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Sample records for quantitative liver function

  1. Quantitative Liver Function Tests: A Realizable Goal?

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    Morgan, Denis J; Susan L Elliott; Hany Ghabrial; Smallwood, Richard A

    1991-01-01

    A variety of tests has been used to assess liver function and predict hepatic functional reserve in patients with liver disease. These tests comprise clinical assessment, simple biochemical measurements and so-called ‘quantitative’ tests of liver function, ie, elimination rate measurements of exogenous markers such as drugs and other compounds. So far no single test or group of tests has proved to be a sufficiently sensitive and accurate measure of overall hepatic function across the whole sp...

  2. Quantitative Liver Function Tests: A Realizable Goal?

    Directory of Open Access Journals (Sweden)

    Denis J Morgan

    1991-01-01

    Full Text Available A variety of tests has been used to assess liver function and predict hepatic functional reserve in patients with liver disease. These tests comprise clinical assessment, simple biochemical measurements and so-called ‘quantitative’ tests of liver function, ie, elimination rate measurements of exogenous markers such as drugs and other compounds. So far no single test or group of tests has proved to be a sufficiently sensitive and accurate measure of overall hepatic function across the whole spectrum of liver disease. This may he due to diversity in the hepatic handling of these compounds and in changes in architecture, hemodynamics and cell function in liver disease. The absence of a satisfactory test emphasizes the value of clinical assessments (eg, the Child-Turcotte or Child-Pugh classifications, because of their relative simplicity.

  3. Could quantitative liver function tests gain wide acceptance among hepatologists?

    Institute of Scientific and Technical Information of China (English)

    Giovanni Tarantino

    2009-01-01

    It has been emphasized that the assessment of residual liver function is of paramount importance to determine the following: severity of acute or chronic liver diseases independent of etiology; long-term prognosis; step-bystep disease progression; surgical risk; and efficacy of antiviral treatment. The most frequently used tools are the galactose elimination capacity to asses hepatocyte cytosol activity, plasma clearance of indocyanine green to assess excretory function, and antipyrine clearance to estimate microsomal activity. However, a widely accepted liver test (not necessarily a laboratory one) to assess quantitative functional hepatic reserve still needs to be established, although there have been various proposals. Furthermore, who are the operators that should order these tests? Advances in analytic methods are expected to allow quantitative liver function tests to be used in clinical practice.

  4. Multiparametric or practical quantitative liver MRI: towards millisecond, fat fraction, kilopascal and function era.

    Science.gov (United States)

    Unal, Emre; Idilman, Ilkay Sedakat; Karçaaltıncaba, Muşturay

    2017-02-01

    New advances in liver magnetic resonance imaging (MRI) may enable diagnosis of unseen pathologies by conventional techniques. Normal T1 (550-620 ms for 1.5 T and 700-850 ms for 3 T), T2, T2* (>20 ms), T1rho (40-50 ms) mapping, proton density fat fraction (PDFF) (≤5%) and stiffness (2-3kPa) values can enable differentiation of a normal liver from chronic liver and diffuse diseases. Gd-EOB-DTPA can enable assessment of liver function by using postcontrast hepatobiliary phase or T1 reduction rate (normally above 60%). T1 mapping can be important for the assessment of fibrosis, amyloidosis and copper overload. T1rho mapping is promising for the assessment of liver collagen deposition. PDFF can allow objective treatment assessment in NAFLD and NASH patients. T2 and T2* are used for iron overload determination. MR fingerprinting may enable single slice acquisition and easy implementation of multiparametric MRI and follow-up of patients. Areas covered: T1, T2, T2*, PDFF and stiffness, diffusion weighted imaging, intravoxel incoherent motion imaging (ADC, D, D* and f values) and function analysis are reviewed. Expert commentary: Multiparametric MRI can enable biopsyless diagnosis and more objective staging of diffuse liver disease, cirrhosis and predisposing diseases. A comprehensive approach is needed to understand and overcome the effects of iron, fat, fibrosis, edema, inflammation and copper on MR relaxometry values in diffuse liver disease.

  5. Improvement of quantitative testing of liver function in patients with chronic hepatitis C after installment of antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    Matthias Ocker; Marion Ganslmayer; Steffen Zopf; Susanne Gahr; Christopher Janson; Eckhart G. Hahn; Christoph Herold

    2005-01-01

    AIM: To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function (QTLF).METHODS: Fifty patients with chronic hepatitis C were either treated with interferon (n = 8), interferon/ribavirin (n = 19) or peg-interferon/ribavirin (n = 23). Quantitative testing of liver function, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance (SCI) and indocyanine green clearance (ICG)was performed before and 3 mo after initiation of antiviral therapy.RESULTS: After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCV-RNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 mo. Parameters of liver perfusion (SCI and ICG) were not affected by antiviral therapy. In the 14 non-responders,no changes in QTLF values were observed during the treatment period.CONCLUSION: ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antivJral treatment in hepatitis C.

  6. Quantitative assessment of hepatic function: modified look-locker inversion recovery (MOLLI) sequence for T1 mapping on Gd-EOB-DTPA-enhanced liver MR imaging

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    Yoon, Jeong Hee [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Lee, Jeong Min; Han, Joon Koo; Choi, Byung Ihn [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Jongno-gu, Seoul (Korea, Republic of); Paek, Munyoung [Siemens Healthcare, Seoul (Korea, Republic of)

    2016-06-15

    To determine whether multislice T1 mapping of the liver using a modified look-locker inversion recovery (MOLLI) sequence on gadoxetic acid-enhanced magnetic resonance imaging (MRI) can be used as a quantitative tool to estimate liver function and predict the presence of oesophageal or gastric varices. Phantoms filled with gadoxetic acid were scanned three times using MOLLI sequence to test repeatability. Patients with chronic liver disease or liver cirrhosis who underwent gadoxetic acid-enhanced liver MRI including MOLLI sequence at 3 T were included (n = 343). Pre- and postcontrast T1 relaxation times of the liver (T1liver), changes between pre- and postcontrast T1liver (ΔT1liver), and adjusted postcontrast T1liver (postcontrast T1liver-T1spleen/T1spleen) were compared among Child-Pugh classes. In 62 patients who underwent endoscopy, all T1 parameters and spleen sizes were correlated with varices. Phantom study showed excellent repeatability of MOLLI sequence. As Child-Pugh scores increased, pre- and postcontrast T1liver were significantly prolonged (P < 0.001), and ΔT1liver and adjusted postcontrast T1liver decreased (P< 0.001). Adjusted postcontrast T1liver and spleen size were independently associated with varices (R{sup 2} = 0.29, P < 0.001). T1 mapping of the liver using MOLLI sequence on gadoxetic acid-enhanced MRI demonstrated potential in quantitatively estimating liver function, and adjusted postcontrast T1liver was significantly associated with varices. (orig.)

  7. Liver function

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008308 Study on transplantation of induced bone marrow mesenchymal stem cells via a series of the treatment of chronic liver injury. SUN Yan(孙艳), et al. Dept Gastroenterol, 1st Hosp, Jilin Univ, Changchun 130021. Chin J Dig 2008;28(3):171-174.Objective To investigate the efficacy of transplantation of induced bone marrow mesenchymal stem cells(MSCs)via a series of treatment of chronic liver injury.Methods MSCs were isolated and expanded by density

  8. Quantitative liver functions in Turner syndrome with and without hormone replacement therapy

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Poulsen, Henrik Enghusen; Ott, Peter

    2007-01-01

    Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes.......Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes....

  9. Liver Function Tests

    Science.gov (United States)

    ... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

  10. Hepatic (Liver) Function Panel

    Science.gov (United States)

    ... 1- to 2-Year-Old Blood Test: Hepatic (Liver) Function Panel KidsHealth > For Parents > Blood Test: Hepatic (Liver) Function Panel Print A A A What's in ... Is The hepatic function panel, also known as liver function tests, is a group of seven tests ...

  11. Assessment of Future Remnant Liver Function Using Hepatobiliary Scintigraphy in Patients Undergoing Major Liver Resection

    NARCIS (Netherlands)

    de Graaf, W.; van Lienden, K.P.; Dinant, S.; Roelofs, J.J.T.H.; Busch, O.R.C.; Gouma, D.J.; Bennink, R.J.; van Gulik, T.M.

    2010-01-01

    Tc-99m-mebrofenin hepatobiliary scintigraphy (HBS) was used as a quantitative method to evaluate liver function. The aim of this study was to compare future remnant liver function assessed by Tc-99m-mebrofenin hepatobiliary scintigraphy with future remnant liver volume in the prediction of liver

  12. Liver Function Tests

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  13. Monitoring of total and regional liver function after SIRT

    Directory of Open Access Journals (Sweden)

    Roelof J Bennink

    2014-06-01

    Full Text Available Selective internal radiation therapy (SIRT is a promising treatment modality for advanced hepatocellular carcinoma or metastatic liver cancer. SIRT is usually well tolerated. However, in most patients, SIRT will result in a (temporary decreased liver function. Occasionally patients develop radioembolization induced liver disease (REILD. In case of a high tumor burden of the liver it could be beneficial to perform SIRT in two sessions enabling the primary untreated liver segments to guarantee liver function until function in the treated segments has recovered, or functional hypertrophy has occurred.Clinically used liver function tests provide evidence of only one of the many liver functions, though all of them lack the possibility of assessment of segmental (regional liver function.Hepatobiliary scintigraphy (HBS has been validated as a tool to assess total and regional liver function in liver surgery. It is also used to assess segmental liver function before and after portal vein embolization. HBS is considered a valuable quantitative liver function test enabling assessment of segmental liver function recovery after regional intervention and determination of future remnant liver function.We present two cases in which HBS was used to monitor total and regional liver function in a patient after repeated whole liver SIRT complicated with REILD and a patient treated unilaterally without complications.

  14. Monitoring of Total and Regional Liver Function after SIRT.

    Science.gov (United States)

    Bennink, Roelof J; Cieslak, Kasia P; van Delden, Otto M; van Lienden, Krijn P; Klümpen, Heinz-Josef; Jansen, Peter L; van Gulik, Thomas M

    2014-01-01

    Selective internal radiation therapy (SIRT) is a promising treatment modality for advanced hepatocellular carcinoma or metastatic liver cancer. SIRT is usually well tolerated. However, in most patients, SIRT will result in a (temporary) decreased liver function. Occasionally patients develop radioembolization-induced liver disease (REILD). In case of a high tumor burden of the liver, it could be beneficial to perform SIRT in two sessions enabling the primary untreated liver segments to guarantee liver function until function in the treated segments has recovered or functional hypertrophy has occurred. Clinically used liver function tests provide evidence of only one of the many liver functions, though all of them lack the possibility of assessment of segmental (regional) liver function. Hepatobiliary scintigraphy (HBS) has been validated as a tool to assess total and regional liver function in liver surgery. It is also used to assess segmental liver function before and after portal vein embolization. HBS is considered as a valuable quantitative liver function test enabling assessment of segmental liver function recovery after regional intervention and determination of future remnant liver function. We present two cases in which HBS was used to monitor total and regional liver function in a patient after repeated whole liver SIRT complicated with REILD and a patient treated unilaterally without complications.

  15. Towards quantitative magnetic resonance assessment in parenchymal liver disease

    NARCIS (Netherlands)

    Runge, J.H.

    2015-01-01

    In this thesis several advanced magnetic resonance (MR) techniques for quantitative measurements in parenchymal liver disease are studied. In particular, certain important hallmarks of liver disease such as steatosis, fibrosis, iron overload and inflammation are studied. Steatosis or fatty liver dis

  16. Quantitative MRI analysis of dynamic enhancement of focal liver lesions

    Directory of Open Access Journals (Sweden)

    S. S. Bagnenko

    2012-01-01

    Full Text Available In our study 45 patients with different focal liver lesions (110 nodules were examined using high field MR-system (1,5 T. During this investigation quantitative MRI analysis of dynamic enhancement of various hepatic lesions and parenchymatous organs of abdomen were performed. It was shown that quantitative evaluation of enhanced MRI improves understanding of vascular transformation processes in pathologic hepatic focuses and in liver itself that is important for differential diagnoses of these diseases.

  17. Ultrasonic elastography in clinical quantitative assessment of fatty liver

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the clinical application of ultrasonic elastography in quantitative assessment of fatty liver grading. METHODS: A total of 105 patients with fatty liver were divided into mild group (n = 46), moderate group (n = 39), and severe group (n = 20). Forty-five healthy individuals served as a normal control group. All patients who underwent routine ultrasound scan and further ultrasonic elastography were evaluated accordingly to the evaluation standards for ultrasonic elastography. The ratio of...

  18. Role of liver functions on liver cell mitosis

    Directory of Open Access Journals (Sweden)

    Takata,Tameyuki

    1974-06-01

    Full Text Available The control mechanism of mitosis in the regenerating rat liver was studied in relation to the cell functions. Partial hepatec· tomy induces a series of changes prior to the initiation of mitosis, i. e. decrease in serum glucose and albumin levels, loss of glycogen from liver cells, and increased lipid mobilization to liver cells. Massive supplies of glucose and fructose suppressed significantly hepatocellu. lar mitosis with suppression of lipid accumulation and preservation of glycogen in the liver cells and of blood sugar level. Homologous serum administration also suppressed the rate of liver cell mitosis after hepatectomy preventing the decrease in serum albumin level, but did not suppress the lipid accumulation in the liver. Starvation, which would relieve the liver cell from the work of detoxication of intesti. nal toxic products, did not show any suppressive effect on the mitotic rate of liver cells after partial hepatectomy in single animals. But starvation induced severe hypoglycemia, moderate hypoalbuminemia and loss of glycogen content in the liver. These changes in metabo. lism by starvation and partial hepatectomy were suppressed by con· jugating the animals with nonhepatectomized fed.partners by aortic anastomosis, and mitosis was suppressed in the residual liver of the fasting animals in this parabiosis. The results indicate that all the major functions of parenchymal live cells tested, sugar metabolism, serum albumin production, and detoxication, are closely related to the control of liver cell mitosis. Accumulation of lipids in the liver remnant after partial hepatectomy is thought to be for the compensa. tion of reduced glycogen storage and not concerned directly with the liver cell mitosis. Discussion was made briefly on the humoral factor and portal blood factor in relation to excess load of functions on resi. dual liver cells.

  19. Study on parameters of L-[1-13C]phenylalanine breath test for quantitative assessment of liver function in healthy subjects and patients with hepatitis B virus-related liver disease

    Institute of Scientific and Technical Information of China (English)

    YAN Wei-Li; LIN Xiang-Tong; JIANG Yi-Bin; SUN Su; SUN Da-Yu

    2005-01-01

    The aims of this study are to investigate the feasibility and validity of the L-[1-13C] phenylalanine breath test (13C-PheBT) which has been used to measure hepatocyte functional capacity in hepatitis B virus-related liver disease patients and to propose validity parameters of the test in 12 healthy volunteer, 8 chronic hepatitis and 26 liver cirrhotic patients. 100mg/body nonradiative L-[1-13C] phenylalanine (13C-Phe) was administered orally to all subjects.Breath samples were taken before and different intervals within 360 min after administration. The 13CO2/12CO2 enrichment was assessed by isotope ratio mass spectrometer. The parameter percentage 13C excretion rate 13CER, (%13C dose/h) all peaked within 10-30 min after oral 13C-Phe application. The parameters such as maximum value of 13C excretion rate, 13CERmax (% 13C dose/h) (controls: 18.0±3.3; Child A: 11.0±3.8; Child B: 5.0±0.5; Child C:3.6±1.2), 13C excretion rate at 30min, 13CER30 (% dose/h) (controls: 11.9±2.1; Child A: 8.1±0.4; Child B: 6.1±0.9;Child C: 3.2±1.2), 13C cumulative excretion of first 60 min, 13Ccum60 (% 13C dose) (controls: 9.3±1.4; Child A: 6.6±0.7;Child B: 4.1±0.3; Child C: 2.6±0.9) and half time of 13C excretion rate, T1/2 (minutes) (controls: 40.4±4.4; chronic hepatitis: 53.4±4.4; Child A: 59.8±4.5;Child B: 102.0±17.3;Child C: 212.1±87.9) were effective indexes which could be employed to stage hepatocyte impairment and liver functional reserve of advanced HBV-related cirrhotic patients (i.e. healthy subjects, Child A, B, C);T1/2 was also useful for distinguishing mild HBV-related liver injure.

  20. Monitoring Hepatocyte Dysfunction and Biliary Complication After Liver Transplantation Using Quantitative Hepatobiliary Scintigraphy

    Science.gov (United States)

    Zou, Si-Juan; Chen, Dong; Li, Yan-Zhao; Du, Dun-Feng; Chen, Zhi-Shui; Zhu, Xiao-Hua

    2015-01-01

    Abstract The significance of hepatobiliary scintigraphy (HBS) for hepatic graft function assessment was established mostly on retrospective studies and was not widely recognized due to the lack of quantitative data and variation in accuracy. This prospective study was performed to investigate the effectiveness of quantitative HBS for assessing hepatocyte dysfunction and biliary complication in liver transplant recipients. In 57 recipients who had undergone orthotopic liver transplantation, a total of 67 dynamic 99mTc-EHIDA scans were performed and quantitative parameters including the hepatocyte extraction fraction (HEF), time to maximum hepatic radioactivity (Tmax), and time for peak activity to decrease by 50% (T1/2) were calculated. The scintigraphic results based on the 3 parameters were compared against the final diagnosis. A ROC curve analysis was carried out to identify the cutoff value of Tmax for diagnosis of biliary stricture. Correlation between the parameters of postoperative HBS and conventional biochemical liver function indices were also analyzed. Quantitative 99mTc-EHIDA HBS had an overall sensitivity of 94.12% (16/17), specificity of 93.33% (42/45), and diagnostic accuracy of 93.55% (58/62) for detecting hepatocyte dysfunction and biliary complication in liver transplant recipients. The recommended cutoff value of Tmax for diagnosis of post-transplant biliary stricture was set at 15.75 min with a sensitivity of 100.0% and a specificity of 94.0%. The scintigraphic parameters (HEF, Tmax) were statistically significantly associated with the conventional liver function parameters. Quantitative 99mTc-EHIDA HBS offers a noninvasive imaging modality with high sensitivity and specificity to diagnose hepatocyte dysfunction as well as distinguish between patients with or without biliary stricture following liver transplantation. Furthermore, HEF and Tmax values obtained from dynamic HBS show good correlation with conventional liver function parameters

  1. Liver expression quantitative trait loci: a foundation for pharmacogenomic research

    Directory of Open Access Journals (Sweden)

    Dylan eGlubb

    2012-08-01

    Full Text Available Expression quantitative trait loci (eQTL analysis can provide insights into the genetic regulation of gene expression at a genomic level and this information is proving extremely useful in many different areas of research. As a consequence of the role of the liver in drug metabolism and disposition, the study of eQTLs in primary human liver tissue could provide a foundation for pharmacogenomics. Thus far, four genome-wide eQTL studies have been performed using human livers. Many liver eQTLs have been found to be reproducible and a proportion of these may be specific to the liver. Already these data have been used to interpret and inform clinic genome-wide association studies, providing potential mechanistic evidence for clinical associations and identifying genes which may impact on clinical phenotypes. However, the utility of liver eQTL data has not yet been fully explored or realized in pharmacogenomics. As further liver eQTL research is undertaken, the genetic regulation of gene expression will become much better characterized and this knowledge will create a rational basis for the prospective pharmacogenomic study of many drugs.

