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Sample records for tissues including liver

  1. Polyploidization in liver tissue.

    Science.gov (United States)

    Gentric, Géraldine; Desdouets, Chantal

    2014-02-01

    Polyploidy (alias whole genome amplification) refers to organisms containing more than two basic sets of chromosomes. Polyploidy was first observed in plants more than a century ago, and it is known that such processes occur in many eukaryotes under a variety of circumstances. In mammals, the development of polyploid cells can contribute to tissue differentiation and, therefore, possibly a gain of function; alternately, it can be associated with development of disease, such as cancer. Polyploidy can occur because of cell fusion or abnormal cell division (endoreplication, mitotic slippage, or cytokinesis failure). Polyploidy is a common characteristic of the mammalian liver. Polyploidization occurs mainly during liver development, but also in adults with increasing age or because of cellular stress (eg, surgical resection, toxic exposure, or viral infections). This review will explore the mechanisms that lead to the development of polyploid cells, our current state of understanding of how polyploidization is regulated during liver growth, and its consequence on liver function. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Improved application of the electrophoretic tissue clearing technology, CLARITY, to intact solid organs including brain, pancreas, liver, kidney, lung, and intestine.

    Science.gov (United States)

    Lee, Hyunsu; Park, Jae-Hyung; Seo, Incheol; Park, Sun-Hyun; Kim, Shin

    2014-12-21

    Mapping of tissue structure at the cellular, circuit, and organ-wide scale is important for understanding physiological and biological functions. A bio-electrochemical technique known as CLARITY used for three-dimensional anatomical and phenotypical mapping within transparent intact tissues has been recently developed. This method provided a major advance in understanding the structure-function relationships in circuits of the nervous system and organs by using whole-body clearing. Thus, in the present study, we aimed to improve the original CLARITY procedure and developed specific CLARITY protocols for various intact organs. We determined the optimal conditions for reducing bubble formation, discoloration, and depositing of black particles on the surface of tissue, which allowed production of clearer organ images. We also determined the appropriate replacement cycles of clearing solution for each type of organ, and convincingly demonstrated that 250-280 mA is the ideal range of electrical current for tissue clearing. We then acquired each type of cleared organs including brain, pancreas, liver, lung, kidney, and intestine. Additionally, we determined the images of axon fibers of hippocampal region, the Purkinje layer of cerebellum, and vessels and cellular nuclei of pancreas. CLARITY is an innovative biochemical technology for the structural and molecular analysis of various types of tissue. We developed improved CLARITY methods for clearing of the brain, pancreas, lung, intestine, liver, and kidney, and identified the appropriate experimental conditions for clearing of each specific tissue type. These optimized methods will be useful for the application of CLARITY to various types of organs.

  3. Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms

    Directory of Open Access Journals (Sweden)

    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.

  4. A composite model including visfatin, tissue polypeptide-specific antigen, hyaluronic acid, and hematological variables for the diagnosis of moderate-to-severe fibrosis in nonalcoholic fatty liver disease: a preliminary study.

    Science.gov (United States)

    Chwist, Alina; Hartleb, Marek; Lekstan, Andrzej; Kukla, Michał; Gutkowski, Krzysztof; Kajor, Maciej

    2014-01-01

    Histopathological risk factors for end-stage liver failure in patients with nonalcoholic fatty liver disease (NAFLD) include nonalcoholic steatohepatitis (NASH) and advanced liver fibrosis. There is a need for noninvasive diagnostic methods for these 2 conditions. The aim of this study was to investigate new laboratory variables with a predictive potential to detect advanced fibrosis (stages 2 and 3) in NAFLD. The study involved 70 patients with histologically proven NAFLD of varied severity. Additional laboratory variables included zonulin, haptoglobin, visfatin, adiponectin, leptin, tissue polypeptide-specific antigen (TPSA), hyaluronic acid, and interleukin 6. Patients with NASH (NAFLD activity score of ≥5) had significantly higher HOMA-IR values and serum levels of visfatin, haptoglobin, and zonulin as compared with those without NASH on histological examination. Advanced fibrosis was found in 16 patients (22.9%) and the risk factors associated with its prevalence were age, the ratio of erythrocyte count to red blood cell distribution width, platelet count, and serum levels of visfatin and TPSA. Based on these variables, we constructed a scoring system that differentiated between NAFLD patients with and without advanced fibrosis with a sensitivity of 75% and specificity of 100% (area under the receiver operating characteristic curve, 0.93). The scoring system based on the above variables allows to predict advanced fibrosis with high sensitivity and specificity. However, its clinical utility should be verified in further studies involving a larger number of patients.

  5. Ectopic Liver Tissue Formation in Rats with Induced Liver Fibrosis

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    Bauyrzhan Umbayev

    2014-12-01

    Full Text Available Introduction: The possible alternative approach to whole-organ transplantation is a cell-based therapy, which can also be used as a "bridge" to liver transplantation.  However, morphological and functional changes in the liver of patients suffering from chronic liver fibrosis and cirrhosis restrict the effectiveness of direct cell transplantation. Therefore, extra hepatic sites for cell transplantation, including the spleen, pancreas, peritoneal cavity, and subrenal capsule, could be a useful therapeutic approach for compensation of liver functions. However, a method of transplantation of hepatocytes into ectopic sites is needed to improve hepatocyte engraftment. Previously published data has demonstrated that mouse lymph nodes can support the engraftment and proliferation of hepatocytes as ES and rescue Fah mice from lethal liver failure. Thus, the aim of the study was to evaluate the engraftment of i.p. injected allogeneic hepatocytes into extra hepatic sites in albino rats with chemically induced liver fibrosis (LF. Materials and methods: Albino rats were randomly divided into 4 groups: (1 intact group (n = 18; (2 rats with induced LF (n = 18; (3 rats with induced LF and transplanted with hepatocytes (n = 18; (4 as a control, rats were treated with cyclosporine A only (n = 18. In order to prevent an immune response, groups 2 and 3 were subjected to immunosuppression by cyclosporine A (25 mg/kg per day. LF was induced using N-nitrosodimethylamine (NDMA, i.p., 10 mg/kg, three times a week for 4 weeks and confirmed by histological analysis of the liver samples. Hepatocytes transplantation (HT was performed two days after NDMA exposure cessation by i.p. injection of 5×106 freshly isolated allogeneic hepatocytes. Liver function was assessed by quantifying blood biochemical parameters (ALT, AST, GGT, total protein, bilirubin, and albumin at 1 week, 1 month, and 2 months after hepatocytes transplantation (HT. To confirm a hepatocytes

  6. Tissue hepatic blood volume and liver function

    International Nuclear Information System (INIS)

    Masuyama, Mamoru

    1997-01-01

    Positron emission tomography (PET) scan has an advantage that it can measure regional organ blood flow and volume not only quantitatively but also non-invasively. In order to estimate the liver function, tissue hepatic blood volume was measured using C 15 O inhalation in conjunction with positron emission tomography. PET scans of the liver were performed after the single breath inhalation of 20 mCi of high specific activity 15 O-labeled carbon monoxide in 105 patients which were classified 3 groups; normal, chronic hepatitis, and cirrhosis. They consist of 61, 14, and 30 patients, respectively. Significant differences between normal and cirrhotic patients were noted in tissue hepatic blood volume (mean 20.4, 18.2, 16.0 ml/100 g, respectively). Tissue hepatic blood volume (tHBV) correlated with the reaction of the peripheral reticuloendothelial compartment and protein synthesis, because there was a potent correlation between tHBV and hepatic fibrosis. In normal livers, we were able to demonstrate significant differences in tissue hepatic blood volume among liver segments. (author)

  7. Radioligand assay for biotin in liver tissues

    International Nuclear Information System (INIS)

    Rettenmaier, R.

    1979-01-01

    A radioligand assay for biotin in liver tissue is described. 3 H-biotin is used as tracer and avidin as binder. The biotin-loaded avidin is separated from free biotin on dextran-coated charcoal, which leaves the avidin-biotin complex in the supernatant liquid. Thus, the avidin-biotin complex can easily be utilized for determination of the radioactivity. Calibration with known additions of biotin in the range 0.25-8.0 ng per assay sample yields a linear logit-log plot. The biotin is extracted from liver tissues by enzymatic proteolysis with papain. This treatment is optimized to liberate the bound forms of the vitamin. Microbiological parallel assays with Lactobacillus plantarum were in good agreement with the radioligand assay giving a regression coefficient of 0.974(n=44). The coefficient of variation was found to be 4.2% in the range 500-1200 ng of biotin per g of liver tissue (n=46). The method is simple and reliable and allows the simultaneous analysis of a considerable number of samples. (Auth.)

  8. The nutritional geometry of liver disease including non-alcoholic fatty liver disease.

    Science.gov (United States)

    Simpson, Stephen J; Raubenheimer, David; Cogger, Victoria C; Macia, Laurence; Solon-Biet, Samantha M; Le Couteur, David G; George, Jacob

    2018-02-01

    Nutrition has a profound effect on chronic liver disease, especially non-alcoholic fatty liver disease (NAFLD). Most observational studies and clinical trials have focussed on the effects of total energy intake, or the intake of individual macronutrients and certain micronutrients, such as vitamin D, on liver disease. Although these studies have shown the importance of nutrition on hepatic outcomes, there is not yet any unifying framework for understanding the relationship between diet and liver disease. The Geometric Framework for Nutrition (GFN) is an innovative model for designing nutritional experiments or interpreting nutritional data that can determine the effects of nutrients and their interactions on animal behaviour and phenotypes. Recently the GFN has provided insights into the relationship between dietary energy and macronutrients on obesity and ageing in mammals including humans. Mouse studies using the GFN have disentangled the effects of macronutrients on fatty liver and the gut microbiome. The GFN is likely to play a significant role in disentangling the effects of nutrients on liver disease, especially NAFLD, in humans. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  9. 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 steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.

  10. 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.

  11. 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.

    2016-01-01

    The surgically-demanding mouse orthotopic liver transplant model was first described in 1991. It has proved a powerful research tool for 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, since 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 has provided valuable mechanistic insights into the immuno- and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in 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. 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 liver and other diseases. PMID:26709949

  12. 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.

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

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    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.

  14. 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 hypoxia-tolerant 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.

  15. Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience.

    Directory of Open Access Journals (Sweden)

    Ricky H Bhogal

    2011-03-01

    Full Text Available Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples.

  16. Liver-cell patterning lab chip: mimicking the morphology of liver lobule tissue.

    Science.gov (United States)

    Ho, Chen-Ta; Lin, Ruei-Zeng; Chen, Rong-Jhe; Chin, Chung-Kuang; Gong, Song-En; Chang, Hwan-You; Peng, Hwei-Ling; Hsu, Long; Yew, Tri-Rung; Chang, Shau-Feng; Liu, Cheng-Hsien

    2013-09-21

    A lobule-mimetic cell-patterning technique for on-chip reconstruction of centimetre-scale liver tissue of heterogeneous hepatic and endothelial cells via an enhanced field-induced dielectrophoresis (DEP) trap is demonstrated and reported. By mimicking the basic morphology of liver tissue, the classic hepatic lobule, the lobule-mimetic-stellate-electrodes array was designed for cell patterning. Through DEP manipulation, well-defined and enhanced spatial electric field gradients were created for in-parallel manipulation of massive individual cells. With this liver-cell patterning labchip design, the original randomly distributed hepatic and endothelial cells inside the microfluidic chamber can be manipulated separately and aligned into the desired pattern that mimicks the morphology of liver lobule tissue. Experimental results showed that both hepatic and endothelial cells were orderly guided, snared, and aligned along the field-induced orientation to form the lobule-mimetic pattern. About 95% cell viability of hepatic and endothelial cells was also observed after cell-patterning demonstration via a fluorescent assay technique. The liver function of CYP450-1A1 enzyme activity showed an 80% enhancement for our engineered liver tissue (HepG2+HUVECs) compared to the non-patterned pure HepG2 for two-day culturing.

  17. POLARIZATION IMAGING AND SCATTERING MODEL OF CANCEROUS LIVER TISSUES

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    DONGZHI LI

    2013-07-01

    Full Text Available We apply different polarization imaging techniques for cancerous liver tissues, and compare the relative contrasts for difference polarization imaging (DPI, degree of polarization imaging (DOPI and rotating linear polarization imaging (RLPI. Experimental results show that a number of polarization imaging parameters are capable of differentiating cancerous cells in isotropic liver tissues. To analyze the contrast mechanism of the cancer-sensitive polarization imaging parameters, we propose a scattering model containing two types of spherical scatterers and carry on Monte Carlo simulations based on this bi-component model. Both the experimental and Monte Carlo simulated results show that the RLPI technique can provide a good imaging contrast of cancerous tissues. The bi-component scattering model provides a useful tool to analyze the contrast mechanism of polarization imaging of cancerous tissues.

  18. Isolation and characterization of adult human liver progenitors from ischemic liver tissue derived from therapeutic hepatectomies.

    Science.gov (United States)

    Stachelscheid, Harald; Urbaniak, Thomas; Ring, Alexander; Spengler, Berlind; Gerlach, Jörg C; Zeilinger, Katrin

    2009-07-01

    Recent evidence suggests that progenitor cells in adult tissues and embryonic stem cells share a high resistance to hypoxia and ischemic stress. To study the ischemic resistance of adult liver progenitors, we characterized remaining viable cells in human liver tissue after cold ischemic treatment for 24-168 h, applied to the tissue before cell isolation. In vitro cultures of isolated cells showed a rapid decline of the number of different cell types with increasing ischemia length. After all ischemic periods, liver progenitor-like cells could be observed. The comparably small cells exhibited a low cytoplasm-to-nucleus ratio, formed densely packed colonies, and showed a hepatobiliary marker profile. The cells expressed epithelial cell adhesion molecule, epithelial-specific (CK8/18) and biliary-specific (CK7/19) cytokeratins, albumin, alpha-1-antitrypsin, cytochrome-P450 enzymes, as well as weak levels of hepatocyte nuclear factor-4 and gamma-glutamyl transferase, but not alpha-fetoprotein or Thy-1. In vitro survival and expansion was facilitated by coculture with mouse embryonic fibroblasts. Hepatic progenitor-like cells exhibit a high resistance to ischemic stress and can be isolated from human liver tissue after up to 7 days of ischemia. Ischemic liver tissue from various sources, thought to be unsuitable for cell isolation, may be considered as a prospective source of hepatic progenitor cells.

  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...... of both liver and adipose tissue regulation in whole body metabolism has come in to focus and it has been shown that both tissues are subject to exercise training-induced adaptations. However, the contribution of endocrine factors to the regulation of exercise training-induced adaptations in liver...... 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...

  20. 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

    -specific phosphorylation sites were identified in tissue-specific enzymes such as those encoded by HMGCS2, BDH1, PCK2, CPS1, and OTC in liver mitochondria, and CKMT2 and CPT1B in heart and skeletal muscle. Kinase prediction showed an important role for PKA and PKC in all tissues but also for proline-directed kinases......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...... 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...

  1. Altered morphology of liver and pancreas tissues of offsprings of ...

    African Journals Online (AJOL)

    The relationship between consumption of charred meat, which is believed to be rich in nitrosamine by pregnant mothers and the adverse effects on the growth of their offsprings, alterations in morphology of tissues like liver and pancreas were studied. Meat was subjected to charcoal fire roasting without curing and was ...

  2. PVA matches human liver in needle-tissue interaction.

    Science.gov (United States)

    de Jong, Tonke L; Pluymen, Loes H; van Gerwen, Dennis J; Kleinrensink, Gert-Jan; Dankelman, Jenny; van den Dobbelsteen, John J

    2017-05-01

    Medical phantoms can be used to study needle-tissue interaction and to train medical residents. The purpose of this research is to study the suitability of polyvinyl alcohol (PVA) as a liver tissue mimicking material in terms of needle-tissue interaction. Insertions into ex-vivo human livers were used for reference. Six PVA samples were created by varying the mass percentage of PVA to water (4m% and 7m%) and the number of freeze-thaw cycles (1, 2 and 3 cycles, 16hours of freezing at -19°C, 8hours of thawing). The inner needle of an 18 Gauge trocar needle with triangular tip was inserted 13 times into each of the samples, using an insertion velocity of 5 mm/s. In addition, 39 insertions were performed in two ex-vivo human livers. Axial forces on the needle were captured during insertion and retraction and characterized by friction along the needle shaft, peak forces, and number of peak forces per unit length. The concentration of PVA and the number of freeze-thaw cycles both influenced the mechanical interaction between needle and specimen. Insertions into 4m% PVA phantoms with 2 freeze-thaw cycles were comparable to human liver in terms of estimated friction along the needle shaft and the number of peak forces. Therefore, these phantoms are considered to be suitable liver mimicking materials for image-guided needle interventions. The mechanical properties of PVA hydrogels can be influenced in a controlled manner by varying the concentration of PVA and the number of freeze-thaw cycles, to mimic liver tissue characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Normal liver tissue sparing by intensity-modulated proton stereotactic body radiotherapy for solitary liver tumours

    International Nuclear Information System (INIS)

    Petersen, Joergen B. B.; Hansen, Anders T.; Lassen, Yasmin; Grau, Cai; Hoeyer, Morten; Muren, Ludvig P.

    2011-01-01

    Background. Stereotactic body radiotherapy (SBRT) is often the preferred treatment for the advanced liver tumours which owing to tumour distribution, size and multi-focality are out of range of surgical resection or radiofrequency ablation. However, only a minority of patients with liver tumours may be candidates for conventional SBRT because of the limited radiation tolerance of normal liver, intestine and other normal tissues. Due to the favourable depth-dose characteristics of protons, intensity-modulated proton therapy (IMPT) may be a superior alternative to photon-based SBRT. The purpose of this treatment planning study was therefore to investigate the potential sparing of normal liver by IMPT compared to photon-based intensity-modulated radiotherapy (IMRT) for solitary liver tumours. Material and methods. Ten patients with solitary liver metastasis treated at our institution with multi-field SBRT were retrospectively re-planned with IMRT and proton pencil beam scanning techniques. For the proton plans, two to three coplanar fields were used in contrast to five to six coplanar and non-coplanar photon fields. The same planning objectives were used for both techniques. A risk adapted dose prescription to the PTV surface of 12.5-16.75 Gy x 3 was used. Results. The spared liver volume for IMPT was higher compared to IMRT in all 10 patients. At the highest prescription dose level, the median liver volume receiving less than 15 Gy was 1411 cm 3 for IMPT and 955 cm 3 for IMRT (p D 15 Gy > 700 cm 3 constraint. For the D mean = 15 Gy constraint, nine of 10 cases could be treated at the highest dose level using IMPT whereas with IMRT, only two cases met this constraint at the highest dose level and six at the lowest dose level. Conclusion. A considerable sparing of normal liver tissue can be obtained using proton-based SBRT for solitary liver tumours

  4. Biomaterials and Culture Technologies for Regenerative Therapy of Liver Tissue.

    Science.gov (United States)

    Perez, Roman A; Jung, Cho-Rok; Kim, Hae-Won

    2017-01-01

    Regenerative approach has emerged to substitute the current extracorporeal technologies for the treatment of diseased and damaged liver tissue. This is based on the use of biomaterials that modulate the responses of hepatic cells through the unique matrix properties tuned to recapitulate regenerative functions. Cells in liver preserve their phenotype or differentiate through the interactions with extracellular matrix molecules. Therefore, the intrinsic properties of the engineered biomaterials, such as stiffness and surface topography, need to be tailored to induce appropriate cellular functions. The matrix physical stimuli can be combined with biochemical cues, such as immobilized functional groups or the delivered actions of signaling molecules. Furthermore, the external modulation of cells, through cocultures with nonparenchymal cells (e.g., endothelial cells) that can signal bioactive molecules, is another promising avenue to regenerate liver tissue. This review disseminates the recent approaches of regenerating liver tissue, with a focus on the development of biomaterials and the related culture technologies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

    Yarpuzlu, Berkay; Ayyildiz, Mehmet; Tok, Olgu Enis; Aktas, Ranan Gulhan; Basdogan, Cagatay

    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 mechanical characterization experiments on three bovine livers to investigate the changes in gross mechanical properties (stiffness, viscosity, and fracture toughness) for the preservation periods of 5, 11, 17, 29, 41 and 53h after harvesting. Then, the histological examination is performed on the samples taken from the same livers to investigate the changes in apoptotic cell count, collagen accumulation, sinusoidal dilatation, and glycogen deposition as a function of the same preservation periods. Finally, the correlation between the mechanical and histological properties is investigated via the Spearman's Rank-Order Correlation method. The results of our study show that stiffness, viscosity, and fracture toughness of bovine liver increase as the preservation period is increased. These macroscopic changes are very strongly correlated with the increase in collagen accumulation and decrease in deposited glycogen level at the microscopic level. Also, we observe that the largest changes in mechanical and histological properties occur after the first 11-17h of preservation. © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2009-04-01

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

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

    Science.gov (United States)

    2016-05-01

    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...effective for processing and preparing microscopy slides of liver spheroids. The general process involved formalin fixation, dehydration in a...DPBS);  formalin (37% neutral buffer formaldehyde);  series of alcohol solutions: 70, 80, 95, and 100% ethanol in water; 2  xylene

  8. Model and methods to assess hepatic function from indocyanine green fluorescence dynamical measurements of liver tissue.

    Science.gov (United States)

    Audebert, Chloe; Vignon-Clementel, Irene E

    2018-03-30

    The indocyanine green (ICG) clearance, presented as plasma disappearance rate is, presently, a reliable method to estimate the hepatic "function". However, this technique is not instantaneously available and thus cannot been used intra-operatively (during liver surgery). Near-infrared spectroscopy enables to assess hepatic ICG concentration over time in the liver tissue. This article proposes to extract more information from the liver intensity dynamics by interpreting it through a dedicated pharmacokinetics model. In order to account for the different exchanges between the liver tissues, the proposed model includes three compartments for the liver model (sinusoids, hepatocytes and bile canaliculi). The model output dependency to parameters is studied with sensitivity analysis and solving an inverse problem on synthetic data. The estimation of model parameters is then performed with in-vivo measurements in rabbits (El-Desoky et al. 1999). Parameters for different liver states are estimated, and their link with liver function is investigated. A non-linear (Michaelis-Menten type) excretion rate from the hepatocytes to the bile canaliculi was necessary to reproduce the measurements for different liver conditions. In case of bile duct ligation, the model suggests that this rate is reduced, and that the ICG is stored in the hepatocytes. Moreover, the level of ICG remains high in the blood following the ligation of the bile duct. The percentage of retention of indocyanine green in blood, which is a common test for hepatic function estimation, is also investigated with the model. The impact of bile duct ligation and reduced liver inflow on the percentage of ICG retention in blood is studied. The estimation of the pharmacokinetics model parameters may lead to an evaluation of different liver functions. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation

    Science.gov (United States)

    Carroll, Jeffrey B.; Deik, Amy; Fossale, Elisa; Weston, Rory M.; Guide, Jolene R.; Arjomand, Jamshid; Kwak, Seung; Clish, Clary B.; MacDonald, Marcy E.

    2015-01-01

    The HTT CAG expansion mutation causes Huntington’s Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue), using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219) in the striatum to 12% (25/212) in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219) of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224) in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and most evident

  10. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Carroll

    Full Text Available The HTT CAG expansion mutation causes Huntington's Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue, using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219 in the striatum to 12% (25/212 in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219 of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224 in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and

  11. Differentiation of diffuse liver disease with computer-aided tissue echo quantification

    International Nuclear Information System (INIS)

    Cha, Joo Hee; Choi, Byung Ihm; Yun, Eun Joo; Ko, Young Hwan; Song, Chi Sung; Kim, Seung Hyup; Han, Joon Koo; Kim, Tae Kyoung; Lee, Dong Hyuk; Kim, Jong Hyo

    1999-01-01

    The purpose of this study was to evaluate the efficacy of computer-aided tissue echo quantification technique in the differentiation of diffuse liver diseases. Sixty-five patients with chronic liver disease including chronic hepatitis in 21 patients, fatty liver in 11, and liver cirrhosis in 33, and 55 normal volunteers were included in this study. The sonographic images by the Sono-PACS(MARO, Seoul) was recalled and the analysis was done for the hepatic parenchymal coarseness by the program using Visual C++. Difference histogram variation (DHV), edge density (ED) and intertia of concurrence matrix (ICM) were used as the coarseness index. These three indexes were statistically significant (p<0.05) in the differentiation of these four groups. The accuracy of the differentiation between any two of four groups was 83.0%. The accuracy of the differentiation of these four groups was 70.8% at the same time. The computer-aided tissue echo quantification technique is a complementary study for the differentiation of diffuse liver disease.

  12. 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.

  13. Analysis of iron storage proteins in chicken liver and spleen tissues in comparison with human liver ferritin by Moessbauer spectroscopy

    International Nuclear Information System (INIS)

    Oshtrakh, M.I.; Milder, O.B.; Semionkin, V.A.; Malakheeva, L.I.; Prokopenko, P.G.

    2006-01-01

    Characterization of iron storage proteins in liver and spleen from normal chicken and chicken with lymphoid leukemia in comparison with human liver ferritin were considered by Moessbauer spectroscopy (preliminary results). Small differences in Moessbauer hyperfine parameters for both normal and lymphoid leukemia chicken liver and spleen were observed. The value of quadrupole splitting for human liver ferritin was higher than those for chicken tissues. A decrease of iron content in lymphoid leukemia chicken tissues was also found, however, the reason of this fact (pathology or feeding) was not clear yet. (author)

  14. Nuclear magnetic resonance (NMR): application to examine liver tissues during invasion of the Liver fluke in cattle

    International Nuclear Information System (INIS)

    Wranicz, M.; Podbielski, T.; Grabiec, S.

    1989-01-01

    The T 1 and T 2 relaxation times of protons of hydrogen in the liver parenchyma and biliary ducts in normal and parazitized by the Liver fluke cows were determined. A method of the NMR in which a lenght or relaxation time is an index was applied. The value of this index is characteristic for determined physiological and pathological states of cells and it reveals changes which developed in body cells. It was found that tissues of cows parazitized by the Liver fluke (parenchyma and biliary ducts) and healthy ones differ significantly by the lenght of relaxation times. Parazitized tissues show a longer relaxation time than tissues of normal cows. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Anna Ludovica Fracanzani

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

  17. Differentiation between chronic hepatitis and normal liver of grayscale ultrasound tissue quantification using adobe photoshop(5.0)

    International Nuclear Information System (INIS)

    Choi, Jong Cheol; Oh, Jong Young; Lim, Jong Uk; Nam, Kyung Jin

    2001-01-01

    To evaluate whether was any difference in the brightness of echogenicity on gray scale ultrasound imaging between the liver with chronic hepatitis and the normal liver using Adobe photoshop 5.0 Seventy-five patients with pathologically proven chronic hepatitis and twenty normal volunteers were included in this study. Adobe photoshop 5.0 histogram was used to measure the brightness of image. The measured brightness of the liver was divided by the brightness of the kidney, and the radio was calculated and compared between patients with chronic hepatitis and the normal control groups. In addition, the degree of fibrosis was also evaluated. The difference in brightness between the normal liver and live with chronic hepatitis was statistically significant, but no statistically significant difference was observed between the brightness of the liver and the degree of fibrosis in the liver. Tissue echo quantification using Adobe Photoshop 5.0 may be a helpful diagnostic methods for the patients with chronic hepatitis.

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

    Directory of Open Access Journals (Sweden)

    Maryna Perepelyuk

    Full Text Available 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.

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

    Science.gov (United States)

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

    2012-01-01

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

  20. Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice.

    Science.gov (United States)

    Xia, Bo; Cai, Guo He; Yang, Hao; Wang, Shu Pei; Mitchell, Grant A; Wu, Jiang Wei

    2017-12-01

    Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency.

  1. Detection and quantitation analysis of cocaine and metabolites in fixed liver tissue and formalin solutions.

    Science.gov (United States)

    Cingolani, Mariano; Cippitelli, Marcello; Froldi, Rino; Gambaro, Veniero; Tassoni, Giovanna

    2004-01-01

    This study reports the results of the detection and quantitation of cocaine and its metabolites in liver tissues fixed in formalin and in the formalin solutions in which the same tissues were fixed. Toxicological analyses were performed on formalin-fixed liver samples from four cases of death of cocaine abusers and on formalin solutions (10% buffered, pH 7) in which the samples were preserved. Analyses carried out at the time of autopsy on body fluids and tissues allowed identification of cocaine and the metabolite benzoylecgonine. Liver tissue samples were preserved in formalin solutions for four weeks before analysis. Results only showed the presence of benzoylecgonine in the studied materials. The mean levels of recovery of benzoylecgonine in fixed tissues were 12.31% in liver and 84.47% in formalin from liver. Results indicated that benzoylecgonine has good stability, even in biological specimens subjected to chemical fixation.

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  3. Effects of radiosensibilization by metronidazole on liver tissue in patients with gastric carcinomas

    International Nuclear Information System (INIS)

    D'yakova, A.M.; Stefani, N.V.; Zagrebin, V.M.; Senokosov, N.I.; Berdov, B.A.

    1985-01-01

    Metronidazole, used as radiosensitizer in preoperative radiotherapy of gastric carcinoma caused an increased glycogen accumulation in the left lobe of the liver with a radiation dose of 80-100 % of the isodose. The glycogen level was higher not only in comparison with the same liver area in patients without radiosensitizer but also with the right lobe of the own liver within in the area of stray radiation. The effect observed after radiation was considered as result of the sensitizing influence on liver tissue. The sensitizing effect of metronidazole depended on its concentration in the patient's serum. In the right lobe of the liver the glycogen level showed no alteration under metronidazole. Metronidazole reduced the activity of lactate dehydrogenase and cholinesterase in liver tissue independently of its concentration in the serum and of the radiation dose on particular parts of the liver. (author)

  4. Ineffectiveness of rat liver tissues in the screening of connective tissue disease

    International Nuclear Information System (INIS)

    Aziz, Khalil A.

    2004-01-01

    To assess the effectiveness of using rat liver tissue (RLT) for the screening of connective tissue disease (CTD). Results of patient samples submitted to the Clinical Immunology Laboratory, Brimingham Heartlands Hospital, Bordsley Green East, Brimingham, United Kingdom for the investigation of CTD between 2001 and 2002 were analyzed. Positive results for anti-double stranded DNA (dsDNA) antibodies and anti-extractable nuclear antigen (ENA) antibodies were correlated with the results of the corresponding antinuclear antibodies (ANA), obtained by indirect immunofluorescence (IIF) using RLT. In the second part of study samples that were previously tested positive for anti-ENA or anti-dsDNA antibodies were investigated prospectively for ANA using both RLTand human epithelial (Hep-2) cell line. The IIF method employing RLT for screening of CTD, failed to detect ANA patterns from 45% and 25%of patients sample know to contain antibodies to dsDNA and ENA.The anti -dsDNA antibodies that failed to be detected by the RLTwere of low avidity and their clinical significance is unknown. In contrast the antibodies to ENAwere mostly directed against the Ro antigen.In cotrast and like RLT, Hep-2 cell line failed to detect the low avidity anti-dsDNA antibdies.The present study has clearly shown that RLT are ineffective for screening of CTD. It is recommended that laboratories which ars still using these tissues should consider replacing them with the Hep-2 cell line. (author)

  5. Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours

    International Nuclear Information System (INIS)

    Meyer, Carsten; Pieper, Claus Christian; Wilhelm, Kai E.; Schild, Hans Heinz; Ezziddin, Samer; Ahmadzadehfar, Hojjat

    2014-01-01

    To describe a new approach to protect nontarget healthy liver tissue using degradable starch microspheres (DSM) as a short-term embolizate during radioembolization of liver tumours with 90 Y microspheres. Between December 2011 and July 2012 radioembolization was performed in 54 patients. Five of these patients (three women, two men; mean age 67 years) underwent protective temporary embolization using DSM (EmboCept registered S) of normal liver tissue that could not be excluded from the area treated by radioembolization through catheter repositioning. Clinical symptoms, laboratory findings, preinterventional imaging, and 99m Tc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with 18 F-FDG PET/CT and MRI, were evaluated in relation to the technical and clinical success of the protective embolization. Temporary embolization of arteries supplying normal liver tissue using DSM was technically successful in all five patients. 99m Tc-MAA SPECT/CT performed in the first two patients after DSM injection showed no increased pulmonary shunting compared to the MAA test injection without DSM. Bremsstrahlung SPECT/CT after radioembolization demonstrated satisfactory irradiation of the tumour and successful protection of normal liver tissue. There were only mild hepatotoxic effects (grade 1) on laboratory follow-up examinations, and no adverse events associated with DSM embolization or radioembolization were recorded. Temporary embolization with DSM before radioembolization is feasible and can effectively protect areas of normal liver tissue from irradiation and avoid permanent embolization if other methods such as catheter repositioning are not possible due to the location of the metastases. (orig.)

  6. Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Carsten [University of Bonn, Department of Radiology, Bonn (Germany); Pieper, Claus Christian; Wilhelm, Kai E.; Schild, Hans Heinz [University of Bonn, Department of Radiology, Bonn (Germany); Ezziddin, Samer; Ahmadzadehfar, Hojjat [University of Bonn, Department of Nuclear Medicine, Bonn (Germany)

    2014-02-15

    To describe a new approach to protect nontarget healthy liver tissue using degradable starch microspheres (DSM) as a short-term embolizate during radioembolization of liver tumours with {sup 90}Y microspheres. Between December 2011 and July 2012 radioembolization was performed in 54 patients. Five of these patients (three women, two men; mean age 67 years) underwent protective temporary embolization using DSM (EmboCept {sup registered} S) of normal liver tissue that could not be excluded from the area treated by radioembolization through catheter repositioning. Clinical symptoms, laboratory findings, preinterventional imaging, and {sup 99m}Tc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with {sup 18}F-FDG PET/CT and MRI, were evaluated in relation to the technical and clinical success of the protective embolization. Temporary embolization of arteries supplying normal liver tissue using DSM was technically successful in all five patients. {sup 99m}Tc-MAA SPECT/CT performed in the first two patients after DSM injection showed no increased pulmonary shunting compared to the MAA test injection without DSM. Bremsstrahlung SPECT/CT after radioembolization demonstrated satisfactory irradiation of the tumour and successful protection of normal liver tissue. There were only mild hepatotoxic effects (grade 1) on laboratory follow-up examinations, and no adverse events associated with DSM embolization or radioembolization were recorded. Temporary embolization with DSM before radioembolization is feasible and can effectively protect areas of normal liver tissue from irradiation and avoid permanent embolization if other methods such as catheter repositioning are not possible due to the location of the metastases. (orig.)

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

    Science.gov (United States)

    Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

    2015-01-01

    Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. 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. PMID:26909307

  8. Mechanics of fresh, frozen-thawed and heated porcine liver tissue.

    Science.gov (United States)

    Wex, Cora; Stoll, Anke; Fröhlich, Marlen; Arndt, Susann; Lippert, Hans

    2014-06-01

    For a better understanding of the effects of thermally altered soft tissue, the biothermomechanics of these tissues need to be studied. Without the knowledge of the underlying physical processes and the parameters that can be controlled clinically, thermal treatment of cancerous hepatic tissue or the preservation of liver grafts are based primarily on trial and error. Thus, this study is concerned with the investigation of the influence of temperature on the rheological properties and the histological properties of porcine liver. Heating previously cooled porcine liver tissue above 40 °C leads to significant, irreversible stiffness changes observed in the amplitude sweep. The increase of the complex shear module of healthy porcine liver from room temperature to 70 °C is approximately 9-fold. Comparing the temperatures -20 °C and 20 °C, no significant difference of the mechanical properties was observed. Furthermore, there is a strong relation between the mechanical and histological properties of the porcine liver. Temperatures above 40 °C destroy the collagen matrix within the liver tissue. This results in the alteration of the biomechanical properties. The time-temperature superposition principle is applied to generate temperature-dependent shift factors that can be described by a two-part exponential function model with an inflection temperature of 45 °C. Tumor ablation techniques such as heating or freezing have a significant influence on the histology of liver tissue. However, only for temperatures above body temperature an influence on the mechanical properties of hepatic tissues was noticeable. Freezing up to -20 °C did not affect the liver mechanics.

  9. Aldolase A isoenzyme levels in serum and tissues of patients with liver diseases

    International Nuclear Information System (INIS)

    Asaka, M.; Nagase, K.; Miyazaki, T.; Alpert, E.

    1983-01-01

    A radioimmunoassay specific for human aldolase A was used to measure human aldolase A levels in human tissue and serum of patients with various liver diseases. The method was a double-antibody technique using radio-iodinated purified aldolase A, chicken antibody to aldolase A, and rabbit antibody to chicken immunoglobulin G. Normal liver tissue contains only a small amount of aldolase A. In contrast, aldolase A predominates in liver cell carcinoma tissue. Aldolase A levels in the sera of normal subjects were 171 +/- 39 ng/ml (mean +/- 2 SD). In almost all of the nonmalignant liver diseases, the aldolase A levels remained less than 210 ng/ml. The serum aldolase A levels increased remarkable only in fulminant hepatitis. in contrast, 32 of 34 patients with liver cell carcinoma and all of 29 patients with metastatic liver carcinoma showed clearly increased serum aldolase A levels. More patients with primary liver cell carcinoma had increased serum aldolase A levels than elevations of serum alpha-fetoprotein. These results suggest that the determination of aldolase A by radioimmunoassay may be useful to differentiate malignant form nonmalignant liver diseases

  10. Liver slices in in vitro pharmacotoxicology with special reference to the use of human liver tissue

    NARCIS (Netherlands)

    Olinga, Peter; Meijer, D.K F; Slooff, M.JH; Groothuis, Geny

    In the early years of research in in vitro pharmacotoxicology liver slices have been used. After a decline in the application of slices in favour of the use of isolated hepatocytes and the isolated perfused liver preparation, the development of the Krumdieck slicer in the 1980s led to a 'comeback'

  11. A Model for Micro-Dosimetry in Virtual Liver Tissues

    Science.gov (United States)

    Motivation: Humans are potentially exposed to over 6,000 environmental chemicals. The liver is the primary organ for metabolism and often the first site of chemical-induced toxicity in animal testing, but it remains difficult to translate these outcomes to humans. To address thi...

  12. 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.

  13. Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic functions useful for drug discovery.

    Science.gov (United States)

    Kizawa, Hideki; Nagao, Eri; Shimamura, Mitsuru; Zhang, Guangyuan; Torii, Hitoshi

    2017-07-01

    The liver plays a central role in metabolism. Although many studies have described in vitro liver models for drug discovery, to date, no model has been described that can stably maintain liver function. Here, we used a unique, scaffold-free 3D bio-printing technology to construct a small portion of liver tissue that could stably maintain drug, glucose, and lipid metabolism, in addition to bile acid secretion. This bio-printed normal human liver tissue maintained expression of several kinds of hepatic drug transporters and metabolic enzymes that functioned for several weeks. The bio-printed liver tissue displayed glucose production via cAMP/protein kinase A signaling, which could be suppressed with insulin. Bile acid secretion was also observed from the printed liver tissue, and it accumulated in the culture medium over time. We observed both bile duct and sinusoid-like structures in the bio-printed liver tissue, which suggested that bile acid secretion occurred via a sinusoid-hepatocyte-bile duct route. These results demonstrated that our bio-printed liver tissue was unique, because it exerted diverse liver metabolic functions for several weeks. In future, we expect our bio-printed liver tissue to be applied to developing new models that can be used to improve preclinical predictions of long-term toxicity in humans, generate novel targets for metabolic liver disease, and evaluate biliary excretion in drug development.

  14. Long-term culture of human liver tissue with advanced hepatic functions.

    Science.gov (United States)

    Ng, Soon Seng; Xiong, Anming; Nguyen, Khanh; Masek, Marilyn; No, Da Yoon; Elazar, Menashe; Shteyer, Eyal; Winters, Mark A; Voedisch, Amy; Shaw, Kate; Rashid, Sheikh Tamir; Frank, Curtis W; Cho, Nam Joon; Glenn, Jeffrey S

    2017-06-02

    A major challenge for studying authentic liver cell function and cell replacement therapies is that primary human hepatocytes rapidly lose their advanced function in conventional, 2-dimensional culture platforms. Here, we describe the fabrication of 3-dimensional hexagonally arrayed lobular human liver tissues inspired by the liver's natural architecture. The engineered liver tissues exhibit key features of advanced differentiation, such as human-specific cytochrome P450-mediated drug metabolism and the ability to support efficient infection with patient-derived inoculums of hepatitis C virus. The tissues permit the assessment of antiviral agents and maintain their advanced functions for over 5 months in culture. This extended functionality enabled the prediction of a fatal human-specific hepatotoxicity caused by fialuridine (FIAU), which had escaped detection by preclinical models and short-term clinical studies. The results obtained with the engineered human liver tissue in this study provide proof-of-concept determination of human-specific drug metabolism, demonstrate the ability to support infection with human hepatitis virus derived from an infected patient and subsequent antiviral drug testing against said infection, and facilitate detection of human-specific drug hepatotoxicity associated with late-onset liver failure. Looking forward, the scalability and biocompatibility of the scaffold are also ideal for future cell replacement therapeutic strategies.

  15. Difference in Uptake of Tetrodotoxin and Saxitoxins into Liver Tissue Slices among Pufferfish, Boxfish and Porcupinefish

    Directory of Open Access Journals (Sweden)

    Yuji Nagashima

    2018-01-01

    Full Text Available Although pufferfish of the family Tetraodontidae contain high levels of tetrodotoxin (TTX mainly in the liver, some species of pufferfish, boxfish of the family Ostraciidae, and porcupinefish of the family Diodontidae do not. To clarify the mechanisms, uptake of TTX and saxitoxins (STXs into liver tissue slices of pufferfish, boxfish and porcupinefish was examined. Liver tissue slices of the pufferfish (toxic species Takifugu rubripes and non-toxic species Lagocephalus spadiceus, L. cheesemanii and Sphoeroides pachygaster incubated with 50 µM TTX accumulated TTX (0.99–1.55 µg TTX/mg protein after 8 h, regardless of the toxicity of the species. In contrast, in liver tissue slices of boxfish (Ostracion immaculatus and porcupinefish (Diodon holocanthus, D. liturosus, D. hystrix and Chilomycterus reticulatus, TTX content did not increase with incubation time, and was about 0.1 µg TTX/mg protein. When liver tissue slices were incubated with 50 µM STXs for 8 h, the STXs content was <0.1 µg STXs/mg protein, irrespective of the fish species. These findings indicate that, like the toxic species of pufferfish T. rubripes, non-toxic species such as L. spadiceus, L. cheesemanii and S. pachygaster, potentially take up TTX into the liver, while non-toxic boxfish and porcupinefish do not take up either TTX or STXs.

  16. Affinity of /sup 167/Tm-citrate for tumor and liver tissue

    Energy Technology Data Exchange (ETDEWEB)

    Ando, A; Ando, I; Hiraki, T; Sakamoto, K; Hisada, K; Takeshita, M

    1983-10-07

    Strong affinity of /sup 167/Tm-citrate for tumor tissue was reconfirmed by using Ehrlich tumor. Excellent tumor imaging was obtained with /sup 167/Tm-citrate because of its strong tumor affinity and because of the suitable physical characteristics of /sup 167/Tm. A large amount of /sup 167/Tm had accumulated in the connective tissue which contained inflammatory tissue, quite large amounts were found in areas containing viable and necrotic tumor tissue, and small amounts were present in viable tumor tissue. /sup 167/Tm was not seen in necrotic tumor tissue. It was concluded that lysosomes did not play a major role in the tumor concentration of /sup 167/Tm, but played an important role in the liver concentration of this nuclide. In the case of hepatoma AH109A, it was presumed that lysosomes played a considerably important role in the tumor concentration of /sup 167/Tm, hepatoma AH109A possessing some residual features of the liver. /sup 167/Tm was bound to acid mucopolysaccharides and transposed by the acid mucopolysaccharides in the tumor tissues and liver. The acid mucopolysaccharides to which /sup 167/Tm were bound in tumor and liver, were heparan sulfate, chondroitin sulfate (or keratosulfate) and heparin (or keratosulfate).

  17. Affinity of 167Tm-citrate for tumor and liver tissue

    International Nuclear Information System (INIS)

    Ando, A.; Ando, I.; Hiraki, T.

    1983-01-01

    Strong affinity of 167 Tm-citrate for tumor tissue was reconfirmed by using Ehrlich tumor. Excellent tumor imaging was obtained with 167 Tm-citrate because of its strong tumor affinity and because of the suitable physical characteristics of 167 Tm. A large amount of 167 Tm had accumulated in the connective tissue which contained inflammatory tissue, quite large amounts were found in areas containing viable and necrotic tumor tissue, and small amounts were present in viable tumor tissue. 167 Tm was not seen in necrotic tumor tissue. It was concluded that lysosomes did not play a major role in the tumor concentration of 167 Tm, but played an important role in the liver concentration of this nuclide. In the case of hepatoma AH109A, it was presumed that lysosomes played a considerably important role in the tumor concentration of 167 Tm, hepatoma AH109A possessing some residual features of the liver. 167 Tm was bound to acid mucopolysaccharides and transposed by the acid mucopolysaccharides in the tumor tissues and liver. The acid mucopolysaccharides to which 167 Tm were bound in tumor and liver, were heparan sulfate, chondroitin sulfate (or keratosulfate) and heparin (or keratosulfate). (orig.)

  18. MR-guided noninvasive thermal coagulation of in-vivo liver tissue using ultrasonic phased array

    Science.gov (United States)

    Daum, Douglas R.; Smith, Nadine; McDannold, Nathan; Hynynen, Kullervo H.

    1999-05-01

    Magnetic resonance (MR) imaging was used to guide and monitor the thermal tissue coagulation of in vivo porcine tissue using a 256 element ultrasonic phased array. The array could coagulate tissue volumes greater than 2 cm3 in liver and 0.5 cm3 in kidney using a single 20 second sonication. This sonication used multiple focus fields which were temporally cycled to heat large tissue volumes simultaneously. Estimates of the coagulated tissue using a thermal dose threshold compare well with T2-weighted images of post sonication lesions. The overlapping large focal volumes could aid in the treatment of large tumor volumes which require multiple overlapping sonications. The ability of MR to detect the presence and undesirable thermal increases at acoustic obstacle such as cartilaginous and bony ribs is demonstrated. This could have a significant impact on the ability to monitor thermal treatments of the liver and other organs which are acoustically blocked.

  19. 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.

  20. 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......-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...

  1. Tissue specific MR contrast media role in the differential diagnosis of cirrhotic liver nodules.

    Science.gov (United States)

    Lupescu, Ioana Gabriela; Capsa, Razvan A; Gheorghe, Liana; Herlea, Vlad; Georgescu, Serban A

    2008-09-01

    State-of-the-art magnetic resonance (MR) imaging using tissue specific contrast media facilitates detection and characterization in most cases of hepatic nodules. According to the currently used nomenclature, in liver cirrhosis there are only two major types of hepatocellular nodular lesions: regenerative lesions and dysplastic or neoplastic lesions. The purpose of this clinical imaging review is to provide information on the properties of tissue-specific MR contrast agents and on their usefulness in the demonstration of the pathologic changes that take place at the level of the hepatobiliary and reticuloendothelial systems during the carcinogenesis in liver cirrhosis.

  2. 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.

  3. Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

    2016-07-26

    Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.

  4. 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....

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

    Science.gov (United States)

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

    2007-06-01

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

  6. Characteristics of liver tissue for attenuate the gamma radiation

    International Nuclear Information System (INIS)

    Arcos P, A.; Rodriguez N, S.; Pinedo S, A.; Amador V, P.; Chacon R, A.; Vega C, H.R.

    2005-01-01

    It was determined the lineal attenuation coefficient of hepatic tissue before gamma radiation of a source of 137 Cs. When exposing organic material before X or gamma radiation fields, part of the energy of the photons is absorbed by the material, while another part crosses it without producing any effect. The quantity of energy that is absorbed is a measure of the dose that receives the material. The three main mechanisms by means of which the gamma rays interacting with the matter are: The Photoelectric Effect, the Compton dispersion and the Even production; the sum of these three processes is translated in the attenuation coefficient of the radiation. In this work we have used hepatic tissue of bovine, as substitute of the human hepatic tissue, and we have measured the lineal attenuation coefficient for photons of 0.662 MeV. Through a series of calculations we have determined the lineal attenuation coefficient for photons from 10 -3 to 10 -5 MeV and the measured coefficient was compared with the one calculated. (Author)

  7. Multi-locus sequence subtypes of Campylobacter detected on the surface and from internal tissue of retail chicken livers

    Science.gov (United States)

    Foodborne campylobacteriosis has been traced to undercooked chicken liver. The objectives of this study were to measure prevalence of Campylobacter associated with chicken livers at retail and determine which subtypes are detected on the surface and inner tissue of livers. Fifteen packages of fres...

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  9. The functional state of perfused liver tissue in X-ray irradiated rats

    International Nuclear Information System (INIS)

    Borovikova, G.V.; Dokshina, G.A.; Lapteva, T.A.

    1981-01-01

    The results of studying the functional state of perfused liver tissue isolated from rates after irradiation in the 18.06x10 - 2 Kl/kg dose, which has been estimated by transamination process rate catalized alanine-(KF 2.6x1.2, ALT and aspartate by aminotransferases (KF 2.6x1.1, ACT), gluconeogenesis and urea production intensity presented. When comparing the results obtained on the perfused liver deprived of homeostatic body effects it has been found that the liver isolated from the body for the first 24 hours of the radiation sickness development possesses a higher radiation activity which manifests itself in intensification of the processes of gluconeogenesis and transamination with substrate addition. The third 24 hours upon irradiation in the isolated liver the intensity of the gluconeogenesis and transamination processes is attenuated

  10. Functional state of perfused liver tissue in X-ray irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Borovikova, G.V.; Dokshina, G.A.; Lapteva, T.A. (Tomskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Biologii i Biofiziki)

    1981-01-01

    The results of studying the functional state of perfused liver tissue isolated from rats after irradiation in the 18.06x10/sup -2/ Kl/kg dose, which has been estimated by transamination process rate catalized alanine-(KF 2.6x1.2, ALT and aspartate by aminotransferases (KF 2.6x1.1, ACT), gluconeogenesis and urea production intensity presented. When comparing the results obtained on the perfused liver deprived of homeostatic body effects it has been found that the liver isolated from the body for the first 24 hours of the radiation sickness development possesses a higher radiation activity which manifests itself in intensification of the processes of gluconeogenesis and transamination with substrate addition. The third 24 hours upon irradiation in the isolated liver the intensity of the gluconeogenesis and transamination processes is attenuated.

