: desmoplastic, pushing, and replacement. In primary colorectal cancer several proteases, involved in the degradation of extracellular matrix components, are up-regulated. In liver metastases, their expression is growth pattern dependent. Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is a strong prognostic marker in plasma from colorectal cancer patients, with significant higher levels in patients with metastatic disease. We therefore wanted to determine the expression pattern of TIMP-1 in primary colorectal cancers and their matching liver metastases. TIMP-1 mRNA was primarily seen in α-smooth-muscle actin (α-SMA)-positive cells. In all primary tumors and liver metastases with desmoplastic growth pattern, TIMP-1 mRNA was primarily found in α-SMA-positive myofibroblasts located at the invasive front. Some α-SMA-positive cells with TIMP-1 mRNA were located adjacent to CD34-positive endothelial cells, identifying them as pericytes. This indicates that TIMP-1 in primary tumors and liver metastases with desmoplastic growth pattern has dual functions; being an MMP-inhibitor at the cancer periphery and involved in tumor-induced angiogenesis in the pericytes. In the liver metastases with pushing or replacement growth patterns, TIMP-1 was primarily expressed by activated hepatic stellate cells at the metastasis/liver parenchyma interface. These cells were located adjacent to CD34-positive endothelial cells, suggesting a function in tumor-induced angiogenesis. We therefore conclude that TIMP-1 expression is growth pattern dependent in colorectal cancer liver metastases.

  3. The metabolic effects of di (2-ethyl hexyl phthalate medium dose on lipid profiles in serum and liver tissue

    Directory of Open Access Journals (Sweden)

    Buang Y

    2011-02-01

    Full Text Available Background: Di (2-ethyl hexyl phthalate is the most widely used  plasticizer in blood storage bag for transfusion. This substance can modify lipid metabolism. This study was aimed to elucidate the metabolic effects of di (2-ethyl hexyl phthalate medium dose on lipid profiles in serum and liver tissue.Methods: Sprague Dawley rats were fed 1.0 % di (2-ethyl hexyl phthalate diet (DEHP group, n=5 or a non-supplemented diet (control group, n=5 for 10 days. The rats were allowed to freely access each food. Serum lipid concentrations were measured using enzyme assay kits. Lipids of liver tissues were extracted and the lipid contents were determined. A peach of liver was prepared to determine the activities of malic enzyme and carnitine palmitoyl transferase-1 (CPT-1.Results: Serum lipid concentrations (mg/dL of DEHP group decreased compared to control (P<0.05. The serum triglyceride (TG concentrations of control and DEHP groups were respectively (100.5±16.5 and (31.2±1.7; phospholipid (PL, (143.3±7.8 and (88.9±3.2; total cholesterol, (88.7±4.6 and (51.9±2.3. The liver TG content of control and DEHP group (mg/g liver were respectively, (40.8±4.4 and (23.7±1.3; liver cholesterol were (3.36±0.29 and (2.33±0.23; and the liver PL were (36.5±1.0 and (41.7±0.6. Malic enzyme and CPT-1 activities (nmol/min/mg protein of DEHP group increased compared to control (P<0.05, in which their increases were approximately by 4.35- and 2.33-folds,  respectively.Conclusion: The di (2-ethyl hexyl phthalate medium dose attenuates lipids secretion from the liver cells into the bloodstream. The increase of liver PL level accompanied with the promotions of malic enzyme and the CPT-1 activities are the key factors of the dietary di (2-ethyl hexyl phthalate effects in rats to attenuate the lipid secretions from the livers. (Med J Indones 2011; 20:20-6Keywords: Di (2-ethyl hexyl phthalate, hyperphospholipids, lipolysis, liver lipids, serum lipids

  4. Long-term effects of evodiamine on expressions of lipogenesis and lipolysis genes in mouse adipose and liver tissues.

    Science.gov (United States)

    Jiang, D F; Li, W T; Yang, H L; Zhang, Z Z; Chen, D; Sun, C

    2014-02-20

    Evodiamine, the major alkaloid component isolated from the fruit of dried, unripened Evodia rutaecarpa Bentham, affects the plasma levels of cholecystokinin and various biological events such as gastric emptying and gastrointestinal transit; these effects of evodiamine were previously investigated in male rats. In this study, we aimed to investigate the effects of evodiamine on average daily weight gain, rectal temperature, and expressions of genes involved in lipid metabolism in liver and adipose tissues. Evodiamine was added as a supplement, comprising 0.02, 0.04, and 0.06% of the diet fed to mice for 1, 2, 3, and 4 weeks. Results showed that average daily weight gain and rectal temperature decreased significantly over time in a dose-dependent manner. Evodiamine changed expressions of the peroxisome proliferator-activated receptor-g (PPARg) in mouse adipose and liver tissues in time- and dose-dependent manners. We found that evodiamine decreased mRNA expression of the sterol-regulatory element binding protein (SREBP-1c) and fatty acid synthase in adipose tissue. In addition, evodiamine increased expressions of hormone-sensitive lipase in both liver and adipose tissues. Interestingly, evodiamine increased the expression of triglyceride hydrolase only in adipose tissue. In conclusion, evodiamine could influence lipid metabolism through regulation of the expressions of its key genes, as well as reduce body heat and body weight.

  5. Gene Expression and Correlation of Pten and Fabp4 in Liver, Muscle, and Adipose Tissues of Type 2 Diabetes Rats.

    Science.gov (United States)

    Su, Di; Zhang, Chuan-Ling; Gao, Ying-Chun; Liu, Xiao-Ying; Li, Cai-Ping; Huangfu, Jian; Xiao, Rui

    2015-11-22

    The aim of this work was to study the Fabp4 and Pten gene expression and correlation in the liver, muscle, and adipose tissues of type 2 diabetes mellitus (T2DM) rats. Male Wistar rats (8 weeks old) were randomly divided into 2 groups (n=12/group): a control group fed a normal diet for 8 weeks and an experimental group fed a high-fat, high-sugar diet for 8 weeks and that received 25 mg/kg streptozotocin by intraperitoneal injection to induce T2DM. The random blood glucose, fasting blood glucose, and fasting insulin levels were measured. The expression of Pten and Fabp4 in the liver, muscle, and epididymal adipose tissues was estimated by real-time quantitative PCR. Pearson correlation coefficient analysis was used to investigate the expression correlation between Pten and Fabp4 in T2DM rats. The gene expressions of Pten and Fabp4 in the liver, muscle, and adipose tissues of T2DM rats were all significantly higher than those in the control group (Pmuscles and Fabp4 was highly expressed in muscle and adipose tissues. Furthermore, expressions of Fabp4 and Pten in the muscle and adipose tissues of T2DM rats were positively correlated (Pmuscles of T2DM rats may play an important role in the insulin resistance of T2DM. However, the mechanism by which these 2 genes function in T2DM needs further study.

  6. [Changes of ultrastructure of the capillary endotheliocytes of ischemized and nonaffected muscular tissue after transplantation of human hemopoietic stem cells of fetal liver in experiment in vivo].

    Science.gov (United States)

    Saliutin, R V; Zadorozhna, T D; Medvets'kyĭ, E B; Driuk, M F; Petrenko, A Iu

    2010-04-01

    In experiment was investigated ultrastructure of the capillaries endothelial cells and histological peculiarities of muscular tissue on various stages after transplantation of hemopoietic stem cells of fetal liver (HSCFL). There was proved, that in ischemic environment HSCFL stimulate processes of angiogenesis, and in the case of transplantation into intact muscular tissue they are differentiating into the tissue macrophages, not interfering with muscular tissue structure.

  7. Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Sulin Cheng

    Full Text Available Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49 and women (n = 52 with and without NAFLD.Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS. Serum samples were analyzed using a nuclear magnetic resonance (NMR metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.Increased branched-chain amino acid (BCAA, aromatic amino acid (AAA and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all. Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all, whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all.Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

  8. Fasting for 21days leads to changes in adipose tissue and liver physiology in juvenile checkered garter snakes (Thamnophis marcianus).

    Science.gov (United States)

    Davis, Mary; Jessee, Renee; Close, Matthew; Fu, Xiangping; Settlage, Robert; Wang, Guoqing; Cline, Mark A; Gilbert, Elizabeth R

    2015-12-01

    Snakes often undergo periods of prolonged fasting and, under certain conditions, can survive years without food. Despite this unique phenomenon, there are relatively few reports of the physiological adaptations to fasting in snakes. At post-prandial day 1 (fed) or 21 (fasting), brain, liver, and adipose tissues were collected from juvenile checkered garter snakes (Thamnophis marcianus). There was greater glycerol-3-phosphate dehydrogenase (G3PDH)-specific activity in the liver of fasted than fed snakes (P=0.01). The mRNA abundance of various fat metabolism-associated factors was measured in brain, liver, and adipose tissue. Lipoprotein lipase (LPL) mRNA was greater in fasted than fed snakes in the brain (P=0.04). Adipose triglyceride lipase (ATGL; P=0.006) mRNA was greater in the liver of fasted than fed snakes. In adipose tissue, expression of peroxisome proliferator-activated receptor (PPAR)γ (P=0.01), and fatty acid binding protein 4 (P=0.03) was greater in fed than fasted snakes. Analysis of adipocyte morphology revealed that cross-sectional area (P=0.095) and diameter (P=0.27) were not significantly different between fed and fasted snakes. Results suggest that mean adipocyte area can be preserved during fasting by dampening lipid biosynthesis while not changing rates of lipid hydrolysis. In the liver, however, extensive lipid remodeling may provide energy and lipoproteins to maintain lipid structural integrity during energy restriction. Because the duration of fasting was not sufficient to change adipocyte size, results suggest that the liver is important as a short-term provider of energy in the snake.

  9. The Effect of Silver Nanoparticles on the Biochemical Parameters of Liver Function in Serum, and the Expression of Caspase-3 in the Liver Tissues of Male Rats

    Directory of Open Access Journals (Sweden)

    Pourhamzeh

    2016-06-01

    Full Text Available Background Silver nanoparticles have antibacterial properties and their use is growing in different industries. Since the toxicity of nanosilver is not well known, it is essential to examine its safety. Objectives This experiment was undertaken to study the effects of nanosilver on rat liver function with an evaluation of blood biochemistry parameters and caspase-3 expression in the liver. Materials and Methods In this experimental study, 40 adult male Sprague-Dawley rats were divided into five groups. In the four experimental groups, nanosilver particles were given orally for 28 consecutive days at doses of 30, 125, 300, or 700 mg/kg. Rats in the control group received equal volumes of deionized water. To evaluate the expression of caspase-3 in liver tissue, the real-time PCR method was used. Albumin, total protein, total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were measured with an RA-1000 autoanalyzer. Results The results indicated that caspase-3 was upregulated in the treated groups compared to the control group (P 0.05. Conclusions Based on the present study, it can be concluded that oral administration of silver nanoparticles for 28 days had no effect on rat liver function, but probably led to early apoptotic stages.

  10. Plasma homocysteine and liver tissue S-adenosylmethionine, S-adenosylhomocysteine status in vitamin B6-deficient rats.

    Science.gov (United States)

    Taysi, S; Keles, M S; Gumustekin, K; Akyuz, M; Boyuk, A; Cikman, O; Bakan, N

    2015-01-01

    The aim of this study was to evaluate plasma homocysteine (Hcy), malondialdehyde (MDA), glutathione (GSH) levels, glutathione peroxidase (GSH-Px) and glutathione-S-transferase (GST) activities and liver tissue S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels in control and vitamin B6-deficient rats. Thirty-two male rats with a weight of 65-75 g were used for the experiment. The rats were divided into control (n=16) and vitamin B6-deficient groups. At the end of the experiment, the animals were anesthetized with ketamine-HCl (Ketalar, 20 mg/kg, i.p.), and the blood was collected by cardiac puncture after thoracotomy. Plasma Hcy, pyridoxal phosphate (PLP), liver SAM, SAH levels measured by an isocratic system with high performance liquid chromatography. Plasma GSH-Px, GSH activities and GSH, MDA levels were carried out using a spectrophotometer. Plasma Hcy, MDA, liver tissue SAH levels were significantly increased, whereas plasma GSH, PLP, liver tissue SAM levels, plasma GST, GSH-Px activities and SAM/SAH ratio were decreased compared to those of control group. Vitamin B6 deficiency causes an increase in plasma homocysteine levels. Thus, we think that vitamin B6 supplementation could be used for therapeutic purposes in hyperhomocysteinemia condition.

  11. The parallel universe: microRNAs and their role in chronic hepatitis, liver tissue damage and hepatocarcinogenesis.

    Science.gov (United States)

    Haybaeck, Johannes; Zeller, Nicolas; Heikenwalder, Mathias

    2011-10-24

    In recent years, enormous progress has been made in identifying microRNAs (miRNAs) as important regulators of gene expression and their association with or control of various liver diseases such as fibrosis, hepatitis and hepatocellular carcinoma (HCC). Indeed, many genes encoding miRNAs as well as their targets have been described and their direct or indirect link to the respective liver diseases has been investigated in various experimental systems as well as in human tissue. Here we discuss current knowledge of miRNAs and their involvement in liver diseases, elaborating in particular on the contribution of miRNAs to hepatitis, fibrosis and HCC formation. We also debate possible prognostic, predictive and therapeutic values of respective miRNAs in liver diseases. The discovery of liver disease related miRNAs has constituted a major breakthrough in liver research and will most likely be of high relevance for future therapeutic strategies, especially when dealing with hepatitis, fibrosis and HCC.

  12. Adipose tissue-secreted miR-27a promotes liver cancer by targeting FOXO1 in obese individuals

    Directory of Open Access Journals (Sweden)

    Sun B

    2015-04-01

    Full Text Available Baozhen Sun,1,* Jing Li,2,* Dan Shao,2 Yue Pan,2 Yujing Chen,2 Suo Li,1 Xiaoxiao Yao,1 Hang Li,1 Weiwei Liu,3 Ming Zhang,2 Xuewen Zhang,1 Li Chen2 1Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, People’s Republic of China; 3School of Stomatology, Jilin University, Changchun, People’s Republic of China *These authors contributed equally to this work Abstract: The current notion that obesity is a major risk factor for the development of and the mortality associated with a subset of liver cancer is well appreciated. However, detailed mechanistic insights underlying this relationship are lacking. Better understanding of the adipose tissue-secreted miRNAs that play a potential role in defining primary liver cancer development and mediating the obesity-cancer communication offers the potential for new insights into tumor growth and interventions to modulate tumor formation and progression. In this study, we clearly demonstrated that miR-27a is more highly upregulated in cancer, plasma, and adipose samples from obese liver cancer cases, and therefore reasoned that miR-27a excreted from adipose tissue leads to liver cancer development. To address this idea, we prepared miR-27a-overexpressing 3T3-L1 adipocytes and cocultured them with HepG2 liver cancer cells. Our results demonstrated that secretory miR-27a promoted liver cancer cell proliferation through the downregulation of the transcription factor FOXO1 and promoted the G1/S cell cycle transition by decreasing the cell cycle inhibitors p21 and p27 and increasing the cell cycle regulator cyclin D1. These findings improve our understanding of the involvement of miR-27a in obesity-liver cancer communication and might provide a novel putative target for obesity

  13. Histochemical demonstration of two mercury pools in trout tissues: mercury in kidney and liver after mercuric chloride exposure

    DEFF Research Database (Denmark)

    Baatrup, E; Nielsen, M G; Danscher, G

    1987-01-01

    Juvenile rainbow trout (Salmo gairdneri) were exposed to 100 ppb mercury (as HgCl2) in the water for 14 days. Concentrations of mercury in water and fish organs were monitored using radiolabeled mercury. Tissues from kidney and liver were fixed, and sections were developed by autometallography......, a method whereby accumulations of mercury sulfides and/or mercury selenides are silver amplified. In the kidney, mercury was found within lysosomes and extracellularly in the basal lamina of proximal tubules. In the liver, mercury was found within lysosomes of the hepatocytes. Additional groups of mercury...

  14. Evaluation of the potential of phase-contrast computed tomography for improved visualization of cancerous human liver tissue

    Energy Technology Data Exchange (ETDEWEB)

    Noel, Peter B.; Fingerle, Alexander A. [Technische Univ. Muenchen (Germany). Dept. of Radiology; Herzen, Julia [Technische Univ. Muenchen (Germany). Physics Dept. and Inst. of Medical Engineering] [and others

    2013-10-01

    Purpose: Phase-contrast X-ray computed tomography (PCCT) is currently investigated and developed as a potentially very interesting extension of conventional CT, and can offer several advantages for specific indications in diagnostic imaging. Current absorption-based computed tomography (CT) without the application of contrast material is limited in the detection of minor density differences in soft-tissue. The purpose of this study is to test whether PCCT can improve soft tissue contrast in healthy and tumorous human liver specimens. Materials and Methods: Two specimens of human liver (one healthy and one metastasized liver sample) were imaged with brilliant X-ray beam at the synchrotron radiation source ESRF in Grenoble, France. For correlation the same specimens were imaged with a magnetic resonance imaging system at 1.5 T. The histopathology confirmed our findings in the corresponding sections of the specimens. Results: In the phase-contrast CT images we observed a significantly enhanced soft-tissue contrast when compared to simultaneously recorded standard absorption CT measurements. Further, we found that the pathological and morphological information in the PCCT reconstructions show significant improvement when compared to those performed on MRI. Based on matching of prominent features, a good correlation between PCCT and the histological section is demonstrated; especially the tumor capsule and the surrounding vascular structures are visible in PCCT. In addition, our study revealed the ability of PCCT to visualize the blood vessels structure in the tumorous liver without the need of any contrast agents. Conclusion: Grating-based PCCT significantly improves the soft-tissue contrast in ex-vivo liver specimens and holds the potential to overcome the need of contrast materials for visualization of the tumor vascularization. (orig.)

  15. High-frequency ultrasound for monitoring changes in liver tissue during preservation

    Energy Technology Data Exchange (ETDEWEB)

    Vlad, Roxana M [Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Czarnota, Gregory J [Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Giles, Anoja [Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Sherar, Michael D [Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Hunt, John W [Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Kolios, Michael C [Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada)

    2005-01-21

    Currently the only method to assess liver preservation injury is based on liver appearance and donor medical history. Previous work has shown that high-frequency ultrasound could detect ischemic cell death due to changes in cell morphology. In this study, we use high-frequency ultrasound integrated backscatter to assess liver damage in experimental models of liver ischemia. Ultimately, our goal is to predict organ suitability for transplantation using high-frequency imaging and spectral analysis techniques. To examine the effects of liver ischemia at different temperatures, livers from Wistar rats were surgically excised, immersed in phosphate buffer saline and stored at 4 and 20 deg. C for 24 h. To mimic organ preservation, livers were excised, flushed with University of Wisconsin (UW) solution and stored at 4 deg. C for 24 h. Preservation injury was simulated by either not flushing livers with UW solution or, before scanning, allowing livers to reach room temperature. Ultrasound images and corresponding radiofrequency data were collected over the ischemic period. No significant increase in integrated backscatter ({approx}2.5 dBr) was measured for the livers prepared using standard preservation conditions. For all other ischemia models, the integrated backscatter increased by 4-9 dBr demonstrating kinetics dependent on storage conditions. The results provide a possible framework for using high-frequency imaging to non-invasively assess liver preservation injury.

  16. CD58 expression of liver tissue in patients with chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    WANG Ping; QI Bao-tai; CHEN Ping; HE Lin-jing; LI Jie; JI Yu-qiang; XIE Ming

    2008-01-01

    Background Several kinds of intercellular adhesion molecules closely relate to hepatitis B.The complex of CD2 and CD58 plays an important role in enhancing the adhesion of T lymphocytes to target cells,hyperplasia and activation of T lymphocytes.In this study,we explored the relationship between the expression of CD58 in liver tissue and chronic hepatitus B infection.Methods We determined the expression of the CD58 molecule on the surface of hepatocytes by using immunohistochemistry and the levels of serum HBV DNA from patients with HBV infection and from normal controls.The biochemical parameters of hepatic function were analyzed as well.Results CD58 expression in hepatocytes significantly increased with the severity progression of chronic HBV infection.The IOD levels(1og10)of CD58 in the control,mild,moderate,and severe chronic HBV infection groups were O,(7.20±4.64)×103,(25.63±7.41)x103 and(37.47±11.17)×103 respectively(P<0.05 compared with the control group,respectively)Conclusion CD58 probably increases cell mediated immunity to eliminate hepatitis B virus and leads to damage of hepatocytes.

  17. Genetic Diversity and Tissue Compartmentalization of the Hepatitis C Virus Genome in Blood Mononuclear Cells, Liver, and Serum from Chronic Hepatitis C Patients

    Science.gov (United States)

    Navas, Sonia; Martín, Julio; Quiroga, Juan Antonio; Castillo, Inmaculada; Carreño, Vicente

    1998-01-01

    The degree of genetic variability in the hypervariable region 1 of hepatitis C virus (HCV) was analyzed by cloning and sequencing HCV genomes obtained in paired samples of serum, liver tissue, and peripheral blood mononuclear cells (PBMC) from four chronic hepatitis C patients. Genetic variability in serum was higher than in liver tissue or PBMC at the level of complexity (the number of different sequences obtained from each type of tissue) as well as at the level of genetic distance between all pairs of sequences within each tissue (compared by the Student t test; P viral genomes differed among the three types of tissue, as shown by segregation of sequences according to their tissue of origin in phylogenetic analysis and by statistical analysis of mean genetic distances observed between sequences obtained from different tissues (P < 0.001), but sequences from liver tissue and PBMC were more closely related to each other than to those from serum. PMID:9445070

  18. Effect of Phenanthrene on the Tissue Structure of Liver and Aminotransferase Enzymes in Yellowfin Seabream (Acanthopagrus latus

    Directory of Open Access Journals (Sweden)

    Mehrnaz Shirmohammadi*

    2017-06-01

    Full Text Available Background: Polycyclic aromatic hydrocarbons (PAHs such as phenanthrene (Phe represent one of the most abundant forms of organic pollutants. The aim of this study was to assess changes in plasma levels of aminotransferase enzymes, total protein and liver tissue as biomarkers of yellowfin seabream (Acanthopagrus latus exposed to Phe for 14 d. Methods: The research was carried out in January 2016 at Khorramshahr University of Marine Sciences and Technology, Khorramshahr, Iran. Some 72 fish were injected with 2, 20, 40 and 70 mg/kg of Phe. Then tissue and blood samples were obtained at 1, 4, 7 and 14 d after injection. Results: Exposure of fish to Phe resulted in a significant increase of alanine aminotransferase (ALT, aspartate aminotransferase (AST and decrease of total protein after 7 d of the experiment (P<0.05. The main histopathological alteration was showed in different sampling days including nucleus margination, hypertrophy, vacuolation, melanomacrophages aggregates, sinusoid dilation, degeneration and picnotic nucleus. Degree of tissue change (DTC of liver was recorded in the Phe-exposed fish from normal range to moderate changes. Conclusion: The studied biomarkers such as changes in concentrations of ALT, AST and total protein as well as tissue damages in liver may be served as beneficial biomarker to assess Phe toxicity in yellowfin seabream.

  19. Osteopontin deletion prevents the development of obesity and hepatic steatosis via impaired adipose tissue matrix remodeling and reduced inflammation and fibrosis in adipose tissue and liver in mice.

    Science.gov (United States)

    Lancha, Andoni; Rodríguez, Amaia; Catalán, Victoria; Becerril, Sara; Sáinz, Neira; Ramírez, Beatriz; Burrell, María A; Salvador, Javier; Frühbeck, Gema; Gómez-Ambrosi, Javier

    2014-01-01

    Osteopontin (OPN) is a multifunctional extracellular matrix (ECM) protein involved in multiple physiological processes. OPN expression is dramatically increased in visceral adipose tissue in obesity and the lack of OPN protects against the development of insulin resistance and inflammation in mice. We sought to unravel the potential mechanisms involved in the beneficial effects of the absence of OPN. We analyzed the effect of the lack of OPN in the development of obesity and hepatic steatosis induced by a high-fat diet (HFD) using OPN-KO mice. OPN expression was upregulated in epididymal white adipose tissue (EWAT) and liver in wild type (WT) mice with HFD. OPN-KO mice had higher insulin sensitivity, lower body weight and fat mass with reduced adipose tissue ECM remodeling and reduced adipocyte size than WT mice under a HFD. Reduced MMP2 and MMP9 activity was involved in the decreased ECM remodeling. Crown-like structure number in EWAT as well as F4/80-positive cells and Emr1 expression in EWAT and liver increased with HFD, while OPN-deficiency blunted the increase. Moreover, our data show for the first time that OPN-KO under a HFD mice display reduced fibrosis in adipose tissue and liver, as well as reduced oxidative stress in adipose tissue. Gene expression of collagens Col1a1, Col6a1 and Col6a3 in EWAT and liver, as well as the profibrotic cytokine Tgfb1 in EWAT were increased with HFD, while OPN-deficiency prevented this increase. OPN deficiency prevented hepatic steatosis via reduction in the expression of molecules involved in the onset of fat accumulation such as Pparg, Srebf1, Fasn, Mogat1, Dgat2 and Cidec. Furthermore, OPN-KO mice exhibited higher body temperature and improved BAT function. The present data reveal novel mechanisms of OPN in the development of obesity, pointing out the inhibition of OPN as a promising target for the treatment of obesity and fatty liver.

  20. Osteopontin deletion prevents the development of obesity and hepatic steatosis via impaired adipose tissue matrix remodeling and reduced inflammation and fibrosis in adipose tissue and liver in mice.

    Directory of Open Access Journals (Sweden)

    Andoni Lancha

    Full Text Available Osteopontin (OPN is a multifunctional extracellular matrix (ECM protein involved in multiple physiological processes. OPN expression is dramatically increased in visceral adipose tissue in obesity and the lack of OPN protects against the development of insulin resistance and inflammation in mice. We sought to unravel the potential mechanisms involved in the beneficial effects of the absence of OPN. We analyzed the effect of the lack of OPN in the development of obesity and hepatic steatosis induced by a high-fat diet (HFD using OPN-KO mice. OPN expression was upregulated in epididymal white adipose tissue (EWAT and liver in wild type (WT mice with HFD. OPN-KO mice had higher insulin sensitivity, lower body weight and fat mass with reduced adipose tissue ECM remodeling and reduced adipocyte size than WT mice under a HFD. Reduced MMP2 and MMP9 activity was involved in the decreased ECM remodeling. Crown-like structure number in EWAT as well as F4/80-positive cells and Emr1 expression in EWAT and liver increased with HFD, while OPN-deficiency blunted the increase. Moreover, our data show for the first time that OPN-KO under a HFD mice display reduced fibrosis in adipose tissue and liver, as well as reduced oxidative stress in adipose tissue. Gene expression of collagens Col1a1, Col6a1 and Col6a3 in EWAT and liver, as well as the profibrotic cytokine Tgfb1 in EWAT were increased with HFD, while OPN-deficiency prevented this increase. OPN deficiency prevented hepatic steatosis via reduction in the expression of molecules involved in the onset of fat accumulation such as Pparg, Srebf1, Fasn, Mogat1, Dgat2 and Cidec. Furthermore, OPN-KO mice exhibited higher body temperature and improved BAT function. The present data reveal novel mechanisms of OPN in the development of obesity, pointing out the inhibition of OPN as a promising target for the treatment of obesity and fatty liver.

  1. Effects of vitamin D and resveratrol on metabolic associated markers in liver and adipose tissue from SAMP8 mice.

    Science.gov (United States)

    Rui, Yehua; Cheng, Jinbo; Qin, Liqiang; Shan, Cheng; Chang, Jie; Wang, Guiping; Wan, Zhongxiao

    2017-07-01

    SAMP8 mice exhibit multiple metabolic characteristics associated with age, and it is a suitable candidate for researching aging associated metabolic dysfunction. We aimed to 1) explore how key metabolic markers will be altered in both liver and adipose tissue with aging in SAMP8 mice; and 2) how the combination of vitamin D (VD) with resveratrol (RSV) will affect aging associated metabolic impairment in liver and adipose tissue from SAMP8 mice. SAMP8 mice and their control SAMR1 mice were divided into 5 groups, i.e. SAMR1, SAMP8, SAMP8 mice supplemented with VD, RSV and VD combined with RSV group, respectively. At the end of the intervention, glucose and insulin tolerance, p-AMP-activated protein kinase (AMPK) and amyloid precursor protein (APP), and endoplasmic reticulum (ER) stress markers in liver and adipose tissue, adiponectin secretion, p-NF-κBp65 and TNF-α protein expression in adipose tissue were determined. Compared to SAMR1 control, SAMP8 mice demonstrate impaired glucose tolerance and reduction in circulating adiponectin level; in the liver, SAMP8 mice have reduction in p-Aktser473, elevation in PTP1B and APP, p-eIF2α, GRP78 and p-JNK protein expression. In epididymal (EPI) fat, SAMP8 mice also have elevated p-Aktser473 and PTP1B compared to SAMR1 mice. In both epididymal (EPI) and subcutaneous (SC) fat, there were elevated ER stress markers, reduced p-AMPK and elevated APP, as well as elevated p-NF-κBp65 and TNF-α protein expression from SAMP8 compared to SAMR1 mice. In liver, the combined intervention significantly restored p-Aktser473, p-eIF2α and p-JNK protein expression. In both EPI and SC fat, the combined intervention is effective for reducing p-NF-κB p65 and TNF-α in both fat depot, while only partially reduced ER stress markers in SC fat. As for adiponectin, their combination is unable to reverse reduction in adiponectin level. Adiponectin secretion in SC fat from VD, RSV and VDRSV group were also significantly reduced compared to SAMR1

  2. Expression of energy metabolism related genes in the gastric tissue of obese individuals with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Mehta, Rohini; Birerdinc, Aybike; Wang, Lei; Younoszai, Zahra; Moazzez, Amir; Elariny, Hazem; Goodman, Zachary; Chandhoke, Vikas; Baranova, Ancha; Younossi, Zobair M

    2014-04-09

    Stomach is an integral part of the energy balance regulating circuit. Studies exploring the effects of cross-system changes in the energy homeostasis in stomach tissue are scarce. The proximity of the stomach to liver--the most common secondary target affected by obesity--suggests that these two organs are exposed to each other's local secretion. Therefore, we aimed at expression profiling of energy metabolism associated genes in the gastric tissue of obese non-alcoholic fatty liver disease (NAFLD) patients. A total of 24 patients with histologically-proven NAFLD were included. In the gastric tissue, gene expression profiling of 84 energy metabolism associated genes was carried out. The accumulation of the fat in the liver parenchyma is accompanied by downregulation of genes encoding for carboxypeptidase E (CPE) and Interleukin 1B (IL1B) in the gastric mucosa of same patient. In patients with high grade hepatic steatosis, Interleukin 1 beta encoding gene with anorexigenic function, IL1B was downregulated. The levels expression of 21 genes, including ADRA2B, CNR1 and LEP were significantly altered in the gastric tissue of NAFLD patients with hepatic inflammation. There were also indications of an increase in the opioid signaling within gastric mucosa that may results in a shift to proinflammatory environment within this organ and contribute to systemic inflammation and the pathogenic processes in hepatic parenchyma. We have shown differential expression of energy metabolism associated genes in the gastric tissue of obese NAFLD patients. Importantly, these gene expression profiles are associated with changes in the hepatic parenchyma as reflected in increased scores for hepatic steatosis, inflammation, fibrosis and NASH. This study suggests the complex interplay of multiple organs in the pathogenesis of obesity-related complications such as NAFLD and provides further evidence supporting an important role for gastric tissue in promoting obesity-related complications.

  3. Expressed sequence tags analysis of a liver tissue cDNA library from a highly inbred minipig line

    Institute of Scientific and Technical Information of China (English)

    CHEN You-nan; TAN Wei-dong; LU Yan-rong; QIN Sheng-fang; LI Sheng-fu; ZENG Yang-zhi; BU Hong; LI You-ping; CHENG Jing-qiu

    2007-01-01

    Background Porcine liver performing efficient physiological functions in the human body is prerequisite for successful liver xenotransplantation. However, the protein differences between pig and human remain largely unexplored. Therefore,we investigated the liver expression profile of a highly inbred minipig line.Methods A cDNA library was constructed from liver tissue of an inbred Banna minipig. Two hundred randomly selected clones were sequenced then analysed by BLAST programme.Results Alignments of the sequences showed 44% encoded previously known porcine genes. Among the 56% unknown genes, sequences of 72 clones had high similarities with known genes of other species and the similarities to human were mostly above 0.80. The other 40 clones showing no similarity to genes in National Centre for Biotechnology Information are newly discovered, expressed sequence tags specific to liver of inbred Banna minipig. Twenty-two of the 200 clones had full length encoding regions, 38 complete 5' terminal sequences and 140 complete 3' terminal sequences.Conclusion These newly discovered expression sequences may be an important resource for research involving physiological characteristics and medical usage of inbred pigs and contribute to matching studies in xenotransplantation.

  4. Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model.

    Science.gov (United States)

    Khokhlova, Tatiana D; Wang, Yak-Nam; Simon, Julianna C; Cunitz, Bryan W; Starr, Frank; Paun, Marla; Crum, Lawrence A; Bailey, Michael R; Khokhlova, Vera A

    2014-06-03

    The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has been recently gaining momentum. In HIFU, ultrasound energy from an extracorporeal source is focused within the body to ablate tissue at the focus while leaving the surrounding organs and tissues unaffected. Most HIFU therapies are designed to use heating effects resulting from the absorption of ultrasound by tissue to create a thermally coagulated treatment volume. Although this approach is often successful, it has its limitations, such as the heat sink effect caused by the presence of a large blood vessel near the treatment area or heating of the ribs in the transcostal applications. HIFU-induced bubbles provide an alternative means to destroy the target tissue by mechanical disruption or, at its extreme, local fractionation of tissue within the focal region. Here, we demonstrate the feasibility of a recently developed approach to HIFU-induced ultrasound-guided tissue fractionation in an in vivo pig model. In this approach, termed boiling histotripsy, a millimeter-sized boiling bubble is generated by ultrasound and further interacts with the ultrasound field to fractionate porcine liver tissue into subcellular debris without inducing further thermal effects. Tissue selectivity, demonstrated by boiling histotripsy, allows for the treatment of tissue immediately adjacent to major blood vessels and other connective tissue structures. Furthermore, boiling histotripsy would benefit the clinical applications, in which it is important to accelerate resorption or passage of the ablated tissue volume, diminish pressure on the surrounding organs that causes discomfort, or insert openings between tissues.

  5. Construction and characterization of a cDNA library from human liver tissue with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-hong; CHEN Zhi; YAO Hang-ping; CHEN Feng; ZHU Hai-hong; ZHOU Hong-juan

    2005-01-01

    Objective: To construct a cDNA library from human liver tissue with chronic hepatitis B and check its quality for investigating the expression level of liver tissue infected by hepatitis B virus. This will then be used to find the relevant genes and interesting proteins associated with the development of hepatitis B. Methods: The total RNA from liver tissue with chronic hepatitis B was extracted and the mRNA was purified using TRIZOL method. Switching mechanism at 5' end of the RNA transcript(SMART) technique and CDS Ⅲ/3' primer were used for first-strand cDNA synthesis. Long distance polymerase chain reaction(LD PCR) was then used to synthesize the double-strand cDNA that was then digested by Sfi I and fractionated by CHROMA SPIN-400 column. The longer than 0.4 kb cDNAs were collected and ligated to λTriplEx2 vector. Then λ phage packaging reaction and library amplification were performed. The qualities of both unamplified and amplified cDNA libraries were strictly checked by conventional titer determination. Fourteen plaques were randomly picked and tested using PCR with universal primers derived from the sequence flanking the vector. Results: The titers of unamplifed and amplified libraries were 1.94×106 pfu/ml and1.49×109 pfu/ml respectively. The percentages of recombinants from both libraries were 98.15% in unamplified library and98.76% in amplified library. The lengths of the inserts were 1.23 kb in average, 1-2 kb in 64.29%, and 0.5-1.0 kb in 35.71%.Conclusion: A high quality cDNA library from human liver tissue with chronic hepatitis B was successfully constructed.

  6. Autologous adipose tissue-derived mesenchymal stem cells are involved in rat liver regeneration following repeat partial hepatectomy

    OpenAIRE

    Liu, Tao; MU, HONG; Shen, Zhongyang; SONG, ZHUOLUN; Chen, Xiaobo; Wang, Yuliang

    2016-01-01

    Adipose tissue-derived mesenchymal stem cells (ADSCs) have been considered to be attractive and readily available adult mesenchymal stem cells, and they are becoming increasingly popular for use in regenerative cell therapy, as they are readily accessible through minimally invasive techniques. The present study investigated whether autologous ADSC transplantation promoted liver regeneration following a repeat partial hepatectomy in rats. The rats were divided into three groups as follows: 70%...

  7. Influence of recipient gender on cytochrome P450 isoforms expression in intrasplenic fetal liver tissue transplants in rats.

    Science.gov (United States)

    Lupp, Amelie; Hugenschmidt, Sabine; Danz, Manfred; Müller, Dieter

    2003-06-30

    Rat livers display a sex-specific cytochrome P450 (P450) isoforms expression pattern which is regulated by a differential profile of growth hormone (GH) secretion. The aim of the present study was to elucidate whether liver cell transplants at an ectopic site are also subject to this influence. Fetal liver tissue suspensions of mixed gender were transplanted into the spleen of adult male or female syngenic recipients. Four months after grafting transplant recipients and age-matched controls were treated with beta-naphthoflavone (BNF), phenobarbital (PB), dexamethasone (DEX) or the solvents and sacrificed 24 or 48 h thereafter. Livers and intrasplenic transplants were evaluated for the expression of the P450 subtypes 1A1, 2B1, 2E1, 3A2 and 4A1 by means of immunohistochemistry. The livers of both male and female rats displayed nearly no P450 1A1, but a distinct P450 2B1, 2E1, 3A2 and 4A1 expression. Whereas no sex differences were seen in the P450 1A1 expression, the immunostaining for P450 2B1, 3A2 and 4A1 was stronger in males and that for P450 2E1 in females. Similarly, in the intrasplenic liver cell transplants almost no P450 1A1, but a noticeable P450 2B1, 2E1, 3A2 and 4A1 expression was observed. Like in the respective livers, the immunostaining for P450 2B1, 3A2 and 4A1 was stronger in the transplants hosted by male than by female rats, whereas the opposite was the case for the P450 2E1 expression. Both in livers and transplants with some sex-specific differences P450 1A1 and 2E1 expression was induced by BNF, that of P450 2B1 by BNF and PB, and that of P450 3A2 by PB and DEX. These results indicate that the P450 system of ectopically transplanted liver cells is influenced by the gender of the recipient organism like that of the orthotopic livers.

  8. A two-equation coupled system model for determination of liver tissue temperature during radio frequency ablation.

    Science.gov (United States)

    O'Neill, D P; Peng, T; Payne, S J

    2009-01-01

    A model is presented that is an alternative approach to the bio-heat equation for use in radio frequency heating of the liver. The model comprises both a tissue subvolume and a blood subvolume. Separate bio-heat equations are determined for each subvolume, but with an additional term exchanging heat between them, thus creating a coupled system. The derivation for the two coupled differential equations is outlined and sample simulations are presented to demonstrate the importance of considering the two subvolumes separately, even when the blood subvolume is a small fraction of the tissue subvolume.

  9. An Immunomodulatory Protein (Ling Zhi-8 from a Ganoderma lucidum Induced Acceleration of Wound Healing in Rat Liver Tissues after Monopolar Electrosurgery

    Directory of Open Access Journals (Sweden)

    Hao-Jan Lin

    2014-01-01

    Full Text Available The purpose of this study was to investigate the effect of an immunomodulatory protein (Ling Zhi-8, LZ-8 on wound healing in rat liver tissues after monopolar electrosurgery. Animals were sacrificed for evaluations at 0, 3, 7, and 28 days postoperatively. It was found that the wound with the LZ-8 treatment significantly increases wound healing. Western blot analysis clearly indicated that the expression of NF-κB was decreased at 3, 7, and 28 days when liver tissues were treated with LZ-8. Moreover, caspase-3 activity of the liver tissue also significantly decreases at 7 and 28 days, respectively. DAPI staining and TUNEL assays revealed that only a minimal dispersion of NF-κB was found on the liver tissue treated with LZ-8 at day 7 as compared with day 3 and tissues without LZ-8 treatment. Similarly, apoptosis was decreased on liver tissues treated with LZ-8 at 7 days when compared to the control (monopolar electrosurgery tissues. Therefore, the analytical results demonstrated that LZ-8 induced acceleration of wound healing in rat liver tissues after monopolar electrosurgery.

  10. A pilot study of the characterization of hepatic tissue strain in children with cystic-fibrosis-associated liver disease (CFLD) by acoustic radiation force impulse imaging

    Energy Technology Data Exchange (ETDEWEB)

    Behrens, Christopher B.; Langholz, Juliane H.; Eiler, Jessika; Jenewein, Raphael; Fuchs, Konstantin; Alzen, Gerhard F.P. [University Hospital Giessen, Department of Pediatric Radiology, Giessen (Germany); Naehrlich, Lutz [University Hospital Giessen, Department of Pediatrics, Giessen (Germany); Harth, Sebastian; Krombach, Gabriele A. [University Hospital Giessen, Department of Radiology, Giessen (Germany)

    2013-03-15

    Progressive fibrotic alterations of liver tissue represent a major complication in children with cystic fibrosis. Correct assessment of cystic-fibrosis-associated liver disease (CFLD) in clinical routine is a challenging issue. Sonographic elastography based on acoustic radiation force impulse imaging (ARFI) is a new noninvasive approach for quantitatively assessing in vivo elasticity of biological tissues in many organs. To characterize ARFI elastography as a diagnostic tool to assess alteration of liver tissue elasticity related to cystic fibrosis in children. ARFI elastography and B-mode US imaging were performed in 36 children with cystic fibrosis. The children's clinical history and laboratory parameters were documented. According to the findings on conventional US, children were assigned to distinct groups indicating severity of hepatic tissue alterations. The relationship between US findings and respective elastography values was assessed. Additionally, differences between ARFI elastography values of each US group were statistically tested. Children with sonomorphologic characteristics of fibrotic tissue remodeling presented significantly increased values for tissue elasticity. Children with normal B-mode US or discrete signs of hepatic tissue alterations showed a tendency toward increased tissue stiffness indicating early tissue remodeling. Assessment of children with CFLD by means of ARFI elastography yields adequate results when compared to conventional US. For detection of early stages of liver disease with mild fibrotic reactions of hepatic tissue, ARFI elastography might offer diagnostic advantages over conventional US. Thus, liver stiffness measured by means of elastography might represent a valuable biological parameter for evaluation and follow-up of CFLD. (orig.)

  11. Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues.

    Science.gov (United States)

    Laing, Suzette; Wang, Guohui; Briazova, Tamara; Zhang, Chunbin; Wang, Aixia; Zheng, Ze; Gow, Alexander; Chen, Alex F; Rajagopalan, Sanjay; Chen, Lung Chi; Sun, Qinghua; Zhang, Kezhong

    2010-10-01

    Recent studies have suggested a link between inhaled particulate matter (PM) exposure and increased mortality and morbidity associated with pulmonary and cardiovascular diseases. However, a precise understanding of the biological mechanism underlying PM-associated toxicity and pathogenesis remains elusive. Here, we investigated the impact of PM exposure in intracellular stress signaling pathways with animal models and cultured cells. Inhalation exposure of the mice to environmentally relevant fine particulate matter (aerodynamic diameter liver tissues as well as in the mouse macrophage cell line RAW264.7. Ambient PM(2.5) exposure activates double-strand RNA-activated protein kinase-like ER kinase (PERK), leading to phosphorylation of translation initiation factor eIF2α and induction of C/EBP homologous transcription factor CHOP/GADD153. Activation of PERK-mediated UPR pathway relies on the production of reactive oxygen species (ROS) and is critical for PM(2.5)-induced apoptosis. Furthermore, PM(2.5) exposure can activate ER stress sensor IRE1α, but it decreases the activity of IRE1α in splicing the mRNA encoding the UPR trans-activator X-box binding protein 1 (XBP1). Together, our study suggests that PM(2.5) exposure differentially activates the UPR branches, leading to ER stress-induced apoptosis through the PERK-eIF2α-CHOP UPR branch. This work provides novel insights into the cellular and molecular basis by which ambient PM(2.5) exposure elicits its cytotoxic effects that may be related to air pollution-associated pathogenesis.

  12. Optical properties of normal and thermally coagulated chicken liver tissue measured ex-vivo with diffuse reflectance

    Science.gov (United States)

    Hafeez-Ullah; Atif, M.; Firdous, S.; Mehmood, M. S.; Hamza, M. Y.; Imran, M.; Hussain, G.; Ikram, M.

    2011-02-01

    The purpose of the present study is to determine the optical properties of normal and thermally coagulated chicken liver at 720, 740, 770, 810, 825 and 840 nm wavelengths of laser irradiation. So, we were able to evaluate these optical properties (absorption and scattering coefficients) with ex-vivo study using Kubelka Munk Model (KMM) from the radial dependence of the diffuse reflectance with femtosecond pulsed laser in near IR region. These coefficients were significantly increased with coagulation. The penetration depths of the diffused light have been reported to a maximum value of 8.12 ± 0.36 mm in normal liver and 2.49 ± 0.17 mm in coagulated liver at 840 nm showing increasing behavior towards IR region. The Monte Carlo simulation was used to check the theoretical validation of measured optical properties of the tissue that showed a good match with our experimental results. We believe that these differences in optical properties will be helpful for the understanding arid optimal use of laser applications in medicine and differential diagnosis of tissues by using different optical methods. Especially for the investigation of biological tissue for photodynamic therapy (PDT), the knowledge of the specific optical properties and their thermo-induced changes is important.