  2. Current Strategies for Quantitating Fibrosis in Liver Biopsy

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2015-01-01

    Full Text Available Objective: The present mini-review updated the progress in methodologies based on using liver biopsy. Data Sources: Articles for study of liver fibrosis, liver biopsy or fibrosis assessment published on high impact peer review journals from 1980 to 2014. Study Selection: Key articles were selected mainly according to their levels of relevance to this topic and citations. Results: With the recently mounting progress in chronic liver disease therapeutics, comes by a pressing need for precise, accurate, and dynamic assessment of hepatic fibrosis and cirrhosis in individual patients. Histopathological information is recognized as the most valuable data for fibrosis assessment. Conventional histology categorical systems describe the changes of fibrosis patterns in liver tissue; but the simplified ordinal digits assigned by these systems cannot reflect the fibrosis dynamics with sufficient precision and reproducibility. Morphometric assessment by computer assist digital image analysis, such as collagen proportionate area (CPA, detects change of fibrosis amount in tissue section in a continuous variable, and has shown its independent diagnostic value for assessment of advanced or late-stage of fibrosis. Due to its evident sensitivity to sampling variances, morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort. Combining state-of-art imaging technology and fundamental principle in Tissue Engineering, structure-based quantitation was recently initiated with a novel proof-of-concept tool, qFibrosis. qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis, but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging. Conclusions: With input from multidisciplinary innovation, liver biopsy assessment as a new "gold standard" is anticipated to substantially support the accelerated

  3. Current Strategies for Quantitating Fibrosis in Liver Biopsy

    Institute of Scientific and Technical Information of China (English)

    Yan Wang; Jin-Lin Hou

    2015-01-01

    Objective:The present mini-review updated the progress in methodologies based on using liver biopsy.Data Sources:Articles for study of liver fibrosis,liver biopsy or fibrosis assessment published on high impact peer review journals from 1980 to 2014.Study Selection:Key articles were selected mainly according to their levels of relevance to this topic and citations.Results:With the recently mounting progress in chronic liver disease therapeutics,comes by a pressing need for precise,accurate,and dynamic assessment of hepatic fibrosis and cirrhosis in individual patients.Histopathological information is recognized as the most valuable data for fibrosis assessment.Conventional histology categorical systems describe the changes of fibrosis patterns in liver tissue; but the simplified ordinal digits assigned by these systems cannot reflect the fibrosis dynamics with sufficient precision and reproducibility.Morphometric assessment by computer assist digital image analysis,such as collagen proportionate area (CPA),detects change of fibrosis amount in tissue section in a continuous variable,and has shown its independent diagnostic value for assessment of advanced or late-stage of fibrosis.Due to its evident sensitivity to sampling variances,morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort.Combining state-of-art imaging technology and fundamental principle in Tissue Engineering,structure-based quantitation was recently initiated with a novel proof-of-concept tool,qFibrosis.qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis,but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging.Conclusions:With input from multidisciplinary innovation,liver biopsy assessment as a new "gold standard" is anticipated to substantially support the accelerated progress of Hepatology medicine.

  4. In vivo, label-free, three-dimensional quantitative imaging of liver surface using multi-photon microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Zhuo, Shuangmu, E-mail: shuangmuzhuo@gmail.com, E-mail: hanry-yu@nuhs.edu.sg [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Institute of Laser and Optoelectronics Technology, Fujian Normal University, Fuzhou 350007 (China); Yan, Jie [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, 138669 Singapore (Singapore); Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, MD 11 #04-01A, 117599 Singapore (Singapore); Kang, Yuzhan [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Xu, Shuoyu [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, 138669 Singapore (Singapore); Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, 117576 Singapore (Singapore); Peng, Qiwen [Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, 138669 Singapore (Singapore); Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, 117576 Singapore (Singapore); Mechanobiology Institute, 5A Engineering Drive 1, T-Lab #05-01, 117411 Singapore (Singapore); and others

    2014-07-14

    Various structural features on the liver surface reflect functional changes in the liver. The visualization of these surface features with molecular specificity is of particular relevance to understanding the physiology and diseases of the liver. Using multi-photon microscopy (MPM), we have developed a label-free, three-dimensional quantitative and sensitive method to visualize various structural features of liver surface in living rat. MPM could quantitatively image the microstructural features of liver surface with respect to the sinuosity of collagen fiber, the elastic fiber structure, the ratio between elastin and collagen, collagen content, and the metabolic state of the hepatocytes that are correlative with the pathophysiologically induced changes in the regions of interest. This study highlights the potential of this technique as a useful tool for pathophysiological studies and possible diagnosis of the liver diseases with further development.

  5. Age dependence of rat liver function measurements

    DEFF Research Database (Denmark)

    Fischer-Nielsen, A; Poulsen, H E; Hansen, B A

    1989-01-01

    Changes in the galactose elimination capacity, the capacity of urea-N synthesis and antipyrine clearance were studied in male Wistar rats at the age of 8, 20 and 44 weeks. Further, liver tissue concentrations of microsomal cytochrome P-450, microsomal protein and glutathione were measured. All...... liver function measurements increased from the age of 8 to 44 weeks when expressed in absolute values. In relation to body weight, these function measurements were unchanged or reduced from week 8 to week 20. At week 44, galactose elimination capacity and capacity of urea-N synthesis related to body...... weight were increased by 10% and 36%, respectively, and antipyrine plasma clearance was reduced to 50%. Liver tissue concentrations of microsomal cytochrome P-450 and microsomal protein increased with age when expressed in absolute values, but were unchanged per g liver, i.e., closely related to liver...

  6. Measurement of liver function for patients with cirrhosis by 13C-methacetin breath test compared with Child-Pugh score and routine liver function tests

    Institute of Scientific and Technical Information of China (English)

    LIU Yun-xiang; HUANG Liu-ye; WU Cheng-rong; CUI Jun

    2006-01-01

    @@ 13C-methacetin breath test was used for the evaluation of liver function, as for quantitative data could be achieved using this method, it had the characteristics of safety,quantification, and repetition and got recognition gradually through the world.1,2 We began this 13C-methacetin test to assess liver function of patients with cirrhosis from January 2002. The aim of this study was to explore the characteristic of this test for liver function evaluation and explore the correlation of this method with some clinical liver biochemical parameters and Child-Pugh score.

  7. Multiphoton microscopy in defining liver function

    Science.gov (United States)

    Thorling, Camilla A.; Crawford, Darrell; Burczynski, Frank J.; Liu, Xin; Liau, Ian; Roberts, Michael S.

    2014-09-01

    Multiphoton microscopy is the preferred method when in vivo deep-tissue imaging is required. This review presents the application of multiphoton microscopy in defining liver function. In particular, multiphoton microscopy is useful in imaging intracellular events, such as mitochondrial depolarization and cellular metabolism in terms of NAD(P)H changes with fluorescence lifetime imaging microscopy. The morphology of hepatocytes can be visualized without exogenously administered fluorescent dyes by utilizing their autofluorescence and second harmonic generation signal of collagen, which is useful in diagnosing liver disease. More specific imaging, such as studying drug transport in normal and diseased livers are achievable, but require exogenously administered fluorescent dyes. If these techniques can be translated into clinical use to assess liver function, it would greatly improve early diagnosis of organ viability, fibrosis, and cancer.

  8. Estimation of the Functional Reserve of Human Liver

    Science.gov (United States)

    Moody, Frank G.; Rikkers, Layton F.; Aldrete, Joaquin S.

    1974-01-01

    Functional hepatic reserve was determined in 32 patients with known liver or biliary tract disease employing kinetic analysis of hepatic removal of indocyanine green (ICG). The initial removal rates of incremental doses of ICG (0.5, 1.0 and 5.0 mg/kg body weight) were plotted as a reciprocal against the inverse of dose (Lineweaver-Burk plot) to provide a means of determining maximal removal rate from submaximal doses (Rmax). This function equalled 3.40 mg/kg/min in ten patients with normal livers, but was only .24 mg/kg/min in eight patients with alcoholic cirrhosis. Portasystemic shunting did not further influence Rmax. Infiltrative liver disease had only a mild depressive effect on this function. The results show that hepatic function can be precisely quantitated by classical enzyme kinetics (Michaelis-Menten). If Rmax is an estimate of protein receptor mass for organic anions, then the technique may allow an indirect means for quantitating hepatocytes even in the presence of changes in blood flow or hepatic function. The profound depression in Rmax observed in patients with alcoholic cirrhosis is consistent with the progressive loss in hepatic mass associated with this disease. PMID:4413286

  9. Simultaneous measurement of hundreds of liver proteins: application in assessment of liver function.

    Science.gov (United States)

    Anderson, N L; Taylor, J; Hofmann, J P; Esquer-Blasco, R; Swift, S; Anderson, N G

    1996-01-01

    Proteins implement most biological functions at the molecular level. As one might expect based on this fact, it appears that the altered functional states associated with toxic effects involve changes in the abundance or structure of proteins. Although numerous specific assays exist to measure changes in the abundance of individual proteins, practical limitations have prevented widespread use of multiple protein assays for the global characterization of toxicity. Recent developments in protein analytical technology are rapidly changing this picture. Two-dimensional gel electrophoresis, a technique capable of resolving and quantitating hundreds of proteins simultaneously, is becoming an automated, high-throughput tool. In parallel, techniques have been developed that allow the resulting deluge of protein measurements to be organized into a prototype Molecular Effects Database describing xenobiotic effects in rodent liver. This database can detect, classify, and characterize a broad range of liver toxicity mechanisms. It currently contains approximately 10 million protein measurements, including data on the liver effects of 43 compounds, with a further 50 compounds to be added in 1995. Observed effects range from very broad (sex steroids alter levels of 45% of all liver proteins) to very specific (e.g., hepatic hydroxymethyl glutaryl coenzyme A reductase inhibitors). Companion 2-dimensional databases describing rodent brain and kidney have been initiated, as have linkages to the genomic sequence databases. Assimilation of this approach into research and regulatory toxicology poses an interesting challenge--one that is likely to lead to a radically more sophisticated understanding of toxicity and its biological basis.

  10. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development

    Directory of Open Access Journals (Sweden)

    Leah Y. Liu

    2013-09-01

    Genome-wide association studies (GWAS have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10 decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50 decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.

  11. Quantitative multivoxel {sup 1}H MR spectroscopy of the brain in children with acute liver failure

    Energy Technology Data Exchange (ETDEWEB)

    Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs [University Medical Center Groningen and University of Groningen, Department of Radiology, Beatrix Children' s Hospital, Groningen (Netherlands); Lunsing, Roelineke J. [University Medical Center Groningen and University of Groningen, Department of Child Neurology, Beatrix Children' s Hospital, Groningen (Netherlands); Spronsen, Francjan J. van; Verkade, Henkjan J. [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Beatrix Children' s Hospital, Groningen (Netherlands)

    2008-11-15

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, {gamma}-glutamyl transpeptidase, alkaline phosphatase). (orig.)

  12. Mechanistic and quantitative aspects of liver tumour promotion in mice

    NARCIS (Netherlands)

    Ravenzwaay, van B.

    1988-01-01

    A variety of xenobiotic compounds is known to induce characteristic changes in the livers of laboratory animals. These changes include enlargement of the liver, usually as a result of cell enlargement (hypertrophy) or Increased cell replication (hyperplasia), induction of drugmetabolizing enzymes

  13. Integrative Quantitative Proteomics Unveils Proteostasis Imbalance in Human Hepatocellular Carcinoma Developed on Nonfibrotic Livers*

    Science.gov (United States)

    Negroni, Luc; Taouji, Said; Arma, Daniela; Pallares-Lupon, Nestor; Leong, Kristen; Beausang, Lee Anne; Latterich, Martin; Bossé, Roger; Balabaud, Charles; Schmitter, Jean-Marie; Bioulac-Sage, Paulette; Zucman-Rossi, Jessica; Rosenbaum, Jean; Chevet, Eric

    2014-01-01

    Proteomics-based clinical studies represent promising resources for the discovery of novel biomarkers or for unraveling molecular mechanisms underlying particular diseases. Here, we present a discovery study of hepatocellular carcinoma developed on nonfibrotic liver (nfHCC) that combines complementary quantitative iTRAQ-based proteomics and phosphoproteomics approaches. Using both approaches, we compared a set of 24 samples (18 nfHCC versus six nontumor liver tissue). We identified 43 proteins (67 peptides) differentially expressed and 32 peptides differentially phosphorylated between the experimental groups. The functional analysis of the two data sets pointed toward the deregulation of a protein homeostasis (proteostasis) network including the up-regulation of the Endoplasmic Reticulum (ER) resident HSPA5, HSP90B1, PDIA6, and P4HB and of the cytosolic HSPA1B, HSP90AA1, HSPA9, UBC, CNDP2, TXN, and VCP as well as the increased phosphorylation of the ER resident calnexin at Ser583. Antibody-based validation approaches (immunohistochemistry, immunoblot, Alphascreen®, and AMMP®) on independent nfHCC tumor sets (up to 77 samples) confirmed these observations, thereby indicating a common mechanism occurring in nfHCC tumors. Based on these results we propose that adaptation to proteostasis imbalance in nfHCC tumors might confer selective advantages to those tumors. As such, this model could provide an additional therapeutic opportunity for those tumors arising on normal liver by targeting the tumor proteostasis network. Data are available via ProteomeXchange with identifier PXD001253. PMID:25225353

  14. Integrative quantitative proteomics unveils proteostasis imbalance in human hepatocellular carcinoma developed on nonfibrotic livers.

    Science.gov (United States)

    Negroni, Luc; Taouji, Said; Arma, Daniela; Pallares-Lupon, Nestor; Leong, Kristen; Beausang, Lee Anne; Latterich, Martin; Bossé, Roger; Balabaud, Charles; Schmitter, Jean-Marie; Bioulac-Sage, Paulette; Zucman-Rossi, Jessica; Rosenbaum, Jean; Chevet, Eric

    2014-12-01

    Proteomics-based clinical studies represent promising resources for the discovery of novel biomarkers or for unraveling molecular mechanisms underlying particular diseases. Here, we present a discovery study of hepatocellular carcinoma developed on nonfibrotic liver (nfHCC) that combines complementary quantitative iTRAQ-based proteomics and phosphoproteomics approaches. Using both approaches, we compared a set of 24 samples (18 nfHCC versus six nontumor liver tissue). We identified 43 proteins (67 peptides) differentially expressed and 32 peptides differentially phosphorylated between the experimental groups. The functional analysis of the two data sets pointed toward the deregulation of a protein homeostasis (proteostasis) network including the up-regulation of the Endoplasmic Reticulum (ER) resident HSPA5, HSP90B1, PDIA6, and P4HB and of the cytosolic HSPA1B, HSP90AA1, HSPA9, UBC, CNDP2, TXN, and VCP as well as the increased phosphorylation of the ER resident calnexin at Ser583. Antibody-based validation approaches (immunohistochemistry, immunoblot, Alphascreen(®), and AMMP(®)) on independent nfHCC tumor sets (up to 77 samples) confirmed these observations, thereby indicating a common mechanism occurring in nfHCC tumors. Based on these results we propose that adaptation to proteostasis imbalance in nfHCC tumors might confer selective advantages to those tumors. As such, this model could provide an additional therapeutic opportunity for those tumors arising on normal liver by targeting the tumor proteostasis network. Data are available via ProteomeXchange with identifier PXD001253.

  15. Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests.

    Science.gov (United States)

    Kukuk, Guido M; Schaefer, Stephanie G; Fimmers, Rolf; Hadizadeh, Dariusch R; Ezziddin, Samer; Spengler, Ulrich; Schild, Hans H; Willinek, Winfried A

    2014-10-01

    To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p function tests, suggesting that hepatobiliary MRI may serve as a valuable biomarker for liver function. The strongest correlation with liver enhancement was found for the MELD Score. • Relative enhancement (RLE) of Gd-EOB-DTPA is related to biochemical liver function tests. • Correlation of RLE with bilirubin, ALT, AST, GGT, INR and MELD Score is reverse. • The correlation of relative liver enhancement with prothrombin time is positive. • AST, ALT, GLDH, prothrombin time, INR and MELD Score correlate with pre-contrast liver-spleen contrast ratio. • Such biomarkers may help to evaluate liver function.

  16. Photoacoustic molecular imaging for in vivo liver iron quantitation

    Science.gov (United States)

    Maccarinelli, Federica; Carmona, Fernando; Regoni, Maria; Arosio, Paolo

    2016-05-01

    A recent study showed that ferritin is a suitable endogenous contrast agent for photoacoustic molecular imaging in cultured mammalian cells. We have therefore tested whether this imaging technique can be used for in vivo quantification of iron in mouse livers. To verify this hypothesis, we used multispectral optoacoustic tomography (MSOT) to image albino CD1 mice before and after experimental iron loading. Postmortem assays showed that the iron treatment caused a 15-fold increase in liver iron and a 40-fold increase in liver ferritin levels, while in vivo longitudinal analysis using MSOT revealed just a 1.6-fold increase in the ferritin/iron photoacoustic signal in the same animals. We conclude that MSOT can monitor changes in ferritin/iron levels in vivo, but its sensitivity is much lower than that of ex vivo iron assays.

  17. Quantitative liver proteomics identifies FGF19 targets that couple metabolism and proliferation

    Science.gov (United States)

    Vos, Harmjan R.; Burgering, Boudewijn M. T.; van Mil, Saskia W. C.

    2017-01-01

    Fibroblast growth factor 19 (FGF19) is a gut-derived peptide hormone that is produced following activation of Farnesoid X Receptor (FXR). FGF19 is secreted and signals to the liver, where it contributes to the homeostasis of bile acid (BA), lipid and carbohydrate metabolism. FGF19 is a promising therapeutic target for the metabolic syndrome and cholestatic diseases, but enthusiasm for its use has been tempered by FGF19-mediated induction of proliferation and hepatocellular carcinoma. To inform future rational design of FGF19-variants, we have conducted temporal quantitative proteomic and gene expression analyses to identify FGF19-targets related to metabolism and proliferation. Mice were fasted for 16 hours, and injected with human FGF19 (1 mg/kg body weight) or vehicle. Liver protein extracts (containing “light” lysine) were mixed 1:1 with a spike-in protein extract from 13C6-lysine metabolically labelled mouse liver (containing “heavy” lysine) and analysed by LC-MS/MS. Our analyses provide a resource of FGF19 target proteins in the liver. 189 proteins were upregulated (≥ 1.5 folds) and 73 proteins were downregulated (≤ -1.5 folds) by FGF19. FGF19 treatment decreased the expression of proteins involved in fatty acid (FA) synthesis, i.e., Fabp5, Scd1, and Acsl3 and increased the expression of Acox1, involved in FA oxidation. As expected, FGF19 increased the expression of proteins known to drive proliferation (i.e., Tgfbi, Vcam1, Anxa2 and Hdlbp). Importantly, many of the FGF19 targets (i.e., Pdk4, Apoa4, Fas and Stat3) have a dual function in both metabolism and cell proliferation. Therefore, our findings challenge the development of FGF19-variants that fully uncouple metabolic benefit from mitogenic potential. PMID:28178326

  18. Quantitative liver proteomics identifies FGF19 targets that couple metabolism and proliferation.

    Science.gov (United States)

    Massafra, Vittoria; Milona, Alexandra; Vos, Harmjan R; Burgering, Boudewijn M T; van Mil, Saskia W C

    2017-01-01

    Fibroblast growth factor 19 (FGF19) is a gut-derived peptide hormone that is produced following activation of Farnesoid X Receptor (FXR). FGF19 is secreted and signals to the liver, where it contributes to the homeostasis of bile acid (BA), lipid and carbohydrate metabolism. FGF19 is a promising therapeutic target for the metabolic syndrome and cholestatic diseases, but enthusiasm for its use has been tempered by FGF19-mediated induction of proliferation and hepatocellular carcinoma. To inform future rational design of FGF19-variants, we have conducted temporal quantitative proteomic and gene expression analyses to identify FGF19-targets related to metabolism and proliferation. Mice were fasted for 16 hours, and injected with human FGF19 (1 mg/kg body weight) or vehicle. Liver protein extracts (containing "light" lysine) were mixed 1:1 with a spike-in protein extract from 13C6-lysine metabolically labelled mouse liver (containing "heavy" lysine) and analysed by LC-MS/MS. Our analyses provide a resource of FGF19 target proteins in the liver. 189 proteins were upregulated (≥ 1.5 folds) and 73 proteins were downregulated (≤ -1.5 folds) by FGF19. FGF19 treatment decreased the expression of proteins involved in fatty acid (FA) synthesis, i.e., Fabp5, Scd1, and Acsl3 and increased the expression of Acox1, involved in FA oxidation. As expected, FGF19 increased the expression of proteins known to drive proliferation (i.e., Tgfbi, Vcam1, Anxa2 and Hdlbp). Importantly, many of the FGF19 targets (i.e., Pdk4, Apoa4, Fas and Stat3) have a dual function in both metabolism and cell proliferation. Therefore, our findings challenge the development of FGF19-variants that fully uncouple metabolic benefit from mitogenic potential.