  11. 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.

  12. Antioxidant Role of Pomegranates on Liver and Brain Tissues of Rats Exposed to an Organophosphorus Insecticide

    International Nuclear Information System (INIS)

    Abd Elmonem, H.A.

    2014-01-01

    Toxicities of organophosphorus insecticides cause oxidative damage on many organs such as the liver and brain due to generation of reactive oxygen species. Pomegranate is among the richest fruit in poly - phenols. The aim of this study was to compare between the antioxidant strength of pomegranate juice (PJ) and pomegranate molasses (PM) and their effects on alanine transferase (ALT), aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and total protein (TP) in liver and levels of malondialdehyde (MAD), reduced glutathione (GSH) and nitric oxide (NO) in rat liver and brain tissues exposed to 1/10 LD 50 diazinon (DI). Six groups each of 6 male albino rats were used comprising control, DI, PJ, PM, PJ + DI and PM + DI for 15 days. The activities of ALT, AST, and TP concentration in liver have been increased due to treatment of rats with DI. These increases restored to normalcy when rats were supplemented with PJ or PM with DI. The results demonstrate that treatment with DI induced significant increase in MDA and NO concentrations and significant decrease in GSH levels of liver and brain tissues. The administration of PJ or PM along with DI significant decrease in MDA and NO levels and significant increase in GSH level compared to DI-group. The present study suggest that PJ or PM has a potential protective effect as it can elevate antioxidant defense system, lessens induced oxidative dam - ages and protect the brain and liver tissue against DI-induced toxicity. In addition, comaring PJ with PM it was noticed that PJ had higher antioxidant activity as evidenced by increased GSH content and decreased NO level in the liver by greater extend than PM.

  13. 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

    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.

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

    Science.gov (United States)

    1980-03-01

    TQuantitative ultrastructural studies were conducted on liver tissue f ran beach Lj mice, Per~ ascus polionotus, exposed to the toxin 2,3, 7f8...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

  15. NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina

    NARCIS (Netherlands)

    Segarra, Nuria Garcia; Ballhausen, Diana; Crawford, Heather; Perreau, Matthieu; Campos-Xavier, Belinda; van Spaendonck-Zwarts, Karin; Vermeer, Cees; Russo, Michel; Zambelli, Pierre-Yves; Stevenson, Brian; Royer-Bertrand, Beryl; Rivolta, Carlo; Candotti, Fabio; Unger, Sheila; Munier, Francis L.; Superti-Furga, Andrea; Bonafé, Luisa

    2015-01-01

    We report two unrelated patients with a multisystem disease involving liver, eye, immune system, connective tissue, and bone, caused by biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene. Both presented as infants with recurrent episodes triggered by fever with vomiting,

  16. Quantification of total mercury in liver and heart tissue of Harbor Seals (Phoca vitulina) from Alaska USA

    International Nuclear Information System (INIS)

    Marino, Kady B.; Hoover-Miller, Anne; Conlon, Suzanne; Prewitt, Jill; O'Shea, Stephen K.

    2011-01-01

    This study quantified the Hg levels in the liver (n=98) and heart (n=43) tissues of Harbor Seals (Phoca vitulina) (n=102) harvested from Prince William Sound and Kodiak Island Alaska. Mercury tissue dry weight (dw) concentrations in the liver ranged from 1.7 to 393 ppm dw, and in the heart from 0.19 to 4.99 ppm dw. Results of this study indicate liver and heart tissues' Hg ppm dw concentrations significantly increase with age. Male Harbor Seals bioaccumulated Hg in both their liver and heart tissues at a significantly faster rate than females. The liver Hg bioaccumulation rates between the harvest locations Kodiak Island and Prince William Sound were not found to be significantly different. On adsorption Hg is transported throughout the Harbor Seal's body with the partition coefficient higher for the liver than the heart. No significant differences in the bio-distribution (liver:heart Hg ppm dw ratios (n=38)) values were found with respect to either age, sex or geographic harvest location. In this study the age at which Hg liver and heart bioaccumulation levels become significantly distinct in male and female Harbor Seals were identified through a Tukey's analysis. Of notably concern to human health was a male Harbor Seal's liver tissue harvested from Kodiak Island region. Mercury accumulation in this sample tissue was determined through a Q-test to be an outlier, having far higher Hg concentrarion (liver 392 Hg ppm dw) than the general population sampled. - Highlights: ► Mercury accumulation in the liver and heart of seals exceed food safety guidelines. ► Accumulation rate is greater in males than females with age. ► Liver mercury accumulation is greater than in the heart tissues. ► Mercury determination by USA EPA Method 7473 using thermal decomposition.

  17. The experimental study of radiation injury on bile duct and liver tissue

    International Nuclear Information System (INIS)

    Cao Guiwen; Wang Bin; Sun Yequan; Shao Xueye; Ning Houfa; Sui Shouguang; Wang Xiuchun; Bai Xuming

    2007-01-01

    Objective: To investigate the safety, acceptance and the effective extent of 192 Ir-internal irradiation, providing theoretical guidelines for HC. Methods: Sixteen male healthy hybrid dogs enrolled in the experiment were divided into 4 groups of 4 each. The brachytherapy applicator was introduced from gall bladder into the convergence of cystic duct with common hepatic duct during the operation and a small chip of 1 cm 3 liver tissue was cut off and taken for control later on. The animals in group A-D were irradiated by 192 Ir-internal irradiation with 30 Gy, 40 Gy, 50 Gy arid 60 Gy at the correlative dose points respectively. Animals were put to death after 10 days subsequently, with sampling specimens obtained from radiation cystic duct and the in between liver tissue with the distant cystic duct. The radiation injury of the cystic duct and liver tissue near bile ducts were observed and studied by light microscope and transmission election microscope. Results: By the limit of the safest endurance dose(50 Gy) of Bile duct, unreversed injury of the nuclei of liver cells occurred at 0 to 15 mm from bile duct revealed by transmission electron microscope and light microscope. The whole biliary duct wall would be undergone necrosis with irradiation dose over 60 Gy. Conclusions: Normal bile duct possesses good endurance to 192 Ir-internal irradiation. Within the safest endurance limit of 50 Gy the effective irradiation field could reach 15 mm from the involved bile duct. (authors)

  18. 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.

  19. The protective effect of pomegranate extract against cisplatin toxicity in rat liver and kidney tissue.

    Science.gov (United States)

    Bakır, Salih; Yazgan, Ümit Can; İbiloğlu, İbrahim; Elbey, Bilal; Kızıl, Murat; Kelle, Mustafa

    2015-01-01

    The purpose of this study was to perform a histopathological investigation, at the light microscopy level, of the protective effects of pomegranate extract in cisplatin-induced liver and kidney damage in rats. Twenty-eight adult male Wistar albino rats were randomly divided into four groups of seven animals: Group 1: Control; Group 2: Treated for 10 consecutive days by gavage with pomegranate juice (2 ml/kg/day); Group 3: Injected intraperitoneally with cisplatin (8 mg/kg body weight, single dose) onset of the day 5, and Group 4: Treated by gavage with pomegranate juice 10 days before and after a single injection of cisplatin onset of the day 5. After 10 days, the animals were sacrificed and their kidneys and liver tissue samples were removed from each animal after experimental procedures. Cisplatin-induced renal and hepatic toxicity and the effect of pomegranate juice were evaluated by histopatological examinations. In the kidney tissue, pomegranate juice significantly ameliorated cisplatin-induced structural alterations when compared with the cisplatin alone group. But in the liver tissue, although pomegranate juice attenuated the cisplatin-induced toxicity only in two rats, significant improvement was not observed. In conclusion, these results demonstrate that the anti-oxidant pomegranate juice might have a protective effect against cisplatin-induced toxicity in rat kidney, but not in liver. Pomegranate juice could be beneficial as a dietary supplement in patients receiving chemotherapy medications.

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

    International Nuclear Information System (INIS)

    Lanza-Jacoby, S.; Tabares, A.

    1990-01-01

    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

  1. 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.

  2. Ultrasound imaging of Nd:YAG laser-induced tissue coagulation in porcine livers.

    Science.gov (United States)

    Ritzel, U; Wietzke-Braun, P; Brinck, U; Leonhardt, U; Ramadori, G

    2001-12-01

    Absorption of laser light energy induces denaturation of proteins and thermocoagulation of irradiated tissue. Recently, MRI-guided laser coagulation in combination with MR thermometry was reported as a treatment of liver tumours. In the present study ultrasonographic imaging was evaluated for its suitability in laser induced tissue thermocoagulation. Fresh porcine livers were used for ex vivo examinations. Placement of the laser catheter and tissue coagulation during laser light emission were online monitored by ultrasonography. Nd:YAG laser-induced tissue damage was evaluated by macroscopical and microscopical examinations of histological sections. During laser light emission a marked hyperdense signal enhancement was observed by ultrasonography which strongly correlated with the extent of macroscopic tissue damage. The size of laser-induced coagulation zone depended on both the power setting and total energy delivered. Carbonization of the tissue surrounding the laser tip is a limiting factor because of laser light absorption. However our data indicate that using appropriate laser energy and exposure time prevent carbonization although carbonization can not be visualized by ultrasonography. It is concluded from the present ex vivo studies that laser coagulation can be effectively performed under ultrasonographic guidance.

  3. 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.

  4. Fuzzy logic algorithm for quantitative tissue characterization of diffuse liver diseases from ultrasound images.

    Science.gov (United States)

    Badawi, A M; Derbala, A S; Youssef, A M

    1999-08-01

    Computerized ultrasound tissue characterization has become an objective means for diagnosis of liver diseases. It is difficult to differentiate diffuse liver diseases, namely cirrhotic and fatty liver by visual inspection from the ultrasound images. The visual criteria for differentiating diffused diseases are rather confusing and highly dependent upon the sonographer's experience. This often causes a bias effects in the diagnostic procedure and limits its objectivity and reproducibility. Computerized tissue characterization to assist quantitatively the sonographer for the accurate differentiation and to minimize the degree of risk is thus justified. Fuzzy logic has emerged as one of the most active area in classification. In this paper, we present an approach that employs Fuzzy reasoning techniques to automatically differentiate diffuse liver diseases using numerical quantitative features measured from the ultrasound images. Fuzzy rules were generated from over 140 cases consisting of normal, fatty, and cirrhotic livers. The input to the fuzzy system is an eight dimensional vector of feature values: the mean gray level (MGL), the percentile 10%, the contrast (CON), the angular second moment (ASM), the entropy (ENT), the correlation (COR), the attenuation (ATTEN) and the speckle separation. The output of the fuzzy system is one of the three categories: cirrhosis, fatty or normal. The steps done for differentiating the pathologies are data acquisition and feature extraction, dividing the input spaces of the measured quantitative data into fuzzy sets. Based on the expert knowledge, the fuzzy rules are generated and applied using the fuzzy inference procedures to determine the pathology. Different membership functions are developed for the input spaces. This approach has resulted in very good sensitivities and specificity for classifying diffused liver pathologies. This classification technique can be used in the diagnostic process, together with the history

  5. Derangements of liver tissue bioenergetics in concanavalin A-induced hepatitis.

    Science.gov (United States)

    Al-Shamsi, Mariam; Shahin, Allen; Mensah-Brown, Eric P K; Souid, Abdul-Kader

    2013-01-12

    A novel in vitro system was employed to investigate liver tissue respiration (mitochondrial O2 consumption) in mice treated with concanavalin A (Con A). This study aimed to investigate hepatocyte bioenergetics in this well-studied hepatitis model. C57Bl/6 and C57Bl/6 IFN-γ-/- mice were injected intravenously with 12 mg ConA/kg. Liver specimens were collected at various timepoints after injection and analyzed for cellular respiration and caspase activation. Serum was analyzed for interferon-gamma (IFN-γ) and aminotransferases. Fluorescence activated cell sorting analysis was used to determine the phenotype of infiltrating cells, and light and electron microscopy were used to monitor morphological changes. Phosphorescence analyzer that measured dissolved O2 as function of time was used to evaluate respiration. In sealed vials, O2 concentrations in solutions containing liver specimen and glucose declined linearly with time, confirming zero-order kinetics of hepatocyte respiration. O2 consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Enhanced liver respiration (by ≈68%, pactivity and serum IFN-γ and aminotransferase levels were noted 3 hr after ConA treatment and progressed with time. The above-noted changes were less pronounced in C57Bl/6 IFN-γ-/- mice treated with ConA. Based on these results, liver tissue bioenergetics is increased 3 hr after ConA exposure. This effect is driven by the pathogenesis of the disease, in which IFN-γ and other cytokines contribute to. Subsequent declines in liver bioenergetics appear to be a result of necrosis and active caspases targeting the mitochondria within hepatocytes.

  6. Derangements of liver tissue bioenergetics in Concanavalin A-induced hepatitis

    Directory of Open Access Journals (Sweden)

    Al-Shamsi Mariam

    2013-01-01

    Full Text Available Abstract Background A novel in vitro system was employed to investigate liver tissue respiration (mitochondrial O2 consumption in mice treated with concanavalin A (Con A. This study aimed to investigate hepatocyte bioenergetics in this well-studied hepatitis model. Methods C57Bl/6 and C57Bl/6 IFN-γ−/− mice were injected intravenously with 12 mg ConA/kg. Liver specimens were collected at various timepoints after injection and analyzed for cellular respiration and caspase activation. Serum was analyzed for interferon-gamma (IFN-γ and aminotransferases. Fluorescence activated cell sorting analysis was used to determine the phenotype of infiltrating cells, and light and electron microscopy were used to monitor morphological changes. Phosphorescence analyzer that measured dissolved O2 as function of time was used to evaluate respiration. Results In sealed vials, O2 concentrations in solutions containing liver specimen and glucose declined linearly with time, confirming zero-order kinetics of hepatocyte respiration. O2 consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Enhanced liver respiration (by ≈68%, pp=0.005 was noted 12 hr after ConA treatment, and occurred in conjunction with deranged mitochondria, areas of necrosis, and prominent infiltrations with immune cells, most significantly, CD3+NKT+ cells. Increases in intracellular caspase activity and serum IFN-γ and aminotransferase levels were noted 3 hr after ConA treatment and progressed with time. The above-noted changes were less pronounced in C57Bl/6 IFN-γ−/− mice treated with ConA. Conclusions Based on these results, liver tissue bioenergetics is increased 3 hr after ConA exposure. This effect is driven by the pathogenesis of the disease, in which IFN-γ and other cytokines contribute to. Subsequent declines in liver bioenergetics appear to be a result of necrosis and active caspases targeting the mitochondria within hepatocytes.

  7. Heart over mind: metabolic control of white adipose tissue and liver.

    Science.gov (United States)

    Nakamura, Michinari; Sadoshima, Junichi

    2014-12-01

    Increasing evidence suggests that the heart controls the metabolism of peripheral organs. Olson and colleagues previously demonstrated that miR‐208a controls systemic energy homeostasis through the regulation of MED13 in cardiomyocytes (Grueter et al, 2012). In their follow‐up study in this issue of EMBO Molecular Medicine, white adipose tissue (WAT) and liver are identified as the physiological targets of cardiac MED13 signaling, most likely through cardiac‐derived circulating factors, which boost energy consumption by upregulating metabolic gene expression and increasing mitochondrial numbers (Baskin et al, 2014). In turn, increased energy expenditure in WAT and the liver confers leanness. These findings strengthen the evidence of metabolic crosstalk between the heart and peripheral tissues through cardiokines and also set the stage for the development of novel treatments for metabolic syndrome.

  8. Lesions in Porcine Liver Tissues Created by Continuous High Intensity Ultrasound Exposures in Vitro

    International Nuclear Information System (INIS)

    Zhang Zhe; Chen Tao; Zhang Dong

    2013-01-01

    Lesions in porcine liver tissues created by continuous high intensity focused ultrasound (HIFU) exposures in vitro are theoretically and experimentally investigated, with the transmitter moving along a linear path at a fixed speed. Numerical simulations of the lesion formation are performed based on the Khokhlov—Zabolotskaya—Kuznetov equation and the bio-heat equation. In order to verify the theoretical predictions, experiments are performed in the one-dimensional scanning mode to measure the cross-sectional area of lesions created in the in vitro porcine liver exposed to 1.01-MHz HIFU pulses with the acoustic power of 70 W. The results indicate that, compared to the traditional discrete treatment protocol, the application of a continuous scanning model can create more uniform lesions in tissues and significantly reduces the total treatment time from 47s to 30s

  9. Transmission electron microscopy of heart and liver tissues from rats fed with gums arabic and tragacanth.

    Science.gov (United States)

    Anderson, D M; Ashby, P; Busuttil, A; Kempson, S A; Lawson, M E

    1984-04-01

    Transmission electron microscopy has been used to examine the ultrastructure of rat hearts and livers after diet supplementation with (a) 0, 0.5, 1.5, 2.5 and 3.5% (w/w) gum tragacanth (GT) for 91 days, (b) 0 and 1% GT for 5 days (c) 0, 1, 4 and 8% (w/w) gum arabic (GA) for 28 days. The preparation and scrutiny of the electron micrographs was undertaken by two independent teams of specialists. There were no detectable abnormalities in any of the organelles in the heart and liver specimens from any of the test animals and no inclusions nor other pathological changes were observed. All micrographs showed normal, healthy tissues; particular attention was given to the mitochondria in hepatocytes as they serve as sensitive indicators of the health and state of activity of cells. In addition, the data obtained from assays of the microsomal protein and cytochrome P-450 content of the livers showed that GA and GT did not cause inductive effects. These results do not support earlier suggestions, based on in vitro assays, that GA and GT cause changes in the function of rat heart and liver mitochondria and liver microsomes; however, they confirm a report by Zbinden that the ingestion of GT does not produce abnormalities in the cardiac function of rats.

  10. (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

    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...

  11. A search for losses of chromium and other trace elements during lyophilization of human liver tissue

    International Nuclear Information System (INIS)

    Goeij, J.J.M. de; Volkers, K.J.; Tjioe, P.S.

    1979-01-01

    Human liver tissues were investigated for possible trace-element losses during lyophilization by comparison of concentrations of lyophilized and untreated (wet) samples. When destructive neutron activation analysis (n.a.a.) was used, no significant losses were observed for As, Br, Cd, Co, Cr, Cu, Fe, Hg, Mo, Sb, Se, and Zn. The advantages of n.a.a. over radio-tracer techniques for studies of trace-element volatility are discussed. (Auth.)

  12. Characterization of in vitro healthy and pathological human liver tissue periodicity using backscattered ultrasound signals.

    Science.gov (United States)

    Machado, Christiano Bittencourt; Pereira, Wagner Coelho de Albuquerque; Meziri, Mahmoud; Laugier, Pascal

    2006-05-01

    This work studied the periodicity of in vitro healthy and pathologic liver tissue, using backscattered ultrasound (US) signals. It utilized the mean scatterer spacing (MSS) as a parameter of tissue characterization, estimated by three methods: the spectral autocorrelation (SAC), the singular spectrum analysis (SSA) and the quadratic transformation method (SIMON). The liver samples were classified in terms of tissue status using the METAVIR scoring system. Twenty tissue samples were classified in four groups: F0, F1, F3 and F4 (five samples for each). The Kolmogorov-Smirnov test (applied on group pairs) resulted as nonsignificant (p > 0.05) for two pairs only: F1/F3 (for SSA) and F3/F4 (for SAC). A discriminant analysis was applied using as parameters the MSS mean (MSS) and standard deviation (sigmaMSS), the estimates histogram mode (mMSS), and the speed of US (mc(foie)) in the medium, to evaluate the degree of discrimination among healthy and pathologic tissues. The better accuracy (Ac) with SAC (80%) was with parameter group (MSS, sigmaMSS, mc(foie)), achieving a sensitivity (Ss) of 92.3% and a specificity (Sp) of 57.1%. For SSA, the group with all four parameters showed an Ac of 75%, an Ss of 78.6% and an Sp of 66.70%. SIMON obtained the best Ac of all (85%) with group (MSS, mMSS, mc(foie)), an Ss of 100%, but with an Sp of 50%.

  13. Effects of gadolinium-based MRI contrast agents on liver tissue.

    Science.gov (United States)

    Mercantepe, Tolga; Tümkaya, Levent; Çeliker, Fatma Beyazal; Topal Suzan, Zehra; Çinar, Seda; Akyildiz, Kerimali; Mercantepe, Filiz; Yilmaz, Adnan

    2018-04-01

    MRI with contrast is often used clinically. However, recent studies have reported a high accumulation of gadolinium-based contrast agents (GBCAs) in kidney, liver, and spleen tissues in several mouse models. To compare the effects on liver tissue of gadolinium-based MRI contrast agents in the light of biochemical and histopathological evaluation. Institutional Review Board (IRB)-approved controlled longitudinal study. In all, 32 male Sprague-Dawley rats were divided into a healthy control group subjected to no procedure (Group 1), a sham group (Group 2), a gadodiamide group (Group 3), and a gadoteric acid group (Group 4). Not applicable. Liver tissues removed at the end of the fifth week and evaluated pathologically (scored Knodell's histological activity index [HAI] method by two histopathologists) immunohistochemical (caspase-3 and biochemical tests (AST, ALT, TAS, TOS, and OSI method by Erel et al) were obtained. Differences between groups were analyzed using the nonparametric Kruskal-Wallis test followed by the Tamhane test, and one-way analysis of variance (ANOVA) followed by Turkey's HSD test. An increase was observed in histological activity scores in sections from rats administered gadodiamide and gadoteric acid, and in caspase-3, AST and ALT values (P total antioxidant and antioxidant capacity. 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

  14. Mechanism of tumor and liver concentration of /sup 67/Ga: /sup 67/Ga binding substances in tumor tissues and liver

    Energy Technology Data Exchange (ETDEWEB)

    Ando, A; Ando, I; Hiraki, T; Takeshita, M; Hisada, K

    1983-01-01

    Tumor-bearing animals were administered with /sup 67/Ga citrate and tumor homogenates, from which nuclear fraction was removed, and mitochondrial fraction of the host livers were digested with protease (pronase P). After digestion, the supernatants of the reaction mixtures were applied to a Sephadex G-100 column. Resultant eluates were analyzed for radioactivity, protein, uronic acid and sialic acids. Three peaks of radioactivity were obtained by gel filtration. The first peak eluted in the void volume contained a species whose molecular weight exceeded 40,000. The second peak consisted of substances with molecular weights of 9400-40,000. Radioactivity in the third peak was from liberated gallium-67. /sup 67/Ga in the second peak was bound to acid mucopolysaccharide and/or the sulfated carbohydrate chain of sulfated glycoprotein. It was thought that /sup 67/Ga in the first peak might be bound to some acid mucopolysaccharides. Considering the results of cellulose acetate electrophoresis, /sup 67/Ga in the second peak seemed to be bound to acid mucopolysaccharide which contained no uronic acids, and/or to the sulfated carbohydrate chain of sulfated glycoprotein. It was concluded that /sup 67/Ga was bound to the acid mucopolysaccharides and/or the sulfated carbohydrate chain of sulfated glycoprotein in tumor tissues and liver lysosomes.

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

    Directory of Open Access Journals (Sweden)

    R. Heru Prasetyo

    2017-06-01

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

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

    Science.gov (United States)

    Prasetyo, R Heru; Hestianah, Eka Pramyrtha

    2017-06-01

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

  17. Liver protective effect of ursodeoxycholic acid includes regulation of ADAM17 activity

    Czech Academy of Sciences Publication Activity Database

    Buryová, Halka; Chalupský, Karel; Žbodáková, Olga; Kanchev, Ivan; Jiroušková, Markéta; Gregor, Martin; Sedláček, Radislav

    2013-01-01

    Roč. 13, 30.10.2013 (2013), s. 155-155 ISSN 1471-230X R&D Projects: GA ČR GAP305/10/2143; GA ČR GAP303/10/2044; GA AV ČR IAA500520812; GA MŠk ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : ursodeoxycholic acid * ADAM17 * shedding * cholestasis * liver Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.113, year: 2013

  18. A protein-based set of reference markers for liver tissues and hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Sun, Stella; Yi, Xin; Poon, Ronnie TP; Yeung, Chun; Day, Philip JR; Luk, John M

    2009-01-01

    During the last decade, investigations have focused on revealing genes or proteins that are involved in HCC carcinogenesis using either genetic or proteomic techniques. However, these studies are overshadowed by a lack of good internal reference standards. The need to identify 'housekeeping' markers, whose expression is stable in various experimental and clinical conditions, is therefore of the utmost clinical relevance in quantitative studies. This is the first study employed 2-DE analysis to screen for potential reference markers and aims to correlate the abundance of these proteins with their level of transcript expression. A Chinese cohort of 224 liver tissues samples (105 cancerous, 103 non-tumourous cirrhotic, and 16 normal) was profiled using 2-DE analysis. Expression of the potential reference markers was confirmed by western blot, immunohistochemistry and real-time quantitative PCR. geNorm algorithm was employed for gene stability measure of the identified reference markers. The expression levels of three protein markers beta-actin (ACTB), heat shock protein 60 (HSP60), and protein disulphide isomerase (PDI) were found to be stable using p-values (p > 0.99) as a ranking tool in all 224 human liver tissues examined by 2-DE analysis. Of high importance, ACTB and HSP 60 were successfully validated at both protein and mRNA levels in human hepatic tissues by western blot, immunohistochemistry and real-time quantitative PCR. In addition, no significant correlation of these markers with any clinicopathological features of HCC and cirrhosis was found. Gene stability measure of these two markers with other conventionally applied housekeeping genes was assessed by the geNorm algorithm, which ranked ACTB and HSP60 as the most stable genes among this cohort of clinical samples. Our findings identified 2 reference markers that exhibited stable expression across human liver tissues with different conditions thus should be regarded as reliable reference

  19. 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

  20. Intrahepatic tissue pO2 during continuous or intermittent vascular inflow occlusion in a pig liver resection model

    NARCIS (Netherlands)

    van Wagensveld, B. A.; van Gulik, T. M.; Gabeler, E. E.; van der Kleij, A. J.; Obertop, H.; Gouma, D. J.

    1998-01-01

    BACKGROUND: Temporary vascular inflow occlusion of the liver (clamping of the hepatic pedicle) can prevent massive blood loss during liver resections. In this study, intrahepatic tissue pO2 was assessed as parameter of microcirculatory disturbances induced by ischemia and reperfusion (I/R) in the

  1. Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization

    NARCIS (Netherlands)

    Mazza, G. (Giuseppe); Al-Akkad, W. (Walid); Telese, A. (Andrea); Longato, L. (Lisa); Urbani, L. (Luca); Robinson, B. (Benjamin); Hall, A. (Andrew); Kong, K. (Kenny); Frenguelli, L. (Luca); Marrone, G. (Giusi); Willacy, O. (Oliver); Shaeri, M. (Mohsen); A.J. Burns (Alan); Malago, M. (Massimo); Gilbertson, J. (Janet); Rendell, N. (Nigel); Moore, K. (Kevin); Hughes, D. (David); Notingher, I. (Ioan); Jell, G. (Gavin); Del Rio Hernandez, A. (Armando); P. de Coppi (Paolo); Rombouts, K. (Krista); Pinzani, M. (Massimo)

    2017-01-01

    textabstractThe development of human liver scaffolds retaining their 3-dimensional structure and extra-cellular matrix (ECM) composition is essential for the advancement of liver tissue engineering. We report the design and validation of a new methodology for the rapid and accurate production of

  2. Effect of alpha-lipoic acid on the removal of arsenic from arsenic-loaded isolated liver tissues of rat

    Directory of Open Access Journals (Sweden)

    Noor-E-Tabassum

    2006-06-01

    Full Text Available The patient of chronic arsenic toxicity shows oxidative stress. To overcome the oxidative stress, several antioxidants such as beta-carotene, ascorbic acid, α-tocopherol, zinc and selenium had been suggested in the treatment of chronic arsenic toxicity. In the present study universal antioxidant (both water and lipid soluble antioxidant α-lipoic acid was used to examine the effectiveness of reducing the amount of arsenic from arsenic-loaded isolated liver tissues of rat. Isolated liver tissues of Long Evans Norwegian rats were cut into small pieces and incubated first in presence or absence of arsenic and then with different concentrations of α-lipoic acid during the second incubation. α-Lipoic acid decreases the amount of arsenic and malondialdehyde (MDA in liver tissues as well as increases the reduced glutathione (GSH level in dose dependent manner. These results suggest that α-lipoic acid remove arsenic from arsenic-loaded isolated liver tissues of rat.

  3. Including osteoprotegerin and collagen IV in a score-based blood test for liver fibrosis increases diagnostic accuracy.

    Science.gov (United States)

    Bosselut, Nelly; Taibi, Ludmia; Guéchot, Jérôme; Zarski, Jean-Pierre; Sturm, Nathalie; Gelineau, Marie-Christine; Poggi, Bernard; Thoret, Sophie; Lasnier, Elisabeth; Baudin, Bruno; Housset, Chantal; Vaubourdolle, Michel

    2013-01-16

    Noninvasive methods for liver fibrosis evaluation in chronic liver diseases have been recently developed, i.e. transient elastography (Fibroscan™) and blood tests (Fibrometer®, Fibrotest®, and Hepascore®). In this study, we aimed to design a new score in chronic hepatitis C (CHC) by selecting blood markers in a large panel and we compared its diagnostic performance with those of other noninvasive methods. Sixteen blood tests were performed in 306 untreated CHC patients included in a multicenter prospective study (ANRS HC EP 23 Fibrostar) using METAVIR histological fibrosis stage as reference. The new score was constructed by non linear regression using the most accurate biomarkers. Five markers (alpha-2-macroglobulin, apolipoprotein-A1, AST, collagen IV and osteoprotegerin) were included in the new function called Coopscore©. Using the Obuchowski Index, Coopscore© shows higher diagnostic performances than for Fibrometer®, Fibrotest®, Hepascore® and Fibroscan™ in CHC. Association between Fibroscan™ and Coopscore© might avoid 68% of liver biopsies for the diagnosis of significant fibrosis. Coopscore© provides higher accuracy than other noninvasive methods for the diagnosis of liver fibrosis in CHC. The association of Coopscore© with Fibroscan™ increases its predictive value. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Influence of nanoparticles accumulation on optical properties of human normal and cancerous liver tissue in vitro estimated by OCT

    International Nuclear Information System (INIS)

    Zhou, Fang; Wei, Huajiang; Guo, Zhouyi; Ye, Xiangping; Hu, Kun; Wu, Guoyong; Yang, Hongqin; Xie, Shusen; He, Yonghong

    2015-01-01

    In this work, the potential use of nanoparticles as contrast agents by using spectral domain optical coherence tomography (SD-OCT) in liver tissue was demonstrated. Gold nanoparticles (average size of 25 and 70 nm), were studied in human normal and cancerous liver tissues in vitro, respectively. Each sample was monitored with SD-OCT functional imaging for 240 min. Continuous OCT monitoring showed that, after application of gold nanoparticles, the OCT signal intensities of normal liver and cancerous liver tissue both increase with time, and the larger nanoparticles tend to produce a greater signal enhancement in the same type of tissue. The results show that the values of attenuation coefficients have significant differences between normal liver tissue and cancerous liver tissue. In addition, 25 nm gold nanoparticles allow higher penetration depth than 70 nm gold nanoparticles in liver tissues. (paper)

  5. Hydrolysis of pyrethroids by human and rat tissues: Examination of intestinal, liver and serum carboxylesterases

    International Nuclear Information System (INIS)

    Crow, J. Allen; Borazjani, Abdolsamad; Potter, Philip M.; Ross, Matthew K.

    2007-01-01

    Hydrolytic metabolism of pyrethroid insecticides in humans is one of the major catabolic pathways that clear these compounds from the body. Rodent models are often used to determine the disposition and clearance rates of these esterified compounds. In this study the distribution and activities of esterases that catalyze pyrethroid metabolism have been investigated in vitro using several human and rat tissues, including small intestine, liver and serum. The major esterase in human intestine is carboxylesterase 2 (hCE2). We found that the pyrethroid trans-permethrin is effectively hydrolyzed by a sample of pooled human intestinal microsomes (5 individuals), while deltamethrin and bioresmethrin are not. This result correlates well with the substrate specificity of recombinant hCE2 enzyme. In contrast, a sample of pooled rat intestinal microsomes (5 animals) hydrolyze trans-permethrin 4.5-fold slower than the sample of human intestinal microsomes. Furthermore, it is demonstrated that pooled samples of cytosol from human or rat liver are ∼ 2-fold less hydrolytically active (normalized per mg protein) than the corresponding microsomal fraction toward pyrethroid substrates; however, the cytosolic fractions do have significant amounts (∼ 40%) of the total esteratic activity. Moreover, a 6-fold interindividual variation in carboxylesterase 1 protein expression in human hepatic cytosols was observed. Human serum was shown to lack pyrethroid hydrolytic activity, but rat serum has hydrolytic activity that is attributed to a single CE isozyme. We purified the serum CE enzyme to homogeneity to determine its contribution to pyrethroid metabolism in the rat. Both trans-permethrin and bioresmethrin were effectively cleaved by this serum CE, but deltamethrin, esfenvalerate, alpha-cypermethrin and cis-permethrin were slowly hydrolyzed. Lastly, two model lipase enzymes were examined for their ability to hydrolyze pyrethroids. However, no hydrolysis products could be detected

  6. Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of gut-liver-adipose tissue axis.

    Science.gov (United States)

    Choi, Youngshim; Abdelmegeed, Mohamed A; Song, Byoung-Joon

    2018-05-01

    Indole-3-carbinol (I3C), found in Brassica family vegetables, exhibits antioxidant, anti-inflammatory, and anti-cancerous properties. Here, we aimed to evaluate the preventive effects of I3C against ethanol (EtOH)-induced liver injury and study the protective mechanism(s) by using the well-established chronic-plus-binge alcohol exposure model. The preventive effects of I3C were evaluated by conducting various histological, biochemical, and real-time PCR analyses in mouse liver, adipose tissue, and colon, since functional alterations of adipose tissue and intestine can also participate in promoting EtOH-induced liver damage. Daily treatment with I3C alleviated EtOH-induced liver injury and hepatocyte apoptosis, but not steatosis, by attenuating elevated oxidative stress, as evidenced by the decreased levels of hepatic lipid peroxidation, hydrogen peroxide, CYP2E1, NADPH-oxidase, and protein acetylation with maintenance of mitochondrial complex I, II, and III protein levels and activities. I3C also restored the hepatic antioxidant capacity by preventing EtOH-induced suppression of glutathione contents and mitochondrial aldehyde dehydrogenase-2 activity. I3C preventive effects were also achieved by attenuating the increased levels of hepatic proinflammatory cytokines, including IL1β, and neutrophil infiltration. I3C also attenuated EtOH-induced gut leakiness with decreased serum endotoxin levels through preventing EtOH-induced oxidative stress, apoptosis of enterocytes, and alteration of tight junction protein claudin-1. Furthermore, I3C alleviated adipose tissue inflammation and decreased free fatty acid release. Collectively, I3C prevented EtOH-induced liver injury via attenuating the damaging effect of ethanol on the gut-liver-adipose tissue axis. Therefore, I3C may also have a high potential for translational research in treating or preventing other types of hepatic injury associated with oxidative stress and inflammation. Copyright © 2017 Elsevier Inc. All

  7. [Treatment Strategy for Liver Metastasis of Colorectal Cancer - Including Treatment for Oligometastasis].

    Science.gov (United States)

    Sato, Takeo; Nakamura, Takatoshi; Yamanashi, Takahiro; Miura, Hirohisa; Tsutsui, Atsuko; Shimazu, Masashi; Watanabe, Masahiko

    2017-10-01

    The mainstay of treatment for metastatic colorectal cancer is surgery. Therefore, colorectal cancer metastasis is distinctive, compared to other cancer types in which chemotherapy is the main treatment. Initially, Japan experienced medical druglag compared with western countries. However, the use of oxaliplatin for unresectable recurrent metastatic colorectal cancer became available in Japan, as well as in western countries, in 2005. We have since shifted chemotherapeutic regimens from monotherapy to combination therapy with molecular targeted agents. The combination therapy has rapidly become a standard therapy for unresectable metastatic colorectal cancer, and prognosis has dramatically increased for patients with this condition. Herein, we describe the treatment of liver metastasis of colorectal cancer, and surgery and adjuvant or neoadjuvant therapy options for resectable cancer. Furthermore, we focus on conversion therapy for unresectable cancer.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    Juvenile rainbow trout (Salmo gairdneri) were exposed to 100 ppb mercury (as HgCl 2 ) 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-exposed trout were subjected to selenium (as Na 2 SeO 3 ), 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 that the mercury visualized prior to selenium treatment represents inorganic mercury, while additional mercury visualized after selenium administration represents an organic form

  9. Impact of Skeletal Muscle Mass Index, Intramuscular Adipose Tissue Content, and Visceral to Subcutaneous Adipose Tissue Area Ratio on Early Mortality of Living Donor Liver Transplantation.

    Science.gov (United States)

    Hamaguchi, Yuhei; Kaido, Toshimi; Okumura, Shinya; Kobayashi, Atsushi; Shirai, Hisaya; Yagi, Shintaro; Kamo, Naoko; Okajima, Hideaki; Uemoto, Shinji

    2017-03-01

    Skeletal muscle depletion has been shown to be an independent risk factor for poor survival in various diseases. However, in surgery, the significance of other body components including visceral and subcutaneous adipose tissue remains unclear. This retrospective study included 250 adult patients undergoing living donor liver transplantation (LDLT) between January 2008 and April 2015. Using preoperative plain computed tomography imaging at the third lumbar vertebra level, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by the skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral to subcutaneous adipose tissue area ratio (VSR), respectively. The cutoff values of these parameters were determined for men and women separately using the data of 657 healthy donors for LDLT between 2005 and 2016. Impact of these parameters on outcomes after LDLT was analyzed. VSR was significantly correlated with patient age (P = 0.041), neutrophil-lymphocyte ratio (P mass index (P normal group. On multivariate analysis, low SMI (hazard ratio [HR], 2.367, P = 0.002), high IMAC (HR, 2.096, P = 0.004), and high VSR (HR, 2.213, P = 0.003) were identified as independent risk factors for death after LDLT. Preoperative visceral adiposity, as well as low muscularity, was closely involved with posttransplant mortality.

  10. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    Science.gov (United States)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  11. Allometric relationships to liver tissue concentrations of cyclic volatile methyl siloxanes in Atlantic cod

    International Nuclear Information System (INIS)

    Warner, Nicholas A.; Nøst, Therese H.; Andrade, Hector; Christensen, Guttorm

    2014-01-01

    Spatial distribution and relationship of allometric measurements (length, weight and age) to liver concentrations of cyclic volatile methyl siloxanes (cVMS) including octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclosiloxane (D6) in Atlantic cod (Gadus morhua) collected near the community of Tromsø in Northern Norway were assessed. These congeners were benchmarked against known persistent polychlorinated biphenyls (PCBs 153 and 180) to assess accumulation behavior of cVMS. D5 was the dominate cVMS detected in all fish livers with lipid normalized concentrations up to 10 times or greater than those observed for PCB 153 and 180. D4 and D6 concentration were negatively correlated with fish length and weight, indicating a greater elimination capacity compared to uptake processes with increasing fish size for these chemicals. These results indicate relationships between allometric measurements and cVMS concentrations may account for concentration variations observed within fish and should be assessed in future studies evaluating cVMS bioaccumulation potential. - Highlights: • cVMS spatial distribution investigated within cod surrounding an Arctic community. • Highest cVMS concentrations detected in biota collected near human settlements. • Cod liver concentrations of D5 were higher compared to PCBs. • D4 and D6 liver concentrations were negatively correlated with fish length/weight. - Liver concentrations of cVMS congeners decreased with increasing fish length and weight in Atlantic cod collected near emission sources of cVMS

  12. Accuracy of Intraoral Digital Impressions for Whole Upper Jaws, Including Full Dentitions and Palatal Soft Tissues.

    Science.gov (United States)

    Gan, Ning; Xiong, Yaoyang; Jiao, Ting

    2016-01-01

    Intraoral digital impressions have been stated to meet the clinical requirements for some teeth-supported restorations, though fewer evidences were proposed for larger scanning range. The aim of this study was to compare the accuracy (trueness and precision) of intraoral digital impressions for whole upper jaws, including the full dentitions and palatal soft tissues, as well as to determine the effect of different palatal vault height or arch width on accuracy of intraoral digital impressions. Thirty-two volunteers were divided into three groups according to the palatal vault height or arch width. Each volunteer received three scans with TRIOS intraoral scanner and one conventional impression of whole upper jaw. Three-dimensional (3D) images digitized from conventional gypsum casts by a laboratory scanner were chose as the reference models. All datasets were imported to a specific software program for 3D analysis by "best fit alignment" and "3D compare" process. Color-coded deviation maps showed qualitative visualization of the deviations. For the digital impressions for palatal soft tissues, trueness was (130.54±33.95)μm and precision was (55.26±11.21)μm. For the digital impressions for upper full dentitions, trueness was (80.01±17.78)μm and precision was (59.52±11.29)μm. Larger deviations were found between intraoral digital impressions and conventional impressions in the areas of palatal soft tissues than that in the areas of full dentitions (pimpressions for palatal soft tissues was slightly better than that for full dentitions (p = 0.049). There was no significant effect of palatal vault height on accuracy of digital impressions for palatal soft tissues (p>0.05), but arch width was found to have a significant effect on precision of intraoral digital impressions for full dentitions (p = 0.016). A linear correlation was found between arch width and precision of digital impressions for whole upper jaws (r = 0.326, p = 0.034 for palatal soft tissues and r

  13. Accuracy of Intraoral Digital Impressions for Whole Upper Jaws, Including Full Dentitions and Palatal Soft Tissues

    Science.gov (United States)

    Gan, Ning; Xiong, Yaoyang; Jiao, Ting

    2016-01-01

    Intraoral digital impressions have been stated to meet the clinical requirements for some teeth-supported restorations, though fewer evidences were proposed for larger scanning range. The aim of this study was to compare the accuracy (trueness and precision) of intraoral digital impressions for whole upper jaws, including the full dentitions and palatal soft tissues, as well as to determine the effect of different palatal vault height or arch width on accuracy of intraoral digital impressions. Thirty-two volunteers were divided into three groups according to the palatal vault height or arch width. Each volunteer received three scans with TRIOS intraoral scanner and one conventional impression of whole upper jaw. Three-dimensional (3D) images digitized from conventional gypsum casts by a laboratory scanner were chose as the reference models. All datasets were imported to a specific software program for 3D analysis by "best fit alignment" and "3D compare" process. Color-coded deviation maps showed qualitative visualization of the deviations. For the digital impressions for palatal soft tissues, trueness was (130.54±33.95)μm and precision was (55.26±11.21)μm. For the digital impressions for upper full dentitions, trueness was (80.01±17.78)μm and precision was (59.52±11.29)μm. Larger deviations were found between intraoral digital impressions and conventional impressions in the areas of palatal soft tissues than that in the areas of full dentitions (pimpressions for palatal soft tissues was slightly better than that for full dentitions (p = 0.049). There was no significant effect of palatal vault height on accuracy of digital impressions for palatal soft tissues (p>0.05), but arch width was found to have a significant effect on precision of intraoral digital impressions for full dentitions (p = 0.016). A linear correlation was found between arch width and precision of digital impressions for whole upper jaws (r = 0.326, p = 0.034 for palatal soft tissues and r

  14. Quantization of liver tissue in dual kVp computed tomography using linear discriminant analysis

    Science.gov (United States)

    Tkaczyk, J. Eric; Langan, David; Wu, Xiaoye; Xu, Daniel; Benson, Thomas; Pack, Jed D.; Schmitz, Andrea; Hara, Amy; Palicek, William; Licato, Paul; Leverentz, Jaynne

    2009-02-01

    Linear discriminate analysis (LDA) is applied to dual kVp CT and used for tissue characterization. The potential to quantitatively model both malignant and benign, hypo-intense liver lesions is evaluated by analysis of portal-phase, intravenous CT scan data obtained on human patients. Masses with an a priori classification are mapped to a distribution of points in basis material space. The degree of localization of tissue types in the material basis space is related to both quantum noise and real compositional differences. The density maps are analyzed with LDA and studied with system simulations to differentiate these factors. The discriminant analysis is formulated so as to incorporate the known statistical properties of the data. Effective kVp separation and mAs relates to precision of tissue localization. Bias in the material position is related to the degree of X-ray scatter and partial-volume effect. Experimental data and simulations demonstrate that for single energy (HU) imaging or image-based decomposition pixel values of water-like tissues depend on proximity to other iodine-filled bodies. Beam-hardening errors cause a shift in image value on the scale of that difference sought between in cancerous and cystic lessons. In contrast, projection-based decomposition or its equivalent when implemented on a carefully calibrated system can provide accurate data. On such a system, LDA may provide novel quantitative capabilities for tissue characterization in dual energy CT.

  15. THE EFFECTS OF GLYCOL METHACRYLATE AS A DEHYDRATING AGENT ON THE DIMENSIONAL CHANGES OF LIVER-TISSUE

    NARCIS (Netherlands)

    GERRITS, PO; HOROBIN, RW; STOKROOS, [No Value

    The dimensional changes of liver sections during the course of processing with glycol methacrylate (GMA) or with ethanol are described. Tissue processing with ethanol served as a control. During prolonged processing steps (24 h each), linear shrinkage of tissue specimens dehydrated with GMA at room

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

    Directory of Open Access Journals (Sweden)

    Anna Kakehashi

    2017-02-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Ye. V. Semichev

    2014-01-01

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

  18. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ying LIU

    2011-03-01

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

  1. Accuracy of Intraoral Digital Impressions for Whole Upper Jaws, Including Full Dentitions and Palatal Soft Tissues.

    Directory of Open Access Journals (Sweden)

    Ning Gan

    Full Text Available Intraoral digital impressions have been stated to meet the clinical requirements for some teeth-supported restorations, though fewer evidences were proposed for larger scanning range. The aim of this study was to compare the accuracy (trueness and precision of intraoral digital impressions for whole upper jaws, including the full dentitions and palatal soft tissues, as well as to determine the effect of different palatal vault height or arch width on accuracy of intraoral digital impressions. Thirty-two volunteers were divided into three groups according to the palatal vault height or arch width. Each volunteer received three scans with TRIOS intraoral scanner and one conventional impression of whole upper jaw. Three-dimensional (3D images digitized from conventional gypsum casts by a laboratory scanner were chose as the reference models. All datasets were imported to a specific software program for 3D analysis by "best fit alignment" and "3D compare" process. Color-coded deviation maps showed qualitative visualization of the deviations. For the digital impressions for palatal soft tissues, trueness was (130.54±33.95μm and precision was (55.26±11.21μm. For the digital impressions for upper full dentitions, trueness was (80.01±17.78μm and precision was (59.52±11.29μm. Larger deviations were found between intraoral digital impressions and conventional impressions in the areas of palatal soft tissues than that in the areas of full dentitions (p0.05, but arch width was found to have a significant effect on precision of intraoral digital impressions for full dentitions (p = 0.016. A linear correlation was found between arch width and precision of digital impressions for whole upper jaws (r = 0.326, p = 0.034 for palatal soft tissues and r = 0.485, p = 0.002 for full dentitions. It was feasible to use the intraoral scanner to obtain digital impressions for whole upper jaws. Wider dental arch contributed to lower precision of an intraoral

  2. Gender, renal function, and outcomes on the liver transplant waiting list: assessment of revised MELD including estimated glomerular filtration rate.

    Science.gov (United States)

    Myers, Robert P; Shaheen, Abdel Aziz M; Aspinall, Alexander I; Quinn, Robert R; Burak, Kelly W

    2011-03-01

    The Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation (LT) may present a disadvantage for women by including serum creatinine, which is typically lower in females. Our objectives were to investigate gender disparities in outcomes among LT candidates and to assess a revised MELD, including estimated glomerular filtration rate (eGFR), for predicting waiting list mortality. Adults registered for LT between 2002 and 2007 were identified using the UNOS database. We compared components of MELD, MDRD-derived eGFR, and the 3-month probability of LT and death between genders. Discrimination of MELD, MELDNa, and revised models including eGFR for mortality were compared using c-statistics. A total of 40,393 patients (36% female) met the inclusion criteria; 9% died and 24% underwent LT within 3 months of listing. Compared with men, women had lower median serum creatinine (0.9 vs. 1.0 mg/dl), eGFR (72 vs. 83 ml/min/1.73 m(2)), and mean MELD (16.5 vs. 17.2; all p discrimination for 3-month mortality (c-statistics: MELD 0.896, MELD-eGFR 0.894, MELDNa 0.911, MELDNa-eGFR 0.905). Women are disadvantaged under MELD potentially due to its inclusion of creatinine. However, since including eGFR in MELD does not improve mortality prediction, alternative refinements are necessary. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  3. Comparison of Species and Cell-Type Differences in Fraction Unbound of Liver Tissues, Hepatocytes, and Cell Lines.

    Science.gov (United States)

    Riccardi, Keith; Ryu, Sangwoo; Lin, Jian; Yates, Phillip; Tess, David; Li, Rui; Singh, Dhirender; Holder, Brian R; Kapinos, Brendon; Chang, George; Di, Li

    2018-04-01

    Fraction unbound ( f u ) of liver tissue, hepatocytes, and other cell types is an essential parameter used to estimate unbound liver drug concentration and intracellular free drug concentration. f u,liver and f u,cell are frequently measured in multiple species and cell types in drug discovery and development for various applications. A comparison study of 12 matrices for f u,liver and f u,cell of hepatocytes in five different species (mouse, rat, dog, monkey, and human), as well as f u,cell of Huh7 and human embryonic kidney 293 cell lines, was conducted for 22 structurally diverse compounds with the equilibrium dialysis method. Using an average bioequivalence approach, our results show that the average difference in binding to liver tissue, hepatocytes, or different cell types was within 2-fold of that of the rat f u,liver Therefore, we recommend using rat f u,liver as a surrogate for liver binding in other species and cell types in drug discovery. This strategy offers the potential to simplify binding studies and reduce cost, thereby enabling a more effective and practical determination of f u for liver tissues, hepatocytes, and other cell types. In addition, f u under hepatocyte stability incubation conditions should not be confused with f u,cell , as one is a diluted f u and the other is an undiluted f u Cell density also plays a critical role in the accurate measurement of f u,cell . Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

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

    Directory of Open Access Journals (Sweden)

    Wen-bing LI

    2014-03-01

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

  5. Toward angiogenesis of implanted bio-artificial liver using scaffolds with type I collagen and adipose tissue-derived stem cells.