  13. Neither bovine somatotropin nor growth hormone-releasing factor alters expression of thyroid hormone receptors in liver and mammary tissues.

    Science.gov (United States)

    Capuco, A V; Binelli, M; Tucker, H A

    2011-10-01

    Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine to specific nuclear receptors. Organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, have been hypothesized to target the action of thyroid hormones on the mammary gland and play a role in mediating or augmenting a galactopoietic response to bovine somatotropin (bST). Additionally, tissue responsiveness to thyroid hormones may be altered by changes in the number or affinity of nuclear receptors for thyroid hormones. In the present study, effects of bST and bovine growth hormone-releasing factor (bGRF) on thyroid hormone receptors in liver and mammary gland were studied. Lactating Holstein cows received continuous infusions of bST or bGRF for 63 d or served as uninfused controls. Nuclei were isolated from harvested mammary and liver tissues and incubated with [(125)I]-triiodothyronine. Treatments did not alter the capacity or affinity of specific binding sites for triiodothyronine in liver or mammary nuclei. Evaluation of transcript abundance for thyroid hormone receptors showed that isoforms of thyroid hormone receptor or retinoid receptor (which may influence thyroid receptor action) expressed in the mammary gland were not altered by bST or bGRF treatment. Data do not support the hypothesis that administration of bST or bGRF alters sensitivity of mammary tissue by changing expression of thyroid hormone receptors.

  14. Estrogen reduces 11beta-hydroxysteroid dehydrogenase type 1 in liver and visceral, but not subcutaneous, adipose tissue in rats.

    Science.gov (United States)

    Andersson, Therése; Söderström, Ingegerd; Simonyté, Kotryna; Olsson, Tommy

    2010-03-01

    Following menopause, body fat is redistributed from peripheral to central depots. This may be linked to the age related decrease in estrogen levels. We hypothesized that estrogen supplementation could counteract this fat redistribution through tissue-specific modulation of glucocorticoid exposure. We measured fat depot masses and the expression and activity of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in fat and liver of ovariectomized female rats treated with or without 17beta-estradiol. 11betaHSD1 converts inert cortisone, or 11-dehydrocorticosterone in rats into active cortisol and corticosterone. Estradiol-treated rats gained less weight and had significantly lower visceral adipose tissue weight than nontreated rats (P adipose weight was unaltered. In addition, 11betaHSD1 activity/expression was downregulated in liver and visceral, but not subcutaneous, fat of estradiol-treated rats (P adipose tissue depots, with higher levels in subcutaneous than visceral adipose tissue of estradiol-treated animals (P effects on tissue-specific glucocorticoid metabolism, suggesting that estrogen replacement therapy could influence obesity related morbidity in postmenopausal women.

  15. Comprehensive qualification and quantification of triacylglycerols with specific fatty acid chain composition in horse adipose tissue, human plasma and liver tissue.

    Science.gov (United States)

    Guan, Ming; Dai, Dongsheng; Li, Lin; Wei, Jinchao; Yang, Hui; Li, Shilei; Zhang, Yangyang; Lin, Yu; Xiong, Shaoxiang; Zhao, Zhenwen

    2017-09-01

    High levels of triacylglycerols (TGs) have been linked to cardiovascular disease and liver diseases. Comprehensively analyzing TGs is helpful to understand the TGs functions in these diseases. However, due to the existence of a large number of isomers TGs and the lack of commercial standards, precise analysis of individual triacylglycerol (TG) with specific fatty acid chain composition is full of challenge. In this work, ultra-performance liquid chromatography (UPLC) coupled with electrospray ionization (ESI) mass spectrometry (MS) were employed for comprehensive qualification and quantification of TGs with specific fatty acid chain composition in horse adipose tissue, human plasma and liver tissues including hepatocellular carcinoma (HCC) and para-carcinoma tissues. Multiple MS detection modes from QTRAP MS and FT-ICR MS were utilized, and hundreds of TG species (including many oxidized TG species) with their specific fatty acid chain compositions have been qualified and quantified. The isomer TGs interference, the isobaric interference, and oxidized TG species interference were firstly indicated. Several isomer TGs, for example, 18:1/20:1/18:2 TG and 20:3/18:1/18:0 TG, which were all 56:4 TG, demonstrated different trends in HCC tissue compared with para-carcinoma tissue, which showed the importance of analysis of TG with specific fatty acid chain composition. In addition, 10 TGs with the degree of unsaturation beyond three were significantly decreased, while 16:0/17:0/18:0 TG, no double bond, was significantly increased in the HCC tissue, which firstly revealed aberrant specific TG metabolism in HCC. This is a systematic report about comprehensive analysis of TGs by UPLC-ESI-MS, which is of significance for accurate analysis of these lipids. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Ketogenic Diet Impairs FGF21 Signaling and Promotes Differential Inflammatory Responses in the Liver and White Adipose Tissue.

    Directory of Open Access Journals (Sweden)

    Mohamed Asrih

    Full Text Available Beside its beneficial effects on weight loss, ketogenic diet (KD causes dyslipidemia, a pro-inflammatory state involved in the development of hepatic steatosis, glucose intolerance and insulin resistance, although the latter is still being debated. Additionally, KD is known to increase fibroblast growth factor 21 (FGF21 plasma levels. However, FGF21 cannot initiate its beneficial actions on metabolism in these conditions. We therefore hypothesized and tested in the present study that KD may impair FGF21 signaling.Using indirect calorimetry, we found that KD-fed mice exhibited higher energy expenditure than regular chow (RC-fed mice associated with increased Ucp1 levels in white adipose tissue (WAT, along with increased plasma FGF21 levels. We then assessed the effect of KD on FGF21 signaling in both the liver and WAT. We found that Fgfr4 and Klb (β-klotho were downregulated in the liver, while Fgfr1 was downregulated in WAT of KD-fed mice. Because inflammation could be one of the mechanisms linking KD to impaired FGF21 signaling, we measured the expression levels of inflammatory markers and macrophage accumulation in WAT and liver and found an increased inflammation and macrophage accumulation in the liver, but surprisingly, a reduction of inflammation in WAT.We also showed that KD enhances lipid accumulation in the liver, which may explain hepatic inflammation and impaired Fgfr4 and Klb expression. In contrast, import of lipids from the circulation was significantly reduced in WAT of KD-fed mice, as suggested by a downregulation of Lpl and Cd36. This was further associated with reduced inflammation in WAT.Altogether, these results indicate that KD could be beneficial for a given tissue but deleterious for another.

  17. Dynamic Expressions of Liver Tissue Apoptosis-related Genes of Vibrio Vulnificus Sepsis Rats and the Effects of Antibacterial Agents

    Institute of Scientific and Technical Information of China (English)

    Zhongqiu LU; Mengfang LI; Huan LIANG; Qiaomeng QIU; Guangtian YANG; Tieli ZHOU; Guangliang HONG

    2009-01-01

    Dynamic changes in mRNA expressions of liver tissue apoptosis-promoting genes Fas and Bax and apoptosis-inhibiting gene Bcl-2 of vibrio vulnificus sepsis rats were detected and the effects of antibacterial agents were examined.The rat model with Vibrio vulnificus sepsis (VV group) was established and some of the Vibrio vulnificus sepsis rats were treated with antibacterial agents (AA group).The mRNA expressions of Fas,Bax and Bcl-2 were measured by reverse transcription polymerase chain reaction (RT-PCR).As compared with normal control group (NC group),the expressions of Fas and Bax mRNA in liver tissue at all different time points in VV group were increased significantly (P<0.05),and the highest levels of Fas and Bax mRNA expressions were 6 and 12 h after the infection,respectively.At the same time,the expression of Bcl-2 mRNA in liver tissue at all different time points in VV group were decreased significantly (P<0.05),and the lowest level of Bcl-2 mRNA expression appeared 2 h after the infection.The mRNA expressions of Bcl-2 in liver tissue 9 and 12 h after the infection in AA group were increased significantly (P<0.05) compared with NC group,while the expressions of Fas and Bax mRNA were not significantly different from those of NC group.Compared with VV group,the expression of Fas mRNA in AA group was decreased (P<0.05) and Bax mRNA was decreased significantly 12 and 16 h after the infection (P<0.05),while the expressions of Bcl-2 mRNA were increased significantly 9,12 and 16 h after the infection (P<0.05).It is concluded that the mRNA expressions of liver tissue apoptosis-promoting genes Fas and Bax were increased remarkably in vibrio vulnificus sepsis rats,whereas the expression of apoptosis-inhibiting gene Bcl-2 mRNA was decreased obviously in sepsis rats in early stage.The treatment with cefoperazone sodium and levofloxacin lactate could inhibit the expression of Fas mR.NA and Bax mRNA and enhance the expression of Bcl-2 mRNA at the same time.

  18. Comparison of In Vivo Effects of Insulin on SREBP-1c Activation and INSIG-1/2 in Rat Liver and Human and Rat Adipose Tissue

    OpenAIRE

    Boden, Guenther; Salehi, Sajad; Cheung, Peter; Homko, Carol; Song, Weiwei; Loveland-Jones, Catherine; Jayarajan, Senthil

    2013-01-01

    The stimulatory effects of insulin on de novo lipogenesis (DNL) in the liver, where it is an important contributor to non-alcoholic fatty liver disease (NAFLD), hepatic and systemic insulin resistance, is strong and well established. In contrast, insulin plays only a minor role in DNL in adipose tissue. The reason why insulin stimulates DNL more in liver than in fat is not known but may be due to differential regulation of the transcription and post-translational activation of sterol regulato...

  19. Effect of ultrasound frequency on the Nakagami statistics of human liver tissues.

    Science.gov (United States)

    Tsui, Po-Hsiang; Zhou, Zhuhuang; Lin, Ying-Hsiu; Hung, Chieh-Ming; Chung, Shih-Jou; Wan, Yung-Liang

    2017-01-01

    The analysis of the backscattered statistics using the Nakagami parameter is an emerging ultrasound technique for assessing hepatic steatosis and fibrosis. Previous studies indicated that the echo amplitude distribution of a normal liver follows the Rayleigh distribution (the Nakagami parameter m is close to 1). However, using different frequencies may change the backscattered statistics of normal livers. This study explored the frequency dependence of the backscattered statistics in human livers and then discussed the sources of ultrasound scattering in the liver. A total of 30 healthy participants were enrolled to undergo a standard care ultrasound examination on the liver, which is a natural model containing diffuse and coherent scatterers. The liver of each volunteer was scanned from the right intercostal view to obtain image raw data at different central frequencies ranging from 2 to 3.5 MHz. Phantoms with diffuse scatterers only were also made to perform ultrasound scanning using the same protocol for comparisons with clinical data. The Nakagami parameter-frequency correlation was evaluated using Pearson correlation analysis. The median and interquartile range of the Nakagami parameter obtained from livers was 1.00 (0.98-1.05) for 2 MHz, 0.93 (0.89-0.98) for 2.3 MHz, 0.87 (0.84-0.92) for 2.5 MHz, 0.82 (0.77-0.88) for 3.3 MHz, and 0.81 (0.76-0.88) for 3.5 MHz. The Nakagami parameter decreased with the increasing central frequency (r = -0.67, p statistical distribution of the backscattered envelopes was not found in the phantom results (r = -0.147, p = 0.0727). The current results demonstrated that the backscattered statistics of normal livers is frequency-dependent. Moreover, the coherent scatterers may be the primary factor to dominate the frequency dependence of the backscattered statistics in a liver.

  20. The role of aerobic training and Pistacia atlantica extract on the levels of protein carbonyl, heat shock protein 70, and glycogen in the liver tissue of diabetic rats

    Directory of Open Access Journals (Sweden)

    Fatemeh Mohammadi Karizno

    2014-05-01

    Conclusion: It was found that aerobic training and Pistacia atlantica extract consumption, either alone or together, led to a significant reduction in PC levels in the liver tissues of diabetic rats. Thus, Pistacia atlantica extract and aerobic training can be good remedies in reducing liver complications resulting from diabetes.

  1. Relationship between HBV DNA and HBeAg in serum and HBcAg and inflammation grad in liver tissue among patients with chronic hepatiti B

    Institute of Scientific and Technical Information of China (English)

    刘兴祥

    2014-01-01

    Objective To investigate the relationship between HBV DNA and HBeAg in serum and HBcAg and inflammation grade in liver tissue among chronic hepatitis B(CHB)patients.Methods A retrospective analysis was performed on 250 CHB patients who underwent liver biopsy.These patients were divided into three groups according to serum levels of HBV

  2. Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity

    NARCIS (Netherlands)

    Wolfs, M. G. M.; Gruben, N.; Rensen, S. S.; Verdam, F. J.; Greve, J. W.; Driessen, A.; Wijmenga, C.; Buurman, W. A.; Franke, L.; Scheja, L.; Koonen, D. P. Y.; Shiri-Sverdlov, R.; van Haeften, T. W.; Hofker, M. H.; Fu, J.

    2015-01-01

    OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is an obesity-associated disease, and in obesity adipokines are believed to be involved in the development of NAFLD. However, it is still not clear whether adipokines in the liver and/or adipose tissues can be related to the development of specif

  3. Comparison of in vivo effects of insulin on SREBP-1c activation and INSIG-1/2 in rat liver and human and rat adipose tissue.

    Science.gov (United States)

    Boden, Guenther; Salehi, Sajad; Cheung, Peter; Homko, Carol; Song, Weiwei; Loveland-Jones, Catherine; Jayarajan, Senthil

    2013-06-01

    The stimulatory effects of insulin on de novo lipogenesis (DNL) in the liver, where it is an important contributor to non-alcoholic fatty liver disease (NAFLD), hepatic and systemic insulin resistance, is strong and well established. In contrast, insulin plays only a minor role in DNL in adipose tissue. The reason why insulin stimulates DNL more in liver than in fat is not known but may be due to differential regulation of the transcription and post-translational activation of sterol regulatory element binding proteins (SREBPs). To test this hypothesis, we have examined effects of insulin on activation of SREBP-1c in liver of rats and in adipose tissue of rats and human subjects. Liver and epidydimal fat were obtained from alert rats and subcutaneous adipose tissue from human subjects in response to 4 h euglycemic-hyperinsulinemic clamps. Here we show that acutely raising plasma insulin levels in rats and humans increased SREBP-1 mRNA comparably 3-4 fold in rat liver and rat and human adipose tissue, but increased post-translational activation of SREBP-1c only in rat liver, while decreasing it in adipose tissue. These differential effects of insulin on SREBP-1c activation in liver and adipose tissue were associated with robust changes in the opposite direction of INSIG-1 and to a lesser extent of INSIG-2 mRNA and proteins. We conclude that these findings support the hypothesis that insulin stimulated activation of SREBP-1c in the liver, at least in part, by suppressing INSIG-1 and -2, whereas in adipose tissue, an increase in INSIG-1 and -2 prevented SREBP-1c activation. Copyright © 2012 The Obesity Society.

  4. Comparison of In Vivo Effects of Insulin on SREBP-1c Activation and INSIG-1/2 in Rat Liver and Human and Rat Adipose Tissue

    Science.gov (United States)

    Boden, Guenther; Salehi, Sajad; Cheung, Peter; Homko, Carol; Song, Weiwei; Loveland-Jones, Catherine; Jayarajan, Senthil

    2012-01-01

    The stimulatory effects of insulin on de novo lipogenesis (DNL) in the liver, where it is an important contributor to non-alcoholic fatty liver disease (NAFLD), hepatic and systemic insulin resistance, is strong and well established. In contrast, insulin plays only a minor role in DNL in adipose tissue. The reason why insulin stimulates DNL more in liver than in fat is not known but may be due to differential regulation of the transcription and post-translational activation of sterol regulatory element binding proteins (SREBPs). To test this hypothesis, we have examined effects of insulin on activation of SREBP-1c in liver of rats and in adipose tissue of rats and human subjects. Liver and epidydimal fat were obtained from alert rats and subcutaneous adipose tissue from human subjects in response to 4 h euglycemic-hyperinsulinemic clamps. Here we show that acutely raising plasma insulin levels in rats and humans increased SREBP-1 mRNA comparably 3-4 fold in rat liver and rat and human adipose tissue, but increased post-translational activation of SREBP-1c only in rat liver, while decreasing it in adipose tissue. These differential effects of insulin on SREBP-1c activation in liver and adipose tissue were associated with robust changes in the opposite direction of INSIG-1 and to a lesser extent of INSIG-2 mRNA and proteins. We conclude that these findings support the hypothesis that insulin stimulated activation of SREBP-1c in the liver, at least in part, by suppressing INSIG-1 and -2, whereas in adipose tissue, an increase in INSIG-1 and -2 prevented SREBP-1c activation. PMID:23913732

  5. Protective Effect of Quercetin Against Oxidative Stress-induced Toxicity Associated With Doxorubicin and Cyclophosphamide in Rat Kidney and Liver Tissue.

    Science.gov (United States)

    Kocahan, Sayad; Dogan, Zumrut; Erdemli, Erman; Taskin, Eylem

    2017-03-01

    Doxorubicin and cyclophosphamide are widely used anticancer drugs with substantial toxicity in noncancerous tissue resulting from oxidative damage. Quercetin is a potent antioxidant compound. We hypothesized that quercetin administration would ameliorate the toxic effects of doxorubicin and cyclophosphamide prior to pregnancy. Cyclophosphamide, 27 mg/kg, and doxorubicin, 1.8 mg/kg, were administered to rats as intraperitoneal doses once every 3 weeks for a total of 10 weeks with or without concurrent treatment with quercetin, 10 mg/kg/d. Oxidative stress parameters were evaluated in maternal kidney and liver tissues after gestation. Doxorubicin was associated with elevated kidney tissue malondialdehyde relative to the controls and quercetin only treatment (P doxorubicin were associated with elevated malondialdehyde levels in the liver tissue (P Doxorubicin treatment was associated with decreased liver glutathione peroxidase (P doxorubicin and cyclophosphamide treatment (P doxorubicin and cyclophosphamide results in therapeutic restoration of homeostatic expression of the antioxidant parameters, reducing oxidative damage to the liver and kidney.

  6. Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes

    National Research Council Canada - National Science Library

    Mirja Tiikkainen; Anna-Maija Häkkinen; Elena Korsheninnikova; Tuulikki Nyman; Sari Mäkimattila; Hannele Yki-Järvinen

    2004-01-01

    Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes Mirja Tiikkainen 1 , Anna-Maija...

  7. Changes in ultrasonic properties of liver tissue in vitro during heating-cooling cycle concomitant with thermal coagulation.

    Science.gov (United States)

    Choi, Min Joo; Guntur, Sitaramanjaneya Reddy; Lee, Joo Myoung; Paeng, Dong Guk; Lee, Kang I L; Coleman, Andrew

    2011-12-01

    The present work considers the ultrasonic properties of porcine liver tissue in vitro measured during heating concomitant with thermal coagulation followed by natural cooling, so as to provide information about changes in the ultrasonic properties of the tissue after thermal coagulation. The excised liver samples were heated in a degassed water bath up to 75°C and naturally cooled down to 30°C. The tissue was observed to begin thermally coagulating at temperatures lower than 75°C. The ultrasonic parameters considered include the speed of sound, the attenuation coefficient, the backscatter coefficient and the nonlinear parameter of B/A. They were more sensitive to temperature when heating than during natural cooling. All of the parameters were shown to rise significantly on completion of the heating-cooling cycle. At 35°C after thermal coagulation, the B/A value was increased by 96%, the attenuation and backscatter coefficients were increased by 50%∼68% and 33%∼37%, respectively, in the typical frequency ranges of 3 MHz∼5 MHz used for ultrasonic imaging and the speed of sound was increased by 1.4%. The results of this study added to the evidence that tissue characterization, in particular, based on the B/A could be valuable for ultrasonically imaging the thermal lesions following high-intensity focused ultrasound (HIFU) surgery. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

  8. [Effects of conjugated linoleic acid and exercise on RBP4 of liver and adipose tissues in adolescent obese rats].

    Science.gov (United States)

    Cui, Jianfei; Bai, Youping; Li, Meng; Xu, Xiaodong; Dai, Yuanyuan; Zhang, Jing

    2015-01-01

    To exploer effects of conjugated linoleic acid and exercise on RBP4 of liver and adipose tissues in adolescent obese rats. 8 adolescent SD rats were selected as blank control (C) with normal diet. Obese rats were modeled with high fat feeding for 7 weeks. 32 obese rats were selected and randomly divided into 4 groups: control group (OC), CLA group ( OCC), exercise group (OM), exercise combined with CLA group (OMC). Exercise treatment were performed on animal treadmill with running speed of 21 - 25 m/min, 60 min/every time. For CLA treatment, each rat was fed 1.6 g/kg, one time/day, 5 times/week, for 8 weeks. Animals were anesthesia treated after experiment, blood and body tissues were collected. The content of blood glucose was measured, the insulin sensitivity was calculated, testing the expression of RBP4 mRNA in visceral adipose tissue, expression of RBP4 protein in liver cells and plasma RBP4 concentration. (1) Weight, weight growth rate and body fat percentage of OM, OMC groups were lower than OC, OCC groups (P OMC groups were significantly lower than OC, OCC groups (P OMC groups was higher than OC, OCC groups (P OMC groups in visceral adipose tissue was lower than OC, OCC groups (P OMC groups in liver cells was significantly lower than OC, OCC groups. RBP4 concentration in plasma of OM, OMC groups was lower than OC, OCC groups (P OMC group were higher than OM group, but the percentage of body fat, blood glucose content and the expression of RBP4 were lower than OM group, there were no significant differences between them. Simple exercise and exercise combined with CLA conld significantly reduced adolescent obese rats weight, weight growth rate, percentage of body fat, blood glucose content and also reduced RBP4 mRNA expression in visceral adipose tissue, RBP4 protein expression in liver tissue, RBP4 level in plasma,but can increase sensitivity to insulin, in a word, the treatment of exercise and exercise combine with CLA is better than the simple complement

  9. Investigation of biochemical and histopathological effects of Mentha piperita Labiatae and Mentha spicata Labiatae on liver tissue in rats.

    Science.gov (United States)

    Akdogan, M; Ozguner, M; Aydin, G; Gokalp, O

    2004-01-01

    The plant Mentha piperita, or peppermint, is commonly used in the treatment of loss of appetite, common cold, bronchitis, sinusitis, fever, nausea and vomiting, and indigestion as a herbal agent. In this study, we aimed to investigate biochemical and histological effects of M. piperita Labiatae, growing in the Yenisar Bademli town of Isparta city, and Mentha spicata Labiatae, growing in the Anamas high plateau of the Yenisar Bademli town, on the rat liver tissue. Forty-eight male Wistar albino rats weighing 200-250 g were used for this study. Rats were divided into four groups of 12 animals: Group I received no herbal tea (control group); Group II received 20 g/L M. piperita tea; Group III received 20 g/L M. spicata tea; and Group IV received 40 g/L M. spicata tea. Herbal teas were prepared daily and provided at all times to the rats during 30 days as drinking water. Liver function tests, including aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) activities were measured. To evaluate liver antioxidant defences, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and thiobarbituric acid reactive substance (TBARS) activities were determined in the homogenates of liver tissue. In addition, liver tissues were submitted for histopathologic examination. AST and ALT activities were increased in Group II, Group III and Group IV gradually when compared with the control group. The difference between Group II and the control group was not statistically significant (P > 0.016). Increases in AST and ALT activities of Group III and Group IV were statistically significant when compared with the control group. SOD, GSH-Px and CAT activities were increased in Group II when compared with the control group but the difference was not statistically significant (P > 0.016). However, SOD, GSH-Px activities and the TBARS level were significantly increased, and CAT activity was significantly decreased in Group III when compared with the

  10. Expression of tissue inhibitor of matrix metalloproteinases-1 during aging in rat liver

    Institute of Scientific and Technical Information of China (English)

    Yu-Mei Zhang; Xiang-Mei Chen; Di Wu; Suo-Zhu Shi; Zhong Yin; Rui Ding; Yang Lü

    2005-01-01

    AIM: To investigate the expression and role of tissueinhibitor of matrix metalloproteinases-1 (TIMP-1) during natural aging in rat liver and to detect the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9.METHODS: The rats were divided into 3-mo-old group (n = 5), 10-mo-old group (n = 5) and 24-mo-old group(n = 5). Histopathologic changes of liver were observed with HE and Masson stain. The location and protein expressions of TIMP-1 were determined by immunohistochemistry and Westem blot; message RNA (mRNA) levels were measured in livers from rats of various ages by semi-quantitative reverse transcriptional polymerase chain reaction (RT-PCR). In addition, the expression of MMP-2 and MMP-9was assessed by RT-PCR and Western blot.RESULTS: Histologic examination showed that the aging liver had excessive fatty degeneration and collagen deposition. Immunohistochemical staining showed that TIMP-1 related antigen in livers was located in cytoplasm. The proteinexpression of TIMP-1 was significantly higher in the oldestanimals and the mRNA expression was increased significantlyin the 24-mo-old rats (t= 4.61, P= 0.002<0.05, 24-vs 10-mo-old rats; t= 4.31, P= 0.003<0.05, 24- vs 3-mo-oldrats). The expression of MMP-2 and MMP-9 had no change during aging; the ratios TIMP-1/MMP-2 and TIMP-1/MMP-9 in aging liver were significantly higher than those in maturation and young livers.CONCLUSION: TIMP-1 may play an important role in the process of liver aging.

  11. Effect of diet on animal performance, lipid composition of subcutaneous adipose and liver tissue of beef cattle.

    Science.gov (United States)

    Hidiroglou, N; McDowell, L R; Johnson, D D

    1987-01-01

    Two trials were carried out with Brahman beef cattle to study animal performance and carcass characteristics as well as fatty acid composition of subcutaneous adipose and hepatic tissue, as influence by length of grain feeding period or a pasturing regimen. In trial 1, steers were allotted to three feedlot finishing periods (76, 104 and 146 days) after being backgrounded on pasture. Steers fed 76 days had greater average daily gains (P 0.·05) in these individual subclasses of liver lipids or in triglycerides were observed between the feedlot groups. Liver polyunsaturated fatty acids (PUFA) were higher (P < 0·001) at 104 than 76 days. In trial 2, steers fed a concentrate diet gained faster (P < 0·05) than the pasture group after 138 days. Marbling scores, yield grade, quality grade, fat over ribeye and per cent KPH were higher (P < 0·01) for the concentrate group while fat color scores were higher (P < 0·01) for the pasture group. Liver fatty acid analysis of summed ω6 PUFAs of triglyceride, phosphatidylcholine, phosphatidylethanolamine were higher for the feedlot than the pasture group. Linoleic acid was higher (P < 0·05) in the TG and PC liver subclass of the feedlot animals while higher (P < 0·05) linolenic acid occurred in the pasture group.

  12. Polyclonal antibody preparation and expression in liver tissues of transactivated protein 5 of hepatitis C virus nonstructural 5A

    Institute of Scientific and Technical Information of China (English)

    Xiao-quan Li; Shu-lin Zhang; Li-hua Zhong; Jun Cheng; Yuan Hong; Meng-dong Lan; Xiao-bin Chen; Cheng-fu Sun

    2009-01-01

    Objective To prepare polyclonal antibody of transactivated protein 5 of hepatitis C virus nonstructural 5A (NA5ATP5) and to explore its expression in the liver tissues. Methods In Escherichia coil BL21, the prokaryotic expression vector pET32a(+)-NS5ATP5 was induced by isopropyl-β-D-thiogalactoside (IPTG), and it was analyzed with sodium dodecyl sulfate-polyaerylamide gel electrophoresis (SDS-PAGE) and Western blotting. And the purified protein was used to immunize the rabbit to prepare polyelonai antibody, with which we studied the function of NSSATP5 by determining the different liver tissues with the streptavidin-perosidase (SP) immunohistochemistry method. Results Recombinant NS5ATP5 (molecular weight: 65 kD) and polyclonal antibody were successfully prepared. NS5ATP5 expression in the liver of patients with chronic HCV infection was much higher than that of a normal person, and it was detected mainly in the cytoplasm. Conclusion The findings of the expression difference between HCV patients and normal people led to a novel diagnostic marker to detect HCV infection.

  13. Thyroid hormone upregulates zinc-α2-glycoprotein production in the liver but not in adipose tissue.

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    Simó, Rafael; Hernández, Cristina; Sáez-López, Cristina; Soldevila, Berta; Puig-Domingo, Manel; Selva, David M

    2014-01-01

    Overproduction of zinc-α2-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α2-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α2-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-α2-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-α2-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α2-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α2-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α2-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α2-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α2-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α2-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α2-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α2-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α2-glycoprotein expression in adipose tissue could be the reason why zinc-α2-glycoprotein is not related to weight

  14. Histopathological study of the kidney, liver and intestine tissues in goldfish (Carassius auratus and angelfish (Pterophyllum sp.

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    Ebtesam Ahmadmoradi

    2012-09-01

    Full Text Available Histopathology is used for diagnosis of diseases in aquatic animals. This study was conductedto investigate histopathological lesions of kidney, liver and intestine of goldfish (Carassius auratus andangelfish (Pterophyllum sp. in some aquarium shops during a period between January-April 2010.Several histological alterations were observed in kidney which include glomerulonephritis, cell swelling ofepithelial cells, tubular epithelium necrosis, hyaline droplets and hyaline cast in renal tubules and tubulardilation. Liver showed vacuolar degeneration of hepatocytes, karyolysis and karyorrhexis and focal areasof necrosis, haemorrhagia and hepatitis. In intestine, atrophy of epithelial cells and enteritis on thelamina propria and submucosal layer were seen. It was concluded that unfavourable environmentalcontamination of aquarium may induced several histopathological alterations in the tissues of goldfishand angelfishes.

  15. Teasing apart socially-induced infertility in non-reproductive female Damaraland mole-rats, Fukomys damarensis (Rodentia: Bathyergidae).

    Science.gov (United States)

    Bennett, Nigel C

    2011-12-01

    The Damaraland mole-rat is a subterranean mammal exhibiting extreme reproductive skew with a single reproductive female in each colony responsible for procreation. Non-reproductive female colony members are physiologically suppressed while in the colony, exhibiting reduced concentrations of plasma luteinizing hormone (LH) and a decreased response of the pituitary, as measured by the release of bioactive LH, to an exogenous dose of gonadotrophin releasing hormone (GnRH). Removal of the reproductive female from the colony results in an elevation of LH and an enhanced response of the pituitary to a GnRH challenge in non-reproductive females comparable to reproductive females, implying control of reproduction in these individuals by the reproductive female. The Damaraland mole-rat is an ideal model for investigating the physiological and behavioral mechanisms that regulate the hypothalamo-pituitary-gonadal axis. In contrast, we know less about the control of reproduction at the level of the hypothalamus. The immunohistochemistry of the GnRH system of both reproductive and non-reproductive female Damaraland mole-rats has revealed no significant differences with respect to morphology, distribution or numbers of immunoreactive GnRH perikarya. We examined whether the endogenous opioid peptide beta-endorphin was responsible for the inhibition of the release of the GnRH from the neurons indirectly by measuring LH concentrations in these non-reproductive females following single, hourly and 8 hourly injections of the opioid antagonist naloxone. The results imply that the endogenous opioid peptide, beta-endorphin, is not responsible for the inhibition of GnRH release from the perikarya in non-reproductive females. Preliminary data examining the circulating levels of cortisol also do not support a role for circulating glucocorticoids. The possible role of kisspeptin is discussed.

  16. THE EXCHANGE OF CONNECTIVE TISSUE BIOPOLYMERS IN THE LIVER OF ALLOXAN DIABETIC RATS

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    S. V. Lomaeva

    2013-01-01

    Full Text Available Aim. Study of the exchange of liver and blood plasma biopolymers of alloxan diabetic rats.Materials and Methods. Diabetes mellitus was modeled in rats by single subcutaneous injection of alloxan tetrahydrate (170 mg per100 gbody weight. Blood glucose, glycosylated hemoglobin were controlled and morphometric study of the pancreas was carried out for the verification of the model. A month later, concentration of glycosaminoglycans, free hydroxyproline and the level of hyaluronidase and collagenolytic activity in plasma were determined. The total concentration of collagen, glycosaminoglycans, and their fractions, the level of hyaluronidase and collagenolytic activity in rat liver homogenate were measured.Results. The level of all the parameters of interest in the liver and blood plasma increased on 30 day after alloxan injection, the accumulation of glycosaminoglycans in the liver occurred mainly due to unsulfonated fraction.Conclusion. The development of experimental diabetes in rats is accompanied by activation of both decay processes and synthesis of biopolymers studied. Accumulation of total collagen and glycosaminoglycans was observed in rats’ liver, which probably lead to the fibrosis changes in it.

  17. RNA deep sequencing reveals novel candidate genes and polymorphisms in boar testis and liver tissues with divergent androstenone levels.

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    Asep Gunawan

    Full Text Available Boar taint is an unpleasant smell and taste of pork meat derived from some entire male pigs. The main causes of boar taint are the two compounds androstenone (5α-androst-16-en-3-one and skatole (3-methylindole. It is crucial to understand the genetic mechanism of boar taint to select pigs for lower androstenone levels and thus reduce boar taint. The aim of the present study was to investigate transcriptome differences in boar testis and liver tissues with divergent androstenone levels using RNA deep sequencing (RNA-Seq. The total number of reads produced for each testis and liver sample ranged from 13,221,550 to 33,206,723 and 12,755,487 to 46,050,468, respectively. In testis samples 46 genes were differentially regulated whereas 25 genes showed differential expression in the liver. The fold change values ranged from -4.68 to 2.90 in testis samples and -2.86 to 3.89 in liver samples. Differentially regulated genes in high androstenone testis and liver samples were enriched in metabolic processes such as lipid metabolism, small molecule biochemistry and molecular transport. This study provides evidence for transcriptome profile and gene polymorphisms of boars with divergent androstenone level using RNA-Seq technology. Digital gene expression analysis identified candidate genes in flavin monooxygenease family, cytochrome P450 family and hydroxysteroid dehydrogenase family. Moreover, polymorphism and association analysis revealed mutation in IRG6, MX1, IFIT2, CYP7A1, FMO5 and KRT18 genes could be potential candidate markers for androstenone levels in boars. Further studies are required for proving the role of candidate genes to be used in genomic selection against boar taint in pig breeding programs.

  18. Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

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    Wen Liang

    Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

  19. The Application of Minimally Invasive Devices with Nanostructured Surface Functionalization: Antisticking Behavior on Devices and Liver Tissue Interface in Rat

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    Li-Hsiang Lin

    2015-01-01

    Full Text Available This study investigated the thermal injury and adhesion property of a novel electrosurgery of liver using copper-doped diamond-like carbon (DLC-Cu surface treatment. It is necessary to reduce the thermal damage of surrounding tissues for clinical electrosurgeries. The surface morphologies of stainless steel (SS coated with DLC (DLC-Cu-SS films were characterized by scanning electron microscopy (SEM and transmission electron microscopy (TEM. Bionic liver models were reconstructed using magnetic resonance imaging (MRI to simulate electrosurgery. Cell cytotoxicity assays showed that the DLC-Cu thin film was nontoxic. The temperature of tissue decreased significantly with use of the electrosurgical device with nanostructured DLC-Cu films and increased with increasing thickness of the films. Thermography revealed that the surgical temperature in the DLC-Cu-SS electrosurgical device was significantly lower than that in the untreated device in the animal model. Moreover, compared to the SS electrosurgical device, the DLC-Cu-SS electrosurgical device caused a relatively small injury area and lateral thermal effect. The results indicate that the DLC-Cu-SS electrosurgical device decreases excessive thermal injury and ensures homogeneous temperature transformation in the tissues.

  20. Induced pluripotent stem cell-derived hepatocytes and endothelial cells in multi-component hydrogel fibers for liver tissue engineering.

    Science.gov (United States)

    Du, Chan; Narayanan, Karthikeyan; Leong, Meng Fatt; Wan, Andrew C A

    2014-07-01

    Liver tissue engineering requires a suitable cell source, methodologies to assemble the cells within their niche microenvironments in a spatially defined manner, and vascularization of the construct in vivo for maintenance of hepatocyte viability and function. Recently, we have developed methods of encapsulating cells within separate domains in multi-component hydrogel fibers and methods of assembling fibers to form 3D-patterned tissue constructs. In the present work, we have combined these approaches to encapsulate hepatocytes and endothelial cells within their specific niches, and to assemble them into endothelialized liver tissue constructs. The hepatocytes and endothelial cells were obtained in parallel by differentiating human recombinant protein-induced human pluripotent stem cells, resulting in a construct which contained genetically identical endothelial and parenchymal elements. We were able to demonstrate that the presence of endothelial cells in the scaffold significantly improved hepatocyte function in vitro and facilitated vascularization of the scaffold when implanted in a mouse partial hepatectomy model. The in vivo studies further asserted that integration of the scaffold with host vasculature had occurred, as demonstrated by the presence of human albumin in the mouse serum. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation

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    Alice Tung Wan Song

    2015-02-01

    Full Text Available Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+, HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+, acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-. All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.

  2. Effects of a High Fat Diet and Voluntary Wheel Running Exercise on Cidea and Cidec Expression in Liver and Adipose Tissue of Mice.

    Science.gov (United States)

    Reynolds, Thomas H; Banerjee, Sayani; Sharma, Vishva Mitra; Donohue, Jacob; Couldwell, Sandrine; Sosinsky, Alexandra; Frulla, Ashton; Robinson, Allegra; Puri, Vishwajeet

    2015-01-01

    Cidea and Cidec play an important role in regulating triglyceride storage in liver and adipose tissue. It is not known if the Cidea and Cidec genes respond to a high fat diet (HFD) or exercise training, two interventions that alter lipid storage. The purpose of the present study was to determine the effect of a HFD and voluntary wheel running (WR) on Cidea and Cidec mRNA and protein expression in adipose tissue and liver of mice. A HFD promoted a significant increase in Cidea and Cidec mRNA levels in adipose tissue and liver. The increase in Cidea and Cidec mRNAs in adipose tissue and liver in response to a HFD was prevented by WR. Similar to the changes in Cidea mRNA, Cidea protein levels in adipose tissue significantly increased in response to a HFD, a process that was, again, prevented by WR. However, in adipose tissue the changes in Cidec mRNA did not correspond to the changes in Cidec protein levels, as a HFD decreased Cidec protein abundance. Interestingly, in adipose tissue Cidea protein expression was significantly related to body weight (R=.725), epididymal adipose tissue (EWAT) mass (R=.475) and insulin resistance (R=.706), whereas Cidec protein expression was inversely related to body weight (R=-.787), EWAT mass (R=-.706), and insulin resistance (R=-.679). Similar to adipose tissue, Cidea protein expression in liver was significantly related to body weight (R=.660), EWAT mass (R=.468), and insulin resistance (R=.599); however, unlike adipose tissue, Cidec protein levels in liver were not related to body weight or EWAT mass and only moderately associated with insulin resistance (R=-.422, P=0.051). Overall, our findings indicate that Cidea is highly associated with adiposity and insulin resistance, whereas Cidec is related to insulin sensitivity. The present study suggests that Cide proteins might play an important functional role in the development of obesity, hepatic steatosis, as well as the pathogenesis of type 2 diabetes.

  3. Cinnamon extract improves the body composition and attenuates lipogenic processes in the liver and adipose tissue of rats.

    Science.gov (United States)

    Lopes, Bruna P; Gaique, Thaiane G; Souza, Luana L; Paula, Gabriela S M; Kluck, George E G; Atella, Georgia C; Gomes, Anne Caroline C; Simas, Naomi K; Kuster, Ricardo M; Ortiga-Carvalho, Tania M; Pazos-Moura, Carmen C; Oliveira, Karen J

    2015-10-01

    In models of metabolic disorders, cinnamon improves glucose and lipid metabolism. This study explores the effect of chronic supplementation with aqueous cinnamon extract (CE) on the lipid metabolism of rats. Male adult Wistar rats were separated into a control group (CTR) receiving water and a CE Group receiving aqueous cinnamon extract (400 mg of cinnamon per kg body mass per day) by gavage for 25 consecutive days. Cinnamon supplementation did not change the food intake or the serum lipid profile but promoted the following changes: lower body mass gain (P = 0.008), lower relative mass of white adipose tissue (WAT) compartments (P = 0.045) and higher protein content (percentage of the carcass) (P = 0.049). The CE group showed lower leptin mRNA expression in the WAT (P = 0.0017) and an important tendency for reduced serum leptin levels (P = 0.059). Cinnamon supplementation induced lower mRNA expression of SREBP1c (sterol regulatory element-binding protein 1c) in the WAT (P = 0.001) and liver (P = 0.013) and lower mRNA expression of SREBP2 (P = 0.002), HMGCoA reductase (3-hydroxy-3-methylglutaryl-CoA reductase) (P = 0.0003), ACAT1 (acetyl-CoA acetyltransferase 1) (P = 0.032) and DGAT2 (diacylglycerol O-acyltransferase 2) (P = 0.03) in the liver. These changes could be associated with the reduced esterified cholesterol and triacylglycerol content detected in this tissue. Our results suggest that chronic ingestion of aqueous cinnamon extract attenuates lipogenic processes, regulating the expression of key enzymes and transcriptional factors and their target genes, which are directly involved in lipogenesis. These molecular changes possibly promote adaptations that would prevent an increase in circulating cholesterol and triacylglycerol levels and prevent lipid accumulation in tissues, such as liver and WAT. Therefore, we speculate that cinnamon may also be useful for preventing or retarding the development of lipid disorders.

  4. Polyclonal antibody preparation and expression in liver tissues of transactivated protein 5 of hepatitis C virus nonstructural 5A

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To prepare polyclonal antibody of transactivated protein 5 of hepatitis C virus nonstructural 5A (NA5ATP5) and to explore its expression in the liver tissues. Methods In Escherichia coli BL21,the prokaryotic expression vector pET32a(+)-NS5ATP5 was induced by isopropyl-β-D-thiogalactoside (IPTG),and it was analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. And the purified protein was used to immunize the rabbit to prepare polyclonal antibody,wi...

  5. Molecular effects of leptin on peroxisome proliferator activated receptor gamma (PPAR-γ) mRNA expression in rat's adipose and liver tissue.

    Science.gov (United States)

    Abbasi, A; Moghadam, A A; Kahrarian, Z; Abbsavaran, R; Yari, K; Alizadeh, E

    2017-08-15

    Leptin is a 16-kDa peptide hormone secreted by adipose tissue that participates in the regulation of energy homeostasis. The aim of this study was to determine the effect of leptin injection on mRNA expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) and comparison of PPAR-γ mRNA expression in rat's adipose and liver tissue. Twenty adult male rats were divided into the following groups: Group 1asa control (n=10) that did not receive any treatment. Group 2as a treatment (n=10) that received leptin (30 µg ⁄ kg BW) intraperitoneally (ip) for two successive days. Blood samples were taken before and one day after second leptin injection for triglyceride (TG), Free Fatty Acid (FFA), HLD-cholesterol, and LDL-cholesterol measurement. Total RNA was extractedfrom the adipose tissue and liver tissues of rats.  Adipose and liver tissue cells' cDNA was synthesized to characterize the expression of PPAR-γ. Gene expression of PPAR-γ mRNA was tested by RT- PCR technique. Results show leptin decreases expression of PPAR-γ on rat. Low levels of PPAR-γ mRNA were detected in adipose and liver tissues of treatment rats in comparison to control group. In treatment group, the level of PPAR-γ mRNA in liver tissue was very lower than the adipose tissue. The levels of HDL and FFA in treatment rats were increased whereas serum levels TG, VLDL and LDL were not changed. It is concluded that leptin signal with suppressing of PPAR-γ mRNA expression in rat's adipose and liver tissues can result in lipolysis instead of lipogenesis.

  6. Raman and UV-Vis Spectroscopy Applied to the Analysis of Liver Tissues from Rats with Myocardial Ischemia Induced by Isoproterenol

    Institute of Scientific and Technical Information of China (English)

    GAO Hai-cheng; ZOU Ying-gang; HUANG Yu-xin; GAO Hai-mei; CHEN Lei; PEI Jin

    2011-01-01

    The application of the laser Raman spectroscopic(LRS) technique for the analysis of liver tissues from rats with myocardial ischemia induced by isoproterenol(ISO) was described.Animal model of myocardial ischemia was established for rats induced by ISO.Rats were randomly divided into four groups as normal group and myocardial ischemia groups.We observed the successful myocardial ischemia model via serum enzymes levels and hematoxylin-eosin(HE) staining,and detected the liver tissue of the rats from normal group and liver tissue of the rats from myocardial ischemia groups via UV-Vis spectroscopy(UV-Vis) and LRS,and the changes of the absorbance spectra were compared in the above four different groups.The results show that ISO can induce rat myocardial ischemia successfully.The spectrum of normal liver tissue supernatant exhibits a strong absorption band at 968 nm,but no absorption band appears in the spectra of liver tissue supernatant solutions from the rats with myocardial ischemia induction after 2,12 and 72 h presented at 968 nm.LRS results show that Raman intensities of the precipitates suffered from ISO-treatment after 2,12 and 72 h were obviously increased compared with that of the precipitate of the liver tissue of the normal rats suffered from 0.9 g/L normal saline(NS) treatment.These results indicate that LRS and UV-Vis can be harmless,nondestructive,rapid and effective methods for analyzing different pathological specimens of liver tissue from myocardial ischemia rats.