  19. How to interpret liver function tests

    African Journals Online (AJOL)

    2017-05-02

    May 2, 2017 ... (AST), but the combination of liver enzyme results you receive depends on ... can also help differentiate a liver versus bone origin. If all other liver tests are ... The half-life of albumin is 20 days and so a low albumin may be ...

  20. Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip.

    Science.gov (United States)

    Du, Yu; Li, Ning; Yang, Hao; Luo, Chunhua; Gong, Yixin; Tong, Chunfang; Gao, Yuxin; Lü, Shouqin; Long, Mian

    2017-02-28

    Physiologically, four major types of hepatic cells - the liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and hepatocytes - reside inside liver sinusoids and interact with flowing peripheral cells under blood flow. It is hard to mimic an in vivo liver sinusoid due to its complex multiple cell-cell interactions, spatiotemporal construction, and mechanical microenvironment. Here we developed an in vitro liver sinusoid chip by integrating the four types of primary murine hepatic cells into two adjacent fluid channels separated by a porous permeable membrane, replicating liver's key structures and configurations. Each type of cells was identified with its respective markers, and the assembled chip presented the liver-specific unique morphology of fenestration. The flow field in the liver chip was quantitatively analyzed by computational fluid dynamics simulations and particle tracking visualization tests. Intriguingly, co-culture and shear flow enhance albumin secretion independently or cooperatively, while shear flow alone enhances HGF production and CYP450 metabolism. Under lipopolysaccharide (LPS) stimulations, the hepatic cell co-culture facilitated neutrophil recruitment in the liver chip. Thus, this 3D-configured in vitro liver chip integrates the two key factors of shear flow and the four types of primary hepatic cells to replicate key structures, hepatic functions, and primary immune responses and provides a new in vitro model to investigate the short-duration hepatic cellular interactions under a microenvironment mimicking the physiology of a liver.

  1. Discoidin domain receptor 1: isoform expression and potential functions in cirrhotic human liver.

    Science.gov (United States)

    Song, Sunmi; Shackel, Nicholas A; Wang, Xin M; Ajami, Katerina; McCaughan, Geoffrey W; Gorrell, Mark D

    2011-03-01

    Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and is activated by collagens. Transcriptional profiling of cirrhosis in human liver using a DNA array and quantitative PCR detected elevated mRNA expression of DDR1 compared with that in nondiseased liver. The present study characterized DDR1 expression in cirrhotic and nondiseased human liver and examined the cellular effects of DDR1 expression. mRNA expression of all five isoforms of DDR1 was detected in human liver, whereas DDR1a demonstrated differential expression in liver with hepatitis C virus and primary biliary cirrhosis compared with nondiseased liver. In addition, immunoblot analysis detected shed fragments of DDR1 more readily in cirrhotic liver than in nondiseased liver. Inasmuch as DDR1 is subject to protease-mediated cleavage after prolonged interaction with collagen, this differential expression may indicate more intense activation of DDR1 protein in cirrhotic compared with nondiseased liver. In situ hybridization and immunofluorescence localized intense DDR1 mRNA and protein expression to epithelial cells including hepatocytes at the portal-parenchymal interface and the luminal aspect of the biliary epithelium. Overexpression of DDR1a altered hepatocyte behavior including increased adhesion and less migration on extracelular matrix substrates. DDR1a regulated extracellular expression of matrix metalloproteinases 1 and 2. These data elucidate DDR1 function pertinent to cirrhosis and indicate the importance of epithelial cell-collagen interactions in chronic liver injury.

  2. The correlation of contrast-enhanced ultrasound and MRI perfusion quantitative analysis in rabbit VX2 liver cancer.

    Science.gov (United States)

    Xiang, Zhiming; Liang, Qianwen; Liang, Changhong; Zhong, Guimian

    2014-12-01

    Our objective is to explore the value of liver cancer contrast-enhanced ultrasound (CEUS) and MRI perfusion quantitative analysis in liver cancer and the correlation between these two analysis methods. Rabbit VX2 liver cancer model was established in this study. CEUS was applied. Sono Vue was applied in rabbits by ear vein to dynamically observe and record the blood perfusion and changes in the process of VX2 liver cancer and surrounding tissue. MRI perfusion quantitative analysis was used to analyze the mean enhancement time and change law of maximal slope increasing, which were further compared with the pathological examination results. Quantitative indicators of liver cancer CEUS and MRI perfusion quantitative analysis were compared, and the correlation between them was analyzed by correlation analysis. Rabbit VX2 liver cancer model was successfully established. CEUS showed that time-intensity curve of rabbit VX2 liver cancer showed "fast in, fast out" model while MRI perfusion quantitative analysis showed that quantitative parameter MTE of tumor tissue increased and MSI decreased: the difference was statistically significant (P 0.05). However, the quantitative parameter of them were significantly positively correlated (P liver cancer lesion and surrounding liver parenchyma, and the quantitative parameters of them are correlated. The combined application of both is of importance in early diagnosis of liver cancer.

  3. Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

    Institute of Scientific and Technical Information of China (English)

    Andrea; De; Gasperi; Ernestina; Mazza; Manlio; Prosperi

    2016-01-01

    Indocyanine green(ICG) kinetics(PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors(pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests.

  4. Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

    Science.gov (United States)

    De Gasperi, Andrea; Mazza, Ernestina; Prosperi, Manlio

    2016-03-08

    Indocyanine green (ICG) kinetics (PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors (pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests.

  5. MRI evaluation of fatty liver in day to day practice: Quantitative and qualitative methods

    Directory of Open Access Journals (Sweden)

    Kiran Gangadhar

    2014-09-01

    Full Text Available Intracellular fat accumulation is a common feature of liver disease. Steatosis is the histological hallmark of non-alcoholic fatty liver disease (NAFLD but also may occur with alcohol abuse, viral hepatitis, HIV and genetic lipodystrophies, and chemotherapy. This condition is common in the Western population and is typically associated with obesity and the metabolic syndrome. Early diagnosis and early treatment of NAFLD are important to prevent the development of end-stage liver disease and cancer. In addition, liver fat is a risk factor for postoperative complications after liver resection and transplantation. MRI has become a primary modality to assess hepatic steatosis, both qualitatively and quantitatively. In this article we discuss various MRI methods for evaluation of hepatic steatosis.

  6. Novel approaches to assessing renal function in cirrhotic liver disease.

    Science.gov (United States)

    Portal, Andrew J; Austin, Mark; Heneghan, Michael A

    2007-09-01

    Renal dysfunction is common in patients with end-stage liver disease. Etiological factors include conditions as diverse as acute tubular necrosis, immunoglobulin A nephropathy and hepatorenal syndrome. Current standard tests of renal function, such as measurement of serum urea and creatinine levels, are inaccurate as the synthesis of these markers is affected by the native liver pathology. This article reviews novel markers of renal function and their potential use in patients with liver disease.

  7. Label-free quantitative proteomics of CD133-positive liver cancer stem cells

    Directory of Open Access Journals (Sweden)

    Tsai Sheng-Ta

    2012-11-01

    Full Text Available Abstract Background CD133-positive liver cancer stem cells, which are characterized by their resistance to conventional chemotherapy and their tumor initiation ability at limited dilutions, have been recognized as a critical target in liver cancer therapeutics. In the current work, we developed a label-free quantitative method to investigate the proteome of CD133-positive liver cancer stem cells for the purpose of identifying unique biomarkers that can be utilized for targeting liver cancer stem cells. Label-free quantitation was performed in combination with ID-based Elution time Alignment by Linear regression Quantitation (IDEAL-Q and MaxQuant. Results Initially, IDEAL-Q analysis revealed that 151 proteins were differentially expressed in the CD133-positive hepatoma cells when compared with CD133-negative cells. We then analyzed these 151 differentially expressed proteins by MaxQuant software and identified 10 significantly up-regulated proteins. The results were further validated by RT-PCR, western blot, flow cytometry or immunofluorescent staining which revealed that prominin-1, annexin A1, annexin A3, transgelin, creatine kinase B, vimentin, and EpCAM were indeed highly expressed in the CD133-positive hepatoma cells. Conclusions These findings confirmed that mass spectrometry-based label-free quantitative proteomics can be used to gain insights into liver cancer stem cells.

  8. Hypothalamic-pituitary-gonadal function in men with liver cirrhosis before and after liver transplantation

    Directory of Open Access Journals (Sweden)

    Bruno T. Zacharias

    2014-12-01

    Full Text Available Objective: To evaluate the influence of end-stage liver disease and orthotopic liver transplantation in the pituitary function and hormone metabolism before and after liver transplantation. Methods: In a prospective study, serum levels of follicle stimulating hormone (FSH, luteinizing hormone (LH, estradiol (E2 and prolactin (PRL of 30 male patients with cirrhosis were determined two to four hours before and six months after liver transplantation. The results were compared according to the Model for End-stage Liver Disease (MELD. Results: male patients with liver cirrhosis have hypogonadism. FSH was normal, but inappropriately low due to androgen failure; E2 and PRL, on their turn, were high. After liver transplantation, FSH and LH levels increased (p 18. The severity of cirrhosis had no influence on FSH, PRL and LH.

  9. Effects of Radix Polygoni Multiflori Preparata and Quantitative Exercise on Rat Liver Microcirculation and Liver Function%制首乌联合定量运动对大鼠肝脏微循环及肝功能的影响

    Institute of Scientific and Technical Information of China (English)

    常青; 赵海娟; 李春; 廖福龙; 王伽伯; 肖小河; 游云

    2014-01-01

    目的:探讨长期服用制首乌联合定量运动对肝脏微循环和肝功能的影响。方法采用2×2析因设计,大鼠随机分为静止不给药(S/C)组,静止给药(S/D)组,游泳不给药(SW/C)组,游泳给药(SW/D)组,每天给予不同水平的制首乌醇提物(0g·kg-1、20g·kg-1 p.o)及不同水平的游泳运动(0h、1h),连续30d。采用激光散斑血流监测视频系统检测大鼠肝脏微循环血流灌注量的变化;检测大鼠血清NOS3含量及肝功能9项生化指标。结果与S/C组比,制首乌醇提物降低大鼠肝脏血流平均灌注量(P<0.01),同时显著降低血清内皮源一氧化氮合成酶(NOS3)含量(P<0.05),并可显著升高大鼠总胆红素(TBIL)、直接胆红素(DBIL),显著降低间接胆红素(IBIL)(均P<0.001)。游泳对制首乌引起的肝脏微循环灌注量和血清NOS3含量下降均有显著恢复作用,但游泳不能改善制首乌引起的血清胆红素异常。结论本研究首次证明大剂量长期服用制首乌可导致肝脏微循环灌注量障碍,而适当的运动则可能拮抗药源性肝脏微循环障碍。%Objective To investigate the long-term effects of taking Radix Polygoni multiflori Preparata combined quantitative exercise on hepatic microcirculation and liver function. Methods 2 ×2 factor experimental design was used. Rats were randomly divided into four groups, namely, static without drug group (S/C), static with drug group (S/D), swim without drug group(SW/C), swim with drug group(SW/D), given the different levels of Radix Polygoni multiflori Preparata alcohol extract (0g·kg-1, 20g·kg-1 p.o) and different levels of swimming(0h, 1h). After 30 days, using Laser Doppler blood flow imaging system to monitor the change of rat hepatic microcirculation blood flow;the serums of rats were collected to determine the content of NOS3 and the biochemical indexes of liver function. Results Compared

  10. Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, P;

    1983-01-01

    The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...... in patients with alcoholic cirrhosis. This decrease seems to be due to decreased liver function, decreasing hepatic blood flow, and increased portosystemic shunting. Oral testosterone loading may therefore be of prognostic significance in patients with alcoholic liver cirrhosis....

  11. The influence of brain death on liver function

    NARCIS (Netherlands)

    Olinga, Peter; Hoeven, Joost Alexander Boreas van der; Merema, M.T.; Freund, R.L.; Ploeg, R.J; Groothuis, Geny

    2005-01-01

    Background: In this study, we investigated the influence of brain death on inflammatory response and the effects of brain death on liver function both directly after explantation and after reoxygenation. Methods: The influence of brain death on liver function was studied in rats using a brain death

  12. Rapid Quantitative Determination of Squalene in Shark Liver Oils by Raman and IR Spectroscopy.

    Science.gov (United States)

    Hall, David W; Marshall, Susan N; Gordon, Keith C; Killeen, Daniel P

    2016-01-01

    Squalene is sourced predominantly from shark liver oils and to a lesser extent from plants such as olives. It is used for the production of surfactants, dyes, sunscreen, and cosmetics. The economic value of shark liver oil is directly related to the squalene content, which in turn is highly variable and species-dependent. Presented here is a validated gas chromatography-mass spectrometry analysis method for the quantitation of squalene in shark liver oils, with an accuracy of 99.0 %, precision of 0.23 % (standard deviation), and linearity of >0.999. The method has been used to measure the squalene concentration of 16 commercial shark liver oils. These reference squalene concentrations were related to infrared (IR) and Raman spectra of the same oils using partial least squares regression. The resultant models were suitable for the rapid quantitation of squalene in shark liver oils, with cross-validation r (2) values of >0.98 and root mean square errors of validation of ≤4.3 % w/w. Independent test set validation of these models found mean absolute deviations of the 4.9 and 1.0 % w/w for the IR and Raman models, respectively. Both techniques were more accurate than results obtained by an industrial refractive index analysis method, which is used for rapid, cheap quantitation of squalene in shark liver oils. In particular, the Raman partial least squares regression was suited to quantitative squalene analysis. The intense and highly characteristic Raman bands of squalene made quantitative analysis possible irrespective of the lipid matrix.

  13. EX VIVO STUDY OF QUANTITATIVE ULTRASOUND PARAMETERS IN FATTY RABBIT LIVERS

    Science.gov (United States)

    Ghoshal, Goutam; Lavarello, Roberto J.; Kemmerer, Jeremy P.; Miller, Rita J.; Oelze, Michael L.

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) affects more than 30% of Americans, and with increasing problems of obesity in the United States, NAFLD is poised to become an even more serious medical concern. At present, accurate classification of steatosis (fatty liver) represents a significant challenge. In this study, the use of high-frequency (8 to 25 MHz) quantitative ultrasound (QUS) imaging to quantify fatty liver was explored. QUS is an imaging technique that can be used to quantify properties of tissue giving rise to scattered ultrasound. The changes in the ultrasound properties of livers in rabbits undergoing atherogenic diets of varying durations were investigated using QUS. Rabbits were placed on a special fatty diet for 0, 3, or 6 weeks. The fattiness of the livers was quantified by estimating the total lipid content of the livers. Ultrasonic properties, such as speed of sound, attenuation, and backscatter coefficients, were estimated in ex vivo rabbit liver samples from animals that had been on the diet for varying periods. Two QUS parameters were estimated based on the backscatter coefficient: effective scatterer diameter (ESD) and effective acoustic concentration (EAC), using a spherical Gaussian scattering model. Two parameters were estimated based on the backscattered envelope statistics (the k parameter and the μ parameter) according to the homodyned K distribution. The speed of sound decreased from 1574 to 1565 m/s and the attenuation coefficient increased from 0.71 to 1.27 dB/cm/MHz, respectively, with increasing fat content in the liver. The ESD decreased from 31 to 17 μm and the EAC increased from 38 to 63 dB/cm3 with increasing fat content in the liver. A significant increase in the μ parameter from 0.18 to 0.93 scatterers/mm3 was observed with increasing fat content in the liver samples. The results of this study indicate that QUS parameters are sensitive to fat content in the liver. PMID:23062376

  14. Quantitative characterization of fatty liver disease using x-ray scattering

    Science.gov (United States)

    Elsharkawy, Wafaa B.; Elshemey, Wael M.

    2013-11-01

    Nonalcoholic fatty liver disease (NAFLD) is a dynamic condition in which fat abnormally accumulates within the hepatocytes. It is believed to be a marker of risk of later chronic liver diseases, such as liver cirrhosis and carcinoma. The fat content in liver biopsies determines its validity for liver transplantation. Transplantation of livers with severe NAFLD is associated with a high risk of primary non-function. Moreover, NAFLD is recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection. Unfortunately, there is a lack in a precise, reliable and reproducible method for quantification of NAFLD. This work suggests a method for the quantification of NAFLD. The method is based on the fact that fatty liver tissue would have a characteristic x-ray scattering profile with a relatively intense fat peak at a momentum transfer value of 1.1 nm-1 compared to a soft tissue peak at 1.6 nm-1. The fat content in normal and fatty liver is plotted against three profile characterization parameters (ratio of peak intensities, ratio of area under peaks and ratio of area under fat peak to total profile area) for measured and Monte Carlo simulated x-ray scattering profiles. Results show a high linear dependence (R2>0.9) of the characterization parameters on the liver fat content with a reported high correlation coefficient (>0.9) between measured and simulated data. These results indicate that the current method probably offers reliable quantification of fatty liver disease.

  15. Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, Patrick;

    1983-01-01

    The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140....

  16. Quantitative multivoxel H-1 MR spectroscopy of the brain in children with acute liver failure

    NARCIS (Netherlands)

    Sijens, Paul E.; Alkefaji, Heyder; Lunsing, Roelineke J.; van Spronsen, Francjan J.; Meiners, Linda C.; Oudkerk, Matthijs; Verkade, Henkjan J.