    Science.gov (United States)

    Lee, Jae Geun; Bak, Seon Young; Nahm, Ji Hae; Lee, Sang Woo; Min, Seon Ok; Kim, Kyung Sik

    2015-05-01

    Stem cell therapies for liver disease are being studied by many researchers worldwide, but scientific evidence to demonstrate the endocrinologic effects of implanted cells is insufficient, and it is unknown whether implanted cells can function as liver cells. Achieving angiogenesis, arguably the most important characteristic of the liver, is known to be quite difficult, and no practical attempts have been made to achieve this outcome. We carried out this study to observe the possibility of angiogenesis of implanted bio-artificial liver using scaffolds. This study used adipose tissue-derived stem cells that were collected from adult patients with liver diseases with conditions similar to the liver parenchyma. Specifically, microfilaments were used to create an artificial membrane and maintain the structure of an artificial organ. After scratching the stomach surface of severe combined immunocompromised (SCID) mice (n=4), artificial scaffolds with adipose tissue-derived stem cells and type I collagen were implanted. Expression levels of angiogenesis markers including vascular endothelial growth factor (VEGF), CD34, and CD105 were immunohistochemically assessed after 30 days. Grossly, the artificial scaffolds showed adhesion to the stomach and surrounding organs; however, there was no evidence of angiogenesis within the scaffolds; and VEGF, CD34, and CD105 expressions were not detected after 30 days. Although implantation of cells into artificial scaffolds did not facilitate angiogenesis, the artificial scaffolds made with type I collagen helped maintain implanted cells, and surrounding tissue reactions were rare. Our findings indicate that type I collagen artificial scaffolds can be considered as a possible implantable biomaterial.

  6. Simulation and performance evaluation of fiber optic sensor for detection of hepatic malignancies in human liver tissues

    Science.gov (United States)

    Sharma, Anuj K.; Gupta, Jyoti; Basu, Rikmantra

    2018-01-01

    A fiber optic sensor is proposed for the identification of healthy and cancerous liver tissues through determination of their corresponding refractive index values. Existing experimental results describing variation of complex refractive index of liver tissues in near infrared (NIR) spectral region are considered for theoretical calculations. The intensity interrogation method with chalcogenide fiber is considered. The sensor's performance is closely analyzed in terms of its sensitivity at multiple operating wavelengths falling in NIR region. Operating at shorter NIR wavelengths leads to greater sensitivity. The effect of design parameters (sensing region length and fiber core diameter), different launching conditions, and fiber glass materials on sensor's performance is examined. The proposed sensor has the potential to provide high sensitivity of liver tissue detection.

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

    International Nuclear Information System (INIS)

    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

    2015-01-01

    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. - Highlights: • We investigated the bioaccumulation of antibiotics in wild fish from the Pearl River Delta region. • Twelve antibiotics were found in fish bile, plasma, liver and muscle tissues. • High log bioaccumulation factors suggested strong bioaccumulation ability for some antibiotics in wild fish tissues. • The presence of antibiotics in fish bile and plasma tissues indicates a novel bioaccumulation pattern. • Potential adverse effects are possibly caused by the high internal antibiotic concentrations in tissues. - Fish bile and plasma displayed strong bioaccumulation ability for some antibiotics, indicating a novel bioaccumulation pattern for antibiotics in the contaminated environment

  8. Comparative study of rabbit VX2 hepatic implantation tumor and normal liver tissue on magnetic resonance perfusion weighted imaging

    International Nuclear Information System (INIS)

    Jiao Zimei; Wang Xizhen; Wang Bin; Liu Feng; Li Haiqing; Sun Yequan; Dong Peng

    2012-01-01

    Objective: To investigate the value of magnetic resonance (MR) perfusion weighted imaging (PWI) in evaluating the blood perfusion of tumor by analyzing the features and indexes of PWI on rabbit VX2 hepatic implantation tumor and normal liver tissue. Methods: Twenty-four New Zealand White rabbits with VX2 carcinoma were established under direct surgical vision embedding tumor tissue. MR examination was performed at 21 days after the tumor implantation. The signal intensity -time curve of hepatic tumor and normal liver tissue were obtained. Mean time to enhance (MTE), negative enhancement integral (NEI), time to minimum (TM), maximum slope of decrease (MSD) and maximum slope of increase (MSI) were measured. Results: MTE, NEI, TM, MSD, and MSI of the normal liver tissue were 208.341±2.226 ms, 78.334±8.152, 24.059±1.927 ms, 38.221±2.443, and 15.389±2.526, respectively. MTE, NEI, TM, MSD, and MSI of the tumor tissue were 175.437±4.182 ms, 123.203±19.455, 17.061±1.834 ms, 125.740±4.842, and 67.832±2.882, respectively. The MTE and TM of tumor were shorter than those of normal hepatic tissue (P<0.05). NEI, MSD, and MSI of tumor were higher than those of normal hepatic tissue (P<0.05). Conclusion: PWI can distinguish the normal liver tissue from the tumor tissue, which is helpful in evaluating blood perfusion of different hepatic tissues. (authors)

  9. Sulfamethoxazole-Trimethoprim (Cotrimoxazole) for Skin and Soft Tissue Infections Including Impetigo, Cellulitis, and Abscess.

    Science.gov (United States)

    Bowen, Asha C; Carapetis, Jonathan R; Currie, Bart J; Fowler, Vance; Chambers, Henry F; Tong, Steven Y C

    2017-01-01

    Skin and soft tissue infections (SSTI) affect millions of people globally, which represents a significant burden on ambulatory care and hospital settings. The role of sulfamethoxazole-trimethoprim (SXT) in SSTI treatment, particularly when group A Streptococcus (GAS) is involved, is controversial. We conducted a systematic review of clinical trials and observational studies that address the utility of SXT for SSTI treatment, caused by either GAS or Staphylococcus aureus , including methicillin-resistant (MRSA). We identified 196 studies, and 15 underwent full text review by 2 reviewers. Observational studies, which mainly focused on SSTI due to S aureus , supported the use of SXT when compared with clindamycin or β-lactams. Of 10 randomized controlled trials, 8 demonstrated the efficacy of SXT for SSTI treatment including conditions involving GAS. These findings support SXT use for treatment of impetigo and purulent cellulitis (without an additional β-lactam agent) and abscess and wound infection. For nonpurulent cellulitis, β-lactams remain the treatment of choice.

  10. Heavy metal concentrations in gill and liver tissues of Rutilus kutum and Chelon aurata in the coast of Babolsar, southern Caspian Sea

    Directory of Open Access Journals (Sweden)

    Fatemeh Kardel

    2016-04-01

    Full Text Available Heavy metal accumulation in the aquatic ecosystems is a main concern which threats human health. In this study two commercial fish species, Rutilus kutum and Chelon aurata were selected for assessing heavy metal (Cd, Pb, Zn concentrations in gill and liver tissues at Babolsar’s coast, the southern Caspian Sea, Iran. Babolsar is one of the important fishery stations in the southern Caspian Sea. The results showed that liver tissue of C. aurata significantly accumulated higher concentration of Cd, Pb and Zn compared to that of R. kutum, but these results were not significant for gill tissue. Liver tissue accumulated higher concentration of Cd and Pb compared to gill tissue in C. aurata, but these results were not significant for R. kutum. It is concluded that the liver tissue of C. aurata has higher potential to accumulate heavy metal pollution compared to liver tissue of R. kutum

  11. A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity-induced inflammation in white adipose tissue and liver.

    Science.gov (United States)

    Gotoh, Koro; Inoue, Megumi; Masaki, Takayuki; Chiba, Seiichi; Shimasaki, Takanobu; Ando, Hisae; Fujiwara, Kansuke; Katsuragi, Isao; Kakuma, Tetsuya; Seike, Masataka; Sakata, Toshiie; Yoshimatsu, Hironobu

    2012-08-01

    Obesity is associated with systemic low-grade inflammation and obesity-related metabolic disorders. Considering that obesity decreases the expression of proinflammatory cytokines in the spleen, we assessed the role of interleukin (IL)-10, an anti-inflammatory cytokine produced by the spleen, in the pathogenesis of obesity. Changes in obesity-related pathogenesis, including inflammatory responses in multiple organs, were assessed after systemic administration of exogenous IL-10 to splenectomy (SPX)-treated obese wild-type and IL-10 knockout (IL-10KO) mice. Obesity resulted in the inability of the spleen to synthesize cytokines, including IL-10, and proinflammatory cytokines in obesity are then likely to emerge from tissues other than the spleen because serum levels of IL-10, but not proinflammatory cytokines, decreased despite the expression of these cytokines in the spleen being reduced in high fat-induced obese mice. SPX aggravated the inflammatory response in white adipose tissue (WAT) and the liver and suppressed adiposity in WAT. However, it accentuated adiposity in the liver. These SPX-induced changes were inhibited by systemic administration of IL-10. Moreover, SPX had little effect on the inflammatory responses in WAT and the liver of IL-10KO mice. These data show the role of spleen-derived IL-10 in diet-induced changes as a result of inflammatory responses in WAT and the liver.

  12. 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.

  13. Liver

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    Science.gov (United States)

    Jansen, Henry J; Vervoort, Gerald M; van der Graaf, Marinette; Stienstra, Rinke; Tack, Cees J

    2013-11-01

    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 association between inflammatory features of the adipose tissue and liver fat content. To analyse associations between inflammatory features of the adipose tissue and liver fat content. A cross-sectional study. Twenty-seven obese patients with insulin-treated T2DM were studied. LFAT content was measured by proton magnetic resonance spectroscopy. A subcutaneous (sc) fat biopsy was obtained to determine morphology and protein levels within adipose tissue. In addition to fat cell size, the percentage of macrophages and the presence of crown-like structures (CLSs) within sc fat were assessed by CD68-immunohistochemical staining. Mean LFAT percentage was 11·1 ± 1·7% (range: 0·75-32·9%); 63% of the patients were diagnosed with an elevated LFAT (upper range of normal ≤5·5%). Whereas adipocyte size did not correlate with LFAT, 3 of 4 subjects with CLSs in sc fat had elevated LFAT and the percentage of macrophages present in sc adipose tissue was positively associated with LFAT. Protein concentrations of adiponectin within adipose tissue negatively correlated with LFAT. Adipose tissue protein levels of the key inflammatory adipokine plasminogen activator inhibitor-1 (PAI-1) were positively associated with LFAT. Several pro-inflammatory changes in sc adipose tissue associate with increased LFAT content in obese insulin-treated patients with T2DM. These findings suggest that inflammatory changes at the level of the adipose tissue may drive liver fat accumulation. © 2012 John Wiley & Sons Ltd.

  15. Histopathological Study of Protective Effects of Honey on Subacute Toxicity of Acrylamide-Induced Tissue Lesions in Rats’ Brain and Liver

    Directory of Open Access Journals (Sweden)

    Parichehr Ahrari Roodi

    2018-04-01

    Full Text Available Background: The therapeutic potential of honey is related to antioxidant activity against reactive oxygen species because it contains compounds such as polyphenols; therefore, we evaluated the potential protective effect of honey on subacute toxicity of ACR by histopathologic study on tissue lesions in rat. Methods: In Ferdowsi University of Mashhad, Mashhad, Iran, 2016, male Wistar rats were divided into 7 groups. To induce toxicity, ACR was injected (50 mg/kg for 11 d to rats in 5 groups. In treatment groups, rats received three doses of honey 1.25, 2.5, and 5 g/kg in addition to the ACR. The two remaining groups received vitamin E (200 IU/kg and normal saline as positive and negative control respectively. On the last day, after necropsy, tissue specimens from brain and liver were collected for histopathological studies. Results: Receiving of ACR caused tissue injuries including degeneration, necrosis, hyperemia, hemorrhage and inflammation in liver; ischemic cell change, hyperemia, hemorrhage and edema in brain tissue. Administration of honey considerably reduced tissue damages caused by ACR, particularly with dosage 5 g/kg. Conclusion: The severity of tissue lesions caused by the ACR can be reduced by honey, likely through its antioxidant activity. Increasing concentrations of honey will enhance its effectiveness.

  16. Kupffer cells activation promoted binge drinking-induced fatty liver by activating lipolysis in white adipose tissues.

    Science.gov (United States)

    Zhao, Yu-Ying; Yang, Rui; Xiao, Mo; Guan, Min-Jie; Zhao, Ning; Zeng, Tao

    2017-09-01

    Kupffer cells (KCs) have been suggested to play critical roles in chronic ethanol induced early liver injury, but the role of KCs in binge drinking-induced hepatic steatosis remains unclear. This study was designed to investigate the roles of KCs inhibitor (GdCl 3 ) and TNF-α antagonist (etanercept) on binge drinking-induced liver steatosis and to explore the underlying mechanisms. C57BL/6 mice were exposed to three doses of ethanol (6g/kg body weight) to mimic binge drinking-induced fatty liver. The results showed that both GdCl 3 and etanercept partially but significantly alleviated binge drinking-induced increase of hepatic triglyceride (TG) level, and reduced fat droplets accumulation in mice liver. GdCl 3 but not etanercept significantly blocked binge drinking-induced activation of KCs. However, neither GdCl 3 nor etanercept could affect binge drinking-induced decrease of PPAR-α, ACOX, FAS, ACC and SCD protein levels, or increase of the LC3 II/LC3 I ratio and p62 protein level. Interestingly, both GdCl 3 and etanercept significantly suppressed binge drinking-induced phosphorylation of HSL in epididymal adipose tissues. Results of in vitro studies with cultured epididymal adipose tissues showed that TNF-α could increase the phosphorylation of HSL in adipose tissues and upgrade the secretion of free fatty acid (FFA) in the culture medium. Taken together, KCs inhibitor and TNF-α antagonist could partially attenuate binge drinking-induced liver steatosis, which might be attributed to the suppression of mobilization of white adipose tissues. These results suggest that KCs activation may promote binge drinking-induced fatty liver by TNF-α mediated activation of lipolysis in white adipose tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Methanolic effect of Clerodendrum myricoides root extract on blood, liver and kidney tissues of mice.

    Science.gov (United States)

    Hayelom, K; Mekbeb, A; Eyasu, M; Wondwossen, E; Kelbesa, U

    2012-12-01

    The present study deals with the toxicological investigations of chronic treatment with methanol root extract of Clerodendrum myricoides on body weight, hematological and biochemical parameters, and liver and kidney tissue sections. Mice treated with 100mg/kg bw/day of methanol extract showed no behavioral changes. However, there was a general reduction of activity in mice treated with 400mg/kg bw/day methanol extract and LD50 treated mice showed hypoactivity, grooming, prostration, piloroerection and irritation during administration towards the last days of the treatment period. The body weight gain difference in the 100mg/kg bw/day methanol extract treated group was not significant, while those of the others were significant as compared with the controls. Hematological results for the RBC count, HCT, MCV, MCH and MCHC in methanol extract treated mice showed no significant changes at both doses of treatments as compared with the controls. However, the value of lymphocytes was found significantly increased at 100 and 400mg/kg bw/day methanol extract. Similarly, HGB was significantly increased at 100 and 400mg/kg bw/day of methanol extract treated groups. On the other hand, WBC and platelets count were significantly decreased after treatment with 400mg/kg bw/day methanol extract. ALT, ALP, AST and urea values were significantly increased respectively at 100mg/kg bw/day and 400mg/kg bw/day methanol extract. Several histopathological changes of liver and kidney were observed in the extract treated mice as compared to the controls. Such histopathological changes observed in both liver and kidneys were inflammations and hydropic degenerations of hepatocytes at both doses of methanol. In addition, in the LD50 treated mice of the extracts there were also hemorrhages and signs in congestion of glomeruli of the kidney. chronic treatment with Clerodendrum myricoides extracts in mice causes reduction in body weight gain, damage to liver & kidney and changes in some

  18. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. SU-F-J-86: Method to Include Tissue Dose Response Effect in Deformable Image Registration

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, J; Liang, J; Chen, S; Qin, A; Yan, D [Beaumont Health Systeml, Royal Oak, MI (United States)

    2016-06-15

    Purpose: Organ changes shape and size during radiation treatment due to both mechanical stress and radiation dose response. However, the dose response induced deformation has not been considered in conventional deformable image registration (DIR). A novel DIR approach is proposed to include both tissue elasticity and radiation dose induced organ deformation. Methods: Assuming that organ sub-volume shrinkage was proportional to the radiation dose induced cell killing/absorption, the dose induced organ volume change was simulated applying virtual temperature on each sub-volume. Hence, both stress and heterogeneity temperature induced organ deformation. Thermal stress finite element method with organ surface boundary condition was used to solve deformation. Initial boundary correspondence on organ surface was created from conventional DIR. Boundary condition was updated by an iterative optimization scheme to minimize elastic deformation energy. The registration was validated on a numerical phantom. Treatment dose was constructed applying both the conventional DIR and the proposed method using daily CBCT image obtained from HN treatment. Results: Phantom study showed 2.7% maximal discrepancy with respect to the actual displacement. Compared with conventional DIR, subvolume displacement difference in a right parotid had the mean±SD (Min, Max) to be 1.1±0.9(−0.4∼4.8), −0.1±0.9(−2.9∼2.4) and −0.1±0.9(−3.4∼1.9)mm in RL/PA/SI directions respectively. Mean parotid dose and V30 constructed including the dose response induced shrinkage were 6.3% and 12.0% higher than those from the conventional DIR. Conclusion: Heterogeneous dose distribution in normal organ causes non-uniform sub-volume shrinkage. Sub-volume in high dose region has a larger shrinkage than the one in low dose region, therefore causing more sub-volumes to move into the high dose area during the treatment course. This leads to an unfavorable dose-volume relationship for the normal organ

  20. Metabolic Circuit Involving Free Fatty Acids, microRNA 122, and Triglyceride Synthesis in Liver and Muscle Tissues.

    Science.gov (United States)

    Chai, Chofit; Rivkin, Mila; Berkovits, Liav; Simerzin, Alina; Zorde-Khvalevsky, Elina; Rosenberg, Nofar; Klein, Shiri; Yaish, Dayana; Durst, Ronen; Shpitzen, Shoshana; Udi, Shiran; Tam, Joseph; Heeren, Joerg; Worthmann, Anna; Schramm, Christoph; Kluwe, Johannes; Ravid, Revital; Hornstein, Eran; Giladi, Hilla; Galun, Eithan

    2017-11-01

    Effective treatments are needed for hepatic steatosis characterized by accumulation of triglycerides in hepatocytes, which leads to hepatocellular carcinoma. MicroRNA 122 (MIR122) is expressed only in the liver, where it regulates lipid metabolism. We investigated the mechanism by which free fatty acids (FFAs) regulate MIR122 expression and the effect of MIR122 on triglyceride synthesis. We analyzed MIR122 promoter activity and validated its target mRNAs by transfection of Luciferase reporter plasmids into Huh7, BNL-1ME, and HEK293 cultured cell lines. We measured levels of microRNAs and mRNAs by quantitative real-time PCR analysis of RNA extracted from plasma, liver, muscle, and adipose tissues of C57BL/6 mice given the FFA-inducer CL316243. MIR122 was inhibited using an inhibitor of MIR122. Metabolic profiles of mice were determined using metabolic chambers and by histologic analyses of liver tissues. We performed RNA sequence analyses to identify metabolic pathways involving MIR122. We validated human Agpat1 and Dgat1 mRNAs, involved in triglyceride synthesis, as targets of MIR122. FFAs increased MIR122 expression in livers of mice by activating the retinoic acid-related orphan receptor alpha, and induced secretion of MIR122 from liver to blood. Circulating MIR122 entered muscle and adipose tissues of mice, reducing mRNA levels of genes involved in triglyceride synthesis. Mice injected with an inhibitor of MIR122 and then given CL316243, accumulated triglycerides in liver and muscle tissues, and had reduced rates of β-oxidation. There was a positive correlation between level of FFAs and level of MIR122 in plasma samples from 6 healthy individuals, collected before and during fasting. In biochemical and histologic studies of plasma, liver, muscle, and adipose tissues from mice, we found that FFAs increase hepatic expression and secretion of MIR122, which regulates energy storage vs expenditure in liver and peripheral tissues. Strategies to reduce

  1. PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators

    International Nuclear Information System (INIS)

    Lamba, Vishal; Yasuda, Kazuto; Lamba, Jatinder K.; Assem, Mahfoud; Davila, Julio; Strom, Stephen; Schuetz, Erin G.

    2004-01-01

    To gain insight on the expression of pregnane X receptor (PXR), we analyzed PXR.1 and PXR alternatively spliced transcripts in a panel of 36 human tissues. PXR.1 was expressed in many more tissues than previously determined, including human bone marrow and select regions of the human brain. In each of these tissues, we observed alternative splicing of various exons of PXR that generated multiple distinct PXR isoforms. The most abundant PXR alternative mRNA transcripts lacked 111 nucleotides, deleting 37 amino acids from the PXR LBD (PXR.2), or lacked 123 nt, deleting 41 amino acids from the PXR LBD (PXR.3). CYP3A4, a gene transcriptionally regulated by PXR, showed incomplete overlap with PXR in its tissue distribution. Quantitation of PXR mRNAs in human liver demonstrated that PXR.2 and PXR.3 represented 6.7% and 0.32% of total PXR mRNA transcripts. Brain expression of PXR prompted analysis of whether some brain acting chemicals were PXR ligands. The neurosteroids allopregnanolone and pregnanolone activated PXR and induced transcription of a CYP3A4-luciferase reporter. Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues

  2. PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators.

    Science.gov (United States)

    Lamba, Vishal; Yasuda, Kazuto; Lamba, Jatinder K; Assem, Mahfoud; Davila, Julio; Strom, Stephen; Schuetz, Erin G

    2004-09-15

    To gain insight on the expression of pregnane X receptor (PXR), we analyzed PXR.1 and PXR alternatively spliced transcripts in a panel of 36 human tissues. PXR.1 was expressed in many more tissues than previously determined, including human bone marrow and select regions of the human brain. In each of these tissues, we observed alternative splicing of various exons of PXR that generated multiple distinct PXR isoforms. The most abundant PXR alternative mRNA transcripts lacked 111 nucleotides, deleting 37 amino acids from the PXR LBD (PXR.2), or lacked 123 nt, deleting 41 amino acids from the PXR LBD (PXR.3). CYP3A4, a gene transcriptionally regulated by PXR, showed incomplete overlap with PXR in its tissue distribution. Quantitation of PXR mRNAs in human liver demonstrated that PXR.2 and PXR.3 represented 6.7% and 0.32% of total PXR mRNA transcripts. Brain expression of PXR prompted analysis of whether some brain acting chemicals were PXR ligands. The neurosteroids allopregnanolone and pregnanolone activated PXR and induced transcription of a CYP3A4-luciferase reporter. Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues.

  3. 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

    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...

  4. 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

  5. Experimental investigation and theoretical modelling of the nonlinear acoustical behaviour of a liver tissue and comparison with a tissue mimicking hydrogel.

    Science.gov (United States)

    Casciaro, Sergio; Demitri, Christian; Conversano, Francesco; Casciaro, Ernesto; Distante, Alessandro

    2008-02-01

    Native harmonics generated by nonlinear distortion of ultrasound during propagation in a medium may cause misinterpretations in spectral analysis when studying contrast agents. The aim of this paper is to quantitatively evaluate nonlinear propagation effects of diagnostic ultrasound pulses in biological tissues and to assess whether a cellulose-based hydrogel can be a suitable material for tissue mimicking purposes. Hydrogel and pig liver tissue samples of various thicknesses were insonified in a through-transmission set-up, employing 2.25-MHz pulses with different mechanical index (MI) values (range 0.06-0.60). Second harmonic and first harmonic amplitudes were extracted from spectra of received signals and their ratio was then used to compare hydrogel and liver behaviours. Resulting trends are very similar for sample thicknesses up to 8 cm and highlight a significant increase in nonlinearity for MI > 0.3, for both liver and hydrogel. A numerical procedure was also employed to calculate pressure distribution along the beam axis: these theoretical results showed a very good agreement with experimental data in the low pressure range, though failed in predicting the MI threshold. In conclusion, the hydrogel resulted to be a suitable material for manufacturing tissue mimicking phantoms, in particular to study contrast agent behaviour with a "low power approach".

  6. Transcriptomic responses of the liver and adipose tissues to altered carbohydrate-fat ratio in diet: an isoenergetic study in young rats.

    Science.gov (United States)

    Tanaka, Mitsuru; Yasuoka, Akihito; Shimizu, Manae; Saito, Yoshikazu; Kumakura, Kei; Asakura, Tomiko; Nagai, Toshitada

    2017-01-01

    To elucidate the effects of altered dietary carbohydrate and fat balance on liver and adipose tissue transcriptomes, 3-week-old rats were fed three kinds of diets: low-, moderate-, and high-fat diets (L, M, and H) containing a different ratio of carbohydrate-fat (C-F) (65:15, 60:20, and 35:45 in energy percent, respectively). The rats consumed the diets for 9 weeks and were subjected to biochemical and DNA microarray analyses. The rats in the H-group exhibited lower serum triacylglycerol (TG) levels but higher liver TG and cholesterol content than rats in the L-group. The analysis of differentially expressed genes (DEGs) between each group (L vs M, M vs H, and L vs H) in the liver revealed about 35% of L vs H DEGs that were regulated in the same way as M vs H DEGs, and most of the others were L- vs H-specific. Gene ontology analysis of these L vs H DEGs indicated that those related to fatty acid synthesis and circadian rhythm were enriched. Interestingly, about 30% of L vs M DEGs were regulated in a reverse way compared with L vs H and M vs H DEGs. These reversed liver DEGs included M-up/H-down genes ( Sds for gluconeogenesis from amino acids) and M-down/H-up genes ( Gpd2 for gluconeogenesis from glycerol, Agpat9 for TG synthesis, and Acot1 for beta-oxidation). We also analyzed L vs H DEGs in white (WAT) and brown (BAT) adipose tissues and found that both oxidation and synthesis of fatty acids were inhibited in these tissues. These results indicate that the alteration of dietary C-F balance differentially affects the transcriptomes of metabolizing and energy-storing tissues.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Asako Kinoshita

    Full Text Available 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.

  9. 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.

  10. 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.

  11. Effect of cadmium on glutathione S-transferase and metallothionein gene expression in coho salmon liver, gill and olfactory tissues

    International Nuclear Information System (INIS)

    Espinoza, Herbert M.; Williams, Chase R.; Gallagher, Evan P.

    2012-01-01

    Highlights: ► Developed qPCR assays to distinguish closely related GST isoforms in salmon. ► Examined the effect of cadmium on GST and metallothionein genes in 3 tissues. ► Modulation of GST varied among isoforms, tissues, and included a loss of expression. ► Metallothionein outperformed, but generally complemented, GSTs as biomarkers. ► 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 cadmium, whereas, more pronounced effects in olfactory and gill GST expression were observed at 48 h relative to earlier time

  12. Peroxisome proliferator-activated receptor α (PPARα mRNA expression in human hepatocellular carcinoma tissue and non-cancerous liver tissue

    Directory of Open Access Journals (Sweden)

    Kurokawa Tsuyoshi

    2011-12-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptor α (PPARα regulates lipid metabolism in the liver. It is unclear, however, how this receptor changes in liver cancer tissue. On the other hand, mouse carcinogenicity studies showed that PPARα is necessary for the development of liver cancer induced by peroxisome proliferators, and the relationship between PPARα and the development of liver cancer have been the focus of considerable attention. There have been no reports, however, demonstrating that PPARα is involved in the development of human liver cancer. Methods The subjects were 10 patients who underwent hepatectomy for hepatocellular carcinoma. We assessed the expression of PPARα mRNA in human hepatocellular carcinoma tissue and non-cancerous tissue, as well as the expression of target genes of PPARα, carnitine palmitoyltransferase 1A and cyclin D1 mRNAs. We also evaluated glyceraldehyde 3-phosphate dehydrogenase, a key enzyme in the glycolytic system. Results The amounts of PPARα, carnitine palmitoyltransferase 1A and glyceraldehyde 3-phosphate dehydrogenase mRNA in cancerous sections were significantly increased compared to those in non-cancerous sections. The level of cyclin D1 mRNA tends to be higher in cancerous than non-cancerous sections. Although there was a significant correlation between the levels of PPARα mRNA and cyclin D1 mRNA in both sections, however the correlation was higher in cancerous sections. Conclusion The present investigation indicated increased expression of PPARα mRNA and mRNAs for PPARα target genes in human hepatocellular carcinoma. These results might be associated with its carcinogenesis and characteristic features of energy production.

  13. Merlin, the product of NF2 gene, is associated with aromatase expression and estrogen formation in human liver tissues and liver cancer cells.

    Science.gov (United States)

    Cocciadiferro, Letizia; Miceli, Vitale; Granata, Orazia M; Carruba, Giuseppe

    2017-09-01

    The product of neurofibromatosis type 2 (NF2) gene, also known as Merlin/neurofibromin 2, homeostatically regulates liver stem cells by controlling abundance and signaling of epidermal growth factor receptor (EGFR), with a mechanism independent of the Hippo pathway. We have reported that locally elevated estrogen formation, driven by abnormally high expression and function of aromatase, may be implicated in development and progression of human hepatocellular carcinoma (HCC) through activation of a rapid signaling pathway mediated by amphiregulin (AREG) and EGFR. We have recently presented a model by which the aromatase-estrogen-amphiregulin-EGFR axis is activated in response to tissue injury and/or inflammatory disease, with its alteration eventually leading to development of major human tumors (liver, breast, prostate) and other chronic diseases (diabetes, obesity, Alzheimer's and heart disease). In this study, we investigated NF2 expression in liver cancer cells and tissues in relation to aromatase expression/function, estrogen receptor (ER) status and amphiregulin. Our data indicate that NF2 expression is associated with aromatase and AREG expression, being elevated in HCC tissues and HepG2 cells, intermediate in cirrhotic tissues and Huh7 cells, and lower in nontumoral liver and HA22T cells. In addition, NF2 expression is inversely related to wild type hERα66 and proportional to the expression of the membrane-associated hERα36 splice variant, as measured by exon-specific RT-PCR analysis, both in vivo and in vitro. Furthermore, incubation with estradiol induced a significant decrease of NF2 expression in both HA22T and Huh7 cells (over 54% and 22%, respectively), while no change could be observed in HepG2 cells, this effect being inversely related to aromatase expression and activity in HCC cell lines. Based on the above combined evidence, we hypothesize that NF2 behaves as a protein sensing tissue damage and aromatase-driven local estrogen formation

  14. Accuracy of real-time shear wave elastography in the assessment of normal liver tissue in the guinea pig (cavia porcellus).

    Science.gov (United States)

    Glińska-Suchocka, K; Kubiak, K; Spużak, J; Jankowski, M; Borusewicz, P

    2017-03-28

    Shear wave elastography is a novel technique enabling real-time measurement of the elasticity of liver tissue. The color map is superimposed on the classic ultrasound image of the assessed tissue, which enables a precise evaluation of the stiffness of the liver tissue. The aim of the study was to assess the stiffness of normal liver tissue in the guinea pig using shear wave elastography. The study was carried out on 36 guinea pigs using the SuperSonic Imagine Aixplorer scanner, and a 1 to 6 MH convex SC6-1 transducer. An ultrasound guided Try-Cut liver core needle biopsy was carried out in all the studied animals and the collected samples were examined to exclude pathological lesions. The mean liver tissue stiffness ranged from 0.89 to 5.40 kPa. We found that shear wave elastography is an easy, non-invasive technique that can be used to assess the stiffness of liver tissue. The obtained results can be used in future studies to assess the types and changes of liver tissue in the course of various types of liver disease.

  15. 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.

  16. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Changes in rat liver and adipose tissue lipogenesis after single lethal X-irradiation: modification by the restricted food intake

    International Nuclear Information System (INIS)

    Sedlakova, A.; Ahlers, I.; Praslicka, M.

    1981-01-01

    Male rats of Wistar strain were adapted during a 4-week period to the nutritional regimes of meal feeding (MF) and ad libitum (AL) and were irradiated with the single whole-body lethal X-ray dose 14.35 Gy after 22 h of fasting. Within the intervals 1, 24, 48 and 72 h after irradiation lipogenesis changes in the liver were studied by measuring 1- 14 C-acetate incorporation (74 KBq) in the total lipids, fatty acids and cholesterol, and in the white adipose tissue pieces by measuring U- 14 C-glucose incorporation (74 KBq) in the total lipids, fatty acids and glyceride glycerol. Lipogenesis increased in the liver of the irradiated rats as compared with sham irradiated rats and reached the maximal values at 72 h after irradiation in AL animals and at 48 h after irradiation in MF animals. Lipogenesis in the adipose tissue decreased in the irradiated rats as compared with the sham irradiated ones and continued to decrease with the post-irradiation period. The adaptation to the nutritional regime of meal feeding markedly modified lipogenesis in the liver and the adipose tissue of the irradiated rats. Long-term fasting (before and after irradiation) was supposed to be another modifying factor in the lipogenesis changes. Lipogenesis changes in the liver depended on the MF nutritional regime. (author)

  18. [Determination of hydroxyproline in liver tissue by hydrophilic interaction chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry].

    Science.gov (United States)

    Liu, Wei; Qi, Shenglan; Xu, Ying; Xiao, Zhun; Fu, Yadong; Chen, Jiamei; Yang, Tao; Liu, Ping

    2017-12-08

    A method for the determination of hydroxyproline (Hyp) in liver tissue of mice by hydrophilic interaction chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (HILIC-HRMS) was developed. The liver tissue samples of normal mice and liver fibrosis mice induced by carbon tetrachloride were hydrolyzed by concentrated hydrochloric acid. After filtrated and diluted by solution, the diluent was separated on an Hypersil GOLD HILIC column (100 mm×2.1 mm, 3 μm). Water-acetonitrile (28:72, v/v)were used as the mobile phases with isocratic elution. Finally, the target analytes were detected in positive model by HRMS equipped with an electrospray ionization source. The linear range of hydroxyproline was from 0.78 to 100.00 μg/L with the correlation coefficient ( R 2 ) of 0.9983. The limit of quantification was 0.78 μg/L. By detecting the spiked samples, the recoveries were in the range of 97.4%-100.9% with the relative standard deviations (RSDs) between 1.4% and 2.0%. In addition, comparison of the measurement results by this method and the chloramine T method was proceeded. It was found that the linear correlation between the two methods was very good, and the Pearson correlation coefficient was 0.927. And this method had simpler operation procedure and higher accuracy than chloramine T method. This method can be used for the quick determination of hydroxyproline in liver tissue samples.

  19. Changes in rat liver and adipose tissue lipogenesis after single lethal X-irradiation: modification by the restricted food intake

    Energy Technology Data Exchange (ETDEWEB)

    Sedlakova, A; Ahlers, I; Praslicka, M [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie

    1981-01-01

    Male rats of Wistar strain were adapted during a 4-week period to the nutritional regimes of meal feeding (MF) and ad libitum (AL) and were irradiated with the single whole-body lethal X-ray dose 14.35 Gy after 22 h of fasting. Within the intervals 1, 24, 48 and 72 h after irradiation lipogenesis changes in the liver were studied by measuring 1-/sup 14/C-acetate incorporation (74 KBq) in the total lipids, fatty acids and cholesterol, and in the white adipose tissue pieces by measuring U-/sup 14/C-glucose incorporation (74 KBq) in the total lipids, fatty acids and glyceride glycerol. Lipogenesis increased in the liver of the irradiated rats as compared with sham irradiated rats and reached the maximal values at 72 h after irradiation in AL animals and at 48 h after irradiation in MF animals. Lipogenesis in the adipose tissue decreased in the irradiated rats as compared with the sham irradiated ones and continued to decrease with the post-irradiation period. The adaptation to the nutritional regime of meal feeding markedly modified lipogenesis in the liver and the adipose tissue of the irradiated rats. Long-term fasting (before and after irradiation) was supposed to be another modifying factor in the lipogenesis changes. Lipogenesis changes in the liver depended on the MF nutritional regime.

  20. Perfluoroalkylated substances in edible livers of farm animals, including depuration behaviour in young sheep fed with contaminated grass

    NARCIS (Netherlands)

    Zafeiraki, Effrosyni; Vassiliadou, Irene; Costopoulou, Danae; Leondiadis, Leondios; Schafft, Helmut A.; Hoogenboom, Ron L.A.P.; Leeuwen, van Stefan P.J.

    2016-01-01

    Perfluoroalkylated substances (PFASs) present a potential health risk for consumers. In animals these compounds are known to accumulate in livers. In order to determine potential PFASs contamination in commercially available livers, samples from farmed sheep, horses, cows, pigs and chicken were

  1. Comparative quantified tissue characterisation of liver by ultrasound and its density by CT

    International Nuclear Information System (INIS)

    Zendel, W.; Wakat, P.; Fischer, G.; Treisch, J.; Langer, R.

    1989-01-01

    A defined region of the right lobe of the liver was measured by grey scale analysis based on similar presets according to a manual input of a Region of Interest (ROI). During 20 days, the livers of healthy subjects were tested by this method in order to test the reproducibility of the results. By prospective studied, the livers of 30 patients were examined by ultrasound and CT regarding the determination of the extent of their fatty liver disease. The value of the density of liver was determined in Hounsfield units (HU). Both methods lead to parameters that characterise the fatty content of the liver. Statistic analysis shows acceptable correlation of both methods. By means of grey scale analysis in ultrasound measurements it it possible to estimate the extent of the fatty content of liver. (orig.) [de

  2. Genome-wide effects of acute progressive feed restriction in liver and white adipose tissue

    International Nuclear Information System (INIS)

    Pohjanvirta, Raimo; Boutros, Paul C.; Moffat, Ivy D.; Linden, Jere; Wendelin, Dominique; Okey, Allan B.

    2008-01-01

    Acute progressive feed restriction (APFR) represents a specific form of caloric restriction in which feed availability is increasingly curtailed over a period of a few days to a few weeks. It is often used for control animals in toxicological and pharmacological studies on compounds causing body weight loss to equalize weight changes between experimental and control groups and thereby, intuitively, to also set their metabolic states to the same phase. However, scientific justification for this procedure is lacking. In the present study, we analyzed by microarrays the impact on hepatic gene expression in rats of two APFR regimens that caused identical diminution of body weight (19%) but differed slightly in duration (4 vs. 10 days). In addition, white adipose tissue (WAT) was also subjected to the transcriptomic analysis on day-4. The data revealed that the two regimens led to distinct patterns of differentially expressed genes in liver, albeit some major pathways of energy metabolism were similarly affected (particularly fatty acid and amino acid catabolism). The reason for the divergence appeared to be entrainment by the longer APFR protocol of peripheral oscillator genes, which resulted in derailment of circadian rhythms and consequent interaction of altered diurnal fluctuations with metabolic adjustments in gene expression activities. WAT proved to be highly unresponsive to the 4-day APFR as only 17 mRNA levels were influenced by the treatment. This study demonstrates that body weight is a poor proxy of metabolic state and that the customary protocols of feed restriction can lead to rhythm entrainment

  3. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  4. 3D printed optical phantoms and deep tissue imaging for in vivo applications including oral surgery

    Science.gov (United States)

    Bentz, Brian Z.; Costas, Alfonso; Gaind, Vaibhav; Garcia, Jose M.; Webb, Kevin J.

    2017-03-01

    Progress in developing optical imaging for biomedical applications requires customizable and often complex objects known as "phantoms" for testing, evaluation, and calibration. This work demonstrates that 3D printing is an ideal method for fabricating such objects, allowing intricate inhomogeneities to be placed at exact locations in complex or anatomically realistic geometries, a process that is difficult or impossible using molds. We show printed mouse phantoms we have fabricated for developing deep tissue fluorescence imaging methods, and measurements of both their optical and mechanical properties. Additionally, we present a printed phantom of the human mouth that we use to develop an artery localization method to assist in oral surgery.

  5. Non-invasive liver fibrosis score calculated by combination of virtual touch tissue quantification and serum liver functional tests in chronic hepatitis C patients.

    Science.gov (United States)

    Takaki, Shintaro; Kawakami, Yoshiiku; Miyaki, Daisuke; Nakahara, Takashi; Naeshiro, Noriaki; Murakami, Eisuke; Tanaka, Mio; Honda, Yohji; Yokoyama, Satoe; Nagaoki, Yuko; Kawaoka, Tomokazu; Hiramatsu, Akira; Tsuge, Masataka; Hiraga, Nobuhiko; Imamura, Michio; Hyogo, Hideyuki; Aikata, Hiroshi; Takahashi, Shoichi; Arihiro, Koji; Chayama, Kazuaki

    2014-03-01

    Acoustic radiation force impulse (ARFI) technology, involving the shear wave velocity (SWV) with virtual touch tissue quantification (VTTQ), are currently available for the assessment of liver fibrosis, while there is no index derived from the combination of SWV and blood tests. The aim of this study was to develop a new index for assessment of liver fibrosis. The subjects were 176 consecutive patients with hepatitis C (training set [n = 120] and validation set [n = 56]) who underwent liver biopsy in our institution. In the training set, SWV, international normalized ratio (INR) and alanine aminotransferase (ALT) correlated independently and significantly with fibrosis. According to this, we developed the VIA index = -1.282 + 0.965 × SWV + 1.785 INR + 0.00185 ALT. The areas under the receiver-operator curve (AUROC) of the VIA index were 0.838 for the diagnosis of significant fibrosis (≥F2), 0.904 for the severe fibrosis (≥F3) and 0.958 for the cirrhosis (F4) in the training set. While in the validation set, AUROC of the VIA index were 0.917 for F2 or higher, 0.906 for F3 or higher and 1.000 for F4, respectively. AUROC of the VIA index was improved compared to SWV alone, equivalent for VIA for the diagnosis of F2 or higher, and superior to that of FIB-4 index and aspartate aminotransferase-to-platelet ratio index for the diagnosis of F3 or higher and F4. The VIA index is potentially more useful for assessment of liver fibrosis than SWV alone, and easily and accurately measures liver fibrosis stage. © 2013 The Japan Society of Hepatology.

  6. SMRT has tissue-specific isoform profiles that include a form containing one CoRNR box

    International Nuclear Information System (INIS)

    Short, Stephen; Malartre, Marianne; Sharpe, Colin

    2005-01-01

    SMRT acts as a corepressor for a range of transcription factors. The amino-terminal part of the protein includes domains that mainly mediate transcriptional repression whilst the carboxy-terminal part includes domains that interact with nuclear receptors using up to three motifs called CoRNR boxes. The region of the SMRT primary transcript encoding the interaction domains is subject to alternative splicing that varies the inclusion of the third CoRNR box. The profile in mice includes an abundant, novel SMRT isoform that possesses just one CoRNR box. Mouse tissues therefore express SMRT isoforms containing one, two or three CoRNR boxes. In frogs, the SMRT isoform profile is tissue-specific. The mouse also shows distinct profiles generated by differential expression levels of the SMRT transcript isoforms. The formation of multiple SMRT isoforms and their tissue-specific regulation indicates a mechanism, whereby cells can define the repertoire of transcription factors regulated by SMRT

  7. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix liver scaffolds.

    Science.gov (United States)

    Sabetkish, Shabnam; Kajbafzadeh, Abdol-Mohammad; Sabetkish, Nastaran; Khorramirouz, Reza; Akbarzadeh, Aram; Seyedian, Sanam Ladi; Pasalar, Parvin; Orangian, Saghar; Beigi, Reza Seyyed Hossein; Aryan, Zahra; Akbari, Hesam; Tavangar, Seyyed Mohammad

    2015-04-01

    To report the results of whole liver decellularization by two different methods. To present the results of grafting rat and sheep decellularized liver matrix (DLM) into the normal rat liver and compare natural cell seeding process in homo/xenograft of DLM. To compare the results of in vitro whole liver recellularization with rats' neonatal green fluorescent protein (GFP)-positive hepatic cells with outcomes of in vivo recellularization process. Whole liver of 8 rats and 4 sheep were resected and cannulated via the hepatic vein and perfused with sodium dodecyl sulfate (SDS) or Triton + SDS. Several examinations were performed to compare the efficacy of these two decellularization procedures. In vivo recellularization of sheep and rat DLMs was performed following transplantation of multiple pieces of both scaffolds in the subhepatic area of four rats. To compare the efficacy of different scaffolds in autologous cell seeding, biopsies of homograft and xenograft were assessed 8 weeks postoperatively. Whole DLMs of 4 rats were also recellularized in vitro by perfusion of rat's fetal GFP-positive hepatic cells with pulsatile bioreactor. Histological evaluation and enzymatic assay were performed for both in vivo and in vitro recellularized samples. The results of this study demonstrated that the triton method was a promising decellularization approach for preserving the three-dimensional structure of liver. In vitro recellularized DLMs were more similar to natural ones compared with in vivo recellularized livers. However, homografts showed better characteristics with more organized structure compared with xenografts. In vitro recellularization of liver scaffolds with autologous cells represents an attractive prospective for regeneration of liver as one of the most compound organs. In vivo cell seeding on the scaffold of the same species may have more satisfactory outcomes when compared with the results of xenotransplantation. This study theoretically may pave the road for

  8. 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

    International Nuclear Information System (INIS)

    Behrens, Christopher B.; Langholz, Juliane H.; Eiler, Jessika; Jenewein, Raphael; Fuchs, Konstantin; Alzen, Gerhard F.P.; Naehrlich, Lutz; Harth, Sebastian; Krombach, Gabriele A.

    2013-01-01

    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.)

  9. 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.)

  10. Nicotine affects hydrogen sulfide concentrations in mouse kidney and heart but not in brain and liver tissues.

    Science.gov (United States)

    Wiliński, Jerzy; Wiliński, Bogdan; Somogyi, Eugeniusz; Piotrowska, Joanna; Kameczura, Tomasz; Zygmunt, Małgorzata

    2017-01-01

    Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1.5 mg/kg b.w. per day of nicotine (group D1, n = 10) or 3 mg/ kg b.w. per day of nicotine (group D2, n = 10). The control group (n = 10) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with the Siegel spectrophotometric modi ed method. ere was a significant increase in H2S concentrations in both nicotine doses groups in the kidney (D1 by 54.2%, D2 by 40.0%). In the heart the higher nicotine dose caused a marked decrease in H2S tissue level (by 65.4%), while the lower dose did not affect H2S content. Nicotine administration had no effect on H2S concentrations in the brain and liver. In conclusion, nicotine affects H2S tissue concentrations in kidney and heart but not in the liver and brain tissues.

  11. [Influence of FPS on the expression of LDL-R mRNA in the liver tissues of hyperlipidemic rats].

    Science.gov (United States)

    Wu, Qing-he; Xing, Yan-hong; Rong, Xiang-lu; Huang, Ping

    2007-08-01

    To explore the effect of FPS on low-density lipoprotein acceptor (LDL-R) mRNA in the liver tissues of hyperlipidemic rats. Sixty healthy male SD rats were randomly divided into six groups: normal control, model control, Gynostemma pentaphyllum, FPS low dosage, FPS moderate dosage, and FPS high dosage group. Excepting the rats in the normal control group, the ones in other groups were all made rats' hyperlipidemic model by irrigating hyperlipidemic emulsion into the stomach and observed the expression of LDL-R mRNA in the liver tissues of rats of each group. Relative content of LDL-RmRNA in low and moderate dosage groups was notably higher than that inmodel group. The contents's difference was not remarkable between FPS moderate dosage group and Gynostemma pentaphyllum group. FPS can appreciably increase the expression of LDL-R mRNA in the liver tissues of hyperlipidemic rats and promote the elimination ofLDL-C to reduce serum cholesterol notably.

  12. Effects of grape seed polyphenols on oxidative damage in liver tissue of acutely and chronically exercised rats.

    Science.gov (United States)

    Belviranlı, Muaz; Gökbel, Hakkı; Okudan, Nilsel; Büyükbaş, Sadık

    2013-05-01

    The objective of the present study was to investigate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant defense markers in liver tissue of acutely and chronically exercised rats. Rats were randomly assigned to six groups: Control (C), Control Chronic Exercise (CE), Control Acute Exercise (AE), GSE-supplemented Control (GC), GSE-supplemented Chronic Exercise(GCE) and GSE-supplemented Acute Exercise (GAE). Rats in the chronic exercise groups were subjected to a six-week treadmill running and in the acute exercise groups performed an exhaustive running. Rats in the GSE supplemented groups received GSE (100 mg.kg(-1) .day(-1) ) in drinking water for 6 weeks. Liver tissues of the rats were taken for the analysis of malondialdehyde (MDA), nitric oxide (NO) levels and total antioxidant activity (AOA) and xanthine oxidase (XO) activities. MDA levels decreased with GSE supplementation in control groups but increased in acute and chronic exercise groups compared to their non-supplemented control. NO levels increased with GSE supplementation. XO activities were higher in AE group compared to the CE group. AOA decreased with GSE supplementation. In conclusion, while acute exercise triggers oxidative stress, chronic exercise has protective role against oxidative stress. GSE has a limited antioxidant effect on exercise-induced oxidative stress in liver tissue.

  13. The Histopathological Characteristics Caused by Trionyx sinensis Hemorrhagic Syndrome Virus (TSHSV) and Comparative Proteomic Analysis of Liver Tissue in TSHSV-Infected Chinese Soft-Shelled Turtles (Pelodiscus sinensis).