  7. The effect of N-acetylcysteine (NAC) on liver and renal tissue inducible nitric oxide synthase (iNOS) and tissue lipid peroxidation in obstructive jaundice stimulated by lipopolysaccharide (LPS).

    Science.gov (United States)

    Cağlikülekci, Mehmet; Pata, Cengiz; Apa, Duygu Dusmez; Dirlik, Musa; Tamer, Lulufer; Yaylak, Faik; Kanik, Arzu; Aydin, Suha

    2004-03-01

    Morbidity and mortality rates are very high in obstructive jaundice when it is associated with sepsis and multiple organ failure. Nitric oxide (NO) formation and increased expression of inducible nitric oxide synthase (iNOS) also take place in obstructive jaundice (OJ). N-Acetylcysteine (NAC) has a beneficial effect by demonstrating anti-inflammatory activity such as inhibits cytokine expression/release, inhibiting the adhesion molecule expression and inhibiting nuclear factor kappa B (NFkappaB). The aim of this study was to investigate the effects of NAC on liver and renal tissue iNOS, and liver tissue lipid peroxidation in lipopolysaccharide (LPS) induced obstructive jaundice. We randomized 48 rats into six groups. Group A: Sham group; group B: OJ group; group C: OJ+NAC; group D: OJ+LPS (Escherichia coli LPS serotype L-2630, 100mg, Sigma) group E: OJ+NAC+LPS; group F: OJ+LPS+NAC. NAC was started subcutaneously 100mg/kg. LPS was injected intraperitoneally and then at the tenth day we sacrificed the rats. Liver malondialdehyde (MDA) increased and liver ATPase decreased in groups B-D when compared to group A. After the administration of NAC (groups C-E), liver MDA levels decreased, tissue ATPase levels increased as compared to other groups. The liver and renal tissue iNOS expression was increased in groups B, D, and F. After the administration of NAC (groups C-E) the liver and renal tissue iNOS expression were decreased. Our results indicated that NAC prevented the deleterious effects of LPS in OJ by reducing iNOS expression via lipid peroxidation in liver and renal tissue; if it was administrated before LPS. But NAC failed to prevent the iNOS expression and lipid peroxidation if there was established endotoxemia in OJ.

  8. Measuring the effect of a Western diet on liver tissue architecture by FLIM autofluorescence and harmonic generation microscopy.

    Science.gov (United States)

    Ranjit, Suman; Dvornikov, Alexander; Dobrinskikh, Evgenia; Wang, Xiaoxin; Luo, Yuhuan; Levi, Moshe; Gratton, Enrico

    2017-07-01

    The phasor approach to auto-fluorescence lifetime imaging was used to identify and characterize a long lifetime species (LLS) (~7.8 ns) in livers of mice fed with a Western diet. The size of the areas containing this LLS species depends on the type of diet and the size distribution shows Western diet has much larger LLS sizes. Combination of third harmonic generation images with FLIM identified the LLS species with fat droplets and the droplet size distribution was estimated. Second harmonic generation microscopy combined with phasor FLIM shows that there is an increase in fibrosis with a Western diet. A new decomposition in three components of the phasor plot shows that a Western diet is correlated with a higher fraction of free NADH, signifying more reducing condition and more glycolytic condition. Multiparametric analysis of phasor distribution shows that from the distribution of phasor points, a Western diet fed versus a low fat diet fed samples of mice livers can be separated. The phasor approach for the analysis of FLIM images of autofluorescence in liver specimens can result in discovery of new fluorescent species and then these new fluorescent species can help assess tissue architecture. Finally integrating FLIM and second and third harmonic analysis provides a measure of the advancement of fibrosis as an effect of diet.

  9. Effect of melatonin on element distribution in the liver tissue of diabetic rats subjected to forced exercise.

    Science.gov (United States)

    Bicer, M; Akil, M; Baltaci, A K; Mogulkoc, R; Sivrikaya, A; Akkus, H

    2015-01-01

    The objective of the present study was to investigate the effects of melatonin supplementation on elements in the liver of diabetic rats subjected to acute swimming exercise. Eighty adult male rats were equally divided into eight groups. Group 1, general control. Group 2, melatonin-supplemented control. Group 3, melatonin-supplemented diabetic control. Group 4, swimming control. Group 5, melatonin-supplemented swimming. Group 6, melatonin-supplemented diabetic swimming. Group 7, diabetic swimming. Group 8, diabetic control. Liver tissue samples were analyzed for lead, cobalt, molybdenum, chrome, sulphur, magnesium, manganese, sodium, potassium, phosphorus, copper, iron, calcium, zinc, selenium. The highest cobalt, chrome values were found in the groups 7, 8 and the groups 5, 6 respectively. Groups 3 and 7 had the highest copper values. Iron and potassium values were higher in the groups 1 and 4. Group 6 had increased magnesium value, and groups 6, 7, 8 were found to have the highest manganese levels. The highest lead values were found in the groups 5 and 6. Group 6 had the highest selenium levels. The highest zinc levels were established in 1 and 2. Groups 1, 2, 5 and 6 were found to have the highest calcium values. The results of our study indicate that melatonin supplementation in diabetes and forced exercise significantly alters the element metabolism in the liver (Tab. 3,Ref. 33).

  10. Real-time tissue elastography in the evaluation of liver cirrhosis in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Zhan-Fang Wei; Yong-Ping Wu; Li-Sha Ma; Ling-Mei Duan

    2016-01-01

    Objective:To explore the feasibility of real-time tissue elastography (RTE) in the evaluation of liver fibrosis and cirrhosis in patients with chronic hepatitis B.Methods:A total of 60 patients with chronic hepatitis B who were admitted in our hospital from March, 2015 to March, 2016 were included in the study and served as the study group, while 30 healthy individuals were served as the control group. RTE was used to detect MEAN, %AREA, SD, COMP, CONT, KURT, SKEW, ENT, IDM, ASM, and CORR. The elastic imaging characteristic quantitative value difference in the two groups and the change of elastic imaging characteristic quantitative values at different fibrosis stages were observed.Results:Except for ENT, ASM, and CORR, the comparison of the rest quantitative values between the two groups was statistically significant. With the change of liver fibrosis staging, the various elastic imaging characteristic quantitative values were correspondingly changed, and the comparison among the various stages was statistically significant by one-way ANOVA.Conclusions: RTE, characterized by simplicity, strong practicability, repeatability, and noninvasiveness, and can provide an accurate evidence for the diagnosis of liver fibrosis and the evaluation of fibrosis degree in patients with chronic hepatitis B.

  11. Evaluating childhood obesity. Magnetic resonance-based quantification of abdominal adipose tissue and liver fat in children

    Energy Technology Data Exchange (ETDEWEB)

    Raschpichler, M.C. [Leipzig Univ. (Germany). Dept. of Paediatric Radiology; Leipzig Univ. Medical Center (Germany). IFB Adiposity Diseases; Sorge, I.; Hirsch, W. [Leipzig Univ. (Germany). Dept. of Paediatric Radiology; Mende, M. [Leipzig Univ. (Germany). Clinical Trial Centre Leipzig; Sergeyev, E.; Koerner, A. [Leipzig Univ. (Germany). University Hospital for Children and Adolescents; Kruber, D. [Leipzig Univ. (Germany). Dept. of Oral, Craniomaxillofacial and Facial Plastic Surgery; Schick, F. [Univ. Hospital Tuebingen (Germany). Section on Experimental Radiology

    2012-04-15

    The purpose of this study is to establish and validate a magnetic resonance (MR)-based fat quantification package that provides an accurate assessment of abdominal adipose tissue and liver fat in children. Ex vivo trials with a torso model and water-oil mixtures are conducted. Abdominal adipose tissue (AAT) is covered by magnetic resonance imaging (MRI) using a fat-selective sequence and is analyzed by a plug-in based on the open source software Image. Liver fat (LF) is measured with localized {sup 1}H Magnetic Resonance Spectroscopy ({sup 1}H MRS) and the jMRUI (java-based Magnetic Resonance User Interface) software package. Evaluation of the clinical methodology involved a study of 10 children in this feasibility study (mean age and body mass index: 13.3 yr; 33.3 kg/m{sup 2}). To evaluate the method's validity, reference measurements were performed. Ex vivo trials with the torso model showed that adipose tissue was measured appropriately with a systematic underestimation by 9.3 {+-} 0.2 % (0.32 {+-} 0.064 kg). Coefficients of variation for both intra- and inter-observer measurements ranged between 0 - 2.7 % and repeated analyses showed significant equivalent results (p < 0.01). The lipid content obtained by {sup 1}H MRS ex vivo revealed significant equivalence with the predefined fat content in water-oil mixtures (p < 0.01). In vivo, the homemade plug-in significantly overestimated the AAT, with the visceral adipose tissue being most affected (+ 15.7 {+-} 8.4 %). Although an overestimation of the AAT by the presented plug-in should be taken into consideration, this children-friendly package enables the quantification of both LF and AAT within 30 min on a freeware-based platform. (orig.)

  12. (13)Carbon and (15)nitrogen isotopes in autopsy liver tissue samples from Greenlandic Inuit and Danes: consumption of marine versus terrestrial food

    DEFF Research Database (Denmark)

    Milman, N.; Laursen, J.; Mulvad, G.

    2010-01-01

    Background/Objectives: The content of C-13 and N-15 isotopes is higher in marine than in terrestrial food. C-13 and N-15 in human tissue therefore reflects the relative proportions of marine and terrestrial food consumed by the individual. The objective of this study was to measure C-13 and N-15...... in liver tissue from Greenlandic Inuit and Danes. Subjects/Methods: Normal liver tissue was obtained at autopsy in 1992-1994 from 60 Inuit with a median age of 61 years (range 25-83) and in 1986 from 15 ethnic Danes with a median age of 84 years (range 66-93). By sieving, liver tissue was separated...

  13. [Effects of TiO₂ nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats].

    Science.gov (United States)

    Wang, Yun; Chen, Zhang-jian; Ba, Te; Pu, Ji; Cui, Xiao-xing; Jia, Guang

    2014-06-18

    To compare the effect of TiO₂ nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats. Forty-eight SD male rats, half in 4-week (youth) old and half in 9-week (adult) old rats, were randomly divided into 8 groups, which were exposed to TiO₂ nanoparticles [(75 ± 15) nm, anatase] through intragastric administration at 0, 10, 50 and 200 mg/kg body weight every day for 30 days. The liver and kidney tissues were collected for antioxidant function and element content analysis. 200 mg/kg TiO₂ nanoparticles exposure significantly increased the liver total superoxide dismutase (T-SOD) activity and the kidney reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios in young rats, and significantly decreased the liver Mo, Co, Mn and P contents and the kidney Rb and Na contents in young rats. 200 mg/kg TiO₂ nanoparticles exposure significantly increased GSH/GSSG ratios and Rb contents and decreased Na contents in the liver of adult rats. No significantly difference was found in antioxidant indexes and elements content in the kidney of adult rats between three experimental groups and control group. TiO₂ nanoparticles can enhance the antioxidant capacity and decrease the elements content in rat liver and kidney tissues. The liver is the more sensitive target organ and the young animals are more susceptible to TiO₂ nanoparticles toxicity by the oral routes.

  14. Interferon-λ4 (IFNL4 transcript expression in human liver tissue samples.

    Directory of Open Access Journals (Sweden)

    Ahmad Amanzada

    Full Text Available Eradication of hepatitis C virus (HCV infection, both spontaneous and treatment-induced, is marked by the wildtype allele C of a single nucleotide polymorphism upstream of the IL28B gene, rs12979860. This favorable allele was recently described to be in linkage disequilibrium with the wildtype allele TT of a dinucleotide polymorphism, ss469415590, located within a new protein-coding gene. While the TT allele introduces a frame-shift and disrupts the open reading frame, only the variant allele, ΔG, creates a novel type III interferon (IFN protein, IFN-λ4/IFNL4. Absence of IFNL4 is thus supposed to favor resolution of HCV infection. As to date IFNL4 mRNA transcription has only been investigated in polyI:C-stimulated primary human hepatocytes and not yet in HCV infection in vivo, this study analyzed IFNL4 mRNA expression in human liver biopsy specimens. Samples were obtained from patients with a broad panel of disorders including no liver disease, liver diseases of non-viral etiology, chronic hepatitis B and chronic hepatitis C. Hepatic IFNL4 transcripts were detectable exclusively in a subgroup of chronic hepatitis C patients (24/45. Their amounts were positively related to liver HCV RNA copy numbers (p = 0.0023, r = 0.56 suggesting that the hepatic viral load influences IFNL4 transcription irrespective of IFNL4 governing genotype. Both, the IFNL4 creating allele ΔG (p<0.0001 and actual IFNL4 transcription (p = 0.0015 were found to be correlated to the activation of IFN stimulatory genes (ISGs. By contrast, IFNL4 ss469415590 genotypes were not found to be related to IFN-λ2/3/IL28 or IFN-λ1/IL29 gene expression. In conclusion, this study is the first report on intrahepatic transcript levels of the recently discovered IFNL4 gene. Data indicate that HCV infection in particular might activate IFNL4 transcription in the liver. It provides a possible explanation as to why hepatitis C patients show ISG stimulation in their livers in the

  15. Intra-Tissue Pressure Measurement in Ex Vivo Liver Undergoing Laser Ablation with Fiber-Optic Fabry-Perot Probe.

    Science.gov (United States)

    Tosi, Daniele; Saccomandi, Paola; Schena, Emiliano; Duraibabu, Dinesh Babu; Poeggel, Sven; Leen, Gabriel; Lewis, Elfed

    2016-04-15

    We report the first-ever intra-tissue pressure measurement performed during 1064 nm laser ablation (LA) of an ex vivo porcine liver. Pressure detection has been performed with a biocompatible, all-glass, temperature-insensitive Extrinsic Fabry-Perot Interferometry (EFPI) miniature probe; the proposed methodology mimics in-vivo treatment. Four experiments have been performed, positioning the probe at different positions from the laser applicator tip (from 0.5 mm to 5 mm). Pressure levels increase during ablation time, and decrease with distance from applicator tip: the recorded peak parenchymal pressure levels range from 1.9 kPa to 71.6 kPa. Different pressure evolutions have been recorded, as pressure rises earlier in proximity of the tip. The present study is the first investigation of parenchymal pressure detection in liver undergoing LA: the successful detection of intra-tissue pressure may be a key asset for improving LA, as pressure levels have been correlated to scattered recurrences of tumors by different studies.

  16. Intra-Tissue Pressure Measurement in Ex Vivo Liver Undergoing Laser Ablation with Fiber-Optic Fabry-Perot Probe

    Directory of Open Access Journals (Sweden)

    Daniele Tosi

    2016-04-01

    Full Text Available We report the first-ever intra-tissue pressure measurement performed during 1064 nm laser ablation (LA of an ex vivo porcine liver. Pressure detection has been performed with a biocompatible, all-glass, temperature-insensitive Extrinsic Fabry-Perot Interferometry (EFPI miniature probe; the proposed methodology mimics in-vivo treatment. Four experiments have been performed, positioning the probe at different positions from the laser applicator tip (from 0.5 mm to 5 mm. Pressure levels increase during ablation time, and decrease with distance from applicator tip: the recorded peak parenchymal pressure levels range from 1.9 kPa to 71.6 kPa. Different pressure evolutions have been recorded, as pressure rises earlier in proximity of the tip. The present study is the first investigation of parenchymal pressure detection in liver undergoing LA: the successful detection of intra-tissue pressure may be a key asset for improving LA, as pressure levels have been correlated to scattered recurrences of tumors by different studies.

  17. Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle

    Science.gov (United States)

    Poggiogalle, Eleonora; Donini, Lorenzo Maria; Lenzi, Andrea; Chiesa, Claudio; Pacifico, Lucia

    2017-01-01

    The estimates of global incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.

  18. Deep Sequencing Reveals Novel Genetic Variants in Children with Acute Liver Failure and Tissue Evidence of Impaired Energy Metabolism.

    Science.gov (United States)

    Valencia, C Alexander; Wang, Xinjian; Wang, Jin; Peters, Anna; Simmons, Julia R; Moran, Molly C; Mathur, Abhinav; Husami, Ammar; Qian, Yaping; Sheridan, Rachel; Bove, Kevin E; Witte, David; Huang, Taosheng; Miethke, Alexander G

    2016-01-01

    The etiology of acute liver failure (ALF) remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism. Twelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were selected from a retrospective cohort of 74 subjects with ALF because their fixed and frozen liver samples were available for histological, ultrastructural, molecular and biochemical analysis. A customized next-generation sequencing panel for 26 genes associated with mitochondrial and fatty acid oxidation defects revealed mutations and sequence variants in five subjects. Variants involved the genes ACAD9, POLG, POLG2, DGUOK, and RRM2B; the latter not previously reported in subjects with ALF. The explanted livers of the patients with heterozygous, truncating insertion mutations in RRM2B showed patchy micro- and macrovesicular steatosis, decreased mitochondrial DNA (mtDNA) content <30% of controls, and reduced respiratory chain complex activity; both patients had good post-transplant outcome. One infant with severe lactic acidosis was found to carry two heterozygous variants in ACAD9, which was associated with isolated complex I deficiency and diffuse hypergranular hepatocytes. The two subjects with heterozygous variants of unknown clinical significance in POLG and DGUOK developed ALF following drug exposure. Their hepatocytes displayed abnormal mitochondria by electron microscopy. Targeted next generation sequencing and correlation with histological, ultrastructural and functional studies on liver tissue in children with elevated lactate/pyruvate ratio expand the spectrum of genes associated with pediatric ALF.

  19. PARP inhibitor rucaparib induces changes in NAD levels in cells and liver tissues as assessed by MRS.

    Science.gov (United States)

    Almeida, Gilberto S; Bawn, Carlo M; Galler, Martin; Wilson, Ian; Thomas, Huw D; Kyle, Suzanne; Curtin, Nicola J; Newell, David R; Maxwell, Ross J

    2017-09-01

    Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy ((1) H-MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD(+) ) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response. SW620 (colorectal) and A2780 (ovarian) cancer cell lines, and PARP1 wild-type (WT) and PARP1 knock-out (KO) mice, were treated with rucaparib, temozolomide (methylating agent) or a combination of both drugs. (1) H-MRS spectra were obtained from perchloric acid extracts of tumour cells and mouse liver. Both cell lines showed an increase in NAD(+) levels following PARP inhibitor treatment in comparison with temozolomide treatment. Liver extracts from PARP1 WT mice showed a significant increase in NAD(+) levels after rucaparib treatment compared with untreated mouse liver, and a significant decrease in NAD(+) levels in the temozolomide-treated group. The combination of rucaparib and temozolomide did not prevent the NAD(+) depletion caused by temozolomide treatment. The (1) H-MRS results show that NAD(+) levels can be used as a biomarker of PARP inhibitor and methylating agent treatments, and suggest that in vivo measurement of NAD(+) would be valuable. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Influence of HBcAg in liver cell plasma on expression of transforming growth factor-beta 1 in liver tissue of low-grade chronic hepatitis B patients

    Institute of Scientific and Technical Information of China (English)

    Yong-Gang Liu; Jun-Qiang Li; Chen-Zhao Song; Jian-Hua Lu; Xin-Xin Wang; Jian-Lin Yang; Zhen-Wei Lang; Xin Meng; Li-Jie Zhang; Lin Sun; Shi-Jie Zhang

    2006-01-01

    AIM: To study the influence of HBcAg on the expression of transforming growth factor-beta 1 (TGF-β1) in liver tissue of low-grade chronic hepatitis B (CHB) patients.METHODS: The expression of TGF-β1 and HBcAg in liver samples from 93 low-grade CHB patients was detected by immunohistochemistry and valuated by semi-quantitative scoring.RESULTS: In the 93 low-grade CHB patients, HBcAg was expressed in cell plasma but not in the liver tissue.There was no significant difference between the two groups.CONCLUSION: The expression of TGF-β1 is not related with HBcAg expressed as plasma type in the tissues of low-grade CHB patients.

  1. Prediction of flunixin tissue residue concentrations in livers from diseased cattle.

    Science.gov (United States)

    Wu, H; Baynes, R E; Tell, L A; Riviere, J E

    2013-12-01

    Flunixin, a widely used non-steroidal anti-inflammatory drug, was a leading cause of violative residues in cattle. The objective of this analysis was to explore how the changes in pharmacokinetic (PK) parameters that may be associated with diseased animals affect the predicted liver residue of flunixin in cattle. Monte Carlo simulations for liver residues of flunixin were performed using the PK model structure and relevant PK parameter estimates from a previously published population PK model for flunixin in cattle. The magnitude of a change in the PK parameter value that resulted in a violative residue issue in more than one percent of a cattle population was compared. In this regard, elimination clearance and volume of distribution affected withdrawal times. Pathophysiological factors that can change these parameters may contribute to the occurrence of violative residues of flunixin.

  2. Skeletal Muscle Derived IL-6 in Liver and Adipose Tissue Metabolism

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet

    Summary Physical activity can lead to metabolic disease and treatment of several metabolic diseases include exercise training. Skeletal muscle has, due to its central role in glucose and fat metabolism at rest and during exercise been studied in detail with regard to exercise training. The role...... indicate that during 1h of exercise the liver utilizes carbohydrates for oxidation rather than gluconeogenesis and that gluconeogenic activity during 1h of exercise is not regulated through increases in protein content. The aim of study III was to investigate the role of skeletal muscle derived IL-6...... indirectly regulate PEPCK protein content when on HFD and that skeletal muscle derived IL-6 may regulate skeletal muscle and hepatic fat metabolism. These findings indicate an indirect role of skeletal muscle derived IL-6 in the regulation of liver metabolism in response to HFD and HFD combined with exercise...

  3. Alcohol,inflammation,and gut-liver-brain interactions in tissue damage and disease development

    Institute of Scientific and Technical Information of China (English)

    H; Joe; Wang; Samir; Zakhari; M; Katherine; Jung

    2010-01-01

    Chronic inflammation is often associated with alcoholrelated medical conditions. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPS). Alcohol can significantly increase the translocation of LPS from the gut. In healthy individuals, the adverse effects of LPS are kept in check by the actions and interactions of multiple organs. The liver plays a central role in detoxifying LPS and producing a balanced cytokine milieu. The central nervous syst...

  4. Histopathological and Ultrastructural Studies of Liver Tissue from TCDD-Exposed Beach Mice (Peromyscus polionotus).

    Science.gov (United States)

    1980-03-01

    gross developmental .7so-i defects such as cleft palate , cleft lip and polydactyly. Body and organ weights were recorded, internal organs were examined...according to the study, sex and treatment , placed in glass jars, frozed and subnitted for TCDD analysis. Hepatic Ultrastructural Study After the liver was...weights per se was not attempted since the ages of the beach mice were not known and the animals could only be classified by sex and treatment . The

  5. Organochlorine-induced histopathology in kidney and liver tissue from Arctic fox (Vulpes lagopus).

    Science.gov (United States)

    Sonne, Christian; Wolkers, Hans; Leifsson, Pall S; Jenssen, Bjørn Munro; Fuglei, Eva; Ahlstrøm, Oystein; Dietz, Rune; Kirkegaard, Maja; Muir, Derek C G; Jørgensen, Even

    2008-04-01

    The effects of persistent organic pollutants on renal and liver morphology in farmed arctic fox (Vulpes lagopus) were studied under experimental conditions. Control animals received a diet containing pork (Sus scrofa) fat with low amounts of persistent organic pollutants, while the diet of the exposed animals contained whale blubber, 'naturally' contaminated with persistent organic pollutants. Polychlorinated biphenyls (PCB) and organochlorine pesticide (OCP) concentrations in the whale blubber were 488 and 395 ng/g wet weight, respectively. Animals were sacrificed and sampled when they were at their fattest (winter) as well as their lowest body weight (summer). The results show that PCB and OCP exposure causes renal (and probably also liver) lesions in arctic foxes. The prevalence of glomerular, tubular and interstitial lesions was significantly highest in the exposed group (chi-square: all p0.05). The prevalence of lesions was not significantly different between lean (winter) and fat (summer) foxes for any of the lesions (chi-square: all p>0.05). We suggest that wild arctic foxes exposed to an environmental cocktail of persistent organic pollutants, such as PCBs and OCPs, in their natural diet are at risk for developing chronic kidney and liver damage. Whether such lesions may have an impact on age and health of the animals remains uncertain.

  6. Different Th17 immunity in gut, liver, and adipose tissues during obesity: the role of diet, genetics, and microbes.

    Science.gov (United States)

    Cavallari, Joseph F; Denou, Emmanuel; Foley, Kevin P; Khan, Waliul I; Schertzer, Jonathan D

    2016-01-01

    Microbes modify immunometabolism responses linking obesity and type 2 diabetes. Immunity helps maintain a host-microbe symbiosis, but inflammation can promote insulin resistance in tissues that control blood glucose. We were interested in compartmentalization of immune responses during obesity and show here that feeding mice an obesity-causing high-fat diet (HFD) decreased a marker of neutrophil activation and cytokines related to Th17 responses in the gut. A HFD decreased IL-17 and IL-21/22 in the ileum and colon, respectively. A HFD increased IL-17, IL-21/22 and other related Th17 responses in the liver. At the whole tissue level, there is divergence in gut and metabolic tissue Th17 cytokines during diet-induced obesity. Deletion of the bacterial peptidoglycan sensor NOD2 had relatively minor effects on these immune responses. We propose a model where diet-induced obesity promotes a permissive gut immune environment and sets the stage for host genetics to contribute to dysbiosis-driven metabolic tissue inflammation.

  7. Inducible Deletion of Protein Kinase Map4k4 in Obese Mice Improves Insulin Sensitivity in Liver and Adipose Tissues.

    Science.gov (United States)

    Danai, Laura V; Flach, Rachel J Roth; Virbasius, Joseph V; Menendez, Lorena Garcia; Jung, Dae Young; Kim, Jong Hun; Kim, Jason K; Czech, Michael P

    2015-07-01

    Studies in vitro suggest that mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) attenuates insulin signaling, but confirmation in vivo is lacking since Map4k4 knockout is lethal during embryogenesis. We thus generated mice with floxed Map4k4 alleles and a tamoxifen-inducible Cre/ERT2 recombinase under the control of the ubiquitin C promoter to induce whole-body Map4k4 deletion after these animals reached maturity. Tamoxifen administration to these mice induced Map4k4 deletion in all tissues examined, causing decreased fasting blood glucose concentrations and enhanced insulin signaling to AKT in adipose tissue and liver but not in skeletal muscle. Surprisingly, however, mice generated with a conditional Map4k4 deletion in adiponectin-positive adipocytes or in albumin-positive hepatocytes displayed no detectable metabolic phenotypes. Instead, mice with Map4k4 deleted in Myf5-positive tissues, including all skeletal muscles tested, were protected from obesity-induced glucose intolerance and insulin resistance. Remarkably, these mice also showed increased insulin sensitivity in adipose tissue but not skeletal muscle, similar to the metabolic phenotypes observed in inducible whole-body knockout mice. Taken together, these results indicate that (i) Map4k4 controls a pathway in Myf5-positive cells that suppresses whole-body insulin sensitivity and (ii) Map4k4 is a potential therapeutic target for improving glucose tolerance and insulin sensitivity in type 2 diabetes.

  8. Paracetamol (acetaminophen) decreases hydrogen sulfide tissue concentration in brain but increases it in the heart, liver and kidney in mice.

    Science.gov (United States)

    Wiliński, Bogdan; Wiliński, Jerzy; Somogyi, Eugeniusz; Góralska, Marta; Piotrowska, Joanna

    2011-01-01

    The biological action ofN-acetyl-p-aminophenol - paracetamol (acetaminophen) has been demonstrated to involve different mechanisms and is still not clear. Hydrogen sulfide (H2S) has been shown to play an important role in many physiological and pathological processes including nociception. The interaction between acetaminophen and endogenous H2S is unknown. Twenty four female CBA strain mice were administered intraperitoneal injections of N-acetyl-p-aminophenol solution: paracetemol in doses of 30 mg/kg b.w. per day (group D1, n = 8) or 100 mg/kg b.w. per day (group D2, n = 8).. The control group (n = 8) received physiological saline in portions of the same volume--0.2 ml. The measurements of tissue H2S concentration were performed with the Siegel spectrophotometric modified method. In the brain, the H2S tissue level decreased, but more significantly in the lower drug dose group. Conversely, there was a significant rise in the H2S tissue concentration in D1 and D2 groups in heart and kidney with the increase more pronounced in the group with the lower paracetamol dose. In the liver only the higher acetaminophen dose elicited a change in H2S concentration, increasing after administration of acetaminophen at 100 mg/kg. Our study demonstrates that paracetamol induces H2S tissue concentration changes in different mouse organs.

  9. Differences in tissue distribution of iron from various clinically used intravenous iron complexes in fetal avian heart and liver.

    Science.gov (United States)

    Spicher, Karsten; Brendler-Schwaab, Susanne; Schlösser, Christoph; Catarinolo, Maria; Fütterer, Sören; Langguth, Peter; Enzmann, Harald

    2015-10-01

    Nanomedicines are more complex than most pharmacologically active substances or medicines and have been considered as non-biological complex drugs. For nanomedicines pivotal pharmacokinetic properties cannot be assessed by plasma concentration data from standard bioequivalence studies. Using intravenous iron complexes (IICs) as model we show that fetal avian tissues can be used to study time dependent tissue concentrations in heart and liver. Clear differences were found between equimolar doses of sucrose, gluconate or carboxymaltose coated iron particles. The range in tissue iron concentrations observed with these clinically widely used IICs provides an orientation as to what should be acceptable for any new IICs. Moreover, sensitivity of the experimental model was high enough to detect a 20% difference in tissue iron concentration. For the authorization of generic products under Article 10 (1) of Directive 2001/83/EC a plasma concentration of an active substance in the range of 80%-125% versus the reference product is usually considered acceptable. Based on its high discriminatory sensitivity this method was used to support a positive marketing authorization decision for a generic nanomedicine product.

  10. Cloning changes the response to obesity of innate immune factors in blood, liver, and adipose tissues in domestic pigs.

    Science.gov (United States)

    Rødgaard, Tina; Skovgaard, Kerstin; Stagsted, Jan; Heegaard, Peter M H

    2013-06-01

    The objective of this study was to evaluate the usefulness of cloned pigs as porcine obesity models reflecting obesity-associated changes in innate immune factor gene expression profiles. Liver and adipose tissue expression of 43 innate immune genes as well as serum concentrations of six immune factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both upregulation and downregulation were observed in the controls. Cloning resulted in a less differentiated adipose tissue expression pattern. Finally, the serum concentrations of two acute-phase proteins (APPs), haptoglobin (HP) and orosomucoid (ORM), were increased in obese clones as compared to obese controls as well as lean clones and controls. Generally, the variation in phenotype between individual pigs was not reduced in cloned siblings as compared to normal siblings. Therefore, we conclude that cloning limits both the number of genes responding to obesity as well as the degree of tissue-differentiated gene expression, concomitantly with an increase in APP serum concentrations only seen in cloned, obese pigs. This may suggest that the APP response seen in obese, cloned pigs is a consequence of the characteristic skewed gene response to obesity in cloned pigs, as described in this work. This should be taken into consideration when using cloned animals as models for innate responses to obesity.

  11. Failure to fix nitrogen by non-reproductive symbiotic rhizobia triggers host sanctions that reduce fitness of their reproductive clonemates.

    Science.gov (United States)

    Oono, Ryoko; Anderson, Carolyn G; Denison, R Ford

    2011-09-07

    The legume-rhizobia symbiosis is a classical mutualism where fixed carbon and nitrogen are exchanged between the species. Nonetheless, the plant carbon that fuels nitrogen (N(2)) fixation could be diverted to rhizobial reproduction by 'cheaters'--rhizobial strains that fix less N(2) but potentially gain the benefit of fixation by other rhizobia. Host sanctions can decrease the relative fitness of less-beneficial reproductive bacteroids and prevent cheaters from breaking down the mutualism. However, in certain legume species, only undifferentiated rhizobia reproduce, while only terminally differentiated rhizobial bacteroids fix nitrogen. Sanctions were, therefore, tested in two legume species that host non-reproductive bacteroids. We demonstrate that even legume species that host non-reproductive bacteroids, specifically pea and alfalfa, can severely sanction undifferentiated rhizobia when bacteroids within the same nodule fail to fix N(2). Hence, host sanctions by a diverse set of legumes play a role in maintaining N(2) fixation.

  12. Malarial Infection of Female BWF1 Lupus Mice Alters the Redox State in Kidney and Liver Tissues and Confers Protection against Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Saleh Al-Quraishy

    2013-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototypic autoimmune disease characterized by an imbalanced redox state and increased apoptosis. Tropical infections, particularly malaria, may confer protection against SLE. Oxidative stress is a hallmark of SLE. We have measured changes in the levels of nitric oxide (NO, hydrogen peroxide (H2O2, malondialdehyde (MDA, and reduced glutathione (GSH in both kidney and liver tissues of female BWF1 lupus mice, an experimental model of SLE, after infection with either live or gamma-irradiated malaria. We observed a decrease in NO, H2O2, and MDA levels in kidney tissues after infection of lupus mice with live malaria. Similarly, the levels of NO and H2O2 were significantly decreased in the liver tissues of lupus mice after infection with live malaria. Conversely, GSH levels were obviously increased in both kidney and liver tissues after infection of lupus mice with either live or gamma-irradiated malaria. Liver and kidney functions were significantly altered after infection of lupus mice with live malaria. We further investigated the ultrastructural changes and detected the number of apoptotic cells in kidney and liver tissues in situ by electron microscopy and TUNEL assays. Our data reveal that infection of lupus mice with malaria confers protection against lupus nephritis.

  13. Melatonin increases intracellular calcium in the liver, muscle, white adipose tissues and pancreas of diabetic obese rats.

    Science.gov (United States)

    Agil, A; Elmahallawy, E K; Rodríguez-Ferrer, J M; Adem, A; Bastaki, S M; Al-Abbadi, I; Fino Solano, Y A; Navarro-Alarcón, M

    2015-08-01

    Melatonin, a widespread substance with antioxidant and anti-inflammatory properties, has been found to act as an antidiabetic agent in animal models, regulating the release and action of insulin. However, the molecular bases of this antidiabetic action are unknown, limiting its application in humans. Several studies have recently shown that melatonin can modify calcium (Ca(2+)) in diabetic animals, and Ca(2+) has been reported to be involved in glucose homeostasis. The objective of the present study was to assess whether the antidiabetic effect of chronic melatonin at pharmacological doses is established via Ca(2+) regulation in different tissues in an animal model of obesity-related type 2 diabetes, using Zücker diabetic fatty (ZDF) rats and their lean littermates, Zücker lean (ZL) rats. After the treatments, flame atomic absorption spectrometry was used to determine Ca(2+) levels in the liver, muscle, main types of internal white adipose tissue, subcutaneous lumbar fat, pancreas, brain, and plasma. This study reports for the first time that chronic melatonin administration (10 mg per kg body weight per day for 6 weeks) increases Ca(2+) levels in muscle, liver, different adipose tissues, and pancreas in ZDF rats, although there were no significant changes in their brain or plasma Ca(2+) levels. We propose that this additional peripheral dual action mechanism underlies the improvement in insulin sensitivity and secretion previously documented in samples from the same animals. According to these results, indoleamine may be a potential candidate for the treatment of type 2 diabetes mellitus associated with obesity.

  14. Effect of estrogen on expression of prohibitin in white adipose tissue and liver of diet-induced obese rats.

    Science.gov (United States)

    Choi, Minji; Chaudhari, Harmesh N; Ji, Young Rae; Ryoo, Zae Young; Kim, Sang Woo; Yun, Jong Won

    2015-09-01

    Prohibitin (PHB) is a ubiquitously expressed and highly conserved protein that participates in diverse cellular processes, and its functions are linked to a variety of diseases. In the present study, to explore transcriptional activation and signaling pathways involved in PHB regulation in response to sex hormone treatment, we investigated the effects of estrogen (17-β-estradiol, E2) on regulation of PHB in several metabolic tissues from male and female rats. Elevated expression of PHB was prominent in white adipose tissue (WAT) and the liver, and E2 stimulated PHB expression in both ND and HFD-fed rats. To further confirm the expression of PHB which was increased in WAT and the liver, we analyzed PHB expression levels in 3T3-L1 and C9 cells after the treatment of E2. Transcription and protein levels of PHB were dose-dependently increased by E2 treatment in both cell types, supporting our in vivo data. To further evaluate the possible role of E2 in elevation of PHB via estrogen receptors (ER), the potent ER inhibitor fulvestrant was treated to 3T3-L1 and C9 cells. Fulvestrant markedly suppressed both transcription and protein levels of PHB, suggesting that PHB expression in both tissues may be regulated through ERs. GeneMANIA, a predictive web interface, was used to show that Phb is regulated via the intracellular steroid hormone receptor signaling pathway, suggesting a role for ERs in expression of Phb as well as other metabolically important genes. Based on these results, we expect that targeting PHB would be a useful therapeutic approach for treatment of obesity.

  15. Developmental changes of cytochrome P450 dependent monooxygenase functions after transplantation of fetal liver tissue suspension into spleens of adult syngenic rats.

    Science.gov (United States)

    Lupp, A; Trautmann, A K; Krausse, T; Klinger, W

    1998-06-01

    Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic Fisher 344 inbred rats. Animals were sacrificed at 3 days, 1, 2, 4 weeks, and 2, 4 and 6 months after transplantation and cytochrome P450 (P450) dependent monooxygenase functions in spleen and liver 9000 g supernatants were assessed by measuring three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; mainly 1A), ethoxycoumarin O-deethylation (ECOD; predominantly 1A, 2A, 2B) and ethylmorphine N-demethylation (END; mainly 3A). Values of transplant recipients were compared to those of sham operated and age matched control rats. Spleen weights were significantly higher in transplanted rats, compared to controls or sham operated animals, but there was no influence of the transplants within the spleens on liver weights. With fetal livers at the 21st day of gestation, the day of transplantation, a weak EROD and ECOD, but no END activity was seen. Spleens of controls or sham operated animals displayed nearly no P450 mediated monooxygenase functions. In the explant containing spleens a significant and increasing EROD activity was found from 4 weeks after surgery on and an ECOD activity already 2 weeks after transplantation. END was only slightly enhanced at 6 months after surgery. The livers of all three groups of rats displayed normal EROD, ECOD and END activities. Transplantation of fetal liver tissue suspensions into the spleens did not influence the P450 dependent monooxygenase functions within the livers of the animals. From these results it can be concluded that intrasplenically transplanted liver cells originating from syngenic fetal liver tissue suspensions proliferate and differentiate within the host organs. They display P450 dependent monooxygenase functions with some developmental changes during the observed time period of 6 months.

  16. Volumetrical changes of liver associated with breathing and its impact to normal tissue complication probability

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jung Hee; Kim, Joo Ho; Park, Je Il [Dept. of Radiation Oncology, Yensei University, College of Medicine, Seoul (Korea, Republic of)

    2001-12-15

    The aim of this study is to investigate geometrical and volumetrical changes of liver due to breathing and its impact to NTCP. In order to attain better treatment results it should be considered deliberately during planning session. Seven patients were examined in this study who have done TACE for accurate tumor margin drawing. After contrast media injection, C-T scan data were obtained in supine position during breathing free, inhalation and exhalation, respectively. For all patients C-T scan were done with same scanning parameters- 5 mm index, 5 mm thickness and pitch 1. Based on C-T data we have measured differences of each variables between breathing status such as changes of total and remained liver volumes, GTV, beam path length and superior to inferior shift. NTCP were calculated using Lyman's effective volume DVH reduction scheme and for this NTCP calculation, the V50 was computed from DVH and each m, n value were referred from Burmans data. The measured total tilter volume and the remained liver volume changed between inspiration and expiration about 1.2-7.7%(mean+2.7%) and 2.5-13.23%(mean=5.8%) respectively, and these results were statistically significant(p>0.1). The GTV difference in each patient varied widely from 1.17% to 30.69%, but this result was not statistically significant. Depending on the breathing status, the beam path length was changed from 0.5 cm to 1.1 cm with the average of 0.7 cm, and it was statistically significant(p=0.006). The measured superior to inferior shifts were ranged from 0.5 cm to 3.74 cm. The NTCPs were changed relatively small in each patient, but the variation was large between the patients. The mean NTCP difference was 10.5%, with the variation ranged from 7% to 23.5%. Variations of liver volume and of beam path length were changed significantly depending on the breathing statues and the range of variation itself was very different between the patients. Since this variance could seriously affect the clinical

  17. New Insights into the Role of Macrophages in Adipose Tissue Inflammation and Fatty Liver Disease: Modulation by Endogenous Omega-3 Fatty Acid-derived Lipid Mediators

    Directory of Open Access Journals (Sweden)

    Joan eClària

    2011-10-01

    Full Text Available Obesity is causally linked to a chronic state of low-grade inflammation in adipose tissue. Prolonged, unremitting inflammation in this tissue has a direct impact on insulin-sensitive tissues (i.e. liver and its timely resolution is a critical step toward reducing the prevalence of related co-morbidities such as insulin resistance and non-alcoholic fatty liver disease. This article describes the current state-of-the-art knowledge and novel insights into the role of macrophages in adipose tissue inflammation, with special emphasis on the progressive changes in macrophage polarization observed over the course of obesity. In addition, this article extends the discussion to the contribution of Kupffer cells, the liver resident macrophages, to metabolic liver disease. Special attention is given to the modulation of macrophage responses by omega-3-PUFAs, and more importantly by resolvins, which are potent anti-inflammatory and pro-resolving autacoids generated from docosahexaenoic and eicosapentaenoic acids. In fact, resolvins have been shown to work as endogenous stop signals in inflamed adipose tissue and to return this tissue to homeostasis by inducing a phenotypic switch in macrophage polarization toward a pro-resolving phenotype. Collectively, this article offers new views on the role of macrophages in metabolic disease and their modulation by endogenously-generated omega-3-PUFA-derived lipid mediators.

  18. FT-Raman study of deferoxamine and deferiprone exhibits potent amelioration of structural changes in the liver tissues of mice due to aluminum exposure

    Science.gov (United States)

    Sivakumar, S.; Khatiwada, Chandra Prasad; Sivasubramanian, J.; Raja, B.

    2014-01-01

    The present study inform the alterations on major biochemical constituents such as lipids, proteins, nucleic acids and glycogen along with phosphodiester linkages, tryptophan bands, tyrosine doublet, disulfide bridge conformations, aliphatic hydrophobic residue, and salt bridges in liver tissues of mice using Fourier transform Raman spectroscopy. In amide I, amide II and amide III, the area value significant decrease due structural alteration in the protein, glycogen and triglycerides levels but chelating agents DFP and DFO upturned it. Morphology changes by aluminium induced alterations and recovery by chelating agents within liver tissues known by histopathological examination. Concentrations of trace elements were found by ICP-OES. FT-Raman study was revealed to be in agreement with biochemical studies and demonstrate that it can successfully specify the molecular alteration in liver tissues. The tyrosyl doublet ratio I899/I831 decreases more in aluminum intoxicated tissues but treatment with DFP and DFO + DFP brings back to nearer control value. This indicates more variation in the hydrogen bonding of the phenolic hydroxyl group due to aluminum poisoning. The decreased Raman intensity ratio (I3220/I3400) observed in the aluminum induced tissues suggests a decreased water domain size, which could be interpreted in terms of weaker hydrogen-bonded molecular species of water in the aluminum intoxicated liver tissues. Finally, FT-Raman spectroscopy might be a useful tool for obtained successfully to indicate the molecular level changes.

  19. New Insights into the Role of Macrophages in Adipose Tissue Inflammation and Fatty Liver Disease: Modulation by Endogenous Omega-3 Fatty Acid-Derived Lipid Mediators

    Science.gov (United States)

    Clària, Joan; González-Périz, Ana; López-Vicario, Cristina; Rius, Bibiana; Titos, Esther

    2011-01-01

    Obesity is causally linked to a chronic state of “low-grade” inflammation in adipose tissue. Prolonged, unremitting inflammation in this tissue has a direct impact on insulin-sensitive tissues (i.e., liver) and its timely resolution is a critical step toward reducing the prevalence of related co-morbidities such as insulin resistance and non-alcoholic fatty liver disease. This article describes the current state-of-the-art knowledge and novel insights into the role of macrophages in adipose tissue inflammation, with special emphasis on the progressive changes in macrophage polarization observed over the course of obesity. In addition, this article extends the discussion to the contribution of Kupffer cells, the liver resident macrophages, to metabolic liver disease. Special attention is given to the modulation of macrophage responses by omega-3-PUFAs, and more importantly by resolvins, which are potent anti-inflammatory and pro-resolving autacoids generated from docosahexaenoic and eicosapentaenoic acids. In fact, resolvins have been shown to work as endogenous “stop signals” in inflamed adipose tissue and to return this tissue to homeostasis by inducing a phenotypic switch in macrophage polarization toward a pro-resolving phenotype. Collectively, this article offers new views on the role of macrophages in metabolic disease and their modulation by endogenously generated omega-3-PUFA-derived lipid mediators. PMID:22566839

  20. Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W [Department of Mechanical Engineering, Drexel University, Philadelphia, PA 19104 (United States); Emami, K; Wu, H, E-mail: sunwei@drexel.edu, E-mail: weisun@tsinghua.edu.cn [Radiation Biophysics Lab, NASA Johnson Space Center, Houston, TX 77586 (United States)

    2011-09-15

    The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

  1. Investigation on Acute Biochemical Effects of Ce(NO3)3 on Liver and Kidney Tissues by MAS 1H NMR Spectroscopic-Based Metabonomic Approach

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    High resolution magic angle spinning (MAS)-1 H nuclear magnetic resonance (NMR) spectroscopic-based metabonomic approach was applied to the investigation on the acute biochemical effects of Ce(NO3)3. Male Wistar rats were liver and kidney tissues were analyzed using principal component analysis to extract toxicity information. The biochemical effects of Ce(NO3)3 were characterized by the increase of triglycerides and lactate and the decrease of glycogen in rat liver tissue, together with an elevation of the triglyceride level and a depletion of glycerophosphocholine and betaine in kidney tissues. The target lesions of Ce(NO3)3 on liver and kidney were found by MAS NMR-based metabonomic method. This study demonstrates that the combination of MAS 1H NMR and pattern recognition analysis can be an effective method for studies of biochemical effects of rare earths.