    2008-01-01

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) an

  17. Quantitation of ketogenesis in periportal and pericentral regions of the liver lobule.

    Science.gov (United States)

    Olson, M J; Thurman, R G

    1987-02-15

    A method has been devised to quantitate rates of ketogenesis (acetoacetate + beta-hydroxybutyrate production) in discrete regions of the liver lobule based on changes in NADH fluorescence. In perfused livers from fasted rats, ketogenesis was inhibited nearly completely with either 2-bromoctanoate (600 microM) or 2-tetradecylglycidic acid (25 microM). During inhibition of ketogenesis, a linear relationship (r = 0.90) was observed between decreases in NADH fluorescence detected from the liver surface and decreases in ketone body production. NADH fluorescence was monitored subsequently from individual regions of the liver lobule by placing microlight guides on periportal and pericentral regions of the liver lobule visible on the liver surface. Rates of ketogenesis in sublobular regions were calculated from regional decreases in NADH fluorescence and changes in the rate of ketone body formation by the whole liver during infusion of inhibitors. In the presence of bromoctanoate, ketogenesis was reduced 80% and local rates of ketogenesis were decreased 31 +/- 4 mumol/g/h in periportal areas and 28 +/- 3 mumol/g/h in pericentral regions. Similar results were observed with tetradecylglycidic acid. Therefore, it was concluded that submaximal rates of ketogenesis from endogenous, mainly long-chain fatty acids are nearly equal in periportal and pericentral regions of the liver lobule in liver from fasted rats. Rates of ketogenesis and NADH fluorescence were strongly correlated during fatty acid infusion. Infusion of 250 microM oleate increased NADH fluorescence maximally by 8 +/- 1% over basal values in periportal regions and 17 +/- 4% in pericentral areas. Local rates of ketogenesis, calculated from these changes in fluorescence, increased 35 +/- 6 mumol/g/h in periportal areas and 55 +/- 5 mumol/g/h in pericentral regions. Thus, oleate stimulated ketogenesis nearly 60% more in pericentral than in periportal regions of the liver lobule.

  18. The proteome of human liver peroxisomes: identification of five new peroxisomal constituents by a label-free quantitative proteomics survey.

    Directory of Open Access Journals (Sweden)

    Thomas Gronemeyer

    Full Text Available The peroxisome is a key organelle of low abundance that fulfils various functions essential for human cell metabolism. Severe genetic diseases in humans are caused by defects in peroxisome biogenesis or deficiencies in the function of single peroxisomal proteins. To improve our knowledge of this important cellular structure, we studied for the first time human liver peroxisomes by quantitative proteomics. Peroxisomes were isolated by differential and Nycodenz density gradient centrifugation. A label-free quantitative study of 314 proteins across the density gradient was accomplished using high resolution mass spectrometry. By pairing statistical data evaluation, cDNA cloning and in vivo colocalization studies, we report the association of five new proteins with human liver peroxisomes. Among these, isochorismatase domain containing 1 protein points to the existence of a new metabolic pathway and hydroxysteroid dehydrogenase like 2 protein is likely involved in the transport or β-oxidation of fatty acids in human peroxisomes. The detection of alcohol dehydrogenase 1A suggests the presence of an alternative alcohol-oxidizing system in hepatic peroxisomes. In addition, lactate dehydrogenase A and malate dehydrogenase 1 partially associate with human liver peroxisomes and enzyme activity profiles support the idea that NAD(+ becomes regenerated during fatty acid β-oxidation by alternative shuttling processes in human peroxisomes involving lactate dehydrogenase and/or malate dehydrogenase. Taken together, our data represent a valuable resource for future studies of peroxisome biochemistry that will advance research of human peroxisomes in health and disease.

  19. The effect of radiofrequency-assisted liver resection on liver function

    Directory of Open Access Journals (Sweden)

    Metin Şen

    2013-06-01

    Full Text Available Aim. To investigate the effects of Radiofrequency (RF-assisted liver parenchyma dissection technique for the treatment of colorectal metastatic liver tumors in liver parenchymal function. Methods. Fifteen patients with colorectal hepatic metastases underwent radiofrequency assisted hepatic resection. Preoperative and postoperative (1st day and 8th day liver function tests were eveluated. Results. Aspartate aminotransferase (AST and Alanine transaminase (ALT was increased in 100% of patients on the day after RF. However, 8 days after surgery ALT and AST levels have almost fully recovered. Serum bilirubine, alkaline phosphatase (ALP and Gamma-glutamyl transpeptidase (GGT, levels were not increased in postoperative period. Conclusion. Hepatic parenchymal transection with RF device is an effective method to resect colorectal hepatic metastases. Careful patient selection will help to minimize the incidence of liver failure which may occur after RFA.

  20. Stem cell-derived hepatocytes for functional liver replacement

    Directory of Open Access Journals (Sweden)

    Bruno eChrist

    2012-06-01

    Full Text Available Mesenchymal stem cells (MSC represent an alternate cell source to substitute for primary hepatocytes in hepatocyte transplantation because of their multiple differentiation potential and nearly unlimited availability. They may differentiate into hepatocyte-like cells in vitro and maintain specific hepatocyte functions also after transplantation into the regenerating livers of mice or rats both under injury and non-injury conditions. Depending on the underlying liver disease their mode of action is either to replace the diseased liver tissue or to support liver regeneration through their anti-inflammatory and anti-apoptotic as well as their pro-proliferative action.

  1. [The general practitioner and abnormal liver function tests].

    Science.gov (United States)

    Hallez, R

    1997-09-01

    In case of abnormal liver function tests, it's necessary to distinguish different situations, starting from this first data. We will successively consider: the high and moderate acute increases of aminotransferase, the chronic increases of aminotransferase, the isolated cholestase picture and the isolated increases of gamma GT or of bilirubine. We will finish with a partial survey about drug-induced liver diseases.

  2. Application of quantitative targeted absolute proteomics to profile protein expression changes of hepatic transporters and metabolizing enzymes during cholic acid-promoted liver regeneration.

    Science.gov (United States)

    Miura, Takayuki; Tachikawa, Masanori; Ohtsuka, Hideo; Fukase, Koji; Nakayama, Shun; Sakata, Naoaki; Motoi, Fuyuhiko; Naitoh, Takeshi; Katayose, Yu; Uchida, Yasuo; Ohtsuki, Sumio; Terasaki, Tetsuya; Unno, Michiaki

    2017-02-26

    Preoperative administration of cholic acid (CA) may be an option to increase the liver volume before elective liver resection surgery, so it is important to understand its effects on liver functionality for drug transport and metabolism. The purpose of this study was to clarify the absolute protein expression dynamics of transporters and metabolizing enzymes in the liver of mice fed CA-containing diet for 5 days (CA1) and mice fed CA-containing diet for 5 days followed by diet without CA for 7 days (CA2), in comparison with non CA-fed control mice. The CA1 group showed the increased liver weight, cell proliferation index, and oxidative stress, but no increase of apoptosis. Quantitative targeted absolute proteomics revealed (i) decreases in basolateral bile acid transporters ntcp, oatp1a1, oatp1b2, bile acid synthesis-related enzymes cyp7a1 and cyp8b1, and drug transporters bcrp, mrp6, ent1, oatp2b1, and (ii) increases in glutathione biosynthetic enzymes and drug-metabolizing enzyme cyp3a11. Liver concentrations of reduced and oxidized glutathione were both increased. In the CA2 group, the increased liver weight was maintained, while the biochemical features and protein profiles were restored to the non-CA-fed control levels. These findings suggest that CA administration alters liver functionality per body during liver regeneration and restoration.

  3. Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests

    Energy Technology Data Exchange (ETDEWEB)

    Kukuk, Guido M.; Schaefer, Stephanie G.; Hadizadeh, Dariusch R.; Schild, Hans H.; Willinek, Winfried A. [University of Bonn, Department of Radiology, Bonn (Germany); Fimmers, Rolf [University of Bonn, Department of Medical Biometry, Informatics and Epidemiology, Bonn (Germany); Ezziddin, Samer [Department of Nuclear Medicine, Bonn (Germany); Spengler, Ulrich [Department of Internal Medicine I, Bonn (Germany)

    2014-10-15

    To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p < 0.001), GLDH (r = -0.55; p = 0.044), INR (r = -0.42; p = 0.003), and MELD Score (r = -0.53; p < 0.001). After administration of Gd-EOB-DTPA bilirubin (r = -0.45; p = 0.001), GGT (r = -0.40; p = 0.004), PT (r = 0.54; p < 0.001), AST (r = -0.46; p = 0.002), ALT (r = -0.31; p = 0.030), INR (r = -0.45; p = 0.001) and MELD Score (r = -0.56; p < 0.001) significantly correlated with LSCR. RLE correlated with bilirubin (r = -0.40; p = 0.004), AST (r = -0.38; p = 0.013), PT (r = 0.42; p = 0.003), GGT (r = -0.33; p = 0.020), INR (r = -0.36; p = 0.011) and MELD Score (r = -0.43; p = 0.003). Liver-spleen contrast ratio and relative liver enhancement using Gd-EOB-DTPA correlate with a number of routinely used biochemical liver function tests, suggesting that hepatobiliary MRI may serve as a valuable biomarker for liver function. The strongest correlation with liver enhancement was found for the MELD Score. (orig.)

  4. Optimizing global liver function in radiation therapy treatment planning

    Science.gov (United States)

    Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.

    2016-09-01

    Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and

  5. Optimizing global liver function in radiation therapy treatment planning

    Science.gov (United States)

    Wu, Victor W; Epelman, Marina A; Wang, Hesheng; Romeijn, H Edwin; Feng, Mary; Cao, Yue; Haken, Randall K Ten; Matuszak, Martha M

    2017-01-01

    Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (ℓEUD) (conventional ‘ℓEUD model’), the so-called perfusion-weighted ℓEUD (fEUD) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting ℓEUD, fEUD, and GLF plans delivering the same target ℓEUD are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6%(7.5%) more liver function than the fEUD (ℓEUD) plan does in 2D cases, and up to 4.5%(5.6%) in 3D cases. The GLF and fEUD plans worsen in ℓEUD of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than ℓEUD model optimization does, the GLF model directly optimizes a more clinically

  6. liver function markers and associated serum electrolytes changes in ...

    African Journals Online (AJOL)

    2013-09-09

    Sep 9, 2013 ... Results: Serum liver function markers were significantly altered in HIV infected individuals compared ... correlated with protein levels (r = 0.917) and vice versa. .... hypertension, diabetes or alcohol abuse or history of jaundice ...

  7. Sexual function of males with chronic liver disease

    African Journals Online (AJOL)

    recently that in patients with liver disease, there is ... sexual function, which is compounded by the dual epidemic of ... Hepatitis B virus in many African countries. In addition, the low ... workers, male circumcision for HIV prevention, and food ...

  8. Function of GATA Factors in the Adult Mouse Liver

    Science.gov (United States)

    Zheng, Rena; Rebolledo-Jaramillo, Boris; Zong, Yiwei; Wang, Liqing; Russo, Pierre; Hancock, Wayne; Stanger, Ben Z.; Hardison, Ross C.; Blobel, Gerd A.

    2013-01-01

    GATA transcription factors and their Friend of Gata (FOG) cofactors control the development of diverse tissues. GATA4 and GATA6 are essential for the expansion of the embryonic liver bud, but their expression patterns and functions in the adult liver are unclear. We characterized the expression of GATA and FOG factors in whole mouse liver and purified hepatocytes. GATA4, GATA6, and FOG1 are the most prominently expressed family members in whole liver and hepatocytes. GATA4 chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) identified 4409 occupied sites, associated with genes enriched in ontologies related to liver function, including lipid and glucose metabolism. However, hepatocyte-specific excision of Gata4 had little impact on gross liver architecture and function, even under conditions of regenerative stress, and, despite the large number of GATA4 occupied genes, resulted in relatively few changes in gene expression. To address possible redundancy between GATA4 and GATA6, both factors were conditionally excised. Surprisingly, combined Gata4,6 loss did not exacerbate the phenotype resulting from Gata4 loss alone. This points to the presence of an unusually robust transcriptional network in adult hepatocytes that ensures the maintenance of liver function. PMID:24367609

  9. Effect of Liver Disease on Hepatic Transporter Expression and Function.

    Science.gov (United States)

    Thakkar, Nilay; Slizgi, Jason R; Brouwer, Kim L R

    2017-09-01

    Liver disease can alter the disposition of xenobiotics and endogenous substances. Regulatory agencies such as the Food and Drug Administration and the European Medicines Evaluation Agency recommend, if possible, studying the effect of liver disease on drugs under development to guide specific dose recommendations in these patients. Although extensive research has been conducted to characterize the effect of liver disease on drug-metabolizing enzymes, emerging data have implicated that the expression and function of hepatobiliary transport proteins also are altered in liver disease. This review summarizes recent developments in the field, which may have implications for understanding altered disposition, safety, and efficacy of new and existing drugs. A brief review of liver physiology and hepatic transporter localization/function is provided. Then, the expression and function of hepatic transporters in cholestasis, hepatitis C infection, hepatocellular carcinoma, human immunodeficiency virus infection, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and primary biliary cirrhosis are reviewed. In the absence of clinical data, nonclinical information in animal models is presented. This review aims to advance the understanding of altered expression and function of hepatic transporters in liver disease and the implications of such changes on drug disposition. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  10. Assessment of hepatic functional reserve by cirrhosis grading and liver volume measurement using CT

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To explore a method for quantitative assessment of hepatic functional reserve by combining computed tomography (CT) volumetry with CT grading of liver cirrhosis before liver resection in patients with hepatocellular carcinoma.METHODS: CT images of 55 patients undergoing liver resection were studied prospectively. The degree of liver cirrhosis was referred as "CT grade" and the percentage of remnant liver volume (PRLV) [PRLV = predicted RLV/predicted total liver volume (PTLV) × 100%;PTLV (mL) = 121.75 + 16.49 × body mass (kg)] were calculated by adding slice by slice of CT liver images.The postoperative RLV, pathologic stages of liver fibrosis in non-tumor area and survival time in these cases were analyzed.RESULTS: There was a significant difference in survival time between the group with PRLV ≤ 50% and the group with PRLV > 50% (χ2= 4.988, P = 0.026), and between the group with CT grade 0/1 and the group with CT grade 2/3 (χ2= 5.429, P = 0.026). With combination of the both parameters, an oblique line was identified according to the distribution of 32 survivors versus 23 deceased subjects. The mortality rate above the line was 7.1% (1/14), and that below the line was 53.7% (22/41),indicating a significant difference between the two rates (χ2 = 9.281, P = 0.002, P < 0.05).CONCLUSION: PRLV and CT grades are significantly correlated with hepatic functional reserve. The predicted line using these two parameters is useful in candidates undergoing liver resection for judging hepatic functional reserve.

  11. Biomechanics and functionality of hepatocytes in liver cirrhosis.

    Science.gov (United States)

    Sun, Shan; Song, Zhenyuan; Cotler, Scott J; Cho, Michael

    2014-06-27

    Cirrhosis is a life-threatening condition that is generally attributed to overproduction of collagen fibers in the extracellular matrix that mechanically stiffens the liver. Chronic liver injury due to causes including viral hepatitis, inherited and metabolic liver diseases and external factors such as alcohol abuse can result in the development of cirrhosis. Progression of cirrhosis leads to hepatocellular dysfunction. While extensive studies to understand the complexity underlying liver fibrosis have led to potential application of anti-fibrotic drugs, no such FDA-approved drugs are currently available. Additional studies of hepatic fibrogenesis and cirrhosis primarily have focused on the extracellular matrix, while hepatocyte biomechanics has received limited attention. The role of hepatocyte biomechanics in liver cirrhosis remains elusive, and how the cell stiffness is correlated with biological functions of hepatocytes is also unknown. In this study, we demonstrate that the biomechanical properties of hepatocytes are correlated with their functions (e.g., glucose metabolism), and that hepatic dysfunction can be restored through modulation of the cellular biomechanics. Furthermore, our results indicate the hepatocyte functionality appears to be regulated through a crosstalk between the Rho and Akt signaling. These novel findings may lead to biomechanical intervention of hepatocytes and the development of innovative tissue engineering for clinical treatment to target liver cells rather than exclusively focusing on the extracellular matrix alone in liver cirrhosis.

  12. Fibrosis assessment: impact on current management of chronic liver disease and application of quantitative invasive tools.

    Science.gov (United States)

    Wang, Yan; Hou, Jin-Lin

    2016-05-01

    Fibrosis, a common pathogenic pathway of chronic liver disease (CLD), has long been indicated to be significantly and most importantly associated with severe prognosis. Nowadays, with remarkable advances in understanding and/or treatment of major CLDs such as hepatitis C, B, and nonalcoholic fatty liver disease, there is an unprecedented requirement for the diagnosis and assessment of liver fibrosis or cirrhosis in various clinical settings. Among the available approaches, liver biopsy remains the one which possibly provides the most direct and reliable information regarding fibrosis patterns and changes in the parenchyma at different clinical stages and with different etiologies. Thus, many endeavors have been undertaken for developing methodologies based on the strategy of quantitation for the invasive assessment. Here, we analyze the impact of fibrosis assessment on the CLD patient care based on the data of recent clinical studies. We discuss and update the current invasive tools regarding their technological features and potentials for the particular clinical applications. Furthermore, we propose the potential resolutions with application of quantitative invasive tools for some major issues in fibrosis assessment, which appear to be obstacles against the nowadays rapid progress in CLD medicine.

  13. Liver volume in thalassaemia major: relationship with body weight, serum ferritin, and liver function

    Energy Technology Data Exchange (ETDEWEB)

    Chan Yuleung; Law Manyee; Howard, Robert [Chinese University of Hong Kong, Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, Hong Kong (China); Li Chikong; Chik Kiwai [Chinese University of Hong Kong, Department of Paediatrics, Prince of Wales Hospital, Hong Kong (China)

    2005-02-01

    It is not known whether body weight alone can adjust for the volume of liver in the calculation of the chelating dose in {beta}-thalassaemia major patients, who frequently have iron overload and hepatitis. The hypothesis is that liver volume in children and adolescents suffering from {beta}-thalassaemia major is affected by ferritin level and liver function. Thirty-five {beta}-thalassaemia major patients aged 7-18 years and 35 age- and sex-matched controls had liver volume measured by MRI. Serum alanine aminotransferase (ALT) and ferritin levels were obtained in the thalassaemia major patients. Body weight explained 65 and 86% of the change in liver volume in {beta}-thalassaemia major patients and age-matched control subjects, respectively. Liver volume/kilogram body weight was significantly higher (P<0.001) in thalassaemia major patients than in control subjects. There was a significant correlation between ALT level and liver volume/kilogram body weight (r=0.55, P=0.001). Patients with elevated ALT had significantly higher liver volume/kilogram body weight (mean 42.9{+-}12 cm{sup 3}/kg) than control subjects (mean 23.4{+-}3.6 cm{sup 3}/kg) and patients with normal ALT levels (mean 27.4{+-}3.6 cm{sup 3}/kg). Body weight is the most important single factor for liver-volume changes in thalassaemia major patients, but elevated ALT also has a significant role. Direct liver volume measurement for chelation dose adjustment may be advantageous in patients with elevated ALT. (orig.)