    Science.gov (United States)

    Liu, Li; Cao, Zheng; Lin, Feng; Ye, Xueping; Lu, Shujuan; Lyv, Sunjian

    2017-01-01

    Trionyx sinensis hemorrhagic syndrome virus (TSHSV) is a pathogen that causes severe hemorrhagic syndrome and irreversible damage to different infected tissues of Pelodis cus sinensis, ending in the death of affected organisms. In the present study, the histopathological characteristics of TSHSV-infected P. sinensis were analyzed and compared by HE staining. Relative and absolute quantification (iTRAQ)-based proteomic analysis was employed to explore the molecular pathology of liver injury. Anatomical features indicated that TSHSV caused obvious congestion in the liver, kidney, intestine, and other tissues of P. sinensis. The typical clinical symptoms included hepatomegaly, fragility, spotty and severe congestion in liver tissue, and also obvious intestinal bleeding. The histopathological studies corroborated such lesions in the liver and kidney, etc. iTRAQ-based proteomic analysis revealed that there were 252 differentially expressed proteins in the liver tissue between healthy and infected P. sinensis, of which 118 proteins were upregulated and 134 proteins were downregulated. GO enrichment analysis and KEGG pathway analysis initially revealed the molecular mechanism of pathological changes in P. sinensis by TSHSV infection. The expression of some differentially expressed proteins was further confirmed by qRT-PCR. These results provided important information for the pathological diagnosis of TSHSV-caused disease, as well as the mechanism underlying TSHSV-caused disease. © 2017 S. Karger AG, Basel.

  14. Zearalenone (ZEN and Its Influence on Regulation of Gene Expression in Carp (Cyprinus carpio L. Liver Tissue

    Directory of Open Access Journals (Sweden)

    Constanze Pietsch

    2017-09-01

    Full Text Available Zearalenone (ZEN is a frequently-occurring mycotoxin in both animal and fish feeds. In order to characterize its effects on carp, three groups of fish were fed for 28 days with feeds contaminated with three different levels of ZEN (low: 332 µg kg−1, medium: 621 µg kg−1, and high: 797 µg kg−1 feed. The reversibility of the effects of ZEN was assessed by feeding all of the groups with uncontaminated feed for a further 14 days. Gene expression of immune genes in the liver tissue of the fish was analysed, revealing reduced expressions of immune, antioxidative, and estrogen-related genes after the fish had been exposed to ZEN. However, the expression of vacuole-type H+ ATPase increased substantially with ZEN exposure, thus supporting the previously-reported sensitivity of lysosomal functions to ZEN. Feeding the fish with a ZEN-free diet for a further two weeks changed the effects of ZEN on the expression of some genes, including the expressions of the cytokines IL-1β, IL-8, IL-10, and arginase 2, which were not influenced after four weeks of treatment, but showed lower values after the recovery phase in fish previously treated with ZEN compared with the control group. In summary, this study confirmed the broad effects of ZEN on different essential functions in carp and suggests that the current maximum allowable levels in compound feed are too high to prevent damage to fish.

  15. Zearalenone (ZEN) and Its Influence on Regulation of Gene Expression in Carp (Cyprinus carpio L.) Liver Tissue.

    Science.gov (United States)

    Pietsch, Constanze

    2017-09-15

    Zearalenone (ZEN) is a frequently-occurring mycotoxin in both animal and fish feeds. In order to characterize its effects on carp, three groups of fish were fed for 28 days with feeds contaminated with three different levels of ZEN (low: 332 µg kg -1 , medium: 621 µg kg -1 , and high: 797 µg kg -1 feed). The reversibility of the effects of ZEN was assessed by feeding all of the groups with uncontaminated feed for a further 14 days. Gene expression of immune genes in the liver tissue of the fish was analysed, revealing reduced expressions of immune, antioxidative, and estrogen-related genes after the fish had been exposed to ZEN. However, the expression of vacuole-type H⁺ ATPase increased substantially with ZEN exposure, thus supporting the previously-reported sensitivity of lysosomal functions to ZEN. Feeding the fish with a ZEN-free diet for a further two weeks changed the effects of ZEN on the expression of some genes, including the expressions of the cytokines IL-1β, IL-8, IL-10, and arginase 2, which were not influenced after four weeks of treatment, but showed lower values after the recovery phase in fish previously treated with ZEN compared with the control group. In summary, this study confirmed the broad effects of ZEN on different essential functions in carp and suggests that the current maximum allowable levels in compound feed are too high to prevent damage to fish.

  16. Acute Toxicity of Captan on Blood Factors Total Immunoglobulin, Liver, and Gill Tissues of Fingerling Grass Carps: Ctenopharyngodon idella

    Directory of Open Access Journals (Sweden)

    Mehdi Mohammadalikhani

    2017-01-01

    Full Text Available The majority of fungicides, including captan, used in gardens and farms are washed into the aquatic environments. These compounds can lead to extensive side effects on the inhabitants living in that exposed area. In this research, toxicity of captan on fingerling grass carps (3-5 g was studied. Based on the results, captan was categorized as an acute toxin with LC5096h and MAC values of 0.9 and 0.09 mg/ml, respectively. This toxin damaged severely the gills and liver of fishes and the toxic severity increased in higher doses of the toxin. Furthermore, hematochemical studies showed significant drops in all red blood cell criteria, except for MCH (mean corpuscular haemoglobin and MCV (mean corpuscular volume. Besides, captan decreased significantly the total immunoglobulin and white blood cell counts, except for monocytes and neutrophils. As a conclusion, captan causes detrimental effects on several tissues of Ctenopharyngodon idella, and therefore limited utilisation of this fungicide is recommended strongly.

  17. Is the propagation speed of ultrasound in human organs a diagnostic parameter for tissue characterization? Evaluation using the liver parenchyma in children and adolescents as an example

    International Nuclear Information System (INIS)

    Born, M.; Franke, I.

    2011-01-01

    New sonographic machines permit the measurement of the propagation speed of ultrasound (PSU) in humans. The liver seems to be an appropriate organ for examining whether the PSU may be used as a diagnostic parameter for tissue characterization since the liver is easily accessible to sonography and its variable content of fat impacts the PSU. Purpose: To determine whether there is a measurable correlation between obesity and PSU in the liver. Methods: In 69 children and adolescents, the PSU in the liver was measured sonographically and correlated to BMI, age, size and weight of the children. Results: A strong correlation was found between the PSU in the liver and the BMI. The PSU was significantly lower in obese children (1507 m/s) than in children with normal body weight (1564 m/s). Conclusion: PSU seems to be promising as an additional diagnostic parameter for characterizing liver tissue. Further evaluation is necessary. (orig.)

  18. Concentrations of 17 elements, including mercury, in the tissues, food and abiotic environment of Arctic shorebirds

    International Nuclear Information System (INIS)

    Hargreaves, Anna L.; Whiteside, Douglas P.; Gilchrist, Grant

    2011-01-01

    concern for breeding bird populations. - Highlights: → We assess elements in soil, invertebrates, and breeding shorebird tissues in the Arctic. → Element levels, invertebrate composition and shorebird use differed among habitat types. → Hg was elevated in blood and eggs and was negatively related to egg volume. → Hg and Se showed significant bioaccumulation and biomagnification. → However, all element levels were within available Canadian safety guidelines.

  19. Concentrations of 17 elements, including mercury, in the tissues, food and abiotic environment of Arctic shorebirds

    Energy Technology Data Exchange (ETDEWEB)

    Hargreaves, Anna L., E-mail: alhargreaves@gmail.com [Calgary Zoo, Centre for Conservation Research, 1300 Zoo Rd NE, Calgary, AB, T2E 7V6 (Canada); Whiteside, Douglas P. [Calgary Zoo, Animal Health Centre, 1300 Zoo Rd NE, Calgary, AB, T2E 7V6 (Canada); University of Calgary, Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, 2500 University Dr. NW, Calgary, AB, T2N 1N4 (Canada); Gilchrist, Grant [Carleton University, National Wildlife Research Centre, Ottawa, ON, KIA OH3 (Canada)

    2011-09-01

    concern for breeding bird populations. - Highlights: {yields} We assess elements in soil, invertebrates, and breeding shorebird tissues in the Arctic. {yields} Element levels, invertebrate composition and shorebird use differed among habitat types. {yields} Hg was elevated in blood and eggs and was negatively related to egg volume. {yields} Hg and Se showed significant bioaccumulation and biomagnification. {yields} However, all element levels were within available Canadian safety guidelines.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Po-Hsiang Tsui

    Full Text Available 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 < 0.0001. However, the effect of ultrasound frequency on the 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.

  2. The Influence of Tissue Procurement Procedures on RNA Integrity, Gene Expression, and Morphology in Porcine and Human Liver Tissue

    Czech Academy of Sciences Publication Activity Database

    Kap, M.; Sieuwerts, A.M.; Kubista, Mikael; Oomen, M.; Arshad, S.; Riegman, P.

    2015-01-01

    Roč. 13, č. 3 (2015), s. 200-206 ISSN 1947-5535 Institutional support: RVO:86652036 Keywords : WARM ISCHEMIA * SPECIMENS * FROZEN TISSUE * PURPOSE Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.804, year: 2015

  3. How predictive quantitative modelling of tissue organisation can inform liver disease pathogenesis.

    Science.gov (United States)

    Drasdo, Dirk; Hoehme, Stefan; Hengstler, Jan G

    2014-10-01

    From the more than 100 liver diseases described, many of those with high incidence rates manifest themselves by histopathological changes, such as hepatitis, alcoholic liver disease, fatty liver disease, fibrosis, and, in its later stages, cirrhosis, hepatocellular carcinoma, primary biliary cirrhosis and other disorders. Studies of disease pathogeneses are largely based on integrating -omics data pooled from cells at different locations with spatial information from stained liver structures in animal models. Even though this has led to significant insights, the complexity of interactions as well as the involvement of processes at many different time and length scales constrains the possibility to condense disease processes in illustrations, schemes and tables. The combination of modern imaging modalities with image processing and analysis, and mathematical models opens up a promising new approach towards a quantitative understanding of pathologies and of disease processes. This strategy is discussed for two examples, ammonia metabolism after drug-induced acute liver damage, and the recovery of liver mass as well as architecture during the subsequent regeneration process. This interdisciplinary approach permits integration of biological mechanisms and models of processes contributing to disease progression at various scales into mathematical models. These can be used to perform in silico simulations to promote unravelling the relation between architecture and function as below illustrated for liver regeneration, and bridging from the in vitro situation and animal models to humans. In the near future novel mechanisms will usually not be directly elucidated by modelling. However, models will falsify hypotheses and guide towards the most informative experimental design. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  4. Cloning Changes the Response to Obesity of Innate Immune Factors in Blood, Liver, and Adipose Tissues in Domestic Pigs

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Rafael Simó

    Full Text Available 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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma

    International Nuclear Information System (INIS)

    Xu ZhiYong; Liang Shixiong; Zhu Ji; Zhu Xiaodong; Zhao Jiandong; Lu Haijie; Yang Yunli; Chen Long; Wang Anyu; Fu Xiaolong; Jiang Guoliang

    2006-01-01

    Purpose: To describe the probability of RILD by application of the Lyman-Kutcher-Burman normal-tissue complication (NTCP) model for primary liver carcinoma (PLC) treated with hypofractionated three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: A total of 109 PLC patients treated by 3D-CRT were followed for RILD. Of these patients, 93 were in liver cirrhosis of Child-Pugh Grade A, and 16 were in Child-Pugh Grade B. The Michigan NTCP model was used to predict the probability of RILD, and then the modified Lyman NTCP model was generated for Child-Pugh A and Child-Pugh B patients by maximum-likelihood analysis. Results: Of all patients, 17 developed RILD in which 8 were of Child-Pugh Grade A, and 9 were of Child-Pugh Grade B. The prediction of RILD by the Michigan model was underestimated for PLC patients. The modified n, m, TD 5 (1) were 1.1, 0.28, and 40.5 Gy and 0.7, 0.43, and 23 Gy for patients with Child-Pugh A and B, respectively, which yielded better estimations of RILD probability. The hepatic tolerable doses (TD 5 ) would be MDTNL of 21 Gy and 6 Gy, respectively, for Child-Pugh A and B patients. Conclusions: The Michigan model was probably not fit to predict RILD in PLC patients. A modified Lyman NTCP model for RILD was recommended

  9. Mechanism of tumor and liver concentration of /sup 111/In and /sup 169/Yb: /sup 111/In and /sup 169/Yb binding substances in tumor tissues and liver

    Energy Technology Data Exchange (ETDEWEB)

    Ando, A; Ando, I; Hiraki, T; Takeshita, M; Hisada, K

    1982-07-01

    Tumor-bearing animals were injected with /sup 111/In- and /sup 169/Yb-citrate. Tumor homogenates, from which the nuclear fraction was removed, and the mitochondrial fractions of the host livers were digested with pronase P. After digestion, the supernatants of the reaction mixtures were applied to Sephadex G-100 columns. The resultant eluates were analyzed for radioactivity, protein, uronic acid, and sialic acids. Three peaks of radioactivity were obtained by gel filtration. The first peak, eluted the void volume, contained a species whose molecular weight exceeded 40000. The second peak consisted of substances with molecular weights of 9400-40000. Radioactivity in the third peak was liberated /sup 111/In and /sup 169/Yb. These two nuclides in the second peak were bound to acid mucopolysaccharide and/or the sulfated carbohydrate chain of sulfated glycorprotein. It was thought that the nuclides in the first peak might be bound to some acid mucopolysaccharides. The second peak nuclides seemed to be bound to acid mucopolysaccharide that contained no uronic acids, and/or to the sulfated carbohydrate chain of sulfated glycoprotein. It was concluded that they were bound to the acid mucopolysaccharides and/or the sulfated carbohydrate chain of sulfated glycoprotein in tumor tissues and liver lysosomes.

  10. Ultrastructural study of liver and lead tissue concentrations in young mallard ducks (Anas platyrhynchos) after ingestion of single lead shot.

    Science.gov (United States)

    Pineau, Alain; Fauconneau, Bernard; Plouzeau, Eric; Fernandez, Béatrice; Quellard, Nathalie; Levillain, Pierre; Guillard, Olivier

    2017-01-01

    Lead (Pb) represents a serious threat to wildlife and ecosystems. The aim of this study was to examine the subcellular effects of dietary Pb pellet ingestion on mallard (Anas platyrhynchos) livers. After ingestion of a single Pb shot (LS4 size class: 0.177 ± 0.03 g) in 41 mallard ducks (22 males and 19 females) versus 10 controls (5 males and 5 females), all 7-week old, a morphologic study was conducted by TEM (transmission electron microscopy) of liver at the subcellular level. The results in treated mallards showed at a magnification of 2500 X that hepatic parenchyma was altered as evidenced by intralysosomal electron-dense deposits, which are compatible with Pb deposits. Further, at a higher magnification (15,000 X) in both genders, deterioration of mitochondria was observed in which the crests and, to a lesser extent, outer membrane were lysed. While the rough endoplasmic reticulum was fragmented, intracytoplasmic electron-dense material compatible with Pb deposits was maximally visible, thereby underscoring the deeply destructive effect of this metal on the subcellular architecture of the liver. In addition, applying an optimized and validated method in a clean room using electrothermal atomic absorption spectrophotometer (ETAAS) with Zeeman background correction, the objective was to improve and refine certain indispensable measurements pertaining to Pb impregnation in tissues other than liver such as kidneys, bones, and feathers of mallards. Data demonstrated show that compared with controls, Pb accumulation increases significantly, not only in the liver (3-fold), but also in the bones and the feathers (14-fold). No significant difference was noted between males and females. Bearing in mind the marked subcellular toxicity attributed to Pb, this study reinforces present-day arguments advocating limitation of game consumption.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. Tissue ablation accelerated by peripheral scanning mode with high-intensity focused ultrasound: a study on isolated porcine liver perfusion.

    Science.gov (United States)

    Bu, Rui; Yin, Li; Yang, Han; Wang, Qi; Wu, Feng; Zou, Jian Zhong

    2013-08-01

    The aims of this study were to investigate the feasibility of accelerated tissue ablation using a peripheral scanning mode with high-intensity focused ultrasound (HIFU) and to explore the effect of flow rate on total energy consumption of the target tissues. Using a model of isolated porcine liver perfusion via the portal vein and hepatic artery, we conducted a scanning protocol along the periphery of the target tissues using linear-scanned HIFU to carefully adjust the varying focal depth, generator power, scanning velocity and line-by-line interval over the entire ablation range. Porcine livers were divided into four ablation groups: group 1, n = 12, with dual-vessel perfusion; group 2, n = 11, with portal vein perfusion alone; group 3, n = 10, with hepatic artery perfusion alone; and group 4, n = 11, control group with no-flow perfusion. The samples were cut open consecutively at a thickness of 3 mm, and the actual ablation ranges were calculated along the periphery of the target tissues after triphenyl tetrazolium chloride staining. Total energy consumption was calculated as the sum of the energy requirements at various focal depths in each group. On the basis of the pre-supposed scanning protocol, the peripheral region of the target tissue formed a complete coagulation necrosis barrier in each group with varying dose combinations, and the volume of the peripheral necrotic area did not differ significantly among the four groups (p > 0.05). Furthermore, total energy consumption in each group significantly decreased with the corresponding decrease in flow rate (p Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  14. Proteomic Profiles of Adipose and Liver Tissues from an Animal Model of Metabolic Syndrome Fed Purple Vegetables

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    Hala M Ayoub

    2018-04-01

    Full Text Available Metabolic Syndrome (MetS is a complex disorder that predisposes an individual to Cardiovascular Diseases and type 2 Diabetes Mellitus. Proteomics and bioinformatics have proven to be an effective tool to study complex diseases and mechanisms of action of nutrients. We previously showed that substitution of the majority of carbohydrate in a high fat diet by purple potatoes (PP or purple carrots (PC improved insulin sensitivity and hypertension in an animal model of MetS (obese Zucker rats compared to a control sucrose-rich diet. In the current study, we used TMT 10plex mass tag combined with LC-MS/MS technique to study proteomic modulation in the liver (n = 3 samples/diet and adipose tissue (n = 3 samples/diet of high fat diet-fed rats with or without substituting sucrose for purple vegetables, followed by functional enrichment analysis, in an attempt to elucidate potential molecular mechanisms responsible for the phenotypic changes seen with purple vegetable feeding. Protein folding, lipid metabolism and cholesterol efflux were identified as the main modulated biological themes in adipose tissue, whereas lipid metabolism, carbohydrate metabolism and oxidative stress were the main modulated themes in liver. We propose that enhanced protein folding, increased cholesterol efflux and higher free fatty acid (FFA re-esterification are mechanisms by which PP and PC positively modulate MetS pathologies in adipose tissue, whereas, decreased de novo lipogenesis, oxidative stress and FFA uptake, are responsible for the beneficial effects in liver. In conclusion, we provide molecular evidence for the reported metabolic health benefits of purple carrots and potatoes and validate that these vegetables are good choices to replace other simple carbohydrate sources for better metabolic health.

  15. European research and commercialisation activities in the field of tissue engineering and liver support in world wide competition.

    Science.gov (United States)

    Marx, U; Bushnaq, H; Yalcin, E

    1998-02-01

    Tissue engineering is seen as an interesting field of technology which could improve medical therapy and could also be considered as a commercial opportunity for the European biotechnological industry. Research in the state of the art of science using the MedLine and the Science Citation Index databases, in the patent situation and of the industry dealing with tissue engineering was done. A special method, based on the Science Citation Index Journal Citation Report 1993, for evaluating scientific work was defined. The main countries working in the field of tissue engineering were evaluated in regard to their scientific performance and their patents. The R&D of German industry was investigated as an exemplary European country. Out of all activities, different tissues were rated with respect to the attention received from research and industry and with regard to the frequency in which patents were applied for. USA, Germany and Japan rank first in most tissues, especially liver. After comparing German patents with the German scientific and industrial work, it seems that the potential in German patents and research is underestimated by German industry and inefficiently exploited.

  16. Adipokines in Liver Cirrhosis.

    Science.gov (United States)

    Buechler, Christa; Haberl, Elisabeth M; Rein-Fischboeck, Lisa; Aslanidis, Charalampos

    2017-06-29

    Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients. Adipokines are proteins released from adipose tissue and modulate hepatic fibrogenesis. These proteins affect various biological processes that are involved in liver function, including angiogenesis, vasodilation, inflammation and deposition of extracellular matrix proteins. The best studied adipokines are adiponectin and leptin. Adiponectin protects against hepatic inflammation and fibrogenesis, and leptin functions as a profibrogenic factor. These and other adipokines are supposed to modulate disease severity in patients with liver cirrhosis. Consequently, circulating levels of these proteins have been analyzed to identify associations with parameters of hepatic function, portal hypertension and its associated complications in patients with liver cirrhosis. This review article briefly addresses the role of adipokines in hepatitis and liver fibrosis. Here, studies having analyzed these proteins in systemic blood in cirrhotic patients are listed to identify adipokines that are comparably changed in the different cohorts of patients with liver cirrhosis. Some studies measured these proteins in systemic, hepatic and portal vein blood or after TIPS to specify the tissues contributing to circulating levels of these proteins and the effect of portal hypertension, respectively.

  17. Features of liver tissue remodeling in intestinal failure during and after weaning off parenteral nutrition.

    Science.gov (United States)

    Mutanen, Annika; Lohi, Jouko; Sorsa, Timo; Jalanko, Hannu; Pakarinen, Mikko P

    2016-09-01

    Intestinal failure is associated frequently with liver injury, which persists after weaning off parenteral nutrition. We compared features of liver remodeling in intestinal failure during and after weaning off parenteral nutrition. Liver biopsies and serum samples were obtained from 25 intestinal failure patients at a median age of 9.7 years (interquartile range: 4.6-18) and from age-matched control patients. Seven patients had been receiving parenteral nutrition for 53 months (22-160), and 18 patients had been weaned off parenteral nutrition 6.3 years (2.4-17) earlier, after having received parenteral nutrition for 10 months (3.3-34). Expression of alpha-smooth muscle actin, collagen 1, proinflammatory cytokines, growth factors, and matrix metalloproteinases (MMPs) was measured. Significant increases in immunohistochemical expression of alpha-smooth muscle actin and collagen 1 were observed predominantly in portal areas and were similar to increases seen in patients currently receiving parenteral nutrition and in patients weaned off parenteral nutrition. Gene and protein expressions of alpha-smooth muscle actin and collagen were interrelated. Gene expression of ACTA2, encoding alpha-smooth muscle actin, was increased only in patients who were receiving parenteral nutrition currently. Comparable upregulation of interleukin-1 (α and ß), epidermal growth factor, integrin-ß6, and MMP9 gene expression was observed in both patient groups, irrespective of whether they were receiving parenteral nutrition currently. Liver expression and serum levels of TIMP1 and MMP7 were increased only in the patients on parenteral nutrition currently but were not increased after weaning off parenteral nutrition. Intestinal failure is characterized by abnormal activation of hepatic myofibroblast and accumulation of collagen both during and after weaning off parenteral nutrition. Persistent transcriptional upregulation of proinflammatory and fibrogenic cytokines after weaning off

  18. A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes

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    Björn eNitzsche

    2015-06-01

    Full Text Available Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams were acquired on a 1.5T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight, age and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM and white (WM matter as well as cerebrospinal fluid (CSF classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM. Overall, a positive correlation of GM volume and body weight explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species.

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

    International Nuclear Information System (INIS)

    Raschpichler, M.C.; Leipzig Univ. Medical Center; Sorge, I.; Hirsch, W.; Mende, M.; Sergeyev, E.; Koerner, A.; Kruber, D.; Schick, F.

    2012-01-01

    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 1 H Magnetic Resonance Spectroscopy ( 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 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 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.)

  20. 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.)

  1. Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice.

    Science.gov (United States)

    Valenzuela, Rodrigo; Echeverria, Francisca; Ortiz, Macarena; Rincón-Cervera, Miguel Ángel; Espinosa, Alejandra; Hernandez-Rodas, María Catalina; Illesca, Paola; Valenzuela, Alfonso; Videla, Luis A

    2017-04-11

    Eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, C20:4n-6) are long-chain polyunsaturated fatty acids (LCPUFAs) with relevant roles in the organism. EPA and DHA are synthesized from the precursor alpha-linolenic acid (ALA, C18:3n-3), whereas AA is produced from linoleic acid (LA, C18:2n-6) through the action of Δ5 and Δ6-desaturases. High-fat diet (HFD) decreases the activity of both desaturases and LCPUFA accretion in liver and other tissues. Hydroxytyrosol (HT), a natural antioxidant, has an important cytoprotective effects in different cells and tissues. Male mice C57BL/6 J were fed a control diet (CD) (10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks. Animals were daily supplemented with saline (CD) or 5 mg HT (HFD), and blood and the studied tissues were analyzed after the HT intervention. Parameters studied included liver histology (optical microscopy), activity of hepatic desaturases 5 and 6 (gas-liquid chromatography of methyl esters derivatives) and antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase by spectrophotometry), oxidative stress indicators (glutathione, thiobarbituric acid reactants, and the antioxidant capacity of plasma), gene expression assays for sterol regulatory element-binding protein 1c (SREBP-1c) (qPCR and ELISA), and LCPUFA profiles in liver, erythrocyte, brain, heart, and testicle (gas-liquid chromatography). HFD led to insulin resistance and liver steatosis associated with SREBP-1c upregulation, with enhancement in plasma and liver oxidative stress status and diminution in the synthesis and storage of n-6 and n-3 LCPUFAs in the studied tissues, compared to animals given control diet. HT supplementation significantly reduced fat accumulation in liver and plasma as well as tissue metabolic alterations induced by HFD. Furthermore, a normalization of desaturase activities

  2. FABP4 dynamics in obesity: discrepancies in adipose tissue and liver expression regarding circulating plasma levels.

    Directory of Open Access Journals (Sweden)

    María Isabel Queipo-Ortuño

    Full Text Available BACKGROUND: FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile. OBJECTIVE: In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed. METHODS: The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot. RESULTS: In obesity FABP4 expression was down-regulated (at both mRNA and protein levels, with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group. CONCLUSION: The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity.

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

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    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.

  4. Serum Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Expression in Patients with Non-alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Taner Akyol

    2015-06-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common chronic liver disease in developed countries. NAFLD may progress to non-alcoholic steatohepatitis (NASH and cirrhosis. Emerging evidence suggests that NAFLD is the hepatic manifestation of metabolic syndrome (MetS. NAFLD is closely linked to MetS, with a significant increase in cardiovascular risk. Several matrix metalloproteinases (MMPs and tissue inhibitors of MMPs (TIMPs play important roles in the pathophysiology of atherosclerosis and liver fibrosis. In this study we investigated the usefulness of serum metalloproteinases as noninvasive markers of NAFLD. Forty-six patients with NAFLD and twenty-six healthy controls were enrolled into the study, in Gulhane Military Medical Academy, Haydarpasa Training Hospital. Liver biopsies were performed on all patients with NAFLD and histopathological evaluations were made by an experienced pathologist. All NAFLD patients were divided into 2 subgroups according to MetS status using ATP III criteria. MMP-9 and TIMP-1 were studied in serum samples of all groups. Results were compared between both groups and subgroups. In this study, the NAFLD and control groups did not differ significantly on MMP-9, TIMP-1 and TIMP-1/MMP-9 ratio (p > 0.05. However, we found a significant relationship between the HOMA and TIMP-1 (p<0.05. Moreover, MMP-9 and TIMP-1/MMP-9 levels were significantly correlated with waist circumference (p<0.05. Our findings are not sufficient to suggest that MMP-9, TIMP-1 and TIMP-1/MMP-9 ratio might be used as noninvasive biochemical diagnostic tests among NAFLD patients. [Dis Mol Med 2015; 3(2.000: 11-17

  5. 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.

  6. [Influence of kaempferol on TGF-β1/Smads signal path in liver tissue of mice with Schistosoma japonicum infection].

    Science.gov (United States)

    Cai, Wen; Zhao, Lei; Li, Hua-rong; Zhang, Shu-ling

    2014-08-01

    To investigate the influence of kaempferol on transforming growth factor(TGF-β1/Smads signal tiransduction in liver tissue of mice with schistosomiasis liver fibrosis. Forty BALB/c mice were randomly divided into a normal control group (8 mice), a praziquantel group (8 mice ), and 4 praziquantel + kaempferol groups with different kaempferol dosages (5, 10, 15, 20 mg/kg respectively, 6 mice each group). Besides the normal control group, all the mice in the other 5 groups were infected with Schistosoma japonicum. After the infection for 6 weeks, the praziquantel group and the 4 praziquantel + kaempferol groups were treated with praziquantel 500 mg/(kg.d) for 2 d, then the mice in the praziquantel group were drenched with normal saline for 6 weeks, and those in the 4 praziquantel + kaempferol groups were drenched with kaempferol 5, 10, 15, 20 mg/kg respectively for 6 weeks. After the treatment, all the animals were sacrificed by the cervical dislocation method, and the area of egg granuloma and the degree of fibrosis in the livers of the mice were observed by HE and Masson staining. The expressions of TGF-β1, Smad2/3, Smad7 proteins were measured by the immunohistochemical method, and the mRNA levels of the 3 proteins were detected by RT-PCR. Compared with the mice in the praziquantel group, the areas of egg granuloma of the liver of the mice in the 4 praziquantel + kaempferol groups were smaller, and the degrees of the hepatic fibrosis of the mice were lesser, and their expressions of Smad2 and Smad3 at protein and their mRNA levels were significantly lower (all P kaempferol can significantly reduce the degrees of hepatic fibrosis and granuloma caused by schistosome eggs after the praziquantel treatment.

  7. Pathological features of liver tissue in autoantibody-positive chronic hepatitis C patients after plasmaphoresis

    Directory of Open Access Journals (Sweden)

    WU Huili

    2018-02-01

    Full Text Available ObjectiveTo investigate the detection rate and features of autoantibodies in chronic hepatitis C (CHC patients after plasmaphoresis, as well as the liver pathological features of autoantibody-positive CHC patients. MethodsA total of 120 patients who were infected with hepatitis C virus after plasmaphoresis in the Hospital of Dingxi County and Dingxi Hospital of Infectious Diseases from January 1992 to December 1995 were selected as test group; 11 healthy people from the same region were selected as control group. Autoantibody detection was performed for the 120 CHC patients, and liver pathological features were compared between the autoantibody-positive group(n=44 and autoantibody-negative group(n=76 of these patients. The t test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data. ResultsOf all 120 CHC patients who underwent plasmaphoresis, 44 (36.7% were found to have serum autoantibodies, with antinuclear antibodies as the most common type (21.7%. Compared with the autoantibody-negative group, the autoantibody-positive group had significantly higher scores of focal necrosis inside the hepatic lobules (211±0.88 vs 164±0.88, t=2.349,P=0.021 and ductular reaction inside the portal area (1.86±0.71 vs 1.13±0.66, t=4.217,P<0.001, as well as a significantly higher rate of interlobular bile duct injury (86.4% vs 55.3%, χ2=12.129,P=0.001. There were no significant differences between the two groups in the degree of liver fibrosis and hepatic steatosis (both P>0.05. ConclusionAutoantibody-positive are common in CHC patients after plasmaphoresis, and autoantibody-positive patients tend to have more severe injuries of the liver.

  8. Estimating functional liver reserve following hepatic irradiation: Adaptive normal tissue response models

    International Nuclear Information System (INIS)

    Stenmark, Matthew H.; Cao, Yue; Wang, Hesheng; Jackson, Andrew; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    2014-01-01

    Purpose: To estimate the limit of functional liver reserve for safe application of hepatic irradiation using changes in indocyanine green, an established assay of liver function. Materials and methods: From 2005 to 2011, 60 patients undergoing hepatic irradiation were enrolled in a prospective study assessing the plasma retention fraction of indocyanine green at 15-min (ICG-R15) prior to, during (at 60% of planned dose), and after radiotherapy (RT). The limit of functional liver reserve was estimated from the damage fraction of functional liver (DFL) post-RT [1 − (ICG-R15 pre-RT /ICG-R15 post-RT )] where no toxicity was observed using a beta distribution function. Results: Of 48 evaluable patients, 3 (6%) developed RILD, all within 2.5 months of completing RT. The mean ICG-R15 for non-RILD patients pre-RT, during-RT and 1-month post-RT was 20.3%(SE 2.6), 22.0%(3.0), and 27.5%(2.8), and for RILD patients was 6.3%(4.3), 10.8%(2.7), and 47.6%(8.8). RILD was observed at post-RT damage fractions of ⩾78%. Both DFL assessed by during-RT ICG and MLD predicted for DFL post-RT (p < 0.0001). Limiting the post-RT DFL to 50%, predicted a 99% probability of a true complication rate <15%. Conclusion: The DFL as assessed by changes in ICG during treatment serves as an early indicator of a patient’s tolerance to hepatic irradiation

  9. Histopathology of the gill and liver tissues of the African catfish ...

    African Journals Online (AJOL)

    An investigation on the effect of the heavy metal, lead (Pb) on the gill and liver of the African catfish Clarias gariepinus was carried out in the laboratory. One hundred and sixty (160) fingerlings of the fish were exposed to continuous exposure to sub-lethal concentrations (0.006 mg/l and 0.008 mg/l) of lead for a period of ...

  10. Age-dependent accumulation of heavy metals in liver, kidney and lung tissues of homing pigeons in Beijing, China.

    Science.gov (United States)

    Cui, Jia; Wu, Bin; Halbrook, Richard S; Zang, Shuying

    2013-12-01

    Biomonitoring provides direct evidence of the bioavailability and accumulation of toxic elements in the environment. In the current study, 1-2, 5-6, and 9-10+ year old homing pigeons collected from the Haidian District of Beijing during 2011 were necropsied and concentrations of cadmium, lead, and mercury were measured in liver, lung, and kidney tissue. At necropsy, gray/black discoloration of the margins of the lungs was observed in 98 % of the pigeons. There were no significant differences in metal concentrations as a function of gender. Cadmium concentrations in all tissues and Pb concentrations in the lung tissues were significantly greater in 9-10+ year old pigeons compared to other age groups indicating that Cd and Pb were bioavailable. Mercury concentrations were not significantly different among age groups. Cadmium concentrations in kidney and lung tissues of 9-10+ year old pigeons were similar to or exceeded concentrations of Cd reported in pigeons from another high traffic urban area and most wild avian species from Korea suggesting that Cd in this region of Beijing may be of concern. Homing pigeons provide valuable exposure and bioaccumulation data not readily available from air monitoring alone, thus providing information regarding potential health effects in wildlife and humans in urban areas. As environmental quality standards are implemented in China, homing pigeons will serve as a valuable bio-monitor of the efficacy of these actions.

  11. 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.

  12. Tissue Hypoperfusion, Hypercoagulopathy, and Kidney and Liver Dysfunction after Ingestion of a Naphazoline-Containing Antiseptic

    Directory of Open Access Journals (Sweden)

    Yuko Ono

    2017-01-01

    Full Text Available Naphazoline is a peripheral α2-adrenergic receptor agonist commonly used as a topical decongestant. In Japan, over-the-counter antiseptics often contain naphazoline to effect local hemostasis. We present the first case involving the development of hypercoagulopathy, with kidney and liver dysfunction, following a naphazoline overdose. A 22-year-old Japanese woman with a history of depression ingested 160 mL of a commercially available antiseptic containing 0.1% naphazoline. Three days later, she was brought to the emergency department because of general fatigue, nausea, and vomiting. Physical examination revealed cool, pale extremities. Laboratory data showed evidence of severe kidney and liver dysfunction (creatinine, 9.2 mg/dL; alanine aminotransferase, 2948 IU/L, hypercoagulation (D-dimers, 58.3 μg/mL, and thrombocytopenia (platelet count, 90,000/μL. After infusion of normal saline, intravenous administration of alprostadil, and hemodiafiltration, her organ function completely recovered. Because both the kidney and liver express α2-adrenergic receptors, their failure was likely associated with naphazoline overdose-induced hypoperfusion. The most plausible causes of hypercoagulation are peripheral low perfusion and subsequent microthrombus formation. This case illustrates that severe organ dysfunction can occur following over-the-counter antiseptic ingestion and serves as a caution for both drug manufacturers and healthcare professionals.

  13. Concentrations of metallic elements in kidney, liver, and lung tissue of Indo-Pacific bottlenose dolphin Tursiops aduncus from coastal waters of Zanzibar, Tanzania.

    Science.gov (United States)

    Mapunda, Edgar C; Othman, Othman C; Akwilapo, Leonard D; Bouwman, Hindrik; Mwevura, Haji

    2017-09-15

    Concentrations of metallic elements in kidney, liver and lung tissues of Indo-Pacific bottlenose dolphins Tursiops aduncus from coastal waters of Zanzibar were determined using inductively coupled plasma - optical emission spectroscopy. Cadmium, chromium, copper, and zinc were quantifiable in all tissues at concentration ranges of 0.10-150, 0.08-3.2, 1.1-88 and 14-210μg/g dry mass, respectively. Copper and zinc was significantly higher in liver, and females had significantly higher Cd in liver, and chromium in lung. Generally, T. aduncus dolphins from coastal waters around Zanzibar carry low concentrations of metals compared with dolphins from other areas. Cadmium increased significantly with age in kidney and lung. Copper decreased significantly with age in liver, probably due to foetal metallothionein. This study supplied baseline data against which future trends in marine mammals in the Indian Ocean, the world's third largest, can be assessed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Rutin ameliorates glycemic index, lipid profile and enzymatic activities in serum, heart and liver tissues of rats fed with a combination of hypercaloric diet and chronic ethanol consumption.

    Science.gov (United States)

    Chuffa, Luiz Gustavo A; Fioruci-Fontanelli, Beatriz A; Bordon, Juliana G; Pires, Rafaelle B; Braga, Camila P; Seiva, Fábio R F; Fernandes, Ana Angélica H

    2014-06-01

    Alcoholism and obesity are strongly associated with several disorders including heart and liver diseases. This study evaluated the effects of rutin treatment in serum, heart and liver tissues of rats subjected to a combination of hypercaloric diet (HD) and chronic ethanol consumption. Rats were divided into three groups: Control: rats fed a standard diet and drinking water ad libitum; G1: rats fed the HD and receiving a solution of 10% (v/v) ethanol; and G2: rats fed the HD and ethanol solution, followed by injections of 50 mg/kg(-1) rutin as treatment. After 53 days of HD and ethanol exposure, the rutin was administered every three days for nine days. At the end of the experimental period (95 days), biochemical analyses were carried out on sera, cardiac and hepatic tissues. Body weight gain and food consumption were reduced in both the G1 and G2 groups compared to control animals. Rutin effectively reduced the total lipids (TL), triglycerides (TG), total cholesterol (TC), VLDL, LDL-cholesterol and glucose levels, while it increased the HDL-cholesterol in the serum of G2 rats, compared to G1. Although rutin had no effect on total protein, albumin, uric acid and cretinine levels, it was able to restore serum activities of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) in animals fed HD and receiving ethanol. Glycogen stores were replenished in both hepatic and cardiac tissues after rutin treatment. Moreover, rutin consistently reduced hepatic levels of TG and TC and cardiac AST, ALT and CK activities. Thus, rutin treatment was effective in reducing the risk factors for cardiac and hepatic disease caused by both HD and chronic ethanol consumption.

  15. Cytokines and Liver Diseases

    Directory of Open Access Journals (Sweden)

    Herbert Tilg

    2001-01-01

    Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

  16. Evaluation the effect of silver nanoparticles on oxidative stress biomarkers in blood serum and liver and kidney tissues

    Directory of Open Access Journals (Sweden)

    Mahsa Tashakori Miyanroudi

    2016-07-01

    Full Text Available Objective(s: Silver nanoparticles (Ag-NPs are one of the most widely used nanomaterials recently. Despite the wide application of nanomaterials, there is limited information concerning their impact on human health and the environment. This study aimed to find the effects of Ag-NPs (40 nm on blood serum, liver and kidney tissues of homing pigeons (Columbia livia.Materials and Methods: Columba livia, in vivo model used in ecotoxicity experiments were gavaged 3 times daily with 75 and 150 ppm of Ag-NPs within 14 days. A group of 30 Pigeon were randomly divided into three groups: Ag-NPs exposed and control groups (n=10. Data analysis was counducted by performing one-way variance (ANOVA in SPSS.v.16.0                                                                         Results: The results of this study illustrated that in the enzyme activity of Glutathione S –transferase (GST, Aspartate amino transferase (AST, Alanine amino transferase (ALT and lactate dehydrogenas (LDH there is a significant difference between treatment groups with Ag-NPs and the control group. Also, lipid peroxidation (LPO analysis and catalase activity CAT suggest Ag-NPs cause the main damage to the liver tissue. On the other hand: Ag-NPs have toxic and harmful effects in both concentrations (75 and 150 ppm, and cause LPO induction, oxidative stress and increase of biomarkers of liver necrosis in under treatment pigeons.Conclusion: The results of this study show that the organism’s exposure to Ag-NPs cause toxicity that is dose-dependant. in this study, the highest damage was observed in the liver. However, this issue will have to be considered more extensively in further studies.

  17. Tissue Liver X-Receptor Alpha (LXRα) Level In Acne Vulgaris

    International Nuclear Information System (INIS)

    Nada, E.A.A.

    2012-01-01

    Acne vulgaris is a disease of the pilosebaceous unit. Increased sebum lipogenesis by sebaceous gland is the major factor in the pathophysiology of acne. LXRα have been recognized in the regulation of genes involved in lipid biosynthesis. Activation of LXRα inhibits proliferation, increase lipogenesis and improve differentiation of sebocytes. Aim: To investigate the level of tissue expression of LXRα in inflammatory and non inflammatory acne lesions and in comparison with normal skin. Patients and methods: Seventeen patients with inflammatory and non inflammatory acne lesions and sixteen age and sex comparable healthy volunteers as control were included in the study. Punch skin biopsies were taken from the acne lesions and normal skin of the volunteers for detection of gene expression of LXRα by RT- PCR. Results: the level of LXRα was significantly higher in the lesional skin either inflammatory (with a mean of 1188.52 ± 129.5) or comedonal acne (with a mean of 892.52 ± 66.08) in a statistically significant manner than the controls (with a mean of 600.50 ± 95.30) where the P value was <0.001. In addition, the level of LXRα was significantly higher in inflammatory acne (with a mean of 1188.52 ± 129.5) in a statistically significant manner) than comedonal acne (with a mean of 892.52 ± 66.08) where the P value was <0.001. Conclusion: the significant increase in the level of LXRα in acne lesions compared to controls suggesting that LXRα may have a role in the pathogenesis of acne vulgaris itself and is not a consequence of inflammation. In addition, it may play a role in the progression of the disease from comedonal to inflammatory. Further studies are recommended to evaluate the therapeutic benefits of the use of LXRα antagonists as a new therapeutic modality for acne vulgaris.

  18. 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.

  19. Precision IORT - Image guided intraoperative radiation therapy (igIORT) using online treatment planning including tissue heterogeneity correction.

    Science.gov (United States)

    Schneider, Frank; Bludau, Frederic; Clausen, Sven; Fleckenstein, Jens; Obertacke, Udo; Wenz, Frederik

    2017-05-01

    To the present date, IORT has been eye and hand guided without treatment planning and tissue heterogeneity correction. This limits the precision of the application and the precise documentation of the location and the deposited dose in the tissue. Here we present a set-up where we use image guidance by intraoperative cone beam computed tomography (CBCT) for precise online Monte Carlo treatment planning including tissue heterogeneity correction. An IORT was performed during balloon kyphoplasty using a dedicated Needle Applicator. An intraoperative CBCT was registered with a pre-op CT. Treatment planning was performed in Radiance using a hybrid Monte Carlo algorithm simulating dose in homogeneous (MCwater) and heterogeneous medium (MChet). Dose distributions on CBCT and pre-op CT were compared with each other. Spinal cord and the metastasis doses were evaluated. The MCwater calculations showed a spherical dose distribution as expected. The minimum target dose for the MChet simulations on pre-op CT was increased by 40% while the maximum spinal cord dose was decreased by 35%. Due to the artefacts on the CBCT the comparison between MChet simulations on CBCT and pre-op CT showed differences up to 50% in dose. igIORT and online treatment planning improves the accuracy of IORT. However, the current set-up is limited by CT artefacts. Fusing an intraoperative CBCT with a pre-op CT allows the combination of an accurate dose calculation with the knowledge of the correct source/applicator position. This method can be also used for pre-operative treatment planning followed by image guided surgery. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  20. A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis

    Czech Academy of Sciences Publication Activity Database

    Muller, M.; Wetzel, S.; Koehn-Gaone, J.; Chalupský, Karel; Luellmann-Rauch, R.; Barikbin, R.; Bergmann, J.; Woehner, B.; Žbodáková, Olga; Leuschner, I.; Gregor, Martin; Tiegs, G.; Rose-John, S.; Sedláček, Radislav; Tirnitz-Parker, J.E.E.; Saftig, P.; Schmidt-Arras, D.

    2016-01-01

    Roč. 7, č. 14 (2016), s. 17431-17441 ISSN 1949-2553 R&D Projects: GA ČR GAP302/11/2048; GA ČR GAP303/10/2044; GA ČR GA13-01710S; GA ČR GA15-23858S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : ADAM10 * liver progenitor cell * c-Met * Notch * hepatocyte differentiation * Pathology Section Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.168, year: 2016

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

    International Nuclear Information System (INIS)

    Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W; Emami, K; Wu, H

    2011-01-01

    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.

  2. 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.

  3. Disrupted G1 to S phase clearance via cyclin signaling impairs liver tissue repair in thioacetamide-treated type 1 diabetic rats

    International Nuclear Information System (INIS)

    Devi, Sachin S.; Mehendale, Harihara M.

    2005-01-01

    Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute liver injury owing to inhibited hepatic tissue repair, primarily due to blockage of G 0 to S phase progression of cell division cycle. On the other hand, DB rats receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a delay in recovery from liver injury and survival. The objective of the present study was to test the hypothesis that impaired cyclin-regulated progression of G 1 to S phase of the cell cycle may explain inhibited liver tissue repair, hepatic failure, and death, contrasted with delayed liver tissue repair but survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg) exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb, inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg TA/kg exhibited delayed up regulation of MAPK signaling that delayed the expression of CD1 and pRb, explaining delayed stimulation of tissue repair observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent adverse effect on cyclin-regulated pRb signaling: the lower dose causes a recoverable delay, whereas the higher dose inhibits it with corresponding effect on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse effect is substantially shifted to the left of the dose response curve in diabetes

  4. 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.

  5. NS3 protease resistance-associated substitutions in liver tissue and plasma samples from patients infected by hepatitis C virus genotype 1A or 1B.

    Science.gov (United States)

    Morsica, Giulia; Andolina, Andrea; Merli, Marco; Messina, Emanuela; Hasson, Hamid; Lazzarin, Adriano; Uberti-Foppa, Caterina; Bagaglio, Sabrina

    2017-08-01

    The presence of naturally occurring resistance-associated substitutions (RASs) in the HCV-protease domain has been poorly investigated in the liver, the main site of HCV replication. We evaluated the natural resistance of the virus to NS3 protease inhibitors in liver tissue and plasma samples taken from HCV-infected patients. RASs were investigated by means of viral population sequencing in liver tissue samples from 18 HCV-infected patients harbouring genotype 1a or genotype 1b; plasma samples from 12 of these patients were also available for virological investigation. A discordant genotype was found in two of the 12 patients (16.6%) who provided samples from both compartments. Sequence analysis of the NS3 protease domain showed the presence of RASs in four of the 18 liver tissue samples (22.2%), two of which showed cross-resistance to protease inhibitors in clinical use or phase 2-3 trials. The analysis of the 12 paired tissues and plasma samples excluded the presence of RASs in the plasma compartment. The dominance of discordant genotypes in the paired liver and plasma samples of some HCV-infected patients suggests mixed infection possibly leading to the selective advantage of different genotype in the two compartments. The presence of RASs at intra-hepatic level is not uncommon and may lead to the early emergence of cross-resistant strains.

  6. Liver X receptor β controls thyroid hormone feedback in the brain and regulates browning of subcutaneous white adipose tissue.

    Science.gov (United States)

    Miao, Yifei; Wu, Wanfu; Dai, Yubing; Maneix, Laure; Huang, Bo; Warner, Margaret; Gustafsson, Jan-Åke

    2015-11-10

    The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type 2 diabetes. Browning is the result of the induction in WAT of a newly discovered type of adipocyte, the beige cell. When mice are exposed to cold or several kinds of hormones or treatments with chemicals, specific depots of WAT undergo a browning process, characterized by highly activated mitochondria and increased heat production and energy expenditure. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride, and glucose metabolism. Following our previous finding that LXRs serve as repressors of uncoupling protein-1 (UCP1) in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyroid-stimulating hormone (TSH)-releasing hormone (TRH)-positive neurons in the paraventricular nucleus area of the hypothalamus and thus stimulated secretion of TSH from the pituitary. Consequently, production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knockout mice and provided support for targeting LXRs in treatment of obesity.

  7. Liver tissue engineering based on aggregate assembly: efficient formation of endothelialized rat hepatocyte aggregates and their immobilization with biodegradable fibres

    International Nuclear Information System (INIS)

    Pang, Y; Shinohara, M; Komori, K; Sakai, Y; Montagne, K

    2012-01-01

    To realize long-term in vitro culture of hepatocytes at a high density while maintaining a high hepatic function for aggregate-based liver tissue engineering, we report here a novel culture method whereby endothelialized rat hepatocyte aggregates were formed using a PDMS microwell device and cultured in a perfusion bioreactor by introducing spacers between aggregates to improve oxygen and nutrient supply. Primary rat hepatocyte aggregates around 100 µm in diameter coated with human umbilical vein endothelial cells were spontaneously and quickly formed after 12 h of incubation, thanks to the continuous supply of oxygen by diffusion through the PDMS honeycomb microwell device. Then, the recovered endothelialized rat hepatocyte aggregates were mixed with biodegradable poly-l-lactic acid fibres in suspension and packed into a PDMS-based bioreactor. Perfusion culture of 7 days was successfully achieved with more than 73.8% cells retained in the bioreactor. As expected, the fibres acted as spacers between aggregates, which was evidenced from the enhanced albumin production and more spherical morphology compared with fibre-free packing. In summary, this study shows the advantages of using PDMS-based microwells to form heterotypic aggregates and also demonstrates the feasibility of spacing tissue elements for improving oxygen and nutrient supply to tissue engineering based on modular assembly. (paper)

  8. Effects of anti-cocaine vaccine and viral gene transfer of cocaine hydrolase in mice on cocaine toxicity including motor strength and liver damage.