  2. The effects of vitamin D3 on lipogenesis in the liver and adipose tissue of pregnant rats.

    Science.gov (United States)

    Kang, Eun-Jin; Lee, Jae-Eon; An, Sung-Min; Lee, Jae Ho; Kwon, Hyeog Soong; Kim, Byoung Chul; Kim, Seon Jong; Kim, Joo Man; Hwang, Dae Youn; Jung, Young-Jin; Yang, Seung Yun; Kim, Seung Chul; An, Beum-Soo

    2015-10-01

    Obesity is a worldwide individual and public health issue, and contributes to the development of numerous chronic diseases. In particular, maternal obesity has harmful effects on both the mother and child during and after pregnancy. The digestion and metabolism of food are controlled by endocrine factors, including insulin, glucagon and estrogen. These hormonal factors are differentially regulated during pregnancy due to the specialized hormonal environment during this period. In the present study, we examined the effects of 1,25-dihydroxyvitamin D3 (VD3), an active hormonal form of nutritional vitamin D3, on lipid metabolism in pregnant rats. The body weight of rats treated with VD3 was significantly reduced compared to that of the rats in the control group. In addition, histological analysis demonstrated that the amount of fat stored in adipocytes was reduced by treatment with VD3. To determine the role of VD3 in lipid metabolism, the expression levels of lipid metabolism‑associated genes were measured in the rat adipose tissue and liver. VD3 negatively regulated the expression of various lipogenic genes, including fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1) and acetyl-CoA carboxylase 1 (ACC1), in both the adipose tissue and liver. However, the regulators of lipogenic enzymes such as, sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-γ (PPAR-γ) and insulin-induced gene 2 (INSIG2) were differentially regulated by VD3 in a tissue‑specific manner. On the whole, these findings suggest that VD3 regulates lipid metabolism and deposition in the liver and adipose tissue, and thereby reduces fat in pregnant animals, as well as body weight. Our results suggest that the alteration of lipogenesis through the administration of VD3 may help to reduce excessive weight gain during pregnancy and prevent obesity‑related pregnancy complications such as pre-eclampsia, gestational diabetes

  3. GRADING SCALE OF VISCERAL ADIPOSE TISSUE THICKNESS AND THEIR RELATION TO THE NONALCOHOLIC FATTY LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    Luís Jesuino de Oliveira ANDRADE

    2014-04-01

    Full Text Available Context The mesenteric fat is drained by the portal system, being related to the metabolic syndrome which is an impor­tant risk factor for non-alcoholic fatty liver disease (NAFLD. Objectives Graduate of visceral fat thickness and correlate with the NAFLD degree through ultrasonography method. Methods We studied 352 subjects for age, gender, measures of subcutaneous fat thickness and visceral fat thickness as well as the presence and degree of liver fatty. Was analyzed the independent relationship between visceral fat thickness and NAFLD, and linear regression analysis was used in order to predict the visceral fat thickness from subcutaneous fat thickness. Results The mean age of 225 women (63.9% and 127 men (36.1% was 47.5 ± 14.0 (18-77 years, 255 subjects had normal examinations, 97 had NAFLD thus distributed, 37 grade 1, 32 grade 2, and 28 grade 3. The subcutaneous fat thickness ranged from 0.26 to 3.50 cm with a mean of 1.3 ± 0.6 cm and visceral fat thickness ranged from 0.83 to 8.86 cm with a mean of 3.6 ± 1.7 cm. Linear regression showed that for every increase of 1 cm in subcutaneous fat thickness the visceral fat thickness will increase 0.9 cm. Conclusions The visceral fat thickness measured by ultrasonography is a useful and seems to be able to help estimate the risk of NAFLD.

  4. Monitoring of human liver and kidney allograft tolerance: a tissue/histopathology perspective.

    Science.gov (United States)

    Demetris, Anthony J; Lunz, John G; Randhawa, Parmjeet; Wu, Tong; Nalesnik, Michael; Thomson, Angus W

    2009-01-01

    Several factors acting together have recently enabled clinicians to seriously consider whether chronic immunosuppression is needed in all solid organ allograft recipients. This has prompted a dozen or so centers throughout the world to prospectively wean immunosuppression from conventionally treated liver allograft recipients. The goal is to lessen the impact of chronic immunosuppression and empirically identify occasional recipients who show operational tolerance, defined as gross phenotype of tolerance in the presence of an immune response and/or immune deficit that has little or no significant clinical impact. Rare operationally tolerant kidney allograft recipients have also been identified, usually by single case reports, but only a couple of prospective weaning trials in conventionally treated kidney allograft recipients have been attempted and reported. Pre- and postweaning allograft biopsy monitoring of recipients adds a critical dimension to these trials, not only for patient safety but also for determining whether events in the allografts can contribute to a mechanistic understanding of allograft acceptance. The following is based on a literature review and personal experience regarding the practical and scientific aspects of biopsy monitoring of potential or actual operationally tolerant human liver and kidney allograft recipients where the goal, intended or attained, was complete withdrawal of immunosuppression.

  5. Extra virgin olive oil reduces liver oxidative stress and tissue depletion of long-chain polyunsaturated fatty acids produced by a high saturated fat diet in mice

    Energy Technology Data Exchange (ETDEWEB)

    Valenzuela, B.R.; Hernandez Rodas, M.C.; Espinosa, A.; Rincon Cervera, M.A.; Romero, N.; Barrera Vazquez, C.; Marambio, M.; Vivero, J.; Valenzuela, B.A.

    2016-07-01

    Long-chain polyunsaturated fatty acids (LCPUFA) which are synthesized mainly in the liver have relevant functions in the organism. A diet high in fat (HFD) generates an increase in the levels of fat and induces oxidative stress (lipo-peroxidation) in the liver, along with a reduction in tissue n-3 and n-6 LCPUFA. Extra virgin olive oil (EVOO) is rich in anti-oxidants (polyphenols and tocopherols) which help to prevent the development of oxidative stress. This study evaluated the role of EVOO in preventing the induction of fat deposition and oxidative stress in the liver and in the depletion of LCPUFA in the liver, erythrocytes and brain generated by a HFD in C57BL/6J mice. Four experimental groups (n = 10/group) were fed a control diet (CD) or a HFD for 12 weeks and were respectively supplemented with EVOO (100 mg/day). The group fed HFD showed a significant increase (p < 0.05) in fat accumulation and oxidative stress in the liver, accompanied by a reduction in the levels of n-3 and n-6 LCPUFA in the liver, erythrocytes and brain. Supplementation with EVOO mitigated the increase in fat and oxidative stress produced by HFD in the liver, along with a normalization of LCPUFA levels in the liver, erythrocytes and brain. It is proposed that EVOO supplementation protects against fat accumulation, and oxidative stress and normalizes n-3 and n-6 LCPUFA depletion induced in mice fed a HFD. (Author)

  6. Three new alternative splicing variants of human cytochrome P450 2D6 mRNA in human extratumoral liver tissue

    Institute of Scientific and Technical Information of China (English)

    Jian Zhuge; Ying-Nian Yu

    2004-01-01

    AIM: To identify the new alternative splicing variants of human CYP2D6 in human extratumoral liver tissue with RT-PCR and sequencing.METHODS: Full length of human CYP2D6 cDNAs was amplificated by reverse transcription-polymerase chain reaction (RT-PCR) from a human extratumoral liver tissue and cloned into pGEM-T vector. The cDNA was sequenced.Exons from 1 to 4 of human CYP2D6 cDNAs were also amplificated by RT-PCR from extratumoral liver tissues of17 human hepatocellular carcinomas. Some RT-PCR products were sequenced. Exons 1 to 4 of CYP2D6 gene were amplified by PCR from extratumoral liver tissue DNA.Two PCR products from extratumoral liver tissues expressing skipped mRNA were partially sequenced.RESULTS: One of the CYP2D6cDNAs had 470 nucleotides from 79 to 548 (3' portion of exons 1 to 5' portion of exon 4),and was skipped. Exons 1 to 4 of CYP2D6 cDNA were assayed with RT-PCR in 17 extratumoral liver tissues. Both wild type and skipped mRNAs were expressed in 4 samples,only wild type mRNA was expressed in 5 samples, and only skipped mRNA was expressed in 8 samples. Two more variants were identified by sequencing the RT-PCR products of exons 1 to 4 of CYP2D6cDNA. The second variant skipped 411 nucleotides from 175 to 585. This variant was identified in 4 different liver tissues by sequencing the RT-PCR products. We sequenced partially 2 of the PCR products amplified of CYP2D6 exon 1 to exon 4 from extratumoral liver tissue genomic DNA that only expressed skipped mRNA by RT-PCR. No point mutations around exon 1, intron 1, and exon 4, and no deletion in CYP2D6gene were detected. The third variant was the skipped exon 3, and 153 bp was lost.CONCLUSION: Three new alternative splicing variants of CYP2D6 mRNA have been identified. They may not be caused by gene mutation and may lose CYP2D6 activity and act as a down-regulator of CYP2D6.

  7. Interaction of mutants of tissue-type plasminogen activator with liver cells: Effect of domain deletions

    NARCIS (Netherlands)

    Kuiper, J.; Hof, A. van 't; Otter, M.; Biessen, E.A.L.; Rijken, D.C.; Berkel, T.J.C. van

    1996-01-01

    The fibrin-specific thrombolyticum tissue-type plasminogen activator (t-PA) has proven to be a potent drug in several clinical trials, but its clinical application is complicated by the rapid clearance of t-PA from the circulation. The rapid plasma clearance of t-PA results from the uptake of t-PA i

  8. Heavy metal concentrations in liver and kidney tissues of pacific walrus

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The U.S. Fish and Wildlife Service continued a 1981-1984 baseline study (Taylor et al. 1989) in 1986-1989, to evaluate contaminant levels in tissues of Pacific...

  9. Protective Effects of Oyster Extract Against Hepatic Tissue Injury in Alcoholic Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    ZHANG Cuiping; LI Xiaoyu; JING Xue; ZHANG Bo; ZHANG Qi; NIU Qinghui; WANG Jianjun; TIAN Zibin

    2014-01-01

    Oyster extract is an effective bioactivity component. It has abundant nutritional value and antiviral, antitumor and im-mune defense functions. The role of oyster extract in treating liver injury has been paid more attention. We use Wistar rats to make alcoholic liver disease model through injecting alcohol into rats’ stomachs. These rats were randomly divided into five groups:model group, control group, low-dose, middle-dose and high-dose experimental group with a dose of 0.12 g kg-1, 0.40 g kg-1, and 1.20 g kg-1 alcoholic. After nine weeks, serum biomarkers (ALT, AST, TG and TCHO), malondialdehyde (MDA), glutathione (GSH), C3a, C5a, IL-17, TNF-ɑ, anti-MAA-HAS IgG, CD3+, CD4+, CD8+, NK cell activation and zinc content were assessed. The results showed that the serum biomarkers(ALT, AST, TG and TCHO), MDA content, anti-MAA-HSA IgG, serum C3a, C5a IL-17 and TNF-ɑlevels of oyster extract treatment groups were significantly decreased in comparison with model group. On the contrary, GSH showed ad-verse trend. Serum CD3+, CD4+ and NK cell activation were significantly increased in middle-dose group and high-dose group compared with model group, and there was decrease of CD8+activity in high-dose group. Plasma Zn level was decreased in model group compared with that in control group. Meanwhile, Mean plasma Zn levels increased dramatically following the dose increase of a given oyster extract.

  10. Prepartal dietary energy alters transcriptional adaptations of the liver and subcutaneous adipose tissue of dairy cows during the transition period.

    Science.gov (United States)

    Selim, S; Salin, S; Taponen, J; Vanhatalo, A; Kokkonen, T; Elo, K T

    2014-05-01

    Overfeeding during the dry period may predispose cows to increased insulin resistance (IR) with enhanced postpartum lipolysis. We studied gene expression in the liver and subcutaneous adipose tissue (SAT) of 16 Finnish Ayrshire dairy cows fed either a controlled energy diet [Con, 99 MJ/day metabolizable energy (ME)] during the last 6 wk of the dry period or high-energy diet (High, 141 MJ/day ME) for the first 3 wk and then gradually decreasing energy allowance during 3 wk to 99 MJ/day ME before the expected parturition. Tissue biopsies were collected at -10, 1, and 9 days, and blood samples at -10, 1, and 7 days relative to parturition. Overfed cows had greater dry matter, crude protein, and ME intakes and ME balance before parturition. Daily milk yield, live weight, and body condition score were not different between treatments. The High cows tended to have greater plasma insulin and lower glucagon/insulin ratio compared with Con cows. No differences in circulating glucose, glucagon, nonesterified fatty acids and β-hydroxybutyrate concentrations, and hepatic triglyceride contents were observed between treatments. Overfeeding compared with Con resulted in lower CPT1A and PCK1 and a tendency for lower G6PC and PC expression in the liver. The High group tended to have lower RETN expression in SAT than Con. No other effects of overfeeding on the expression of genes related to IR in SAT were observed. In conclusion, overfeeding energy prepartum may have compromised hepatic gluconeogenic capacity and slightly affected IR in SAT based on gene expression.

  11. Porous Lactose-Modified Chitosan Scaffold for Liver Tissue Engineering: Influence of Galactose Moieties on Cell Attachment and Mechanical Stability

    Directory of Open Access Journals (Sweden)

    Birong Wang

    2016-01-01

    Full Text Available Galactosylated chitosan (CTS has been widely applied in liver tissue engineering as scaffold. However, the influence of degree of substitution (DS of galactose moieties on cell attachment and mechanical stability is not clear. In this study, we synthesized the lactose-modified chitosan (Lact-CTS with various DS of galactose moieties by Schiff base reaction and reducing action of NaBH4, characterized by FTIR. The DS of Lact-CTS-1, Lact-CTS-2, and Lact-CTS-3 was 19.66%, 48.62%, and 66.21% through the method of potentiometric titration. The cell attachment of hepatocytes on the CTS and Lact-CTS films was enhanced accompanied with the increase of galactose moieties on CTS chain because of the galactose ligand-receptor recognition; however, the mechanical stability of Lact-CTS-3 was reduced contributing to the extravagant hydrophilicity, which was proved using the sessile drop method. Then, the three-dimensional Lact-CTS scaffolds were fabricated by freezing-drying technique. The SEM images revealed the homogeneous pore bearing the favorable connectivity and the pore sizes of scaffolds with majority of 100 μm; however, the extract solution of Lact-CTS-3 scaffold significantly damaged red blood cells by hemolysis assay, indicating that exorbitant DS of Lact-CTS-3 decreased the mechanical stability and increased the toxicity. To sum up, the Lact-CTS-2 with 48.62% of galactose moieties could facilitate the cell attachment and possess great biocompatibility and mechanical stability, indicating that Lact-CTS-2 was a promising material for liver tissue engineering.

  12. Doppler Tissue Evaluation of Atrial Conduction Properties in Patients With Non-alcoholic Fatty-liver Disease.

    Science.gov (United States)

    Ozveren, Olcay; Izgi, Cemil; Eroglu, Elif; Simsek, Mustafa Aytek; Turer, Ayca; Kucukdurmaz, Zekeriya; Cinar, Veysel; Degertekin, Muzaffer

    2016-05-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in clinical practice, and there is an increasing trend in its prevalence in the general population. Recent studies have demonstrated increased risk of atrial fibrillation (AF) in NAFLD. However, information on the mechanism of increased risk of AF in NAFLD is lacking. Impaired atrial conduction is an important factor in the pathophysiology of AF. We aimed to investigate atrial conduction properties in patients with NAFLD by tissue Doppler echocardiography. Fifty-nine ultrasound diagnosed NAFLD patients without clinical diagnosis of hypertension, diabetes mellitus, or cardiac disease and 22 normal subjects as controls were included in this study. Atrial conduction properties were assessed by electromechanical delay (EMD) derived from Doppler tissue echocardiography examination and P-wave dispersion (PWD) calculated from the 12-lead electrocardiogram. Inter-atrial and intra-atrial EMD intervals were significantly longer in NAFLD patients than in controls (inter-atrial EMD, 31.9 ± 8.5 ms vs. 23.4 ± 4.6 ms,p= 0.0001, and intra-atrial EMD, 14.3 ± 5.2 vs. 10.2 ± 4.0 ms,p= 0.001). Similarly, PWD was significantly higher in NAFLD patients compared with controls (49.2 ± 6.3 ms vs. 43.3 ± 4.2 ms,p= 0.0001). Maximum left atrial volume was also significantly higher in the NAFLD group than in controls (51 ± 11 mL vs. 34 ± 9 mL,pNAFLD. Also, in a patient population of NAFLD without any clinical diagnosis of cardiac disease, diabetes, or hypertension, left atrial volume was increased compared with controls. These findings suggest impaired atrial conduction as a factor in increased risk of AF in NAFLD.

  13. Sublethal toxicity of commercial formulations of deltamethrin and permethrin on selected biochemical constituents and enzyme activities in liver and muscle tissues of Anabas testudineus.

    Science.gov (United States)

    Sapana Devi, Maisnam; Gupta, Abhik

    2014-10-01

    The freshwater fish Anabas testudineus was exposed for 21 days to two commercial formulations of synthetic pyrethroids deltamethrin and permethrin at sublethal concentrations of 0.007 and 0.0007 mg L(-1), and 0.093 and 0.0093 mg L(-1), that represented 10% and 1%, respectively, of the 96 h LC50 of these two pesticides for this fish. The glycogen, protein and lactic acid contents, along with succinate dehydrogenase (SDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) enzyme activities in liver and muscle tissues of control and pesticide-exposed fish were estimated. When compared with those of control fish, significant depletion of glycogen content was observed in liver, and that of protein in muscle tissue of fish treated with both the pesticides at their higher as well as lower concentrations. Lactic acid reduction was significant only in fish muscle treated with deltamethrin. SDH level was reduced significantly in both liver and muscle tissues except in fish exposed to 0.0093 mg L(-1) permethrin. AST level was reduced significantly in liver and muscle tissues and ALT in muscle tissue of deltamethrin treated fish only. It is concluded that deltamethrin, a type-II pyrethroid, is more toxic to fish than the type-I pyrethroid permethrin and is capable of rendering toxicity at a dose as low as 1% of its LC50 value. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Levels of Metals in Kidney, Liver, and Muscle Tissue and their Influence on the Fitness for the Consumption of Wild Boar from Western Slovakia.

    Science.gov (United States)

    Gašparík, Jozef; Binkowski, Łukasz J; Jahnátek, Andrej; Šmehýl, Peter; Dobiaš, Milan; Lukáč, Norbert; Błaszczyk, Martyna; Semla, Magdalena; Massanyi, Peter

    2017-06-01

    Due to environmental pollution, wild animals are exposed to various pollutants. Some game animals, such as wild boars are used by people for food, but their meat is not evaluated regarding pollution transfer, since they are unavailable on the official market. The aim of this paper is to present the concentrations of chosen metals (Cd, Co, Cu, Hg, Pb, and Zn) in the kidneys, liver, and muscles of wild boars (n = 40) hunted in eastern Slovakia, as derivatives of physiological distribution and anthropogenic pollution. We found that sex was not a statistically significant factor for metal concentrations. Tissue differences were observed for all the metals studied except for Co. Cd, Cu, and Hg showed the highest median concentrations in kidney tissue with the lowest in muscle tissue (2.73, 3.78, and 0.061 μg/g w.w., respectively). The highest Zn median concentration was noted in the liver tissue with the lowest in muscle tissue. Co and Cu concentrations varied according to the age groups. Correlations between metal concentrations in muscle and kidney tissue were not especially strong; such relationships were not found in liver tissue. Among all the potential relationships of the given metal concentrations between tissues, the only significant relationship, albeit weak, was noted for Pb in muscle and liver tissue. The concentrations found seem not to be extremely high, but according to EU maximum permitted residue levels for Cd and Pb concentrations in meat, none of the samples studied was fully fit for human consumption. TWI and risk was also excessive for both metals.

  15. Effects of adrenal hormones on the expression of adiponectin and adiponectin receptors in adipose tissue, muscle and liver.

    Science.gov (United States)

    de Oliveira, Cristiane; Iwanaga-Carvalho, Carla; Mota, João F; Oyama, Lila M; Ribeiro, Eliane B; Oller do Nascimento, Cláudia M

    2011-11-01

    Adiponectin, an insulin-sensitive hormone that is primarily synthesized in adipose tissue, exerts its effects by binding to two receptors, adipoR1 and adipoR2. Little is known regarding the effects of glucocorticoids on the expression of adiponectin receptors. Male Wistar rats were bilaterally adrenalectomized and treated with dexamethasone (0.2 mg/100 g) twice daily for 3 days. To analyze the potential effects of glucocorticoids, rats received two daily injections of the glucocorticoid receptor antagonist (RU-486, 5.0 mg) over the course of 3 days. Additionally, 3T3-L1 adipocytes and C2C12 myotubes were treated with dexamethasone, adrenaline or RU-486. The gene expression of adiponectin, adipoR1 and adipoR2 was determined by real-time PCR, and protein secretion was examined by Western blotting using lysates from retroperitoneal, epididymal and subcutaneous adipose tissue depots, liver and muscle. In rats, excess glucocorticoids increased the levels of insulin in serum and decreased serum adiponectin concentrations, whereas adrenalectomy decreased the mRNA expression of adiponectin (3-fold) and adipoR2 (7-fold) in epididymal adipose tissue and increased adipoR2 gene expression in muscle (3-fold) compared to control group sham-operated. Dexamethasone treatment did not reverse the effects of adrenalectomy, and glucocorticoid receptor blockade did not reproduce the effects of adrenalectomy. In 3T3-L1 adipocytes, dexamethasone and adrenaline both increased adipoR2 mRNA levels, but RU-486 reduced adipoR2 gene expression in vitro. Dexamethasone treatment induces a state of insulin resistance but does not affect adiponectin receptor expression in adipose tissue. However, the effects of catecholamines on insulin resistance may be due to their effects on adipoR2. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. RNA-Seq gene expression profiling of HepG2 cells: the influence of experimental factors and comparison with liver tissue.

    Science.gov (United States)

    Tyakht, Alexander V; Ilina, Elena N; Alexeev, Dmitry G; Ischenko, Dmitry S; Gorbachev, Alexey Y; Semashko, Tatiana A; Larin, Andrei K; Selezneva, Oksana V; Kostryukova, Elena S; Karalkin, Pavel A; Vakhrushev, Igor V; Kurbatov, Leonid K; Archakov, Alexander I; Govorun, Vadim M

    2014-12-15

    Human hepatoma HepG2 cells are used as an in vitro model of the human liver. High-throughput transcriptomic sequencing is an advanced approach for assessing the functional state of a tissue or cell type. However, the influence of experimental factors, such as the sample preparation method and inter-laboratory variation, on the transcriptomic profile has not been evaluated. The whole-transcriptome sequencing of HepG2 cells was performed using the SOLiD platform and validated using droplet digital PCR. The gene expression profile was compared to the results obtained with the same sequencing method in another laboratory and using another sample preparation method. We also compared the transcriptomic profile HepG2 cells with that of liver tissue. Comparison of the gene expression profiles between the HepG2 cell line and liver tissue revealed the highest variation, followed by HepG2 cells submitted to two different sample preparation protocols. The lowest variation was observed between HepG2 cells prepared by two different laboratories using the same protocol. The enrichment analysis of the genes that were differentially expressed between HepG2 cells and liver tissue mainly revealed the cancer-associated gene signature of HepG2 cells and the activation of the response to chemical stimuli in the liver tissue. The HepG2 transcriptome obtained with the SOLiD platform was highly correlated with the published transcriptome obtained with the Illumina and Helicos platforms, with moderate correspondence to microarrays. In the present study, we assessed the influence of experimental factors on the HepG2 transcriptome and identified differences in gene expression between the HepG2 cell line and liver cells. These findings will facilitate robust experimental design in the fields of pharmacology and toxicology. Our results were supported by a comparative analysis with previous HepG2 gene expression studies.

  17. Moving-shot versus fixed electrode techniques for radiofrequency ablation: Comparison in an ex-vivo bovine liver tissue model

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Eun Ju; Baek, Jung Hwan; Lee, Jeong Hyun [Dept. of Radiology and the Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2014-12-15

    To compare the ablation characteristics of the moving-shot technique (MST) and the fixed electrode technique (FET) for radiofrequency (RF) ablation in an ex-vivo bovine liver tissue model. We performed RF ablation using FET in 110 bovine liver blocks using 11 different ablation times ranging from 5 seconds to 5 minutes (10 blocks per each time duration). Ten bovine liver blocks at each ablation time of 1- or 2-minute, were ablated with MST, which treated conceptual ablation units by moving the electrode tip. We evaluated the ablation volume obtained with FET across ablation time lengths. The results of FET and MST performed with the same ablation time lengths, i.e., 1- and 2-minute ablation time were also compared. The ablation volume achieved with FET gradually increased with increasing ablation time; however, the pair-wise statistical comparison between 2 neighboring ablation time lengths was not significant after 30 seconds. MST with either 1- or 2-minute ablation time achieved larger ablation volumes (1.1 +/- 0.2 mL vs. 2.7 +/- 0.3 mL, p < 0.001; and 1.4 +/- 0.2 mL vs. 5.6 +/- 0.4 mL, p < 0.001, respectively), longer true RF times (46.7 +/- 4.6 seconds vs. 60 seconds, p < 0.001; and 64.8 +/- 4.6 seconds vs. 120 seconds, p < 0.001, respectively), fewer numbers of RF cut-offs (1.6 +/- 0.5 vs. 0, p < 0.001; and 5.5 +/- 0.5 vs. 0, p < 0.001, respectively), and greater energy deposition (2050.16 +/- 209.2 J vs. 2677.76 +/- 83.68 J, p < 0.001; and 2970.64 +/- 376.56 J vs. 5564.72 +/- 5439.2 J, p < 0.001, respectively), than FET. The MST can achieve a larger ablation volume by preventing RF cut-off, compared with the FET in an ex-vivo bovine liver model.

  18. Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi-Liang; Luo, Zhi, E-mail: luozhi99@yahoo.com.cn; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

    2013-07-15

    Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

  19. Differential gene expression in liver tissues of streptozotocin-induced diabetic rats in response to resveratrol treatment.

    Directory of Open Access Journals (Sweden)

    Gökhan Sadi

    Full Text Available This study was conducted to elucidate the genome-wide gene expression profile in streptozotocin induced diabetic rat liver tissues in response to resveratrol treatment and to establish differentially expressed transcription regulation networks with microarray technology. In addition to measure the expression levels of several antioxidant and detoxification genes, real-time quantitative polymerase chain reaction (qRT-PCR was also used to verify the microarray results. Moreover, gene and protein expressions as well as enzymatic activities of main antioxidant enzymes; superoxide dismutase (SOD-1 and SOD-2 and glutathione S-transferase (GST-Mu were analyzed. Diabetes altered 273 genes significantly and 90 of which were categorized functionally which suggested that genes in cellular catalytic activities, oxidation-reduction reactions, co-enzyme binding and terpenoid biosynthesis were dominated by up-regulated expression in diabetes. Whereas; genes responsible from cellular carbohydrate metabolism, regulation of transcription, cell signal transduction, calcium independent cell-to-cell adhesion and lipid catabolism were down-regulated. Resveratrol increased the expression of 186 and decreased the expression of 494 genes in control groups. While cellular and extracellular components, positive regulation of biological processes, biological response to stress and biotic stimulants, and immune response genes were up-regulated, genes responsible from proteins present in nucleus and nucleolus were mainly down-regulated. The enzyme assays showed a significant decrease in diabetic SOD-1 and GST-Mu activities. The qRT-PCR and Western-blot results demonstrated that decrease in activity is regulated at gene expression level as both mRNA and protein expressions were also suppressed. Resveratrol treatment normalized the GST activities towards the control values reflecting a post-translational effect. As a conclusion, global gene expression in the liver tissues is

  20. Livers, guts and gills: mapping the decay profiles of soft tissues to understand authigenic mineral replacement.

    Science.gov (United States)

    Clements, Thomas; Purnell, Mark; Gabbott, Sarah

    2016-04-01

    The hard mineralised parts of organisms such as shells, teeth and bones dominate the fossil record. There are, however, sites around the world where soft-tissues are preserved often through rapid replacement of original tissue by rapidly-precipitating authigenic minerals. These exceptionally well-preserved soft-bodied fossils are much more informative about the anatomy, physiology, ecology and behaviour of ancient organisms as well as providing a more inclusive picture of ecosystems and evolution throughout geological time. However, despite the wealth of information that soft-bodied fossils can provide they must first be correctly interpreted as the processes of both decay and preservation act to modify the carcass from its in vivo condition. Decay leads to alteration of the appearance and topology of anatomy, and ultimately to loss. Preservation is selective with some anatomical features being more likely to be captured than others. These problems are especially germane to the interpretation of deep-time and/or enigmatic fossils where no modern analogue exist for comparative anatomical analysis. It is therefore of vital importance to understand the processes carcasses undergo during the fossilisation process, , in order to interpret the anatomical remains of fossils and thus extract true evolutionary presence or absence of anatomy from absence due to taphonomic biases. We have designed a series of novel experiments to investigate, in real time, how decay processes affect the fossilisation potential of soft-tissues - especially of internal anatomy. Our data allow us to unravel both the timing and sequence of anatomical decay of different organs. At the same time through measuring Eh and pH in selected organs we can predict when anatomical features will fall in to the window of authigenic mineralization and thus potentially become preserved. We can also place constraints on which minerals will operate to capture tissues. Our findings are applied to the fossil record

  1. Insulin Resistance in Adipose Tissue but Not in Liver Is Associated with Aortic Valve Calcification.

    Science.gov (United States)

    Jorge-Galarza, Esteban; Posadas-Romero, Carlos; Torres-Tamayo, Margarita; Medina-Urrutia, Aida X; Rodas-Díaz, Marco A; Posadas-Sánchez, Rosalinda; Vargas-Alarcón, Gilberto; González-Salazar, María Del Carmen; Cardoso-Saldaña, Guillermo C; Juárez-Rojas, Juan G

    2016-01-01

    Background. Insulin resistance is involved in the pathogenesis of cardiovascular disease, but its relationship with cardiovascular calcification has yielded conflicting results. The purpose of the present study was to investigate the role of hepatic and adipose tissue insulin resistance on the presence of coronary artery (CAC > 0) and aortic valve calcification (AVC > 0). Methods. In 1201 subjects (52% women, 53.6 ± 9.3 years old) without familiar and personal history of coronary heart disease, CAC and AVC were assessed by multidetector-computed tomography. Cardiovascular risk factors were documented and lipid profile, inflammation markers, glucose, insulin, and free fatty acids were measured. Hepatic insulin resistance (HOMA-IR) and adipose tissue insulin resistance (Adipo-IR) indices were calculated. Results. There was a significant relationship between HOMA-IR and Adipo-IR indices (r = 0.758, p 0 and AVC > 0. After full adjustment, subjects in the highest quartile of Adipo-IR index had higher odds of AVC > 0 (OR: 2.40; 95% CI: 1.30-4.43), as compared to those in the lowest quartile. Conclusions. Adipo-IR was independently associated with AVC > 0. This suggests that abnormal adipose tissue function favors insulin resistance that may promote the development and progression of AVC.

  2. Insulin Resistance in Adipose Tissue but Not in Liver Is Associated with Aortic Valve Calcification

    Directory of Open Access Journals (Sweden)

    Esteban Jorge-Galarza

    2016-01-01

    Full Text Available Background. Insulin resistance is involved in the pathogenesis of cardiovascular disease, but its relationship with cardiovascular calcification has yielded conflicting results. The purpose of the present study was to investigate the role of hepatic and adipose tissue insulin resistance on the presence of coronary artery (CAC > 0 and aortic valve calcification (AVC > 0. Methods. In 1201 subjects (52% women, 53.6±9.3 years old without familiar and personal history of coronary heart disease, CAC and AVC were assessed by multidetector-computed tomography. Cardiovascular risk factors were documented and lipid profile, inflammation markers, glucose, insulin, and free fatty acids were measured. Hepatic insulin resistance (HOMA-IR and adipose tissue insulin resistance (Adipo-IR indices were calculated. Results. There was a significant relationship between HOMA-IR and Adipo-IR indices (r=0.758, p 0 and AVC > 0. After full adjustment, subjects in the highest quartile of Adipo-IR index had higher odds of AVC > 0 (OR: 2.40; 95% CI: 1.30–4.43, as compared to those in the lowest quartile. Conclusions. Adipo-IR was independently associated with AVC > 0. This suggests that abnormal adipose tissue function favors insulin resistance that may promote the development and progression of AVC.

  3. Dietary Omega-3 Polyunsaturated Fatty Acids Alter Fatty Acid Composition of Lipids and CYP2E1 Expression in Rat Liver Tissue.

    Science.gov (United States)

    Maksymchuk, Oksana; Shysh, Angela; Chashchyn, Mykola; Moibenko, Olexyi

    2016-07-21

    Omega-3 polyunsaturated fatty acids (PUFAs) are used for the treatment and prevention of numerous pathologies in humans. As recently found, PUFAs play significantly protective roles in liver, cardiovascular system and kidney. They also are widely used in total parenteral nutrition. We evaluated the effect of omega-3 PUFA consumption on liver fatty acid composition and the expression of CYP2E1, one of the key enzymes in detoxification and prooxidant systems of liver cells. To estimate the oxidative stress in liver tissue, the antioxidant status and the level of lipid peroxidation were determined in a rodent model. Animals were divided into two groups: control (n = 10) and experimental (n = 10). Epadol-containing omega-3 PUFA fish oil capsules were administered to Wistar rats within 4 weeks (0.1 mL/100 g b.w./day). The consumption of omega-3 PUFAs resulted in changes of fatty acid composition of liver tissue. A significant increase was detected in the α-linolenic, eicosapentaenoic and docosahexaenoic acid content (5.1-, 16-, and 1.3-fold, respectively, p omega-3:omega-6 ratio. Consumption of omega-3 PUFAs led to a 3-fold (p < 0.05) increase in CYP2E1 content, which could entail enhanced Nrf2 expression levels and increases in the HO-1 content in rat liver. The alteration in CYP2E1 expression did not have an impact on the level of lipid peroxidation and on the prooxidant/antioxidant balance.

  4. Effects of a High Fat Diet and Voluntary Wheel Running Exercise on Cidea and Cidec Expression in Liver and Adipose Tissue of Mice.

    Directory of Open Access Journals (Sweden)

    Thomas H Reynolds

    Full Text Available Cidea and Cidec play an important role in regulating triglyceride storage in liver and adipose tissue. It is not known if the Cidea and Cidec genes respond to a high fat diet (HFD or exercise training, two interventions that alter lipid storage. The purpose of the present study was to determine the effect of a HFD and voluntary wheel running (WR on Cidea and Cidec mRNA and protein expression in adipose tissue and liver of mice. A HFD promoted a significant increase in Cidea and Cidec mRNA levels in adipose tissue and liver. The increase in Cidea and Cidec mRNAs in adipose tissue and liver in response to a HFD was prevented by WR. Similar to the changes in Cidea mRNA, Cidea protein levels in adipose tissue significantly increased in response to a HFD, a process that was, again, prevented by WR. However, in adipose tissue the changes in Cidec mRNA did not correspond to the changes in Cidec protein levels, as a HFD decreased Cidec protein abundance. Interestingly, in adipose tissue Cidea protein expression was significantly related to body weight (R=.725, epididymal adipose tissue (EWAT mass (R=.475 and insulin resistance (R=.706, whereas Cidec protein expression was inversely related to body weight (R=-.787, EWAT mass (R=-.706, and insulin resistance (R=-.679. Similar to adipose tissue, Cidea protein expression in liver was significantly related to body weight (R=.660, EWAT mass (R=.468, and insulin resistance (R=.599; however, unlike adipose tissue, Cidec protein levels in liver were not related to body weight or EWAT mass and only moderately associated with insulin resistance (R=-.422, P=0.051. Overall, our findings indicate that Cidea is highly associated with adiposity and insulin resistance, whereas Cidec is related to insulin sensitivity. The present study suggests that Cide proteins might play an important functional role in the development of obesity, hepatic steatosis, as well as the pathogenesis of type 2 diabetes.

  5. Distribution of inorganic mercury in liver and kidney of beluga and bowhead whales through autometallographic development of light microscopic tissue sections.

    Science.gov (United States)

    Woshner, Victoria M; Ohara, Todd M; Eurell, Jo Ann; Wallig, Matthew A; Bratton, Gerald R; Suydam, Robert S; Beasley, Val R

    2002-01-01

    Inorganic mercury was localized through autometallography (AMG) in kidney and liver of free-ranging, subsistence-harvested beluga (Delphinapterus leucus: n = 20) and bowhead (Balaena mysticetrus: n = 5) whales. AMG granules were not evident in bowhead tissues, confirming nominal mercury (Hg) concentrations (range = 0.011 to 0.038 microg/g ww for total Hg). In belugas, total Hg ranged from 0.30 to 17.11 and from 0.33 to 82.47 microg/g ww in liver and kidney, respectively. AMG granules were restricted to cortical tubular epithelial cytoplasm in belugas with lower tissue burdens; whales with higher tissue burdens had granules throughout the uriniferous tubular epithelium. In liver, AMG granular densities differed between lobular zones, concentrating in stellate macrophages and bile cannalicular domains of hepatocytes. AMG granules aggregated in periportal regions in belugas with lower hepatic Hg concentrations, yet among whales with higher Hg, AMG granule deposition extended to pericentral and midzonal regions of liver lobules. Mean areas occupied by AMG granules correlated well with hepatic Hg concentrations and age. In beluga livers, AMG staining density was not associated with lipofuscin quantity (an index of oxidative damage). Occasionally, AMG granules and lipofuscin were colocalized, but more often were not, implying that Hg was not a prominent factor in hepatic lipofuscin deposition in belugas.

  6. Trans-10,cis-12-CLA-caused lipodystrophy is associated with profound changes of fatty acid profiles of liver, white adipose tissue and erythrocytes in mice: possible link to tissue-specific alterations of fatty acid desaturation.

    Science.gov (United States)

    Jaudszus, Anke; Moeckel, Peter; Hamelmann, Eckard; Jahreis, Gerhard

    2010-01-01

    Dietary supplementation with conjugated linoleic acid (CLA) has been shown to reduce body fat mass. To investigate the effects of individual CLA isomers on the fatty acid profiles of lipogenic (liver and white adipose) and lipid sensitive (erythrocyte) tissues, BALB/c mice were fed with 1 of 2 diets supplemented with either a c9,t11-CLA-enriched and t10,c12-CLA-free or a CLA-mixture containing both isomers in equal amounts (1% w/w of the diet) for 5 weeks. A control group was fed with a diet enriched in sunflower oil to energy balance the CLA. Compared to the t10,c12-CLA-free and the control diets, we observed a significant reduction of adipose tissue accompanied by fatty livers in the CLA-mix-fed group. These alterations in body fat distribution entailed a conspicuous shift of the fatty acid profiles of adipose tissue and livers. Liver enlargement was mainly caused by accumulation of C18 monoenes that accounted for 67 ± 1% of total fatty acid methyl esters. The significant reduction of the 18:0/18:1 desaturation index in the liver upon CLA-mix diet indicated high stearoyl-CoA desaturase activity. In contrast, reduction in white adipose tissue was largely driven by percental reduction of monounsaturated fatty acids (p ≤ 0.001). 16:0/ 16:1 and 18:0/18:1 desaturation indices for white adipose tissue significantly increased, suggesting an inhibition of stearoyl-CoA desaturase upon CLA-mix diet. The fatty acid profile of the erythrocytes widely reflected that of livers, depending on the supplemented diet. These profound changes in fatty acid composition of lipogenic organs due to t10,c12-CLA intake may be the consequence of functional alterations of lipid metabolism.

  7. Inhibition of soluble epoxide hydrolase modulates inflammation and autophagy in obese adipose tissue and liver: Role for omega-3 epoxides

    Science.gov (United States)

    López-Vicario, Cristina; Alcaraz-Quiles, José; García-Alonso, Verónica; Rius, Bibiana; Hwang, Sung H.; Titos, Esther; Lopategi, Aritz; Hammock, Bruce D.; Arroyo, Vicente; Clària, Joan

    2015-01-01

    Soluble epoxide hydrolase (sEH) is an emerging therapeutic target in a number of diseases that have inflammation as a common underlying cause. sEH limits tissue levels of cytochrome P450 (CYP) epoxides derived from omega-6 and omega-3 polyunsaturated fatty acids (PUFA) by converting these antiinflammatory mediators into their less active diols. Here, we explored the metabolic effects of a sEH inhibitor (t-TUCB) in fat-1 mice with transgenic expression of an omega-3 desaturase capable of enriching tissues with endogenous omega-3 PUFA. These mice exhibited increased CYP1A1, CYP2E1, and CYP2U1 expression and abundant levels of the omega-3–derived epoxides 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic (19,20-EDP) in insulin-sensitive tissues, especially liver, as determined by LC-ESI-MS/MS. In obese fat-1 mice, t-TUCB raised hepatic 17,18-EEQ and 19,20-EDP levels and reinforced the omega-3–dependent reduction observed in tissue inflammation and lipid peroxidation. t-TUCB also produced a more intense antisteatotic action in obese fat-1 mice, as revealed by magnetic resonance spectroscopy. Notably, t-TUCB skewed macrophage polarization toward an antiinflammatory M2 phenotype and expanded the interscapular brown adipose tissue volume. Moreover, t-TUCB restored hepatic levels of Atg12-Atg5 and LC3-II conjugates and reduced p62 expression, indicating up-regulation of hepatic autophagy. t-TUCB consistently reduced endoplasmic reticulum stress demonstrated by the attenuation of IRE-1α and eIF2α phosphorylation. These actions were recapitulated in vitro in palmitate-primed hepatocytes and adipocytes incubated with 19,20-EDP or 17,18-EEQ. Relatively similar but less pronounced actions were observed with the omega-6 epoxide, 14,15-EET, and nonoxidized DHA. Together, these findings identify omega-3 epoxides as important regulators of inflammation and autophagy in insulin-sensitive tissues and postulate sEH as a druggable target in metabolic

  8. Tissue localization of C1q in HBs antigen positive liver disease patients by direct immunofluorescent technique

    Directory of Open Access Journals (Sweden)

    Tsuji,Takao

    1977-02-01

    Full Text Available Tissue localization of a subcomponent of the first component of complement (CLq was examined in one postmortem case of HBs antigen (HBs Ag positive hepatocellular carcinoma and in six cases of chronic hepatitis from liver biopsy specimens. The direct immunofluorescent method was used after fixation with 2% para-formaldehyde in concentrated ammonium sulfate. CLq localization was found in collagen fibers and the cytoplasm of fibroblasts in the connective tissues of specimens examined. The localization was particularly marked in the region of the fundal glands of the gastric wall. Apart from collagen fibers, other sites of localization included the surface membrane of lymphocytes, especially those cells of the mesenteric lymph nodes. In HBs Ag positive specimens, immune deposit-like substances appeared localized intra-hepatically and in the renal glomeruli. Since C3 and C4 were identified concomitantly, it indicates that these substances were indeed immune diposits. Despite the finding that C3 and C4 were identified together in the hepatic cell cytoplasm, C1q itself was not demonstrated in all hepatic cell cytoplasms.

  9. BAR502, a dual FXR and GPBAR1 agonist, promotes browning of white adipose tissue and reverses liver steatosis and fibrosis

    Science.gov (United States)

    Carino, Adriana; Cipriani, Sabrina; Marchianò, Silvia; Biagioli, Michele; Santorelli, Chiara; Donini, Annibale; Zampella, Angela; Monti, Maria Chiara; Fiorucci, Stefano

    2017-01-01

    Non-alcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease. Here, we have investigated whether BAR502, a non-bile acid, steroidal dual ligand for FXR and GPBAR1, reverses steato-hepatitis in mice fed a high fat diet (HFD) and fructose. After 9 week, mice on HFD gained ≈30% of b.w (P CYP7A1 mRNA. BAR502 increased the expression of SHP and ABCG5 in the liver and SHP, FGF15 and GLP1 in intestine. BAR502 promoted the browning of epWAT and reduced liver fibrosis induced by CCl4. In summary, BAR502, a dual FXR and GPBAR1 agonist, protects against liver damage caused by HFD by promoting the browning of adipose tissue. PMID:28202906

  10. Accumulation of Copper in Gill, Liver, Spleen, Kidney and Muscle Tissues of Clarias gariepinus Exposed to the Metal Singly and in Mixture with Chitosan.