  14. Quantitative evaluation of liver functional reserve by asialoglycoprotein receptor and clinical test indexs%应用去唾液酸糖蛋白受体及临床指标建立肝储备功能定量评估系统

    Institute of Scientific and Technical Information of China (English)

    李勤涛; 丁振昊; 郭立民; 穆毅; 蒋力; 张珂; 黄容海; 李宝亮; 贾哲; 鲁岩; 赫嵘

    2014-01-01

    目的:探讨应用肝细胞表面ASGPR流式细胞分析及临床指标建立肝储备功能定量评估系统,并与Child-Pugh评分进行比较,了解其在患者术前肝储备功能评估中的临床应用价值。方法选择32例肝占位病变行肝部分切除术患者,术前检测ICGR15与EHBF、R值与K值以及临床生化指标、Child-Pugh评分,以此作为自变量(Xn),以肝组织标本PHCASGPR+为因变量(Y),通过多元线性回归分析,建立肝储备功能定量评估系统,并与Child-Pugh评分进行比较,了解两种方法预测术后肝功能代偿情况的准确率。按照回归方程计算46例肝占位病变接受肝部分切除术及肝硬化并门脉高压症接受断流术患者肝储备功能定量值,评估肝储备功能情况,预测术后肝功能恢复情况,比较术前不同Child-Pugh分级与Y值患者术后肝功能恢复情况。结果在预测术后肝功能代偿良好准确率方面,Y值优于Child-Pugh分级(P =0.030);而在预测术后肝功能代偿不良准确率方面,Y值与Child-Pugh分级无统计学差异(P =1.000)。结论新肝储备功能定量评估系统能一定程度提高肝切除或肝硬化患者术前肝储备功能评价准确度,具有临床应用价值。%Objective To investigate a quantitative assessment of hepatic functional reserve using flow cytometric analysis of asialoglycoprotein receptors (ASGPR) on the liver cell surface and regular clinical indexes. This assessment method was compared with the Child-Pugh score to evaluate its predictive value for hepatic functional reserve in patients undergoing liver resection or devascularization. Methods Total of 32 patients with liver tumors had partial hepatectomy. The percentage of the ASGPR+hepatocyte (PHCASGPR+), ICGR15, effective hepatic blood flow (EHBF), the R value, the K value and regular clinical parameters were examined to evaluate a quantitative assessment method for liver functional

  15. Treatment assessment of radiotherapy using MR functional quantitative imaging

    Institute of Scientific and Technical Information of China (English)

    Zheng; Chang; Chunhao; Wang

    2015-01-01

    Recent developments in magnetic resonance(MR) functional quantitative imaging have made it a potentially powerful tool to assess treatment response in radiation therapy. With its abilities to capture functional information on underlying tissue characteristics, MR functional quantitative imaging can be valuable in assessing treatment response and as such to optimize therapeutic outcome. Various MR quantitative imaging techniques, including diffusion weighted imaging, diffusion tensor imaging, MR spectroscopy and dynamic contrastenhanced imaging, have been investigated and found useful for assessment of radiotherapy. However, various aspects including data reproducibility, interpretation of biomarkers, image quality and data analysis impose challenges on applications of MR functional quantitative imaging in radiotherapy assessment. All of these challenging issues shall be addressed to help us understand whether MR functional quantitative imaging is truly beneficial and contributes to future development of radiotherapy. It is evident that individualized therapy is the future direction of patient care. MR functional quantitative imaging might serves as an indispensable tool towards this promising direction.

  16. Hepatic mitochondrial function analysis using needle liver biopsy samples.

    Directory of Open Access Journals (Sweden)

    Michael J J Chu

    Full Text Available BACKGROUNDS AND AIM: Current assessment of pre-operative liver function relies upon biochemical blood tests and histology but these only indirectly measure liver function. Mitochondrial function (MF analysis allows direct measurement of cellular metabolic function and may provide an additional index of hepatic health. Conventional MF analysis requires substantial tissue samples (>100 mg obtained at open surgery. Here we report a method to assess MF using <3 mg of tissue obtained by a Tru-cut® biopsy needle making it suitable for percutaneous application. METHODS: An 18G Bard® Max-core® biopsy instrument was used to collect samples. The optimal Tru-cut® sample weight, stability in ice-cold University of Wisconsin solution, reproducibility and protocol utility was initially evaluated in Wistar rat livers then confirmed in human samples. MF was measured in saponin-permeabilized samples using high-resolution respirometry. RESULTS: The average mass of a single rat and human liver Tru-cut® biopsy was 5.60±0.30 and 5.16±0.15 mg, respectively (mean; standard error of mean. Two milligram of sample was found the lowest feasible mass for the MF assay. Tissue MF declined after 1 hour of cold storage. Six replicate measurements within rats and humans (n = 6 each showed low coefficient of variation (<10% in measurements of State-III respiration, electron transport chain (ETC capacity and respiratory control ratio (RCR. Ischemic rat and human liver samples consistently showed lower State-III respiration, ETC capacity and RCR, compared to normal perfused liver samples. CONCLUSION: Consistent measurement of liver MF and detection of derangement in a disease state was successfully demonstrated using less than half the tissue from a single Tru-cut® biopsy. Using this technique outpatient assessment of liver MF is now feasible, providing a new assay for the evaluation of hepatic function.

  17. Quantitative optical imaging of paracetamol-induced metabolism changes in the liver

    Science.gov (United States)

    Liang, Xiaowen; Wang, Haolu; Liu, Xin; Roberts, Michael

    2016-12-01

    Paracetamol is the most readily available and widely used painkiller. However, its toxicity remains the most common cause of liver injury. The toxicity of paracetamol has been attributing to its toxic metabolite, which depletes cellular glutathione (GSH) stores and reacts within cells to increase oxidative stress, leading to mitochondrial dysfunction and cell necrosis. Multiphoton microscopy (MPM) and fluorescence lifetime imaging (FLIM) can provide quantitative imaging of biological tissues and organs in vivo and allow direct visualization of cellular events, which were used to monitor cellular metabolism in paracetamol-induced toxicity in this study. To better understand mechanisms of paracetamol induced liver injury, the redox ratio of NADH/FAD in liver cells were detected and quantified by MPM imaging to represent the relative rates of glycolysis and oxidative phosphorylation within cells. Compared to normal liver, average fluorescence lifetime of NADH and redox ratio of NADH/FAD in hepatocytes was significantly decreased after paracetamol overdose for 12 and 24 hrs, reflecting impaired metabolic activity. GSH levels of treatment groups were significantly lower than those of normal livers, with gradually decreasing from periportal to centrilobular zonation. This imaging technique has significant implications for investigating metabolic mechanisms of paracetamol toxicity.

  18. Functions of autophagy in normal and diseased liver

    Science.gov (United States)

    Czaja, Mark J.; Ding, Wen-Xing; Donohue, Terrence M.; Friedman, Scott L.; Kim, Jae-Sung; Komatsu, Masaaki; Lemasters, John J.; Lemoine, Antoinette; Lin, Jiandie D.; Ou, Jing-hsiung James; Perlmutter, David H.; Randall, Glenn; Ray, Ratna B.; Tsung, Allan; Yin, Xiao-Ming

    2013-01-01

    Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases. PMID:23774882

  19. DIETARY FOOD FORTIFIED WITH OROTIC ACID AND LIVER FUNCTION

    Directory of Open Access Journals (Sweden)

    Yohanes Buang

    2011-11-01

    Full Text Available The effects of dietary food fortified with orotic acid (1.0% on liver function were studied in rats. The rats fed withorotic acid promoted liver triglyceride content markedly, that was 5-fold higher than that of the control. The livermalondialdehyde (MDA content increased by 10%, but the gluthation peroxidase (GSH-Px activity decreased by 50%.The serum aspartate aminotransferase (AST and alanine aminotransferase (ALT activities increased by 25% and 30%,respectively. Therefore, the decreased GSH-Px activity was associated with the promotions of AST, ALT, and the liverMDA levels. In conclusion: dietary orotic acid promotes lipid peroxidation but reduces the rate of the antioxidantenzyme. Therefore, dietary food fortified with orotic acid attenuates the liver function.

  20. Structure, regulation and function of gap junctions in liver

    Science.gov (United States)

    Maes, Michaël; Decrock, Elke; Wang, Nan; Leybaert, Luc; da Silva, Tereza Cristina; Veloso Alves Pereira, Isabel; Jaeschke, Hartmut; Cogliati, Bruno; Vinken, Mathieu

    2016-01-01

    Gap junctions are a specialized group of cell-to-cell junctions that mediate direct intercellular communication between cells. They arise from the interaction of 2 hemichannels of adjacent cells, which in turn are composed of 6 connexin proteins. In liver, gap junctions are predominantly found in hepatocytes and play critical roles in virtually all phases of the hepatic life cycle, including cell growth, differentiation, liver-specific functionality and cell death. Liver gap junctions are directed through a broad variety of mechanisms ranging from epigenetic control of connexin expression to posttranslational regulation of gap junction activity. This paper reviews established and novel aspects regarding the architecture, control and functional relevance of liver gap junctions. PMID:27001459

  1. Quantitative MRI for hepatic fat fraction and T2* measurement in pediatric patients with non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Jie; Rigsby, Cynthia K.; Donaldson, James S. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Fishbein, Mark H. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Gastroenterology, Hepatology, and Nutrition, Chicago, IL (United States); Zhang, Gang [Ann and Robert H. Lurie Children' s Hospital of Chicago, Biostatistics Research Core, Chicago, IL (United States); Schoeneman, Samantha E. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States)

    2014-11-15

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The gold standard for diagnosis is liver biopsy. MRI is a non-invasive imaging method to provide quantitative measurement of hepatic fat content. The methodology is particularly appealing for the pediatric population because of its rapidity and radiation-free imaging techniques. To develop a multi-point Dixon MRI method with multi-interference models (multi-fat-peak modeling and bi-exponential T2* correction) for accurate hepatic fat fraction (FF) and T2* measurements in pediatric patients with NAFLD. A phantom study was first performed to validate the accuracy of the MRI fat fraction measurement by comparing it with the chemical fat composition of the ex-vivo pork liver-fat homogenate. The most accurate model determined from the phantom study was used for fat fraction and T2* measurements in 52 children and young adults referred from the pediatric hepatology clinic with suspected or identified NAFLD. Separate T2* values of water (T2*{sub W}) and fat (T2*{sub F}) components derived from the bi-exponential fitting were evaluated and plotted as a function of fat fraction. In ten patients undergoing liver biopsy, we compared histological analysis of liver fat fraction with MRI fat fraction. In the phantom study the 6-point Dixon with 5-fat-peak, bi-exponential T2* modeling demonstrated the best precision and accuracy in fat fraction measurements compared with other methods. This model was further calibrated with chemical fat fraction and applied in patients, where similar patterns were observed as in the phantom study that conventional 2-point and 3-point Dixon methods underestimated fat fraction compared to the calibrated 6-point 5-fat-peak bi-exponential model (P < 0.0001). With increasing fat fraction, T2*{sub W} (27.9 ± 3.5 ms) decreased, whereas T2*{sub F} (20.3 ± 5.5 ms) increased; and T2*{sub W} and T2*{sub F} became increasingly more similar when fat

  2. Safety and Yield of Diagnostic ERCP in Liver Transplant Patients with Abnormal Liver Function Tests

    Directory of Open Access Journals (Sweden)

    Jayapal Ramesh

    2014-01-01

    Full Text Available Background. Abnormal liver enzymes postorthotopic liver transplant (OLT may indicate significant biliary pathology or organ rejection. There is very little known in the literature regarding the current role of diagnostic ERCP in this scenario. Aim. To review the utility of diagnostic ERCP in patients presenting with abnormal liver function tests in the setting of OLT. Methods. A retrospective review of diagnostic ERCPs in patients with OLT from 2002 to 2013 from a prospectively maintained, IRB approved database. Results. Of the 474 ERCPs performed in OLT patients, 210 (44.3%; 95% CI 39.8–48.8 were performed for abnormal liver function tests during the study period. Majority of patients were Caucasian (83.8%, male (62.4% with median age of 55 years (IQR 48–62 years. Biliary cannulation was successful in 99.6% of cases and findings included stricture in 45 (21.4 %; biliary stones/sludge in 23 (11%; biliary dilation alone in 31 (14.8%; and normal in 91 (43.3%. Three (1.4% patients developed mild, self-limiting pancreatitis; one patient (0.5% developed cholangitis and two (1% had postsphincterotomy bleeding. Multivariate analyses showed significant association between dilated ducts on imaging with a therapeutic outcome. Conclusion. Diagnostic ERCP in OLT patients presenting with liver function test abnormalities is safe and frequently therapeutic.

  3. The Platelet and Platelet Function Testing in Liver Disease

    NARCIS (Netherlands)

    Hugenholtz, Greg G. C.; Porte, Robert J.; Lisman, Ton

    2009-01-01

    Patients who have liver disease commonly present with alterations in platelet number and function. Recent data have questioned the contribution of these changes to bleeding complications in these patients. Modern tests of platelet function revealed compensatory mechanisms for the decreased platelet

  4. Bilirubin binding with liver cystatin induced structural and functional changes.

    Science.gov (United States)

    Mustafa, Mir Faisal; Bano, Bilqees

    2014-05-01

    Cysteine proteinases and their inhibitors play a significant role in the proteolytic environment of the cells. Inhibitors of cysteine proteinases regulate the activity of these enzymes helping in checking the degdration activity of cathepsins. The bilirubin secreated by liver cells can bind to cystatin present in the liver resulting in its functional inactivation, which may further lead to the increase in cathepsins level causing liver cirrhosis. In case of some pathophysiological conditions excess bilirubin gets accumulated e.g. in presence of Fasciola hepatica (liver fluke) in mammals and humans, leading to liver cirrhosis and possibly jaundice or normal blockade of bile duct causing increased level of bilirubin in blood. Protease-cystatin imbalance causes disease progression. In the present study, Bilirubin (BR) and liver cystatin interaction was studied to explore the cystatin inactivation and structural alteration. The binding interaction was studied by UV-absorption, FT-IR and fluorescence spectroscopy. The quenching of protein fluorescence confirmed the binding of BR with buffalo liver cystatin (BLC). Stern-Volmer analysis of BR-BLC system indicates the presence of static component in the quenching mechanism and the number of binding sites to be close to 1. The fluorescence data proved that the fluorescence quenching of liver cystatin by BR was the result of BR-cystatin complex formation. FTIR analysis of BR-Cystatin complex revealed change in the secondary structure due to perturbation in the microenvironment further confirmed by the decreased caseinolytic activity of BLC against papain. Fluorescence measurements also revealed quenching of fluorescence and shift in peak at different time intervals and at varying pH values. Photo-illumination of BR-cystatin complex causes change in the surrounding environment of liver cystatin as indicated by red-shift. The binding constant for BR-BLC complex was found to be 9.279 × 10(4) M(-1). The cystatin binding with

  5. Quantitative computed tomography of the liver in juvenile green sea turtles (Chelonia mydas).

    Science.gov (United States)

    Bonelli, Marília de Albuquerque; de Oliveira, Daniel Capucho; Costa, Lorena Adão Vescovi Séllos; Forattini, Jannine Garcia; Júnior, João Luiz Rossi; Leite, Flaviana Lima Guião; Costa, Fabiano Séllos

    2013-06-01

    Quantitative computed tomography (QCT) is a highly sensitive, applicable technique for determining the x-ray attenuation of organs. This technique reveals great precision in the detection of alterations in the x-ray attenuation of hepatic parenchyma, although the lack of studies establishing normal values limits its application in wild animals. The objective of this study was to establish mean hepatic attenuation values in four healthy juvenile sea turtles (Chelonia mydas) using QCT. Helical computed tomography scans were performed and regions of interest selected in the liver after multi-planar reconstruction images were obtained. The mean attenuation value for the hepatic parenchyma in these four turtles was 60.09 +/- 5.3 standard deviation Hounsfield units. Determining normal x-ray attenuation values of the liver increases knowledge of the computed tomographic anatomy of this species and may be useful in the investigation of hepatic diseases.

  6. Mesenchymal stem cells support hepatocyte function in engineered liver grafts.

    Science.gov (United States)

    Kadota, Yoshie; Yagi, Hiroshi; Inomata, Kenta; Matsubara, Kentaro; Hibi, Taizo; Abe, Yuta; Kitago, Minoru; Shinoda, Masahiro; Obara, Hideaki; Itano, Osamu; Kitagawa, Yuko

    2014-01-01

    Recent studies suggest that organ decellularization is a promising approach to facilitate the clinical application of regenerative therapy by providing a platform for organ engineering. This unique strategy uses native matrices to act as a reservoir for the functional cells which may show therapeutic potential when implanted into the body. Appropriate cell sources for artificial livers have been debated for some time. The desired cell type in artificial livers is primary hepatocytes, but in addition, other supportive cells may facilitate this stem cell technology. In this context, the use of mesenchymal stem cells (MSC) is an option meeting the criteria for therapeutic organ engineering. Ideally, supportive cells are required to (1) reduce the hepatic cell mass needed in an engineered liver by enhancing hepatocyte function, (2) modulate hepatic regeneration in a paracrine fashion or by direct contact, and (3) enhance the preservability of parenchymal cells during storage. Here, we describe enhanced hepatic function achieved using a strategy of sequential infusion of cells and illustrate the advantages of co-cultivating bone marrow-derived MSCs with primary hepatocytes in the engineered whole-liver scaffold. These co-recellularized liver scaffolds colonized by MSCs and hepatocytes were transplanted into live animals. After blood flow was established, we show that expression of adhesion molecules and proangiogenic factors was upregulated in the graft.

  7. Effect of human liver source on the functionality of isolated hepatocytes and liver slices

    NARCIS (Netherlands)

    Olinga, Peter; Hof, I.H; de Jong, Kurt; Slooff, M.JH; Meijer, D.K F; Groothuis, Geny; Merema, M.T.

    1998-01-01

    In vitro experiments using human liver tissue to study drug metabolism and transport are usually performed and interpreted without real consideration of the differences in procurement of the tissue, if it is obtained from different sources. Therefore, in this study the functionality of isolated hepa

  8. Quantitative Evaluation of Scintillation Camera Imaging Characteristics of Isotopes Used in Liver Radioembolization

    OpenAIRE

    Mattijs Elschot; Johannes Franciscus Wilhelmus Nijsen; Alida Johanna Dam; Hugo Wilhelmus Antonius Maria de Jong

    2011-01-01

    BACKGROUND: Scintillation camera imaging is used for treatment planning and post-treatment dosimetry in liver radioembolization (RE). In yttrium-90 (90Y) RE, scintigraphic images of technetium-99m (99mTc) are used for treatment planning, while 90Y Bremsstrahlung images are used for post-treatment dosimetry. In holmium-166 (166Ho) RE, scintigraphic images of 166Ho can be used for both treatment planning and post-treatment dosimetry. The aim of this study is to quantitatively evaluate and compa...

  9. Effect of ultrasound combined with laparoscopic radiofrequency ablation on liver function and immunological function in patients with liver cancer

    Institute of Scientific and Technical Information of China (English)

    Xin Li

    2016-01-01

    Objective:To explore the effect of ultrasound combined with laparoscopic radiofrequency ablation (LRFA) on the liver function and immunological function in patients with liver cancer. Methods: A total of 76 patients with liver cancer who were admitted in our hospital were included in the study and randomized into the treatment group and the control group with 38 cases in each group. The patients in the treatment group were given ultrasound in combined with LRFA, while the patients in the control group were given TACE. The changes of liver function and immunological function indicators before and after treatment in the two groups were compared.Results: The serum AST, ALT, T-BIL, and D-BIL after operation in the two groups were significantly reduced when compared with before operation (P<0.05); moreover, the reduced degree in the treatment group was significantly lower than that in the control group (P<0.05). The plasma IgG, IgA, and IgM levels after operation in the two groups were significantly elevated when compared with before operation (P<0.05), and the difference between the two groups was statistically significant (P<0.05). CD3+, CD4+, CD8+, and NK levels after operation in the two groups were significantly elevated when compared with before operation (P<0.05), while CD4+/CD8+ was significantly reduced when compared with before operation (P<0.05); moreover, the difference between the two groups was statistically significant (P<0.05).Conclusions:Ultrasound combined with LRFA in the treatment of liver cancer can protect the liver function and immunological function; therefore, it can be served as a preferred scheme.