    Science.gov (United States)

    Gao, Yang; Geng, Liyi; Orson, Frank; Kinsey, Berma; Kosten, Thomas R; Shen, Xiaoyun; Brimijoin, Stephen

    2013-03-25

    In developing an vivo drug-interception therapy to treat cocaine abuse and hinder relapse into drug seeking provoked by re-encounter with cocaine, two promising agents are: (1) a cocaine hydrolase enzyme (CocH) derived from human butyrylcholinesterase and delivered by gene transfer; (2) an anti-cocaine antibody elicited by vaccination. Recent behavioral experiments showed that antibody and enzyme work in a complementary fashion to reduce cocaine-stimulated locomotor activity in rats and mice. Our present goal was to test protection against liver damage and muscle weakness in mice challenged with massive doses of cocaine at or near the LD50 level (100-120 mg/kg, i.p.). We found that, when the interceptor proteins were combined at doses that were only modestly protective in isolation (enzyme, 1mg/kg; antibody, 8 mg/kg), they provided complete protection of liver tissue and motor function. When the enzyme levels were ~400-fold higher, after in vivo transduction by adeno-associated viral vector, similar protection was observed from CocH alone. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. 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

  10. 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)

  11. Segmental liver resection assisted by HIFU: tissue precauterization using a toroidal-shaped HIFU transducer

    Science.gov (United States)

    N'Djin, W. A.; Melodelima, D.; Schenone, F.; Rivoire, M.; Chapelon, J. Y.

    2010-03-01

    The development of new cauterization techniques for hepatic resection is critical for improving the safety of the procedure. Previous studies showed the feasibility of using HIFU or radiofrequency precoagulation to limit blood loss during dissection of the organ. Here we report a new therapeutic modality using high intensity focused ultrasound (HIFU) to perform a bloodless hepatic resection that could represent a promising alternative. A comparative study was performed to evaluate the interest of using this complementary tool to improve surgical resection in the liver. This study used a 3 MHz HIFU toroidal-shaped phased array transducer which allows the generation of a single conical lesion of 7 cm3 in 40 seconds. In order to minimize blood loss and dissection time, a barrier of coagulative necrosis was generated with the HIFU device before hepatectomy, by juxtaposing single conical lesions on the line of dissection. Resection assisted by HIFU (RA-HIFU) was compared with classical dissections with clamping (RC) and without clamping (Control). For each technique 14 partial liver resections were performed in seven pigs. The parameters examined were vascular control and times of treatment. Precoagulation allowed the vascular isolation of small vessels and surgical clips were mainly used for the control of vessels>5 mm in diameter. The number of clips used per unit of liver surface dissected in RA-HIFU (0.8±0.3 cm-2) was significantly lower than in the other groups (RC: 1.6±0.4 cm-2, Control: 1.8±0.8 cm-2, p<0.01). In addition, blood loss was lower in RA-HIFU (7.4±6.5 ml.cm-2) than in RC (11.2±4.5 ml.cm-2) and Control (14.0±6.7 ml.cm-2). The time of dissection in RA-HIFU (13±5 min) was shorter than in RC (23±8 minutes) and Control (18±5 minutes). The feasibility and the efficiency of RA-HIFU using a toroidal-shaped HIFU transducer without additional devices were demonstrated. This technique enhances the resection procedure and will be able to be tested in

  12. 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 rep...

  13. 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

    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...

  14. Replacement of soybean oil by fish oil increases cytosolic lipases activities in liver and adipose tissue from rats fed a high-carbohydrate diets.

    Science.gov (United States)

    Rodrigues, Angélica Heringer; Moreira, Carolina Campos Lima; Neves, Maria José; Botion, Leida Maria; Chaves, Valéria Ernestânia

    2018-06-01

    Several studies have demonstrated that fish oil consumption improves metabolic syndrome and comorbidities, as insulin resistance, nonalcoholic fatty liver disease, dyslipidaemia and hypertension induced by high-fat diet ingestion. Previously, we demonstrated that administration of a fructose-rich diet to rats induces liver lipid accumulation, accompanied by a decrease in liver cytosolic lipases activities. In this study, the effect of replacement of soybean oil by fish oil in a high-fructose diet (FRUC, 60% fructose) for 8 weeks on lipid metabolism in liver and epididymal adipose tissue from rats was investigated. The interaction between fish oil and FRUC diet increased glucose tolerance and decreased serum levels of triacylglycerol (TAG), VLDL-TAG secretion and lipid droplet volume of hepatocytes. In addition, the fish oil supplementation increased the liver cytosolic lipases activities, independently of the type of carbohydrate ingested. Our results firmly establish the physiological regulation of liver cytosolic lipases to maintain lipid homeostasis in hepatocytes. In epididymal adipose tissue, the replacement of soybean oil by fish oil in FRUC diet did not change the tissue weight and lipoprotein lipase activity; however, there was increased basal and insulin-stimulated de novo lipogenesis and glucose uptake. Increased cytosolic lipases activities were observed, despite the decreased basal and isoproterenol-stimulated glycerol release to the incubation medium. These findings suggest that fish oil increases the glycerokinase activity and glycerol phosphorylation from endogenous TAG hydrolysis. Our findings are the first to show that the fish oil ingestion increases cytosolic lipases activities in liver and adipose tissue from rats treated with high-carbohydrate diets. Copyright © 2018. Published by Elsevier Inc.

  15. 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.

  16. Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice

    Directory of Open Access Journals (Sweden)

    Sabrina Le Bouter

    2010-01-01

    Full Text Available Rosiglitazone (RSG, developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d with untreated non-diabetic littermates (db/+. For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs and free fatty acids (FFAs in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues.

  17. Soapwort extract supplementation alters antioxidant status of serum, liver and heart tissues in growing Japanese quails reared under chronic intermittent cold stress

    Directory of Open Access Journals (Sweden)

    Bestami Dalkilic

    2017-01-01

    Full Text Available Antioxidant effect of dietary soapwort extract supplementation was studied in growing Japanese quails suffering from chronic intermittent cold stress. For this purpose, a total of ninety 15-d-old quails were divided into three groups with three replicates. Chronic intermittent cold stress was applied every night between 22.00 to 06.00 h; starting at 14 °C for the first week, and gradually weekly lowered to 8 °C. Three groups were fed with corn-soy based standard diets supplemented with 0, 50, and 100 ppm soapwort extract for four weeks. At the end of the study, three males and three females were slaughtered to determine total antioxidant and oxidant status of serum, malondialdehyde, glutathione, glutathione peroxidase activity, superoxide dismutase of liver and heart tissues. Although the dietary soapwort extract had no effect on serum total antioxidant capacity, it significantly lowered the total oxidant status of serum in cold stressed quails. Glutathione and superoxide dismutase enzyme activity of liver and heart tissues were similar among groups. While the dietary soapwort extract had no effect on glutathione peroxidase activity of the heart tissue, it significantly increased glutathione peroxidase activity in the liver tissue. In relation to the control group, malondialdehyde concentrations in the liver and heart tissues were significantly lower in soapwort extract groups. These data suggest that dietary soapwort extract could alleviate the detrimental effects of oxidative stress in growing Japanese quails exposed to cold stress.

  18. Blood flow and tissue oxygen pressures of liver and pancreas in rats: effects of volatile anesthetics and of hemorrhage.

    Science.gov (United States)

    Vollmar, B; Conzen, P F; Kerner, T; Habazettl, H; Vierl, M; Waldner, H; Peter, K

    1992-09-01

    The object of this investigation was to compare the effects of volatile anesthetics and of hemorrhage at comparable arterial blood pressures on splanchnic blood flow (radioactive microspheres) and tissue oxygenation of the liver and pancreas (surface PO2 [PSO2] electrodes). In contrast to earlier studies, we did not use identical minimum alveolar anesthetic concentration multiples as a reference to compare volatile anesthetics; rather, we used the splanchnic perfusion pressure. Under general anesthesia (intravenous chloralose) and controlled ventilation, 12 Sprague-Dawley rats underwent laparotomy to allow access to abdominal organs. Mean arterial pressure was decreased from 84 +/- 3 mm Hg (mean +/- SEM) at control to 50 mm Hg by 1.0 +/- 0.1 vol% halothane, 2.2 +/- 0.2 vol% enflurane, and 2.3 +/- 0.1 vol% isoflurane in a randomized sequence. For hemorrhagic hypotension, blood was withdrawn gradually until a mean arterial pressure of 50 mm Hg was attained. Volatile anesthetics and hemorrhage reduced cardiac output, and hepatic arterial, portal venous, and total hepatic blood flows by comparable degrees. Mean hepatic PSO2 decreased significantly from 30.7 +/- 2.6 mm Hg at control to 17.4 +/- 2 and 17.5 +/- 2 mm Hg during enflurane and isoflurane (each P less than 0.05) anesthesia, respectively. The decrease to 11.5 +/- 2.5 mm Hg was more pronounced during halothane anesthesia. Hemorrhagic hypotension was associated with the lowest hepatic PSO2 (3.4 +/- 1.3 mm Hg) and the highest number of hypoxic (0-5 mm Hg 86%) and anoxic PSO2 values (0 mm Hg 46%). Pancreatic blood flow and oxygenation remained unchanged from control during halothane and enflurane administration, whereas isoflurane increased both variables. Hemorrhagic hypotension slightly reduced pancreatic flow (-8%) but significantly decreased PSO2 from 58 +/- 5 mm Hg at control to 36 +/- 3 mm Hg, with 7% of all measured values in the hypoxic range. Thus, volatile anesthetics preserved pancreatic but not hepatic

  19. 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.

  20. 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

    International Nuclear Information System (INIS)

    Chen, Qi-Liang; Luo, Zhi; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

    2013-01-01

    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

  1. 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

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

    International Nuclear Information System (INIS)

    Ha, Eun Ju; Baek, Jung Hwan; Lee, Jeong Hyun

    2014-01-01

    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.

  3. 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

  4. 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

  5. Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation.

    Science.gov (United States)

    Vargas, Hugo E; Laskus, Tomasz; Radkowski, Marek; Wilkinson, Jeff; Balan, Vijay; Douglas, David D; Harrison, M Edwyn; Mulligan, David C; Olden, Kevin; Adair, Debra; Rakela, Jorge

    2002-11-01

    Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureussis. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA-negative strand, which is the viral replicative form, was determined by strand-specific Tth-based reverse-transcriptase polymerase chain reaction. Viral sequences were compared by means of single-strand conformation polymorphism and direct sequencing. HCV RNA-negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA-negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5' untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. The exact lineage of cells permissive for HCV replication and the possible interaction between viral replication and cerebral function that may lead to depression remain to be elucidated.

  6. Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance.

    Science.gov (United States)

    Baranova, Ancha; Gowder, Shobha J; Schlauch, Karen; Elariny, Hazem; Collantes, Rochelle; Afendy, Arian; Ong, Janus P; Goodman, Zachary; Chandhoke, Vikas; Younossi, Zobair M

    2006-09-01

    Adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance, type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal adipose tissue of morbidly obese patients undergoing bariatric surgery. Morbidly obese patients undergoing bariatric surgery were studied. Patients were classified into two groups: Group A (with insulin resistance) (N=11; glucose 149.84 +/- 40.56 mg/dL; serum insulin 8.28 +/- 3.52 microU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 +/- 8.43 mg/dL; serum insulin 3.431 +/- 1.162 microU/mL). Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin was higher in Group A than in Group B patients (P<0.005), resistin gene expression was not different between the two groups. Finally, for leptin, neither serum level nor gene expression was different between the two groups. Serum adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH) in this study (P=0.024). Obese patients with insulin resistance have decreased serum adiponectin and increased serum resistin. Additionally, adiponectin gene expression is also decreased in the adipose tissue of these patients. This low level of adiponectin expression may predispose patients to the progressive form of NAFLD or NASH.

  7. Elastin in the Liver

    Directory of Open Access Journals (Sweden)

    Jiri Kanta

    2016-10-01

    Full Text Available A characteristic feature of liver cirrhosis is the accumulation of large amounts of connective tissue with the prevailing content of type I collagen. Elastin is a minor connective tissue component in normal liver but it is actively synthesized by hepatic stellate cells and portal fibroblasts in diseased liver. The accumulation of elastic fibers in later stages of liver fibrosis may contribute to the decreasing reversibility of the disease with advancing time. Elastin is formed by polymerization of tropoelastin monomers. It is an amorphous protein highly resistant to the action of proteases that forms the core of elastic fibers. Microfibrils surrounding the core are composed of fibrillins that bind a number of proteins involved in fiber formation. They include microfibril-associated glycoproteins (MAGPs, microfibrillar-associated proteins (MFAPs and fibulins. Lysyl oxidase (LOX and lysyl oxidase-like proteins (LOXLs are responsible for tropoelastin cross-linking and polymerization. TGF-β complexes attached to microfibrils release this cytokine and influence the behavior of the cells in the neighborhood. The role of TGF-β as the main profibrotic cytokine in the liver is well-known and the release of the cytokines of TGF-β superfamily from their storage in elastic fibers may affect the course of fibrosis. Elastic fibres are often studied in the tissues where they provide elasticity and resilience but their role is no longer viewed as purely mechanical. Tropoelastin, elastin polymer and elastin peptides resulting from partial elastin degradation influence fibroblastic and inflammatory cells as well as angiogenesis. A similar role may be performed by elastin in the liver. This article reviews the results of the research of liver elastic fibers on the backgound of the present knowledge of elastin biochemistry and physiology. The regulation of liver elastin synthesis and degradation may be important for the outcome of liver fibrosis.

  8. 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.

  9. 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...... RNase inhibitors during thawing to reduce the loss of biological activity....

  10. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Defraene, Gilles; Van den Bergh, Laura; Al-Mamgani, Abrahim; Haustermans, Karin; Heemsbergen, Wilma; Van den Heuvel, Frank; Lebesque, Joos V.

    2012-01-01

    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011–0.013) clinical factor was “previous abdominal surgery.” As second significant (p = 0.012–0.016) factor, “cardiac history” was included in all three rectal bleeding fits, whereas including “diabetes” was significant (p = 0.039–0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003–0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D 50 . Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints. Conclusions

  11. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Defraene, Gilles, E-mail: gilles.defraene@uzleuven.be [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Van den Bergh, Laura [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Al-Mamgani, Abrahim [Department of Radiation Oncology, Erasmus Medical Center - Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Haustermans, Karin [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Heemsbergen, Wilma [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Van den Heuvel, Frank [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Lebesque, Joos V. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2012-03-01

    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was 'previous abdominal surgery.' As second significant (p = 0.012-0.016) factor, 'cardiac history' was included in all three rectal bleeding fits, whereas including 'diabetes' was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D{sub 50}. Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints

  12. Characterization of the Embryogenic Tissue of the Norway Spruce Including a Transition Layer between the Tissue and the Culture Medium by Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Kořínek R.

    2017-02-01

    Full Text Available The paper describes the visualization of the cells (ESEs and mucilage (ECMSN in an embryogenic tissue via magnetic resonance imaging (MRI relaxometry measurement combined with the subsequent multi-parametric segmentation. The computed relaxometry maps T1 and T2 show a thin layer (transition layer between the culture medium and the embryogenic tissue. The ESEs, mucilage, and transition layer differ in their relaxation times T1 and T2; thus, these times can be used to characterize the individual parts within the embryogenic tissue. The observed mean values of the relaxation times T1 and T2 of the ESEs, mucilage, and transition layer are as follows: 1469 ± 324 and 53 ± 10 ms, 1784 ± 124 and 74 ± 8 ms, 929 ± 164 and 32 ± 4.7 ms, respectively. The multi-parametric segmentation exploiting the T1 and T2 relaxation times as a classifier shows the distribution of the ESEs and mucilage within the embryogenic tissue. The discussed T1 and T2 indicators can be utilized to characterize both the growth-related changes in an embryogenic tissue and the effect of biotic/abiotic stresses, thus potentially becoming a distinctive indicator of the state of any examined embryogenic tissue.

  13. Elevated Liver Enzymes

    Science.gov (United States)

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

  14. Liver fibrosis and regeneration in dogs and cats: An immunohistochemical approach

    NARCIS (Netherlands)

    IJzer, J.

    2008-01-01

    In this thesis we focus on liver tissue repair processes in canine and feline hepatitis, on formalin fixed paraffin embedded archival liver specimens. Hepatitis was diagnosed using histological standard criteria, and always includes hepatocellular cell death and an inflammatory infiltrate.

  15. 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

  16. Tissue-engineered cartilaginous constructs for the treatment of caprine cartilage defects, including distribution of laminin and type IV collagen.

    Science.gov (United States)

    Jeng, Lily; Hsu, Hu-Ping; Spector, Myron

    2013-10-01

    The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineered constructs; and (2) the tissue filling cartilage defects in a goat model into which the constructs were implanted, particularly for the presence of the basement membrane molecules, laminin and type IV collagen. Basement membrane molecules are localized to the pericellular matrix in normal adult articular cartilage, but have not been examined in tissue-engineered constructs cultured in vitro or in tissue filling cartilage defects into which the constructs were implanted. Cartilaginous constructs were engineered in vitro using caprine chondrocyte-seeded type II collagen scaffolds. Autologous constructs were implanted into 4-mm-diameter defects created to the tidemark in the trochlear groove in the knee joints of skeletally mature goats. Eight weeks after implantation, the animals were sacrificed. Constructs underwent immunohistochemical and histomorphometric evaluation. Widespread staining for the two basement membrane molecules was observed throughout the extracellular matrix of in vitro and in vivo samples in a distribution unlike that previously reported for cartilage. At sacrifice, 70% of the defect site was filled with reparative tissue, which consisted largely of fibrous tissue and some fibrocartilage, with over 70% of the reparative tissue bonded to the adjacent host tissue. A novel finding of this study was the observation of laminin and type IV collagen in in vitro engineered cartilaginous constructs and in vivo cartilage repair samples from defects into which the constructs were implanted, as well as in normal caprine articular cartilage. Future work is needed to elucidate the role of basement membrane molecules during cartilage repair and regeneration.

  17. Study of Fe, Zn, Cu, Cd, Pb concentrations in liver, kidney and muscle tissue of cow and sheep marketed in Hamedan in 2011

    Directory of Open Access Journals (Sweden)

    S Sobhanardakani

    2012-11-01

    Full Text Available Importance of heavy metals in food safety and detrimental effects of their high concentrations in food stuff is well documented. In this study, concentrations of Fe, Zn, Cu, Cd and Pb in kidney, liver and muscle tissues of cow and sheep at Hamedan retails were evaluated. A total number of 180 samples was assessed for the amount of heavy metals as ppb in wet weight. For this, wet-digestion method was used to determine the concentration of given elements by ICP (Varian ES-710. Results showed that the highest concentration of heavy metals was determined in the liver and kidney samples, while the lowest concentration was found in muscle tissue. Among the heavy metals, Fe in cow’s liver had the highest concentration (25507±879 ppb and Cd in muscle tissue of sheep has the lowest concentration (192±54 ppb. In overall, accumulation of heavy metals in tissues of cows was higher than sheep. Statistical comparison of accumulated metals concentration in various tissues of these two animal groups showed significant difference (P

  18. 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 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...

  19. Polyploidization of liver cells.

    Science.gov (United States)

    Celton-Morizur, Séverine; Desdouets, Chantal

    2010-01-01

    Eukaryotic organisms usually contain a diploid complement of chromosomes. However, there are a number of exceptions. Organisms containing an increase in DNA content by whole number multiples of the entire set of chromosomes are defined as polyploid. Cells that contain more than two sets of chromosomes were first observed in plants about a century ago and it is now recognized that polyploidy cells form in many eukaryotes under a wide variety of circumstance. Although it is less common in mammals, some tissues, including the liver, show a high percentage of polyploid cells. Thus, during postnatal growth, the liver parenchyma undergoes dramatic changes characterized by gradual polyploidization during which hepatocytes of several ploidy classes emerge as a result of modified cell-division cycles. This process generates the successive appearance of tetraploid and octoploid cell classes with one or two nuclei (mononucleated or binucleated). Liver cells polyploidy is generally considered to indicate terminal differentiation and senescence and to lead both to the progressive loss of cell pluripotency and a markedly decreased replication capacity. In adults, liver polyploidization is differentially regulated upon loss of liver mass and liver damage. Interestingly, partial hepatectomy induces marked cell proliferation followed by an increase in liver ploidy. In contrast, during hepatocarcinoma (HCC), growth shifts to a nonpolyploidizing pattern and expansion of the diploid hepatocytes population is observed in neoplastic nodules. Here we review the current state of understanding about how polyploidization is regulated during normal and pathological liver growth and detail by which mechanisms hepatocytes become polyploid.

  20. The effect of ZnO Nps of 20 nm on changes of enzyme and liver tissues of pregnant NMRI mice

    Directory of Open Access Journals (Sweden)

    bager Seyed Alipour

    2015-01-01

    Full Text Available Background :Nowadays, nanotechnology has been developing rapidly and may have considerable effects on industry, society and the environment. In this research the toxicity properties of zinc oxide nanoparticles with a size of 20 nm on enzyme and liver tissue of NMRI mice were studied. Materials and Methods: This experimental study was performed in standard conditions on 25 NMRI mice with an average weight of 30 ± 3 g so that they received different doses of zinc oxide nanoparticles, an a days, for 15 days intraperitoneally. Then, blood samples were taken on day 17 of NMRI mice. The collected tissues were washed with saline and fixed in Boin΄s fluied buffer and stained with hematoxylin and eosin for histopathology evaluation. After data collection, statistical analysis was done using SAS software. Results: The results showed that activity of ALT enzyme at concentrations 50, 100, 150 and 200 mg/kg ZnO Nps at a significant level (p<0.05 increased in comparison with the control group. Histopathological investigation showed that zinc oxide nanoparticles caused severe damage in liver. Damaged liver cells develop leaky membranes and escape of intracellular enzymes into the bloodstream. Conclusion: Our findings showed that using different concentration of zinc oxide nanoparticles could be caused undesirable effects on liver with damage to hepatocyte and level elevation of liver enzymes.

  1. 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.

  2. 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.

  3. 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

  4. Validation of an LC-MS/MS method to measure tacrolimus in rat kidney and liver tissue and its application to human kidney biopsies.

    Science.gov (United States)

    Noll, Benjamin D; Coller, Janet K; Somogyi, Andrew A; Morris, Raymond G; Russ, Graeme R; Hesselink, Dennis A; Van Gelder, Teun; Sallustio, Benedetta C

    2013-10-01

    Tacrolimus (TAC) has a narrow therapeutic index and high interindividual and intraindividual pharmacokinetic variability, necessitating therapeutic drug monitoring to individualize dosage. Recent evidence suggests that intragraft TAC concentrations may better predict transplant outcomes. This study aimed to develop a method for the quantification of TAC in small biopsy-sized samples of rat kidney and liver tissue, which could be applied to clinical biopsy samples from kidney transplant recipients. Kidneys and livers were harvested from Mrp2-deficient TR- Wistar rats administered TAC (4 mg·kg·d for 14 days, n = 8) or vehicle (n = 10). Tissue samples (0.20-1.00 mg of dry weight) were solubilized enzymatically and underwent liquid-liquid extraction before analysis by liquid chromatography tandem mass spectrometry method. TAC-free tissue was used in the calibrator and quality control samples. Analyte detection was accomplished using positive electrospray ionization (TAC: m/z 821.5 → 768.6; internal standard ascomycin m/z 809.3 → 756.4). Calibration curves (0.04-2.6 μg/L) were linear (R > 0.99, n = 10), with interday and intraday calibrator coefficients of variation and bias <17% at the lower limit of quantification and <15% at all other concentrations (n = 6-10). Extraction efficiencies for TAC and ascomycin were approximately 70%, and matrix effects were minimal. Rat kidney TAC concentrations were higher (range 109-190 pg/mg tissue) than those in the liver (range 22-53 pg/mg of tissue), with median tissue/blood concentrations ratios of 72.0 and 17.6, respectively. In 2 transplant patients, kidney TAC concentrations ranged from 119 to 285 pg/mg of tissue and were approximately 20 times higher than whole blood trough TAC concentrations. The method displayed precision and accuracy suitable for application to TAC measurement in human kidney biopsy tissue.

  5. New description of gradual substitution of graft by bone tissue including biomechanical and structural effects, nutrients supply and consumption

    Science.gov (United States)

    Lu, Yanfei; Lekszycki, Tomasz

    2018-03-01

    A new description of graft substitution by bone tissue is proposed in this work. The studied domain is considered as a continuum model consisting of a mixture of the bone tissue and the graft material. Densities of both components evolve in time as a result of cellular activity and biodegradation. The proposed model focuses on the interaction between the bone cell activity, mechanical stimuli, nutrients supply and scaffold microstructure. Different combinations of degradation rate and stiffness of the graft material were examined by numerical simulation. It follows from the calculations that the degradation rate of the scaffold should be tuned to the synthesis/resorption rate of the tissue, which are dependent among the others on scaffold porosity changes. Simulation results imply potential criteria to choose proper bone substitute material in consideration of degradation rate, initial porosity and mechanical characteristics.

  6. Molecular signature of adipose tissue in patients with both non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS).

    Science.gov (United States)

    Baranova, Ancha; Tran, Thuy Phuong; Afendy, Arian; Wang, Lei; Shamsaddini, Amirhossein; Mehta, Rohini; Chandhoke, Vikas; Birerdinc, Aybike; Younossi, Zobair M

    2013-05-31

    Polycystic ovarian syndrome (PCOS) is one of the most common reproductive disorders with strong association with both insulin resistance and non-alcoholic fatty liver disease (NAFLD). To untangle the complex relationship between PCOS and NAFLD, we analyzed serum biomarkers of apoptosis, some adipokines and mRNA profiles in the visceral adipose tissue of obese patients with NAFLD who were also diagnosed with PCOS and compared to a group with NAFLD only. We included patients with biopsy-proven NAFLD and PCOS (N = 12) and BMI-matched biopsy-proven NAFLD patients without PCOS (N = 12). Expression levels of individual mRNAs and soluble serum biomarkers were compared by non-parametric Mann-Whitney test. The analysis also included Spearman rank correlation tests and multiple regression analysis. For co-correlated genes, the factor analysis was performed. The total serum levels of apoptotic biomarker M30 were significantly elevated in PCOS patients with liver steatosis as compared to non-PCOS NAFLD controls (P < 0.02), pointing that androgen-dependent proapoptotic PCOS environment that may directly contribute to NAFLD progression in these patients. Similarly, hyperandrogenism may explain the observed PCOS-specific decrease (P < 0.04) in adipose LDLR mRNA expression that may be connected to the proneness of PCOS patients to NAFLD. The levels of mRNA encoding angiogenesis-associated GSK-3B interacting protein ninein were also significantly increased in the adipose tissue of NAFLD patients with PCOS (P < 0.007). Furthermore, the levels of resistin positively correlated with expression levels of LDLR and prothrombin time (PT). An androgen-dependent proapoptotic PCOS environment may directly contribute to NAFLD progression in these patients. Hyperandrogenism may explain an observed decrease in adipose LDLR mRNA expression. An inflammation-associated increase in the release of resistin into circulation might contribute to the prothrombotic state observed

  7. PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

    Science.gov (United States)

    Karakan, Tarkan; Kerem, Mustafa; Cindoruk, Mehmet; Engin, Doruk; Alper, Murat; Akın, Okan

    2013-01-01

    Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.

  8. Macro- and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo.

    Science.gov (United States)

    Orct, Tatjana; Jurasović, Jasna; Micek, Vedran; Karaica, Dean; Sabolić, Ivan

    2017-03-01

    Concentrations of macro- and microelements in animal organs indicate the animal health status and represent reference data for animal experiments. Their levels in blood and tissues could be different between sexes, and could be different with and without blood in tissues. To test these hypotheses, in adult female and male rats the concentrations of various elements were measured in whole blood, blood plasma, and tissues from blood-containing (nonperfused) and blood-free liver, kidneys, and brain (perfused in vivo with an elements-free buffer). In these samples, 6 macroelements (Na, Mg, P, S, K, Ca) and 14 microelements (Fe, Mn, Co, Cu, Zn, Se, I, As, Cd, Hg, Pb, Li, B, Sr) were determined by inductively coupled plasma mass spectrometry following nitric acid digestion. In blood and plasma, female- or male-dominant sex differences were observed for 6 and 5 elements, respectively. In nonperfused organs, sex differences were observed for 3 (liver, brain) or 9 (kidneys) elements, whereas in perfused organs, similar differences were detected for 9 elements in the liver, 5 in the kidneys, and none in the brain. In females, perfused organs had significantly lower concentrations of 4, 5, and 2, and higher concentrations of 10, 4, and 7 elements, respectively, in the liver, kidneys, and brain. In males, perfusion caused lower concentrations of 4, 7, and 2, and higher concentrations of 1, 1, and 7 elements, respectively, in the liver, kidneys, and brain. Therefore, the residual blood in organs can significantly influence tissue concentrations of various elements and their sex-dependency. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. Effect of inulin supplementation and dietary fat source on performance, blood serum metabolites, liver lipids, abdominal fat deposition, and tissue fatty acid composition in broiler chickens.

    Science.gov (United States)

    Velasco, S; Ortiz, L T; Alzueta, C; Rebolé, A; Treviño, J; Rodríguez, M L

    2010-08-01

    A study was conducted to evaluate the effect of adding inulin to diets containing 2 different types of fat as energy sources on performance, blood serum metabolites, liver lipids, and fatty acids of abdominal adipose tissue and breast and thigh meat. A total of 240 one-day-old female broiler chicks were randomly allocated into 1 of 6 treatments with 8 replicates per treatment and 5 chicks per pen. The experiment consisted of a 3 x 2 factorial arrangement of treatments including 3 concentrations of inulin (0, 5, and 10 g/kg of diet) and 2 types of fat [palm oil (PO) and sunflower oil (SO)] at an inclusion rate of 90 g/kg of diet. The experimental period lasted from 1 to 34 d. Dietary fat type did not affect BW gain but impaired feed conversion (P abdominal fat deposition and serum lipid and glucose concentrations. Triacylglycerol contents in liver were higher in the birds fed PO diets. Dietary fat type also modified fatty acids of abdominal and i.m. fat, resulting in a higher concentration of C16:0 and C18:1n-9 and a lower concentration of C18:2n-6 in the birds fed PO diets. The addition of inulin to diets modified (P = 0.017) BW gain quadratically without affecting feed conversion. Dietary inulin decreased the total lipid concentration in liver (P = 0.003) and that of triacylglycerols and very low density lipoprotein cholesterol (up to 31%) in blood serum compared with the control groups. The polyunsaturated fatty acid:saturated fatty acid ratio increased in abdominal and i.m. fat when inulin was included in the SO-containing diets. The results from the current study suggest that the addition of inulin to broiler diets has a beneficial effect on blood serum lipids by decreasing triacylglyceride concentrations The results also support the use of inulin to increase the capacity of SO for enhancing polyunsaturated fatty acid:saturated fatty acid ratio of i.m. fat in broilers.

  10. Bio-inspired fabrication of fibroin cryogels from the muga silkworm Antheraea assamensis for liver tissue engineering

    International Nuclear Information System (INIS)

    Kundu, Banani; Kundu, S C

    2013-01-01

    Conventional scaffold fabrication techniques result in narrow pore architectures causing a limited interconnectivity and use of porogens, which affects the bio- or cyto-compatibility. To ameliorate this, cryogels are immensely explored due to their macro-porous nature, ease in fabrication, using ice crystals as porogens, the shape property, easy reproducibility and cost-effective fabrication technique. Cryogels in the present study are prepared from nonmulberry Indian muga silk gland protein fibroin of Antheraea assamensis using two different fabrication temperatures (−20 and −80 °C). Anionic surfactant sodium dodecyl sulfate is used to solubilize fibroin, which in turn facilitates gelation by accelerating the ß-sheet formation. Ethanol is employed to stabilize the 3D network and induces bimodal porosity. The gels thus formed demonstrate increased ß-sheet content (FTIR) and a considerable effect of pre-freezing temperatures on 3D micro-architectures. The cryogels are capable of absorbing large amounts of water and withstanding mechanical compression without structure deformation. Further, cell impregnated cryogels well support the viability of human hepatocarcinoma cells (live/dead assay). The formation of cellular aggregates (confocal laser and scanning electron microscope), derivation in metabolic activity and proliferation rate are obtained in constructs fabricated at different temperatures. In summary, the present work reveals promising insights in the development of a biomimetic functional template for biomedical therapeutics and liver tissue engineering. (paper)

  11. A Weight-Loss Diet Including Coffee-Derived Mannooligosaccharides Enhances Adipose Tissue Loss in Overweight Men but Not Women

    Science.gov (United States)

    St-Onge, Marie-Pierre; Salinardi, Taylor; Herron-Rubin, Kristin; Black, Richard M.

    2013-01-01

    Mannooligosaccharides (MOS), extracted from coffee, have been shown to promote a decrease in body fat when consumed as part of free-living, weight-maintaining diets. Our objective was to determine if MOS consumption (4 g/day), in conjunction with a weight-loss diet, would lead to greater reductions in adipose tissue compartments than placebo. We conducted a double-blind, placebo-controlled weight-loss study in which 60 overweight men and women consumed study beverages and received weekly group counseling for 12 weeks. Weight and blood pressure were measured weekly, and adipose tissue distribution was assessed at baseline and at end point using magnetic resonance imaging. A total of 54 subjects completed the study. Men consuming the MOS beverage had greater loss of body weight than men consuming the Placebo beverage (−6.0 ± 0.6% vs. −2.3 ± 0.5%, respectively, P coffee-derived MOS to a weight-loss diet enhanced both weight and adipose tissue losses in men, suggesting a potential functional use of MOS for weight management and improvement in adipose tissue distribution. More studies are needed to investigate the apparent gender difference in response to MOS consumption. PMID:21938072

  12. Fade-out sign on hepatic tissue harmonic compound sonography: A value as a new sign in the diagnosis of fatty liver

    International Nuclear Information System (INIS)

    Lee, Chang Hee; Kim, Kyeong Ah; Lee, Jongmee; Park, Yang Shin; Choi, Jae Woong; Seo, Tae Seok; Park, Cheol Min

    2011-01-01

    Objective: To evaluate the value of the fade-out sign in the diagnosis of fatty liver (FL) on hepatic ultrasound (US). Methods: We evaluated 127 patients who underwent hepatic US, including 70 patients with FL and 57 normal control subjects. US images were qualitatively evaluated for the presence of the fade-out sign. This sign was considered present if there was a dark band on the deep portion of the liver on the harmonic image when compound sonography (CS) was converted to tissue harmonic CS mode. The degrees of FL were classified into mild, moderate, and severe. The distribution of lengths of dark bands in three groups was examined, and a multiple comparison of the average dark band length was carried out using one-way ANOVA. Results: The fade-out sign was seen in 55 of 70 FL patients (78.6%) compared to 3 of 57 control subjects (5.3%) (p < 0.001). The sensitivity, specificity, accuracy, and positive predictive value of the fade-out sign for the US diagnosis of FL were 78%, 94%, 85.8%, and 94.8%, respectively. Among the 70 FL, there were 28 mild FL (mean length of dark band; 8.3 mm ± 8.2), 31 moderate FL (mean; 28 mm ± 6.3), and 11 severe FL (mean; 51 mm ± 8.3). There were significant differences in band length according to severity (p < 0.01). Conclusion: The fade-out sign on hepatic harmonic US was frequently present in FL. As fat infiltration increased, the fade-out sign lengthened. The fade-out sign offers a specific and new sign of FL.

  13. 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. © 2015 Wiley Periodicals, Inc.

  14. Comparison of different magnetic resonance cholangiography techniques in living liver donors including Gd-EOB-DTPA enhanced T1-weighted sequences.

    Directory of Open Access Journals (Sweden)

    Sonja Kinner

    Full Text Available Preoperative evaluation of potential living liver donors (PLLDs includes the assessment of the biliary anatomy to avoid postoperative complications. Aim of this study was to compare T2-weighted (T2w and Gd-EOB-DTPA enhanced T1-weighted (T1w magnetic resonance cholangiography (MRC techniques in the evaluation of PLLDs.30 PLLDs underwent MRC on a 1.5 T Magnetom Avanto (Siemens, Erlangen, Germany using (A 2D T2w HASTE (Half Fourier Acquisition Single Shot Turbo Spin Echo fat saturated (fs in axial plane, (B 2D T2w HASTE fs thick slices in coronal plane, (C free breathing 3D T2w TSE (turbo spin echo RESTORE (high-resolution navigator corrected plus (D maximum intensity projections (MIPs, (E T2w SPACE (sampling perfection with application optimized contrasts using different flip angle evolutions plus (F MIPs and (G T2w TSE BLADE as well as Gd-EOB-DTPA T1w images without (G and with (H inversion recovery. Contrast enhanced CT cholangiography served as reference imaging modality. Two independent reviewers evaluated the biliary tract anatomy on a 5-point scale subjectively and objectively. Data sets were compared using a Mann-Whitney-U-test. Kappa values were also calculated.Source images and maximum intensity projections of 3D T2w TSE sequences (RESTORE and SPACE proved to be best for subjective and objective evaluation directly followed by 2D HASTE sequences. Interobserver variabilities were good to excellent (k = 0.622-0.804.3D T2w sequences are essential for preoperative biliary tract evaluation in potential living liver donors. Furthermore, our results underline the value of different MRCP sequence types for the evaluation of the biliary anatomy in PLLDs including Gd-EOB-DTPA enhanced T1w MRC.

  15. Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue

    International Nuclear Information System (INIS)

    Laperle, Christopher M; Wintermeyer, Philip; Derdak, Zoltan; Wands, Jack R; Hamilton, Theron J; Walker, Evan J; Diebold, Gerald; Rose-Petruck, Christoph; Shi, Daxin; Anastasio, Mark A

    2008-01-01

    We report a new preparative method for providing contrast through reduction in electron density that is uniquely suited for propagation-based differential x-ray phase contrast imaging. The method, which results in an air or fluid filled vasculature, makes possible visualization of the smallest microvessels, roughly down to 15 μm, in an excised murine liver, while preserving the tissue for subsequent histological workup. We show the utility of spatial frequency filtering for increasing the visibility of minute features characteristic of phase contrast imaging, and the capability of tomographic reconstruction to reveal microvessel structure and three-dimensional visualization of the sample. The effect of water evaporation from livers during x-ray imaging on the visibility of blood vessels is delineated. The deformed vascular tree in a cancerous murine liver is imaged.

  16. 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.

  17. Blood cell oxidative stress precedes hemolysis in whole blood-liver slice co-cultures of rat, dog, and human tissues

    International Nuclear Information System (INIS)

    Vickers, Alison E.M.; Sinclair, John R.; Fisher, Robyn L.; Morris, Stephen R.; Way, William

    2010-01-01

    A novel in vitro model to investigate time-dependent and concentration-dependent responses in blood cells and hemolytic events is studied for rat, dog, and human tissues. Whole blood is co-cultured with a precision-cut liver slice. Methimazole (MMI) was selected as a reference compound, since metabolism of its imidazole thione moiety is linked with hematologic disorders and hepatotoxicity. An oxidative stress response occurred in all three species, marked by a decline in blood GSH levels by 24 h that progressed, and preceded hemolysis, which occurred at high MMI concentrations in the presence of a liver slice with rat (≥ 1000 μM at 48 h) and human tissues (≥ 1000 μM at 48 h, ≥ 750 μM at 72 h) but not dog. Human blood-only cultures exhibited a decline of GSH levels but minimal to no hemolysis. The up-regulation of liver genes for heme degradation (Hmox1 and Prdx1), iron cellular transport (Slc40a1), and GSH synthesis and utilization (mGST1 and Gclc) were early markers of the oxidative stress response. The up-regulation of the Kupffer cell lectin Lgals3 gene expression indicated a response to damaged red blood cells, and Hp (haptoglobin) up-regulation is indicative of increased hemoglobin uptake. Up-regulation of liver IL-6 and IL-8 gene expression suggested an activation of an inflammatory response by liver endothelial cells. In summary, MMI exposure led to an oxidative stress response in blood cells, and an up-regulation of liver genes involved with oxidative stress and heme homeostasis, which was clearly separate and preceded frank hemolysis.

  18. 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.

  19. Fatty Liver

    International Nuclear Information System (INIS)

    Filippone, A.; Digiovandomenico, V.; Digiovandomenico, E.; Genovesi, N.; Bonomo, L.

    1991-01-01

    The authors report their experience with the combined use of US and CT in the study of diffuse and subtotal fatty infiltration of the liver. An apparent disagreement was initially found between the two examinations in the study of fatty infiltration. Fifty-five patients were studied with US and CT of the upper abdomen, as suggested by clinics. US showed normal liver echogenicity in 30 patients and diffuse increased echogenicity (bright liver) in 25 cases. In 5 patients with bright liver, US demonstrated a solitary hypoechoic area, appearing as a 'skip area', in the quadrate lobe. In 2 patients with bright liver, the hypoechoic area was seen in the right lobe and exhibited no typical US features of 'Skip area'. Bright liver was quantified by measuring CT density of both liver and spleen. The relative attenuation values of spleen and liver were compared on plain and enhanced CT scans. In 5 cases with a hypoechoic area in the right lobe, CT findings were suggestive of hemangioma. A good correlation was found between broght liver and CT attenuation values, which decrease with increasing fat content of the liver. Moreover, CT attenuation values confirmed US findings in the study of typical 'skip area', by demonstrating normal density - which suggests that CT can characterize normal tissue in atypical 'skip area'

  20. Distribution of sterol carrier protein2 (SCP2) in rat tissues and evidence for slow turnover in liver and adrenal cortex

    International Nuclear Information System (INIS)

    Kharroubi, A.; Chanderbhan, R.; Fiskum, G.; Noland, B.J.; Scallen, T.J.; Vahouny, G.V.

    1986-01-01

    Sterol carrier protein 2 (SCP 2 ) has been implicated in the regulation of the terminal stages of hepatic cholesterol biosynthesis, and in sterol utilization for adrenal steroid hormone and hepatic bile acid synthesis. In the present studies, a highly sensitive radioimmunoassay, using [ 125 I] SCP 2 , has been developed. Highest levels of SCP 2 were found in rat liver with progressively lower levels in intestinal mucosa, adrenal, kidney, lung and testis. SCP 2 levels were low or absent in heart, brain, skeletal muscle and serum. Liver SCP 2 was largely (44%) associated with the microsomal fraction, while in adrenal, 46% was associated with mitochondria, a distribution which is consistent with the proposed roles for SCP 2 in these tissues. Levels of SCP 2 in AS 30D hepatoma cells were only 5% of those in normal liver. In liver there was no indication of diurnal rhythm of SCP 2 in the cytosol and only slight variation of the microsomal SCP 2 levels. Fasting has only slight effects on SCP 2 concentration of rat liver microsomes and cytosol. Neither ACTH nor cycloheximide treatment of rats had a significant effect on SCP 2 distribution in the adrenal. In general, these findings indicate that SCP 2 has a low turn-over rate

  1. 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...

  2. Diagnostic value of static MR imaging of soft tissue tumours including lesion size, borders and local extend

    International Nuclear Information System (INIS)

    Tacikowska, M.

    2001-01-01

    The usefulness of MR imaging in the evaluation of the degree of soft tissue malignancy is widely discussed. The aim of this study was to analyse the diagnostic value of MR imaging in the evaluation of local progression of soft tissue tumours and to analyse the usefulness of MR imaging in the differential diagnosis (malignant versus benign lesions). One hundred and ten patients with soft tissue tumours were examined by MR imaging (60 men and 50 women, aged 16 to 84 years). MR imaging was carried out with an Elscint 2T or 0.5T unit. Surface coils (passive) or circular polarized coils (active) depending on the localisation of the lesions were used with field vision from 20x24 cm or 40x40 cm, matrices 200x256, 256x256, or 22x315, layer thickness from 3 to 10 mm, gap 20-30%. SE T1 sequences (TR = 500 - 800 ms, TE = 15 - 20 ms) and FSE T2 (Tr = 2000-4500 ms, TE = 96-104 ms) were routinely used in at least two planes: transverse, frontal or saggital, and SE T1 sequences were used after administration of gadolinium Gd-DTPA in 0.1 m - 0.2 mmol/kg body weigh doses. The tumour dimensions by MR imaging were compared with the results of histological examination of samples obtained during surgery (65 cases) - the statistical analysis was performed using Student's t-test, with statistically significant difference accepted at p = 0.05 or less. The borders of the lesions were assessed in the entire material and in the group of 65 patients treated surgically. The latter were compared with the results of histological examination after surgery, thus calculating MR sensitivity and specificity. Static imaging is a valuable diagnostic method for preoperative assesment of the local progression of soft tissue tumours, however it is not suitable for differentiating malignant lesions from benign according to tumour size, borders and local extent. (author)

  3. Excessive Endoplasmic Reticulum Stress Correlates with Impaired Mitochondrial Dynamics, Mitophagy and Apoptosis, in Liver and Adipose Tissue, but Not in Muscles in EMS Horses

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz

    2018-01-01

    Full Text Available Nowadays, endocrine disorders have become more frequent in both human and veterinary medicine. In horses, reduced physical activity combined with carbohydrate and sugar overload may result in the development of the so-called equine metabolic syndrome (EMS. EMS is characterized by insulin resistance, hyperinsulinemia, elevated blood triglyceride concentrations and usually obesity. Although the phenotypic features of EMS individuals are well known, the molecular mechanism underlying disease development remains elusive. Therefore, in the present study, we analyzed insulin-sensitive tissues, i.e., muscles, liver and adipose tissue in order to evaluate insulin resistance and apoptosis. Furthermore, we assessed mitochondrial dynamics and mitophagy in those tissues, because mitochondrial dysfunction is linked to the development of metabolic syndrome. We established the expression of genes related to insulin resistance, endoplasmic reticulum (ER stress and mitochondria clearance by mitophagy using RT-PCR and Western blot. Cell ultrastructure was visualized using electron transmission microscopy. The results indicated that adipose tissue and liver of EMS horses were characterized by increased mitochondrial damage and mitophagy followed by triggering of apoptosis as mitophagy fails to restore cellular homeostasis. However, in muscles, apoptosis was reduced, suggesting the existence of a protective mechanism allowing that tissue to maintain homeostasis.

  4. Novel feed including bioactive compounds from winery wastes improved broilers' redox status in blood and tissues of vital organs.

    Science.gov (United States)

    Makri, Sotiria; Kafantaris, Ioannis; Stagos, Dimitrios; Chamokeridou, Theodora; Petrotos, Konstantinos; Gerasopoulos, Konstantinos; Mpesios, Anastasios; Goutzourelas, Nikolaos; Kokkas, Stylianos; Goulas, Panagiotis; Komiotis, Dimitrios; Kouretas, Dimitrios

    2017-04-01

    Currently, there is a great interest in the production of animal feed with antioxidant activity. The aim of this study was to examine the potential antioxidant effects of a feed supplemented with grape pomace (GP), a winery by-product with high environmental load, in chickens. Broilers of 15 days post birth were separated into two groups fed either with standard diet or with diet supplemented with GP for 35 days. Blood and tissues collections were performed after feeding for 15 and 35 days with the experimental diet (i.e. at 30 and 50 days post birth). Free radical toxicity markers, namely thiobarbituric acid reactive substances, protein carbonyls, total antioxidant capacity, reduced glutathione, catalase activity and rate of H 2 O 2 decomposition were determined in blood and tissues of vital organs. The results indicated that feed supplemented with GP decreased oxidative stress-induced toxic effects and improved chickens' redox status, and so it may also improve their wellness and productivity. On the other hand, this exploitation of GP may solve problems of environmental pollution in areas with wineries. Copyright © 2017. Published by Elsevier Ltd.

  5. Up-regulation of calreticulin in mouse liver tissues after long-term irradiation with low-dose-rate gamma rays.

    Science.gov (United States)

    Yi, Lan; Hu, Nan; Yin, Jie; Sun, Jing; Mu, Hongxiang; Dai, Keren; Ding, Dexin

    2017-01-01

    The biological effects of low-dose or low-dose-rate ionizing radiation on normal tissues has attracted attention. Based on previous research, we observed the morphology of liver tissues of C57BL/6J mice that received irradiation dose rates increased. Additionally, differential protein expression in liver tissues was analyzed using a proteomics approach. Compared with the matched group in the 2D gel analysis of the irradiated groups, 69 proteins had ≥ 1.5-fold changes in expression. Twenty-three proteins were selected based on ≥2.5-fold change in expression, and 22 of them were meaningful for bioinformatics and protein fingerprinting analysis. These molecules were relevant to cytoskeleton processes, cell metabolism, biological defense, mitochondrial damage, detoxification and tumorigenesis. The results from real-time PCR and western blot (WB) analyses showed that calreticulin (CRT) was up-regulated in the irradiated groups, which indicates that CRT may be relevant to stress reactions when mouse livers are exposed to low-dose irradiation and that low-dose-rate ionizing radiation may pose a cancer risk. The CRT protein can be a potential candidate for low-dose or low-dose-rate ionizing radiation early-warning biomarkers. However, the underlying mechanism requires further investigation.

  6. Lipasin/betatrophin is differentially expressed in liver and white adipose tissue without association with insulin resistance in Wistar and Goto-Kakizaki rats.

    Science.gov (United States)

    Cahová, M; Habart, D; Olejár, T; Berková, Z; Papáčková, Z; Daňková, H; Lodererova, A; Heczková, M; Saudek, F

    2017-05-04

    Lipasin is a recently identified lipokine expressed predominantly in liver and in adipose tissue. It was linked to insulin resistance in mice and to type 1 and type 2 diabetes (T1D, T2D) in humans. No metabolic studies concerning lipasin were performed yet in rats. Therefore, we used rat model of T2D and insulin resistance, Goto-Kakizaki (GK) rats, to determine changes of lipasin expression in liver and in white adipose tissue (WAT) over 52 weeks in the relation to glucose tolerance, peripheral tissue insulin sensitivity and adiposity. GK rats were grossly glucose intolerant since the age of 6 weeks and developed peripheral insulin resistance at the age of 20 weeks. Expression of lipasin in the liver did not differ between GK and Wistar rats, declining with age, and it was not related to hepatic triacylglycerol content. In WAT, the lipasin expression was significantly higher in Wistar rats where it correlated positively with adiposity. No such correlation was found in GK rats. In conclusion, lipasin expression was associated neither with a mild age-related insulin resistance (Wistar), nor with severe genetically-based insulin resistance (GK).