    Science.gov (United States)

    Tunçsoy, Mustafa; Duran, Servet; Ay, Özcan; Cicik, Bedii; Erdem, Cahit

    2016-10-01

    Accumulation of copper (Cu), applied singly and in mixture with chitosan (CT), in gill, liver, spleen, kidney and muscle tissues of Clarias gariepinus was studied after exposing the fish to no Cu (control), 5 ppm Cu, 5 ppm Cu + 75 ppm CT mixture over 1, 7 and 15 days. Metal levels in tissues were determined using an ICP-AES spectrophotometer. No mortality was observed during the experiments. Highest accumulation of Cu was observed in liver while lowest accumulation was observed in muscle tissue. Exposure to Cu-CT mixture decreased Cu accumulation in liver at all exposure periods and in kidney on the 15th day compared to Cu alone. Exposure to Cu alone and Cu-CT mixture had no effect on Cu accumulation in spleen or muscle tissue. Copper accumulation increased in gill tissue compared to control when exposed to Cu alone at all exposure periods, and exposure to the Cu-CT mixture significantly increased Cu accumulation in this tissue at all exposure periods compared to Cu alone.

  11. In vitro study of the biological activity of RNAs after incubation of hog liver, heart and brain tissue at room temperature

    DEFF Research Database (Denmark)

    Reichert, G H; Issinger, O G

    1985-01-01

    The biological activity of RNA, isolated from tissue which was incubated for 1, 3, or 6 hours at room temperature (simulation of post-mortem conditions), was preserved. However, the different organs used differ from each other. When liver is used, qualitative differences in the in vitro translati...

  12. Correlation of severity of non-alcoholic fatty liver disease with viseral adipose tissue area,body mass index,and waist circumference

    Institute of Scientific and Technical Information of China (English)

    黄志鹏

    2013-01-01

    Objective To analyze the correlation of the severity of non-alcoholic fatty liver disease (NAFLD) with visceral adipose tissue area (VAT) ,body mass index (BMI) ,and waist circumference (WC) .Methods A total of 127NAFLD patients were divided into mild NAFLD group

  13. Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss

    Directory of Open Access Journals (Sweden)

    J. Schmitz

    2016-05-01

    Conclusions: These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as well as in a significant subpopulation of obese patients.

  14. The dietary protein/carbohydrate ratio differentially modifies lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation.

    Directory of Open Access Journals (Sweden)

    Laura A Velázquez-Villegas

    Full Text Available During gestation and lactation, a series of metabolic changes that are affected by the diet occurs in various organs of the mother. However, little is known about how the dietary protein (DP/carbohydrate (DCH ratio regulates the expression of metabolic genes in the mother. Therefore, the purpose of this work was to study the effect of consuming different percentages of DP/DCH, specifically 10/73, 20/63 and 30/53%, on the expression of genes involved in lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation in dams. While the amount of weight gained during gestation was similar for all groups, only dams fed with 30/53% DP/DCH maintained their weight during lactation. In the mammary gland, the expression of the genes involved in lipogenesis, specifically SREBP1 and FAS, was dramatically increased, and the expression of the genes involved in protein synthesis, such as mTOR1, and the phosphorylation of its target protein, S6K, were also increased throughout pregnancy and lactation, regardless of the concentration of DP/DCH. In the liver and adipose tissue, the expression of the genes and proteins involved in lipid metabolism was dependent on the proportion of DP/DCH. The consumption of a low-protein/high-carbohydrate diet increased the expression of lipogenic genes in the liver and adipose tissue and the amount of lipid deposition in the liver. Conversely, the consumption of a high-protein/low-carbohydrate diet increased the expression of genes involved in amino acid oxidation in the liver during gestation. The metabolic adaptations reflected by the changes in the expression of metabolic genes indicate that the mammary gland has a priority for milk synthesis, whereas the adaptations in the liver and adipose tissue are responsible for providing nutrients to the mammary gland to sustain milk synthesis.

  15. Metastatic Tissue Proteomic Profiling Predicts 5-Year Outcomes in Patients with Colorectal Liver Metastases

    Directory of Open Access Journals (Sweden)

    Santiago Marfà

    2016-10-01

    Full Text Available Colorectal cancer (CRC is one of the most common cancers in the developed countries, and nearly 70% of patients with CRC develop colorectal liver metastases (CRLMs. During the last decades, several scores have been proposed to predict recurrence after CRLM resection. However, these risk scoring systems do not accurately reflect the prognosis of these patients. Therefore, this investigation was designed to identify a proteomic profile in human hepatic tumor samples to classify patients with CRLM as “mild” or “severe” based on the 5-year survival. The study was performed on 85 CRLM tumor samples. Firstly, to evaluate any distinct tumor proteomic signatures between mild and severe CRLM patients, a training group of 57 CRLM tumor samples was characterized by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, and a classification and regression tree (CART analysis was subsequently performed. Finally, 28 CRLM tumor samples were used to confirm and validate the results obtained. Based on all the protein peaks detected in the training group, the CART analysis was generated, and four peaks were considered to be the most relevant to construct a diagnostic algorithm. Indeed, the multivariate model yielded a sensitivity of 85.7% and a specificity of 86.1%, respectively. In addition, the receiver operating characteristic (ROC curve showed an excellent diagnostic accuracy to discriminate mild from severe CRLM patients (area under the ROC: 0.903. Finally, the validation process yielded a sensitivity and specificity of 68.8% and 83.3%, respectively. We identified a proteomic profile potentially useful to determine the prognosis of CRLM patients based on the 5-year survival.

  16. Rice Germosprout Extract Protects Erythrocytes from Hemolysis and the Aorta, Brain, Heart, and Liver Tissues from Oxidative Stress In Vitro

    Science.gov (United States)

    Hussain, Jakir; Islam, Saiful

    2016-01-01

    Identifying dietary alternatives for artificial antioxidants capable of boosting antihemolytic and antioxidative defense has been an important endeavor in improving human health. In the present study, we studied antihemolytic and antioxidative effects of germosprout (i.e., the germ part along with sprouted stems plus roots) extract prepared from the pregerminated rice. The extract contained considerable amounts of antioxidant β-carotene (414 ± 12 ng/g of extract) and phytochemicals such as total polyphenols (12.0 ± 1.1 mg gallic acid equivalent/g of extract) and flavonoids (11.0 ± 1.4 mg catechin equivalent/g of extract). The antioxidant potential of the extract was assessed by its DPPH- (2,2-diphenyl-1-picrylhydrazyl-) free radical scavenging activity where we observed that germosprout extract had considerable antioxidative potentials. To evaluate antihemolytic effect of the extract, freshly prepared erythrocytes were incubated with either peroxynitrite or Fenton's reagent in the absence or presence of the extract. We observed that erythrocytes pretreated with the extract exhibited reduced degree of in vitro hemolysis. To support the proposition that germosprout extract could act as a good antioxidative agent, we also induced in vitro oxidative stress in erythrocyte membranes and in the aorta, brain, heart, and liver tissue homogenates in the presence of the extract. As expected, germosprout extract decreased oxidative stress almost to the same extent as that of vitamin E, as measured by lipid peroxide levels, in all the mentioned tissues. We conclude that rice germosprout extract could be a good natural source of antioxidants to reduce oxidative stress-induced hemolysis and damage of blood vessels and other tissues. PMID:27413391

  17. Rice Germosprout Extract Protects Erythrocytes from Hemolysis and the Aorta, Brain, Heart, and Liver Tissues from Oxidative Stress In Vitro

    Directory of Open Access Journals (Sweden)

    Shahdat Hossain

    2016-01-01

    Full Text Available Identifying dietary alternatives for artificial antioxidants capable of boosting antihemolytic and antioxidative defense has been an important endeavor in improving human health. In the present study, we studied antihemolytic and antioxidative effects of germosprout (i.e., the germ part along with sprouted stems plus roots extract prepared from the pregerminated rice. The extract contained considerable amounts of antioxidant β-carotene (414±12 ng/g of extract and phytochemicals such as total polyphenols (12.0±1.1 mg gallic acid equivalent/g of extract and flavonoids (11.0±1.4 mg catechin equivalent/g of extract. The antioxidant potential of the extract was assessed by its DPPH- (2,2-diphenyl-1-picrylhydrazyl- free radical scavenging activity where we observed that germosprout extract had considerable antioxidative potentials. To evaluate antihemolytic effect of the extract, freshly prepared erythrocytes were incubated with either peroxynitrite or Fenton’s reagent in the absence or presence of the extract. We observed that erythrocytes pretreated with the extract exhibited reduced degree of in vitro hemolysis. To support the proposition that germosprout extract could act as a good antioxidative agent, we also induced in vitro oxidative stress in erythrocyte membranes and in the aorta, brain, heart, and liver tissue homogenates in the presence of the extract. As expected, germosprout extract decreased oxidative stress almost to the same extent as that of vitamin E, as measured by lipid peroxide levels, in all the mentioned tissues. We conclude that rice germosprout extract could be a good natural source of antioxidants to reduce oxidative stress-induced hemolysis and damage of blood vessels and other tissues.

  18. Borate-aided anion exchange high-performance liquid chromatography of uridine diphosphate-sugars in brain, heart, adipose and liver tissues.

    Science.gov (United States)

    Oikari, Sanna; Venäläinen, Tuula; Tammi, Markku

    2014-01-03

    In this paper we describe a method optimized for the purification of uridine diphosphate (UDP)-sugars from liver, adipose tissue, brain, and heart, with highly reproducible up to 85% recoveries. Rapid tissue homogenization in cold ethanol, lipid removal by butanol extraction, and purification with a graphitized carbon column resulted in isolation of picomolar quantities of the UDP-sugars from 10 to 30mg of tissue. The UDP-sugars were baseline separated from each other, and from all major nucleotides using a CarboPac PA1 anion exchange column eluted with a gradient of acetate and borate buffers. The extraction and purification protocol produced samples with few unidentified peaks. UDP-N-acetylglucosamine was a dominant UDP-sugar in all the rat tissues studied. However, brain and adipose tissue showed high UDP-glucose levels, equal to that of UDP-N-acetylglucosamine. The UDP-N-acetylglucosamine showed 2.3-2.7 times higher levels than UDP-N-acetylgalactosamine in all tissues, and about the same ratio was found between UDP-glucose and UDP-galactose in adipose tissue and brain (2.6 and 2.8, respectively). Interestingly, the UDP-glucose/UDP-galactose ratio was markedly lower in liver (1.1) and heart (1.7). The UDP-N-acetylglucosamine/UDP-glucuronic acid ratio was also constant, between 9.7 and 7.7, except in liver with the ratio as low as 1.8. The distinct UDP-glucose/galactose ratio, and the abundance of UDP-glucuronic acid may reflect the specific role of liver in glycogen synthesis, and metabolism of hormones and xenobiotics, respectively, using these UDP-sugars as substrates.

  19. Effect of cadmium on glutathione S-transferase and metallothionein gene expression in coho salmon liver, gill and olfactory tissues

    Energy Technology Data Exchange (ETDEWEB)

    Espinoza, Herbert M.; Williams, Chase R. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105-6099 (United States); Gallagher, Evan P., E-mail: evang3@u.washington.edu [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105-6099 (United States)

    2012-04-15

    Highlights: Black-Right-Pointing-Pointer Developed qPCR assays to distinguish closely related GST isoforms in salmon. Black-Right-Pointing-Pointer Examined the effect of cadmium on GST and metallothionein genes in 3 tissues. Black-Right-Pointing-Pointer Modulation of GST varied among isoforms, tissues, and included a loss of expression. Black-Right-Pointing-Pointer Metallothionein outperformed, but generally complemented, GSTs as biomarkers. Black-Right-Pointing-Pointer Salmon olfactory genes were among the most responsive to cadmium. - Abstract: The glutathione S-transferases (GSTs) are a multifunctional family of phase II enzymes that detoxify a variety of environmental chemicals, reactive intermediates, and secondary products of oxidative damage. GST mRNA expression and catalytic activity have been used as biomarkers of exposure to environmental chemicals. However, factors such as species differences in induction, partial analyses of multiple GST isoforms, and lack of understanding of fish GST gene regulation, have confounded the use of GSTs as markers of pollutant exposure. In the present study, we examined the effect of exposure to cadmium (Cd), a prototypical environmental contaminant and inducer of mammalian GST, on GST mRNA expression in coho salmon (Oncorhynchus kisutch) liver, gill, and olfactory tissues. GST expression data were compared to those for metallothionein (MT), a prototypical biomarker of metal exposure. Data mining of genomic databases led to the development of quantitative real-time PCR (qPCR) assays for salmon GST isoforms encompassing 9 subfamilies, including alpha, mu, pi, theta, omega, kappa, rho, zeta and microsomal GST. In vivo acute (8-48 h) exposures to low (3.7 ppb) and high (347 ppb) levels of Cd relevant to environmental scenarios elicited a variety of transient, albeit minor changes (<2.5-fold) in tissue GST profiles, including some reductions in GST mRNA expression. In general, olfactory GSTs were the earliest to respond to

  20. Effect of bax, bcl-2 and bcl-xL on regulating apoptosis in tissues of normal liver and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Zhong Guo; Xiao-Dong Shao; Min-Pei Liu; Jian-Hua Xu; Li-Nan Ren; Jia-Jun Zhao; Hong-Yu Li; Di Wang

    2002-01-01

    AIM: To investigate the expression of bax, bcl-2 and bcl-xL mRNA in the tissues of normal liver and hepatocellular carcinoma (HCC), and analyze the relationship between the expression of bax, bcl-2 and bcl-xL mRNA and clinical parameters of HCC patients.METHODS: The expression of bax, bcl-2 and bcl-xL mRNA of normal liver and HCC was measured by Northern blot. Statistical analyses were made by t test and correlation analysis.RESULTS: A very low mRNA level was indicated at bax,bcl-2 and bcl-xL in the HCC tissues in contrast to the tissues of normal liver by Northern blot analysis. The analyses of mRNA level revealed that HCC tissues exhibited a mean 7.6-fold decrease in bax, 4.2-fold in bcl-2 and 3.5-fold in bcl-xL in comparison with normal control tissues, respectively. Positive correlation was found between bax and bcl-xL (r=0.7061,P<0.01). There was no significance between the mRNA expression of these three genes and age, gender, tumor differentiation and tumor stage of HCC patients. CONCLUSION: The results are consistent with the fact that apoptosis rarely occurs in normal livers but increases in HCC, indicating that bcl-2 and bcl-xL may play a very important role in regulating the apoptosis of normal liver and HCC.

  1. Teratogenic study of phenobarbital and levamisole on mouse fetus liver tissue using biospectroscopy.

    Science.gov (United States)

    Ashtarinezhad, Azadeh; Panahyab, Ataollah; Shaterzadeh-Oskouei, Shahrzad; Khoshniat, Hessam; Mohamadzadehasl, Baharak; Shirazi, Farshad H

    2016-09-05

    Biospectroscopic investigations have attracted attention of both the clinicians and basic sciences researchers in recent years. Scientists are discovering new areas for FTIR biospectroscopy applications in medicine. The aim of this study was to measure the possibility of FTIR-MSP application for the recognition and detection of fetus abnormalities after exposure of pregnant mouse to phenobarbital (PB) and levamisole (LEV) alone or in combination. PB is one of the most widely used antiepileptic drugs (AEDs), with sedative and hypnotic effects. When used by pregnant women, it is known to be a teratogenic agent. LEV is an antihelminthic drug with some applications in immune-deficiency as well as colon cancer therapy. Four groups of ten pregnant mice were selected for the experiments as follows: one control group received only standard diet, one group was injected with 120mg/kg of BP, one group was injected with 10mg/kg of LEV, and the last group was treated simultaneously with both BP and LEV at the above mentioned doses. Drugs administration was performed on gestation day 9 and fetuses were dissected on pregnancy day 15. Each dissected fetus was fixed, dehydrated and embedded in paraffin. Sections of liver (10μm) were prepared from control and treated groups by microtome and deparaffinized with xylene. The spectra were taken by FTIR-MSP in the region of 4000-400cm(-1). All the spectra were normalized based on amide II band (1545cm(-1)) after baseline correction of the entire spectrum, followed by classification using PCA, ANN and SVM. Both morphological and spectral changes were shown in the treated fetuses as compared to the fetuses in the control group. While cleft palate and C-R elongation were seen in PB injected fetuses, developmental retardation was mostly seen in the LEV injected group. Biospectroscopy revealed that both drugs mainly affected the cellular lipids and proteins, with LEV causing more changes in amide I and lipid regions than PB. Application of

  2. The dissection profile and mechanism of tissue-selective dissection of the piezo actuator-driven pulsed water jet as a surgical instrument: laboratory investigation using Swine liver.

    Science.gov (United States)

    Yamada, Masato; Nakano, Toru; Sato, Chiaki; Nakagawa, Atsuhiro; Fujishima, Fumiyoshi; Kawagishi, Naoki; Nakanishi, Chikashi; Sakurai, Tadashi; Miyata, Go; Tominaga, Teiji; Ohuchi, Noriaki

    2014-01-01

    The water jet technique dissects tissue while sparing cord-like structures such as blood vessels. The mechanism of such tissue-selective dissection has been unknown. The novel piezo actuator-driven pulsed water jet (ADPJ) system can achieve dissection with remarkably reduced water consumption compared to the conventional water jet; however, the system's characteristics and dissection capabilities on any organ have not been clarified. The purposes of this study were to characterize the physical properties of the novel ADPJ system, evaluate the dissection ability in swine organs, and reveal the mechanism of tissue-selective dissection. The pulsed water jet system comprised a pump chamber driven by a piezo actuator, a stainless steel tube, and a nozzle. The peak pressure of the pulsed water jet was measured through a sensing hole using a pressure sensor. The pulsed water jet technique was applied on swine liver in order to dissect tissue on a moving table using one-way linear ejection at a constant speed. The dissection depth was measured with light microscopy and evaluated histologically. The physical properties of swine liver were evaluated by breaking strength tests using tabletop universal testing instruments. The liver parenchyma was also cut with three currently available surgical devices to compare the histological findings. The peak pressure of the pulsed water jet positively correlated with the input voltage (R(2) = 0.9982, p dissection depth. The dissection depth negatively correlated with the breaking strength of the liver parenchyma (R(2) = 0.6694, p dissected, preserving the hepatic veins and Glisson's sheaths in contrast to what is commonly observed with electrocautery or ultrasonic instruments. The dissection depth of liver tissue is well controlled by input voltage and is influenced by the moving velocity and the physical properties of the organ. We showed that the device can be used to assure liver resection with tissue selectivity due to tissue

  3. Influence of Tissue Microstructure on Shear Wave Speed Measurements in Plane Shear Wave Elastography: A Computational Study in Lossless Fibrotic Liver Media.

    Science.gov (United States)

    Wang, Yu; Jiang, Jingfeng

    2017-07-01

    Shear wave elastography (SWE) has been used to measure viscoelastic properties for characterization of fibrotic livers. In this technique, external mechanical vibrations or acoustic radiation forces are first transmitted to the tissue being imaged to induce shear waves. Ultrasonically measured displacement/velocity is then utilized to obtain elastographic measurements related to shear wave propagation. Using an open-source wave simulator, k-Wave, we conducted a case study of the relationship between plane shear wave measurements and the microstructure of fibrotic liver tissues. Particularly, three different virtual tissue models (i.e., a histology-based model, a statistics-based model, and a simple inclusion model) were used to represent underlying microstructures of fibrotic liver tissues. We found underlying microstructures affected the estimated mean group shear wave speed (SWS) under the plane shear wave assumption by as much as 56%. Also, the elastic shear wave scattering resulted in frequency-dependent attenuation coefficients and introduced changes in the estimated group SWS. Similarly, the slope of group SWS changes with respect to the excitation frequency differed as much as 78% among three models investigated. This new finding may motivate further studies examining how elastic scattering may contribute to frequency-dependent shear wave dispersion and attenuation in biological tissues.

  4. A comparative study of accumulated total mercury among white muscle, red muscle and liver tissues of common carp and silver carp from the Sanandaj Gheshlagh Reservoir in Iran.

    Science.gov (United States)

    Khoshnamvand, Mehdi; Kaboodvandpour, Shahram; Ghiasi, Farzad

    2013-01-01

    The Sanandaj Gheshlagh Reservoir (SGR) is a mercury polluted lake that is located in the West of Iran. Common carp (Cyprinus carpio) and silver carp (Hypophthalmichthys molitrix) are the most abundant fishes in the SGR. A total of 48 common and silver carps (24 each) were captured randomly, using 50×6 m gill net (mesh size: 5×5 cm) during July to December 2009. Each month, the levels of accumulated total mercury (T-Hg) in white muscle, red muscle and liver tissues of these fishes were measured using an Advanced Mercury Analyzer (Model; Leco 254 AMA, USA) on the dry weight basis. There were no statistically significant differences between T-Hg concentrations in white muscle, red muscle and liver in common carp in comparison with similar tissues in silver carp (P>0.05). The content of T-Hg in liver tissue of both species was lower than of white and red muscle tissues. Higher levels of accumulated T-Hg were observed during summer. Results showed that T-Hg concentrations in common and silver carps target tissues were strongly dependent on age, length and weight (Ptissues of all samples with weights of over 850 g were greater than those limits established by WHO and FAO (500 ng g(-1)). Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. In vitro study of the biological activity of RNAs after incubation of hog liver, heart and brain tissue at room temperature

    DEFF Research Database (Denmark)

    Reichert, G H; Issinger, O G

    1985-01-01

    The biological activity of RNA, isolated from tissue which was incubated for 1, 3, or 6 hours at room temperature (simulation of post-mortem conditions), was preserved. However, the different organs used differ from each other. When liver is used, qualitative differences in the in vitro translation...... products are observed, after one hour incubation at room temperature, whereas when heart and brain are used these differences are not observed. We have also shown that relatively small amounts of post-mortem tissue is sufficient for RNA extraction. When using frozen tissue it is absolutely necessary to add...

  6. Sexually dimorphic effects of maternal nutrient reduction on expression of genes regulating cortisol metabolism in fetal baboon adipose and liver tissues.

    Science.gov (United States)

    Guo, Chunming; Li, Cun; Myatt, Leslie; Nathanielsz, Peter W; Sun, Kang

    2013-04-01

    Maternal nutrient reduction (MNR) during fetal development may predispose offspring to chronic disease later in life. Increased regeneration of active glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in metabolic tissues is fundamental to the developmental programming of metabolic syndrome, but underlying mechanisms are unknown. Hexose-6-phosphate dehydrogenase (H6PD) generates NADPH, the cofactor for 11β-HSD1 reductase activity. CCAAT/enhancer binding proteins (C/EBPs) and the glucocorticoid receptor (GR) regulate 11β-HSD1 expression. We hypothesize that MNR increases expression of fetal C/EBPs, GR, and H6PD, thereby increasing expression of 11β-HSD1 and reductase activity in fetal liver and adipose tissues. Pregnant MNR baboons ate 70% of what controls ate from 0.16 to 0.9 gestation (term, 184 days). Cortisol levels in maternal and fetal circulations increased in MNR pregnancies at 0.9 gestation. MNR increased expression of 11β-HSD1; H6PD; C/EBPα, -β, -γ; and GR in female but not male perirenal adipose tissue and in male but not female liver at 0.9 gestation. Local cortisol level and its targets PEPCK1 and PPARγ increased correspondingly in adipose and liver tissues. C/EBPα and GR were found to be bound to the 11β-HSD1 promoter. In conclusion, sex- and tissue-specific increases of 11β-HSD1, H6PD, GR, and C/EBPs may contribute to sexual dimorphism in the programming of exaggerated cortisol regeneration in liver and adipose tissues and offsprings' susceptibility to metabolic syndrome.

  7. Top-Down and Bottom-Up Identification of Proteins by Liquid Extraction Surface Analysis Mass Spectrometry of Healthy and Diseased Human Liver Tissue

    Science.gov (United States)

    Sarsby, Joscelyn; Martin, Nicholas J.; Lalor, Patricia F.; Bunch, Josephine; Cooper, Helen J.

    2014-09-01

    Liquid extraction surface analysis mass spectrometry (LESA MS) has the potential to become a useful tool in the spatially-resolved profiling of proteins in substrates. Here, the approach has been applied to the analysis of thin tissue sections from human liver. The aim was to determine whether LESA MS was a suitable approach for the detection of protein biomarkers of nonalcoholic liver disease (nonalcoholic steatohepatitis, NASH), with a view to the eventual development of LESA MS for imaging NASH pathology. Two approaches were considered. In the first, endogenous proteins were extracted from liver tissue sections by LESA, subjected to automated trypsin digestion, and the resulting peptide mixture was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) (bottom-up approach). In the second (top-down approach), endogenous proteins were extracted by LESA, and analyzed intact. Selected protein ions were subjected to collision-induced dissociation (CID) and/or electron transfer dissociation (ETD) mass spectrometry. The bottom-up approach resulted in the identification of over 500 proteins; however identification of key protein biomarkers, liver fatty acid binding protein (FABP1), and its variant (Thr→Ala, position 94), was unreliable and irreproducible. Top-down LESA MS analysis of healthy and diseased liver tissue revealed peaks corresponding to multiple (~15-25) proteins. MS/MS of four of these proteins identified them as FABP1, its variant, α-hemoglobin, and 10 kDa heat shock protein. The reliable identification of FABP1 and its variant by top-down LESA MS suggests that the approach may be suitable for imaging NASH pathology in sections from liver biopsies.

  8. Top-down and bottom-up identification of proteins by liquid extraction surface analysis mass spectrometry of healthy and diseased human liver tissue.

    Science.gov (United States)

    Sarsby, Joscelyn; Martin, Nicholas J; Lalor, Patricia F; Bunch, Josephine; Cooper, Helen J

    2014-11-01

    Liquid extraction surface analysis mass spectrometry (LESA MS) has the potential to become a useful tool in the spatially-resolved profiling of proteins in substrates. Here, the approach has been applied to the analysis of thin tissue sections from human liver. The aim was to determine whether LESA MS was a suitable approach for the detection of protein biomarkers of nonalcoholic liver disease (nonalcoholic steatohepatitis, NASH), with a view to the eventual development of LESA MS for imaging NASH pathology. Two approaches were considered. In the first, endogenous proteins were extracted from liver tissue sections by LESA, subjected to automated trypsin digestion, and the resulting peptide mixture was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) (bottom-up approach). In the second (top-down approach), endogenous proteins were extracted by LESA, and analyzed intact. Selected protein ions were subjected to collision-induced dissociation (CID) and/or electron transfer dissociation (ETD) mass spectrometry. The bottom-up approach resulted in the identification of over 500 proteins; however identification of key protein biomarkers, liver fatty acid binding protein (FABP1), and its variant (Thr→Ala, position 94), was unreliable and irreproducible. Top-down LESA MS analysis of healthy and diseased liver tissue revealed peaks corresponding to multiple (~15-25) proteins. MS/MS of four of these proteins identified them as FABP1, its variant, α-hemoglobin, and 10 kDa heat shock protein. The reliable identification of FABP1 and its variant by top-down LESA MS suggests that the approach may be suitable for imaging NASH pathology in sections from liver biopsies.

  9. Effect of Danshao Huaxian capsule on expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in fibrotic liver of rats

    Institute of Scientific and Technical Information of China (English)

    Qin Yang; Ru-Jia Xie; Xiao-Xia Geng; Xin-Hua Luo; Bing Han; Ming-Liang Cheng

    2005-01-01

    AIM: To investigate the effects of Danshao Huaxian (DSHX)capsules, a preparation of traditional Chinese medicine,on the expression of matrix metalloproteinase-1 (MMP-1),and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the fibrous livers of rats.METHODS: Eighty male Wistar rats were randomly divided into normal control group (group A), CCl4-induced hepatic fibrosis group (group B), non-DSHX-treated group (group C), low dose-treated group (group D), and high dose-treated group (group E). Fibrous liver models in rats were induced by subcutaneous injection of CCl4, oral administration of alcohol and high-lipid/low-protein diet for 8 wk. After the models were established, the rats in groups D and E were orally given a low dose (0.5 g/kg) and a high dose (1.0 g/kg) of DSHX daily for 8 wk, respectively.Then, the liver indexes, serum hyaluronic acid (HA) and alanine aminotransferase (ALT) were examined. The degree of hepatic fibrosis was evaluated by optical microscopy.Hydroxyproline (Hyp) in the urine was determined, and the expression of MMP-1 and TIMP-1 was detected by immunohistochemical techniques.RESULTS: In groups D and E, the liver indexes, levels of serum HA and ALT reduced and development of hepaticfibrosis weakened significantly. The urinary Hyp and expression of MMP-1 in the liver tissues elevated, but the expression of TIMP-1 decreased obviously, as compared to groups B and C.CONCLUSION: DSHX enhances the expression of MMP-1but decreases that of TIMP-1 in liver tissues of CCl4-induced hepatic fibrotic rats, which may result in its elevated activity that contributes to fighting against hepatic fibrosis.

  10. Heavy metal levels in the liver and muscle tissues of the four commercial fishes from Lake Balik, Kızılırmak Delta (Samsun, Turkey

    Directory of Open Access Journals (Sweden)

    Levent Bat

    2015-12-01

    Full Text Available Objective: To determine the levels of some heavy metals in the liver and edible tissues of four fish species [Mugil cephalus L., 1758 (M. cephalus, Cyprinus carpio L., 1758 (C. carpio, Perca fluviatilis L., 1758 (P. fluviatilis and Stizostedion lucioperca L., 1758 (S. lucioperca] collected from Lake Balik, Kizilirmak Delta (Samsun for analysis of Cu, Co, Pb, Zn, Cd, Mn, Ni and Fe. These metals were chosen because at higher concentrations there might be toxic to the fish and by extension humans that depends on such fish as food. Methods: The concentrations of the metals were carried out by the flame atomic absorption spectrophotometer (UNICAM 929. Results: Large differences in heavy metal levels were observed between liver and muscle tissues within each fish. The results showed that the Fe concentrations were the highest and Cd concentrations were the lowest in livers and edible tissues of the four species. The muscles of C. carpio accumulated significant higher levels of Co, Zn and Ni than other species. Cu was higher in the muscles of S. lucioperca than those in other species, while M. cephalus showed more of Mn and Fe levels. The muscles of P. fluviatilis accumulated significant higher levels of Pb and Cd than other species. However, the liver of M. cephalus accumulated significant higher levels of Co, Mn and Fe than other species. The level of Cd was the highest in the liver of P. fluviatilis, while S. lucioperca showed more of Cu and Pb, and the higher levels of Zn and Ni was measured in the liver of C. carpio. Conclusions: The metal levels obtained were compared with the maximum permitted levels in food of the Turkish Food Codex and Commission Regulation (EC. The results of this study showed that estimated daily and weekly intakes of selected metals via consumption of fish were below the permissible tolerable daily intake and provisional tolerable weekly intake values established by Food and Agriculture Organization/World Health

  11. [11C]-Labeled Metformin Distribution in the Liver and Small Intestine Using Dynamic Positron Emission Tomography in Mice Demonstrates Tissue-Specific Transporter Dependency.

    Science.gov (United States)

    Jensen, Jonas B; Sundelin, Elias I; Jakobsen, Steen; Gormsen, Lars C; Munk, Ole L; Frøkiær, Jørgen; Jessen, Niels

    2016-06-01

    Metformin is the most commonly prescribed oral antidiabetic drug, with well-documented beneficial preventive effects on diabetic complications. Despite being in clinical use for almost 60 years, the underlying mechanisms for metformin action remain elusive. Organic cation transporters (OCT), including multidrug and toxin extrusion proteins (MATE), are essential for transport of metformin across membranes, but tissue-specific activity of these transporters in vivo is incompletely understood. Here, we use dynamic positron emission tomography with [(11)C]-labeled metformin ([(11)C]-metformin) in mice to investigate the role of OCT and MATE in a well-established target tissue, the liver, and a putative target of metformin, the small intestine. Ablation of OCT1 and OCT2 significantly reduced the distribution of metformin in the liver and small intestine. In contrast, inhibition of MATE1 with pyrimethamine caused accumulation of metformin in the liver but did not affect distribution in the small intestine. The demonstration of OCT-mediated transport into the small intestine provides evidence of direct effects of metformin in this tissue. OCT and MATE have important but separate roles in uptake and elimination of metformin in the liver, but this is not due to changes in biliary secretion. [(11)C]-Metformin holds great potential as a tool to determine the pharmacokinetic properties of metformin in clinical studies.

  12. A Comprehensive MicroRNA Expression Profile of Liver and Lung Metastases of Colorectal Cancer with Their Corresponding Host Tissue and Its Prognostic Impact on Survival

    Science.gov (United States)

    Pecqueux, Mathieu; Liebetrau, Isabell; Werft, Wiebke; Dienemann, Hendrik; Muley, Thomas; Pfannschmidt, Joachim; Müssle, Benjamin; Rahbari, Nuh; Schölch, Sebastian; Büchler, Markus W.; Weitz, Jürgen; Reissfelder, Christoph; Kahlert, Christoph

    2016-01-01

    MicroRNAs are small non-coding RNAs with a length of 18–25 nucleotides. They can regulate tumor invasion and metastasis by changing the expression and translation of their target mRNAs. Their expression is substantially altered in colorectal cancer cells as well as in the adjacent tumor-associated stroma. Both of these compartments have a mutual influence on tumor progression. In the development of metastases, cancer cells initially interact with the host tissue. Therefore, compartment-specific expression signatures of these three locations—tumor, associated stroma, and host tissue—can provide new insights into the complex tumor biology of colorectal cancer. Frozen tissue samples of colorectal liver (n = 25) and lung metastases (n = 24) were laser microdissected to separate tumor cells and the adjacent tumor-associated stroma cells. Additionally, normal lung and liver tissue was collected from the same patients. We performed a microarray analysis in four randomly selected liver metastases and four randomly selected lung metastases, analyzing a total of 939 human miRNAs. miRNAs with a significant change >2-fold between the tumor, tumor stroma, and host tissue were analyzed in all samples using RT-qPCR (11 miRNAs) and correlated with the clinical data. We found a differential expression of several miRNAs between the tumor, the tumor-associated stroma, and the host tissue compartment. When comparing liver and lung metastases, miR-194 showed a 1.5-fold; miR-125, miR-127, and miR-192 showed a 2.5-fold; miR-19 and miR-215 a 3-fold; miR-145, miR-199-3, and miR-429 a 5-fold; miR-21 a 7-fold; and, finally, miR-199-5 a 12.5-fold downregulation in liver metastases compared to lung metastases. Furthermore miR-19, miR-125, miR-127, miR-192, miR-194, miR-199-5, and miR-215 showed a significant upregulation in the normal liver tissue compared to the normal lung tissue. Univariate analysis identified an association of poor survival with the expression of miR-125 (p = 0

  13. Effects of various extremely low frequency magnetic fields on the free radical processes, natural antioxidant system and respiratory burst system activities in the heart and liver tissues.

    Science.gov (United States)

    Canseven, Ayse Gulnihal; Coskun, Sule; Seyhan, Nesrin

    2008-10-01

    Magnetic fields (MFs) can affect biological systems by increasing the release of free radicals that are able to alter cell defense systems and breakdown tissue homeostasis. In the present study, the effects of extremely low frequency (ELF) electromagnetic fields (EMF) were investigated on free radical levels, natural antioxidant systems and respiratory burst system activities in heart and liver tissues of guinea pigs exposed to 50 Hz MFs of 1, 2 and 3 mT for 4 h/day and 8 h/day for 5 days by measuring malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH) levels and myeloperoxidase (MPO) activity. A total of sixty-two male guinea pigs, 10-12 weeks old were studied in seven groups as control and exposure groups: Group I (control), II (1 mT, 4 h/day), III (1 mT, 8 h/day), IV (2 mT, 4 h/day), V (2 mT, 8 h/day), VI (3 mT, 4 h/day), and VII (3 mT, 8 h/day). Controls were kept under the same conditions without any exposure to MF. MDA levels increased in liver in groups II and IV, but decreased in group VII for both liver and heart tissues. NOx levels declined in heart in groups II and III and in liver in groups III, V, and VI, but increased in liver in group VII. GSH levels increased in heart in groups II, IV, V, and in liver in groups V and VI and VI, but decreased in groups II and IV in liver. MPO activity decreased in liver in groups III, IV, VI and VII with respect to controls and in heart tissues in groups II, III and IV; however, there was a significant increase MPO activity in heart in group VII. From the results, it can be concluded that the intensity and exposure duration of MFs are among the effective conditions on the formation of free radicals and behaviour of antioxidant enzymes.

  14. Changes of biochemical indices in brain, liver tissue and serum in mice with Alzheimer disease after Chinese medicine treatment

    Institute of Scientific and Technical Information of China (English)

    Xiangyang Wang; Lili Zhang; Haode Huang; Qiang Qin; Guimei Luo; Chaogan Li; Shuqiu Zhang

    2007-01-01

    BACKGROUND: Alzheimer disease is a main type of dementia, and the important clinical characteristic is the rapid declines of memory and cognitive ability.OBJECTIVE: To study changes of biochemical indices in brain, liver tissue and serum, as well as memory of mice with Alzheimer disease after Chinese medicine treatment. DESIGN: A comparative animal experimental observation. SETTING: Haierfu Research Center of Youjiang Medical College for Nationalities.MATERIALS: Forty-eight healthy Kunming mice (24 males and 24 females), 3 months old, were provided by the animal room of Youjiang Medical College for Nationalities. The animals were divided into four groups according to sex and body mass: control group, model group, Wuyuan Buxue treated group, Haierfu treated group, and 12 mice in each group. Wuyuan Buxue oral liquid was extracted from Polygonum multiflorum Thunb (red, radix) and longan meat (country medicine quasi- word B20020828). Haierfu oral liquid was extracted from Yinhua, poriacocos, licorice, etc (Q/452600RYYLC01-92). METHODS: The experiment was completed in Haierfu Research Center and Institute of Heavy Metal and Fluorosis-Arsenism of Youjiang Medical College for Nationalities from May 2006 to December 2006. ①All animals except those in the control group were given feed which was mixed with AlC3 (12 g/L), and they could freely drink 3 g/L Al(NO3)3. The mice in the control group were given normal feed. Wuyuan Buxue oral liquid and Haierfu oral liquid were distilled by distilled water for one time respectively. Five months after model establishment, mice in the Wuyuan Buxue treated group and Haierfu treated group were given intrapastric perfusion of Wuyuan Buxue oral liquid and Haierfu oral liquid respectively, and those in the model group and control group were given intrapastric perfusion of distilled water of the same volume. All the mice were treated for 45 days. ②The swimming time (s) and error times were determined with Y-shape water maze before and

  15. Identification of phenylsulfone-substituted quinoxaline (WYE-672) as a tissue selective liver X-receptor (LXR) agonist.

    Science.gov (United States)

    Hu, Baihua; Unwalla, Rayomand J; Goljer, Igor; Jetter, James W; Quinet, Elaine M; Berrodin, Thomas J; Basso, Michael D; Feingold, Irene B; Nilsson, Annika Goos; Wilhelmsson, Anna; Evans, Mark J; Wrobel, Jay E

    2010-04-22

    A series of phenyl sulfone substituted quinoxaline were prepared and the lead compound 13 (WYE-672) was shown to be a tissue selective LXR Agonist. Compound 13 demonstrated partial agonism for LXRbeta in kidney HEK-293 cells but did not activate Gal4 LXRbeta fusion proteins in huh-7 liver cells. Although 13 showed potent binding affinity to LXRbeta (IC(50) = 53 nM), it had little binding affinity for LXRalpha (IC(50) > 1.0 microM) and did not recruit any coactivator/corepressor peptides in the LXRalpha multiplex assay. However, compound 13 showed good agonism in THP-1 cells with respect to increasing ABCA1 gene expression and good potency on cholesterol efflux in THP-1 foam cells. In an eight-week lesion study in LDLR -/- mice, compound 13 showed reduction of aortic arch lesion progression and no plasma or hepatic triglyceride increase. These results suggest quinoxaline 13 may have an improved biological profile for potential use as a therapeutic agent.

  16. Cross talk of the immune system in the adipose tissue andthe liver in non-alcoholic steatohepatitis: Pathology andbeyond

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Non-alcoholic steatohepatitis (NASH) is considered to bethe hepatic manifestation of the metabolic syndrome,thus has a tight correlation with systemic metabolicimpairment. The complex mechanisms underlying thepathogenesis of NASH involve different organs andsystems that cross talk together contributing to theonset of NASH. A crucial role is played by inflammatorymediators, especially those deriving from the adiposetissue and the liver, which are involved in the cascadeof inflammation, fibrosis and eventually tumorigenesis.In this setting cytokines and adipokines as well asimmunity are emerging drivers of the key features ofNASH. The immune system participates in this processwith disturbances of the cells constituting both theinnate and the adaptive immune systems that havebeen reported in different organs, such as in the liverand in the adipose tissue, in clinical and preclinicalstudies. The role of the immune system in NASH isincreasingly studied, not only because of its contributionto the pathogenetic mechanisms of NASH but alsobecause of the new potential therapeutic options itoffers in this setting. Indeed, novel treatments actingon the immune system could offer new options inthe management of NASH and the correlated clinicalconsequences.

  17. Orosomucoid expression profiles in liver, adipose tissues and serum of lean and obese domestic pigs, Göttingen minipigs and Ossabaw minipigs

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard; Stagsted, Jan; Christoffersen, Berit Ø.;

    2013-01-01

    , the expression of ORM has not yet been characterized in such pig models. The objective of this study was to investigate the expression of ORM1 mRNA in liver, visceral adipose tissue, subcutaneous adipose tissue (SAT) from the abdomen or retroperitoneal abdominal adipose tissue (RPAT) and SAT from the neck......, as well as the serum concentration of ORM protein in three porcine obesity models; the domestic pig, Göttingen minipigs and Ossabaw minipigs.No changes in ORM1 mRNA expression were observed in obese pigs compared to lean pigs in the four types of tissues. However, obese Ossabaw minipigs, but none...... of the other breeds, showed significantly elevated ORM serum concentrations compared to their lean counterparts. Studies in humans have shown that the expression of ORM was unchanged in adipose tissue depots in obese humans with an increased serum concentration of ORM. Thus in this respect, obese Ossabaw...

  18. A descriptive study to provide evidence of the teratogenic and cellular effects of sibutramine and ephedrine on cardiac- and liver-tissue of chick embryos.

    Science.gov (United States)

    Oberholzer, Hester Magdalena; Van Der Schoor, Ciska; Taute, Helena; Bester, Megan Jean

    2015-08-01

    Exposure to drugs during pregnancy is a major concern, as some teratogenic compounds can influence normal foetal development. Although the use of drugs during pregnancy should generally be avoided, exposure of the developing foetus to teratogens may occur unknowingly since these compounds may be hidden in products that are being marketed as "all natural." The aim of the current study was to investigate the possible teratogenic and cellular effects of sibutramine-a serotonin-norepinephrine reuptake inhibitor used in the treatment of obesity-on the heart and liver tissue of chick embryos. Ephedrine was used as a positive control. The chick embryo model was chosen because it has been used in studying developmental and experimental biology and teratology with great success. The embryos were exposed to three different concentrations of sibutramine and ephedrine respectively. The results obtained revealed that both compounds exhibited embryotoxicity when compared to the control groups. Liver and heart tissue of the exposed embryos was severely affected by these compounds in a dose-related manner. Morphology similar to that of muscle dystrophy was observed in the heart, where the muscle tissue was infiltrated by adipose and connective tissue. Severe liver steatosis was also noted. A more in-depth investigation into the molecular pathways involved might provide more information on the exact mechanism of toxicity of these products influencing embryonic development.

  19. Evaluation of five DNA extraction methods for detection of H. pylori in formalin-fixed paraffin-embedded (FFPE) liver tissue from patients with hepatocellular carcinoma.

    Science.gov (United States)

    Rabelo-Gonçalves, Elizabeth; Roesler, Bruna; Guardia, Ana Carolina; Milan, Arlete; Hara, Natalicia; Escanhoela, Cecília; Almeida, Jazon; Boin, Ilka; Zeitune, José Murilo

    2014-03-01

    Since Helicobacter spp. DNA was identified in liver tissue resected from patients with hepatocelullar carcinoma (HCC), researchers have suggested a role of this bacterium in hepatic carcinogenesis. Archives of formalin-fixed, paraffin-embedded (FFPE) tissues represent an extraordinary source for clinical studies providing many advantages. However, DNA extraction from FFPE tissues is laborious, time-consuming and still remains a challenge. The aim of this study was to evaluate five protocols for DNA extraction from FFPE liver obtained from patients with HCC in order to detect Helicobacter pylori DNA. These methods were: (1) QIAamp FFPE Tissue Kit, (2) QIAamp DNA Mini Kit, (3) Wizard SV Genomic DNA Purification System, (4) RealiaPrep FFPE gDNA Miniprep System and (5) phenol-chloroform. H. pylori detection was performed using 16S rRNA gene amplification by PCR. The highest total amount of DNA was obtained using the phenol-chloroform method. Analyses of 16S rRNA gene amplification did not show statistically significant differences among the methods (p=0.466), although the highest percentage of positive cases (70%) was found in samples extracted with phenol-chloroform. We suggest that of the five methods evaluated, phenol/chloroform is the most suitable for detection of H. pylori in FFPE liver from patients with HCC.