  10. Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease

    Institute of Scientific and Technical Information of China (English)

    Jin-Ping Li; De-Li Zhao; Hui-Jie Jiang; Ya-Hua Huang; Da-Qing Li; Yong Wan; Xin-Ding Liu; Jin-E Wang

    2011-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhoticliverdiseasebythisfastimagingmethod. METHODS: CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. RESULTS: In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The

  11. Structural and functional aspects of the liver and liver sinusoidal cells in relation to colon carcinoma metastasis

    Institute of Scientific and Technical Information of China (English)

    Katrien Vekemans; Filip Braet

    2005-01-01

    Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely described in physiologic conditions and in relation to metastasis during the past 30 years. This paper provides an "overview" of how these cells function in health and in diseases such as liver metastasis.

  12. Assessment of thyroid and gonadal function in liver diseases

    Directory of Open Access Journals (Sweden)

    Sandeep Kharb

    2015-01-01

    Full Text Available Introduction: Liver is involved with the synthesis of carrier proteins and metabolism of various hormones and liver diseases may, therefore, be associated with various endocrine disturbances. This study was conducted to assess thyroid and gonadal function in subjects with acute hepatitis (AH, chronic liver disease (CLD, and those who had undergone liver transplantation (LT. Materials and Methods: Patients with AH, CLD with Child-Pugh stage A (CLD-1 and Child-Pugh stage B or C (CLD-2, and LT seen at our tertiary level hospital were assessed clinically, biochemically, and for thyroid and gonadal functions besides 25 healthy controls. Results: Thyroid dysfunction and hypogonadism were present in 14 (16% and 24 (28% patients with liver diseases respectively. Among thyroid dysfunction, the commonest was sick euthyroid syndrome six (7%, followed by subclinical hypothyroidism in three patients (3.5%, subclinical hyperthyroidism and thyrotoxicosis in two patients each (2.3% and overt hypothyroidism in one patient. Among patients with LT and AH groups, the only abnormality was significantly lower total T3 compared with healthy controls. The CLD2 group had significantly lower levels of all thyroid hormones compared with controls and CLD1 group. Hypogonadism was commonest in patients with CLD-2 (14; 50% followed by LT (3; 33%, CLD-1 (4; 20%, and AH (3; 14%. Hypogonadism was predicted by older age, lower levels of serum albumin, total cholesterol, and triglycerides and higher levels of plasma glucose, serum bilirubin, aspartate transaminases, and international normalized ratio. Gonadal functions showed recovery following LT. Conclusions: Thyroid dysfunction and hypogonadism form an important part of the spectrum of acute and CLD, and patients with LT. Deterioration of synthetic functions of liver disease predicts presence of hypogonadism.

  13. Volume-assisted estimation of liver function based on Gd-EOB-DTPA-enhanced MR relaxometry

    Energy Technology Data Exchange (ETDEWEB)

    Haimerl, Michael; Schlabeck, Mona; Verloh, Niklas; Fellner, Claudia; Stroszczynski, Christian; Wiggermann, Philipp [University Hospital Regensburg, Department of Radiology, Regensburg (Germany); Zeman, Florian [University Hospital Regensburg, Center for Clinical Trials, Regensburg (Germany); Nickel, Dominik [MR Applications Development, Siemens AG, Healthcare Sector, Erlangen (Germany); Barreiros, Ana Paula [University Hospital Regensburg, Department of Internal Medicine I, Regensburg (Germany); Loss, Martin [University Hospital Regensburg, Department of Surgery, Regensburg (Germany)

    2016-04-15

    To determine whether liver function as determined by indocyanine green (ICG) clearance can be estimated quantitatively from hepatic magnetic resonance (MR) relaxometry with gadoxetic acid (Gd-EOB-DTPA). One hundred and seven patients underwent an ICG clearance test and Gd-EOB-DTPA-enhanced MRI, including MR relaxometry at 3 Tesla. A transverse 3D VIBE sequence with an inline T1 calculation was acquired prior to and 20 minutes post-Gd-EOB-DTPA administration. The reduction rate of T1 relaxation time (rrT1) between pre- and post-contrast images and the liver volume-assisted index of T1 reduction rate (LVrrT1) were evaluated. The plasma disappearance rate of ICG (ICG-PDR) was correlated with the liver volume (LV), rrT1 and LVrrT1, providing an MRI-based estimated ICG-PDR value (ICG-PDR{sub est}). Simple linear regression model showed a significant correlation of ICG-PDR with LV (r = 0.32; p = 0.001), T1{sub post} (r = 0.65; p < 0.001) and rrT1 (r = 0.86; p < 0.001). Assessment of LV and consecutive evaluation of multiple linear regression model revealed a stronger correlation of ICG-PDR with LVrrT1 (r = 0.92; p < 0.001), allowing for the calculation of ICG-PDR{sub est}. Liver function as determined using ICG-PDR can be estimated quantitatively from Gd-EOB-DTPA-enhanced MR relaxometry. Volume-assisted MR relaxometry has a stronger correlation with liver function than does MR relaxometry. (orig.)

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  16. Intraoperative simulation of remnant liver function during anatomic liver resection with indocyanine green clearance (LiMON) measurements.

    Science.gov (United States)

    Thomas, Michael N; Weninger, Ernst; Angele, Martin; Bösch, Florian; Pratschke, Sebastian; Andrassy, Joachim; Rentsch, Markus; Stangl, Manfred; Hartwig, Werner; Werner, Jens; Guba, Markus

    2015-06-01

    Post-hepatectomy liver failure (PHLF) is the major cause of death following liver resection. The aim of this study was to evaluate the feasibility of an intraoperative simulation of post-resection liver function. Intraoperative liver function was measured by indocyanine green (ICG) clearance using the LiMON technology. In 20 patients undergoing anatomic liver resection, ICG plasma disappearance rate (PDR (%/min) and ICG retention at 15 min (R15 ) (%) were measured immediately after the induction of anaesthesia (t0 ), after selective arterial and portovenous inflow trial clamping (TC) of the resected liver segments (t1 ), after the completion of resection (t2 ) and before the closure of the abdominal cavity (t3 ). The median baseline (t0 ) PDR was 16.5%/min. Trial clamping of the inflow (t1 ) resulted in a significant reduction in PDR to 10.5%/min. Results under TC were similar to those obtained after resection (t2 ) (median PDR: 10.5%/min). Linear regression modelling showed that post-resection liver volume could be accurately predicted by TC of liver inflow (P < 0.0001), but not by determining the resected liver volume. Simulated post-resection liver function under TC correlated well with PHLF and length of hospital stay. Intraoperative ICG clearance measurements allow real-time monitoring of intraoperative liver function during surgery. Trial clamping of arterial and portovenous inflow accurately predicts immediate post-resection liver function. The intraoperative measurement of liver function and simulation of post-resection liver function may help to avoid PHLF. © 2015 International Hepato-Pancreato-Biliary Association.

  17. Liver function tests in acute hepatitis in children

    Directory of Open Access Journals (Sweden)

    Shweta

    2016-08-01

    Conclusions: This study helps us to analyze the incidence of HBsAg positive cases presenting with clinical features of acute hepatitis and degree of alteration of liver functions would help the physician in better management of the cases. [Int J Res Med Sci 2016; 4(8.000: 3184-3187

  18. Bioreactor Technologies to Support Liver Function In Vitro

    Science.gov (United States)

    Ebrahimkhani, Mohammad R; Neiman, Jaclyn A Shepard; Raredon, Micah Sam B; Hughes, David J; Griffith, Linda G

    2014-01-01

    Liver is a central nexus integrating metabolic and immunologic homeostasis in the human body, and the direct or indirect target of most molecular therapeutics. A wide spectrum of therapeutic and technological needs drive efforts to capture liver physiology and pathophysiology in vitro, ranging from prediction of metabolism and toxicity of small molecule drugs, to understanding off-target effects of proteins, nucleic acid therapies, and targeted therapeutics, to serving as disease models for drug development. Here we provide perspective on the evolving landscape of bioreactor-based models to meet old and new challenges in drug discovery and development, emphasizing design challenges in maintaining long-term liver-specific function and how emerging technologies in biomaterials and microdevices are providing new experimental models. PMID:24607703

  19. Hypothalamic-pituitary-gonadal function in relation to liver function in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, Patrick;

    1983-01-01

    affected liver function (no. = 18) had significantly (P less than 0.05) raised serum concentrations of testosterone, FSH, and LH when compared with both controls and patients with severely affected liver function (no. = 13). Serum concentrations of testosterone, FSH, and LH in the latter group showed......Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20......). No significant difference was observed when comparing serum testosterone concentrations. Patients were divided into three groups in accordance with the severity of liver cirrhosis, using biochemical and clinical criteria. Patients with the best-preserved liver function (no. = 11) and patients with moderately...

  20. Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni.

    Directory of Open Access Journals (Sweden)

    Luiz Arthur Calheiros Leite

    Full Text Available Schistosomiasis mansoni is a chronic liver disease, in which some patients (5-10% progress to the most severe form, hepatosplenic schistosomiasis. This form is associated with portal hypertension and splenomegaly, and often episodes of gastrointestinal bleeding, even with liver function preserved. Splenectomy is a validated procedure to reduce portal hypertension following digestive bleeding. Here, we evaluate beneficial effects of splenectomy on blood coagulation factors and liver function tests in hepatosplenic schistosomiasis mansoni compared to non-operated patients.Forty-five patients who had undergone splenectomy surgery were assessed by laboratory analyses and ultrasound examination and compared to a non-operated group (n = 55. Blood samples were obtained for liver function tests, platelet count and prothrombin time. Coagulation factors (II, VII, VIII, IX and X, protein C and antithrombin IIa, plasminogen activator inhibitor-1 were measured by routine photometric, chromogenic or enzyme-linked immunosorbent assays, while hyperfibrinolysis was defined by plasminogen activator inhibitor-1 levels. Both groups had similar age, gender and pattern of periportal fibrosis. Splenectomized patients showed significant reductions in portal vein diameter, alkaline phosphatase and bilirubin levels compared to non-operated patients, while for coagulation factors there were significant improvement in prothrombin, partial thromboplastin times and higher levels of factor VII, VIII, IX, X, protein C and plasminogen activator inhibitor-1.This study shows that the decrease of flow pressure in portal circulation after splenectomy restores the capacity of hepatocyte synthesis, especially on the factor VII and protein C levels, and these findings suggest that portal hypertension in patients with hepatosplenic schistosomiasis influences liver functioning and the blood coagulation status.

  1. Epidemiology and Genetic Epidemiology of the Liver Function Test Proteins

    Science.gov (United States)

    Rahmioglu, Nilufer; Andrew, Toby; Cherkas, Lynn; Surdulescu, Gabriela; Swaminathan, Ramasamyiyer; Spector, Tim; Ahmadi, Kourosh R.

    2009-01-01

    Background The liver function test (LFT) is among the most commonly used clinical investigations to assess hepatic function, severity of liver diseases and the effect of therapies, as well as to detect drug-induced liver injury (DILI). Aims To determine the relative contribution of genetic and environmental factors as well as test and quantify the effects of sex, age, BMI and alcohol consumption to variation in liver function test proteins - including alanine amino transaminase (ALT), Albumin, gamma glutamyl transpeptidase (GGT), total bilirubin, total protein, total globulin, aspartate transaminase (AST), and alkaline phosphotase (ALP) - using the classical twin model. Methods Blood samples were collected from a total of 5380 twin pairs from the TwinsUK registry. We measured the expression levels of major proteins associated with the LFT, calculated BMI from measured weight and height and questionnaires were completed for alcohol consumption by the twins. The relative contribution of genetic and environmental factors to variation in the LFT proteins was assessed and quantified using a variance components model fitting approach. Results Our results show that (1) variation in all the LFTs has a significant heritable basis (h2 ranging from 20% to 77%); (2) other than GGT, the LFTs are all affected to some extent by common environmental factors (c2 ranging from 24% to 54%); and (3) a small but significant proportion of the variation in the LFTs was due to confounding effects of age, sex, BMI, and alcohol use. Conclusions Variation in the LFT proteins is under significant genetic and common environmental control although sex, alcohol use, age and BMI also contribute significantly to inter-individual variation in the LFT proteins. Understanding the underlying genetic contribution of liver function tests may help the interpretation of their results and explain wide variation among individuals. PMID:19209234

  2. Quantitative Evaluation of Bioorthogonal Chemistries for Surface Functionalization of Nanoparticles

    DEFF Research Database (Denmark)

    Feldborg, Lise Nørkjær; Jølck, Rasmus Irming; Andresen, Thomas Lars

    2012-01-01

    We present here a highly efficient and chemoselective liposome functionalization method based on oxime bond formation between a hydroxylamine and an aldehyde-modified lipid component. We have conducted a systematic and quantitative comparison of this new approach with other state-of-the-art...... affinity between the peptide and the liposome surface. These studies demonstrate the importance of hoosing the correct chemistry in order to obtain a quantitative surface functionalization of liposomes....

  3. Quantitation of renal function using radioisotopic techniques.

    Science.gov (United States)

    O'Malley, J P; Ziessman, H A

    1993-03-01

    Radioisotopic methods are practical for clinical use because they do not require continuous intravenous infusion or urine collection. This obviously is of great advantage in infants and small children, in whom accurate urine collection is difficult, but the techniques apply to adults as well. The ability to determine individual kidney function is a major benefit. Accuracies of the radioisotopic techniques vary but generally are within clinically acceptable ranges. The need for accuracy and reproducibility can be balanced with the desire for speed and convenience when choosing among the different techniques. Methods that use plasma sampling provide greater accuracy and are recommended in cases of severe dysfunction, whereas methods such as Gates' camera method, which eliminates plasma samples, can be completed in minutes. Radioisotopic techniques are most useful in the ranges of mild to moderately decreased function, in which serum creatinine concentration is nondiagnostic, and although they are much less accurate at markedly low renal function levels, so is 24-hour creatinine clearance. In conclusion, radiopharmaceutical agents offer a wide array of possible techniques for simple, accurate, and noninvasive measurement of global as well as individual GFR and ERPF.

  4. Unani Treatment Decreased Fibrosis and Improved Liver Functions in Decompensated Cirrhosis of Liver: A Case Series

    Directory of Open Access Journals (Sweden)

    Akhtar Siddiqui

    2016-03-01

    Full Text Available At present, liver transplantation remains the only curative option for the patients with cirrhosis and end-stage liver diseases. The survival rate and recurrent diseases remain the major issues in the patient post-transplantation. Unani medicine is one of the oldest traditional systems of medicine which has been treating chronic liver diseases and cirrhosis (Talayyaful-Kabid for centuries. The current study aimed to assess the impact of Unani treatment on decompensated cirrhosis and collect data to warrant further clinical trials. Authors conducted a case series on five patients with decompensated cirrhosis and portal hypertension. The disease was confirmed through FibroScan and ultrasound and treated with Unani treatment orally for seven months. Results were evaluated based on FibroScan, liver function test (LFT, EuroQol-5D (EQ5D, Child-Pugh and TTO-TIME (trade-off question. Significant improvements in LFT, fibrosis and quality of life were achieved in the studied patients. The literature related to the herbal constituents of chief medicines used to treat in this case was reviewed. The herbs proved their potential anti-oxidative, anti-inflammatory, hepato-protective, immuno-modulator and antiviral activities, suggesting plausible mechanisms of action in the cases. The preliminary findings indicated the potential therapeutic role of Unani treatment in decompensated cirrhosis. Clinical trials should be conducted to explore further therapeutic potential of Unani treatment in decompensated cirrhosis.

  5. The diagnostic efficacy of quantitative liver MR imaging with diffusion-weighted, SWI, and hepato-specific contrast-enhanced sequences in staging liver fibrosis - a multiparametric approach

    Energy Technology Data Exchange (ETDEWEB)

    Feier, Diana [Medical University of Vienna, General Hospital of Vienna (AKH), Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Emergency County Hospital, Department of Radiology, Cluj-Napoca (Romania); Balassy, Csilla; Bastati, Nina; Fragner, Romana; Ba-Ssalamah, Ahmed [Medical University of Vienna, General Hospital of Vienna (AKH), Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Wrba, Friedrich [Medical University of Vienna, General Hospital of Vienna (AKH), Department of Pathology, Vienna (Austria)

    2016-02-15

    To assess the diagnostic efficacy of multiparametric MRI using quantitative measurements of the apparent diffusion coefficient (ADC) of the liver parenchyma on diffusion-weighted imaging (DWI), signal intensity (SI) on susceptibility-weighted imaging (SWI), and gadoxetic acid-enhanced T1-weighted imaging during the hepatobiliary phase for the staging of liver fibrosis. Seventy-seven patients underwent a 3T MRI examination, including DWI/SWI sequences and gadoxetic acid-enhanced T1-weighted MRI. Liver fibrosis according to liver biopsy was staged using the Metavir fibrosis score: F0 (n = 21, 27.3 %); F1 (n = 7, 9.1 %); F2 (n = 8, 10.4 %); F3 (n = 12, 15.6 %); and F4 (n = 29, 37.7 %). SI of the liver was defined using region-of-interest measurements to calculate the ADC values, the relative enhancement (RE) in the hepatobiliary phase, and the liver-to-muscle ratio (LMR) measurements for SWI. The values of RE, LMR, and ADC measurements were statistically significantly different among the five fibrosis stages (p < 0.004). Combining the three parameters in a multiparametric approach, the AUC for detecting F1 stage or greater (≥ F1) was 94 %, for F2 or greater (≥F2) was 95 %, for F3 or greater (≥F3) was 90 %, and for stage F4 was 93 %. Multiparametric MRI is an efficient non-invasive diagnostic tool for the staging of liver fibrosis. (orig.)

  6. Implication of altered proteasome function in alcoholic liver injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The proteasome is a major protein-degrading enzyme,which catalyzes degradation of oxidized and aged proteins, signal transduction factors and cleaves peptides for antigen presentation. Proteasome exists in the equilibrium of 26S and 20S particles. Proteasome function is altered by ethanol metabolism, depending on oxidative stress levels: low oxidative stress induces proteasome activity, while high oxidative stress reduces it. The proposed mechanisms for modulation of proteasome activity are related to oxidative modification of proteasomal proteins with primary and secondary products derived from ethanol oxidation.Decreased proteolysis by the proteasome results in the accumulation of insoluble protein aggregates, which cannot be degraded by proteasome and which further inhibit proteasome function. Mallory bodies, a common signature of alcoholic liver diseases, are formed by liver cells, when proteasome is unable to remove cytokeratins.Proteasome inhibition by ethanol also promotes the accumulation of pro-apoptotic factors in mitochondria of ethanol-metabolizing liver cells that are normally degraded by proteasome. In addition, decreased proteasome function also induces accumulation of the negative regulators of cytokine signaling (Ⅰ-κB and SOCS), thereby blocking cytokine signal transduction.Finally, ethanol-elicited blockade of interferon type 1 and 2 signaling and decreased proteasome function impairs generation of peptides for MHC class Ⅰ-restricted antigen presentation.