  7. 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.

  8. Quantitative PET of liver functions.

    Science.gov (United States)

    Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

    2018-01-01

    Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[ 18 F]fluoro- D -galactose ( 18 F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value ( SUV ) from a static liver 18 F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11 C-palmitate and with the conjugated bile acid tracer [ N -methyl- 11 C]cholylsarcosine ( 11 C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood ( K 1 ; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion , SUV of non-invasive static PET with 18 F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET.

  9. Quantitative PET of liver functions

    Science.gov (United States)

    Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

    2018-01-01

    Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[18F]fluoro-D-galactose (18F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value (SUV) from a static liver 18F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11C-palmitate and with the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood (K 1; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion, SUV of non-invasive static PET with 18F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET. PMID:29755841

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

    NARCIS (Netherlands)

    Cheng, Sulin; Wiklund, Petri; Autio, Reija; Borra, Ronald; Ojanen, Xiaowei; Xu, Leiting; Törmäkangas, Timo; Alen, Markku

    2015-01-01

    BACKGROUND: 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. METHODS: Hepatic fat content was

  11. Effect of cholesterol feeding on tissue lipid perioxidation, glutathione peroxidase activity and liver microsomal functions in rats and guinea pigs

    NARCIS (Netherlands)

    TSAI, A. C.; THIE, G. M.; Lin, C. R.

    1977-01-01

    The effect of cholesterol feeding on liver and aortic nonenzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was

  12. 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

    differently expressed genes in both liver and neck SAT were upregulated (seven out of eight). Remarkably, acute phase proteins (APPs) dominated the upregulated genes in the liver, whereas APP expression was either unchanged or downregulated in abdominal SAT and VAT. The general conclusion from this work...

  13. 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

    2014-01-01

    Trichloroethylene (TCE) is a widely used organic solvent. Although TCE is classified as carcinogenic to humans, substantial gaps remain in our understanding of inter-individual variability in TCE metabolism and toxicity, especially in the liver. We tested a hypothesis that amounts of oxidative metabolites of TCE in mouse liver are associated with liver-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-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 liver toxicity phenotypes. In sub-acute study, inter-strain variability in TCE metabolite amounts was observed in serum and liver. No induction of Cyp2e1 protein levels in liver was detected. Serum and liver 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 sub-chronic study, serum and liver levels of oxidative metabolites gradually decreased over time despite continuous dosing. Liver 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. PMID:25424544

  14. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation

    International Nuclear Information System (INIS)

    Kovalchuk, Olga; Burke, Paula; Besplug, Jill; Slovack, Mark; Filkowski, Jody; Pogribny, Igor

    2004-01-01

    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 INKa and DNA repair gene O 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 INKa promoter methylation upon LDR exposure. In male liver tissue, p16 INKa promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16 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 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

  15. Laser-induced thermotherapy (LITT) elevates mRNA expression of connective tissue growth factor (CTGF) associated with reduced tumor growth of liver metastases compared to hepatic resection.

    Science.gov (United States)

    Isbert, Christoph; Ritz, Jörg-Peter; Roggan, André; Schuppan, Detlef; Ajubi, Navid; Buhr, Heinz Johannes; Hohenberger, Werner; Germer, Christoph-Thomas

    2007-01-01

    Proliferation and synthesis of hepatocellular tissue after tissue damage are promoted by specific growth factors such as hepatic tissue growth factor (HGF) and connective growth factor (CTGF). Laser-induced thermotherapy (LITT) for the treatment of liver metastases is deemed to be a parenchyma-saving procedure compared to hepatic resection. The aim of this study was to compare the impact of LITT and hepatic resection on intrahepatic residual tumor tissue and expression levels of mRNA HGF/CTGF within liver and tumor tissue. Two independent adenocarcinomas (CC531) were implanted into 75 WAG rats, one in the right (untreated tumor) and one in the left liver lobe (treated tumor). The left lobe tumor was treated either by LITT or partial hepatectomy. The control tumor was submitted to in-situ hybridization of HGF and CTGF 24-96 hours and 14 days after intervention. Volumes of the untreated tumors prior to intervention were 38+/-8 mm(3) in group I (laser), 39 +/- 7 mm(3) in group II (resection), and 42 +/- 12 mm(3) in group III (control) and did not differ significantly (P > 0.05). Fourteen days after the intervention the mean tumor+/-SEM volume of untreated tumor in group I (laser) [223 +/- 36] was smaller than in group II (resection) [1233.28 +/- 181.52; P tumor growth in comparison to hepatic resection. Accelerated tumor growth after hepatic resection is associated with higher mRNA level of HGF and reduced tumor growth after LITT with higher mRNA level of CTGF. The increased CTGF-mediated regulation of ECM may cause reduced residual tumor growth after LITT. (c) 2006 Wiley-Liss, Inc.

  16. Thyroid Hormone Receptor β (TRβ) and Liver X Receptor (LXR) Regulate Carbohydrate-response Element-binding Protein (ChREBP) Expression in a Tissue-selective Manner*

    Science.gov (United States)

    Gauthier, Karine; Billon, Cyrielle; Bissler, Marie; Beylot, Michel; Lobaccaro, Jean-Marc; Vanacker, Jean-Marc; Samarut, Jacques

    2010-01-01

    Thyroid hormone (TR) and liver X (LXR) receptors are transcription factors involved in lipogenesis. Both receptors recognize the same consensus DNA-response element in vitro. It was previously shown that their signaling pathways interact in the control of cholesterol elimination in the liver. In the present study, carbohydrate-response element-binding protein (ChREBP), a major transcription factor controlling the activation of glucose-induced lipogenesis in liver, is characterized as a direct target of thyroid hormones (TH) in liver and white adipose tissue (WAT), the two main lipogenic tissues in mice. Using genetic and molecular approaches, ChREBP is shown to be specifically regulated by TRβ but not by TRα in vivo, even in WAT where both TR isoforms are expressed. However, this isotype specificity is not found in vitro. This TRβ specific regulation correlates with the loss of TH-induced lipogenesis in TRβ−/− mice. Fasting/refeeding experiments show that TRβ is not required for the activation of ChREBP expression particularly marked in WAT following refeeding. However, TH can stimulate ChREBP expression in WAT even under fasting conditions, suggesting completely independent pathways. Because ChREBP has been described as an LXR target, the interaction of LXR and TRβ in ChREBP regulation was assayed both in vitro and in vivo. Each receptor recognizes a different response element on the ChREBP promoter, located only 8 bp apart. There is a cross-talk between LXR and TRβ signaling on the ChREBP promoter in liver but not in WAT where LXR does not regulate ChREBP expression. The molecular basis for this cross-talk has been determined in in vitro systems. PMID:20615868

  17. Chronic Dietary Intake of Enniatin B in Broiler Chickens Has Low Impact on Intestinal Morphometry and Hepatic Histology, and Shows Limited Transfer to Liver Tissue

    Directory of Open Access Journals (Sweden)

    Sophie Fraeyman

    2018-01-01

    Full Text Available The Fusarium mycotoxin enniatin B (ENN B is a so-called emerging mycotoxin frequently contaminating poultry feed. To investigate the impact of chronic ENN B exposure on animal health, broiler chickens were fed either a diet naturally contaminated with ENN B (2352 µg/kg or a control diet (135 µg/kg for 2, 7, 14, or 21 days. ENN B concentrations were determined in plasma and liver using a validated ultra-high performance liquid chromatography—tandem mass spectrometry UHPLC-MS/MS method. Liver was evaluated histologically, and the villus length and crypt depth of the duodenum, jejunum, and ileum were measured. Histopathology of the livers did not reveal major abnormalities. Feeding an ENN B-contaminated diet could possibly inhibit the proliferation of enterocytes in the duodenal crypts, but did not affect villus length, crypt depth, or villus length-crypt depth ratio of the jejunum and ileum. ENN B levels in plasma and liver were significantly higher in the ENN B-fed group and ranged between <25–264 pg/mL and <0.05–0.85 ng/g, respectively. ENN B carry-over rates from feed to liver tissue were 0.005–0.014% and 0.034–0.109% in the ENN B and control group, respectively. Carry-over rates were low and indicated a limited contribution of poultry tissue-derived products to the total dietary ENN B intake for humans. The above results support the opinion of the European Food Safety Authority stating that adverse health effects from ENN B in broiler chickens are unlikely.

  18. Accumulation of radioactivity in rat brain and peripheral tissues including salivary gland after intravenous administration of 14C-D-aspartic acid

    International Nuclear Information System (INIS)

    Imai, Kazuhiro; Fukushima, Takeshi; Santa, Tomofumi; Homma, Hiroshi; Sugihara, Juko; Kodama, Hirohiko; Yoshikawa, Masayoshi.

    1997-01-01

    After the intravenous administration of 14 C-D-aspartic acid (Asp) into Sprague-Dawley rats (male, 7-week-old), the distribution and elimination of radioactivity was investigated by the whole body autoradiography. High radioactivities were detected in pineal gland, pituitary gland and salivary gland at 30 min after administration. The other tissues detected were liver, lung, adrenal gland, pancreas and spleen where D-Asp was reported to occur naturally. After 24 hr, the radioactivities were still detected at high levels in the pineal, pituitary and salivary glands. The data suggested the natural occurrence of D-Asp in salivary gland. After careful examination utilizing fluorescent derivatization and chiral separation by high-performance liquid chromatography, the presence of D-Asp was, for the first time, demonstrated in salivary gland in situ, the concentration of which was 7.85 ± 1.0 nmol/g. The administration of 14 C-L-Asp was also carried out. The data suggested that D-Asp in the circulating blood is one of the sources of the tissue D-Asp. (author)

  19. Diet - liver disease

    Science.gov (United States)

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

  20. A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation.

    Science.gov (United States)

    Bjørndal, Bodil; Berge, Christ; Ramsvik, Marie Sannes; Svardal, Asbjørn; Bohov, Pavol; Skorve, Jon; Berge, Rolf K

    2013-10-07

    There is growing evidence that fish protein hydrolysate (FPH) diets affect mitochondrial fatty acid metabolism in animals. The aim of the study was to determine if FPH could influence fatty acid metabolism and inflammation in transgene mice expressing human tumor necrosis factor alpha (hTNFα). hTNFα mice (C57BL/6 hTNFα) were given a high-fat (23%, w/w) diet containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for two weeks. After an overnight fast, blood, adipose tissue, and liver samples were collected. Gene expression and enzyme activity was analysed in liver, fatty acid composition was analyzed in liver and ovarian white adipose tissue, and inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma. The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in mice fed the control diet in both adipose tissue and liver, and the FPH diet affected the gene expression of ∆6 and ∆9 desaturases. Mice fed this diet also demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a lower plasma INF-γ level was observed. Plasma carnitine and the carnitine precursor γ-butyrobetaine was higher in the FPH-group compared to control, as was plasma short-chained and medium-chained acylcarnitine esters. The higher level of plasma acetylcarnitine may reflect a stimulated mitochondrial and peroxisomal β-oxidation of fatty acids, as the hepatic activities of peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase-II were higher in the FPH-fed mice. The FPH diet was shown to influence hepatic fatty acid metabolism and fatty acid composition. This indicates that effects on fatty acid metabolism are important for the bioactivity of protein hydrolysates of marine origin.

  1. Liver collagen in cirrhosis correlates with portal hypertension and liver dysfunction

    DEFF Research Database (Denmark)

    Nielsen, Kåre; Clemmesen, Jens Otto; Vassiliadis, Efstathios

    2014-01-01

    livers. In 20 of the livers, CPA was measured in more than one tissue sample. CPA showed significant correlations with HVPG and with various surrogate markers of hepatic dysfunction including albumin, bilirubin, INR, MELD score and Child-Pugh score. CPA reliably discriminated HVPG ≥10 mmHg, termed...

  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. Magnetic resonance imaging after radiofrequency ablation in a rodent model of liver tumor: tissue characterization using a novel necrosis-avid contrast agent

    International Nuclear Information System (INIS)

    Ni, Yicheng; Yu, Jie; Marchal, Guy; Chen, Feng; Mulier, Stefaan; Sun, Xihe; Landuyt, Willy; Verbruggen, Alfons

    2006-01-01

    We exploited a necrosis-avid contrast agent ECIV-7 for magnetic resonance imaging (MRI) in rodent liver tumors after radiofrequency ablation (RFA). Rats bearing liver rhabdomyosarcoma (R1) were randomly allocated to three groups: group I, complete RFA, group II, incomplete RFA, and group III, sham ablation. Within 24 h after RFA, T1-weighted (T1-w) MRI was performed before and after injection of ECIV-7 at 0.05 mmol/kg and followed up from 6-24 h. Signal intensities (SIs) were measured with relative enhancement (RE) and contrast ratio (CR) calculated. The MRI findings were verified histomorphologically. On plain T1-w MRI the contrasts between normal liver, RFA lesion, residual and/or intact tumor were vague. Early after administration of ECIV-7, the liver SI was strongly enhanced (RE=40-50%), leaving the RFA lesion as a hypointense region in groups I and II. At delayed phase, two striking peri-ablational enhancement patterns appeared (RE=90% and CR=1.89%), i.e., ''O'' type of hyperintense rim in group I and ''C'' type of incomplete rim in group II. These MRI manifestations could be proven histologically. In this study, tissue components after RFA could be characterized with discernable contrasts by necrosis-avid contrast agent (NACA)-enhanced MRI, especially at delayed phase. This approach may prove useful for defining the ablated area and identifying residual tumor after RFA. (orig.)

  4. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

    Directory of Open Access Journals (Sweden)

    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.

  5. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

    Science.gov (United States)

    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.

  6. 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

  7. Effects of Liver Fibrosis Progression on Tissue Relaxation Times in Different Mouse Models Assessed by Ultrahigh Field Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    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.

  8. Model for end-stage liver disease (MELD score as a predictor and monitor of mortality in patients with Vibrio vulnificus necrotizing skin and soft tissue infections.

    Directory of Open Access Journals (Sweden)

    Kuo-Chin Huang

    2015-04-01

    Full Text Available Vibrio vulnificus necrotizing skin and soft tissue infections (VNSSTIs usually predispose patients with or without preexisting liver disease to septic shock, and then evolve to multiple organ dysfunction syndrome (MODS, thus resulting in high mortality in humans. However, clinicians do not have a valid prediction model to provide a reliable estimate of case-fatality rate when caring for these acutely and/or critically ill patients.We retrospectively analyzed 39 consecutive patients with VNSSTIs (mean age: 65.7 ± 11.3 years at our institution between 2007 and 2010. All patients were treated with the same protocol. Demographic and clinical characteristics, disease severity on admission, treatment details, and outcomes were collected for each patient and extracted for analyses. We studied the predictive value of the model for end-stage liver disease (MELD, modified MELD including sodium (MELD-Na, and laboratory risk indicator for necrotizing fasciitis (LRINEC scores for case-fatality. Logistic regression and receiver operating characteristic (ROC curve analyses were performed. The mean MELD, MELD-Na and LRINEC scores on admission were 15.1 ± 1.1, 17.7 ± 1.1, and 3.4 ± 0.4 points, respectively. After admission, these patients had temporary or progressive deterioration of nearly all their scores and lab values. The area under the ROC curve for the MELD and ΔMELD scoring models were 0.929 (p = 0.002 and 0.897 (p = 0.005, respectively. An optimal MELD/ΔMELD cutoff value ≥ 20/2 had a good sensitivity and specificity (all > 80%, with a 64/13-fold increased odds for case-fatality. Additionally, the development of severe forms of anemia (p = 0.014 and hypoalbuminemia (p = 0.019 were associated with an increased case-fatality rate.The MELD/ΔMELD scoring model is an effective risk stratification indicator at the time of admission and also an excellent condition monitor during hospitalization for medical care of acutely and/or critically ill patients

  9. Fasting-induced G0/G1 switch gene 2 and FGF21 expression in the liver are under regulation of adipose tissue derived fatty acids

    Science.gov (United States)

    Jaeger, Doris; Schoiswohl, Gabriele; Hofer, Peter; Schreiber, Renate; Schweiger, Martina; Eichmann, Thomas O.; Pollak, Nina M.; Poecher, Nadja; Grabner, Gernot F.; Zierler, Kathrin A.; Eder, Sandra; Kolb, Dagmar; Radner, Franz P.W.; Preiss-Landl, Karina; Lass, Achim; Zechner, Rudolf; Kershaw, Erin E.; Haemmerle, Guenter

    2015-01-01

    Background & Aims Adipose tissue (AT)-derived fatty acids (FAs) are utilized for hepatic triacylglycerol (TG) generation upon fasting. However, their potential impact as signaling molecules is not established. Herein we examined the role of exogenous AT-derived FAs in the regulation of hepatic gene expression by investigating mice with a defect in AT-derived FA supply to the liver. Methods Plasma FA levels, tissue TG hydrolytic activities and lipid content were determined in mice lacking the lipase co-activator comparative gene identification-58 (CGI-58) selectively in AT (CGI-58-ATko) applying standard protocols. Hepatic expression of lipases, FA oxidative genes, transcription factors, ER stress markers, hormones and cytokines were determined by qRT-PCR, Western blotting and ELISA. Results Impaired AT-derived FA supply upon fasting of CGI-58-ATko mice causes a marked defect in liver PPARα-signaling and nuclear CREBH translocation. This severely reduced the expression of respective target genes such as the ATGL inhibitor G0/G1 switch gene-2 (G0S2) and the endocrine metabolic regulator FGF21. These changes could be reversed by lipid administration and raising plasma FA levels. Impaired AT-lipolysis failed to induce hepatic G0S2 expression in fasted CGI-58-ATko mice leading to enhanced ATGL-mediated TG-breakdown strongly reducing hepatic TG deposition. On high fat diet, impaired AT-lipolysis counteracts hepatic TG accumulation and liver stress linked to improved systemic insulin sensitivity. Conclusions AT-derived FAs are a critical regulator of hepatic fasting gene expression required for the induction of G0S2-expression in the liver to control hepatic TG-breakdown. Interfering with AT-lipolysis or hepatic G0S2 expression represents an effective strategy for the treatment of hepatic steatosis. PMID:25733154

  10. Pyogenic liver abscess

    Science.gov (United States)

    Liver abscess; Bacterial liver abscess ... There are many possible causes of liver abscesses, including: Abdominal infection, such as appendicitis , diverticulitis , or a perforated bowel Infection in the blood Infection of the bile draining tubes ...

  11. Liver Fibrosis in HCV Monoinfected and HIV/HCV Coinfected Patients: Dysregulation of Matrix Metalloproteinases (MMPs and Their Tissue Inhibitors TIMPs and Effect of HCV Protease Inhibitors

    Directory of Open Access Journals (Sweden)

    Tiziana Latronico

    2016-03-01

    Full Text Available An imbalance between matrix metalloproteinases (MMPs and tissue inhibitors of metalloproteinases (TIMPs may contribute to liver fibrosis in patients with hepatitis C (HCV infection. We measured the circulating levels of different MMPs and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated the potential for anti-HCV therapy to modulate MMP and TIMP levels in HCV subjects. We analyzed 83 plasma samples from 16 HCV monoinfected patients undergoing dual or triple anti-HCV therapy, 15 HIV/HCV coinfected patients with undetectable HIV load, and 10 healthy donors (HD. Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, TIMP-1, and TIMP-2 were measured by a SearchLight Multiplex Immunoassay Kit. MMP-2 and MMP-9 were the highest expressed MMPs among all the analyzed samples and their levels significantly increased in HCV monoinfected and HIV/HCV coinfected subjects compared to HD. TIMP-1 levels were significantly higher in HCV and HIV/HCV subjects compared to HD and were correlated with liver stiffness. These findings raise the possibility of using circulating TIMP-1 as a non-invasive marker of liver fibrosis in HCV infection. A longitudinal study demonstrated that MMP-9 levels significantly decreased (40% reduction from baseline in patients receiving dual as well as triple direct-acting antivirals (DAA anti-HCV therapy, which had no effect on MMP-2, TIMP-1, and TIMP-2. As the dysregulation of MMP-2 and MMP-9 may reflect inflammatory processes in the liver, the decrease of MMP-9 following HCV protease inhibitor treatment suggests a positive effect on the reduction of liver inflammation.

  12. Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering

    DEFF Research Database (Denmark)

    Starokozhko, Viktoriia; Hemmingsen, Mette; Larsen, Layla

    2018-01-01

    Hepatic differentiation of human-induced pluripotent stem cells (hiPSCs) under flow conditions in a 3D scaffold is expected to be a major step forward for construction of bioartificial livers. The aims of this study were to induce hepatic differentiation of hiPSCs under perfusion conditions...... and to perform functional comparisons with fresh human precision-cut liver slices (hPCLS), an excellent benchmark for the human liver in vivo. The majority of the mRNA expression of CYP isoenzymes and transporters and the tested CYP activities, Phase II metabolism, and albumin, urea, and bile acid synthesis...... in the hiPSC-derived cells reached values that overlap those of hPCLS, which indicates a higher degree of hepatic differentiation than observed until now. Differentiation under flow compared with static conditions had a strong inducing effect on Phase II metabolism and suppressed AFP expression but resulted...

  13. Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering

    DEFF Research Database (Denmark)

    Starokozhko, Viktoriia; Hemmingsen, Mette; Larsen, Layla

    2018-01-01

    and to perform functional comparisons with fresh human precision-cut liver slices (hPCLS), an excellent benchmark for the human liver in vivo. The majority of the mRNA expression of CYP isoenzymes and transporters and the tested CYP activities, Phase II metabolism, and albumin, urea, and bile acid synthesis...... in the hiPSC-derived cells reached values that overlap those of hPCLS, which indicates a higher degree of hepatic differentiation than observed until now. Differentiation under flow compared with static conditions had a strong inducing effect on Phase II metabolism and suppressed AFP expression but resulted...... in slightly lower activity of some of the Phase I metabolism enzymes. Gene expression data indicate that hiPSCs differentiated into both hepatic and biliary directions. In conclusion, the hiPSC differentiated under flow conditions towards hepatocytes express a wide spectrum of liver functions at levels...

  14. Proteomics-Based Identification of the Molecular Signatures of Liver Tissues from Aged Rats following Eight Weeks of Medium-Intensity Exercise

    Directory of Open Access Journals (Sweden)

    Fanghui Li

    2016-01-01

    Full Text Available Physical activity has emerged as a powerful intervention that promotes healthy aging by maintaining the functional capacity of critical organ systems. Here, by combining functional and proteomics analyses, we examined how hepatic phenotypes might respond to exercise treatment in aged rats. 16 male aged (20 months old SD rats were divided into exercise and parallel control groups at random; the exercise group had 8 weeks of treadmill training with medium intensity. Whole protein samples of the liver were extracted from both groups and separated by two-dimensional gel electrophoresis. Alternatively objective protein spots with >2-fold difference in expression were selected for enzymological extraction and MS/MS identification. Results show increased activity of the manganese superoxide dismutase and elevated glutathione levels in the livers of exercise-treated animals, but malondialdehyde contents obviously decreased in the liver of the exercise group. Proteomics-based identification of differentially expressed proteins provided an integrated view of the metabolic adaptations occurring in the liver proteome during exercise, which significantly altered the expression of several proteins involved in key liver metabolic pathways including mitochondrial sulfur, glycolysis, methionine, and protein metabolism. These findings indicate that exercise may be beneficial to aged rats through modulation of hepatic protein expression profiles.

  15. 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

  16. Treating fructose-induced metabolic changes in mice with high-intensity interval training: insights in the liver, white adipose tissue, and skeletal muscle.

    Science.gov (United States)

    Motta, Victor F; Bargut, Thereza L; Aguila, Marcia B; Mandarim-de-Lacerda, Carlos A

    2017-10-01

    Fructose-rich caloric sweeteners induce adverse changes in the metabolism of humans. The study evaluated the effects of high-intensity interval training (HIIT) on a fructose feeding model, focusing on the liver, white adipose tissue (WAT), skeletal muscle, and their interplay. Male C57BL/6 mice were fed for 18 wk one of the following diets: control (C; 5% of total energy from fructose) or fructose (F; 55% of total energy from fructose). In the 10th week, for an additional 8-wk period, the groups were divided into nontrained (NT) or HIIT groups, totaling four groups: C-NT, C-HIIT, F-NT, and F-HIIT. At the end of the experiment, fructose consumption in the F-NT group led to a high systolic blood pressure, high plasma triglycerides, insulin resistance with glucose intolerance, and lower insulin sensitivity. We also observed liver steatosis, adipocyte hypertrophy, and diminished gene expressions of peroxisome proliferator-activated receptor-γ coactivator 1-α and fibronectin type III domain containing 5 (FNDC5; irisin) in this F-NT group. These results were accompanied by decreased gene expressions of nuclear respiratory factor 1 and mitochondrial transcription factor A (markers of mitochondrial biogenesis), and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1 (markers of β-oxidation). HIIT improved all of these data in the C-HIIT and F-HIIT groups. In conclusion, in mice fed a fructose diet, HIIT improved body mass, blood pressure, glucose metabolism, and plasma triglycerides. Liver, WAT, and skeletal muscle were positively modulated by HIIT, indicating HIIT as a coadjutant treatment for diseases affecting these tissues. NEW & NOTEWORTHY We investigated the effects of high-intensity interval training (HIIT) in mice fed a fructose-rich diet and the resulting severe negative effect on the liver, white adipose tissue (WAT), and skeletal muscle, which reduced the expression of fibronectin type III domain containing 5 (FNDC5, irisin) and

  17. Enlarged Liver

    Science.gov (United States)

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

  18. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain?liver axis

    OpenAIRE

    Yang, B; Ren, Q; Zhang, J-c; Chen, Q-X; Hashimoto, K

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of these proteins in psychiatric disorders is unknown. We sought to determine whether expression of these proteins is altered in the brain and peripheral tissues from patients with psychiatric disorders. We measured protein expression of proBDNF, mature BDNF...

  20. 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 ...

  1. The Carcinogenic Liver Fluke, Clonorchis sinensis: New Assembly, Reannotation and Analysis of the Genome and Characterization of Tissue Transcriptomes

    Science.gov (United States)

    Wang, Xiaoyun; Liu, Hailiang; Chen, Yangyi; Guo, Lei; Luo, Fang; Sun, Jiufeng; Mao, Qiang; Liang, Pei; Xie, Zhizhi; Zhou, Chenhui; Tian, Yanli; Lv, Xiaoli; Huang, Lisi; Zhou, Juanjuan; Hu, Yue; Li, Ran; Zhang, Fan; Lei, Huali; Li, Wenfang; Hu, Xuchu; Liang, Chi; Xu, Jin; Li, Xuerong; Yu, Xinbing

    2013-01-01

    Clonorchis sinensis (C. sinensis), an important food-borne parasite that inhabits the intrahepatic bile duct and causes clonorchiasis, is of interest to both the public health field and the scientific research community. To learn more about the migration, parasitism and pathogenesis of C. sinensis at the molecular level, the present study developed an upgraded genomic assembly and annotation by sequencing paired-end and mate-paired libraries. We also performed transcriptome sequence analyses on multiple C. sinensis tissues (sucker, muscle, ovary and testis). Genes encoding molecules involved in responses to stimuli and muscle-related development were abundantly expressed in the oral sucker. Compared with other species, genes encoding molecules that facilitate the recognition and transport of cholesterol were observed in high copy numbers in the genome and were highly expressed in the oral sucker. Genes encoding transporters for fatty acids, glucose, amino acids and oxygen were also highly expressed, along with other molecules involved in metabolizing these substrates. All genes involved in energy metabolism pathways, including the β-oxidation of fatty acids, the citrate cycle, oxidative phosphorylation, and fumarate reduction, were expressed in the adults. Finally, we also provide valuable insights into the mechanism underlying the process of pathogenesis by characterizing the secretome of C. sinensis. The characterization and elaborate analysis of the upgraded genome and the tissue transcriptomes not only form a detailed and fundamental C. sinensis resource but also provide novel insights into the physiology and pathogenesis of C. sinensis. We anticipate that this work will aid the development of innovative strategies for the prevention and control of clonorchiasis. PMID:23382950

  2. The carcinogenic liver fluke, Clonorchis sinensis: new assembly, reannotation and analysis of the genome and characterization of tissue transcriptomes.

    Directory of Open Access Journals (Sweden)

    Yan Huang

    Full Text Available Clonorchis sinensis (C. sinensis, an important food-borne parasite that inhabits the intrahepatic bile duct and causes clonorchiasis, is of interest to both the public health field and the scientific research community. To learn more about the migration, parasitism and pathogenesis of C. sinensis at the molecular level, the present study developed an upgraded genomic assembly and annotation by sequencing paired-end and mate-paired libraries. We also performed transcriptome sequence analyses on multiple C. sinensis tissues (sucker, muscle, ovary and testis. Genes encoding molecules involved in responses to stimuli and muscle-related development were abundantly expressed in the oral sucker. Compared with other species, genes encoding molecules that facilitate the recognition and transport of cholesterol were observed in high copy numbers in the genome and were highly expressed in the oral sucker. Genes encoding transporters for fatty acids, glucose, amino acids and oxygen were also highly expressed, along with other molecules involved in metabolizing these substrates. All genes involved in energy metabolism pathways, including the β-oxidation of fatty acids, the citrate cycle, oxidative phosphorylation, and fumarate reduction, were expressed in the adults. Finally, we also provide valuable insights into the mechanism underlying the process of pathogenesis by characterizing the secretome of C. sinensis. The characterization and elaborate analysis of the upgraded genome and the tissue transcriptomes not only form a detailed and fundamental C. sinensis resource but also provide novel insights into the physiology and pathogenesis of C. sinensis. We anticipate that this work will aid the development of innovative strategies for the prevention and control of clonorchiasis.

  3. Immunological detection of the type V collagen propeptide fragment, PVCP-1230, in connective tissue remodeling associated with liver fibrosis

    DEFF Research Database (Denmark)

    Vassiliadis, Efstathios; Veidal, Sanne Skovgård; Simonsen, Henrik

    2011-01-01

    AIM: Liver fibrosis involves excessive remodeling and deposition of fibrillar extracellular matrix (ECM) components, which leads to malfunction of the organ, causing significant morbidity and mortality. The aim of this study was to assess whether levels of a type V collagen fragment, the propepti...

  4. Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring.

    Directory of Open Access Journals (Sweden)

    María Teresa Ramírez-López

    Full Text Available Recent studies have linked gestational exposure to highly caloric diets with a disrupted endogenous cannabinoid system (ECS. In the present study, we have extended these studies by analyzing the impact of the exposure to a palatable diet during gestation and lactation on a the adult expression of endocannabinoid-related behaviors, b the metabolic profile of adult offspring and c the mRNA expression of the signaling machinery of the ECS in the hypothalamus, the liver and the adipose tissue of adult offspring of both sexes. Exposure to a palatable diet resulted in a sex-dimorphic and perinatal diet specific feeding behaviors, including the differential response to the inhibitory effects of the cannabinoid receptor inverse agonist AM251, b features of metabolic syndrome including increased adiposity, hyperleptinemia, hypertriglyceridemia and hypercholesterolemia and c tissue and sex-specific changes in the expression of both CB1 and CB2 receptors and in that of the endocannabinoid-degrading enzymes FAAH and MAGL, being the adipose tissue the most affected organ analyzed. Since the effects were observed in adult animals that were weaned while consuming a normal diet, the present results indicate that the ECS is one of the targets of maternal programming of the offspring energy expenditure. These results clearly indicate that the maternal diet has long-term effects on the development of pups through multiple alterations of signaling homeostatic pathways that include the ECS. The potential relevance of these alterations for the current obesity epidemic is discussed.

  5. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. 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

    International Nuclear Information System (INIS)

    Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

    2015-01-01

    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 57 Fe hyperfine parameters for normal and patient’s tissues were detected and related to small variations in the 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

  7. 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.

  8. 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.

  9. Health and economic benefits of reducing sugar intake in the USA, including effects via non-alcoholic fatty liver disease: a microsimulation model.

    Science.gov (United States)

    Vreman, Rick A; Goodell, Alex J; Rodriguez, Luis A; Porco, Travis C; Lustig, Robert H; Kahn, James G

    2017-08-03

    Excessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars. Using data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015-2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%. The model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%. The decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All

  10. Health and economic benefits of reducing sugar intake in the USA, including effects via non-alcoholic fatty liver disease: a microsimulation model

    Science.gov (United States)

    Vreman, Rick A; Goodell, Alex J; Rodriguez, Luis A; Porco, Travis C; Lustig, Robert H; Kahn, James G

    2017-01-01

    Objectives Excessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars. Methods Using data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015–2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%. Findings The model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%. Conclusions The decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits. PMID:28775179

  11. Metabolic turnover of pyridine nucleotides in ascites cells of sarcoma Sa 180 and in the liver tissue of rats before and after ionizing radiation

    International Nuclear Information System (INIS)

    Kunz, K.; Musil, J.

    1979-01-01

    The metabolic turnover of NADP + labeled with 14 C in the ribose moiety of their molecules was determined in the ascites cells of sarcoma Sa 180 and in the rat liver tissue. The half-lives of NAD + and NADP + in the Sa 180 sarcoma cells were 60 mins (NAD + ) and 90 mins (NADP + ), the corresponding values in the liver cells were 80 mins (NAD + ) and 120 mins (NADP + ). Experiments were conducted on animals aimed at ascertaining the time-dependent effect of ionizing radiation on the values of pooled NAD + and NADP + after 0.129 C/kg (500 R) and 0.387 C/kg (1500 R) whole-body irradiation, and the metabolic turnover of these nucleotides 5 h after whole-body irradiation with 0.387 C/kg (1500 R). Exposure to 0.129 C/kg (500 R) whole-body irradiation induced no apparent changes compared with the controls. Within 5 h of irradiation the whole-body dose of 0.387 C/kg (1500 R) produced changes in rat liver cells characterized by a reduction in the nucleotide biological half-lives (NAD + from 80 to 60 mins and NADP + from 120 to 70 mins). No such changes in the pyridine nucleotide turnover were detected in the Sa 180 ascites sarcoma cells. (author)

  12. Tissue explant coculture model of the hypothalamic-pituitary-gonadal-liver axis of the fathead minnow (Pimephales promelas) as a predictive tool for endocrine disruption.

    Science.gov (United States)

    Johnston, Theresa K; Perkins, Edward; Ferguson, Duncan C; Cropek, Donald M

    2016-10-01

    Endocrine-disrupting compounds (EDCs) can impact the reproductive system by interfering with the hypothalamic-pituitary-gonadal (HPG) axis. Although in vitro testing methods have been developed to screen chemicals for endocrine disruption, extrapolation of in vitro responses to in vivo action shows inconsistent accuracy. The authors describe a tissue coculture of the fathead minnow (Pimephales promelas) HPG axis and liver (HPG-L) as a tissue explant model that mimics in vivo results. Brain (hypothalamus), pituitary, gonad, and liver tissue explants from adult fish were examined for function both individually and in coculture to determine combinations and conditions that could replicate in vivo behavior. Only cocultures had the ability to respond to an EDC, trenbolone, similarly to in vivo studies, based on estradiol, testosterone, and vitellogenin production trends, where lower exposure doses suppressed hormone production but higher doses increased production, resulting in distinctive U-shaped curves. These data suggest that a coculture system with all components of the HPG-L axis can be used as a link between in vitro and in vivo studies to predict endocrine system disruption in whole organisms. This tissue-based HPG-L system acts as a flexible deconstructed version of the in vivo system for better control and examination of the minute changes in system operation and response on EDC exposure with options to isolate, interrogate, and recombine desired components. Environ Toxicol Chem 2016;35:2530-2541. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.

  13. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus

    OpenAIRE

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki

    2016-01-01

    The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between ...

  14. 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.

  15. Detection of tumor-like inclusions embedded within human liver tissue using a short-pulsed near-infrared laser beam: Parallel simulations with radiative transfer equation

    International Nuclear Information System (INIS)

    Asllanaj, Fatmir; Addoum, Ahmad; Contassot-Vivier, Sylvain

    2015-01-01

    An efficient solution to detect tumor-like inclusions embedded within a human liver tissue model is presented, using illumination by a short-pulsed laser beam. Light propagation was accurately solved using the time-dependent radiative transfer equation, with multithreaded parallel computing. A modified finite volume method based on unstructured grids and the fourth-order Runge–Kutta approach was employed to solve the equation in the (2-D/3-D) spatial and time domains. The normalization technique applied to the Henyey–Greenstein phase function was adopted to ensure numerical stability for values of the anisotropy factor that were close to unity. The presence of one or two circular/spherical inclusions was analyzed from the time and spatially resolved reflectance on the medium bounding surface. The results allowed a minimal size and a maximum distance for the detection of the inclusion to be highlighted. - Highlights: • We detect tumor-like inclusions embedded within a (2D/3D) human liver tissue model. • The technique is based on a short-pulsed near-infrared laser beam. • We solve the (2D/3D) time-dependent RTE, with multithreaded parallel computing. • The presence of one or two circular/spherical inclusions is analyzed. • The results allows a minimal size and a maximum distance for the detection

  16. Integrative systems analysis of diet-induced obesity identified a critical transition in the transcriptomes of the murine liver and epididymal white adipose tissue.

    Science.gov (United States)

    Kim, J; Kwon, E-Y; Park, S; Kim, J-R; Choi, S-W; Choi, M-S; Kim, S-J

    2016-02-01

    It is well known that high-fat diet (HFD) can cause immune system-related pathological alterations after a significant body weight gain. The mechanisms of the delayed pathological alterations during the development of diet-induced obesity (DIO) are not fully understood. To elucidate the mechanisms underlying DIO development, we analyzed time-course microarray data obtained from a previous study. First, differentially expressed genes (DEGs) were identified at each time point by comparing the hepatic transcriptome of mice fed HFD with that of mice fed normal diet. Next, we clustered the union of DEGs and identified annotations related to each cluster. Finally, we constructed an 'integrated obesity-associated gene regulatory network (GRN) in murine liver'. We analyzed the epididymal white adipose tissue (eWAT) transcriptome usig the same procedure. Based on time-course microarray data, we found that the genes associated with immune responses were upregulated with an oscillating expression pattern between weeks 2 and 8, relatively downregulated between weeks 12 and 16, and eventually upregulated after week 20 in the liver of the mice fed HFD. The genes associated with immune responses were also upregulated at late stage, in the eWAT of the mice fed HFD. These results suggested that a critical transition occurred in the immune system-related transcriptomes of the liver and eWAT around week 16 of the DIO development, and this may be associated with the delayed pathological alterations. The GRN analysis suggested that Maff may be a key transcription factor for the immune system-related critical transition thatoccurred at week 16. We found that transcription factors associated with immune responses were centrally located in the integrated obesity-associated GRN in the liver. In this study, systems analysis identified regulatory network modules underlying the delayed immune system-related pathological changes during the development of DIO and could suggest possible

  17. [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.

  18. 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 male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P brain, liver, and kidney (all P male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P female mice and in kidney (male and female mice) but decreased 55% in brain (P 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. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  19. Liver regenerative medicine: advances and challenges.

    Science.gov (United States)

    Chistiakov, Dimitry A

    2012-01-01

    Liver transplantation is the standard care for many end-stage liver diseases. However, donor organs are scarce and some people succumb to liver failure before a donor is found. Liver regenerative medicine is a special interdisciplinary field of medicine focused on the development of new therapies incorporating stem cells, gene therapy and engineered tissues in order to repair or replace the damaged organ. In this review we consider the emerging progress achieved in the hepatic regenerative medicine within the last decade. The review starts with the characterization of liver organogenesis, fetal and adult stem/progenitor cells. Then, applications of primary hepatocytes, embryonic and adult (mesenchymal, hematopoietic and induced pluripotent) stem cells in cell therapy of liver diseases are considered. Current advances and challenges in producing mature hepatocytes from stem/progenitor cells are discussed. A section about hepatic tissue engineering includes consideration of synthetic and natural biomaterials in engineering scaffolds, strategies and achievements in the development of 3D bioactive matrices and 3D hepatocyte cultures, liver microengineering, generating bioartificial liver and prospects for fabrication of the bioengineered liver. Copyright © 2012 S. Karger AG, Basel.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Heiko eMühl

    2016-05-01

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

  2. Interface-Targeting Strategy Enables Two-Photon Fluorescent Lipid Droplet Probes for High-Fidelity Imaging of Turbid Tissues and Detecting Fatty Liver.

    Science.gov (United States)

    Guo, Lifang; Tian, Minggang; Feng, Ruiqing; Zhang, Ge; Zhang, Ruoyao; Li, Xuechen; Liu, Zhiqiang; He, Xiuquan; Sun, Jing Zhi; Yu, Xiaoqiang

    2018-04-04

    Lipid droplets (LDs) with unique interfacial architecture not only play crucial roles in protecting a cell from lipotoxicity and lipoapoptosis but also closely relate with many diseases such as fatty liver and diabetes. Thus, as one of the important applied biomaterials, fluorescent probes with ultrahigh selectivity for in situ and high-fidelity imaging of LDs in living cells and tissues are critical to elucidate relevant physiological and pathological events as well as detect related diseases. However, available probes only utilizing LDs' waterless neutral cores but ignoring the unique phospholipid monolayer interfaces exhibit low selectivity. They cannot differentiate neutral cores of LDs from intracellular other lipophilic microenvironments, which results in extensively cloud-like background noise and severely limited their bioapplications. Herein, to design LD probes with ultrahigh selectivity, the exceptional interfacial architecture of LDs is considered adequately and thus an interface-targeting strategy is proposed for the first time. According to the novel strategy, we have developed two amphipathic fluorescent probes (N-Cy and N-Py) by introducing different cations into a lipophilic fluorophore (nitrobenzoxadiazole (NBD)). Consequently, their cationic moiety precisely locates the interfaces through electrostatic interaction and simultaneously NBD entirely embeds into the waterless core via hydrophobic interaction. Thus, high-fidelity and background-free fluorescence imaging of LDs are expectably realized in living cells in situ. Moreover, LDs in turbid tissues like skeletal muscle slices have been clearly imaged (up to 82 μm depth) by a two-photon microscope. Importantly, using N-Cy, we not only intuitively monitored the variations of LDs in number, size, and morphology but also clearly revealed their abnormity in hepatic tissues resulting from fatty liver. Therefore, these unique probes provide excellent imaging tools for elucidating LD

  3. 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.

  4. Bimodal electric tissue ablation (BETA) - in-vivo evaluation of the effect of applying direct current before and during radiofrequency ablation of porcine liver

    International Nuclear Information System (INIS)

    Cockburn, J.F.; Maddern, G.J.; Wemyss-Holden, S.A.

    2007-01-01

    Aim: To examine the effect of applying increasing amounts of direct current (DC) before and during alternating current radiofrequency ablation of porcine liver. Materials and methods: Using a Radiotherapeutics RF3000 generator, a 9 V AC/DC transformer and a 16 G plain aluminium tube as an electrode, a control group of 24 porcine hepatic radiofrequency ablation zones was compared with 24 zones created using a bimodal electric tissue ablation (BETA) technique in three pigs. All ablations were terminated when tissue impedance rose to greater than 999 Ω or radiofrequency energy input fell below 5 W on three successive measurements taken at 1 min intervals. BETA ablations were performed in two phases: an initial phase of variable duration DC followed by a second phase during which standard radiofrequency ablation was applied simultaneously with DC. During this second phase, radiofrequency power input was regulated by the feedback circuitry of the RF3000 generator according to changes in tissue impedance. The diameters (mm) of each ablation zone were measured by two observers in two planes perpendicular to the plane of needle insertion. The mean short axis diameter of each ablation zone was subjected to statistical analysis. Results: With increased duration of prior application of DC, there was a progressive increase in the diameter of the ablation zone (p < 0.001). This effect increased sharply up to 300 s of pre-treatment after which a further increase in diameter occurred, but at a much lesser rate. A maximum ablation zone diameter of 32 mm was produced (control diameters 10-13 mm). Conclusion: Applying a 9 V DC to porcine liver in vivo, and continuing this DC application during subsequent radiofrequency ablation, results in larger ablation zone diameters compared with radiofrequency ablation alone

  5. A method to fabricate solid free form scaffolds for liver tissue engineering by using 3D printing

    OpenAIRE

    Mallikarjunaiah, Chetan Aradhya

    2015-01-01

    In recent years, there has been a great demand for the development of bio-artificial organs/tissues in the field of organ transplantation and in-vitro toxicological drug screening (L. G. Griffith & Swartz, 2006). Engineering of functional tissue/organs by controlling the cells microenvironment to resemble in vivo situation is of central importance. This has led to the evolution of various techniques for controlling the cellular microenvironment to facilitate cell proliferation, organization a...

  6. Liver scintigraphy

    International Nuclear Information System (INIS)

    Tateno, Yukio

    1996-01-01

    Liver scintigraphy can be classified into 3 major categories according to the properties of the radiopharmaceuticals used, i.e., methods using radiopharmaceuticals which are (1) incorporated by hepatocytes, (2) taken up by reticulo endothelial cells, and (3) distributed in the blood pool of the liver. Of these three categories, the liver scintigraphy of the present research falls into category 2. Radiopharmaceuticals which are taken up by endothelial cells include 198 Au colloids and 99m Tc-labelled colloids. Liver scintigraphy takes advantage of the property by which colloidal microparticles are phagocytosed by Kupffer cells, and reflect the distribution of endothelial cells and the intensity of their phagocytic capacity. This examination is indicated in the following situations: (i) when you suspect a localized intrahepatic lesion (tumour, abscess, cyst, etc.), (ii) when you want to follow the course of therapy of a localized lesion, (iii) when you suspect liver cirrhosis, (iv) when you want to know the severity of liver cirrhosis or hepatitis, (v) when there is hepatomegaly and you want to determine the morphology of the liver, (vi) differential diagnosis of upper abdominal masses, and (vii) when there are abnormalities of the right diaphragm and you want to know their relation to the liver

  7. An optimized method for fatty acid analysis, including quantification of trans fatty acids, in human adipose tissue by gas-liquid chromatography

    DEFF Research Database (Denmark)

    Bysted, Anette; Cold, S; Hølmer, Gunhild Kofoed

    1999-01-01

    Considering the need for a quick direct method for measurement of the fatty acid composition including trans isomers ofhuman adipose tissue we have developed a procedure using gas-liquid chromatography (GLC) alone, which is thussuitable for validation of fatty acid status in epidemiological studies...... for 25 min, and finally raised at 25 degrees C/min to 225 degrees C. The trans and cis isomers of18:1 were well separated from each other, as shown by silver-ion thin-layer chromatography. Verification by standardsshowed that the trans 18:1 isomers with a double bond in position 12 or lower were...

  8. Quetiapine mitigates the ethanol-induced oxidative stress in brain tissue, but not in the liver, of the rat

    Directory of Open Access Journals (Sweden)

    Han JH

    2015-06-01

    Full Text Available Jin-hong Han,1,2 Hong-zhao Tian,2 Yang-yang Lian,1 Yi Yu,1 Cheng-biao Lu,2 Xin-min Li,3 Rui-ling Zhang,1 Haiyun Xu4 1The Second Affiliated Hospital of Xinxiang Medical University, 2School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 3Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; 4The Mental Health Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Quetiapine, an atypical antipsychotic, has been employed to treat alcoholic patients with comorbid psychopathology. It was shown to scavenge hydroxyl radicals and to protect cultured cells from noxious effects of oxidative stress, a pathophysiological mechanism involved in the toxicity of alcohol. This study compared the redox status of the liver and the brain regions of prefrontal cortex, hippocampus, and cerebellum of rats treated with or without ethanol and quetiapine. Ethanol administration for 1 week induced oxidative stress in the liver and decreased the activity of glutathione peroxidase and total antioxidant capacity (TAC there. Coadministration of quetiapine did not protect glutathione peroxidase and TAC in the liver against the noxious effect of ethanol, thus was unable to mitigate the ethanol-induced oxidative stress there. The ethanol-induced alteration in the redox status in the prefrontal cortex is mild, whereas the hippocampus and cerebellum are more susceptible to ethanol intoxication. For all the examined brain regions, coadministration of quetiapine exerted effective protection on the antioxidants catalase and total superoxide dismutase and on the TAC, thus completely blocking the ethanol-induced oxidative stress in these brain regions. These protective effects may explain the clinical observations that quetiapine reduced psychiatric symptoms intensity and maintained a good level of tolerability in chronic alcoholism with

  9. Real-time monitoring of radiofrequency ablation of liver tumors using thermal-dose calculation by MR temperature imaging: initial results in nine patients, including follow-up

    International Nuclear Information System (INIS)

    Lepetit-Coiffe, Matthieu; Quesson, Bruno; Moonen, Chrit T.W.; Laumonier, Herve; Trillaud, Herve; Seror, Olivier; Sesay, Musa-Bahazid; Grenier, Nicolas

    2010-01-01

    To assess the practical feasibility and effectiveness of real-time magnetic resonance (MR) temperature monitoring for the radiofrequency (RF) ablation of liver tumours in a clinical setting, nine patients (aged 49-87 years, five men and four women) with one malignant tumour (14-50 mm, eight hepatocellular carcinomas and one colorectal metastasis), were treated by 12-min RF ablation using a 1.5-T closed magnet for real-time temperature monitoring. The clinical monopolar RF device was filtered at 64 MHz to avoid electromagnetic interference. Real-time computation of thermal-dose (TD) maps, based on Sapareto and Dewey's equation, was studied to determine its ability to provide a clear end-point of the RF procedure. Absence of local recurrence on follow-up MR images obtained 45 days after the RF ablation was used to assess the apoptotic and necrotic prediction obtained by real-time TD maps. Seven out of nine tumours were completely ablated according to the real-time TD maps. Compared with 45-day follow-up MR images, TD maps accurately predicted two primary treatment failures, but were not relevant in the later progression of one case of secondary local tumour. The real-time TD concept is a feasible and promising monitoring method for the RF ablation of liver tumours. (orig.)