  20. Non-Invasive Quantification of White and Brown Adipose Tissues and Liver Fat Content by Computed Tomography in Mice

    Science.gov (United States)

    Lubura, Marko; Hesse, Deike; Neumann, Nancy; Scherneck, Stephan; Wiedmer, Petra; Schürmann, Annette

    2012-01-01

    Objectives Obesity and its distribution pattern are important factors for the prediction of the onset of diabetes in humans. Since several mouse models are suitable to study the pathophysiology of type 2 diabetes the aim was to validate a novel computed tomograph model (Aloka-Hitachi LCT-200) for the quantification of visceral, subcutaneous, brown and intrahepatic fat depots in mice. Methods Different lean and obese mouse models (C57BL/6, B6.V-Lepob, NZO) were used to determine the most adequate scanning parameters for the detection of the different fat depots. The data were compared with those obtained after preparation and weighing the fat depots. Liver fat content was determined by biochemical analysis. Results The correlations between weights of fat tissues on scale and weights determined by CT were significant for subcutaneous (r2 = 0.995), visceral (r2 = 0.990) and total white adipose tissue (r2 = 0.992). Moreover, scans in the abdominal region, between lumbar vertebrae L4 to L5 correlated with whole-body fat distribution allowing experimenters to reduce scanning time and animal exposure to radiation and anesthesia. Test-retest reliability and measurements conducted by different experimenters showed a high reproducibility in the obtained results. Intrahepatic fat content estimated by CT was linearly related to biochemical analysis (r2 = 0.915). Furthermore, brown fat mass correlated well with weighted brown fat depots (r2 = 0.952). In addition, short-term cold-expose (4°C, 4 hours) led to alterations in brown adipose tissue attributed to a reduction in triglyceride content that can be visualized as an increase in Hounsfield units by CT imaging. Conclusion The 3D imaging of fat by CT provides reliable results in the quantification of total, visceral, subcutaneous, brown and intrahepatic fat in mice. This non-invasive method allows the conduction of longitudinal studies of obesity in mice and therefore enables experimenters to investigate

  1. PEPCK-C reexpression in the liver counters neonatal hypoglycemia in Pck1 (del/del) mice, unmasking role in non-gluconeogenic tissues.

    Science.gov (United States)

    Semakova, Jana; Hyroššová, Petra; Méndez-Lucas, Andrés; Cutz, Ernest; Bermudez, Jordi; Burgess, Shawn; Alcántara, Soledad; Perales, José C

    2017-02-01

    Whole body cytosolic phosphoenolpyruvate carboxykinase knockout (PEPCK-C KO) mice die early after birth with profound hypoglycemia therefore masking the role of PEPCK-C in adult, non-gluconeogenic tissues where it is expressed. To investigate whether PEPCK-C deletion in the liver was critically responsible for the hypoglycemic phenotype, we reexpress this enzyme in the liver of PEPCK-C KO pups by early postnatal administration of PEPCK-C-expressing adenovirus. This maneuver was sufficient to partially rescue hypoglycemia and allow the pups to survive and identifies the liver as a critical organ, and hypoglycemia as the critical pathomechanism, leading to early postnatal death in the whole-body PEPCK-C knockout mice. Pathology assessment of survivors also suggest a possible role for PEPCK-C in lung maturation and muscle metabolism.

  2. Cytokine and acute phase protein mRNA expression in liver tissue from pigs with severe sepsis caused by intravenous inoculation of Staphylococcus aureus

    DEFF Research Database (Denmark)

    Nielsen, Ole Lerberg; Olsen, Helle Gerda; Iburg, Tine

    2010-01-01

    The aim was to substantiate previous findings of hepatic dysfunction in a porcine model of Staphylococcus aureus induced severe sepsis. Nine pigs were inoculated intravenously once or twice with 108S. aureus per kilogram body weight and killed 12, 24 and 48 h later. Three pigs served as controls....... Blood was sampled for bacteriology, haematology and clinical pathology. Tissues were collected at necropsy for bacteriology, gene expression analysis and histology. Bacterial counts in blood remained low, decreased in the lungs, liver and spleen, but increased in bone. All infected pigs developed sepsis...... of IL-6, IL-8, IL-1β, and CRP. N o increase could be detected in the IL-1α or TNFα liver-mRNA levels. IL-6, IL-8 and IL-1β expression peaked at 24 hours (2-5 fold compared to the control group). In conclusion, the increased liver cytokine mRNA levels indicate a local hepatic, non-infectious inflammatory...

  3. Preparation and characterization of oxidized alginate covalently cross-linked galactosylated chitosan scaffold for liver tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Chen Feng [College of Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan 610065 (China); Suzhou Institute of Sichuan University, Suzhou 215123 (China); Tian Meng; Zhang Dongming; Wang Jianyun; Wang Qiguang [College of Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan 610065 (China); Yu Xixun [College of Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan 610065 (China); Suzhou Institute of Sichuan University, Suzhou 215123 (China); Zhang Xiaohua [College of Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan 610065 (China); Wan Changxiu, E-mail: wanchangxiu@163.com [College of Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan 610065 (China)

    2012-02-01

    Liver tissue engineering (LTE) requires a perfect extracellular matrix (ECM) for hepatocytes culture to maintain high level of liver-specific functions. Here, we reported a LTE scaffold derived from oxidized alginate covalently cross-linked galactosylated chitosan via Schiff base reaction, without employing any extraneous chemical cross-linking agent. The structure of galactosylated chitosan (GC) and oxidized alginate was confirmed by Fourier transformed infrared (FTIR) spectra, proton nuclear magnetic resonance ({sup 1}H-NMR) spectroscopy, X-ray diffraction (XRD) or thermogravimetric (TG) analysis. The structure and properties of a series of the scaffolds were characterized by FTIR, XRD, scanning electron microscopy (SEM), porosity, equilibrium swelling, mechanical properties, thermal stability and in vitro degradation. FTIR spectra confirmed the characteristic peak of Schiff base groups in the scaffolds and XRD indicated the scaffolds could be amorphous. SEM analysis showed that the scaffolds displayed highly porous surfaces with average pore size of 50-150 {mu}m and interconnected pore structure in the internal structure with average pore size of 100-250 {mu}m. Porosity measurement suggested the scaffolds had a porosity of about 70%. The compressive modulus of the scaffolds (hydrated) was in the range of 4.2-6.3 kPa. Further studies showed that, with the increase of the oxidized alginate content, the equilibrium swelling and in vitro degradation rate of the scaffolds decreased and the thermal stability slightly increased, which might mainly attribute to the difference of the degree of cross-linking and the nature properties of the raw materials. Additionally, the biocompatibility of the scaffolds was evaluated in vitro. The results showed that the hepatocytes cultured on the scaffolds had a typical spheroidal morphology, formed multi-cellular aggregates and presented perfect integration with the scaffolds, which suggested that the scaffolds may be potential

  4. The Investigation of the Antioxidative Properties of the Synthetic Organoselenium Compounds in Liver Tissue of Rat with Histological and Biochemical Analyses

    Directory of Open Access Journals (Sweden)

    Zeliha Selamoglu

    2015-10-01

    Full Text Available  Background: Oxidative stress is described as the formation of toxic effect due to the deficiency of cellular antioxidative level toward the level of reactive oxygen species (ROS. The excess production of ROS or the decrease in the antioxidative defense system could be the cause for oxidative stress. 7,12-dimethylbenz[a]anthracene (DMBA that is known to be the major cause the increment in lipid peroxidation level and the oxidative damage in the rat liver. As a fundamental trace elements, selenium as a part of anti-oxidative defense system is responsible for the immune system as part of enzymes in defense system.  Methods:Organoselenium compounds [1-isopropyl-3- methylbenzimidazole-2-selenone (Se I and 1, 3-di-pmethoxybenzylpyrimidine- 2-selenone (Se II] that were prepared in the laboratories. The effects of synthetic organoselenium compounds (Se I and Se II against DMBA-induced changes in levels of some [catalase (CAT, superoxide dismutase (SOD, glutathione peroxidase (GPx, and glutathione reductase (GR activities and total glutathione (GSH, malonedialdehyde (MDA] parameters in rat liver were investigated. Histopathological changes in the liver tissues of rats were examined by light microscopy. Results:Because the selenium has an anti-oxidative properties toward the damaged induced cells, organoselenium compounds prepared in our laboratories, Se I and Se II, have tested for chemically induced rat liver tissues. The results showed that endogen antioxidant enzymatic activities changes and the preventing of oxidative damage in lipid peroxidation are important findings in vivo of this research. Conclusion:Various changes were observed in liver tissue of rats in the all experimental groups.

  5. Measurement of real-time tissue elastography in a phantom model and comparison with transient elastography in pediatric patients with liver diseases

    Science.gov (United States)

    Schenk, Jens-Peter; Alzen, Gerhard; Klingmüller, Volker; Teufel, Ulrike; Sakka, Saroa El; Engelmann, Guido; Selmi, Buket

    2014-01-01

    PURPOSE We aimed to determine the comparability of real-time tissue elastography (RTE) and transient elastography (TE) in pediatric patients with liver diseases. MATERIALS AND METHODS RTE was performed on the Elasticity QA Phantom Model 049 (Computerized Imaging Reference Systems Company Inc., Norfolk, Virginia, USA), which has five areas with different levels of stiffness. RTE measurements of relative stiffness (MEAN [mean value of tissue elasticity], AREA [% of blue color-coded stiffer tissue]) in the phantom were compared with the phantom stiffness specified in kPa (measurement unit of TE). RTE and TE were performed on 147 pediatric patients with various liver diseases. A total of 109 measurements were valid. The participants had following diseases: metabolic liver disease (n=25), cystic fibrosis (n=20), hepatopathy of unknown origin (n=11), autoimmune hepatitis (n=12), Wilson’s disease (n=11), and various liver parenchyma alterations (n=30). Correlations between RTE and TE measurements in the patients were calculated. In addition, RTE was performed on a control group (n=30), and the RTE values between the patient and control groups were compared. RESULTS The RTE parameters showed good correlation in the phantom model with phantom stiffness (MEAN/kPa, r=−0.97; AREA/kPa, r=0.98). However, the correlation of RTE and TE was weak in the patient group (MEAN/kPa, r=−0.23; AREA/kPa, r=0.24). A significant difference was observed between the patient and control groups (MEAN, P = 5.32 e-7; AREA, P = 1.62 e-6). CONCLUSION In the phantom model, RTE was correlated with kPa, confirming the presumed comparability of the methods. However, there was no direct correlation between RTE and TE in patients with defined liver diseases under real clinical conditions. PMID:24317333

  6. Potential role of growth hormone in impairment of insulin signaling in skeletal muscle, adipose tissue, and liver of rats chronically treated with arginine.

    Science.gov (United States)

    de Castro Barbosa, Thais; de Carvalho, José Edgar Nicoletti; Poyares, Leonice Lourenço; Bordin, Silvana; Machado, Ubiratan Fabres; Nunes, Maria Tereza

    2009-05-01

    We have shown that rats chronically treated with Arginine (Arg), although normoglycemic, exhibit hyperinsulinemia and decreased blood glucose disappearance rate after an insulin challenge. Attempting to investigate the processes underlying these alterations, male Wistar rats were treated with Arg (35 mg/d), in drinking water, for 4 wk. Rats were then acutely stimulated with insulin, and the soleus and extensorum digitalis longus muscles, white adipose tissue (WAT), and liver were excised for total and/or phosphorylated insulin receptor (IR), IR substrate 1/2, Akt, Janus kinase 2, signal transducer and activator of transcription (STAT) 1/3/5, and p85alpha/55alpha determination. Muscles and WAT were also used for plasma membrane (PM) and microsome evaluation of glucose transporter (GLUT) 4 content. Pituitary GH mRNA, GH, and liver IGF-I mRNA expression were estimated. It was shown that Arg treatment: 1) did not affect phosphotyrosine-IR, whereas it decreased phosphotyrosine-IR substrate 1/2 and phosphoserine-Akt content in all tissues studied, indicating that insulin signaling is impaired at post-receptor level; 2) decreased PM GLUT4 content in both muscles and WAT; 3) increased the pituitary GH mRNA, GH, and liver IGF-I mRNA expression, the levels of phosphotyrosine-STAT5 in both muscles, phosphotyrosine-Janus kinase 2 in extensorum digitalis longus, phosphotyrosine-STAT3 in liver, and WAT as well as total p85alpha in soleus, indicating that GH signaling is enhanced in these tissues; and 4) increased p55alpha total content in muscles, WAT, and liver. The present findings provide the molecular mechanisms by which insulin resistance and, by extension, reduced GLUT4 content in PM of muscles and WAT take place after chronic administration of Arg, and further suggest a putative role for GH in its genesis, considering its diabetogenic effect.

  7. Beneifcial effect of reifned red palm oil on lipid peroxidation and monocyte tissue factor in HCV-related liver disease:a randomized controlled study

    Institute of Scientific and Technical Information of China (English)

    Roberto Catanzaro; Nicola Zerbinati; Umberto Solimene; Massimiliano Marcellino; Dheeraj Mohania; Angelo Italia; Antonio Ayala; Francesco Marotta

    2016-01-01

    BACKGROUND: A large amount of endotoxin can be detected in the peripheral venous blood of patients with liver cirrhosis, contributing to the pathogenesis of hepatotoxicity because of its role in oxidative stress. The present study aimed to test the effect of the supplementation with red palm oil (RPO), which is a natural oil obtained from oil palm fruit (Elaeis guineensis) rich in natural fat-soluble tocopherols, tocotrienols and carot-enoids, on lipid peroxidation and endotoxemia with plasma endotoxin-inactivating capacity, proinlfammatory cytokines proifle, and monocyte tissue factor in patients with chronic liver disease. METHODS: The study group consisted of sixty patients (34 males and 26 females; mean age 62 years, range 54-75) with Child A/B, genotype 1 HCV-related cirrhosis without a history of ethanol consumption, randomly enrolled into an 8-week oral daily treatment with either vitamin E or RPO. All patients had undergone an upper gastrointestinal endoscopy 8 months before, and 13 out of them showed esophageal varices. RESULTS: Both treatments signiifcantly decreased erythro-cyte malondialdehyde and urinary isoprostane output, only RPO signiifcantly affected macrophage-colony stimulating fac-tor and monocyte tissue factor. Liver ultrasound imaging did not show any change. CONCLUSIONS: RPO beneifcially modulates oxidative stress and, not least, downregulates macrophage/monocyte inlfam-matory parameters. RPO can be safely advised as a valuable nutritional implementation tool in the management of chron-ic liver diseases.

  8. Histopathological finding of liver and kidney tissues of the yellow mystus, Hemibagrus filamentus (Fang and Chaux, 1949, from the Tapee River, Thailand

    Directory of Open Access Journals (Sweden)

    Sinlapachai Senarat

    2015-02-01

    Full Text Available A histological finding of liver and kidney tissues of yellow mystus, Hemibagrus filamentus (Fang and Chaux, 1949, collected from the Tapee River (Chawang District, Nakhon Si Thammarat Province, Thailand was conducted to examine the pathological lesions. Lesions, including cellular swelling, hydropic degeneration, or vacuolation of hepatocytes were found. From this, coagulative necrosis with pyknotic nuclei, infiltration of macrophage, constriction of sinusoidal capillaries and damage of endothelial cells of blood vessels were observed in liver tissues. The dilation of both Bowman’s space and the glomerulus were observed from kidney lesions. Moreover, necrosis in renal tubular cells was also observed in some areas. Although preliminary, the results from this study clearly show the need for further investigation into stress factors and vectors affecting the health of H. filamentus and other fish species within the Tapee River.

  9. Ablation of systemic SIRT1 activity promotes nonalcoholic fatty liver disease by affecting liver-mesenteric adipose tissue fatty acid mobilization

    Science.gov (United States)

    The incidence of nonalcoholic fatty liver disease (NAFLD) is escalating paralleled with obesity rates in both adults and children. Mammalian sirtuin 1 (SIRT1), a highly conserved NAD+-dependent protein deacetylase, has been identified as a metabolic regulator of lipid homeostasis and a potential tar...

  10. Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic beta-cells

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Dela, Flemming

    2005-01-01

    OBJECTIVES: Lipodystrophy and insulin resistance are prevalent among human immunodeficiency virus (HIV)-infected patients on combined antiretroviral therapy (HAART). Aiming to provide a detailed description of the metabolic adverse effects of HIV-lipodystrophy, we investigated several aspects of ....... CONCLUSION: Our data suggest that normoglycaemic lipodystrophic HIV-infected patients display impaired glucose and lipid metabolism in multiple pathways involving liver, muscle tissue and beta-cell function....

  11. Implantation of healthy matrix-embedded endothelial cells rescues dysfunctional endothelium and ischaemic tissue in liver engraftment.

    Science.gov (United States)

    Melgar-Lesmes, Pedro; Balcells, Mercedes; Edelman, Elazer R

    2017-07-01

    Liver transplantation is limited by ischaemic injury which promotes endothelial cell and hepatocyte dysfunction and eventually organ failure. We sought to understand how endothelial state determines liver recovery after hepatectomy and engraftment. Matrix-embedded endothelial cells (MEECs) with retained healthy phenotype or control acellular matrices were implanted in direct contact with the remaining median lobe of donor mice undergoing partial hepatectomy (70%), or in the interface between the remaining median lobe and an autograft or isograft from the left lobe in hepatectomised recipient mice. Hepatic vascular architecture, DNA fragmentation and apoptosis in the median lobe and grafts, serum markers of liver damage and phenotype of macrophage and lymphocyte subsets in the liver after engraftment were analysed 7 days post-op. Healthy MEECs create a functional vascular splice in donor and recipient liver after 70% hepatectomy in mouse protecting these livers from ischaemic injury, hepatic congestion and inflammation. Macrophages recruited adjacent to the vascular nodes into the implants switched to an anti-inflammatory and regenerative profile M2. MEECs improved liver function and the rate of liver regeneration and prevented apoptosis in donor liver lobes, autologous grafts and syngeneic engraftment. Implants with healthy endothelial cells rescue liver donor and recipient endothelium and parenchyma from ischaemic injury after major hepatectomy and engraftment. This study highlights endothelial-hepatocyte crosstalk in hepatic repair and provides a promising new approach to improve regenerative medicine outcomes and liver transplantation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Determination of boron concentration in blood and tissue samples from patients with liver metastases of colorectal carcinoma using Prompt Gamma Ray Activation Analysis (PGAA)

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, T., E-mail: schmito@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany); Appelman, K., E-mail: k.appelman@hetnet.n [Institute for Energy, Joint Research Centre of the European Commission, Petten (Netherlands); Kudejova, P., E-mail: petra.kudejova@frm2.tum.d [Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Universitaet Muenchen, D-85748 Garching (Germany); Schuetz, C., E-mail: schuetc@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany); Kratz, J.V., E-mail: jvkratz@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany); Moss, R., E-mail: raymond.moss@ec.europa.e [Institute for Energy, Joint Research Centre of the European Commission, Petten (Netherlands); Otto, G., E-mail: gerd.otto@unimedizin-mainz.d [Department of Hepatobiliary, Pancreatic and Transplantation Surgery, University of Mainz, Langenbeckstr. 1, D-55131 Mainz (Germany); Hampel, G., E-mail: gabriele.hampel@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany)

    2011-07-15

    As part of the studies on Boron Neutron Capture Therapy at the University of Mainz, Germany, a clinical trial has been started in which, four patients suffering from liver metastases of colorectal carcinoma have been enrolled. Specimens of blood and healthy tissue samples taken from the patients were measured at the PGAA facilities at the HFR in Petten, The Netherlands, and at the FRM II in Munich, Germany. From the measured boron concentrations, pharmacokinetic curves and blood-to-tissue concentration ratios were produced.

  13. Knockdown expression and hepatic deficiency reveal anatheroprotective role for SR-BI in liver and peripheral tissues

    Energy Technology Data Exchange (ETDEWEB)

    Huby, Thierry; Doucet, Chantal; Dachet, Christiane; Ouzilleau,Betty; Ueda, Yukihiko; Afzal, Veena; Rubin, Edward; Chapman, M. John; Lesnik, Philippe

    2006-07-18

    Scavenger receptor SR-BI has been implicated inHDL-dependent atheroprotective mechanisms. We report the generation of anSR-BI conditional knockout mouse model in which SR-BI gene targeting byloxP site insertion produced a hypomorphic allele (hypomSR-BI).Attenuated SR-BI expression in hypomSR-BI mice resulted in 2-foldelevation in plasma total cholesterol (TC) levels. Cre-mediated SR-BIgene inactivation of the hypomorphic SR-BI allele in hepatocytes(hypomSR-BI-KOliver) was associated with high plasma TC concentrations,increased plasma free cholesterol/TC (FC/TC) ratio, and alipoprotein-cholesterol profile typical of SR-BI-/- mice. Plasma TClevels were increased 2-fold in hypomSR-BI and control mice fed anatherogenic diet, whereas hypomSR-BI-KOliver and SR-BI-/- mice developedsevere hypercholesterolemia due to accumulation of FC-rich, VLDL-sizedparticles. Atherosclerosis in hypomSR-BI mice was enhanced (2.5-fold)compared with that in controls, but to a much lower degree than inhypomSR-BI-KOliver (32-fold) and SR-BI-/- (48-fold) mice. The lattermodels did not differ in either plasma lipid levels or in the capacity ofVLDL-sized lipoproteins to induce macrophage cholesterol loading.However, reduced atherosclerosis in hypomSR-BI-KOliver mice wasassociated with decreased lesional macrophage content as compared withthat in SR-BI-/- mice. These data imply that, in addition to its majoratheroprotective role in liver, SR-BI may exert an antiatherogenic rolein extrahepatic tissues.

  14. 激光照射猪肝组织的温度场研究%Research on Temperature Field in Porcine Liver Tissue Irradiated by Laser

    Institute of Scientific and Technical Information of China (English)

    王群超; 苑洁; 邓琦林; 章家福; 朱训生

    2011-01-01

    The dynamic properties of temperature spatial distribution during laser induced porcine liver tissue thermal conduction process was studied. By the method of finite element analysis and distribution formula of laser, the temperature distribution simulation results were obtained, and the temperature of surface and internal porcine liver tissue was measured by using K-type thermocouple and thermocouple amplifiers, the measurement results and the simulation results are consistent, and the variational relationship between the blood perfusion and the temperature of porcine liver tissue was obtained. This research has some significance in the choice of laser therapy parameters during laser medicine application.%研究了激光照射下猪肝组织传热过程温度场空间分布的动态规律.采用有限元分析法,利用激光分布公式获得猪肝组织的温度场空间分布,并采用K型热电偶和热电偶放大器来测量猪肝组织表面和内部温度,实验测量结果和模拟结果基本吻合,同时得出血液灌注率和猪肝组织温度的关系.研究结果对于激光临床应用中激光参数的合理选择有一定的指导意义.

  15. Transplantation of fetal liver tissue suspension into the spleens of adult syngenic rats: inducibility of cytochrome P450 dependent monooxygenase functions by beta-naphthoflavone, phenobarbital and dexamethasone.

    Science.gov (United States)

    Lupp, A; Lau, K; Trautmann, A K; Krausse, T; Klinger, W

    1999-01-01

    In the present study the effects of beta-naphthoflavone (BNF), phenobarbital (PB) and dexamethasone (DEX) on cytochrome P450 (P450) dependent monooxygenase functions were investigated in intrasplenic liver cell explants in comparison to adult liver. Fetal liver tissue suspensions were transplanted into the spleens of 60-90 days old adult male syngenic Fisher 344 inbred rats. 2, 4 or 6 months after surgery, transplant recipients and age matched controls were orally treated with BNF (1x50 mg/kg body weight (b.wt.)), PB (1x50 mg/kg b.wt.), DEX (for 3 days 4 mg/kg b.wt. per day), or the respective solvents (dimethylsulfoxide or 0.9% NaCl). The animals were sacrificed 24 (BNF, DEX) or 48 (PB) hours after the last treatment. P450 mediated monooxygenase functions were measured in spleen and liver 9000 g supernatants by three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; 1A), ethoxycoumarin O-deethylation (ECOD; 1A, 2A, 2B), and ethylmorphine N-demethylation (END; 3A). Spleen weights were significantly higher in transplanted rats, compared to controls, at all three time points after surgery. Induction with PB or DEX, and in some cases also with BNF, lead to a significant increase in liver weights of transplant recipients and control rats independent of the time after transplantation. In contrast, there was no influence on spleen weights due to BNF or PB. At all time points after surgery, with DEX a marked decrease in body weights, weights of adrenal glands and of lymphatic organs like thymus glands and spleens was observed, with the weights of the transplant containing spleens being still higher in comparison to control organs. Spleens of control animals displayed nearly no P450 mediated monooxygenase functions neither without nor with induction. After transplantation, however, significant EROD and ECOD, but hardly any END activities were seen in the host organs at all three time points after surgery. In transplant containing spleens

  16. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kovalchuk, Olga; Burke, Paula; Besplug, Jill; Slovack, Mark; Filkowski, Jody; Pogribny, Igor

    2004-04-14

    The biological and genetic effects of chronic low-dose radiation (LDR) exposure and its relationship to carcinogenesis have received a lot of attention in the recent years. For example, radiation-induced genome instability, which is thought to be a precursor of tumorogenesis, was shown to have a transgenerational nature. This indicates a possible involvement of epigenetic mechanisms in LDR-induced genome instability. Genomic DNA methylation is one of the most important epigenetic mechanisms. Existing data on radiation effects on DNA methylation patterns is limited, and no one has specifically studied the effects of the LDR. We report the first study of the effects of whole-body LDR exposure on global genome methylation in muscle and liver tissues of male and female mice. In parallel, we evaluated changes in promoter methylation and expression of the tumor suppressor gene p16{sup INKa} and DNA repair gene O{sup 6}-methylguanine-DNA methyltransferase (MGMT). We observed different patterns of radiation-induced global genome DNA methylation in the liver and muscle of exposed males and females. We also found sex and tissue-specific differences in p16{sup INKa} promoter methylation upon LDR exposure. In male liver tissue, p16{sup INKa} promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16{sup INKa} promoter methylation were noted in the muscle tissue of exposed males and females. Radiation also did not significantly affect methylation status of MGMT promoter. We also observed substantial sex differences in acute and chronic radiation-induced expression of p16{sup INKa} and MGMT genes. Another important outcome of our study was the fact that chronic low-dose radiation exposure proved to be a more potent inducer of epigenetic effects than the acute exposure. This supports previous findings that chronic exposure leads to greater genome destabilization than acute exposure.

  17. Perfluoroalkyl sulfonates and carboxylic acids in liver, muscle and adipose tissues of black-footed albatross (Phoebastria nigripes) from Midway Island, North Pacific Ocean.

    Science.gov (United States)

    Chu, Shaogang; Wang, Jun; Leong, Gladys; Woodward, Lee Ann; Letcher, Robert J; Li, Qing X

    2015-11-01

    The Great Pacific Garbage Patch (GPGP) is a gyre of marine plastic debris in the North Pacific Ocean, and nearby is Midway Atoll which is a focal point for ecological damage. This study investigated 13 C4-C16 perfluorinated carboxylic acids (PFCAs), four (C4, C6, C8 and C10) perfluorinated sulfonates and perfluoro-4-ethylcyclohexane sulfonate [collectively perfluoroalkyl acids (PFAAs)] in black-footed albatross tissues (collected in 2011) from Midway Atoll. Of the 18 PFCAs and PFSAs monitored, most were detectable in the liver, muscle and adipose tissues. The concentrations of PFCAs and PFSAs were higher than those in most seabirds from the arctic environment, but lower than those in most of fish-eating water birds collected in the U.S. mainland. The concentrations of the PFAAs in the albatross livers were 7-fold higher than those in Laysan albatross liver samples from the same location reported in 1994. The concentration ranges of PFOS were 22.91-70.48, 3.01-6.59 and 0.53-8.35 ng g(-1) wet weight (ww), respectively, in the liver, muscle and adipose. In the liver samples PFOS was dominant, followed by longer chain PFUdA (8.04-18.70 ng g(-1) ww), PFTrDA, and then PFNA, PFDA and PFDoA. Short chain PFBA, PFPeA, PFBS and PFODA were below limit of quantification. C8-C13 PFCAs showed much higher composition compared to those found in other wildlife where PFOS typically predominated. The concentrations of PFUdA in all 8 individual albatross muscle samples were even higher than those of PFOS. This phenomenon may be attributable to GPGP as a pollution source as well as PFAA physicochemical properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. The effect of Prometheus device on laboratory markers of inflammation and tissue regeneration in acute liver failure management.

    Science.gov (United States)

    Rocen, M; Kieslichova, E; Merta, D; Uchytilova, E; Pavlova, Y; Cap, J; Trunecka, P

    2010-11-01

    Prometheus, based on modified fractionated plasma separation and adsorption (FPSA) method, is used in the therapy of acute liver failure as a bridge to liver transplantation. As the therapeutic effect of Prometheus is caused not only by the elimination of terminal metabolites, the aim of the study was to identify the effect of FPSA on the levels of cytokines and markers of inflammation and liver regeneration. Previous studies assessing cytokine levels involved mostly acute-on-chronic liver failure patients. Data concerning markers of inflammation and liver regeneration are not published yet. Eleven patients (three males, eight females) with acute liver failure were investigated. These patients underwent 37 therapeutic sessions on Prometheus device. Before and after each treatment, the plasma levels of selected cytokines, tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), procalcitonin (PCT), hepatocyte growth factor (HGF), and α(1) fetoprotein, were measured, and the kinetics of their plasma concentrations was evaluated. Before the therapy, elevated levels of interleukin (IL)-6, IL-8, IL-10, TNFα, CRP, and PCT were detected. The level of TNFα, CRP, PCT, and α(1) fetoprotein decreased significantly during the therapy. In contrast, an increase of HGF was detected. The decline of IL-6, IL-8, and IL-10 concentrations was not significant. Our results show that Prometheus is highly effective in clearing inflammatory mediators responsible for systemic inflammatory response syndrome and affects the serum levels of inflammatory and regeneration markers important for management of acute liver failure.

  19. Unraveling the molecular signatures of oxidative phosphorylation to cope with the nutritionally changing metabolic capabilities of liver and muscle tissues in farmed fish.

    Science.gov (United States)

    Bermejo-Nogales, Azucena; Calduch-Giner, Josep Alvar; Pérez-Sánchez, Jaume

    2015-01-01

    Mitochondrial oxidative phosphorylation provides over 90% of the energy produced by aerobic organisms, therefore the regulation of mitochondrial activity is a major issue for coping with the changing environment and energy needs. In fish, there is a large body of evidence of adaptive changes in enzymatic activities of the OXPHOS pathway, but less is known at the transcriptional level and the first aim of the present study was to define the molecular identity of the actively transcribed subunits of the mitochondrial respiratory chain of a livestock animal, using gilthead sea bream as a model of farmed fish with a high added value for European aquaculture. Extensive BLAST searches in our transcriptomic database (www.nutrigroup-iats.org/seabreamdb) yielded 97 new sequences with a high coverage of catalytic, regulatory and assembly factors of Complex I to V. This was the basis for the development of a PCR array for the simultaneous profiling of 88 selected genes. This new genomic resource allowed the differential gene expression of liver and muscle tissues in a model of 10 fasting days. A consistent down-regulated response involving 72 genes was made by the liver, whereas an up-regulated response with 29 and 10 differentially expressed genes was found in white skeletal muscle and heart, respectively. This differential regulation was mostly mediated by nuclear-encoded genes (skeletal muscle) or both mitochondrial- and nuclear-encoded genes (liver, heart), which is indicative of a complex and differential regulation of mitochondrial and nuclear genomes, according to the changes in the lipogenic activity of liver and the oxidative capacity of glycolytic and highly oxidative muscle tissues. These insights contribute to the identification of the most responsive elements of OXPHOS in each tissue, which is of relevance for the appropriate gene targeting of nutritional and/or environmental metabolic disturbances in livestock animals.

  20. Zinc transport in rabbit tissues. Some hormonal aspects of the turnover of zinc in female reproductive organs, liver and body fluids.

    Science.gov (United States)

    McIntosh, J E; Lutwak-Mann, C

    1972-02-01

    1. To investigate the influence of hormonal conditions upon the kinetics of zinc transport, specific radioactivity of (65)Zn was determined in certain tissues and fluids from unmated or pregnant rabbits during the first half of gestation. 2. Compartmental analysis was used to find the simplest mathematical model that simulated satisfactorily tracer behaviour. Models were fitted to experimental results by a numerical procedure using a computer. 3. The kinetics of zinc exchange in most tissues investigated could adequately be described by a three-compartment model, in which total tissue zinc content was divided into a rapidly exchanging pool, with a turnover time of about 1h, and a slowly exchanging pool, the turnover time of which was in liver 15h, in peak-stage corpus luteum 8h, and in the other tissues 30-70h. 4. In rabbit endometrium zinc transport varied with hormonal conditions, the turnover rate being higher in non-pregnant than pregnant endometrium. 5. Uptake of (65)Zn by uterine fluid was slow, and in the free-lying embryos (blastocysts) slower still, in keeping with uterine fluid acting as carrier of zinc into the unimplanted embryos. 6. In placental tissue zinc transport varied with gestational stage. Foetal placenta exchanged zinc with blood plasma four times faster than maternal placenta. In foetuses zinc turnover time and flux equalled that of the slow zinc compartment in foetal placenta. 7. Corpus luteum on days 5-6 of gestation showed peak specific radioactivity and zinc flux values, which exceeded those of all other tissues. 8. In liver the slow zinc compartment had a higher rate of turnover than corresponding compartments in tissues other than peak-stage corpus luteum, but no hormone-dependent changes were observed. 9. Zinc uptake by erythrocytes was the slowest of all examined.

  1. Induction by mercury compounds of metallothioneins in mouse tissues: inorganic mercury accumulation is not a dominant factor for metallothionein induction in the liver.

    Science.gov (United States)

    Yasutake, Akira; Nakamura, Masaaki

    2011-06-01

    Among the naturally occurring three mercury species, metallic mercury (Hg(0)), inorganic mercury (Hg(II)) and methylmercury (MeHg), Hg(II) is well documented to induce metallothionein (MT) in tissues of injected animals. Although Hg(0) and MeHg are considered to be inert in terms of directly inducing MT, MT can be induced by them after in vivo conversion to Hg(II) in an animal body. In the present study we examined accumulations of inorganic mercury and MT inductions in mouse tissues (brain, liver and kidney) up to 72 hr after treatment by one of three mercury compounds of sub-lethal doses. Exposure to mercury compounds caused significant mercury accumulations in mouse tissues examined, except for the Hg(II)-treated mouse brain. Although MeHg caused the highest total mercury accumulation in all tissues among mercury compounds, the rates of inorganic mercury were less than 10% through the experimental period. MT inductions that depended on the inorganic mercury accumulation were observed in kidney and brain. However, MT induction in the liver could not be accounted for by the inorganic mercury accumulation, but by plasma IL6 levels, marked elevation of which was observed in Hg(II) or MeHg-treated mouse. The present study demonstrated that MT was induced in mouse tissues after each of three mercury compounds, Hg(0), Hg(II) and MeHg, but the induction processes were different among tissues. The induction would occur directly through accumulation of inorganic mercury in brain and kidney, whereas the hepatic MT might be induced secondarily through mercury-induced elevation in the plasma cytokines, rather than through mercury accumulation in the tissue.

  2. Effects of a Diet Enriched with Polyunsaturated, Saturated, or Trans Fatty Acids on Cytokine Content in the Liver, White Adipose Tissue, and Skeletal Muscle of Adult Mice

    Directory of Open Access Journals (Sweden)

    Bruno dos Santos

    2013-01-01

    Full Text Available This study analyzed the effect of diet enriched with 30% lipids on cytokines content in different tissues. Swiss male mice were distributed into four groups treated for 8 weeks with control (C, normolipidic diet; soybean oil (S; lard (L; and hydrogenated vegetable fat (H. We observed an increase in carcass fat in groups S and L, and the total amount of fatty deposits was only higher in group L compared with C group. The serum levels of free fatty acids were lower in the L group, and insulin, adiponectin, lipid profile, and glucose levels were similar among the groups. IL-10 was lower in group L in mesenteric and retroperitoneal adipose tissues. H reduced IL-10 only in retroperitoneal adipose tissue. There was an increase in IL-6 in the gastrocnemius muscle of the L group, and a positive correlation between TNF-α and IL-10 was observed in the livers of groups C, L, and H and in the muscles of all groups studied. The results suggested relationships between the quantity and quality of lipids ingested with adiposity, the concentration of free fatty acids, and cytokine production in white adipose tissue, gastrocnemius muscle, and liver.

  3. A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture.

    Science.gov (United States)

    Wagner, Ilka; Materne, Eva-Maria; Brincker, Sven; Süssbier, Ute; Frädrich, Caroline; Busek, Mathias; Sonntag, Frank; Sakharov, Dmitry A; Trushkin, Evgeny V; Tonevitsky, Alexander G; Lauster, Roland; Marx, Uwe

    2013-09-21

    Current in vitro and animal tests for drug development are failing to emulate the systemic organ complexity of the human body and, therefore, to accurately predict drug toxicity. In this study, we present a multi-organ-chip capable of maintaining 3D tissues derived from cell lines, primary cells and biopsies of various human organs. We designed a multi-organ-chip with co-cultures of human artificial liver microtissues and skin biopsies, each a (1)/100,000 of the biomass of their original human organ counterparts, and have successfully proven its long-term performance. The system supports two different culture modes: i) tissue exposed to the fluid flow, or ii) tissue shielded from the underlying fluid flow by standard Transwell® cultures. Crosstalk between the two tissues was observed in 14-day co-cultures exposed to fluid flow. Applying the same culture mode, liver microtissues showed sensitivity at different molecular levels to the toxic substance troglitazone during a 6-day exposure. Finally, an astonishingly stable long-term performance of the Transwell®-based co-cultures could be observed over a 28-day period. This mode facilitates exposure of skin at the air-liquid interface. Thus, we provide here a potential new tool for systemic substance testing.

  4. 5-Fluorouracil concentration in blood, liver and tumor tissues and apoptosis of tumor cells after preoperative oral 5'-deoxy-5-fluorouridine in patients with hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jin-Fang Zheng; Hai-Dong Wang

    2005-01-01

    AIM: To study the levels of 5-fluorouracail (5-FU) in plasma,liver and tumor in patients with hepatocellular carcinoma after oral administration of 5'-deoxy-5-fluorouridine (5'-DFUR).METHODS: Thirty-nine patients with hepatocellular carcinoma were treated with oral 5'-DFUR for more than 4 d before operation. The contents of 5-FU in plasma,liver and tumor were measured by high performance liquid chromatography (HPLC) and apoptosis of tumor cells was evaluated by in-situ TUNEL after resection of tumor.RESULTS: The concentrations of 5-FU were 1.1 μg/mL,5.6, 5.9, and 10.5 μg/g in plasma, the liver tissue, the center of tumor and the periphery of tumor, respectively.5-FU concentration was significantly higher in the periphery of tumor than that in the liver tissue and the center of tumor (10.5±1.6 μg/g vs 5.6±0.8 μg/g, t= 21.38, P<0.05;10.5±1.6 μg/g vs 5.9±0.9 μg/g, t= 20.07, P<0.05). 5-FU level was significantly lower in plasma than that in the liver and the tumor (1.1±0.3 μg/mL vs 5.6±0.8 μg/g, t= 19.63,P<0.05; 1.1±0.3 μg/mL vs 10.5±1.6 μg/g, t= 41.01, P<0.05).Apoptosis of tumor cells was significantly increased after oral 5'-DFUR compared to the control group without 5'-DFUR treatment.CONCLUSION: There is a higher concentration of 5-FU distributed in the tumor compared with liver tissue and apoptosis of tumor cells is increased following oral 5'-DFUR compared with the control group. The results indicate that 5'-DFUR is hopeful as neo-adjuvant chemotherapy to prevent recurrence after resection of hepatocellular carcinoma.

  5. Heavy metal levels in the liver and muscle tissues of the four commercial fishes from Lake Balik, Kızılırmak Delta (Samsun, Turkey)

    Institute of Scientific and Technical Information of China (English)

    Levent Bat; Elif Arıcı; Murat Sezgin; FatihŞahin

    2015-01-01

    Objective:To determine the levels of some heavy metals in the liver and edible tissues of four fish species [Mugil cephalus L., 1758 (M. cephalus),Cyprinus carpio L., 1758 (C. carpio), Perca fluviatilis L., 1758 (P. fluviatilis) andStizostedion lucioperca L., 1758 (S. lucioperca)] collected from Lake Balik, Kizilirmak Delta (Samsun) for analysis of Cu, Co, Pb, Zn, Cd, Mn, Ni and Fe. These metals were chosen because at higher concentrations there might be toxic to the fish and by extension humans that depends on such fish as food. Methods: The concentrations of the metals were carried out by the flame atomic absorption spectrophotometer (UNICAM 929). Results: Large differences in heavy metal levels were observed between liver and muscle tissues within each fish. The results showed that the Fe concentrations were the highest and Cd concentrations were the lowest in livers and edible tissues of the four species. The muscles of C. carpio accumulated significant higher levels of Co, Zn and Ni than other species. Cu was higher in the muscles ofS. lucioperca than those in other species, whileM. cephalus showed more of Mn and Fe levels. The muscles ofP. fluviatilis accumulated significant higher levels of Pb and Cd than other species. However, the liver ofM. cephalus accumulated significant higher levels of Co, Mn and Fe than other species. The level of Cd was the highest in the liver ofP. fluviatilis, whileS. lucioperca showed more of Cu and Pb, and the higher levels of Zn and Ni was measured in the liver ofC. carpio. Conclusions: The metal levels obtained were compared with the maximum permitted levels in food of the Turkish Food Codex and Commission Regulation (EC). The results of this study showed that estimated daily and weekly intakes of selected metals via consumption of fish were below the permissible tolerable daily intake and provisional tolerable weekly intake values established by Food and Agriculture Organization/World Health Organization.

  6. Deep Sequencing Reveals Novel Genetic Variants in Children with Acute Liver Failure and Tissue Evidence of Impaired Energy Metabolism

    OpenAIRE

    Valencia, C. Alexander; Wang, Xinjian; Wang, Jin; Peters, Anna; Simmons, Julia R.; Moran, Molly C.; Mathur, Abhinav; Husami, Ammar; Qian, Yaping; Sheridan, Rachel; Bove, Kevin E.; Witte, David; Huang, Taosheng; Miethke, Alexander G.

    2016-01-01

    Background & Aims The etiology of acute liver failure (ALF) remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism. Methods Twelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were selected from a retrospective cohort of 74 subjects with ALF because their fixed and frozen liver sampl...

  7. Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    E Louise Thomas; Audrey E Brynes; Gavin Hamilton; Nayna Patel; Adam Spong; Robert D Goldin; Gary Frost; Jimmy D Bell; Simon D Taylor-Robinson

    2006-01-01

    AIM: To assess the effectiveness of the current UK clinical practice in reducing hepatic fat (IHCL).METHODS: Whole body MRI and 1H MRS were obtained, before and after 6 mo nutritional counselling,from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease (NAFLD).RESULTS: A 500 Kcal-restricted diet resulted in an average weight loss of 4% (-3.4 kg,) accompanied by significant reductions in most adipose tissue (AT)depots, including subcutaneous (-9.9%), abdominal subcutaneous (-10.2%) and intra-abdominalAT (-11.4%). Intramyocellular lipids (IMCL) were significantly reduced in the tibialis muscle (-28.2%).Decreases in both IHCL (-39.9%) and soleus IMCL (-12.2%) content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT,but not with changes in IHCL.CONCLUSION: This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LFTs.

  8. Effects of Liver Fibrosis Progression on Tissue Relaxation Times in Different Mouse Models Assessed by Ultrahigh Field Magnetic Resonance Imaging.

    Science.gov (United States)

    Müller, Andreas; Hochrath, Katrin; Stroeder, Jonas; Hittatiya, Kanishka; Schneider, Günther; Lammert, Frank; Buecker, Arno; Fries, Peter

    2017-01-01

    Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 and T2(⁎) may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 and T2(⁎) in different models of liver fibrosis to compare alternate pathophysiologies in their effects on relaxation times and to further develop noninvasive quantification methods of liver fibrosis. MRI was performed with a fast spin echo sequence for measurement of T1 and a multigradient echo sequence for determination of T2(⁎). Toxic liver fibrosis was induced by injections of carbon tetrachloride (1.4 mL CCl4 per kg bodyweight and week, for 3 or 6 weeks) in BALB/cJ mice. Chronic sclerosing cholangitis was mimicked using the ATP-binding cassette transporter B4 knockout (Abcb4 (-/-)) mouse model. Untreated BALB/cJ mice served as controls. To assess hepatic fibrosis, we ascertained collagen contents and fibrosis scores after Sirius red staining. T1 and T2(⁎) correlate differently to disease severity and etiology of liver fibrosis. T2(⁎) shows significant decrease correlating with fibrosis in CCl4 treated animals, while demonstrating significant increase with disease severity in Abcb4 (-/-) mice. Measurements of T1 and T2(⁎) may therefore facilitate discrimination between different stages and causes of liver fibrosis.