  7. MR Prediction of Liver Function and Pathology Using Gd-EOB-DTPA: Effect of Liver Volume Consideration

    Directory of Open Access Journals (Sweden)

    Dai Shimamoto

    2015-01-01

    Full Text Available Purpose. To evaluate whether the diagnostic performance of Gd-EOB-DTPA-enhanced MRI in evaluating liver function and pathology is improved by considering liver volume (LV. Methods. This retrospective study included 104 patients who underwent Gd-EOB-DTPA-enhanced MRI before liver surgery. For each patient, using the precontrast and hepatobiliary phase images, we calculated the increase rate of the liver-to-spleen signal intensity ratio (LSR, that is, the “ΔLSR,” and the increase rate of the liver-to-muscle signal intensity ratio (LMR, that is, the “ΔLMR.” ΔLSR × LV and ΔLMR × LV were also calculated. The correlation of each MR parameter with liver function data or liver pathology was assessed. The correlation coefficients were compared between ΔLSR (ΔLMR and ΔLSR (ΔLMR × LV. Results. The correlation coefficient between ΔLSR (ΔLMR × LV and cholinesterase was significantly higher than that between ΔLSR (ΔLMR and cholinesterase. The correlation coefficient between ΔLSR (ΔLMR × LV and the degree of fibrosis or necroinflammatory activity was significantly lower than that between ΔLSR (ΔLMR and the degree of fibrosis or necroinflammatory activity. Conclusion. The inclusion of liver volume may improve Gd-EOB-DTPA-based predictions of liver function, but not in predictions of liver pathology.

  8. [Quantitative assessment of intrahepatic fat content in children and adolescents with non-alcoholic fatty liver disease].

    Science.gov (United States)

    Zhang, Hong-Xi; Fu, Jun-Fen; Huang, Ke; Lai, Can; Liang, Li; Jiang, Ke-Wen

    2012-08-01

    To quantitatively evaluate clinical significance of intrahepatic fat (IHF) content in children and adolescents with non-alcoholic fatty liver disease (NAFLD). Ninety-three obese children were enrolled in this study. Physical parameters, liver function, serum lipids, glycemic and insulin related parameters were measured. Liver B-mode ultrasound (US) examination was performed. IHF content was quantified by 1H magnetic resonance spectroscopy (1H MRS). Three subgroups were classified according to the conditional diagnostic criteria for obese children: simple obesity (n=31), NAFLD-1 (US fatty liver and normal alanine aminotransterase, n=33) and NAFLD-2 (US fatty liver and elevated alanine aminotransterase, n=29). Twenty healthy age- and sex-matched children served as a control group. IHF content among the four groups was compared. The relationship of IHF content with other common clinical laboratory parameters and independent factors influencing increased IHF content were investigated. IHF content measured by 1H MRS was 0.80% (0.4%-1.0%), 2.9% (1.7%-4.30%), 14.0% (7.2%-17.5%) and 18.8% (14.0%-29.1%) respectively in the control, simple obese, NAFLD-1 and NAFLD-2 groups. There were significant differences in IHF content between the groups. Univariate correlation analysis demonstrated that IHF content was positively correlated with waist circumference, hip circumference, waisttohip ratio, body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, aspartate aminoreansferase, γ-glutamic acid transtetase, triglyceride, low-density lipoprotein, OGTT 2-hour plasma glucose, fasting insulin, 2-hour insulin and insulin resisfence, and negatively correlated with high-density lipoprotein. Multivariate linear regression analysis demonstrated three independent risk factors for increased IHF content: increased waist circumference, increased 2-hour plasma glucose and decreased high-density lipoprotein levels. IHF content determined by 1H MRS can

  9. Quantitative assessment of fibrinogen cross-linking by epsilon aminocaproic acid in patients with end-stage liver disease.

    Science.gov (United States)

    Quach, Thien; Tippens, Melissa; Szlam, Fania; Van Dyke, Rebecca; Levy, Jerrold H; Csete, Marie

    2004-01-01

    Analysis of the effectiveness of antifibrinolytic therapy for liver transplant recipients is hampered by lack of quantitative assays for assessing drug effects. We adapted chemical engineering tools used in polymerization studies to quantify fibrinogen cross-linking by plasma from liver transplant patients obtained before and after epsilon aminocaproic acid (EACA) therapy. A target fluorescein isothiocyanate-fibrinogen (FITC-fibrinogen) molecule was constructed; it fluoresces in a quantifiable pattern when in solution, and undergoes cross-linking in the presence of plasmin inhibitors. Cross-linking quenches the fluorescent signal, and the quenching is a quantifiable endpoint. Thus fluorescence from this reporter molecule can be used to assess functional improvement in fibrinogen cross-linking as a result of antifibrinolytic therapies, and it is sensitive to picomolar amounts of plasmin inhibitors and activators. Cross-linking of FITC-fibrinogen by patient plasma, before and after EACA therapy, was assessed using fluorescence spectrometry. Fluorescence patterns from FITC-fibrinogen indicated no significant cross-linking of the target fibrinogen as a consequence of EACA in posttreatment plasma. When the fibrinogen-FITC target was assayed without plasma in the presence of EACA at concentrations that bracket therapeutic levels (100 and 400 microg/ml), significant fluorescence quenching (target FITC-fibrinogen cross-linking) was achieved. These results suggest that fibrinogen-FITC fluorescence is sensitive enough to detect EACA activity in clinically relevant ranges, but that EACA given in usual doses is insufficient to promote fibrinogen cross-linking in patients with end-stage liver disease.

  10. Quantitative dual energy CT measurements in rabbit VX2 liver tumors: Comparison to perfusion CT measurements and histopathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Long Jiang, E-mail: kevinzhanglongjiang@yahoo.com.cn [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Wu, Shengyong, E-mail: cjr.wushengyong@vip.163.com [Institute of Tianjin Medical Imaging, Tianjin 300192 (China); Wang, Mei, E-mail: 281406196@qq.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Lu, Li, E-mail: xuzhoululi@163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Chen, Bo, E-mail: chenbo1985@yahoo.com.cn [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Jin, Lixin, E-mail: lixin.jin@siemens.com [Siemens Healthcare, MR Collaboration NE Asia, Shanghai (China); Wang, Jiandong, E-mail: jdwang1216@163.com [Department of Pathology, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 200012 (China); Larson, Andrew C., E-mail: a-larson@northwestern.edu [Department of Radiology, Northwestern University, Chicago, IL (United States); Lu, Guang Ming, E-mail: cjr.luguangming@vip.163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China)

    2012-08-15

    Purpose: To evaluate the correlation between quantitative dual energy CT and perfusion CT measurements in rabbit VX2 liver tumors. Materials and methods: This study was approved by the institutional animal care and use committee at our institution. Nine rabbits with VX2 liver tumors underwent contrast-enhanced dual energy CT and perfusion CT. CT attenuation for the tumors and normal liver parenchyma and tumor-to-liver ratio were obtained at the 140 kVp, 80 kVp, average weighted images and dual energy CT iodine maps. Quantitative parameters for the viable tumor and adjacent liver were measured with perfusion CT. The correlation between the enhancement values of the tumor in iodine maps and perfusion CT parameters of each tumor was analyzed. Radiation dose from dual energy CT and perfusion CT was measured. Results: Enhancement values for the tumor were higher than that for normal liver parenchyma at the hepatic arterial phase (P < 0.05). The highest tumor-to-liver ratio was obtained in hepatic arterial phase iodine map. Hepatic blood flow of the tumor was higher than that for adjacent liver (P < 0.05). Enhancement values of hepatic tumors in the iodine maps positively correlated with permeability of capillary vessel surface (r = 0.913, P < 0.001), hepatic blood flow (r = 0.512, P = 0.010), and hepatic blood volume (r = 0.464, P = 0.022) at the hepatic arterial phases. The effective radiation dose from perfusion CT was higher than that from DECT (P < 0.001). Conclusions: The enhancement values for viable tumor tissues measured in iodine maps were well correlated to perfusion CT measurements in rabbit VX2 liver tumors. Compared with perfusion CT, dual energy CT of the liver required a lower radiation dose.

  11. Insights on augmenter of liver regeneration cloning and function

    Institute of Scientific and Technical Information of China (English)

    Elisavet Gatzidou; Gregory Kouraklis; Stamatios Theocharis

    2006-01-01

    Hepatic stimulator substance (HSS) has been referred to as a liver-specific but species non-specific growth factor. Gradient purification and sequence analysis of HSS protein indicated that it contained the augmenter of liver regeneration (ALR), also known as hepatopoietin (HPO).ALR, acting as a hepatotrophic growth factor, specifically stimulated proliferation of cultured hepatocytes as well as hepatoma cells in vitro, promoted liver regeneration and recovery of damaged hepatocytes and rescued acute hepatic failure in vivo. ALR belongs to the new Erv1/Alr protein family, members of which are found in lower and higher eukaryotes from yeast to man and even in some double-stranded DNA viruses. The present review article focuses on the molecular biology of ALR, examining the ALR gene and its expression from yeast to man and the biological function of ALR protein. ALR protein seems to be non-liver-specific as was previously believed, increasing the necessity to extend research on mammalian ALR protein in different tissues, organs and developmental stages in conditions of normal and abnormal cellular growth.

  12. A quantitative map of the liver mitochondrial phosphoproteome reveals posttranslational control of ketogenesis.

    Science.gov (United States)

    Grimsrud, Paul A; Carson, Joshua J; Hebert, Alex S; Hubler, Shane L; Niemi, Natalie M; Bailey, Derek J; Jochem, Adam; Stapleton, Donald S; Keller, Mark P; Westphall, Michael S; Yandell, Brian S; Attie, Alan D; Coon, Joshua J; Pagliarini, David J

    2012-11-07

    Mitochondria are dynamic organelles that play a central role in a diverse array of metabolic processes. Elucidating mitochondrial adaptations to changing metabolic demands and the pathogenic alterations that underlie metabolic disorders represent principal challenges in cell biology. Here, we performed multiplexed quantitative mass spectrometry-based proteomics to chart the remodeling of the mouse liver mitochondrial proteome and phosphoproteome during both acute and chronic physiological transformations in more than 50 mice. Our analyses reveal that reversible phosphorylation is widespread in mitochondria, and is a key mechanism for regulating ketogenesis during the onset of obesity and type 2 diabetes. Specifically, we have demonstrated that phosphorylation of a conserved serine on Hmgcs2 (S456) significantly enhances its catalytic activity in response to increased ketogenic demand. Collectively, our work describes the plasticity of this organelle at high resolution and provides a framework for investigating the roles of proteome restructuring and reversible phosphorylation in mitochondrial adaptation.

  13. Homocysteine, Liver Function Derangement and Brain Atrophy in Alcoholics.

    Science.gov (United States)

    Fernández-Rodríguez, Camino; González-Reimers, Emilio; Quintero-Platt, Geraldine; de la Vega-Prieto, María José; Pérez-Hernández, Onán; Martín-González, Candelaria; Espelosín-Ortega, Elisa; Romero-Acevedo, Lucía; Santolaria-Fernández, Francisco

    2016-11-01

    Hyperhomocysteinemia may be involved in the development of brain atrophy in alcoholics. Its pathogenesis is multifactorial. In the present study, we analyse the relationship between homocysteine levels and brain atrophy, and the relative weight of co-existing factors such as liver function impairment, the amount of ethanol consumed, serum vitamin B12, B6, and folic acid levels on homocysteine levels and brain alterations in alcoholic patients. We included 59 patients admitted to this hospital for major withdrawal symptoms and 24 controls. The mini-mental state examination test and a brain computed tomography (CT) scan were performed and several indices were calculated. Serum levels of homocysteine, folic acid, vitamin B6 and vitamin B12 were determined. Liver function was assessed by Child-Pugh score. The daily consumption of ethanol in grams per day and years of addiction were recorded. A total of 83.6% and 80% of the patients showed cerebellar or frontal atrophy, respectively. Patients showed altered values of brain indices, higher levels of homocysteine and vitamin B12, but lower levels of folic acid, compared with controls. Homocysteine, B12 and liver function variables showed significant correlations with brain CT indices. Multivariate analyses disclosed that Pugh's score, albumin and bilirubin were independently related to cerebellar atrophy, frontal atrophy, cella index or ventricular index. Serum vitamin B12 was the only factor independently related to Evans index. It was also related to cella index, but after bilirubin. Homocysteine levels were independently related to ventricular index, but after bilirubin. Vitamin B12 and homocysteine levels are higher among alcoholics. Liver function derangement, vitamin B12 and homocysteine are all independently related to brain atrophy, although not to cognitive alterations. Hyperhomocysteinemia has been described in alcoholics and may be related to brain atrophy, a reversible condition with an obscure pathogenesis

  14. Basic investigation on acoustic velocity change imaging method for quantitative assessment of fat content in human liver

    Science.gov (United States)

    Mano, Kazune; Tanigawa, Shohei; Hori, Makoto; Yokota, Daiki; Wada, Kenji; Matsunaka, Toshiyuki; Morikawa, Hiroyasu; Horinaka, Hiromichi

    2016-07-01

    Fatty liver is a disease caused by the excess accumulation of fat in the human liver. The early diagnosis of fatty liver is very important, because fatty liver is the major marker linked to metabolic syndrome. We already proposed the ultrasonic velocity change imaging method to diagnose fatty liver by using the fact that the temperature dependence of ultrasonic velocity is different in water and in fat. For the diagonosis of a fatty liver stage, we attempted a feasibility study of the quantitative assessment of the fat content in the human liver using our ultrasonic velocity change imaging method. Experimental results showed that the fat content in the tissue mimic phantom containing lard was determined by its ultrasonic velocity change in the flat temperature region formed by a circular warming ultrasonic transducer with an acoustic lens having an appropriate focal length. By considering the results of our simulation using a thermal diffusion equation, we determined whether this method could be applied to fatty liver assessment under the condition that the tissue had the thermal relaxation effect caused by blood flow.

  15. Functional state of rat liver RNA polymerase IA and IB.

    Science.gov (United States)

    Zoncheddu, A; Accomando, R; Pertica, M; Orunesu, M

    1979-01-01

    Phosphocellulose chromatography has been employed to characterize RNA polymerase I present in two different functional states in rat liver cells. The actively transcribing enzyme solubilized from nuclei appears to belong both to the IA and IB classes, whereas the non-transcribing enzyme present in the cytoplasmic fraction has been found to belong only to the IA class. Indirect and direct evidence indicates, however, that in isolated nuclei only the IB form is to be regarded as the physiological form of the enzyme, the IA form arising as a procedural artefact during the extraction process. It may, therefore, be concluded that rat liver IA and IB RNA polymerase are to be strictly regarded as the non-transcribing and transcribing form of the enzyme, respectively.

  16. Quantitative and qualitative comparison of 1.5 and 3.0 Tesla MRI in patients with chronic liver diseases.

    Science.gov (United States)

    Ramalho, Miguel; Herédia, Vasco; Tsurusaki, Masakatsu; Altun, Ersan; Semelka, Richard C

    2009-04-01

    To compare the quantitative and qualitative image quality intra-individually, at 1.5 and 3.0 Tesla (T) in patients with chronic liver diseases. The study group included 24 consecutive patients (17 males, 7 females; mean age +/- standard deviation 56.5 +/- 11.5) who had chronic liver diseases and underwent abdominal MRI for the liver evaluation at both 1.5 and 3.0 T within a 4-month period. All MRI studies were retrospectively evaluated quantitatively and qualitatively. Quantitative analysis was performed by measuring signal to noise ratio (SNR) on various abdominal organs. Qualitative analysis was performed by two reviewers to assess image quality, artifacts, and imaging findings of chronic liver diseases. Quantitative and qualitative analyses findings were compared between 1.5 and 3.0 T using the paired Student t-test and Wilcoxon signed rank test, respectively. The statistically significant increase in SNRs in various abdominal tissues ranged from 1.3- to 3.5-fold at 3.0 T compared to 1.5 T. Three-dimensional gradient echo (3D-GE) sequences demonstrated significantly higher image quality at 3.0 T (P 0.05). The SNRs of various abdominal tissues demonstrated significant increases at 3.0 T. The image quality of 3D-GE sequences was higher at 3.0 T, whereas the image quality of precontrast SGE sequences was higher at 1.5T.

  17. Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy

    OpenAIRE

    Reeder, Scott B.; Cruite, Irene; Hamilton, Gavin; Sirlin, Claude B.

    2011-01-01

    Hepatic steatosis is characterized by abnormal and excessive accumulation of lipids within hepatocytes. It is an important feature of diffuse liver disease, and the histological hallmark of non-alcoholic fatty liver disease (NAFLD). Other conditions associated with steatosis include alcoholic liver disease, viral hepatitis, HIV and genetic lipodystrophies, cystic fibrosis liver disease, and hepatotoxicity from various therapeutic agents. Liver biopsy, the current clinical gold standard for as...

  18. Qualitative and quantitative image analysis of CT and MR imaging in patients with neuroendocrine liver metastases in comparison to {sup 68}Ga-DOTATOC PET

    Energy Technology Data Exchange (ETDEWEB)

    Flechsig, Paul [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology, INF 110, 69120 Heidelberg (Germany); German Cancer Research Center (dkfz), Clinical Cooperations Unit Nuclear Medicine, INF 280, 69120 Heidelberg (Germany); Zechmann, Christian M. [University Hospital Heidelberg, Department of Nuclear Medicine, INF 400, 69120 Heidelberg (Germany); Rinecker Proton Therapy Center, Schäftlarnstraße 133, 81371 Munich (Germany); Schreiweis, Julian; Kratochwil, Clemens; Rath, Daniel [University Hospital Heidelberg, Department of Nuclear Medicine, INF 400, 69120 Heidelberg (Germany); Schwartz, Lawrence H. [Department of Radiology, Columbia University College of Physicians and Surgeons (United States); New York Presbyterian Hospital, 630 West 168th Street, New York, NY 10032 (United States); Schlemmer, Heinz-Peter [German Cancer Research Center (dkfz), Department of Radiology, INF 280, 69120 Heidelberg (Germany); Kauczor, Hans-Ulrich [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology, INF 110, 69120 Heidelberg (Germany); German Cancer Research Center (dkfz), Clinical Cooperations Unit Nuclear Medicine, INF 280, 69120 Heidelberg (Germany); Haberkorn, Uwe [University Hospital Heidelberg, Department of Nuclear Medicine, INF 400, 69120 Heidelberg (Germany); German Cancer Research Center (dkfz), Clinical Cooperations Unit Nuclear Medicine, INF 280, 69120 Heidelberg (Germany); Giesel, Frederik L., E-mail: frederik@egiesel.com [University Hospital Heidelberg, Department of Nuclear Medicine, INF 400, 69120 Heidelberg (Germany); Department of Radiology, Columbia University College of Physicians and Surgeons (United States); New York Presbyterian Hospital, 630 West 168th Street, New York, NY 10032 (United States); German Cancer Research Center (dkfz), Clinical Cooperations Unit Nuclear Medicine, INF 280, 69120 Heidelberg (Germany)

    2015-08-15

    Highlights: • Qualitative analysis revealed significantly higher results for spatial lesion detectability of liver metastasis in CE-MRI as compared to DW-imaging (p < 0.05). • Primary visibility of liver metastases was scored equally in CE-MRI and DW-imaging. • Contrast-enhancement ratios in liver metastases reached highest values for DW-imaging (p < 0.05). • Staging of liver metastases in patients with GEP-NETs should rather be performed using a combination of PET and MRI than of PET and CT. • The combination of functional and morphologic native MR-sequences seems to be sufficient for follow-up imaging in clinical routine, especially in post-interventional follow-up. - Abstract: Purpose: To compare lesion conspicuity in patients with liver metastases arising from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using MRI, PET and CT. Materials and methods: 16 patients with GEP-NETs were evaluated using non-contrast MRI, contrast-enhanced (CE) MRI using Gd-EOB-DTPA and CE-{sup 68}Ga-DOTATOC PET. Quantitative analyses were performed by two blinded readers using ROI-analyses quantifying contrast ratios (CR) between normal liver-tissue and GEP-NET-metastases. Qualitative analyses were performed evaluating primary visibility and spatial detectability of all lesions. Results: 103 of the same liver metastases were detected on all modalities. Qualitatively, lesion conspicuity was superior on CE-MRI imaging compared to non-contrast MR-sequences (T2, DWI, fl2D, fl3D), as well as arterial- and portal-venous phase CT. Concerning detectability of lesions, CE-MRI was superior to all other modalities. The quantitative ROI-analysis demonstrated improved CR for DWI compared to all other non-contrast MR-sequences (p < 0.001). CE-MRI presented with higher CR-values compared to CE-{sup 68}Ga-DOTATOC PET/CT (p < 0.001). Conclusions: Anatomic imaging using non contrast MRI with fl2D-and fl3D-sequences in combination with the molecular imaging modality {sup 68}Ga

  19. Quantitative and qualitative comparison of 3.0T and 1.5T MR imaging of the liver in patients with diffuse parenchymal liver disease.