  10. Real-time monitoring of radiofrequency ablation of liver tumors using thermal-dose calculation by MR temperature imaging: initial results in nine patients, including follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Lepetit-Coiffe, Matthieu; Quesson, Bruno; Moonen, Chrit T.W. [Universite Victor Segalen Bordeaux 2, Laboratoire Imagerie Moleculaire et Fonctionnelle: de la physiologie a la therapie CNRS UMR 5231, Bordeaux Cedex (France); Laumonier, Herve; Trillaud, Herve [Universite Victor Segalen Bordeaux 2, Laboratoire Imagerie Moleculaire et Fonctionnelle: de la physiologie a la therapie CNRS UMR 5231, Bordeaux Cedex (France); Service de Radiologie, Hopital Saint-Andre, CHU Bordeaux, Bordeaux (France); Seror, Olivier [Universite Victor Segalen Bordeaux 2, Laboratoire Imagerie Moleculaire et Fonctionnelle: de la physiologie a la therapie CNRS UMR 5231, Bordeaux Cedex (France); Service de Radiologie, Hopital Jean Verdier, Bondy (France); Sesay, Musa-Bahazid [Service d' Anesthesie Reanimation III, Hopital Pellegrin, CHU Bordeaux, Bordeaux (France); Grenier, Nicolas [Universite Victor Segalen Bordeaux 2, Laboratoire Imagerie Moleculaire et Fonctionnelle: de la physiologie a la therapie CNRS UMR 5231, Bordeaux Cedex (France); Service d' Imagerie Diagnostique et Therapeutique de l' Adulte, Hopital Pellegrin, CHU Bordeaux, Bordeaux (France)

    2010-01-15

    To assess the practical feasibility and effectiveness of real-time magnetic resonance (MR) temperature monitoring for the radiofrequency (RF) ablation of liver tumours in a clinical setting, nine patients (aged 49-87 years, five men and four women) with one malignant tumour (14-50 mm, eight hepatocellular carcinomas and one colorectal metastasis), were treated by 12-min RF ablation using a 1.5-T closed magnet for real-time temperature monitoring. The clinical monopolar RF device was filtered at 64 MHz to avoid electromagnetic interference. Real-time computation of thermal-dose (TD) maps, based on Sapareto and Dewey's equation, was studied to determine its ability to provide a clear end-point of the RF procedure. Absence of local recurrence on follow-up MR images obtained 45 days after the RF ablation was used to assess the apoptotic and necrotic prediction obtained by real-time TD maps. Seven out of nine tumours were completely ablated according to the real-time TD maps. Compared with 45-day follow-up MR images, TD maps accurately predicted two primary treatment failures, but were not relevant in the later progression of one case of secondary local tumour. The real-time TD concept is a feasible and promising monitoring method for the RF ablation of liver tumours. (orig.)

  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. Effect of acetyl salicylic acid (aspirin) and Prostaglandins on thyroid tissue and carbohydrate metabolism in liver of male albino rats

    International Nuclear Information System (INIS)

    Balasubramanian, A.; Ramakrishnan, S.

    1979-01-01

    Aspirin, both in chronic and acute doses, led to a considerable decrease in percentage uptake of labelled iodine (Na 131 I) and serum protein-bound iodine by the thyroid gland whereas prostaglandins (PGs) did not exhibit any significant effect on both the parameters. Simultaneous administration of aspirin and PGs caused a significant decrease in the two parameters, and on withdrawal of aspirin from the diet the two parameters were restored to normal levels, thus suggesting that the effect of aspirin on thyroid is direct and reversible. Aspirin, both in acute and chronic doses, effected decrease in glycogen levels, in vivo and in vitro incorporation of [U- 14 C] glucose into glycogen, and glycogen synthetase activity in the liver of both fed, and fasting, rat. Prostaglandins, on the other hand, resulted in a significant increase in the three parameters, thus enhancing the rate of liver glycogenesis. Normal levels were restored when both aspirin and PGs were given together. Withdrawal of aspirin also restored normal hepatic glycogenesis. Significant reduction in the activities of hepatic gluconeogenic enzymes, viz. glucose 6-phosphatase, fructose 1,6-diphosphatase, phosphopyruvate carboxylase, pyruvate carboxylase, aspartate aminotransferase and glutamate dehydrogenase was observed due to chronic and acute administration of aspirin and PGs were devoid of any significant effect on gluconeogenic enzymes, thus ruling out the mediation of PGs. (auth.)

  13. Effect of acetyl salicylic acid (aspirin) and Prostaglandins on thyroid tissue and carbohydrate metabolism in liver of male albino rats

    Energy Technology Data Exchange (ETDEWEB)

    Balasubramanian, A; Ramakrishnan, S [Jawaharlal Inst. of Postgraduate Medical Education and Research, Pondicherry (India)

    1979-04-01

    Aspirin, both in chronic and acute doses, led to a considerable decrease in percentage uptake of labelled iodine (Na/sup 131/I) and serum protein-bound iodine by the thyroid gland whereas prostaglandins (PGs) did not exhibit any significant effect on both the parameters. Simultaneous administration of aspirin and PGs caused a significant decrease in the two parameters, and on withdrawal of aspirin from the diet the two parameters were restored to normal levels, thus suggesting that the effect of aspirin on thyroid is direct and reversible. Aspirin, both in acute and chronic doses, effected decrease in glycogen levels, in vivo and in vitro incorporation of (U-/sup 14/C) glucose into glycogen, and glycogen synthetase activity in the liver of both fed, and fasting, rat. Prostaglandins, on the other hand, resulted in a significant increase in the three parameters, thus enhancing the rate of liver glycogenesis. Normal levels were restored when both aspirin and PGs were given together. Withdrawal of aspirin also restored normal hepatic glycogenesis. Significant reduction in the activities of hepatic gluconeogenic enzymes, viz. glucose 6-phosphatase, fructose 1,6-diphosphatase, phosphopyruvate carboxylase, pyruvate carboxylase, aspartate aminotransferase and glutamate dehydrogenase was observed due to chronic and acute administration of aspirin and PGs were devoid of any significant effect on gluconeogenic enzymes, thus ruling out the mediation of PGs.

  14. A survey of spontaneous occurrence of ochratoxin A residues in chicken tissues and concurrence with histopathological changes in liver and kidneys

    Science.gov (United States)

    Milicevic, Dragan; Jovanovic, Milijan; Matekalosverak, Vesna; Radicevic, Tatjana; Petrovic, Milan M.; Lilic, Slobodan

    2011-01-01

    Toxicological and histopathological investigations of tissues of commercially slaughtered chickens were carried out to provide a preliminary evaluation of the incidence of occurrence of ochratoxin A (OTA) in chicken sold in Serbian retail market. In addition, the etiology of nephropathies of these chickens was elucidated. The majority of these tissue samples were not found to contain measurable amounts of OTA. Moreover, the OTA levels found in analyzed tissues were generally low and there was no positive correlation between the presence of OTA and the frequency of histopathological changes. Histopathological changes such as degenerative changes in the kidneys and liver differed from the classical description of the mycotoxic nephropathy, indicating that the chicken nephropathy observed in Serbia may have a multitoxic etiology with possible synergistic effect between microorganisms and natural toxins, usually present in low concentrations. The low OTA results also suggested that chicken meat available in the retail market in Serbia are unlikely to pose any significant adverse health risk to the consumers with respect to OTA toxicity.

  15. Computed tomographic and ultrasound appearances of focal spared areas in fatty infiltration of the liver

    International Nuclear Information System (INIS)

    McKenzie, A.; Gill, G.; Hennessy, O.; Pryde, D.

    1991-01-01

    Computed tomography (CT) and utrasound (US) appearances of diffuse and focal fatty infiltration of the liver (FIL) are well recognized as pseudo tumours of the liver. Characteristic appearances of fat free areas in FIL which help differentiate these areas from other focal liver lesions include location in the medical segment of the left lobe of the liver, absence of mass effect on surrounding vessels and liver tissue, and presence of typical changes of FIL elsewhere in the liver on CT or US examination. 16 refs., 1 tab., 5 figs

  16. Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running.

    Science.gov (United States)

    Holland, Angelia Maleah; Kephart, Wesley C; Mumford, Petey W; Mobley, Christopher Brooks; Lowery, Ryan P; Shake, Joshua J; Patel, Romil K; Healy, James C; McCullough, Danielle J; Kluess, Heidi A; Huggins, Kevin W; Kavazis, Andreas N; Wilson, Jacob M; Roberts, Michael D

    2016-08-01

    We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P diets [total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum β-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss. Copyright © 2016 the American Physiological Society.

  17. Risk Factors for Pressure Ulcers Including Suspected Deep Tissue Injury in Nursing Home Facility Residents: Analysis of National Minimum Data Set 3.0.

    Science.gov (United States)

    Ahn, Hyochol; Cowan, Linda; Garvan, Cynthia; Lyon, Debra; Stechmiller, Joyce

    2016-04-01

    To provide information on risk factors associated with pressure ulcers (PrUs), including suspected deep tissue injury (sDTI), in nursing home residents in the United States. This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Examine the literature related to risk factors for the development of PrUs.2. Compare risk factors associated with the prevalence of PrUs and sDTI from the revised Minimum Data Set 3.0 2012 using a modified Defloor's conceptual model of PrUs as a theoretical framework. This study aims to characterize and compare risk factors associated with pressure ulcers (PrUs), including suspected deep tissue injury (sDTI), in nursing home (NH) residents in the United States. Secondary analysis of the 2012 Minimum Data Set (MDS 3.0). Medicare- or Medicaid-certified NHs in the United States. Nursing home residents (n = 2,936,146) 18 years or older with complete PrU data, who received comprehensive assessments from January to December 2012. Pressure ulcer by stage was the outcome variable. Explanatory variables (age, gender, race and ethnicity, body mass index, skin integrity, system failure, disease, infection, mobility, and cognition) from the MDS 3.0 were aligned with the 4 elements of Defloor's conceptual model: compressive forces, shearing forces, tissue tolerance for pressure, and tissue tolerance for oxygen. Of 2,936,146 NH residents who had complete data for PrU, 89.9% had no PrU; 8.4% had a Stage 2, 3, or 4 or unstagable PrU; and 1.7% had an sDTI. The MDS variables corresponding to the 4 elements of Defloor's model were significantly predictive of both PrU and sDTI. Black residents had the highest risk of any-stage PrU, and Hispanic residents had the highest risk of sDTI. Skin integrity, system failure, infection, and disease risk factors had larger effect sizes for sDTI than for other PrU stages

  18. Energy Metabolism in the Liver

    Science.gov (United States)

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

  19. Maternal sodium butyrate supplement elevates the lipolysis in adipose tissue and leads to lipid accumulation in offspring liver of weaning-age rats.

    Science.gov (United States)

    Zhou, Jiabin; Gao, Shixing; Chen, Jinglong; Zhao, Ruqian; Yang, Xiaojing

    2016-07-22

    Sodium butyrate (SB) is reported to regulate lipid metabolism in mammals, and the relationship between maternal nutrition and offspring growth has drawn much attention in the last several years. To elucidate the effects of maternal dietary SB supplementation on hepatic lipid metabolism in weaning rats, we fed 16 primiparous purebred female SD rats either a chow-diet or a 1 % sodium butyrate diet throughout pregnancy and lactation. At weaning age, samples of the maternal subcutaneous adipose tissue and offspring liver were taken. The serum indexes and expressions of proteins related to lipid metabolism were detected in the mother and offspring, respectively. The results showed that the maternal SB supplement increased the concentration of non-esterified fatty acid (NEFA) in the maternal and offspring serum (P pregnancy and lactation increased the hepatic total cholesterol (Tch) content (P pregnancy and the lactation period promotes maternal fat mobilization, which may result in fatty acid uptake and lipid accumulation in the liver of the offspring.

  20. Effects of iron chloride/zeolıte on G6PD of rainbow trout (Oncorhynchus mykiss)'s liver tissue

    Science.gov (United States)

    Alak, Gonca; Uçar, Arzu; Parlak, Veysel; Kocaman, Esat Mahmut; Atamanalp, Muhammed

    2016-04-01

    Aquatic ecosystems have been negatively affected by the contamination of ground and surface waters as a result of various activities. Due to the ferrous chloride (FeCl2), which is used as the reducing agent for the organic synthesis reactions in the contamination of water column and sediment, iron salts may be very toxic for some aquatic organisms. In order to minimize these effects, natural products such as zeolite have been widely used in recently years. For this reason, rainbow trout were exposed to FeCl2 and/or zeolite ((FeCl2 (0.002 mg/l)(A), FeCl2+zeolite (0.002 mg/l+1 gr/l) (B), zeolite (1 gr/l) (C) and control (without FeCl2 and/or zeolite (D)). for 28 days and their oxidative stress responses were investigated. At the end of the treatment period, Glucose-6- phosphate dehydrogenase (G6PD) activity was determined in the samples taken from livers. G6PD values for liver tissues were found statistically important in the control and treatment groups (p<0.01).

  1. Study of expression of genes cIAP and cMET, in liver tissue with and without neoplasia of Rattus norvegicus

    International Nuclear Information System (INIS)

    Coto Valverde, Daniel Esteban

    2010-01-01

    The expression levels of cIAP genes and cMET were determined in liver tissues with and without neoplasm of the organism Rattus norvegicus, for prevention, diagnosis and treatment of hepatocellular carcinoma. The technique of reaction Polymerase Chain in real time (qPCR), is used to obtain the expression, of both genes cIAP and cMET, and this has decreased in neoplastic samples compared to samples not affected. The expression of these genes has been analyzed in samples with neoplastic formations, but treated with an anti-tumor agent. The expression has presented an increase of the cMET gene, unlike the cIAP gene, which has decreased its expression. Perform statistical analysis has been impossible because the number of samples used has been reduced. The results obtained differ with those expected theoretically. (author) [es

  2. Histopathological changes in the liver and kidney tissues of marsh frog (Pelophylax ridibundus induced by the action of Talstar 10EC insecticide

    Directory of Open Access Journals (Sweden)

    Alina PĂUNESCU

    2012-05-01

    Full Text Available Histopathological biomarkers of toxicity in frog organs are a useful indicator of environmental pollution. The frogs were experimentally exposed to sub-lethal concentrations (0.5mg bifenthrin/g of body weight of Talstar 10EC for 3 weeks. The present study proves its toxic potential in terms of the damages in liver and kidney level. Tissues were normal in the control group. Hepatic lesions in frog exposed to bifenthrin were characterized by vacuolation of hepatocytes and nuclear pycnosis, perisinusoidal and periportal fibrosis, dilatation of Disse space and sinusoid capillaries, presence of cellular infiltrates. Kidney lesions consisted of dilation of Bowman’s space, tubular necrosis, and epithelial cells shows pycnotic nuclei, discrete degree of interstitial edema.

  3. Chronic alcohol exposure disturbs lipid homeostasis at the adipose tissue-liver axis in mice: analysis of triacylglycerols using high-resolution mass spectrometry in combination with in vivo metabolite deuterium labeling.

    Directory of Open Access Journals (Sweden)

    Xiaoli Wei

    Full Text Available A method of employing high-resolution mass spectrometry in combination with in vivo metabolite deuterium labeling was developed in this study to investigate the effects of alcohol exposure on lipid homeostasis at the white adipose tissue (WAT-liver axis in a mouse model of alcoholic fatty liver. In order to differentiate the liver lipids synthesized from the fatty acids that were transported back from adipose tissue and the lipids synthesized from other sources of fatty acids, a two-stage mouse feeding experiment was performed to incorporate deuterium into metabolites. Hepatic lipids extracted from mouse liver, epididymal white adipose tissue (eWAT and subcutaneous white adipose tissue (sWAT were analyzed. It was found that 13 and 10 triacylglycerols (TGs incorporated with a certain number of deuterium were significantly increased in alcohol induced fatty liver at two and four weeks of alcohol feeding periods, respectively. The concentration changes of these TGs ranged from 1.7 to 6.3-fold increase. A total of 14 deuterated TGs were significantly decreased in both eWAT and sWAT at the two and four weeks and the fold-change ranged from 0.19 to 0.77. The increase of deuterium incorporated TGs in alcohol-induced fatty liver and their decrease in both eWAT and sWAT indicate that alcohol exposure induces hepatic influx of fatty acids which are released from WATs. The results of time course analysis further indicate a mechanistic link between adipose fat loss and hepatic fat gain in alcoholic fatty liver.

  4. Magnetic resonance elastography is as accurate as liver biopsy for liver fibrosis staging.

    Science.gov (United States)

    Morisaka, Hiroyuki; Motosugi, Utaroh; Ichikawa, Shintaro; Nakazawa, Tadao; Kondo, Tetsuo; Funayama, Satoshi; Matsuda, Masanori; Ichikawa, Tomoaki; Onishi, Hiroshi

    2018-05-01

    Liver MR elastography (MRE) is available for the noninvasive assessment of liver fibrosis; however, no previous studies have compared the diagnostic ability of MRE with that of liver biopsy. To compare the diagnostic accuracy of liver fibrosis staging between MRE-based methods and liver biopsy using the resected liver specimens as the reference standard. A retrospective study at a single institution. In all, 200 patients who underwent preoperative MRE and subsequent surgical liver resection were included in this study. Data from 80 patients were used to estimate cutoff and distributions of liver stiffness values measured by MRE for each liver fibrosis stage (F0-F4, METAVIR system). In the remaining 120 patients, liver biopsy specimens were obtained from the resected liver tissues using a standard biopsy needle. 2D liver MRE with gradient-echo based sequence on a 1.5 or 3T scanner was used. Two radiologists independently measured the liver stiffness value on MRE and two types of MRE-based methods (threshold and Bayesian prediction method) were applied. Two pathologists evaluated all biopsy samples independently to stage liver fibrosis. Surgically resected whole tissue specimens were used as the reference standard. The accuracy for liver fibrosis staging was compared between liver biopsy and MRE-based methods with a modified McNemar's test. Accurate fibrosis staging was achieved in 53.3% (64/120) and 59.1% (71/120) of patients using MRE with threshold and Bayesian methods, respectively, and in 51.6% (62/120) with liver biopsy. Accuracies of MRE-based methods for diagnoses of ≥F2 (90-91% [108-9/120]), ≥F3 (79-81% [95-97/120]), and F4 (82-85% [98-102/120]) were statistically equivalent to those of liver biopsy (≥F2, 79% [95/120], P ≤ 0.01; ≥F3, 88% [105/120], P ≤ 0.006; and F4, 82% [99/120], P ≤ 0.017). MRE can be an alternative to liver biopsy for fibrosis staging. 3. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1268-1275. © 2017

  5. Liver transplant for cholestatic liver diseases.

    Science.gov (United States)

    Carrion, Andres F; Bhamidimarri, Kalyan Ram

    2013-05-01

    Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Characteristics of liver tissue for attenuate the gamma radiation; Caracteristicas del tejido hepatico para atenuar la radiacion gamma

    Energy Technology Data Exchange (ETDEWEB)

    Arcos P, A.; Rodriguez N, S.; Pinedo S, A.; Amador V, P.; Chacon R, A.; Vega C, H.R. [Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico)

    2005-07-01

    It was determined the lineal attenuation coefficient of hepatic tissue before gamma radiation of a source of {sup 137} Cs. When exposing organic material before X or gamma radiation fields, part of the energy of the photons is absorbed by the material, while another part crosses it without producing any effect. The quantity of energy that is absorbed is a measure of the dose that receives the material. The three main mechanisms by means of which the gamma rays interacting with the matter are: The Photoelectric Effect, the Compton dispersion and the Even production; the sum of these three processes is translated in the attenuation coefficient of the radiation. In this work we have used hepatic tissue of bovine, as substitute of the human hepatic tissue, and we have measured the lineal attenuation coefficient for photons of 0.662 MeV. Through a series of calculations we have determined the lineal attenuation coefficient for photons from 10{sup -3} to 10{sup -5} MeV and the measured coefficient was compared with the one calculated. (Author)

  7. Endothelial dysfunction in high fructose containing diet fed rats: Increased nitric oxide and decreased endothelin-1 levels in liver tissue

    Directory of Open Access Journals (Sweden)

    Zeki Arı

    2010-09-01

    Full Text Available Objectives: Dietary high fructose consumption which is closely associated with endothelial dysfunction via insulin re-sistance has recently increased in developed countries. Insulin resistance has a promoter effect on many metabolic disorders such as syndrome X, polycystic ovary syndrome, Type 2 diabetes mellitus etc. Our aim in this study is to understand the impact of increased fructose intake on metabolisms of glucose, insulin and endothelial dysfunction by measuring nitric oxide (NO and endothelin-1 (ET-1 levels in hepatic tissue which is crucial in fructose metabolism.Materials and Methods: We designed an animal study to understand increased fructose intake on hepatic endothe-lium. Twenty adult male albino rats were divided into two groups; the study group (group 1, n=10 received isocaloric fructose enriched diet (fructose-fed rats, containing 18.3% protein, 60.3% fructose and 5.2% fat while the control group received purified regular chow (group 2, n=10 for 2 weeks. After feeding period, blood and hepatic tissue samples were collected and glucose, insulin, NO and ET-1 levels were analysed.Results: We found increased fasting glucose and insulin levels and impaired glucose tolerance in fructose fed rats. Higher NO and lower ET–1 levels were also detected in hepatic tissue samples of the group 1.Conclusion: Increased fructose consumption has deleterious effects on glucose tolerance, insulin resistance and may cause to endothelial dysfunction.

  8. Insulin-induced inhibition of gluconeogenesis genes, including glutamic pyruvic transaminase 2, is associated with reduced histone acetylation in a human liver cell line.

    Science.gov (United States)

    Honma, Kazue; Kamikubo, Michiko; Mochizuki, Kazuki; Goda, Toshinao

    2017-06-01

    Hepatic glutamic pyruvic transaminase (GPT; also known as alanine aminotransferase) is a gluconeogenesis enzyme that catalyzes conversions between alanine and pyruvic acid. It is also used as a blood biomarker for hepatic damage. In this study, we investigated whether insulin regulates GPT expression, as it does for other gluconeogenesis genes, and if this involves the epigenetic modification of histone acetylation. Human liver-derived HepG2 cells were cultured with 0.5-100nM insulin for 8h, and the mRNA expression of GPT, glutamic-oxaloacetic transaminase (GOT), γ-glutamyltransferase (GGT), PCK1, G6PC and FBP1 was measured. We also investigated the extent of histone acetylation around these genes. Insulin suppressed the mRNA expression of gluconeogenesis genes (GPT2, GOT1, GOT2, GGT1, GGT2, G6PC, and PCK1) in HepG2 cells in a dose-dependent manner. mRNA levels of GPT2, but not GPT1, were decreased by insulin. Histone acetylation was also reduced around GPT2, G6PC, and PCK1 in response to insulin. The expression of GPT2 and other gluconeogenesis genes such as G6PC and PCK1 was suppressed by insulin, in association with decreases in histone H3 and H4 acetylation surrounding these genes. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Effects of Supplemental Acerola Juice on the Mineral Concentrations in Liver and Kidney Tissue Samples of Mice Fed with Cafeteria Diet.

    Science.gov (United States)

    Leffa, Daniela Dimer; dos Santos, Carla Eliete Iochims; Daumann, Francine; Longaretti, Luiza Martins; Amaral, Livio; Dias, Johnny Ferraz; da Silva, Juliana; Andrade, Vanessa Moraes

    2015-09-01

    We evaluated the impact of a supplemental acerola juice (unripe, ripe, and industrial) and its main pharmaceutically active components on the concentrations of minerals in the liver and kidney of mice fed with cafeteria diet. Swiss male mice were fed with a cafeteria (CAF) diet for 13 weeks. The CAF consisted of a variety of supermarket products with high energy content. Subsequently, animals received one of the following food supplements for 1 month: water, unripe acerola juice, ripe acerola juice, industrial acerola juice, vitamin C, or rutin. Mineral concentrations of the tissues were determined by particle-induced X-ray emission (PIXE). Our study suggests that the simultaneous intake of acerola juices, vitamin C, or rutin in association with a hypercaloric and hyperlipidic diet provides change in the mineral composition of organisms in the conditions of this study, which plays an important role in the antioxidant defenses of the body. This may help to reduce the metabolism of the fat tissue or even to reduce the oxidative stress.

  10. Alterations to proteome and tissue recovery responses in fish liver caused by a short-term combination treatment with cadmium and benzo[a]pyrene

    International Nuclear Information System (INIS)

    Costa, P.M.; Chicano-Galvez, E.; Lopez Barea, J.; DelValls, T.A.; Costa, M.H.

    2010-01-01

    The livers of soles (Solea senegalensis) injected with subacute doses of cadmium (Cd), benzo[a]pyrene (B[a]P), or their combination, were screened for alterations to cytosolic protein expression patterns, complemented by cytological and histological analyses. Cadmium and B[a]P, but not combined, induced hepatocyte apoptosis and Kupfer cell hyperplasia. Proteomics, however, suggested that apoptosis was triggered through distinct pathways. Cadmium and B[a]P caused upregulation of different anti-oxidative enzymes (peroxiredoxin and glutathione peroxidase, respectively) although co-exposure impaired induction. Similarly, apoptosis was inhibited by co-exposure, to which may have contributed a synergistic upregulation of tissue metalloproteinase inhibitor, β-actin and a lipid transport protein. The regulation factors of nine out of eleven identified proteins of different types revealed antagonistic or synergistic effects between Cd and B[a]P at the prospected doses after 24 h of exposure. The results indicate that co-exposure to Cd and B[a]P may enhance toxicity by impairing specific responses and not through cumulative damage. - The interaction between cadmium and benzo[a]pyrene impairs specific responses to toxicity and tissue repair mechanisms.

  11. Liver Transplant

    Science.gov (United States)

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  12. Differential effect of weight loss with low-fat diet or high-fat diet restriction on inflammation in the liver and adipose tissue of mice with diet-induced obesity

    Science.gov (United States)

    We studied the effects of weight loss induced by either a low-fat normal diet or restriction of high-fat diet on hepatic steatosis, inflammation in the liver and adipose tissue, and blood monocytes of obese mice. In mice with high-fat diet-induced obesity, weight loss was achieved by switching from ...

  13. Diffuse Reflectance Spectroscopy for Surface Measurement of Liver Pathology.

    Science.gov (United States)

    Nilsson, Jan H; Reistad, Nina; Brange, Hannes; Öberg, Carl-Fredrik; Sturesson, Christian

    2017-01-01

    Liver parenchymal injuries such as steatosis, steatohepatitis, fibrosis, and sinusoidal obstruction syndrome can lead to increased morbidity and liver failure after liver resection. Diffuse reflectance spectroscopy (DRS) is an optical measuring method that is fast, convenient, and established. DRS has previously been used on the liver with an invasive technique consisting of a needle that is inserted into the parenchyma. We developed a DRS system with a hand-held probe that is applied to the liver surface. In this study, we investigated the impact of the liver capsule on DRS measurements and whether liver surface measurements are representative of the whole liver. We also wanted to confirm that we could discriminate between tumor and liver parenchyma by DRS. The instrumentation setup consisted of a light source, a fiber-optic contact probe, and two spectrometers connected to a computer. Patients scheduled for liver resection due to hepatic malignancy were included, and DRS measurements were performed on the excised liver part with and without the liver capsule and alongside a newly cut surface. To estimate the scattering parameters and tissue chromophore volume fractions, including blood, bile, and fat, the measured diffuse reflectance spectra were applied to an analytical model. In total, 960 DRS spectra from the excised liver tissue of 18 patients were analyzed. All factors analyzed regarding tumor versus liver tissue were significantly different. When measuring through the capsule, the blood volume fraction was found to be 8.4 ± 3.5%, the lipid volume fraction was 9.9 ± 4.7%, and the bile volume fraction was 8.2 ± 4.6%. No differences could be found between surface measurements and cross-sectional measurements. In measurements with/without the liver capsule, the differences in volume fraction were 1.63% (0.75-2.77), -0.54% (-2.97 to 0.32), and -0.15% (-1.06 to 1.24) for blood, lipid, and bile, respectively. This study shows that it is possible to manage DRS

  14. Intravital imaging of the immune responses during liver-stage malaria infection: An improved approach for fixing the liver.

    Science.gov (United States)

    Akbari, Masoud; Kimura, Kazumi; Houts, James T; Yui, Katsuyuki

    2016-10-01

    The host-parasite relationship is one of the main themes of modern parasitology. Recent revolutions in science, including the development of various fluorescent proteins/probes and two-photon microscopy, have made it possible to directly visualize and study the mechanisms underlying the interaction between the host and pathogen. Here, we describe our method of preparing and setting-up the liver for our experimental approach of using intravital imaging to examine the interaction between Plasmodium berghei ANKA and antigen-specific CD8 + T cells during the liver-stage of the infection in four dimensions. Since the liver is positioned near the diaphragm, neutralization of respiratory movements is critical during the imaging process. In addition, blood circulation and temperature can be affected by the surgical exposure due to the anatomy and tissue structure of the liver. To control respiration, we recommend anesthesia with isoflurane inhalation at 1% during the surgery. In addition, our protocol introduces a cushion of gauze around the liver to avoid external pressure on the liver during intravital imaging using an inverted microscope, which makes it possible to image the liver tissue for long periods with minimal reduction in the blood circulation and with minimal displacement and tissue damage. The key point of this method is to reduce respiratory movements and external pressure on the liver tissue during intravital imaging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. The Preotective effects of Okra Powder (Abelmoschus esculentus on Histological and Histochemical Changes of Pancreatic Beta Cells and Liver Tissue of Diabetic Rat

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    Naeim Erfani Majd

    2017-04-01

    Full Text Available Background and Objective: Since Abelmoschus esculentus plant has many medical benefits, the present study aimed to investigate the therapeutic effects of Okra Powder (Abelmoschus esculentus against high-fat diet fed-streptozotocin (HFD/STZ-induced diabetic rats. Methods: In this experimental study, 25 Wistar Albino female rats were randomly divided into 5 groups: I: control group; II: healthy rats receiving A. esculentus (200 mg/kg; III (HFD/STZ group: Rats fed with high-fat diet (HFD (60% fat for 4 weeks and then injected low-dose STZ (35 mg/kg; IV: diabetic rats receiving A. esculentus (200mg/kg and V: diabetic rats receiving metformin (200 mg/kg. At the end of experiment, biochemical parameters, including Fasting Blood Glucose (FBG, insulin levels, Homa-IR index, ALT, AST and lipid profile were measured. Pancreas and Liver samples were removed, and 5-6 µ sections were prepared and stained by H&E and aldehyde fuchsin staining. Results: All the biochemical parameters, except HDL-C and insulin, were increased in diabetic rats, while these parameters were decreased in Okra supplementation group compared to diabetic rats (p<0.05. Furthermore, Okra improved the histological impairments of pancreas and liver, including vacuolization, and decrease of β-cells as well as hypertrophy and vacuolization of hepatocytes in diabetic rats. Conclusion: Okra powder improved biochemical parameters, liver structure and restoration of beta cells of pancreas in diabetic rats. Thus, it can be considered a complementary therapy to improve diabetic patients.

  16. Short-term vitamin E treatment impairs reactive oxygen species signaling required for adipose tissue expansion, resulting in fatty liver and insulin resistance in obese mice.

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    Martin Alcala

    Full Text Available The use of antioxidant therapy in the treatment of oxidative stress-related diseases such as cardiovascular disease, diabetes or obesity remains controversial. Our aim is to demonstrate that antioxidant supplementation may promote negative effects if used before the establishment of oxidative stress due to a reduced ROS generation under physiological levels, in a mice model of obesity.C57BL/6J mice were fed with a high-fat diet for 14 weeks, with (OE group or without (O group vitamin E supplementation.O mice developed a mild degree of obesity, which was not enough to induce metabolic alterations or oxidative stress. These animals exhibited a healthy expansion of retroperitoneal white adipose tissue (rpWAT and the liver showed no signs of lipotoxicity. Interestingly, despite achieving a similar body weight, OE mice were insulin resistant. In the rpWAT they presented a reduced generation of ROS, even below physiological levels (C: 1651.0 ± 212.0; O: 3113 ± 284.7; OE: 917.6 ±104.4 RFU/mg protein. C vs OE p< 0.01. ROS decay may impair their action as second messengers, which could account for the reduced adipocyte differentiation, lipid transport and adipogenesis compared to the O group. Together, these processes limited the expansion of this fat pad and as a consequence, lipid flux shifted towards the liver, causing steatosis and hepatomegaly, which may contribute to the marked insulin resistance.This study provides in vivo evidence for the role of ROS as second messengers in adipogenesis, lipid metabolism and insulin signaling. Reducing ROS generation below physiological levels when the oxidative process has not yet been established may be the cause of the controversial results obtained by antioxidant therapy.

  17. Functional pitch of a liver: fatty liver disease diagnosis with photoacoustic spectrum analysis

    Science.gov (United States)

    Xu, Guan; Meng, Zhuoxian; Lin, Jiandie; Carson, Paul; Wang, Xueding

    2014-03-01

    To provide more information for classification and assessment of biological tissues, photoacoustic spectrum analysis (PASA) moves beyond the quantification of the intensities of the photoacoustic (PA) signals by the use of the frequency-domain power distribution, namely power spectrum, of broadband PA signals. The method of PASA quantifies the linear-fit to the power spectrum of the PA signals from a biological tissue with 3 parameters, including intercept, midband-fit and slope. Intercept and midband-fit reflect the total optical absorption of the tissues whereas slope reflects the heterogeneity of the tissue structure. Taking advantage of the optical absorption contrasts contributed by lipid and blood at 1200 and 532 nm, respectively and the heterogeneous tissue microstructure in fatty liver due to the lipid infiltration, we investigate the capability of PASA in identifying histological changes of fatty livers in mouse model. 6 and 9 pairs of normal and fatty liver tissues from rat models were examined by ex vivo experiment with a conventional rotational PA measurement system. One pair of rat models with normal and fatty livers was examined non-invasively and in situ with our recently developed ultrasound and PA parallel imaging system. The results support our hypotheses that the spectrum analysis of PA signals can provide quantitative measures of the differences between the normal and fatty liver tissues and that part of the PA power spectrum can suffice for characterization of microstructures in biological tissues. Experimental results also indicate that the vibrational absorption peak of lipid at 1200nm could facilitate fatty liver diagnosis.

  18. Comparative analysis of distinctive transcriptome profiles with biochemical evidence in bisphenol S- and benzo[a]pyrene-exposed liver tissues of the olive flounder Paralichthys olivaceus.

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    Jee-Hyun Jung

    Full Text Available Flounder is a promising model species for environmental monitoring of coastal regions. To assess the usefulness of liver transcriptome profiling, juvenile olive flounder Paralichthys olivaceus were exposed to two pollutants, bisphenol S (BPS and benzo[a]pyrene (BaP, which have different chemical characteristics and have distinct modes of metabolic action in teleost. Six hours after intraperitoneal injection with BPS (50 mg/kg bw or BaP (20 mg/kg bw, liver transcriptomes were analyzed using the Illumina Hiseq 3000 platform. Interestingly, the transcriptome was highly sensitive and was distinctively expressed in response to each chemical. The primary effect of BPS was significantly increased transcription of egg process and vitellogenesis related genes, including vitellogenins (vtg1, vtg2, zona pellucida sperm-binding proteins (zp3, zp4, and estrogen receptors (erα, erβ, with increases in plasma 17β-estradiol (E2 and vitellogenin (VTG concentrations. Following BaP treatment, detoxification- and biotransformation-related genes such as cyp1a1 and UDP-glucuronosyltransferase (ugt1a1 were significantly increased, with an increase in EROD activity. In both transcriptomes, mRNA expression of genes involved in antioxidant defense systems was increased, while genes involved in innate immunity were decreased upon BPS or BaP exposure with a decrease in complement activity. This study provides useful insight into the chemical-specific hepatic transcriptional response of P. olivaceus and suggests a basis for further studies examining biomarker application of liver transcriptomes for environmental pollution.

  19. Supplementation with antioxidant-rich extra virgin olive oil prevents hepatic oxidative stress and reduction of desaturation capacity in mice fed a high-fat diet: Effects on fatty acid composition in liver and extrahepatic tissues.

    Science.gov (United States)

    Rincón-Cervera, Miguel Angel; Valenzuela, Rodrigo; Hernandez-Rodas, María Catalina; Marambio, Macarena; Espinosa, Alejandra; Mayer, Susana; Romero, Nalda; Barrera M Sc, Cynthia; Valenzuela, Alfonso; Videla, Luis A

    2016-01-01

    The aim of this study was to assess the effect of dietary supplementation with extra virgin olive oil (EVOO) in mice on the reduction of desaturase and antioxidant enzymatic activities in liver, concomitantly with long-chain polyunsaturated fatty acids (LCPUFA) profiles in liver and extrahepatic tissues induced by a high-fat diet (HFD). Male mice C57 BL/6 J were fed with a control diet (CD; 10% fat, 20% protein, 70% carbohydrates) or an HFD (60% fat, 20% protein, 20% carbohydrates) for 12 wk. Animals were supplemented with 100 mg/d EVOO with different antioxidant contents (EVOO I, II, and III). After the intervention, blood and several tissues were analyzed. Dietary supplementation with EVOO with the highest antioxidant content and antioxidant capacity (EVOO III) significantly reduced fat accumulation in liver and the plasmatic metabolic alterations caused by HFD and produced a normalization of oxidative stress-related parameters, desaturase activities, and LCPUFA content in tissues. Data suggest that dietary supplementation with EVOO III may prevent oxidative stress and reduction of biosynthesis and accretion of ω-3 LCPUFA in the liver of HFD-fed mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. ACOUSTIC RADIATION FORCE IMPULSE IS EQUIVALENT TO LIVER BIOPSY TO EVALUATE LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C AND NONALCOHOLIC FATTY LIVER DISEASE

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    Juliana Ayres de Alencar Arrais GUERRA

    2015-09-01

    Full Text Available BackgroundLiver biopsy is recommended as the gold standard method for assessing the stage of liver fibrosis in patients with chronic liver disease. However, it is invasive, with potential risks and complications. Elastography is an ultrasound technique that provides information of changes in the liver tissue, evaluating tissue elasticity and acoustic radiation force impulse is one of the available techniques.ObjectiveThe main objective of this study was to evaluate the sensitivity and specificity of acoustic radiation force impulse comparing to liver biopsy to evaluate fibrosis in patients with chronic hepatitis C virus and nonalcoholic fatty liver disease.MethodsTwenty four patients were included, everyone underwent liver biopsy and acoustic radiation force impulse, and the results were compared with values described in the literature by several authors.ResultsIn the population of patients with chronic hepatitis C, our data were better correlated with data published by Carmen Fierbinteanu-Braticevici et al., with an accuracy of 82.4%, sensitivity of 71.4% and specificity of 90%. For nonalcoholic fatty liver disease, our data were better correlated with data published by Masato Yoneda et al., with an accuracy of 85.7%, sensitivity 80% and specificity of 100%.ConclusionAcoustic radiation force impulse is a method with good accuracy to distinguish initial fibrosis from advanced fibrosis in hepatitis C virus and nonalcoholic fatty liver disease and can replace biopsy in most cases.

  1. Identification of differentially expressed genes induced by energy restriction using annealing control primer system from the liver and adipose tissues of broilers.

    Science.gov (United States)

    Wang, J W; Chen, W; Kang, X T; Huang, Y Q; Tian, Y D; Wang, Y B

    2012-04-01

    Female Arbor Acre broilers were divided into 2 groups at 18 d of age. One group of chickens had free access to feed (AL), and the other group of chickens had 30% energy restriction (ER). Adipose and hepatic RNA samples were collected at 48 d of age. We employed an accurate reverse-transcription (RT) PCR method that involves annealing control primers to identify the differentially expressed genes (DEG) between ER and AL groups. Using 20 annealing control primers, 43 differentially expressed bands (40 downregulated and 3 upregulated in the ER group) were detected from the hepatic tissue, whereas no differentially expressed bands were detected from the adipose tissue. It seems that energy restriction could induce more DEG in hepatic tissue than that in adipose tissue and could result in more gene-expression downregulation in hepatic tissue. Eight DEG (6 known and 2 unknown genes) were gained from hepatic tissue and confirmed by RT-PCR, which were all supported by released expressed sequence tag sequences. Their expressions were all downregulated by energy restriction in hepatic tissues. Six known genes are RPL7, RPLP1, FBXL12, ND1, ANTXR2, and SLC22A18, respectively, which seem to play essential roles in the protein translation, energy metabolism, and tumor inhibition. The alterations of gene expression in 3 selected genes, including ND1 (P < 0.01), FBXL12 (P < 0.01), and RPLP1 (P < 0.05), were supported by real-time quantitative RT-PCR reaction. Our data provide new insights on the metabolic state of broilers changed by energy restriction.

  2. Effect of functional sympathetic nervous system impairment of the liver and abdominal visceral adipose tissue on circulating triglyceride-rich lipoproteins.

    Science.gov (United States)

    La Fountaine, Michael F; Cirnigliaro, Christopher M; Kirshblum, Steven C; McKenna, Cristin; Bauman, William A

    2017-01-01

    Interruption of sympathetic innervation to the liver and visceral adipose tissue (VAT) in animal models has been reported to reduce VAT lipolysis and hepatic secretion of very low density lipoprotein (VLDL) and concentrations of triglyceride-rich lipoprotein particles. Whether functional impairment of sympathetic nervous system (SNS) innervation to tissues of the abdominal cavity reduce circulating concentrations of triglyceride (TG) and VLDL particles (VLDL-P) was tested in men with spinal cord injury (SCI). One hundred-three non-ambulatory men with SCI [55 subjects with neurologic injury at or proximal to the 4th thoracic vertebrae (↑T4); 48 subjects with SCI at or distal to the 5th thoracic vertebrae (↓T5)] and 53 able-bodied (AB) subjects were studied. Fasting blood samples were obtained for determination of TG, VLDL-P concentration by NMR spectroscopy, serum glucose by autoanalyzer, and plasma insulin by radioimmunoassay. VAT volume was determined by dual energy x-ray absorptiometry imaging with calculation by a validated proprietary software package. Significant group main effects for TG and VLDL-P were present; post-hoc tests revealed that serum TG concentrations were significantly higher in ↓T5 group compared to AB and ↑T4 groups [150±9 vs. 101±8 (plipoproteins (i.e., TG or Large VLDL-P) and VAT volume or HOMA-IR was significant only in the ↓T5 group. Despite a similar VAT volume and insulin resistance in both SCI groups, the ↓T5 group had significantly higher serum TG and VLDL-P values than that observed in the ↑T4 and the AB control groups. Thus, level of injury is an important determinate of the concentration of circulating triglyceride rich lipoproteins, which may play a role in the genesis of cardiometabolic dysfunction.

  3. 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

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    Valenzuela, R.

    2016-06-01

    Full Text Available 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 Los ácidos grasos poliinsaturados de cadena larga (AGPICL sintetizados principalmente por el hígado, cumplen funciones relevantes en el organismo. Una dieta alta en grasa (DAG genera un incremento en los niveles de grasa y estrés oxidativo (lipoperoxidación en hígado y una reducción en los niveles de AGPICL n-3 y n-6 en diferentes tejidos. El aceite de oliva extra virgen (AOEV es rico en antioxidantes (polifenoles y tocoferoles que ayudan a prevenir el desarrollo del estrés oxidativo. Este trabajo evaluó el rol del AOEV en la prevención del depósito de grasa, estrés oxidativo hepático y reducción de los AGPICL n-3 y n-6 en diferentes tejidos generado por una DAG en ratones C57BL/6J. Cuatro grupos experimentales (n=10/grupo fueron alimentados (12 semanas con dieta control (DC o DAG y suplementados con AOEV (100 mg/día. El grupo alimentado con DAG presentó un incremento (p < 0,05 en la acumulación de grasa y estrés oxidativo hepático, acompañado de una reducción en los niveles de AGPICL n-3 y n-6 en hígado, eritrocitos y cerebro. La suplementación con AOEV logr

  4. Radiofrequency tissue ablation with cooled-tip electrodes:an experimental study in a bovine liver model on variables influencing lesion size

    International Nuclear Information System (INIS)

    Han, Hyun Young; Lee, Jeong Min; Kim, Chong Soo

    2001-01-01

    The purpose of this study was to determine the influence of various factors on the extent of thermal coagulation necrosis after radiofrequency (RF) tissue ablation using a cooled-tip electrode in bovine liver. RF ablation was induced by a monopolar 500 KHz-RF generator (CC-1; Radionics, Burlington, Mass., U.S.A.) and an 18-G cooled-tip with single or clustered electrodes. The ablation protocol involved a combination of varying current, ablation time, power output, gradual or abrupt increase of this out-put, and pulsed radiofrequency techniques. The maximum diameter of all thermal lesions which showed a color change was measured perpendicular to the electrode axis by two observers who reached their decisions by consensus. Twenty representative lesions were pathologically examined. With increasing current lesion diameter also increased, but above 1500 mA no further increase was induced. Extending the ablation time to 9 minutes for a single electrode and 15 minutes for a clustered electrode increased lesion diameter until a steady state was reached. Higher power levels caused larger lesions, but above 100 W no increase was observed. Ample exposure time coupled with a stepwise increase in power level induced a lesion larger than that resulting from an abrupt increase. Continuous pulsed RF with a high current led to increased coagulation necrosis diameter. These experimental findings may be useful thermotherapy. The data suggest that all involved factors significantly affect lesion size:if the factors are better understood, cancer thermotherapy can be better controlled

  5. Effect of Pistacia Atlantica Extract on Glutathione Peroxidase Tissue Levels and Total Oxidative Capacity of Liver and Plasma Lipid Profile of Rats

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    Parvin Farzanegi

    2013-11-01

    Full Text Available Background: Exercise causes increased oxygen consumption, leaving cells exposed to oxidative stress. Antioxidants may have a protective effect by inhibiting lipid peroxidation. Thus, this study aims to examine the effect of Pistacia atlantica extract on glutathione peroxidase levels and total oxidative capacity of liver and plasma lipid profile of rats. Materials and Methods: In this experimental study, 28 female rats’ weight 155.8±2.7 grams were randomly and equally divided into 4 groups of exercise-saline, control-saline, exercise-mastic, and control-mastic. The exercise groups exercised for 8 weeks (5 days per week, 60 minutes daily, 25 meters per minute, on a zero degree slope. The rats received equal volumes of mastic and saline orally for 4 weeks. Blood and tissue samples were taken 72 hours after the last exercise session. Data were analyzed using one-way variance analysis (ANOVA.Results: Consumption of Pistacia atlantica extract together with endurance exercising for 8 weeks did not significantly affect glutathione peroxidase concentration, total oxidative capacity, LDL, triglyceride, or cholesterol, but significantly reduced HDL (p=0.002.Conclusion: Results showed that antioxidant and lipid profile levels were not affected by consumption of supplements and endurance exercising. However, further studies are required to assess the long term effects of this herbal extract.

  6. Combination of high-intensity focused ultrasound irradiation and hydroxyapatite nanoparticle injection to injure normal goat liver tissue in vivo without costal bone incision.

    Science.gov (United States)

    Liu, L; Xiao, Z; Xiao, Y; Wang, Z; Li, F; Li, M; Peng, X

    2014-10-20

    The aims of this study were to evaluate the in vivo safety of intravenous nano-hydroxyapatite (nano-HA), to explore how nano-HA might influence the effects of high-intensity focused ultrasound (HIFU) on normal liver tissue, and to investigate whether intravenous nano-HA could enhance HIFU for hepatocellular carcinoma ablation in a goat model. The present study, for the first time, indicated that the delivery of abundant nano-HA into the body over short periods of time could be assembled by the hepatic reticuloendothelial system, subsequently leading to a rapid rise of ultrasound-induced overheating, and ultimately resulting in enlargement of the coagulation necrotic area for ablated hepatocellular carcinoma in goats both in vivo and ex vivo. On the other hand, therapeutic doses of nano-HA were much lower than the lethal dose, and consequently presented transient and mild abnormalities of hepatic enzymes and renal function during the first 24 h after nano-HA injection. These results suggested that the combined application of nano-HA and HIFU is potentially a more effective alternative option compared to surgery for hepatocellular carcinoma local ablation in a safe and feasible manner.

  7. Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan.

    Science.gov (United States)

    Sakitani, Kosuke; Enooku, Kenichiro; Kubo, Hirokazu; Tanaka, Akifumi; Arai, Hisakatsu; Kawazu, Shoji; Koike, Kazuhiko

    2017-06-01

    Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male and 253 female; mean age 64.4 years), 175 males (24.4%) and 60 females (23.7%) had fatty liver. None of the 28 patients with type 1 diabetes had fatty liver. In male patients with type 2 diabetes, age, visceral adipose tissue (VAT), albumin, alanine amino-transferase (ALT), and triglycerides were independently associated with fatty liver. In females, age and bilirubin were associated with fatty liver. Conclusions Fatty liver is associated with type 2 diabetes characteristics, including younger age and elevated VAT, albumin, ALT, and triglycerides in males and younger age and elevated bilirubin levels in females.

  8. Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan

    Science.gov (United States)

    Sakitani, Kosuke; Enooku, Kenichiro; Kubo, Hirokazu; Tanaka, Akifumi; Arai, Hisakatsu; Kawazu, Shoji; Koike, Kazuhiko

    2017-01-01

    Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male and 253 female; mean age 64.4 years), 175 males (24.4%) and 60 females (23.7%) had fatty liver. None of the 28 patients with type 1 diabetes had fatty liver. In male patients with type 2 diabetes, age, visceral adipose tissue (VAT), albumin, alanine amino-transferase (ALT), and triglycerides were independently associated with fatty liver. In females, age and bilirubin were associated with fatty liver. Conclusions Fatty liver is associated with type 2 diabetes characteristics, including younger age and elevated VAT, albumin, ALT, and triglycerides in males and younger age and elevated bilirubin levels in females. PMID:28553763

  9. Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis.

    Science.gov (United States)

    Koo, Seung-Hoi

    2013-09-01

    Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.

  10. Energy metabolism in the liver.

    Science.gov (United States)

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic function is controlled by insulin and other metabolic hormones. Glucose is converted into pyruvate through glycolysis in the cytoplasm, and pyruvate is subsequently oxidized in the mitochondria to generate ATP through the TCA cycle and oxidative phosphorylation. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and/or cholesterol esters in hepatocytes. These complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as very low-density lipoprotein particles. In the fasted state, the liver secretes glucose through both glycogenolysis and gluconeogenesis. During pronged fasting, hepatic gluconeogenesis is the primary source for endogenous glucose production. Fasting also promotes lipolysis in adipose tissue, resulting in release of nonesterified fatty acids which are converted into ketone bodies in hepatic mitochondria though β-oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver energy metabolism is tightly regulated by neuronal and hormonal signals. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis but suppresses gluconeogenesis, and glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze key steps of metabolic pathways, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases. © 2014 American Physiological Society.