  9. Effects of Liver Fibrosis Progression on Tissue Relaxation Times in Different Mouse Models Assessed by Ultrahigh Field Magnetic Resonance Imaging

    Science.gov (United States)

    Müller, Andreas; Hochrath, Katrin; Stroeder, Jonas; Hittatiya, Kanishka; Schneider, Günther; Lammert, Frank; Buecker, Arno

    2017-01-01

    Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 and T2⁎ may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 and T2⁎ in different models of liver fibrosis to compare alternate pathophysiologies in their effects on relaxation times and to further develop noninvasive quantification methods of liver fibrosis. MRI was performed with a fast spin echo sequence for measurement of T1 and a multigradient echo sequence for determination of T2⁎. Toxic liver fibrosis was induced by injections of carbon tetrachloride (1.4 mL CCl4 per kg bodyweight and week, for 3 or 6 weeks) in BALB/cJ mice. Chronic sclerosing cholangitis was mimicked using the ATP-binding cassette transporter B4 knockout (Abcb4 −/−) mouse model. Untreated BALB/cJ mice served as controls. To assess hepatic fibrosis, we ascertained collagen contents and fibrosis scores after Sirius red staining. T1 and T2⁎ correlate differently to disease severity and etiology of liver fibrosis. T2⁎ shows significant decrease correlating with fibrosis in CCl4 treated animals, while demonstrating significant increase with disease severity in Abcb4 −/− mice. Measurements of T1 and T2⁎ may therefore facilitate discrimination between different stages and causes of liver fibrosis. PMID:28194423

  10. [Study on expression of Fas/FasL and HBV antigens in liver tissue of patients with hepatitis B].

    Science.gov (United States)

    Wang, H; Hu, J; Zhu, K

    2001-03-01

    To evaluate the role of apoptosis mediated by Fas/FasL in the liver of hepatitis B and the expression status of Fas, FasL, and HBV antigens. We studied the expression of Fas antigen, Fas-ligand (FasL) and hepatitis B virus(HBV) antigens(HBsAg and HBcAg) in the livers of 62 patients with hepatitis B using immunohistochemistry ABC method. Six normal liver samples were used as control. Hepatocytes in normal liver had no Fas/FasL expression, but in the cases of hepatitis B, Fas was expressed mainly in the cytoplasm in 58 cases(93.5%); FasL was observed in infiltrating mononuclear cells and in the cytoplasm of hepatocytes in 37 cases (59.7%). The expressions of Fas/FasL were closely related to the liver histological inflammation degrees. The apoptosis mediated by Fas/FasL may play an important role in the hepatocellular injury in hepatitis B. No correlation was found between the degrees of Fas/FasL expression and the presence of HBsAg and HBcAg in the liver.

  11. Effects of Liver Fibrosis Progression on Tissue Relaxation Times in Different Mouse Models Assessed by Ultrahigh Field Magnetic Resonance Imaging

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    Andreas Müller

    2017-01-01

    Full Text Available Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 and T2⁎ may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 and T2⁎ in different models of liver fibrosis to compare alternate pathophysiologies in their effects on relaxation times and to further develop noninvasive quantification methods of liver fibrosis. MRI was performed with a fast spin echo sequence for measurement of T1 and a multigradient echo sequence for determination of T2⁎. Toxic liver fibrosis was induced by injections of carbon tetrachloride (1.4 mL CCl4 per kg bodyweight and week, for 3 or 6 weeks in BALB/cJ mice. Chronic sclerosing cholangitis was mimicked using the ATP-binding cassette transporter B4 knockout (Abcb4 -/- mouse model. Untreated BALB/cJ mice served as controls. To assess hepatic fibrosis, we ascertained collagen contents and fibrosis scores after Sirius red staining. T1 and T2⁎ correlate differently to disease severity and etiology of liver fibrosis. T2⁎ shows significant decrease correlating with fibrosis in CCl4 treated animals, while demonstrating significant increase with disease severity in Abcb4 -/- mice. Measurements of T1 and T2⁎ may therefore facilitate discrimination between different stages and causes of liver fibrosis.

  12. "Comparative Glutathione S-Transferases (GSTs Inhibition Assay in the Whole Extract of Fasciola hepatica and Sheep Liver Tissue by Hexachlorophene"

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    A Farahnak

    2001-09-01

    Full Text Available Recent research highlights the importance of GSTs in the establishment of chronic helminth infections. GSTs have the potential to protect the parasite against the host immune response. In this present study, GST enzyme assay has been investigated on whole extract of F. hepatica and sheep liver tissue. To the 1-ml plastic cuvette, added 200 mM potassium phosphate buffer. Then added 50 Mm GSH reduced. Was placed the required volume of F. hepatica or sheep liver extract into the cuvette and mixed well. Added water and equilibrated at room temperature for 5 minutes. Meanwhile was set up the UV spectrophotometer at 340 nm for the GST assay. Finally was placed the cuvette into the barrel of the UV spectrophotometer and added 1-chloro-2, 4-dinitorbenzene (CDNB and stirred well. For testing an inhibitor of GSTs such as hexachlorophene, mixed the appropriate volume of compound with GSH,reduced buffer, water and protein before equilibrating at room temperature. For calculation of IC50% value a computer package was used. The inhibitor concentration for 50% remaining activity of GSTs calculated graphically and wasobtained 10µl for F. hepatica and 20 µl for liver tissue.

  13. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

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    Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W; Becker, Lance B

    2016-01-01

    Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  14. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

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    Junhwan Kim

    2016-01-01

    Full Text Available Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  15. Modeling function-perfusion behavior in liver lobules including tissue, blood, glucose, lactate and glycogen by use of a coupled two-scale PDE-ODE approach.

    Science.gov (United States)

    Ricken, T; Werner, D; Holzhütter, H G; König, M; Dahmen, U; Dirsch, O

    2015-06-01

    This study focuses on a two-scale, continuum multicomponent model for the description of blood perfusion and cell metabolism in the liver. The model accounts for a spatial and time depending hydro-diffusion-advection-reaction description. We consider a solid-phase (tissue) containing glycogen and a fluid-phase (blood) containing glucose as well as lactate. The five-component model is enhanced by a two-scale approach including a macroscale (sinusoidal level) and a microscale (cell level). The perfusion on the macroscale within the lobules is described by a homogenized multiphasic approach based on the theory of porous media (mixture theory combined with the concept of volume fraction). On macro level, we recall the basic mixture model, the governing equations as well as the constitutive framework including the solid (tissue) stress, blood pressure and solutes chemical potential. In view of the transport phenomena, we discuss the blood flow including transverse isotropic permeability, as well as the transport of solute concentrations including diffusion and advection. The continuum multicomponent model on the macroscale finally leads to a coupled system of partial differential equations (PDE). In contrast, the hepatic metabolism on the microscale (cell level) was modeled via a coupled system of ordinary differential equations (ODE). Again, we recall the constitutive relations for cell metabolism level. A finite element implementation of this framework is used to provide an illustrative example, describing the spatial and time-depending perfusion-metabolism processes in liver lobules that integrates perfusion and metabolism of the liver.

  16. Assessment of some heavy metals in the tissues (gills, liver and muscle) of Clarias gariepinus from Calabar River, Cross River State, South-eastern Nigeria

    Institute of Scientific and Technical Information of China (English)

    Akaninyene Paul Joseph; Victor Oscar Eyo; Andem BasseyAndem; Joseph Udo Idung

    2016-01-01

    Objective: To assess the pollution status of Calabar River in relation to the levels of heavy metal in the tissue of the African catfish [Clarias gariepinus (C. gariepinus)]. Methods: A total of 45 samples of C. gariepinus were purchased from fishermen on landing at Nsidung beach along Calabar River within three months (15 samples monthly) from June to August, 2014. The samples were then put into a cold box containing ice blocks immediately after buying from the fishermen. The fish samples were transported immediately to the Chemistry Laboratory, University of Calabar for digestion and heavy metal analysis. Portions of the muscle, gills and liver were removed from the fresh samples and oven dried at temperature of 120 °C to constant weight and digested using standard methods. The digested tissue portions were analyzed for lead, iron, manganese, cobalt, chromium and cadmium concentrations using atomic absorption spectrophotometer. Results: Mercury was not detected at all in the muscle, liver and gills of C. gariepinus. The mean ± SD of metals in liver of C. gariepinus were: (0.080 ± 0.014), (0.110 ± 0.014), (6.480 ± 1.279) and (0.295 ± 0.021) mg/kg for Cd, Cr, Fe and Mn, respectively. In the gills, heavy metals values were: (0.065 ± 0.021), (0.115 ± 0.035), (5.843 ± 0.558), and (0.345 ± 0.007) mg/kg for Cd, Cr, Fe and Mn, respectively. In the muscles, heavy metals values were (0.045 ± 0.021), (0.115 ± 0.353), (5.150 ± 1.075), and (0.187 ± 0.045) mg/kg for Cd, Cr, Fe and Mn, respectively. The general trend of metals accumulation in tissues of C. gariepinus showed a decreasing trend of Fe > Mn > Cr > Cd. Also, the metal accumulation in the three tissues showed a decreasing trend of liver > gills > muscle. Conclusions: The metal concentrations in the muscle, gills and liver of C. gariepinus were all below the World Health Organization acceptable range, and as such fishery resources from Calabar River are safe for consumption.

  17. Assessment of some heavy metals in the tissues (gills, liver and muscle of Clarias gariepinus from Calabar River, Cross River State, South-eastern Nigeria

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    Akaninyene Paul Joseph

    2016-06-01

    Full Text Available Objective: To assess the pollution status of Calabar River in relation to the levels of heavy metal in the tissue of the African catfish [Clarias gariepinus (C. gariepinus]. Methods: A total of 45 samples of C. gariepinus were purchased from fishermen on landing at Nsidung beach along Calabar River within three months (15 samples monthly from June to August, 2014. The samples were then put into a cold box containing ice blocks immediately after buying from the fishermen. The fish samples were transported immediately to the Chemistry Laboratory, University of Calabar for digestion and heavy metal analysis. Portions of the muscle, gills and liver were removed from the fresh samples and oven dried at temperature of 120 °C to constant weight and digested using standard methods. The digested tissue portions were analyzed for lead, iron, manganese, cobalt, chromium and cadmium concentrations using atomic absorption spectrophotometer. Results: Mercury was not detected at all in the muscle, liver and gills of C. gariepinus. The mean ± SD of metals in liver of C. gariepinus were: (0.080 ± 0.014, (0.110 ± 0.014, (6.480 ± 1.279 and (0.295 ± 0.021 mg/kg for Cd, Cr, Fe and Mn, respectively. In the gills, heavy metals values were: (0.065 ± 0.021, (0.115 ± 0.035, (5.843 ± 0.558, and (0.345 ± 0.007 mg/kg for Cd, Cr, Fe and Mn, respectively. In the muscles, heavy metals values were (0.045 ± 0.021, (0.115 ± 0.353, (5.150 ± 1.075, and (0.187 ± 0.045 mg/kg for Cd, Cr, Fe and Mn, respectively. The general trend of metals accumulation in tissues of C. gariepinus showed a decreasing trend of Fe > Mn > Cr > Cd. Also, the metal accumulation in the three tissues showed a decreasing trend of liver > gills > muscle. Conclusions: The metal concentrations in the muscle, gills and liver of C. gariepinus were all below the World Health Organization acceptable range, and as such fishery resources from Calabar River are safe for consumption.

  18. The Effects of Thyroid Hormones on Gene Expression of Acyl-Coenzyme A Thioesterases in Adipose Tissue and Liver of Mice.

    Science.gov (United States)

    Krause, Kerstin; Weiner, Juliane; Hönes, Sebastian; Klöting, Nora; Rijntjes, Eddy; Heiker, John T; Gebhardt, Claudia; Köhrle, Josef; Führer, Dagmar; Steinhoff, Karen; Hesse, Swen; Moeller, Lars C; Tönjes, Anke

    2015-09-01

    Thyroid hormones (TH) exert pleiotropic effects on glucose and lipid homeostasis. However, it is as yet unclear how TH regulate lipid storage and utilization in order to adapt to metabolic needs. Acyl-CoA thioesterases (ACOTs) have been proposed to play a regulatory role in the metabolism of fatty acids. We investigated the interaction between thyroid dysfunction and Acot expression in adipose tissues and livers of thyrotoxic and hypothyroid mice. Ten-week-old female C57BL/6NTac mice (n = 10/group) were made hyperthyroid by the application of L-thyroxine (2 µg/ml in drinking water) for 4 weeks. Hypothyroidism was induced in 10-week-old mice by feeding an iodine-free chow supplemented with 0.15% PTU for 4 weeks. We measured mRNA expression levels of Acot8, 11 and 13 in the liver and epididymal and inguinal white and brown adipose tissues (BAT). Furthermore, we investigated hepatic Acot gene expression in TRα- and TRβ-deficient mice. We showed that the expression of Acot8, 11 and 13 is predominantly stimulated by a thyrotoxic state in the epididymal white adipose tissue. In contrast, hypothyroidism predominantly induces the expression of Acot8 in BAT in comparison with BAT of thyrotoxic and euthyroid mice (p adipose tissue. In liver, Acot gene expression is collectively elicited by a thyrotoxic state. These data suggest that ACOTs are targets of TH and are likely to influence 3,5,3'-triiodo-L-thyronine-orchestrated mechanisms of lipid uptake, storage and utilization to adapt the regulation of metabolic demands.

  19. Functional abolition of carotid body activity restores insulin action and glucose homeostasis in rats: key roles for visceral adipose tissue and the liver.

    Science.gov (United States)

    Sacramento, Joana F; Ribeiro, Maria J; Rodrigues, Tiago; Olea, Elena; Melo, Bernardete F; Guarino, Maria P; Fonseca-Pinto, Rui; Ferreira, Cristiana R; Coelho, Joana; Obeso, Ana; Seiça, Raquel; Matafome, Paulo; Conde, Sílvia V

    2017-01-01

    We recently described that carotid body (CB) over-activation is involved in the aetiology of insulin resistance and arterial hypertension in animal models of the metabolic syndrome. Additionally, we have demonstrated that CB activity is increased in animal models of insulin resistance, and that carotid sinus nerve (CSN) resection prevents the development of insulin resistance and arterial hypertension induced by high-energy diets. Here, we tested whether the functional abolition of CB by CSN transection would reverse pre-established insulin resistance, dyslipidaemia, obesity, autonomic dysfunction and hypertension in animal models of the metabolic syndrome. The effect of CSN resection on insulin signalling pathways and tissue-specific glucose uptake was evaluated in skeletal muscle, adipose tissue and liver. Experiments were performed in male Wistar rats submitted to two high-energy diets: a high-fat diet, representing a model of insulin resistance, hypertension and obesity, and a high-sucrose diet, representing a lean model of insulin resistance and hypertension. Half of each group was submitted to chronic bilateral resection of the CSN. Age-matched control rats were also used. CSN resection normalised systemic sympathetic nervous system activity and reversed weight gain induced by high-energy diets. It also normalised plasma glucose and insulin levels, insulin sensitivity lipid profile, arterial pressure and endothelial function by improving glucose uptake by the liver and perienteric adipose tissue. We concluded that functional abolition of CB activity restores insulin sensitivity and glucose homeostasis by positively affecting insulin signalling pathways in visceral adipose tissue and liver.

  20. Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss

    Science.gov (United States)

    Schmitz, J.; Evers, N.; Awazawa, M.; Nicholls, H.T.; Brönneke, H.S.; Dietrich, A.; Mauer, J.; Blüher, M.; Brüning, J.C.

    2016-01-01

    Objective Obesity represents a major risk factor for the development of type 2 diabetes mellitus, atherosclerosis and certain cancer entities. Treatment of obesity is hindered by the long-term maintenance of initially reduced body weight, and it remains unclear whether all pathologies associated with obesity are fully reversible even upon successfully maintained weight loss. Methods We compared high fat diet-fed, weight reduced and lean mice in terms of body weight development, adipose tissue and liver insulin sensitivity as well as inflammatory gene expression. Moreover, we assessed similar parameters in a human cohort before and after bariatric surgery. Results Compared to lean animals, mice that demonstrated successful weight reduction showed increased weight gain following exposure to ad libitum control diet. However, pair-feeding weight-reduced mice with lean controls efficiently stabilized body weight, indicating that hyperphagia was the predominant cause for the observed weight regain. Additionally, whereas glucose tolerance improved rapidly after weight loss, systemic insulin resistance was retained and ameliorated only upon prolonged pair-feeding. Weight loss enhanced insulin action and resolved pro-inflammatory gene expression exclusively in the liver, whereas visceral adipose tissue displayed no significant improvement of metabolic and inflammatory parameters compared to obese mice. Similarly, bariatric surgery in humans (n = 55) resulted in massive weight reduction, improved hepatic inflammation and systemic glucose homeostasis, while adipose tissue inflammation remained unaffected and adipocyte-autonomous insulin action only exhibit minor improvements in a subgroup of patients (42%). Conclusions These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue

  1. Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss.

    Science.gov (United States)

    Schmitz, J; Evers, N; Awazawa, M; Nicholls, H T; Brönneke, H S; Dietrich, A; Mauer, J; Blüher, M; Brüning, J C

    2016-05-01

    Obesity represents a major risk factor for the development of type 2 diabetes mellitus, atherosclerosis and certain cancer entities. Treatment of obesity is hindered by the long-term maintenance of initially reduced body weight, and it remains unclear whether all pathologies associated with obesity are fully reversible even upon successfully maintained weight loss. We compared high fat diet-fed, weight reduced and lean mice in terms of body weight development, adipose tissue and liver insulin sensitivity as well as inflammatory gene expression. Moreover, we assessed similar parameters in a human cohort before and after bariatric surgery. Compared to lean animals, mice that demonstrated successful weight reduction showed increased weight gain following exposure to ad libitum control diet. However, pair-feeding weight-reduced mice with lean controls efficiently stabilized body weight, indicating that hyperphagia was the predominant cause for the observed weight regain. Additionally, whereas glucose tolerance improved rapidly after weight loss, systemic insulin resistance was retained and ameliorated only upon prolonged pair-feeding. Weight loss enhanced insulin action and resolved pro-inflammatory gene expression exclusively in the liver, whereas visceral adipose tissue displayed no significant improvement of metabolic and inflammatory parameters compared to obese mice. Similarly, bariatric surgery in humans (n = 55) resulted in massive weight reduction, improved hepatic inflammation and systemic glucose homeostasis, while adipose tissue inflammation remained unaffected and adipocyte-autonomous insulin action only exhibit minor improvements in a subgroup of patients (42%). These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as

  2. High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice.

    Science.gov (United States)

    van der Heijden, Roel A; Sheedfar, Fareeba; Morrison, Martine C; Hommelberg, Pascal P H; Kor, Danny; Kloosterhuis, Niels J; Gruben, Nanda; Youssef, Sameh A; de Bruin, Alain; Hofker, Marten H; Kleemann, Robert; Koonen, Debby P Y; Heeringa, Peter

    2015-04-01

    Metabolic inflammation in adipose tissue and the liver is frequently observed as a result of diet-induced obesity in human and rodent studies. Although the adipose tissue and the liver are both prone to become chronically inflamed with prolonged obesity, their individual contribution to the development of metabolic inflammation remains speculative. Thus, we aimed to elucidate the sequence of inflammatory events in adipose and hepatic tissues to determine their contribution to the development of metabolic inflammation and insulin resistance (IR) in diet-induced obesity. To confirm our hypothesis that adipose tissue (AT) inflammation is initiated prior to hepatic inflammation, C57BL/6J male mice were fed a low-fat diet (LFD; 10% kcal fat) or high-fat diet (HFD; 45% kcal fat) for either 24, 40 or 52 weeks. Lipid accumulation and inflammation was measured in AT and liver. Glucose tolerance was assessed and plasma levels of glucose, insulin, leptin and adiponectin were measured at various time points throughout the study. With HFD, C57BL/6j mice developed a progressive obese phenotype, accompanied by IR at 24 and 40 weeks of HFD, but IR was attenuated after 52 weeks of HFD. AT inflammation was present after 24 weeks of HFD, as indicated by the increased presence of crown-like structures and up-regulation of pro-inflammatory genes Tnf, Il1β, Mcp1 and F4/80. As hepatic inflammation was not detected until 40 weeks of HFD, we show that AT inflammation is established prior to the development of hepatic inflammation. Thus, AT inflammation is likely to have a greater contribution to the development of IR compared to hepatic inflammation.

  3. An LC-MS/MS method for the determination of salidroside and its metabolite p-tyrosol in rat liver tissues.

    Science.gov (United States)

    Guo, Na; Ding, Weimin; Wang, Yu; Hu, Zhiwei; Wang, Ziming; Wang, Yang

    2014-05-01

    Salidroside and its metabolite p-tyrosol are two major phenols in the genus Rhodiola L. (Crassulaceae). They have been confirmed to possess various pharmacological properties and are used for the prophylaxis and therapeutics of many diseases. Several analytical methods have been developed for the determination of the two compounds in plant materials and biological plasma matrices. However, these methods are not optimal for biological samples containing complex organic interferences, such as liver and brain tissues. This study aimed to further develop and validate a simple and specific LC-MS/MS method for the determination of salidroside and its metabolite p-tyrosol in rat liver tissues using paracetamol as the internal standard (IS). Salidroside and p-tyrosol with the IS paracetamol and liver tissues were used as model compounds and biological samples. Samples were processed by protein precipitation (PP) with methanol, the supernatant was dried under nitrogen and the residue was reconstituted in a mobile phase that consisted of a mixture of acetonitrile and water (1:9, v/v). Salidroside and p-tyrosol were detected in negative mode under multiple reaction monitoring (MRM) by a triple quadrupole tandem mass spectrometer coupled with electrospray ionization. Standard curves were linear over the concentration range of 50-2000 ng/mL with correlation coefficients of 0.995 or better for both salidroside and p-tyrosol. The intra- and inter-day accuracy for salidroside ranged between 104.90 and 112.73% with a precision of 3.51-14.27%. For p-tyrosol, the intra- and inter-day accuracy was between 92.38 and 100.59%, and the precision was 8.54% or less. The stability data showed that no significant degradation occurred under the experimental conditions. The recoveries were 111.44, 108.10, and 102.00% for salidroside at concentrations of 50, 500 and 2000 ng/mL, respectively, and were 105.44, 105.50, and 113.04% for tyrosol at concentrations of 50, 500 and 2000

  4. Dietary supplementation of thyme (Thymus vulgaris L.) essential oil during the lifetime of the rat: its effects on the antioxidant status in liver, kidney and heart tissues.

    Science.gov (United States)

    Youdim, K A; Deans, S G

    1999-09-08

    This study aimed not only to identify age-related changes in certain antioxidant systems, but to assess whether dietary supplementation of thyme oil could address the unfavourable antioxidant-pro-oxidant balance that occurs with age. The present study has shown that there were significant declines in the superoxide dismutase activities in the liver and heart of old rats, although kidney showed no decline. Liver glutathione peroxidase (GSHPx) activity was found to have increased significantly in old rats, while a significant decrease was observed in kidney. Heart GSHPX activity was not found to differ significantly between young and old rats. There were also significant declines in the total antioxidant status in each tissue examined. A general feature of these various antioxidant parameters measured was that their activities remained higher in rats whose diets were supplemented with thyme oil, suggesting that they retained a more favourable antioxidant capacity during their life span.

  5. Synthesis and tissue distribution of CoFe2O4 Nanoparticles Coated with DMSA in rats liver

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    Faranak Mansouri

    2016-07-01

    Full Text Available Objective(s: According to the unique properties of magnetic nanoparticles, their usages in medicine and industry have increased in the last decade. Due to the vital role of liver in the body, the accumulation of CoFe2O4 and CoFe2O4@DMSA was studied. Materials and Methods:The nanoparticles were synthesized by co-precipitation method and were coated with DMSA. The techniques XRD, TEM, DLS, FTIR, AGFM and UV-Visible spectroscopy were used to characterize the nanoparticles. Nanoparticles were injected intraperitoneally in rat and blood samples were collected from the rats’ heart, at 15 and 30 day post injection. The liver of each rat was removed and kept frozen at -70 oC. Results:The size of the pure cobalt ferrite and DMSA coated cobalt ferrite nanoparticles were about 10 nm and 12 nm, respectively. The saturation magnetization of CoFe2O4 and CoFe2O4@DMSA nanoparticles were 44.8 and 33 emu/g, respectively. Statistical analysis of the results indicated that cobalt ferrite nanoparticles were accumulated in liver in all groups. Conclusion: The accumulation of nanoparticles in liver was significantly higher than those of the control group and the level of liver iron accumulation was significantly lower after 30 days of injection in comparison with 15 days post injection in all groups.

  6. Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

    Science.gov (United States)

    Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

    2015-08-01

    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P brain (P brain, liver, and kidney (all P brain (all P brain (P drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences.

  7. Absence of effects of dietary wheat bran on the activities of some key enzymes of carbohydrate and lipid metabolism in mouse liver and adipose tissue.

    Science.gov (United States)

    Stanley, J C; Lambadarios, J A; Newsholme, E A

    1986-03-01

    1. The effects of a 100 g/kg dietary substitution of wheat bran on the body-weight gain, food consumption and faecal dry weight of mice given a high-sucrose diet and on the activities of some key enzymes of carbohydrate and lipid metabolism in liver and adipose tissue were studied. 2. Wheat bran had no effect on body-weight gain, food consumption or faecal dry weight. 3. Wheat bran had no effect on the activities of hepatic glucose-6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) (EC 1.1.1.40), ATP-citrate (pro-3S)-lyase (EC 4.1.3.8), pyruvate kinase (EC 2.7.1.40) and fructose-1,6-bisphosphatase (EC 3.1.3.11). The activity of hepatic 6-phosphofructokinase (EC 2.7.1.11) increased but only when expressed on a body-weight basis. 4. Wheat bran had no effect on the activities of adipose tissue glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+), ATP-citrate (pro-3S)-lyase, hexokinase (EC 2.7.1.1), 6-phosphofructokinase and pyruvate kinase. 5. These results suggest that unlike guar gum and bagasse, wheat bran does not change the flux through some pathways of lipogenesis in liver and adipose tissue when mice are given high-sucrose diets.

  8. Sonographically measured suprailiac adipose tissue is a useful predictor of non-alcoholic fatty liver disease in obese children and adolescents.

    Science.gov (United States)

    Schlieske, C; Denzer, C; Wabitsch, M; Oeztuerk, S; Mason, R A; Thiere, D; Kratzer, W

    2015-08-01

    The objective of the present study was to identify ultrasonographic and anthropometric parameters that are highly associated with the presence of non-alcoholic fatty liver disease (NAFLD) in overweight children and adolescents. A total of 447 overweight children and adolescents (body mass index, 32.4 ± 5.2 kg m(-2) ; mean age, 14.2 ± 1.9 years; range 10.1-20.3 years) were analysed. Subjects underwent ultrasound examination of the liver as well as ultrasonographic measurement of the amount of adipose tissue overlying the biceps brachii and triceps brachii muscles, and of subscapular, suprailiac and abdominal subcutaneous adipose tissue and intra-abdominal depth. Anthropometric parameters such as body mass index, waist and hip circumference were documented. The prevalence of NAFLD was 27.1%; it was significantly associated with the above-cited anthropometric parameters (P children and adolescents, we identified intra-abdominal depth for both gender and the ultrasonographically easily determined subcutaneous suprailiac adipose tissue in females as independent predictor of NAFLD. © 2014 World Obesity.

  9. Characterization of Purified Glutathione S-Transferase (GSTs from Fasciola hepatica and Liver Tissue by Two-Dimensional Electrophoresis (2-DE

    Directory of Open Access Journals (Sweden)

    A Farahnak 1

    2005-07-01

    Full Text Available Two-dimensional electrophoresis (2-D electrophoresis is a powerful and extensively used method for analysis of complex protein mixtures extracted from cells, tissue, or other biological samples such as helminth parasites including, F. hepatica. Each spot on the resulting two-dimensional collection corresponds to a single protein species in the sample. This study was carried out to detect of GSTs isoenzyme spots map for collection of highly specific proteins. For this purpose, GSTs were purified from adult parasite of F.hepatica and sheep liver tissue as an enzyme pool by a glutathione affinity matrix using a wash-bath method and investigated for sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE pattern. For 2-DE, purified GSTs from F.hepatica and sheep liver tissue were resuspended in sample buffer and then run on a IPG strip in the first dimension and then on an Excel Gel SDS in the second dimension before protein spots staining with Coomassie blue. The obtaining spots in the gels were compared and GSTs protein spots were detected with similar molecular weight, 26 kDa. The protein spots which are recorded in this paper could be GSTs isoenzymes and are highly specific peptids. These findings may be considered for vaccination or chemotherapeutic targets in sheep and human fascioliasis.

  10. T1-Weighted MR imaging of liver tumor by gadolinium-encapsulated glycol chitosan nanoparticles without non-specific toxicity in normal tissues

    Science.gov (United States)

    Na, Jin Hee; Lee, Sangmin; Koo, Heebeom; Han, Hyounkoo; Lee, Kyung Eun; Han, Seung Jin; Choi, Seung Hong; Kim, Hyuncheol; Lee, Seulki; Kwon, Ick Chan; Choi, Kuiwon; Kim, Kwangmeyung

    2016-05-01

    Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the amine groups on the surface of Gd(iii)-CNPs could be protonated and could induce fast cellular uptake at acidic pH in tumor tissue. To assay the tumor-targeting ability of Cy5.5-labeled Gd(iii)-CNPs, near-infrared fluorescence (NIRF) imaging and MR imaging were used in a liver tumor model as well as a subcutaneous tumor model. Cy5.5-labeled Gd(iii)-CNPs generated highly intense fluorescence and T1 MR signals in tumor tissues after intravenous injection, while DOTAREM®, the commercialized control MR contrast agent, showed very low tumor-targeting efficiency on MR images. Furthermore, damaged tissues were found in the livers and kidneys of mice injected with DOTAREM®, but there were no obvious adverse effects with Gd(iii)-CNPs. Taken together, these results demonstrate the superiority of Gd(iii)-CNPs as a tumor-targeting T1 MR agent.Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the

  11. Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: liver effects.

    Science.gov (United States)

    Yoo, Hong Sik; Bradford, Blair U; Kosyk, Oksana; Shymonyak, Svitlana; Uehara, Takeki; Collins, Leonard B; Bodnar, Wanda M; Ball, Louise M; Gold, Avram; Rusyn, Ivan

    2015-01-01

    Trichloroethylene (TCE) is a widely used organic solvent. Although TCE is classified as carcinogenic to humans, substantial gaps remain in our understanding of interindividual variability in TCE metabolism and toxicity, especially in the liver. A hypothesis was tested that amounts of oxidative metabolites of TCE in mouse liver are associated with hepatic-specific toxicity. Oral dosing with TCE was conducted in subacute (600 mg/kg/d; 5 d; 7 inbred mouse strains) and subchronic (100 or 400 mg/kg/d; 1, 2, or 4 wk; 2 inbred mouse strains) designs. The quantitative relationship was evaluated between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P-450-mediated oxidation (trichloroacetic acid [TCA], dichloroacetic acid [DCA], and trichloroethanol) and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione] in serum and liver, and various hepatic toxicity phenotypes. In subacute study, interstrain variability in TCE metabolite amounts was observed in serum and liver. No marked induction of Cyp2e1 protein levels in liver was detected. Serum and hepatic levels of TCA and DCA were correlated with increased transcription of peroxisome proliferator-marker genes Cyp4a10 and Acox1 but not with degree of induction in hepatocellular proliferation. In subchronic study, serum and liver levels of oxidative metabolites gradually decreased over time despite continuous dosing. Hepatic protein levels of CYP2E1, ADH, and ALDH2 were unaffected by treatment with TCE. While the magnitude of induction of peroxisome proliferator-marker genes also declined, hepatocellular proliferation increased. This study offers a unique opportunity to provide a scientific data-driven rationale for some of the major assumptions in human health assessment of TCE.

  12. Study on Glutathione S-Transferase (GST Inhibition Assay by Triclabendazole. І: Protoscoleces (Hydatid Cyst; Echinococcus granulosus and Sheep Liver Tissue

    Directory of Open Access Journals (Sweden)

    MA Seyyedi

    2005-06-01

    Full Text Available Hydatid disease is a term used to refer infection with the methacestode of Echinococcus granulosus parasite in humans, and echinococcusis is restricted to infection with the adult stage in carnivores.Glutathione S-Transferase (GST represents the major class of detoxification enzymes from helminth parasites such as Echinococcus protoscoleces (PSC and it is candidate for chemotherapeutic and vaccine design. Therefore, GST of protoscoleces could be a target for evaluation of drug effect as triclabendazole in hydatid cyst. For this purpose, GST enzymes were purified from protoscoleces of hydatid cyst and sheep liver tissue by glutathione affinity chromatography using a wash-batch method and subsequently detected their SDS-PAGE pattern. Afterward, GST specific activity levels were assayed in the whole extract and purified solutions spectrophotometrically at 30°C with reduced glutathione (GSH and 1-chloro-2, 4-dinitrobenzen (CDNB substrate. Finally, GST inhibition assay was investigated in the solutions by powder and bolus of triclabendazole. GST fraction as a 26 kDa (MW band was obtained on SDS-PAGE. The level of GST specific activity in purified solutions was detected 10.24 µmol/min/mg proteins for protoscoleces and 37.84 µmol/min/mg protein for liver tissue. Comparison of the effect of powder and bolus of triclabendazole in solutions revealed inhibition concentration (IC50 8.71 and 11.16 µg/ml for protoscoleces GST and 8.65 and 9.70 µg/ml for liver tissue GSTs, respectively. These findings suggest the possibility of selective inhibition of protoscoleces. GSTs by triclabendazol in vitro and use of these results for understanding of its molecular effect in vivo.

  13. Chronic subordination stress selectively downregulates the insulin signaling pathway in liver and skeletal muscle but not in adipose tissue of male mice.

    Science.gov (United States)

    Sanghez, Valentina; Cubuk, Cankut; Sebastián-Leon, Patricia; Carobbio, Stefania; Dopazo, Joaquin; Vidal-Puig, Antonio; Bartolomucci, Alessandro

    2016-01-01

    Chronic stress has been associated with obesity, glucose intolerance, and insulin resistance. We developed a model of chronic psychosocial stress (CPS) in which subordinate mice are vulnerable to obesity and the metabolic-like syndrome while dominant mice exhibit a healthy metabolic phenotype. Here we tested the hypothesis that the metabolic difference between subordinate and dominant mice is associated with changes in functional pathways relevant for insulin sensitivity, glucose and lipid homeostasis. Male mice were exposed to CPS for four weeks and fed either a standard diet or a high-fat diet (HFD). We first measured, by real-time PCR candidate genes, in the liver, skeletal muscle, and the perigonadal white adipose tissue (pWAT). Subsequently, we used a probabilistic analysis approach to analyze different ways in which signals can be transmitted across the pathways in each tissue. Results showed that subordinate mice displayed a drastic downregulation of the insulin pathway in liver and muscle, indicative of insulin resistance, already on standard diet. Conversely, pWAT showed molecular changes suggestive of facilitated fat deposition in an otherwise insulin-sensitive tissue. The molecular changes in subordinate mice fed a standard diet were greater compared to HFD-fed controls. Finally, dominant mice maintained a substantially normal metabolic and molecular phenotype even when fed a HFD. Overall, our data demonstrate that subordination stress is a potent stimulus for the downregulation of the insulin signaling pathway in liver and muscle and a major risk factor for the development of obesity, insulin resistance, and type 2 diabetes mellitus.

  14. Modular, pumpless body-on-a-chip platform for the co-culture of GI tract epithelium and 3D primary liver tissue.

    Science.gov (United States)

    Esch, Mandy B; Ueno, Hidetaka; Applegate, Dawn R; Shuler, Michael L

    2016-07-05

    We have developed an expandable modular body-on-a-chip system that allows for a plug-and-play approach with several in vitro tissues. The design consists of single-organ chips that are combined with each other to yield a multi-organ body-on-a-chip system. Fluidic flow through the organ chips is driven via gravity and controlled passively via hydraulic resistances of the microfluidic channel network. Such pumpless body-on-a-chip devices are inexpensive and easy to use. We tested the device by culturing GI tract tissue and liver tissue within the device. Integrated Ag/AgCl electrodes were used to measure the resistance across the GI tract cell layer. The transepithelial resistance (TEER) reached values between 250 to 650 Ω cm(2) throughout the 14 day co-culture period. These data indicate that the GI tract cells retained their viability and the GI tract layer as a whole retained its barrier function. Throughout the 14 day co-culture period we measured low amounts of aspartate aminotransferase (AST, ∼10-17.5 U L(-1)), indicating low rates of liver cell death. Metabolic rates of hepatocytes were comparable to those of hepatocytes in single-organ fluidic cell culture systems (albumin production ranged between 3-6 μg per day per million hepatocytes and urea production ranged between 150-200 μg per day per million hepatocytes). Induced CYP activities were higher than previously measured with microfluidic liver only systems.

  15. Tissue inhibitor of matrix metalloproteinase-1 expression in colorectal cancer liver metastases is associated with vascular structures

    DEFF Research Database (Denmark)

    Illemann, Martin; Eefsen, Rikke Helene Løvendahl; Bird, Nigel Charles

    2016-01-01

    , with significant higher levels in patients with metastatic disease. We therefore wanted to determine the expression pattern of TIMP-1 in primary colorectal cancers and their matching liver metastases. TIMP-1 mRNA was primarily seen in α-smooth-muscle actin (α-SMA)-positive cells. In all primary tumors and liver...... metastases with desmoplastic growth pattern, TIMP-1 mRNA was primarily found in α-SMA-positive myofibroblasts located at the invasive front. Some α-SMA-positive cells with TIMP-1 mRNA were located adjacent to CD34-positive endothelial cells, identifying them as pericytes. This indicates that TIMP-1...

  16. Hibernation impact on the catalytic activities of the mitochondrial D-3-hydroxybutyrate dehydrogenase in liver and brain tissues of jerboa (Jaculus orientalis

    Directory of Open Access Journals (Sweden)

    Hafiani Assia

    2003-09-01

    Full Text Available Abstract Background Jerboa (Jaculus orientalis is a deep hibernating rodent native to subdesert highlands. During hibernation, a high level of ketone bodies i.e. acetoacetate (AcAc and D-3-hydroxybutyrate (BOH are produced in liver, which are used in brain as energetic fuel. These compounds are bioconverted by mitochondrial D-3-hydroxybutyrate dehydrogenase (BDH E.C. 1.1.1.30. Here we report, the function and the expression of BDH in terms of catalytic activities, kinetic parameters, levels of protein and mRNA in both tissues i.e brain and liver, in relation to the hibernating process. Results We found that: 1/ In euthemic jerboa the specific activity in liver is 2.4- and 6.4- fold higher than in brain, respectively for AcAc reduction and for BOH oxidation. The same differences were found in the hibernation state. 2/ In euthermic jerboa, the Michaelis constants, KM BOH and KM NAD+ are different in liver and in brain while KM AcAc, KM NADH and the dissociation constants, KD NAD+and KD NADH are similar. 3/ During prehibernating state, as compared to euthermic state, the liver BDH activity is reduced by half, while kinetic constants are strongly increased except KD NAD+. 4/ During hibernating state, BDH activity is significantly enhanced, moreover, kinetic constants (KM and KD are strongly modified as compared to the euthermic state; i.e. KD NAD+ in liver and KM AcAc in brain decrease 5 and 3 times respectively, while KD NADH in brain strongly increases up to 5.6 fold. 5/ Both protein content and mRNA level of BDH remain unchanged during the cold adaptation process. Conclusions These results cumulatively explained and are consistent with the existence of two BDH enzymatic forms in the liver and the brain. The apoenzyme would be subjected to differential conformational folding depending on the hibernation state. This regulation could be a result of either post-translational modifications and/or a modification of the mitochondrial membrane state

  17. Dietary fat source affects metabolism of fatty acids in pigs as evaluated by altered expression of lipogenic genes in liver and adipose tissues

    DEFF Research Database (Denmark)

    Duran-Montge, P; Theil, Peter Kappel; Lauridsen, Charlotte

    2009-01-01

    ), linseed oil (LO), blend (FB) (55% T, 35% SFO and 10% LO) and fish oil (FO) blend (40% FO and 60% LO). Pigs were slaughtered at 100 kg BW and autopsies from liver, adipose tissue and muscle semimembranousus were collected for qPCR. The messenger ribonucleic acid (mRNA) abundances of genes related...... of seven dietary treatments (eight animals per treatment): a semi-synthetic diet containing a very low level of fat (no fat (NF)) and six fat-supplemented diets (ca. 10%) based on barley and soybean meal. The supplemental fat sources were tallow (T), high-oleic sunflower oil (HOSF), sunflower oil (SFO...

  18. 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 ...

  19. Augmenter of liver regeneration, a protective factor against ROS-induced oxidative damage in muscle tissue of mitochondrial myopathy affected patients.

    Science.gov (United States)

    Polimeno, Lorenzo; Rossi, Roberta; Mastrodonato, Maria; Montagnani, Monica; Piscitelli, Domenico; Pesetti, Barbara; De Benedictis, Leonarda; Girardi, Bruna; Resta, Leonardo; Napoli, Anna; Francavilla, Antonio

    2013-11-01

    Mitochondria-related myopathies (MM) are a group of different diseases defined by a varying degree of dysfunctions of the mitochondrial respiratory chain which leads to reactive oxygen species (ROS) generation followed by oxidative stress and cellular damage. In mitochondrial myopathy muscle tissue an overexpression of antioxidant enzymes has been documented probably as an attempt to counteract the free radical generation. We previously documented, in human non-pathological muscle fibres, the expression of the augmenter of liver regeneration (ALR), a sulfhydryl oxidase enzyme, whose presence is related to the mitochondria; indeed it has been demonstrated that ALR mainly localizes in the mitochondrial inter-membrane space. Furthermore we reported, in different experimental models, in vivo and in vitro, the anti-apoptotic and anti-oxidative capacities of ALR, achieved by up-regulating Bcl-2 anti-apoptotic family factors and the anti-apoptotic/anti-oxidative secretory isoform of clusterin (sClu). With the present study we aimed to determine ALR, Bcl-2 protein, clusterin and ROS expression in muscle tissue biopsies from MM-affected patients. Non-pathological muscle tissue was used as control. Enzymatic, histochemical, immunohistochemical and immune electron microscopy techniques were performed. The data obtained revealed in MM-derived muscle tissue, compared to non-pathological tissue, the over-expression of ROS, ALR and Bcl-2 and the induction of the nuclear, pro-apoptotic, isoform of clusterin (nCLU).

  20. Orosomucoid expression profiles in liver, adipose tissues and serum of lean and obese domestic pigs, Göttingen minipigs and Ossabaw minipigs.

    Science.gov (United States)

    Rødgaard, Tina; Stagsted, Jan; Christoffersen, Berit Ø; Cirera, Susanna; Moesgaard, Sophia G; Sturek, Michael; Alloosh, Mouhamad; Heegaard, Peter M H

    2013-02-15

    The acute phase protein orosomucoid (ORM) has anti-inflammatory and immunomodulatory effects, and may play an important role in the maintenance of metabolic homeostasis in obesity-induced low-grade inflammation. Even though the pig is a widely used model for obesity related metabolic symptoms, the expression of ORM has not yet been characterized in such pig models. The objective of this study was to investigate the expression of ORM1 mRNA in liver, visceral adipose tissue, subcutaneous adipose tissue (SAT) from the abdomen or retroperitoneal abdominal adipose tissue (RPAT) and SAT from the neck, as well as the serum concentration of ORM protein in three porcine obesity models; the domestic pig, Göttingen minipigs and Ossabaw minipigs. No changes in ORM1 mRNA expression were observed in obese pigs compared to lean pigs in the four types of tissues. However, obese Ossabaw minipigs, but none of the other breeds, showed significantly elevated ORM serum concentrations compared to their lean counterparts. Studies in humans have shown that the expression of ORM was unchanged in adipose tissue depots in obese humans with an increased serum concentration of ORM. Thus in this respect, obese Ossabaw minipigs behave more similarly to obese humans than the other two pig breeds investigated.

  1. Arsenic trioxide treatment of rabbit liver VX-2 carcinoma via hepatic arterial cannulation-induced apoptosis and decreased levels of survivin in the tumor tissue.

    Science.gov (United States)

    Li, Hong; Gong, Jian; Jiang, Xuyuan; Shao, Haibo

    2013-02-01

    To investigate the role of tumor apoptosis-inhibitory protein survivin in arsenic trioxide-induced apoptosis in VX-2 carcinoma in the rabbit liver by means of transcatheter arterial chemoembolization. Sixteen rabbits with 32 implanted hepatic VX-2 tumors were randomly divided into two groups. The experimental group received 2 mg of arsenic trioxide and 1 mL of ultra-fluid lipiodol co-injected via hepatic arterial cannulation and the control group received only 1 mL of lipiodol. Animals were sacrificed 3 weeks after trans-catheterial arterial chemoembolization. Tumor tissue and tumor-peripheral tissue were collected for analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining was used to assess tumor cells apoptosis. Immunohistochemistry was used to assess the presence of survivin protein. Reverse transcription polymerase chain reaction was used to determine the expression of survivin gene. The number of apoptotic cells significantly increased in the tumor tissue (5.20 ± 0.60%) compared to tumor-peripheral tissue (1.29 ± 0.42%) of the arsenic trioxide-treated group. Survivin expression levels in the tumor tissue were significantly reduced in arsenic trioxide-treated group (7.68 ± 0.65) compared to the control group (35.30 ± 4.63). Transcatheter arterial chemoembolization with arsenic trioxide induced apoptosis of VX-2 carcinoma, in which tumor apoptosis-inhibitory protein survivin may have played a role.