  11. The Role of Oxidative Stress and Antioxidants in Liver Diseases

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    Sha Li

    2015-11-01

    Full Text Available A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

  12. Visualisation of distribution of gold nanoparticles in liver tissues ex vivo and in vitro using the method of optical coherence tomography

    International Nuclear Information System (INIS)

    Genina, Elina A; Terentyuk, G S; Khlebtsov, B N; Bashkatov, A N; Tuchin, Valerii V

    2012-01-01

    The possibility of visualising the distribution of gold nanoparticles in liver by means of the method of optical coherence tomography is studied experimentally in model samples of beef liver in vitro and rat liver ex vivo. In the experiments we used the gold nanoparticles in the form of nanocages with resonance absorption in the near-IR spectral region. In the model studies the suspension of nanoparticles was applied to the surface of the sample, which then was treated with ultrasound. In the ex vivo studies the suspension of nanoparticles was injected to the laboratory rats intravenously. The image contrast and the optical depth of detection of blood vessels and liver structure components are calculated, as well as the depth of liver optical probing before and after the injection of nanoparticles. It was shown that the administration of the nanoparticle increases significantly the imaging contrast of liver blood vessels owing to the localisation of the nanoparticles therein.

  13. Visualisation of distribution of gold nanoparticles in liver tissues ex vivo and in vitro using the method of optical coherence tomography

    Energy Technology Data Exchange (ETDEWEB)

    Genina, Elina A; Terentyuk, G S; Khlebtsov, B N; Bashkatov, A N; Tuchin, Valerii V

    2012-06-30

    The possibility of visualising the distribution of gold nanoparticles in liver by means of the method of optical coherence tomography is studied experimentally in model samples of beef liver in vitro and rat liver ex vivo. In the experiments we used the gold nanoparticles in the form of nanocages with resonance absorption in the near-IR spectral region. In the model studies the suspension of nanoparticles was applied to the surface of the sample, which then was treated with ultrasound. In the ex vivo studies the suspension of nanoparticles was injected to the laboratory rats intravenously. The image contrast and the optical depth of detection of blood vessels and liver structure components are calculated, as well as the depth of liver optical probing before and after the injection of nanoparticles. It was shown that the administration of the nanoparticle increases significantly the imaging contrast of liver blood vessels owing to the localisation of the nanoparticles therein.

  14. Apoptosis and Necrosis in the Liver

    Science.gov (United States)

    Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

    2013-01-01

    Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

  15. Role of liver progenitors in liver regeneration.

    Science.gov (United States)

    Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A; Canbay, Ali

    2015-02-01

    During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs.

  16. Liver disease in pregnancy

    Institute of Scientific and Technical Information of China (English)

    Noel M Lee; Carla W Brady

    2009-01-01

    Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy.

  17. Spatial and temporal trends of selected trace elements in liver tissue from polar bears (Ursus maritimus) from Alaska, Canada and Greenland

    Science.gov (United States)

    Routti, H.; Letcher, R.J.; Born, E.W.; Branigan, M.; Dietz, R.; Evans, T.J.; Fisk, A.T.; Peacock, E.; Sonne, C.

    2011-01-01

    Spatial trends and comparative changes in time of selected trace elements were studied in liver tissue from polar bears from ten different subpopulation locations in Alaska, Canadian Arctic and East Greenland. For nine of the trace elements (As, Cd, Cu, Hg, Mn, Pb, Rb, Se and Zn) spatial trends were investigated in 136 specimens sampled during 2005-2008 from bears from these ten subpopulations. Concentrations of Hg, Se and As were highest in the (northern and southern) Beaufort Sea area and lowest in (western and southern) Hudson Bay area and Chukchi/Bering Sea. In contrast, concentrations of Cd showed an increasing trend from east to west. Minor or no spatial trends were observed for Cu, Mn, Rb and Zn. Spatial trends were in agreement with previous studies, possibly explained by natural phenomena. To assess temporal changes of Cd, Hg, Se and Zn concentrations during the last decades, we compared our results to previously published data. These time comparisons suggested recent Hg increase in East Greenland polar bears. This may be related to Hg emissions and/or climate-induced changes in Hg cycles or changes in the polar bear food web related to global warming. Also, Hg:Se molar ratio has increased in East Greenland polar bears, which suggests there may be an increased risk for Hg 2+-mediated toxicity. Since the underlying reasons for spatial trends or changes in time of trace elements in the Arctic are still largely unknown, future studies should focus on the role of changing climate and trace metal emissions on geographical and temporal trends of trace elements. ?? 2011 The Royal Society of Chemistry.

  18. Spatial and temporal trends of selected trace elements in liver tissue from polar bears (Ursus maritimus) from Alaska, Canada and Greenland.

    Science.gov (United States)

    Routti, Heli; Letcher, Robert J; Born, Erik W; Branigan, Marsha; Dietz, Rune; Evans, Thomas J; Fisk, Aaron T; Peacock, Elizabeth; Sonne, Christian

    2011-08-01

    Spatial trends and comparative changes in time of selected trace elements were studied in liver tissue from polar bears from ten different subpopulation locations in Alaska, Canadian Arctic and East Greenland. For nine of the trace elements (As, Cd, Cu, Hg, Mn, Pb, Rb, Se and Zn) spatial trends were investigated in 136 specimens sampled during 2005-2008 from bears from these ten subpopulations. Concentrations of Hg, Se and As were highest in the (northern and southern) Beaufort Sea area and lowest in (western and southern) Hudson Bay area and Chukchi/Bering Sea. In contrast, concentrations of Cd showed an increasing trend from east to west. Minor or no spatial trends were observed for Cu, Mn, Rb and Zn. Spatial trends were in agreement with previous studies, possibly explained by natural phenomena. To assess temporal changes of Cd, Hg, Se and Zn concentrations during the last decades, we compared our results to previously published data. These time comparisons suggested recent Hg increase in East Greenland polar bears. This may be related to Hg emissions and/or climate-induced changes in Hg cycles or changes in the polar bear food web related to global warming. Also, Hg:Se molar ratio has increased in East Greenland polar bears, which suggests there may be an increased risk for Hg(2+)-mediated toxicity. Since the underlying reasons for spatial trends or changes in time of trace elements in the Arctic are still largely unknown, future studies should focus on the role of changing climate and trace metal emissions on geographical and temporal trends of trace elements.

  19. Effect of functional sympathetic nervous system impairment of the liver and abdominal visceral adipose tissue on circulating triglyceride-rich lipoproteins.

    Directory of Open Access Journals (Sweden)

    Michael F La Fountaine

    Full Text Available Interruption of sympathetic innervation to the liver and visceral adipose tissue (VAT in animal models has been reported to reduce VAT lipolysis and hepatic secretion of very low density lipoprotein (VLDL and concentrations of triglyceride-rich lipoprotein particles. Whether functional impairment of sympathetic nervous system (SNS innervation to tissues of the abdominal cavity reduce circulating concentrations of triglyceride (TG and VLDL particles (VLDL-P was tested in men with spinal cord injury (SCI.One hundred-three non-ambulatory men with SCI [55 subjects with neurologic injury at or proximal to the 4th thoracic vertebrae (↑T4; 48 subjects with SCI at or distal to the 5th thoracic vertebrae (↓T5] and 53 able-bodied (AB subjects were studied. Fasting blood samples were obtained for determination of TG, VLDL-P concentration by NMR spectroscopy, serum glucose by autoanalyzer, and plasma insulin by radioimmunoassay. VAT volume was determined by dual energy x-ray absorptiometry imaging with calculation by a validated proprietary software package.Significant group main effects for TG and VLDL-P were present; post-hoc tests revealed that serum TG concentrations were significantly higher in ↓T5 group compared to AB and ↑T4 groups [150±9 vs. 101±8 (p<0.01 and 112±8 mg/dl (p<0.05, respectively]. VLDL-P concentration was significantly elevated in ↓T5 group compared to AB and ↑T4 groups [74±4 vs. 58±4 (p<0.05 and 55±4 μmol/l (p<0.05]. VAT volume was significantly higher in both SCI groups than in the AB group, and HOMA-IR was higher and approached significance in the SCI groups compared to the AB group. A linear relationship between triglyceride rich lipoproteins (i.e., TG or Large VLDL-P and VAT volume or HOMA-IR was significant only in the ↓T5 group.Despite a similar VAT volume and insulin resistance in both SCI groups, the ↓T5 group had significantly higher serum TG and VLDL-P values than that observed in the ↑T4 and the AB

  20. Relationship between liver tissue stiffness and histopathological findings analyzed by shear wave elastography and compression testing in rats with non-alcoholic steatohepatitis.

    Science.gov (United States)

    Ogawa, Saori; Moriyasu, Fuminori; Yoshida, Keiko; Oshiro, Hisashi; Kojima, Mayumi; Sano, Takatomo; Furuichi, Yoshihiro; Kobayashi, Yoshiyuki; Nakamura, Ikuo; Sugimoto, Katsutoshi

    2016-07-01

    The aim of the present study was to investigate two methods of determining liver stiffness in rats with various degrees of non-alcoholic steatohepatitis induced by a methionine- and choline-deficient (MCD) diet by comparing each finding with reference to histopathological liver findings. Twenty male Wister rats were fed an MCD diet for up to 32 weeks, and four were fed a normal diet. Ultrasound-based shear wave elastography (SWE) and mechanical compression testing using an Instron Universal Testing machine were performed on each rat at designated time points. After each examination, liver histopathology was analyzed to evaluate the degrees of steatosis, inflammation, and fibrosis based on non-alcoholic fatty liver disease (NAFLD) activity score, and each finding was compared with reference to liver histopathologic findings. Median liver stiffness values measured using SWE showed a stepwise increase with increasing histological inflammation score (P = 0.002), hepatic fibrosis stage (P = 0.029), ballooning score (P = 0.012), and steatosis grade (P = 0.030). Median liver stiffness measured using an Instron machine showed a stepwise increase only with increasing histological fibrosis stage (P = 0.033). Degree of liver stiffness measured by SWE and the Instron machine differed. SWE reflected mainly inflammation, whereas Instron machine-derived values primarily reflected fibrosis. This is the main source of discrepancies between measurements made with these two modalities.

  1. Bisphenol A sulfonation is impaired in metabolic and liver disease

    International Nuclear Information System (INIS)

    Yalcin, Emine B.; Kulkarni, Supriya R.; Slitt, Angela L.; King, Roberta

    2016-01-01

    Background: Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood. Objectives: To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. Methods: The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice. Results: In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers. Conclusion: Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers. - Highlights: • Present study demonstrates that hepatic SULT 1A1/1A3 are primarily sulfonate BPA in mouse and human. • Hepatic BPA sulfonation is profoundly reduced steatosis, diabetes and cirrhosis. • With BPA-S detectable in urine under low or common exposures, these findings are novel and important.

  2. Bisphenol A sulfonation is impaired in metabolic and liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Yalcin, Emine B.; Kulkarni, Supriya R.; Slitt, Angela L., E-mail: angela_slitt@uri.edu; King, Roberta, E-mail: rking@uri.edu

    2016-02-01

    Background: Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood. Objectives: To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. Methods: The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice. Results: In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers. Conclusion: Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers. - Highlights: • Present study demonstrates that hepatic SULT 1A1/1A3 are primarily sulfonate BPA in mouse and human. • Hepatic BPA sulfonation is profoundly reduced steatosis, diabetes and cirrhosis. • With BPA-S detectable in urine under low or common exposures, these findings are novel and important.

  3. COMPLICATIONS OF ALCOHOLIC LIVER DISEASE AND DIAGNOSTIC MARKERS

    Directory of Open Access Journals (Sweden)

    Milena Ilić

    2011-12-01

    Full Text Available Alcoholism is one of the leading diseases affecting people’s health and immunity worldwide. Nearly 30 thousand people in the USA die from chronic liver damage. The liver is the central organ in the metabolism of alcohol. Alcohol is primarily a hepatotoxic agent. Hepatotoxicity of alcohol is clinically manifested by the development of alcoholic fatty liver, alcoholic hepatitis and alcoholic cirrhosis. It is characterized by appropriate symptomatology, depending on the degree of liver damage. Excessive use of alcohol for a long period of time, along with malnutrition, genetic and ethnic predisposition, leads to alcoholic cirrhosis and the development of its complications. Portal hypertension damages other organs and organ systems, causing hepatopulmonary syndrome, hepatorenal syndrome, hepatic encephalopathy, spontaneous bacterial peritonitis, etc. For these reasons, alcoholism reduction is given priority, as well as reduction of morbidity and mortality of people with alcoholic chronic liver damage. Therefore, early diagnosis of alcohol abuse is necessary, as well as timely diagnosis of different degrees of alcoholic liver damage. The diagnosis of chronic alcoholic liver damage is set on the basis of confirmed data of alcohol consumption; liver function test (serum markers aminotransferase, gammaglutamyl transferase, prothrombin time, serum bilirubin and albumin level; serum markers of liver fibrosis. Fibrosis markers are directly involved in sedimentation and dissolution of extracellular matrix, i.e. in the process of fibrogenesis and fibrinolysis of liver tissues. They include markers and enzymes of metabolism, as well as cytokines and chemokines.

  4. Implementation of an interactive liver surgery planning system

    Science.gov (United States)

    Wang, Luyao; Liu, Jingjing; Yuan, Rong; Gu, Shuguo; Yu, Long; Li, Zhitao; Li, Yanzhao; Li, Zhen; Xie, Qingguo; Hu, Daoyu

    2011-03-01

    Liver tumor, one of the most wide-spread diseases, has a very high mortality in China. To improve success rates of liver surgeries and life qualities of such patients, we implement an interactive liver surgery planning system based on contrastenhanced liver CT images. The system consists of five modules: pre-processing, segmentation, modeling, quantitative analysis and surgery simulation. The Graph Cuts method is utilized to automatically segment the liver based on an anatomical prior knowledge that liver is the biggest organ and has almost homogeneous gray value. The system supports users to build patient-specific liver segment and sub-segment models using interactive portal vein branch labeling, and to perform anatomical resection simulation. It also provides several tools to simulate atypical resection, including resection plane, sphere and curved surface. To match actual surgery resections well and simulate the process flexibly, we extend our work to develop a virtual scalpel model and simulate the scalpel movement in the hepatic tissue using multi-plane continuous resection. In addition, the quantitative analysis module makes it possible to assess the risk of a liver surgery. The preliminary results show that the system has the potential to offer an accurate 3D delineation of the liver anatomy, as well as the tumors' location in relation to vessels, and to facilitate liver resection surgeries. Furthermore, we are testing the system in a full-scale clinical trial.

  5. Is the propagation speed of ultrasound in human organs a diagnostic parameter for tissue characterization? Evaluation using the liver parenchyma in children and adolescents as an example; Die Schallleitgeschwindigkeit im menschlichen Gewebe. Ein diagnostisch verwertbarer Parameter? Evaluation am Beispiel der Leber bei Kindern und Jugendlichen

    Energy Technology Data Exchange (ETDEWEB)

    Born, M. [Bonn Univ. (Germany). Radiologische Klinik - Kinderradiologie; Franke, I. [Bonn Univ. (Germany). Kinderklinik

    2011-09-15

    New sonographic machines permit the measurement of the propagation speed of ultrasound (PSU) in humans. The liver seems to be an appropriate organ for examining whether the PSU may be used as a diagnostic parameter for tissue characterization since the liver is easily accessible to sonography and its variable content of fat impacts the PSU. Purpose: To determine whether there is a measurable correlation between obesity and PSU in the liver. Methods: In 69 children and adolescents, the PSU in the liver was measured sonographically and correlated to BMI, age, size and weight of the children. Results: A strong correlation was found between the PSU in the liver and the BMI. The PSU was significantly lower in obese children (1507 m/s) than in children with normal body weight (1564 m/s). Conclusion: PSU seems to be promising as an additional diagnostic parameter for characterizing liver tissue. Further evaluation is necessary. (orig.)

  6. The association between content of the elements S, Cl, K, Fe, Cu, Zn and Br in normal and cirrhotic liver tissue from Danes and Greenlandic Inuit examined by dual hierarchical clustering analysis.

    Science.gov (United States)

    Laursen, Jens; Milman, Nils; Pind, Niels; Pedersen, Henrik; Mulvad, Gert

    2014-01-01

    Meta-analysis of previous studies evaluating associations between content of elements sulphur (S), chlorine (Cl), potassium (K), iron (Fe), copper (Cu), zinc (Zn) and bromine (Br) in normal and cirrhotic autopsy liver tissue samples. Normal liver samples from 45 Greenlandic Inuit, median age 60 years and from 71 Danes, median age 61 years. Cirrhotic liver samples from 27 Danes, median age 71 years. Element content was measured using X-ray fluorescence spectrometry. Dual hierarchical clustering analysis, creating a dual dendrogram, one clustering element contents according to calculated similarities, one clustering elements according to correlation coefficients between the element contents, both using Euclidian distance and Ward Procedure. One dendrogram separated subjects in 7 clusters showing no differences in ethnicity, gender or age. The analysis discriminated between elements in normal and cirrhotic livers. The other dendrogram clustered elements in four clusters: sulphur and chlorine; copper and bromine; potassium and zinc; iron. There were significant correlations between the elements in normal liver samples: S was associated with Cl, K, Br and Zn; Cl with S and Br; K with S, Br and Zn; Cu with Br. Zn with S and K. Br with S, Cl, K and Cu. Fe did not show significant associations with any other element. In contrast to simple statistical methods, which analyses content of elements separately one by one, dual hierarchical clustering analysis incorporates all elements at the same time and can be used to examine the linkage and interplay between multiple elements in tissue samples. Copyright © 2013 Elsevier GmbH. All rights reserved.

  7. Immunohistochemical analysis of restenotic tissue after transjugular portosystemic shunt

    International Nuclear Information System (INIS)

    Lu Qin; An Yanli; Deng Gang; Fang Wen; Zhu Guangyu; Li Guozhao; Wei Xiaoying; Liu Yuanyuan; Teng Gaojun

    2005-01-01

    Objective: To investigate the changes of several restenotic tissue elements after transjugular portosystemic shunt, and to provide more informations for the mechanism of TIPS restenosis. Methods: TIPS was performed in 6 swine to set up TIPS animal models. 14-21 days after operation, the models were sacrificed to obtain the TIPS tissues for pathological examinations, including electric microscope, HE staining, and immunohistochemical staining of anti-SMC-actin-α, PCNA, Vementin, myoglobulin, eNOS and iNOS. Then , the results were comparatively analyzed between TIPS obstructed shunt tissues and non-obstructed shunt tissues. Results: Restenosis was occurred with different degrees in 4 swine of the 6 TIPS models. Electric microscopic results showed that the restenosis tissues were composed of over proliferated collagen, SMCs and fibroblasts. Anti-SMC-actin-α and PCNA were strongly positive expression in restenotic tissues, and also positive in patent tissues. Vimentin expressed strongly in unstenotic tissues, on the contrary, it expressed obviously weaker in restenotic tissues. Myoglobulin expressed more strongly in restenotic tissues and weakened in unstenotic tissues. eNOS expressed positive in normal liver tissues, and expressed weaker near TIPS restenotic tissues. iNOS showed stronger expression in restenotic tissues and could hardly expressed in normal liver tissues. Conclusions: Restenotic rate may be 67% in TIPS swine models. Restenotic tissues may be mainly composed of proliferated SMCs positively expressed anti-SMC-actin-α with strong ability of movement. eNOS may be expressed in normal liver tissues and instead iNOS be expressed in strongly injured liver tissues. (authors)

  8. Liver Hemangioma

    Science.gov (United States)

    Liver hemangioma Overview A liver hemangioma (he-man-jee-O-muh) is a noncancerous (benign) mass in the liver. A liver hemangioma is made up of a tangle of blood vessels. Other terms for a liver hemangioma are hepatic hemangioma and cavernous hemangioma. Most ...

  9. Perioperative liver and spleen elastography in patients without chronic liver disease.

    Science.gov (United States)

    Eriksson, Sam; Borsiin, Hanna; Öberg, Carl-Fredrik; Brange, Hannes; Mijovic, Zoran; Sturesson, Christian

    2018-02-27

    To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic tumors. Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated. Results are presented as median (interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41 (1.24-1.63) m/s to 2.20 (1.72-2.44) m/s ( P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31 (1.15-1.52) m/s vs 1.37 (1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16% (7%-33%) increase in spleen stiffness, more ( P = 0.047) than after a minor resection [2 (-1-13) %]. Patients who underwent preoperative chemotherapy ( n = 20) did not differ from others in preoperative right liver lobe [1.31 (1.16-1.50) vs 1.38 (1.12-1.56) m/s, P = 0.569] or spleen [2.79 (2.33-3.11) vs 2.71 (2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin ( R 2 = 0.154, Pearson's r = 0.392, P = 0.032) and international normalized ratio ( R 2 = 0.285, Pearson's r = 0.534, P = 0.003). Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease.

  10. Periodontal disease and liver cirrhosis

    DEFF Research Database (Denmark)

    Grønkjær, Lea Ladegaard

    2015-01-01

    and liver cirrhosis and to identify opportunities and directions for future research in this area. METHODS: A systematic review of English articles in the PubMed, EMBASE, and Scopus databases was conducted using search terms including 'liver cirrhosis', 'end-stage liver disease', 'liver diseases', 'oral...

  11. Animal experimental studies on the influence of fatty infiltration of the liver on tissue relaxation times and signal changes in MRT

    International Nuclear Information System (INIS)

    Kreft, B.; Stark, D.; Schild, H.

    1995-01-01

    Using a spectrometer (n=60) in vitro and MRT imaging (n=8) in vivo, we studied the influence of fatty changes of liver cells on the relaxation times of the liver (two animal models of fatty liver disease/orotic acid, L-ethionine). Induction of fatty degeneration of the liver by means of an orotic acid diet resulted in pure deposition of fat in the liver without any histological or serological proof of inflammatory changes. Although accumulation of triglyceride in the liver reduced the T 1 relaxation time only relatively slightly (-15%), there was good correlation (r=0.88) between fat content and T 1 . There was also good correlation (r=0.92) between T 2 and histological fat content. Inflammatory changes besides fatty deposition were seen both serologically and histologically in the L-ethionine model, so that the fatty content did not correlate with T 1 . In-vivo MRT imaging showed that spin-echo sequences are inappropriate for diagnosing fatty infiltration of the liver despite the relaxation time changes produced by the fatty deposition. On the other hand, chemical-shift imaging sequences are very sensitive to identify fatty deposits, and are also independent of any additionally existing inflammatory changes. (orig.) [de

  12. Early postnatal feed restriction reduces liver connective tissue levels and affects H3K9 acetylation state of regulated genes associated with protein metabolism in low birth weight pigs.

    Science.gov (United States)

    Nebendahl, Constance; Görs, Solvig; Albrecht, Elke; Krüger, Ricarda; Martens, Karen; Giller, Katrin; Hammon, Harald M; Rimbach, Gerald; Metges, Cornelia C

    2016-03-01

    Intrauterine growth retardation is associated with metabolic consequences in adulthood. Since our previous data indicate birth weight-dependent effects of feed restriction (R) on protein degradation processes in the liver, it should be investigated whether effects on connective tissue turnover are obvious and could be explained by global changes of histone H3K9me3 and H3K9ac states in regulated genes. For this purpose, female littermate pigs with low (U) or normal (N) birth weight were subjected to 3-week R (60% of ad libitum fed controls) with subsequent refeeding (REF) for further 5 weeks. The 3-week R-period induced a significant reduction of connective tissue area by 43% in the liver of U animals at 98 d of age, which was not found in age-matched N animals. Of note, after REF at 131 d of age, in previously feed-restricted U animals (UR), the percentage of mean connective tissue was only 53% of ad libitum fed controls (UK), indicating a persistent effect. In U animals, R induced H3K9 acetylation of regulated genes (e.g. XBP1, ERLEC1, GALNT2, PTRH2), which were inter alia associated with protein metabolism. In contrast, REF was mostly accompanied by deacetylation in U and N animals. Thus, our epigenetic data may give a first explanation for the observed birth weight-dependent differences in this connective tissue phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Liver biopsy

    Science.gov (United States)

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

  14. Digital quantification of fibrosis in liver biopsy sections: description of a new method by Photoshop software.

    Science.gov (United States)

    Dahab, Gamal M; Kheriza, Mohamed M; El-Beltagi, Hussien M; Fouda, Abdel-Motaal M; El-Din, Osama A Sharaf

    2004-01-01

    The precise quantification of fibrous tissue in liver biopsy sections is extremely important in the classification, diagnosis and grading of chronic liver disease, as well as in evaluating the response to antifibrotic therapy. Because the recently described methods of digital image analysis of fibrosis in liver biopsy sections have major flaws, including the use of out-dated techniques in image processing, inadequate precision and inability to detect and quantify perisinusoidal fibrosis, we developed a new technique in computerized image analysis of liver biopsy sections based on Adobe Photoshop software. We prepared an experimental model of liver fibrosis involving treatment of rats with oral CCl4 for 6 weeks. After staining liver sections with Masson's trichrome, a series of computer operations were performed including (i) reconstitution of seamless widefield images from a number of acquired fields of liver sections; (ii) image size and solution adjustment; (iii) color correction; (iv) digital selection of a specified color range representing all fibrous tissue in the image and; (v) extraction and calculation. This technique is fully computerized with no manual interference at any step, and thus could be very reliable for objectively quantifying any pattern of fibrosis in liver biopsy sections and in assessing the response to antifibrotic therapy. It could also be a valuable tool in the precise assessment of antifibrotic therapy to other tissue regardless of the pattern of tissue or fibrosis.

  15. 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

    elevated at 36 and 48 h. Microabscesses were found in the livers from pigs killed at 12 h only. The livers from pigs killed at 48 h also showed light, diffuse fibrin exudation (vascular leakage). Real-time PCR showed a decreased hepatic expression of mRNA coding for albumin and increased hepatic expression...... 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...

  16. GPR39 splice variants versus antisense gene LYPD1: expression and regulation in gastrointestinal tract, endocrine pancreas, liver, and white adipose tissue

    DEFF Research Database (Denmark)

    Egerod, Kristoffer L; Holst, Birgitte; Petersen, Pia S

    2007-01-01

    nervous system as characterized with both quantitative RT-PCR and in situ hybridization analysis. A functional analysis of the GPR39 promoter region identified sites for the hepatocyte nuclear factors 1alpha and 4alpha (HNF-1alpha and -4alpha) and specificity protein 1 (SP1) transcription factors as being......G protein-coupled receptor 39 (GPR39) is a constitutively active, orphan member of the ghrelin receptor family that is activated by zinc ions. GPR39 is here described to be expressed in a full-length, biologically active seven-transmembrane form, GPR39-1a, as well as in a truncated splice variant...... five-transmembrane form, GPR39-1b. The 3' exon of the GPR39 gene overlaps with an antisense gene called LYPD1 (Ly-6/PLAUR domain containing 1). Quantitative RT-PCR analysis demonstrated that GPR39-1a is expressed selectively throughout the gastrointestinal tract, including the liver and pancreas...

  17. Digital Genome-Wide ncRNA Expression, Including SnoRNAs, across 11 Human Tissues Using PolyA-Neutral Amplification

    Science.gov (United States)

    Castle, John C.; Armour, Christopher D.; Löwer, Martin; Haynor, David; Biery, Matthew; Bouzek, Heather; Chen, Ronghua; Jackson, Stuart; Johnson, Jason M.; Rohl, Carol A.; Raymond, Christopher K.

    2010-01-01

    Non-coding RNAs (ncRNAs) are an essential class of molecular species that have been difficult to monitor on high throughput platforms due to frequent lack of polyadenylation. Using a polyadenylation-neutral amplification protocol and next-generation sequencing, we explore ncRNA expression in eleven human tissues. ncRNAs 7SL, U2, 7SK, and HBII-52 are expressed at levels far exceeding mRNAs. C/D and H/ACA box snoRNAs are associated with rRNA methylation and pseudouridylation, respectively: spleen expresses both, hypothalamus expresses mainly C/D box snoRNAs, and testes show enriched expression of both H/ACA box snoRNAs and RNA telomerase TERC. Within the snoRNA 14q cluster, 14q(I-6) is expressed at much higher levels than other cluster members. More reads align to mitochondrial than nuclear tRNAs. Many lincRNAs are actively transcribed, particularly those overlapping known ncRNAs. Within the Prader-Willi syndrome loci, the snoRNA HBII-85 (group I) cluster is highly expressed in hypothalamus, greater than in other tissues and greater than group II or III. Additionally, within the disease locus we find novel transcription across a 400,000 nt span in ovaries. This genome-wide polyA-neutral expression compendium demonstrates the richness of ncRNA expression, their high expression patterns, their function-specific expression patterns, and is publicly available. PMID:20668672

  18. Digital genome-wide ncRNA expression, including SnoRNAs, across 11 human tissues using polyA-neutral amplification.

    Directory of Open Access Journals (Sweden)

    John C Castle

    Full Text Available Non-coding RNAs (ncRNAs are an essential class of molecular species that have been difficult to monitor on high throughput platforms due to frequent lack of polyadenylation. Using a polyadenylation-neutral amplification protocol and next-generation sequencing, we explore ncRNA expression in eleven human tissues. ncRNAs 7SL, U2, 7SK, and HBII-52 are expressed at levels far exceeding mRNAs. C/D and H/ACA box snoRNAs are associated with rRNA methylation and pseudouridylation, respectively: spleen expresses both, hypothalamus expresses mainly C/D box snoRNAs, and testes show enriched expression of both H/ACA box snoRNAs and RNA telomerase TERC. Within the snoRNA 14q cluster, 14q(I-6 is expressed at much higher levels than other cluster members. More reads align to mitochondrial than nuclear tRNAs. Many lincRNAs are actively transcribed, particularly those overlapping known ncRNAs. Within the Prader-Willi syndrome loci, the snoRNA HBII-85 (group I cluster is highly expressed in hypothalamus, greater than in other tissues and greater than group II or III. Additionally, within the disease locus we find novel transcription across a 400,000 nt span in ovaries. This genome-wide polyA-neutral expression compendium demonstrates the richness of ncRNA expression, their high expression patterns, their function-specific expression patterns, and is publicly available.

  19. Real time monitoring of rat liver energy state during ischemia.

    Science.gov (United States)

    Barbiro, E; Zurovsky, Y; Mayevsky, A

    1998-11-01

    Hepatic failure is one of the major problems developed during the posttransplantation period. A possible cause of hepatic failure is the prolonged ischemia induced during the implantation procedure. Hepatic ischemia leads to a reduction in oxygen supply, ATP level decline, liver metabolism impairment, and finally organ failure. The purpose of this study was to estimate the functional state of the liver by monitoring liver blood flow and the mitochondrial NADH redox state simultaneously and continuously during in situ liver ischemia followed by reperfusion. Measurements were performed using the multiprobe developed in our laboratory consisting of fibers for the measurement of relative liver blood flow (laser Doppler flowmetry) and mitochondrial redox state (NADH fluorescence). The experimental procedure included the temporary interruption of blood flow to the liver using three types of ischemia, hepatic artery occlusion, portal vein occlusion, and simultaneous occlusion of hepatic artery and portal vein, followed by a reperfusion period. These preliminary experiments showed a significant decrease in liver blood flow, following the three types of liver ischemia, and a significant increase in NADH levels. The probe used in this study incorporates the advantage of monitoring NADH and liver blood flow simultaneously and continuously from the same area on the surface of the liver. Since each of these two parameters is not calibrated in absolute units, the simultaneous monitoring decreases possible artifacts. Also, it will allow us to determine of the coupling between tissue blood flow and oxidative phosphorylation. It is believed that the measurements of respiratory chain dysfunction might predict organ viability in clinical organ transplantation situations. Using this probe may also help to decrease the variability in liver blood flow monitoring since liver blood flow monitoring is supported simultaneously with the mitochondrial redox state, which supplies the

  20. [Various pathways leading to the progression of chronic liver diseases].

    Science.gov (United States)

    Egresi, Anna; Lengyel, Gabriella; Somogyi, Anikó; Blázovics, Anna; Hagymási, Krisztina

    2016-02-21

    As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression.

  1. Chronic stress does not impair liver regeneration in rats

    DEFF Research Database (Denmark)

    Andersen, Kasper J; Knudsen, Anders Riegels; Wiborg, Ove

    2015-01-01

    a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate. RESULTS: None......BACKGROUND: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects...... of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. METHODS: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent...

  2. Efficacy of humidity retention bags for the reduced adsorption and improved cleaning of tissue proteins including prion-associated amyloid to surgical stainless steel surfaces.

    Science.gov (United States)

    Secker, T J; Pinchin, H E; Hervé, R C; Keevil, C W

    2015-01-01

    Increasing drying time adversely affects attachment of tissue proteins and prion-associated amyloid to surgical stainless steel, and reduces the efficacy of commercial cleaning chemistries. This study tested the efficacy of commercial humidity retention bags to reduce biofouling on surgical stainless steel and to improve subsequent cleaning. Surgical stainless steel surfaces were contaminated with ME7-infected brain homogenates and left to dry for 15 to 1,440 min either in air, in dry polythene bags or within humidity retention bags. Residual contamination pre/post cleaning was analysed using Thioflavin T/SYPRO Ruby dual staining and microscope analysis. An increase in biofouling was observed with increased drying time in air or in sealed dry bags. Humidity retention bags kept both protein and prion-associated amyloid minimal across the drying times both pre- and post-cleaning. Therefore, humidity bags demonstrate a cheap, easy to implement solution to improve surgical instrument reprocessing and to potentially reduce associated hospital acquired infections.

  3. Ultrasound elastographic techniques in focal liver lesions.

    Science.gov (United States)

    Conti, Clara Benedetta; Cavalcoli, Federica; Fraquelli, Mirella; Conte, Dario; Massironi, Sara

    2016-03-07

    Elastographic techniques are new ultrasound-based imaging techniques developed to estimate tissue deformability/stiffness. Several ultrasound elastographic approaches have been developed, such as static elastography, transient elastography and acoustic radiation force imaging methods, which include point shear wave and shear wave imaging elastography. The application of these methods in clinical practice aims at estimating the mechanical tissues properties. One of the main settings for the application of these tools has been liver stiffness assessment in chronic liver disease, which has been studied mainly using transient elastography. Another field of application for these techniques is the assessment of focal lesions, detected by ultrasound in organs such as pancreas, prostate, breast, thyroid, lymph nodes. Considering the frequency and importance of the detection of focal liver lesions through routine ultrasound, some studies have also aimed to assess the role that elestography can play in studying the stiffness of different types of liver lesions, in order to predict their nature and thus offer valuable non-invasive methods for the diagnosis of liver masses.

  4. Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

    Science.gov (United States)

    Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

    2018-01-01

    Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

  5. Differentially regulated protein kinase A (PKA) activity in adipose tissue and liver is associated with resistance to diet-induced obesity and glucose intolerance in mice that lack PKA regulatory subunit type IIα.

    Science.gov (United States)

    London, Edra; Nesterova, Maria; Sinaii, Ninet; Szarek, Eva; Chanturiya, Tatyana; Mastroyannis, Spyridon A; Gavrilova, Oksana; Stratakis, Constantine A

    2014-09-01

    The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism in all organ systems affected by obesity. PKA has four regulatory (RIα, RIIα, RIβ, RIIβ) and four catalytic (Cα, Cβ, Cγ, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIβ, the primary PKA regulatory subunit in adipose tissue or knockout of the catalytic subunit Cβ resulted in a lean phenotype that resists diet-induced obesity and associated metabolic complications. Here we report that the disruption of the ubiquitously expressed PKA RIIα subunit in mice (RIIαKO) confers resistance to diet-induced obesity, glucose intolerance, and hepatic steatosis. After 2-week high-fat diet exposure, RIIαKO mice weighed less than wild-type littermates. Over time this effect was more pronounced in female mice that were also leaner than their wild-type counterparts, regardless of the diet. Decreased intake of a high-fat diet contributed to the attenuated weight gain in RIIαKO mice. Additionally, RIIα deficiency caused differential regulation of PKA in key metabolic organs: cAMP-stimulated PKA activity was decreased in liver and increased in gonadal adipose tissue. We conclude that RIIα represents a potential target for therapeutic interventions in obesity, glucose intolerance, and nonalcoholic fatty liver disease.

  6. Metabolic Profiling of Liver Tissue in Diabetic Mice Treated with Artemisia Capillaris and Alisma Rhizome Using LC-MS and CE-MS.

    Science.gov (United States)

    Kim, Yumi; Lee, In-Seung; Kim, Kang-Hoon; Park, Jiyoung; Lee, Ji-Hyun; Bang, Eunjung; Jang, Hyeung-Jin; Na, Yun-Cheol

    2016-01-01

    Artemisia Capillaris (AC) and Alisma Rhizome (AR) are natural products for the treatment of liver disorders in oriental medicine clinics. Here, we report metabolomic changes in the evaluation of the treatment effects of AC and AR on fatty livers in diabetic mice, along with a proposition of the underlying metabolic pathway. Hydrophobic and hydrophilic metabolites extracted from mouse livers were analyzed using HPLC-QTOF and CE-QTOF, respectively, to generate metabolic profiles. Statistical analysis of the metabolites by PLS-DA and OPLA-DA fairly discriminated between the diabetic, and the AC- and AR-treated mice groups. Various PEs mostly contributed to the discrimination of the diabetic mice from the normal mice, and besides, DG (18:1/16:0), TG (16:1/16:1/20:1), PE (21:0/20:5), and PA (18:0/21:0) were also associated with discrimination by s-plot. Nevertheless, the effects of AC and AR treatment were indistinct with respect to lipid metabolites. Of the 97 polar metabolites extracted from the CE-MS data, 40 compounds related to amino acid, central carbon, lipid, purine, and pyrimidine metabolism, with [Formula: see text] values less than 0.05, were shown to contribute to liver dysregulation. Following treatment with AC and AR, the metabolites belonging to purine metabolism preferentially recovered to the metabolic state of the normal mice. The AMP/ATP ratio of cellular energy homeostasis in AR-treated mice was more apparently increased ([Formula: see text]) than that of AC-treated mice. On the other hand, amino acids, which showed the main alterations in diabetic mice, did not return to the normal levels upon treatment with AR or AC. In terms of metabolomics, AR was a more effective natural product in the treatment of liver dysfunction than AC. These results may provide putative biomarkers for the prognosis of fatty liver disorder following treatment with AC and AR extracts.

  7. Ultrastructural and cytochemical study of membrane alterations in x-irradiated liver tissue from normal and vitamin E-deficient ducklings

    International Nuclear Information System (INIS)

    Huijbers, W.A.R.; Oosterbaan, J.A.; Meskendorp-Haarsma, T.J.; Hardonk, M.J.; Molenaar, I.

    1979-01-01

    An investigation into the differential susceptibility of liver cellular membranes to peroxidative processes has been performed, using x irradiation on the liver surface, resulting in a a 3-mm penetrating gradient of membrane damage. Ultrastructural, cytochemical, and histochemical findings in this area point to a differential sensitivity of cellular membranes to x irradiation. The plasma membrane and the lysosomal membrane, containing much lipid and cholesterol and little membrane and the lysosomal membrane, containing much lipid and cholesterol and little vitamin E, are highly susceptible to x irradiation. Less sensitive are the membranes of mitochondria and endoplasmic reticulum, containing relatively much vitamin E and proteins and a lower amount of lipids and cholesterol

  8. Study of chicken liver and spleen by Moessbauer spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Oshtrakh, M. I., E-mail: oshtrakh@mail.utnet.ru [Ural State Technical University-UPI, Division of Applied Biophysics, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University-UPI, Faculty of Experimental Physics (Russian Federation); Malakheeva, L. I. [Simbio Holding, Science Consultation Department (Russian Federation); Prokopenko, P. G. [Russian State Medical University, Faculty of Biochemistry (Russian Federation)

    2005-09-15

    A preliminary study of purified normal human liver ferritin, normal chicken liver and spleen tissues in lyophilized form showed differences in room temperature Moessbauer hyperfine parameters. An additional study of liver and spleen tissues with lower iron content from chicken with lymphoid leukemia indicated small differences between the quadrupole splittings in these samples compared with those in normal tissues.

  9. Study of chicken liver and spleen by Moessbauer spectroscopy

    International Nuclear Information System (INIS)

    Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Malakheeva, L. I.; Prokopenko, P. G.

    2005-01-01

    A preliminary study of purified normal human liver ferritin, normal chicken liver and spleen tissues in lyophilized form showed differences in room temperature Moessbauer hyperfine parameters. An additional study of liver and spleen tissues with lower iron content from chicken with lymphoid leukemia indicated small differences between the quadrupole splittings in these samples compared with those in normal tissues.

  10. Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis

    Directory of Open Access Journals (Sweden)

    Christoph Niemietz

    2015-09-01

    Full Text Available The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR, expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP. Misfolded variants of TTR are linked to the establishment of extracellular protein deposition in various tissues, including the heart and the peripheral nervous system. Recent progress in the chemistry and formulation of antisense (ASO and small interfering RNA (siRNA designed for a knockdown of TTR mRNA in the liver has allowed to address the issue of gene-specific molecular therapy in a clinical setting of FAP. The two therapeutic oligonucleotides bind to RNA in a sequence specific manner but exploit different mechanisms. Here we describe major developments that have led to the advent of therapeutic oligonucleotides for treatment of TTR-related disease.

  11. CT Perfusion Characteristics Identify Metastatic Sites in Liver

    Directory of Open Access Journals (Sweden)

    Yuan Wang

    2015-01-01

    Full Text Available Tissue perfusion plays a critical role in oncology because growth and migration of cancerous cells require proliferation of new blood vessels through the process of tumor angiogenesis. Computed tomography (CT perfusion is an emerging functional imaging modality that measures tissue perfusion through dynamic CT scanning following intravenous administration of contrast medium. This noninvasive technique provides a quantitative basis for assessing tumor angiogenesis. CT perfusion has been utilized on a variety of organs including lung, prostate, liver, and brain, with promising results in cancer diagnosis, disease prognostication, prediction, and treatment monitoring. In this paper, we focus on assessing the extent to which CT perfusion characteristics can be used to discriminate liver metastases from neuroendocrine tumors from normal liver tissues. The neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow (BF, blood volume (BV, mean transit time (MTT, permeability (PS, and hepatic arterial fraction (HAF, for tumor and normal liver. The result reveals the potential of CT perfusion as a tool for constructing biomarkers from features of the hepatic vasculature for guiding cancer detection, prognostication, and treatment selection.

  12. [Liver and sport].

    Science.gov (United States)

    Watelet, J

    2008-11-01

    The liver is a vital organ and plays a central role in energy exchange, protein synthesis as well as the elimination of waste products from the body. Acute and chronic injury may disturb a variety of liver functions to different degrees. Over the last three decades, the effects of physical activity and competitive sport on the liver have been described by various investigators. These include viral hepatitis and drug-induced liver disorders. Herein, we review acute and chronic liver diseases potentially caused by sport. Team physicians, trainers and others, responsible for the health of athletes, should be familiar with the risk factors, clinical features, and consequences of liver diseases that occur in sports.

  13. Computational Modeling in Liver Surgery

    Directory of Open Access Journals (Sweden)

    Bruno Christ

    2017-11-01

    Full Text Available The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery.

  14. Hypervascular liver lesions in radiologically normal liver

    Energy Technology Data Exchange (ETDEWEB)

    Amico, Enio Campos; Alves, Jose Roberto; Souza, Dyego Leandro Bezerra de; Salviano, Fellipe Alexandre Macena; Joao, Samir Assi; Liguori, Adriano de Araujo Lima, E-mail: ecamic@uol.com.br [Hospital Universitario Onofre Lopes (HUOL/UFRN), Natal, RN (Brazil). Clinica Gastrocentro e Ambulatorios de Cirurgia do Aparelho Digestivo e de Cirurgia Hepatobiliopancreatica

    2017-09-01

    Background: The hypervascular liver lesions represent a diagnostic challenge. Aim: To identify risk factors for cancer in patients with non-hemangiomatous hypervascular hepatic lesions in radiologically normal liver. Method: This prospective study included patients with hypervascular liver lesions in radiologically normal liver. The diagnosis was made by biopsy or was presumed on the basis of radiologic stability in follow-up period of one year. Cirrhosis or patients with typical imaging characteristics of haemangioma were excluded. Results: Eighty eight patients were included. The average age was 42.4. The lesions were unique and were between 2-5 cm in size in most cases. Liver biopsy was performed in approximately 1/3 of cases. The lesions were benign or most likely benign in 81.8%, while cancer was diagnosed in 12.5% of cases. Univariate analysis showed that age >45 years (p< 0.001), personal history of cancer (p=0.020), presence of >3 nodules (p=0.003) and elevated alkaline phosphatase (p=0.013) were significant risk factors for cancer. Conclusion: It is safe to observe hypervascular liver lesions in normal liver in patients up to 45 years, normal alanine amino transaminase, up to three nodules and no personal history of cancer. Lesion biopsies are safe in patients with atypical lesions and define the treatment to be established for most of these patients. (author)

  15. Estimation of ellagic acid and/or repaglinide effects on insulin signaling, oxidative stress, and inflammatory mediators of liver, pancreas, adipose tissue, and brain in insulin resistant/type 2 diabetic rats.

    Science.gov (United States)

    Amin, Mohamed M; Arbid, Mahmoud S

    2017-02-01

    Even though ellagic acid has previously been valued in many models of cancer, so far its full mechanistic effect as a natural antiapoptotic agent in the prevention of type 2 diabetes complications has not been completely elucidated, which was the goal of this study. We fed albino rats a high-fat fructose diet (HFFD) for 2 months to induce insulin resistance/type 2 diabetes and then treated the rats with ellagic acid (10 mg/kg body weight, orally) and/or repaglinide (0.5 mg/kg body weight, orally) for 2 weeks. At the serum level, ellagic acid challenged the consequences of HFFD, significantly improving the glucose/insulin balance, liver enzymes, lipid profile, inflammatory cytokines, redox level, adipokines, ammonia, and manganese. At the tissue level (liver, pancreas, adipose tissue, and brain), ellagic acid significantly enhanced insulin signaling, autophosphorylation, adiponectin receptors, glucose transporters, inflammatory mediators, and apoptotic markers. Remarkably, combined treatment with both ellagic acid and repaglinide had a more pronounced effect than treatment with either alone. These outcomes give new insight into the promising molecular mechanisms by which ellagic acid modulates numerous factors induced in the progression of diabetes.

  16. Automatic liver contouring for radiotherapy treatment planning

    International Nuclear Information System (INIS)

    Li, Dengwang; Kapp, Daniel S; Xing, Lei; Liu, Li

    2015-01-01

    To develop automatic and efficient liver contouring software for planning 3D-CT and four-dimensional computed tomography (4D-CT) for application in clinical radiation therapy treatment planning systems.The algorithm comprises three steps for overcoming the challenge of similar intensities between the liver region and its surrounding tissues. First, the total variation model with the L1 norm (TV-L1), which has the characteristic of multi-scale decomposition and an edge-preserving property, is used for removing the surrounding muscles and tissues. Second, an improved level set model that contains both global and local energy functions is utilized to extract liver contour information sequentially. In the global energy function, the local correlation coefficient (LCC) is constructed based on the gray level co-occurrence matrix both of the initial liver region and the background region. The LCC can calculate the correlation of a pixel with the foreground and background regions, respectively. The LCC is combined with intensity distribution models to classify pixels during the evolutionary process of the level set based method. The obtained liver contour is used as the candidate liver region for the following step. In the third step, voxel-based texture characterization is employed for refining the liver region and obtaining the final liver contours.The proposed method was validated based on the planning CT images of a group of 25 patients undergoing radiation therapy treatment planning. These included ten lung cancer patients with normal appearing livers and ten patients with hepatocellular carcinoma or liver metastases. The method was also tested on abdominal 4D-CT images of a group of five patients with hepatocellular carcinoma or liver metastases. The false positive volume percentage, the false negative volume percentage, and the dice similarity coefficient between liver contours obtained by a developed algorithm and a current standard delineated by the expert group

  17. Epicardial adipose tissue relating to anthropometrics, metabolic derangements and fatty liver disease independently contributes to serum high-sensitivity C-reactive protein beyond body fat composition: a study validated with computed tomography.

    Science.gov (United States)

    Lai, Yau-Huei; Yun, Chun-Ho; Yang, Fei-Shih; Liu, Chuan-Chuan; Wu, Yih-Jer; Kuo, Jen-Yuan; Yeh, Hung-I; Lin, Tin-Yu; Bezerra, Hiram G; Shih, Shou-Chuan; Tsai, Cheng-Ho; Hung, Chung-Lieh

    2012-02-01

    Epicardial adipose tissue (EAT) measured by echocardiography has been proposed to be associated with metabolic syndrome and increased cardiovascular risks. However, its independent association with fatty liver disease and systemic inflammation beyond clinical variables and body fat remains less well known. The relationships between EAT and various factors of metabolic derangement were retrospectively examined in consecutive 359 asymptomatic subjects (mean age, 51.6 years; 31% women) who participated in a cardiovascular health survey. Echocardiography-derived regional EAT thickness from parasternal long-axis and short-axis views was quantified. A subset of data from 178 randomly chosen participants were validated using 16-slice multidetector computed tomography. Body fat composition was evaluated using bioelectrical impedance from foot-to-foot measurements. Increased EAT was associated with increased waist circumference, body weight, and body mass index (all P values for trend = .005). Graded increases in serum fasting glucose, insulin resistance, and alanine transaminase levels were observed across higher EAT tertiles as well as a graded decrease of high-density lipoprotein (all P values for trend <.05). The areas under the receiver operating characteristic curves for identifying metabolic syndrome and fatty liver disease were 0.8 and 0.77, with odds ratio estimated at 3.65 and 2.63, respectively. In a multivariate model, EAT remained independently associated with higher high-sensitivity C-reactive protein and fatty liver disease. These data suggested that echocardiography-based epicardial fat measurement can be clinically feasible and was related to several metabolic abnormalities and independently associated fatty liver disease. In addition, EAT amount may contribute to systemic inflammation beyond traditional cardiovascular risks and body fat composition. Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

  18. Liver Immunology

    Science.gov (United States)

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323