  2. Tracing from fat tissue, liver, and pancreas: a neuroanatomical framework for the role of the brain in type 2 diabetes.

    NARCIS (Netherlands)

    Kreier, F.; Kap, Y.S.; Mettenleiter, T.C.; Heijningen, C. van; Vliet, J. van der; Kalsbeek, A.; Sauerwein, H.P.; Fliers, E.; Romijn, J.A.; Buijs, R.M.

    2006-01-01

    The hypothalamus uses hormones and the autonomic nervous system to balance energy fluxes in the body. Here we show that the autonomic nervous system has a distinct organization in different body compartments. The same neurons control intraabdominal organs (intraabdominal fat, liver, and pancreas), w

  3. Tissue localization of Toll-like receptors in biopsy specimens of liver from children infected with hepatitis C virus.

    Science.gov (United States)

    Mozer-Lisewska, I; Sluzewski, W; Kaczmarek, M; Jenek, R; Szczepanski, M; Figlerowicz, M; Kowala-Piaskowska, A; Zeromski, J

    2005-10-01

    Toll-like receptors (TLR) are important tools of innate immunity, localized mainly on cells of the immune system, but also have been shown on cells of other origin. In the current study, they have been searched in biopsy specimens of liver from children bearing chronic viral hepatitis of C type (HCV). TLR2, TLR3 and TLR4 were traced by means of polyclonal antibodies and avidin-biotin complex (ABC) immunohistochemistry. Besides, mRNA for TLR was looked for using specific primers and polymerase chain reaction. Several controls, including neutralization of primary antibody with respective blocking peptide, confirmed the specificity of the immunohistochemical reaction. All TLR tested could be visualized in a focal distribution in single hepatocytes and some cells of inflammatory infiltrates. There was no reaction whatsoever in liver samples not infected with hepatotropic virus. In molecular studies, mRNA for TLR2 and TLR4 was detected in both noninfected and hepatitis B virus-infected established cell lines of human hepatoma as well as in HCV(+) biopsy samples. These data indicate that TLR can be traced in liver cells, both at the protein and at the mRNA level. Their irregular and focal distribution in HCV(+), but not in HCV(-), liver suggests some role of TLR in the pathogenesis of chronic viral hepatitis, at least in children.

  4. Histochemical demonstration of two mercury pools in trout tissues: mercury in kidney and liver after mercuric chloride exposure

    DEFF Research Database (Denmark)

    Baatrup, E; Nielsen, M G; Danscher, G

    1987-01-01

    -exposed trout were subjected to selenium (as Na2SeO3), administered intraperitoneally 2 hr before fixation. Following this treatment, additional mercury could be visualized in the kidney circulatory system, including glomeruli, and in the nucleus and endoplasmic reticulum of liver cells. It is suggested...

  5. Thromboxane A{sub 2} receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment

    Energy Technology Data Exchange (ETDEWEB)

    Minamino, Tsutomu [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ito, Yoshiya [Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ohkubo, Hirotoki [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Hosono, Kanako; Suzuki, Tatsunori [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sato, Takehito [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ae, Takako; Shibuya, Akitaka [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sakagami, Hiroyuki [Departments of Anatomy, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Narumiya, Shuh [Department of Pharmacology, Kyoto University School of Medicine, Kyoto, 606-8315 (Japan); Koizumi, Wasaburo [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Majima, Masataka, E-mail: mmajima@med.kitasato-u.ac.jp [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan)

    2012-02-15

    It is thought that thromboxane A{sub 2} (TxA{sub 2}) contributes to the progression of inflammation during acute hepatic injury; however, it is still unknown whether TxA{sub 2} is involved in liver repair. The objective of the present study was to examine the role of TxA{sub 2} receptor (TP) signaling in liver injury and repair in response to toxic injury. Carbon tetrachloride (CCl{sub 4}) was used to induce liver injury in TP knockout (TP{sup −/−}) mice and wild-type (WT) mice. In WT mice, serum levels of alanine aminotransferase (ALT) and the size of the necrotic area peaked at 24 and 48 h, respectively, and then declined. In TP{sup −/−} mice, the changes in ALT levels were similar to WT mice, but liver regeneration was impaired as evidenced by remained elevated levels of hepatic necrosis and by delayed hepatocyte proliferation, which was associated with the reduced expression of growth factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and hepatocyte growth factor (HGF). In TP{sup −/−} mice, the accumulation of hepatic CD11b{sup +}/F4/80{sup +} macrophages in injured livers was attenuated, and the hepatic expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, the C―C chemokine receptor (CCR2), was reduced compared to WT. Additionally, the application of the TP receptor agonist, U-46619, enhanced the expression of MCP-1/CCL2 and CCR2 in peritoneal macrophages, which was associated with increased levels of IL-6, TNFα and HGF. These results suggested that TP receptor signaling facilitates liver recovery following CCl{sub 4}-induced hepatotoxicity by affecting the expression of hepatotrophic growth factors, and through the recruitment of macrophages mediated by MCP-1/CCL2-CCR2 expression. -- Highlights: ► TP enhances liver regeneration by CCl{sub 4}. ► TP accumulates macrophages. ► TP up-regulates MCP-1.

  6. THE TISSUE HYDRATION STATE IN UW-PRESERVED HUMAN DONOR LIVERS - A CLINICAL-STUDY OF THE RELATION BETWEEN PROTON MAGNETIC-RESONANCE RELAXATION-TIMES, DONOR CONDITION, PRESERVATION PROCEDURE, AND EARLY GRAFT FUNCTION

    NARCIS (Netherlands)

    WOLF, RFE; DENBUTTER, G; KAMMAN, RL; DEKETH, HP; SLUTTER, WJ; SLOOFF, MJH

    1994-01-01

    To determine the relation between tissue hydration state-as indicated by tissue proton magnetic resonance relaxation times-in UW-preserved human donor livers and viability parameters of the donor and early graft function, ''ex vivo'' magnetic resonance relaxometry was performed with a clinical MR im

  7. THE TISSUE HYDRATION STATE IN UW-PRESERVED HUMAN DONOR LIVERS - A CLINICAL-STUDY OF THE RELATION BETWEEN PROTON MAGNETIC-RESONANCE RELAXATION-TIMES, DONOR CONDITION, PRESERVATION PROCEDURE, AND EARLY GRAFT FUNCTION

    NARCIS (Netherlands)

    WOLF, RFE; DENBUTTER, G; KAMMAN, RL; DEKETH, HP; SLUTTER, WJ; SLOOFF, MJH

    1994-01-01

    To determine the relation between tissue hydration state-as indicated by tissue proton magnetic resonance relaxation times-in UW-preserved human donor livers and viability parameters of the donor and early graft function, ''ex vivo'' magnetic resonance relaxometry was performed with a clinical MR

  8. Levels of metals in kidney, liver and muscle tissue and their relation to the occurrence of parasites in the red fox in the Lower Silesian Forest in Europe.

    Science.gov (United States)

    Binkowski, Łukasz J; Merta, Dorota; Przystupińska, Anna; Sołtysiak, Zenon; Pacoń, Jarosław; Stawarz, Robert

    2016-04-01

    Together with the occurrence of parasites, increased concentrations of xenobiotics, to which scavengers are greatly exposed, may significantly influence the physiology of red foxes. It is also suspected that these two factors interact. The accumulation of various metals (Ca, Cd, Cu, Fe, Hg, K, Mg, Ni, Pb, Zn) in kidney, liver and muscle tissue was investigated, as well as the occurrence of parasites, and the potential link to the presence of metals. Generally speaking, neither sex nor age influenced these concentrations. K, Mg and Fe were found in the highest concentrations and Hg was found in the lowest. Various relationships between the concentrations of metals were observed in the tissues. 34% of the specimens studied were hosts to parasites. No clear, significant connection between the concentrations and the occurrence of parasites was noted, but the discernible trend confirmed by the logistic regression, needs further study.

  9. Reduction of obesity-associated white adipose tissue inflammation by rosiglitazone is associated with reduced non-alcoholic fatty liver disease in LDLr-deficient mice

    Science.gov (United States)

    Mulder, Petra; Morrison, Martine C.; Verschuren, Lars; Liang, Wen; van Bockel, J. Hajo; Kooistra, Teake; Wielinga, Peter Y.; Kleemann, Robert

    2016-01-01

    Obesity is associated with chronic low-grade inflammation that drives the development of metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). We recently showed that white adipose tissue (WAT) constitutes an important source of inflammatory factors. Hence, interventions that attenuate WAT inflammation may reduce NAFLD development. Male LDLr−/− mice were fed a high-fat diet (HFD) for 9 weeks followed by 7 weeks of HFD with or without rosiglitazone. Effects on WAT inflammation and NAFLD development were analyzed using biochemical and (immuno)histochemical techniques, combined with gene expression analyses. Nine weeks of HFD feeding induced obesity and WAT inflammation, which progressed gradually until the end of the study. Rosiglitazone fully blocked progression of WAT inflammation and activated PPARγ significantly in WAT. Rosiglitazone intervention did not activate PPARγ in liver, but improved liver histology and counteracted the expression of genes associated with severe NAFLD in humans. Rosiglitazone reduced expression of pro-inflammatory factors in WAT (TNF-α, leptin) and increased expression of adiponectin, which was reflected in plasma. Furthermore, rosiglitazone lowered circulating levels of pro-inflammatory saturated fatty acids. Together, these observations provide a rationale for the observed indirect hepatoprotective effects and suggest that WAT represents a promising therapeutic target for the treatment of obesity-associated NAFLD. PMID:27545964

  10. The {sup 57}Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    Energy Technology Data Exchange (ETDEWEB)

    Oshtrakh, M. I., E-mail: oshtrakh@gmail.com; Alenkina, I. V. [Ural Federal University, Department of Physical Techniques and Devices for Quality Control, Institute of Physics and Technology (Russian Federation); Vinogradov, A. V.; Konstantinova, T. S. [Ural State Medical University (Russian Federation); Semionkin, V. A. [Ural Federal University, Department of Physical Techniques and Devices for Quality Control, Institute of Physics and Technology (Russian Federation)

    2015-04-15

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the {sup 57}Fe hyperfine parameters for normal and patient’s tissues were detected and related to small variations in the {sup 57}Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients’ spleen and liver tissues.

  11. The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    Science.gov (United States)

    Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

    2015-04-01

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57Fe hyperfine parameters for normal and patient's tissues were detected and related to small variations in the 57Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients' spleen and liver tissues.

  12. Transarterial chemoembolization in soft-tissue sarcoma metastases to the liver – The use of imaging biomarkers as predictors of patient survival

    Energy Technology Data Exchange (ETDEWEB)

    Chapiro, Julius [Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, 1800 Orleans St, Baltimore, MD, USA 21287 (United States); Department of Diagnostic and Interventional Radiology, Charite Universitätsmedizin, Berlin (Germany); Duran, Rafael [Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, 1800 Orleans St, Baltimore, MD, USA 21287 (United States); Lin, MingDe [U/S Imaging and Interventions (UII), Philips Research North America, Briarcliff Manor, NY (United States); Mungo, Benedetto [Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD (United States); Schlachter, Todd; Schernthaner, Rüdiger [Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, 1800 Orleans St, Baltimore, MD, USA 21287 (United States); Gorodetski, Boris [Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, 1800 Orleans St, Baltimore, MD, USA 21287 (United States); Department of Diagnostic and Interventional Radiology, Charite Universitätsmedizin, Berlin (Germany); Wang, Zhijun [Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, 1800 Orleans St, Baltimore, MD, USA 21287 (United States); and others

    2015-03-15

    Highlights: •TACE is effective in achieving tumor response in sarcoma liver metastases. •Enhancement-based response criteria are beneficial as compared to RECIST. •3D quantitative image response assessment is the best predictor of survival. -- Abstract: Background: The clinical management of patients with metastatic soft-tissue sarcoma of the liver is complicated by the paucity of reliable clinical data. This study evaluated the safety profile, survival outcome as well as the role of imaging biomarkers of tumor response in metastatic soft-tissue sarcoma (mSTS) of the liver treated with conventional transarterial chemoembolization (cTACE). Materials/methods: This retrospective analysis included 30 patients with mSTS of the liver treated with cTACE. The safety profile, overall survival (OS) and progression-free survival (PFS) after the procedure were evaluated. Tumor response in each patient was assessed using RECIST, modified (m) RECIST and EASL guidelines. In addition, a 3D quantification of the enhancing tumor volume (quantitative [q] EASL) was performed. For each method, patients were classified as responders (R) and non-responders (NR), and evaluated using Kaplan-Meier and multivariate Cox proportional hazard ratio (HR) analysis. Results: No Grade III or IV toxicities were reported in a total of 77 procedures (mean, 2.6/patient). Median OS was 21.2 months (95% CI, 13.4–28.9) and PFS was 6.3 months (95% CI, 4.4–8.2). The enhancement-based techniques identified 11 (44%), 12 (48%) and 12 (48%) patients as R according to EASL, mRECIST and qEASL, respectively. No stratification was achieved with RECIST. Multivariate analysis identified tumor response according to mRECIST and qEASL as reliable predictors of improved patient survival (P = 0.019; HR 0.3 [0.1–0.8] and P = 0.006; HR 0.2 [0.1–0.6], respectively). Conclusion: This study confirmed the role of cTACE as a safe salvage therapy option in patients with mSTS of the liver. The demonstrated advantages

  13. Molecular cloning, tissue expression and regulation of liver X receptor (LXR) transcription factors of Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Cruz-Garcia, L; Minghetti, M; Navarro, I; Tocher, D R

    2009-05-01

    to LXRs of zebrafish, frog and human (LXRalpha). The trout LXR ORF showed 96%, 92% and 82% identity to LXRs of zebrafish, frog and human (LXRalpha). Surprisingly, the expression of LXR was lowest in liver of all tissues examined and in salmon the greatest expression was observed in pyloric caeca with liver showing intermediate expression. It is likely that tissue expression was affected by the physiological status of the sampled animals. Certainly, nutritional, environmental and/or developmental regulation was evident in salmon, where the expression of LXR in liver was higher in fish in seawater than in freshwater, and higher in fish fed fish oil compared to fish fed vegetable oil in adult salmon.

  14. Microarray analysis of gene expression in liver, adipose tissue and skeletal muscle in response to chronic dietary administration of NDGA to high-fructose fed dyslipidemic rats.

    Science.gov (United States)

    Zhang, Haiyan; Shen, Wen-Jun; Li, Yihang; Bittner, Alex; Bittner, Stefanie; Tabassum, Juveria; Cortez, Yuan F; Kraemer, Fredric B; Azhar, Salman

    2016-01-01

    Nordihydroguaiaretic acid (NDGA), the main metabolite of Creosote Bush, has been shown to have profound effects on the core components of metabolic syndrome, including lowering of blood glucose, free fatty acids and triglyceride levels, attenuating elevated blood pressure in several rodent models of dyslipidemia, and improving body weight, insulin resistance, diabetes and hypertension. In the present study, a high-fructose diet fed rat model of hypertriglyceridemia, dyslipidemia, insulin resistance and hepatic steatosis was employed to investigate the global transcriptional changes in the lipid metabolizing pathways in three insulin sensitive tissues: liver, skeletal muscle and adipose tissue in response to chronic dietary administration of NDGA. Sprague-Dawley male rats (SD) were fed a chow (control) diet, high-fructose diet (HFrD) or HFrD supplemented with NDGA (2.5 g/kg diet) for eight weeks. Dietary administration of NDGA decreased plasma levels of TG, glucose, and insulin, and attenuated hepatic TG accumulation. DNA microarray expression profiling indicated that dietary administration of NDGA upregulated the expression of certain genes involved in fatty acid oxidation and their transcription regulator, PPARα, decreased the expression of a number of lipogenic genes and relevant transcription factors, and differentially impacted the genes of fatty acid transporters, acetyl CoA synthetases, elongases, fatty acid desaturases and lipid clearance proteins in liver, skeletal muscle and adipose tissues. These findings suggest that NDGA ameliorates hypertriglyceridemia and steatosis primarily by inhibiting lipogenesis and enhancing fatty acid catabolism in three major insulin responsive tissues by altering the expression of key enzyme genes and transcription factors involved in de novo lipogenesis and fatty acid oxidation.

  15. Determination of the Mercury Fraction Linked to Protein of Muscle and Liver Tissue of Tucunaré (Cichla spp.) from the Amazon Region of Brazil.

    Science.gov (United States)

    Vieira, José C S; Cavecci, Bruna; Queiroz, João V; Braga, Camila P; Padilha, Cilene C F; Leite, Aline L; Figueiredo, Wllyane S; Buzalaf, Marília A R; Zara, Luiz F; Padilha, Pedro M

    2015-11-01

    This study used metalloproteomic techniques to characterize mercury (Hg)-bound proteins in the muscle and liver tissue of Tucunaré (Cichla spp.) collected at the Jirau Hydroelectric Power Plant in Madeira River Basin, Brazil. The proteome of the muscle and liver tissue was obtained after two steps of fractional precipitation and separating the proteins by 2-D polyacrylamide gel electrophoresis. Hg was identified and quantified in the protein spots by graphite furnace atomic absorption spectrometry after acid mineralization in an ultrasound bath. Hg with a molecular weight <20 kDa and a concentration between 13.30 and 33.40 mg g(-1) was found in the protein spots. These protein spots were characterized by electrospray ionization tandem mass spectrometry after trypsin digestion. From a total of 12 analyzed spots, seven proteins showing Hg biomarker characteristics were identified: parvalbumin and its isoforms, ubiquitin-40S ribosomal protein S27a, zinc (Zn) finger and BTB domain-containing protein 24, and dual-specificity protein phosphatase 22-B.

  16. Soy isoflavones modulate adipokines and myokines to regulate lipid metabolism in adipose tissue, skeletal muscle and liver of male Huanjiang mini-pigs.

    Science.gov (United States)

    Yang, Huansheng; Li, Fengna; Xiong, Xia; Kong, Xiangfeng; Zhang, Bin; Yuan, Xiaoxue; Fan, Juexin; Duan, Yefei; Geng, Meimei; Li, Lili; Yin, Yulong

    2013-01-05

    Although a growing body of evidence suggests that soy isoflavones help regulate lipid metabolism, the underlying mechanism has not yet been thoroughly clarified. The present study was undertaken to determine the effects of soy isoflavones on the expression of genes involved in lipid metabolism in different adipose tissue depots, skeletal muscle and liver of male Huanjiang mini-pigs, as well as the expression of adipokines and myokines. A total of 36 male Huanjiang mini-pigs were fed basal diet (control, Con), low-dose soy isoflavones (LSI) and high-dose soy isoflavones (HSI). The results showed that LSI and HSI regulated the expression of genes involved in the anabolism and catabolism of fatty acids in dorsal subcutaneous (DSA), abdominal subcutaneous (ASA) and perirenal (PRA) adipose tissue depots, as well as longissimus dorsi muscle (LDM) and liver. LSI and HSI also regulated the expression of adipokines in DSA, ASA and PRA, and the expression of myokines in LDM in male Huanjiang mini-pigs. In addition, soy isoflavones regulated plasma glucose, leptin and adiponectin contents after treatment for two months. Our results indicate that soy isoflavones, by regulating the expression of adipokines and myokines, may regulate the metabolism of lipids and could have potential therapeutic applications in lipid abnormalities.

  17. Protective Effect of Tulbaghia violacea Harv. on Aortic Pathology, Tissue Antioxidant Enzymes and Liver Damage in Diet-Induced Atherosclerotic Rats

    Directory of Open Access Journals (Sweden)

    Anthony J. Afolayan

    2012-10-01

    Full Text Available The protective effect Tulbaghia violacea rhizomes (TVR against derangements in serum lipid profile, tissue antioxidant enzyme depletion, endothelium dysfunction and histopathological changes in the aorta and liver of rats fed with an atherosclerogenic (Ath diet (4% cholesterol, 1% cholic acid and 0.5% thiouracil was investigated in this study. Co-treatment with the TVR extracts (250 and 500 mg/kg body weight for two weeks significantly (p < 0.05 protected against elevated serum triglyceride (TG, total cholesterol (TC, LDL-cholesterol, VLDL-cholesterol and decreased HDL-cholesterol in a dose-dependent manner when compared with the atherogenic control. The extracts also reduced (p < 0.05 elevated thiobabutric reacting substance (TBARS and reversed endothelial dysfunction parameters (fibrinogen and total NO levels and tissue antioxidant enzyme activities to near normal. The protective ability of the extract was confirmed by the significant (p < 0.05 reduction in the activities of serum markers of liver (LDH, AST, ALT, ALP, bilirubin and kidney damage (creatinine and bilirubin in extract-treated groups compared with the atherogenic control group. Also, histopathology evaluations of aorta sections revealed that the extracts protected against the development of fatty streak plaques (aorta and fatty changes in hepatocytes. The observed activities of the extracts compared favorably with standard drug atorvastatin. Our study thus showed that the methanolic extract of TVR could protect against the early onset of atherosclerosis.

  18. Bioaccumulation of mercury, cadmium, zinc, chromium, and lead in muscle, liver, and spleen tissues of a large commercially valuable catfish species from Brazil

    Directory of Open Access Journals (Sweden)

    Fábio P. Arantes

    2016-03-01

    Full Text Available The increasing amounts of heavy metals entering aquatic environments can result in high accumulation levels of these contaminants in fish and their consumers, which pose a serious risk to ecosystems and human health. We investigated the concentrations of mercury (Hg, cadmium (Cd, zinc (Zn, chromium (Cr, and lead (Pb in muscle, liver, and spleen tissues of Pseudoplatystoma corruscans specimens collected from two sites on the Paraopeba River, Brazil. The level of heavy metals concentrations in the tissues was often higher in viscera (i.e. liver and spleen than in muscle, and thus, the viscera should not be considered for human consumption. Correlations between metal concentrations and fish size were not significant. Although the levels of muscle bioaccumulation of Hg, Cd, Zn, Cr, and Pb, generally do not exceed the safe levels for human consumption, the constant presence of heavy metals in concentrations near those limits considered safe for human consumption, is a reason for concern, and populations who constantly consume fish from polluted rivers should be warned. Our findings also indicate that in a river network where certain areas are connected to other areas with high rates of environmental pollutants, people should be cautious about the regular consumption of fish, even when the fish consumed are caught in stretches of the basin where contamination levels are considered low, since many of the freshwater fish with high commercial value, such as the catfish surubim, are migratory.

  19. Effect of Tissue-Culture Substratum and Extracellular Matrix Overlay on Liver-Selective and Xenobiotic Inducible Gene Expression in Primary Rat Hepatocytes

    Science.gov (United States)

    SIDHU, J.S.; FARIN, F.M.; KAVANAGH, T.J.; OMIECINSKI, C.J.

    2012-01-01

    In a previous study (Sidhu et al., 1993), we demonstrated that a combination of certain cell culture media, hormone addition, and extracellular matrix (ECM) overlay coordinately modulated the expression of certain liver-selective genes in primary rat hepatocyte cultures, including the responsiveness of genes to phenobarbital. However, little is known about the interactions between the type of substratum upon which hepatocytes are adhered and the ECM overlay, as codeterminants of liver-selective gene expression. The present study was undertaken to compare specific substrata, including tissue culture-grade plastic, Primaria, and type 1 collagen-coated plastic, in combination with the presence or absence of standard ECM or a growth-factor-reduced ECM overlay. Hepatocyte cultures were assessed either as control cultures or subsequent to treatment for 24 h with phenobarbital (0.1 or 1 mM), or beta-naphthoflavone (22 μM), to monitor responses of hepatocytes to two prototypic gene-inducing agents. Analyses of maintenance and induction of cytochrome P450 and liver-selective gene expression included measures of mRNA levels using Northern blot and slot-blot hybridization and single cell immunofluorescence assays to measure levels of specific cytochrome P450 proteins. The results of these experiments demonstrated that hepatocyte-selective expression, including the absolute level of induction response (relative to those observed in the rat liver in vivo) was highly dependent on the presence of ECM overlay but independent of the substratum employed. As studied herein, the establishment of optimal conditions for primary hepatocyte culture, enabling reproduction of responses observed in vivo, is important to further prospects for in vitro toxicity testing and for investigating molecular mechanisms of phenobarbital-mediated gene regulation. PMID:24817786

  20. [Correlation between the mRNA expression of tissue inhibitor of metalloproteinase-1 and apparent diffusion coefficient on diffusion-weighted imaging in rats' liver fibrosis].

    Science.gov (United States)

    Zhan, Yuefu; Liang, Xianwen; Han, Xiangjun; Chen, Jianqiang; Zhang, Shufang; Tan, Shun; Li, Qun; Wang, Xiong; Liu, Fan

    2017-02-28

    To explore the correlation between the apparent diffusion coefficient (ADC) and mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in different stages of liver fibrosis in rats.
 Methods: A model of liver fibrosis in rats was established by intraperitoneal injection of high-fat diet combined with porcine serum. After drug administration for 4 weeks, 48 rats served as a model group and 12 rats served as a control group, then they underwent diffusion weighted imaging (DWI) scanning. The value of ADC was calculated at b value=800 s/mm2. The rats were sacrificed and carried out pathologic examination after DWI scanning immediately. The mRNA expression of TIMP-1 was detected by real time-polymerase chain reaction (RT-PCR). The rats of hepatic fibrosis were also divided into a S0 group (n=4), a S1 group (n=11), a S2 group (n=12), a S3 group (n=10), and a S4 group (n=9) according to their pathological stage. The value of ADC and the expression of TIMP-1 mRNA among the different stage groups of liver fibrosis were compared, and the correlation between ADC and the TIMP-1 mRNA were analyzed.
 Results: The ADC value and the TIMP-1 mRNA expression were significantly different between the control group and the liver fibrosis group (F=46.54 and 53.87, P0.05). For the comparison of TIMP-1 mRNA, there was no significant difference between the S1 group and the S2 group, the S3 group and the S4 group (both P>0.05). There were significant differences among the rest of the groups (all Pcorrelation analysis showed that there was a negative correlation between the ADC value and the TIMP-1 mRNA expression (r=-0.76, Pcorrelation between them.

  1. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Oluwafemi O. Oguntibeju

    2016-01-01

    Full Text Available Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ- induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg aqueous solution was administered (daily orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC, ferric reducing antioxidant power (FRAP, catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

  2. Identification of the novel candidate genes and variants in boar liver tissues with divergent skatole levels using RNA deep sequencing.

    Directory of Open Access Journals (Sweden)

    Asep Gunawan

    Full Text Available Boar taint is the unpleasant odour of meat derived from non-castrated male pigs, caused by the accumulation of androstenone and skatole in fat. Skatole is a tryptophan metabolite produced by intestinal bacteria in gut and catabolised in liver. Since boar taint affects consumer's preference, the aim of this study was to perform transcriptome profiling in liver of boars with divergent skatole levels in backfat by using RNA-Seq. The total number of reads produced for each liver sample ranged from 11.8 to 39.0 million. Approximately 448 genes were differentially regulated (p-adjusted 1.5. Differentially regulated genes in the high skatole liver samples were enriched in metabolic processes such as small molecule biochemistry, protein synthesis, lipid and amino acid metabolism. Pathway analysis identified the remodeling of epithelial adherens junction and TCA cycle as the most dominant pathways which may play important roles in skatole metabolism. Differential gene expression analysis identified candidate genes in ATP synthesis, cytochrome P450, keratin, phosphoglucomutase, isocitrate dehydrogenase and solute carrier family. Additionally, polymorphism and association analysis revealed that mutations in ATP5B, KRT8, PGM1, SLC22A7 and IDH1 genes could be potential markers for skatole levels in boars. Furthermore, expression analysis of exon usage of three genes (ATP5B, KRT8 and PGM1 revealed significant differential expression of exons of these genes in different skatole levels. These polymorphisms and exon expression differences may have impacts on the gene activity ultimately leading to skatole variation and could be used as genetic marker for boar taint related traits. However, further validation is required to confirm the effect of these genetic markers in other pig populations in order to be used in genomic selection against boar taint in pig breeding programs.

  3. mPGES-1 expression in non-cancerous liver tissue impacts on postoperative recurrence of HCC

    Institute of Scientific and Technical Information of China (English)

    Koichi; Nonaka; Hikaru; Fujioka; Yasushi; Takii; Seigo; Abiru; Kiyoshi; Migita; Masahiro; Ito; Takashi; Kanematsu; Hiromi; Ishibashi

    2010-01-01

    AIM:To investigate whether microsomal prostaglandin E synthase-1 (mPGES-1) expression in hepatocellular carcinoma (HCC) and in non-cancerous liver affects HCC prognosis after hepatectomy. METHODS: The relationship between patient clinical prof iles, tumor factors, surgical determinants, and mPGES-1 expression and the recurrence-free survival rate were examined in 64 patients who underwent curative hepatectomy between March 2003 and December 2006. RESULTS: The scores for mPGES-1 expression were higher in wel...

  4. Expression of hnRNPK & Claudin-4 in HCV-Induced Early HCC and Adjacent Liver Tissue

    Directory of Open Access Journals (Sweden)

    Olfat Hammam

    2017-07-01

    CONCLUSION: Combination of hnRNPK and Claudin-4 can indicate early HCC development in HCV cirrhotic livers using hnRNPK ³ 30/5HPFs & Claudin-4 £ 10% cut offs. Also, combination of hnRNPK ³ 30/5HPFs & Claudin-4 ³ 40% can distinguish low grade eHCC (G1 from high grade eHCC (G2&G3.

  5. Effects of trans n-6 fatty acids on the fatty acid profile of tissues and liver microsomal desaturation in the rat

    Directory of Open Access Journals (Sweden)

    Berdeaux, Olivier

    1996-04-01

    Full Text Available 18:2Δ 9c,12t and 18:2 Δ9t,12c are present in our diet, as result of heat treatment of vegetable oils. A nutritional study was carried out in order to obtain more precise information on the conversion of these two isomers into long chain polyunsaturated fatty acids (PUFA by rat tissues. This in vivo study performed using rat fed with small quantities of mono trans linoleic acid isomers (0.6% of total energy showed that 18:2 Δ9c,12t was converted into 20:4 Δ5c,8c,11c,14t while 18:2 Δ9t,12c was only slightly converted into 20:4 Δ5c,8c,11t,14c. Furthermore 18:2 Δ9t,12c was preferentially elongated into 20:2 Δ11t,14c. Each C20 metabolite of these mono trans 18:2 isomers was isolated as methyl ester by semi-preparative high-performance liquid chromatography (HPLC followed by silver nitrate thin layer chromatography (AgNO3-TLC.The structure of the components was identified using partial hydrazine reduction, AgNO3-TLC of the resulting monoenes and gas-liquid chromatography coupled with mass spectrometry (GC-MS of the 4,4-dimethyloxazoline (DMOX derivatives. Fourier-transform-infrared spectroscopy (GC-FTIR confirmed the frans geometry. Gas-liquid chromatography (GC analyses showed that 18:2 Δ9c,12t and 18:2 Δ9t,12c were present in different tissue lipids (liver, heart, testes, brain and adipose tissue, and without any modification in the amount of 20:4n-6. 20:4 Δ5c, 8c,11c,14t was incorporated in different rat tissues except in brain. Furthermore, its incorporation followed that of its structural analogue, 20:3n-9 in liver phospholipid classes (phosphatidylethanolamine, phosphatidylinositol and phosphatidylcholine. Finally, an in vitro study carried out with rat liver microsomes showed that dietary trans 18:2 isomers could inhibit the Δ6- desaturation of 18:2n-6 to 18:3n-6 and the Δ5-desaturation of 20:3n-6 to 20:4n-6.

  6. Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue.

    Directory of Open Access Journals (Sweden)

    Jialin Xu

    Full Text Available AIMS: The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD, regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting. METHODS AND RESULTS: Male C57BL/6 (WT and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36 and Fatty acid transport protein (FATP 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. CONCLUSION: Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation.

  7. Expression of insulin-like growth factor system genes in liver tissue during embryonic and early post-hatch development in duck (Anas platyrhynchos Domestica).

    Science.gov (United States)

    Jianmin, Zou; Jingting, Shu; Yanju, Shan; Yan, Hu; Chi, Song; Wenqi, Zhu

    2014-04-01

    The IGF system is one of the most important endocrine and paracrine growth factor systems that regulate fetal and placental growth, whereas the liver is the principal source of circulation IGF-I. In the present study, expression of IGF-I, IGF type-I receptor (IGF-IR), and IGF binding protein (IGFBP)-3 genes was quantified by RT-PCR in the liver tissue on days 13, 17, 21, 25, and 27 of embryonic development, as well as at 7 days post-hatching (PH) in meat-type Gaoyou ducks and egg-type Jinding ducks. The results showed that IGF-I mRNA could be detected as early as on E 13d, but the expression level was low throughout embryonic development before increasing dramatically by E 27d and 7 days PH in both duck breeds. However, Gaoyou ducks exhibited higher IGF-I mRNA level than Jinding ducks, and the differences were significant on E 13d, E 21d, and at 7 days PH. Expression of IGF-IR in liver increased gradually in the former stages of the embryonic development, reaching its highest point on E 21d, and then declined up until 7 days PH. The expression pattern of IGFBP-3 gene was similar to that of IGF-IR gene, increasing significantly from E 17d. The expression peak appeared on E 25d, then declined significantly just prior to hatching (day 27) and was followed by an increase at 7 days PH. In general, the expression level of IGF-IR and IGFBP-3 genes in Jinding ducks was higher than that in Gaoyou ducks. Inverse relationships were observed for the expression of IGF-I and IGF-IR, and IGF-I and IGFBP-3, whereas a positive relationship was observed for the expression of IGF-IR and IGFBP-3. Our data indicate a differential expression of selected genes that comprise the IGF system in the duck liver tissue during embryonic and early PH growth and development.

  8. Useful properties of undifferentiated mesenchymal stromal cells and adipose tissue as the source in liver-regenerative therapy studied in an animal model of severe acute fulminant hepatitis.

    Science.gov (United States)

    Manzini, Bruna Maria; da Silva Santos Duarte, Adriana; Sankaramanivel, Sundararaj; Ramos, Aline Lisie; Latuf-Filho, Paulo; Escanhoela, Cecilia; Kharmandayan, Paulo; Olalla Saad, Sara Teresinha; Boin, Ilka; Malheiros Luzo, Ângela Cristina

    2015-08-01

    End-stage liver diseases frequently require liver transplantation. Cell therapy could be an alternative. This study aimed to analyze whether undifferentiated mesenchymal stromal cells (U-MSCs) or MSC-derived hepatocyte-like cells (DHLCs) from adipose tissue (AT), umbilical cord blood (UCB) and bone marrow (BM) would better restore damaged liver. AT was obtained from lipo-aspiration, UCB from an Umbilical Cord Blood Bank and BM from a BM Transplantation Unit. AT (collagenase digestion), UCB and BM (Ficoll gradient) were cultured (Dulbecco's modified Eagle's medium, low glucose, FBS) for 3 days. Detached adherent cells, at passage 4, were characterized as MSCs. Genetic stability was investigated by means of telomerase enzyme activity and karyotype. Hepatocyte differentiation protocol was performed with the use of Dulbecco's modified Eagle's medium, hepatocyte growth factor, basic fibroblast growth factor and nicotinamide (7 days); maturation medium (oncostatin, dexamethasone, insulin, transferrin and selenium) was added at 36 days. Hepatogenesis analyses were performed by use of morphology and albumin, AF, tyrosine-aminotransferase and glutamine synthetase gene expression and quantitative reverse transcription-polymerase chain reaction on days 9, 18, 25 and 36. Functionality was assessed through glycogen storage detection, indocyanine green absorption and transplantation procedure. U-MSCs and DHLCs were injected 48 h after induced fulminant hepatitis (intraperitoneal injection of carbon tetrachloride) in SCID/BALB-c mice. Histopathologic analyses were performed on days 7 and 15. Human origin included albumin and CK19 human markers. All MSCs differentiated into functional hepatocyte-like cells, stored glycogen and absorbed indocyanine green. AT-MSC DHLC gene expression was more consistent with a normal hepatogenic-differentiation profile. UCB-MSCs expanded weakly, impairing their use for the transplantation procedure. AT and BM U-MSCs and DHLCs regenerated liver

  9. MicroRNA-30a expression in liver fibrotic tissues and its influence on liver fibrosis%微小RNA-30a在肝纤维化中的表达及其影响

    Institute of Scientific and Technical Information of China (English)

    陈建亮; 李书; 刘雨亭; 周澍; 曹守纪; 李国强

    2016-01-01

    目的 观察微小RNA(miRNA,miR)-30a在肝纤维化中的表达及其对肝纤维化的影响.方法 通过C57BL/6小鼠胆管结扎(对照组10例,胆管结扎组15例)和10 ng/ml转化生长因子-β1(TGF-β1)处理肝星状细胞(LX-2和HSC-T6)分别构建体内和体外肝纤维化模型.通过转染miR-30a mimics和miR-30a agomir分别在肝星状细胞和小鼠体内过表达miR-30a.提取总RNA和全蛋白进行反转录-聚合酶链反应(RT-PCR)和Western blot实验检测miR-30a、α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(collagen Ⅰ)和基质金属蛋白酶抑制剂-1(TIMP-1).通过苏木素-伊红(HE)染色、胶原纤维染色(Masson染色)检测肝组织纤维化程度.结果 RT-PCR检测10例对照组和15例胆管结扎组小鼠肝脏miR-30a相对表达水平(2.037 ±0.256,n=10;1.007 ±0.126,n=15;P<0.01).10 ng/ml TGF-β1处理肝星状细胞24h和48 hmiR-30a相对表达水平(LX-2:24 h,0.578±0.055,48 h,0.585±0.048;HSC-T6:24 h,0.698±0.055,48 h,0.610±0.033),明显低于对照组(LX-2:1.013±0.080;HSC-T6:1.001±0.013,P<0.05),表明miR-30a在体内和体外诱导的肝纤维化模型中表达下降.通过miR-30a mimics转染肝星状细胞株诱导细胞内过表达miR-30a、α-SMA相对表达水平(LX-2:对照组1.024±0.106,miR-30a高表达组0.464±0.021,P<0.05;HSC-T6:对照组1.031±0.095,miR-30a高表达组0.352±0.042,P<0.05).通过尾静脉注射miR-30a agomir在小鼠体内高表达miR-30a,胆管结扎预处理小鼠α-SMA相对表达水平(对照组2.618±0.116,miR-30a高表达组1.207±0.197,P<0.05).表明过表达miR-30a能够抑制体内和体外肝纤维化进程.结论 miR-30a在肝纤维化中表达下降,过表达miR-30a能抑制肝纤维化进程.%Objective To observe the expression of microRNA (miRNA,miR)-30a in liver fibrotic tissues and its effect on liver fibrosis.Methods Hepatic stellate cells (HSCs:LX-2,HSC-T6) were treated with 10 ng/ml transforming growth factor (TGF)-β1,C57BL/6 mice were treated by

  10. Characterization of phospholipid hydroperoxide glutathione metabolizing peroxidase (gpx4) isoforms in Coho salmon olfactory and liver tissues and their modulation by cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Wang Lu; Harris, Sean M.; Espinoza, Herbert M.; McClain, Valerie [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Gallagher, Evan P., E-mail: evang3@uw.edu [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Cloned two gpx4 isoforms (gpx4a and gpx4b) from the Coho salmon peripheral olfactory system. Black-Right-Pointing-Pointer Developed qPCR assays for a comprehensive analysis of gpx4 expression in 10 tissues. Black-Right-Pointing-Pointer High initial rates of GPx4 enzymatic activity in Coho olfactory and liver tissues. Black-Right-Pointing-Pointer Examined the effect of cadmium on gpx4 expression in olfactory and liver tissues. - Abstract: Exposure to environmental contaminants, including various pesticides and trace metals, can disrupt critical olfactory-driven behaviors of fish such as homing to natal streams, mate selection, and an ability to detect predators and prey. These neurobehavioral injuries have been linked to reduced survival and population declines. Despite the importance of maintaining proper olfactory signaling processes in the presence of chemical exposures, little is known regarding chemical detoxification in the salmon olfactory system, and in particular, the antioxidant defenses that maintain olfactory function. An understudied, yet critical component of cellular antioxidant defense is phospholipid hydroperoxide glutathione peroxidase (PHGPx/GPx4), an isoform within the family of selenium-dependent glutathione peroxidase (GPx) enzymes that can directly reduce lipid peroxides and other membrane-bound complex hydroperoxides. In this study, we cloned two gpx4 isoforms (gpx4a and gpx4b) from Coho salmon olfactory tissues and compared their modulation in olfactory and liver tissues by cadmium, an environmental pollutant and olfactory toxicant that cause oxidative damage as a mechanism of toxicity. Amino acid sequence comparisons of the two gpx4 isoforms shared 71% identity, and also relatively high sequence identities when compared with other fish GPx4 isoforms. Sequence comparisons with human GPx4 indicated conservation of three important active sites at selenocysteine (U46), glutamine (Q81), and tryptophan (W

  11. Comparative study of the iron cores in human liver ferritin, its pharmaceutical models and ferritin in chicken liver and spleen tissues using Moessbauer spectroscopy with a high velocity resolution

    Energy Technology Data Exchange (ETDEWEB)

    Alenkina, I.V.; Semionkin, V.A. [Faculty of Physical Techniques and Devices for Quality Control, Ural Federal University, Ekaterinburg (Russian Federation); Faculty of Experimental Physics, Ural Federal University, Ekaterinburg (Russian Federation); Oshtrakh, M.I. [Faculty of Physical Techniques and Devices for Quality Control, Ural Federal University, Ekaterinburg (Russian Federation); Klepova, Yu.V.; Sadovnikov, N.V. [Faculty of Physiology and Biotechnology, Ural State Agricultural Academy, Ekaterinburg, (Russian Federation); Dubiel, S.M. [Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Krakow (Poland)

    2011-07-01

    Full text: Application of the Moessbauer spectroscopy with a high velocity resolution (4096 channels) for a study of iron-containing biological species is of great interest. Improving the velocity resolution allows to reveal small variations in the electronic structure of iron, and to obtain hyperfine parameters with smaller instrumental (systematic) errors in comparison with measurements performed in 512 channels or less. It also allows a more reliable fitting of complex Moessbauer spectra. In the present study the Moessbauer spectroscopy with the high velocity resolution was used for a comparative analysis of ferritin and its pharmaceutically important models as well as iron storage proteins in a chicken liver and a spleen. The ferritin, an iron storage protein, consists of a nanosized polynuclear iron core formed by a ferrihydrite surrounded by a protein shell. Iron-polysaccharide complexes contain {beta}-FeOOH iron cores coated with various polysaccharides. The Moessbauer spectra of the ferritin and commercial products Imferon, MaltoferR and Ferrum Lek as well as those of the chicken liver and spleen tissues were measured with the high velocity resolution at 295 and 90 K. They were fitted using two models: (1) with a homogeneous iron core (an approximation using one quadrupole doublet), and (2) with a heterogeneous iron core (an approximation using several quadrupole doublets). The model (1) can be used as the first approximation fit to visualize small variations in the hyperfine parameters. Using this model, differences in the Moessbauer hyperfine parameters were obtained in both 295 and 90 K Moessbauer spectra. However, this model was considered as a rough approximation because the measured Moessbauer spectra had non-Lorentzian line shapes. Therefore, the spectra of the ferritin, Imferon, MaltoferR and Ferrum Lek as well as those of the liver and spleen tissues were fitted again using the model (2) in which a different number of the quadrupole doublets was

  12. Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.

    Directory of Open Access Journals (Sweden)

    Ori Nov

    Full Text Available The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed to mainly function locally, could regulate dysfunctional inter-organ crosstalk in obesity. Here we show that High-fat-fed (HFF mice exhibited a preferential increase of IL-1β in portal compared to systemic blood. Moreover, portally-drained mesenteric fat transplantation from IL-1βKO donors resulted in lower pyruvate-glucose flux compared to mice receiving wild-type (WT transplant. These results raised a putative endocrine function for visceral fat-derived IL-1β in regulating hepatic gluconeogenic flux. IL-1βKO mice on HFF exhibited only a minor or no increase in adipose expression of pro-inflammatory genes (including macrophage M1 markers, Mac2-positive crown-like structures and CD11b-F4/80-double-positive macrophages, all of which were markedly increased in WT-HFF mice. Further consistent with autocrine/paracrine functions of IL-1β within adipose tissue, adipose tissue macrophage lipid content was increased in WT-HFF mice, but significantly less in IL-1βKO mice. Ex-vivo, adipose explants co-cultured with primary hepatocytes from WT or IL-1-receptor (IL-1RI-KO mice suggested only a minor direct effect of adipose-derived IL-1β on hepatocyte insulin resistance. Importantly, although IL-1βKOs gained weight similarly to WT-HFF, they had larger fat depots with similar degree of adipocyte hypertrophy. Furthermore, adipogenesis genes and markers (pparg, cepba, fabp4, glut4 that were decreased by HFF in WT, were paradoxically elevated in IL-1βKO-HFF mice. These local alterations in adipose tissue inflammation and expansion correlated with a lower liver size, less hepatic steatosis, and preserved insulin