    Science.gov (United States)

    Tsurusaki, Masakatsu; Semelka, Richard C; Zapparoli, Mauricio; Elias, Jorge; Altun, Ersan; Pamuklar, Ertan; Sugimura, Kazuro

    2009-11-01

    The purpose of our study was to compare signal characteristics and image qualities of MR imaging at 3.0T and 1.5T in patients with diffuse parenchymal liver disease. 25 consecutive patients with diffuse parenchymal liver disease underwent abdominal MR imaging at both 3.0T and 1.5T within a 6-month interval. A retrospective study was conducted to obtain quantitative and qualitative data from both 3.0T and 1.5T MRI. Quantitative image analysis was performed by measuring the signal-to-noise ratios (SNRs) and the contrast-to-noise ratios (CNRs) by the Students t-test. Qualitative image analysis was assessed by grading each sequence on a 3- and 4-point scale, regarding the presence of artifacts and image quality, respectively. Statistical analysis consisted of the Wilcoxon signed-rank test. the mean SNRs and CNRs of the liver parenchyma and the portal vein were significantly higher at 3.0T than at 1.5T on portal and equilibrium phases of volumetric interpolated breath-hold examination (VIBE) images (Pquantitative and qualitative advantages of evaluating for diffuse parenchymal liver disease.

  20. Some liver function indicators in guinea pigs injected with cyanide

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    Idonije O. Blessing

    2013-08-01

    Full Text Available To determine the lethal effect of cyanide poisoning on the liver cells using ALP, AST, ALT and Bilirubin (Total and Conjugated as test indicators, eighteen (18 male guinea pigs, age matched were used for this study. This included 12 guinea pigs which served as test groups and injected with different concentrations of potassium cyanide saline solution while 6 guinea pigs without cyanide injection served as control group. Blood samples were collected from the guinea pigs three hours after the injections of the cyanide saline solution. The blood samples were analysed for liver enzymes and bilirubin using standard methods. The result of the plasma AST and ALT at the different concentrations showed decreased levels which were significant when compared with the controls. The plasma levels of Total and Conjugated bilirubin were also significantly decreased when compared with controls. However, the levels of the ALP in both test and control groups showed no significant difference. This study therefore highlighted the need to determine the levels of these liver function indicators in cases of cyanide poisoning to ensure efficient management of patients who are exposed to the cyanide.

  1. Overnight salivary caffeine clearance: a liver function test suitable for routine use.

    Science.gov (United States)

    Jost, G; Wahlländer, A; von Mandach, U; Preisig, R

    1987-01-01

    The feasibility of measuring caffeine clearance from saliva (SCl) was assessed in ambulatory patients with liver disease and in a control group, and the results were compared with quantitative liver function tests. For this purpose, the subjects were given 280 mg caffeine p.o. in decaffeinated coffee powder between noon and 4 p.m., and caffeine concentrations were measured in saliva (using an enzyme immunoassay) before bedtime and upon arising. In the cirrhotics (n = 29), SCl was 0.58 +/- S.D. 0.45 ml per min X kg, thus being reduced to approximately one-third of drug-free, nonsmoking controls (1.53 +/- 0.46, n = 18); although patients with noncirrhotic liver disease showed intermediate values (0.95 +/- 0.47), their reduction in SCl was significant (p less than 0.001). SCl was correlated with indocyanine green fractional clearance, galactose elimination capacity and aminopyrine breath test; however, the closest relationship (Rs = 0.80) was observed with the aminopyrine breath test. It is suggested that the measurement of SCl represents a noninvasive and innocuous procedure for quantifying hepatic microsomal function, and is suitable for routine use. Since a.m. saliva concentrations of caffeine are highly correlated (Rs = -0.94) with SCl, further simplification of the test to a single-point measurement appears possible.

  2. Cerebral blood flow and liver function in patients with encephalopathy due to acute and chronic liver diseases

    DEFF Research Database (Denmark)

    Almdal, T; Schroeder, T; Ranek, L

    1989-01-01

    The purpose of the present investigation was to study changes in cerebral blood flow (CBF) in hepatic encephalopathy, to ascertain whether this was related to the changes in liver function and whether these changes gave any prognostic information. CBF, determined by the intravenous xenon-133 method......, and liver functions, assessed by the prothrombin index, bilirubin concentration, and the galactose elimination capacity, were studied in patients with acute fulminant liver failure and in patients with encephalopathy due to chronic liver diseases--that is, cirrhosis of various etiologies. The CBF range...... any differences between patients with acute or chronic liver diseases or the different degrees of hepatic encephalopathy. In conclusion, a marked reduction of the CBF was seen in hepatic encephalopathy, irrespective of the etiology of the disease....

  3. Quantitative evaluation of scintillation camera imaging characteristics of isotopes used in liver radioembolization.

    Directory of Open Access Journals (Sweden)

    Mattijs Elschot

    Full Text Available BACKGROUND: Scintillation camera imaging is used for treatment planning and post-treatment dosimetry in liver radioembolization (RE. In yttrium-90 (90Y RE, scintigraphic images of technetium-99m (99mTc are used for treatment planning, while 90Y Bremsstrahlung images are used for post-treatment dosimetry. In holmium-166 (166Ho RE, scintigraphic images of 166Ho can be used for both treatment planning and post-treatment dosimetry. The aim of this study is to quantitatively evaluate and compare the imaging characteristics of these three isotopes, in order that imaging protocols can be optimized and RE studies with varying isotopes can be compared. METHODOLOGY/PRINCIPAL FINDINGS: Phantom experiments were performed in line with NEMA guidelines to assess the spatial resolution, sensitivity, count rate linearity, and contrast recovery of 99mTc, 90Y and 166Ho. In addition, Monte Carlo simulations were performed to obtain detailed information about the history of detected photons. The results showed that the use of a broad energy window and the high-energy collimator gave optimal combination of sensitivity, spatial resolution, and primary photon fraction for 90Y Bremsstrahlung imaging, although differences with the medium-energy collimator were small. For 166Ho, the high-energy collimator also slightly outperformed the medium-energy collimator. In comparison with 99mTc, the image quality of both 90Y and 166Ho is degraded by a lower spatial resolution, a lower sensitivity, and larger scatter and collimator penetration fractions. CONCLUSIONS/SIGNIFICANCE: The quantitative evaluation of the scintillation camera characteristics presented in this study helps to optimize acquisition parameters and supports future analysis of clinical comparisons between RE studies.

  4. SU-E-J-260: Quantitative Image Feature Analysis of Multiphase Liver CT for Hepatocellular Carcinoma (HCC) in Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, W; Wang, J; Lu, W [University of Maryland School of Medicine, Baltimore, MD (United States); Kang, M [University of Maryland School of Medicine, Baltimore, MD (United States); Yeungnam University Medical Center, Daegu (Korea, Republic of)

    2015-06-15

    Purpose: To identify the effective quantitative image features (radiomics features) for prediction of response, survival, recurrence and metastasis of hepatocellular carcinoma (HCC) in radiotherapy. Methods: Multiphase contrast enhanced liver CT images were acquired in 16 patients with HCC on pre and post radiation therapy (RT). In this study, arterial phase CT images were selected to analyze the effectiveness of image features for the prediction of treatment outcome of HCC to RT. Response evaluated by RECIST criteria, survival, local recurrence (LR), distant metastasis (DM) and liver metastasis (LM) were examined. A radiation oncologist manually delineated the tumor and normal liver on pre and post CT scans, respectively. Quantitative image features were extracted to characterize the intensity distribution (n=8), spatial patterns (texture, n=36), and shape (n=16) of the tumor and liver, respectively. Moreover, differences between pre and post image features were calculated (n=120). A total of 360 features were extracted and then analyzed by unpaired student’s t-test to rank the effectiveness of features for the prediction of response. Results: The five most effective features were selected for prediction of each outcome. Significant predictors for tumor response and survival are changes in tumor shape (Second Major Axes Length, p= 0.002; Eccentricity, p=0.0002), for LR, liver texture (Standard Deviation (SD) of High Grey Level Run Emphasis and SD of Entropy, both p=0.005) on pre and post CT images, for DM, tumor texture (SD of Entropy, p=0.01) on pre CT image and for LM, liver (Mean of Cluster Shade, p=0.004) and tumor texture (SD of Entropy, p=0.006) on pre CT image. Intensity distribution features were not significant (p>0.09). Conclusion: Quantitative CT image features were found to be potential predictors of the five endpoints of HCC in RT. This work was supported in part by the National Cancer Institute Grant R01CA172638.

  5. [Progress in quantitative methods based on liquid chromatography-mass spectrometry for drug metabolizing enzymes in human liver microsomes].

    Science.gov (United States)

    Wang, Huanhuan; Lu, Yayao; Peng, Bo; Qian, Xiaohong; Zhang, Yangjun

    2015-06-01

    Cytochrome P450 (CYP) enzymes and uridine 5-diphospho-glucuronosyltransferase (UGT) enzymes are critical enzymes for drug metabolism. Both chemical drugs and traditional Chinese medicines are converted to more readily excreted compounds by drug metabolizing enzymes in human livers. Because of the disparate expression of CYP and UGT enzymes among different individuals, accurate quantification of these enzymes is essential for drug pharmacology, drug-drug interactions and drug clinical applications. The research progress in quantitative methods based on liquid chromatography-mass spectrometry for drug metabolizing enzymes in human liver microsomes in the recent decade is reviewed.

  6. Sorafenib in Liver Function Impaired Advanced Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    You-xin Ji; Lei Sun; Zong-chun Zhang; Zhong-fa Zhang; Ke-tao Lan; Ke-ke Nie; Chuan-xin Geng; Shi-chao Liu; Ling Zhang; Xing-jun Zhuang; Xiao Zou

    2014-01-01

    Objective To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC). Methods In this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib (400 mg a time, twice a day) and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival. Results The median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75;P=0.002). The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.48;95%confidence interval, 0.35-0.68;P Conclusions Sorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.

  7. Diagnosis of. Hepatocellular Carcinoma in Patients with Liver Cir­rhosis Using Liver Function Assays

    Directory of Open Access Journals (Sweden)

    Itoshima,Tatsuya

    1984-04-01

    Full Text Available Sex, age and 21 routine liver function assays were analyzed by stepwise selection and the best-of-all-possible-combinations method to identify a small group of assays valuable in establishing which liver cirrhosis (LC patients have a high risk of hepatocellular carcinoma (HCC, when alpha-fetoprotein (AFP is not elevated. Data was obtained from 115 HCC and 122 LC patients on admission. Tumor size correlated with AFP (0.73, alkaline phosphatase (ALP, 0.47, leucine aminopeptidase (LAP, 0.42, lactic dehydrogenase (LDH, 0.42, and the glutamic oxaloacetic transaminase (GOT/glutamic pyruvic transaminase (GPT ratio (GOT/GPT, 0.41. The mean of the correct diagnosis rates (CDR of HCC and LC utilizing AFP as the sole parameter (89% was markedly higher than those of the other parameters. The best-of-all-possible-combinations method presented a more powerful combination than stepwise selection. The best combination of 7 parameters (LAP, GOT/GPT, choline esterase, one-hour erythrocyte sedimentation rate, age, albumin/globulin ratio, and total bilirubin presented a mean CDR of 80%, HCC CDR of 77%, and false positive rate of 18%. LC patients statistically diagnosed as having HCC by these 7 parameters are proposed as high risk patients. Fourteen (78% of 18 HCC patients who were AFP-negative were statistically diagnosed. This analysis can be applied to LC patients to distinguish those that should be followed closely by imaging diagnostic techniques.

  8. [Tests of liver function in obese school children].

    Science.gov (United States)

    Angulo, Nerkis; de Szarvas, Sobeida Barbella; Guevara, Harold; González, Dora; Hernández, Ana

    2015-03-01

    The non alcoholic fatty liver disease (NAFLD) manifests with liver damage and it is associated with obesity. The objective of this work was to detect the risk of obese school students of developing NAFLD, through an analytical, observational study, comparing their liver function with that of a control group, and its relationship with physical activity, dietary, biochemical and anthropometric variables. One hundred and sixty school students (ages 7-11) were evaluated according to their socio-economic status; nutritional status by the body mass index (BMI) and mid-upper arm fat area (MUAC) (Project Venezuela 1994); body fat percentage by anthropometry (% BF), waist circumference (WC); and metabolism by oral glucose tolerance, basal insulin and post-load glucose, total cholesterol (TC), cLDL, cVLDL, cHDL, triglycerides (TG), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma glutamil transpeptidasa (GGTP) and albumin. Their diet was analyzed by the 24-hour recall and their physical activity by a clinical trial. Mean levels of GPT (p < 0.05), greater frequencies of elevated GOT and GPT (p < 0.05) and lower albumin levels (p < 0.05) were observed in 88 obese school students when compared to controls. The GPT correlated significantly with the BMI, MUAC, % BF, WC, basal insulin and post-load glucose, HOMA, cVLDL, cHDL and TG, while the GOT correlated with MUAC and the GGTP with MUAC, basal insulin, HOMA and cLDL. Albumin was negatively correlated with BMI, MUAC, % BF and WC. TGP reflected better the hepatic compromise of obesity. To assess the risk of NAFLD, the TGO/TGP values should be standardized according to age, gender and race.

  9. Evaluation of liver function and electroacupuncture efficacy of animals with alcoholic liver injury by the novel imaging methods.

    Science.gov (United States)

    Zhang, Dong; Song, Xiao-Jing; Li, Shun-Yue; Wang, Shu-You; Chen, Bing-Jun; Bai, Xiao-Dong; Tang, Li-Mei

    2016-07-22

    Imaging methods to evaluate hepatic microcirculation (HM) and liver function (LF) by directly monitoring overall liver tissue remain lacking. This study establish imaging methods for LF that combines Laser speckle perfusion imaging (LSPI) and in vivo optical imaging (IVOI) technologies to investigate changes of hepatic microcirculation and reserve function in the animals gavaged with 50% ethanol (15 ml/kg·bw) for a model of acute alcoholic liver injury (ALI), and for evaluation of electroacupuncture (EA) effect. The liver blood perfusion and indocyanine green (ICG) distribution were observe by LSPI and IVOI separately. After EA, the livers were collected to measure the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), thromboxane A (TXA2), prostacyclin (PGI2) and endothelin (ET). The acquisitions of newly established LSPI of liver and ICG in vivo fluorescence imaging (ICG-IVFI), combining the results of other indexes showed: hepatic microcirculation perfusion (HMP) significantly reduced, ICG metabolism reduced, and ALT/AST increased in animal model with acute ALI. EA can reverse these changes. The use of LSPI of liver and ICG-IVFI, which was novel imaging methods for LF established in this study, could display the LF characteristics of ALI and the EA efficacy.

  10. Liver function and immunoglobulins in skin lichen palnus

    Directory of Open Access Journals (Sweden)

    Sharma P

    1990-01-01

    Full Text Available Fifty-two patients of skin lichen planus conforming to the clinical and histopathological description were subjected to the different liver function tests. Age and sex matched clinically normal equal number of persons were taken as controls to exclude liver disorders.] Seven (13.46% of the patients used to consume mild to moderate amount of alcohol. Nine (17.30% cases gave the history of jaundice in the past and all of them had hepatomegaly. Otherwise hepatomegaly was observed in 37 (71.15% cases. None of the healthy controls had hepatomegaly. Aspartase iminotransferase (AST alanine aminotransferase (ALT and alkaline phosphatase was raised in 11 (21.15%, 4 (7.69% and 10 (19.23% cases respectively. HBsAg was not detected in any of the 52 patients.The most contradictory finding was the revelation of raised immunoglo bulin of G, A or M either singly or in different combinations. IgG and IgA were raised in 32 (61.53% cases while IgM in 26 (50.0%.

  11. Adrenal function in cats with cholestatic liver disease.

    Science.gov (United States)

    Buckley, Faith I; Mahony, Orla; Webster, Cynthia R L

    2017-01-01

    Cats with cholestatic liver disease experience significant morbidity and mortality when they undergo invasive procedures under anesthesia. Although inadequate adrenal response might account for these outcomes, adrenal function in cats with cholestatic liver disease has not been documented, to our knowledge. The goal of our study was to describe adrenal function in these cats. Twenty-seven cats with a serum bilirubin >230 µmol/L (3 mg/dL) and serum alanine aminotransferase >2 times the upper limit of normal had pre- and 60-min post-adrenocorticotropic hormone (ACTH) cortisol analysis after administration of 5 µg/kg cosyntropin intravenously. The change in cortisol concentrations (delta cortisol) was calculated. Pre- and post-ACTH cortisol concentrations were compared to reference values. Pre-ACTH, post-ACTH, and delta cortisol values were compared between cats surviving to discharge or for 30 d postdischarge. Mean pre-ACTH cortisol levels (205 ± 113 nmol/L [7.4 ± 4.2 µg/dL]) and post-ACTH cortisol levels (440 ± 113 nmol/L [15.9 ± 4.1 g/dL]) in cholestatic cats were significantly greater than reference values in clinically normal cats. There was no association of pre- or post-ACTH cortisol with survival. Cats with a delta cortisol cats with delta cortisol >179 nmol/L (6.5 µg/dL). Results indicate that cats with cholestasis have high basal and ACTH-stimulated cortisol values. A delta cortisol cats that have decreased 30-d survival.

  12. Assessing liver function by liver enhancement during the hepatobiliary phase with Gd-EOB-DTPA-enhanced MRI at 3 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Verloh, N.; Haimerl, M.; Schlabeck, M.; Schreyer, A.G.; Stroszczynski, C.; Fellner, C.; Wiggermann, P. [University Hospital Regensburg, Department of Radiology, Regensburg (Germany); Zeman, F. [University Hospital Regensburg, Center for Clinical Trials, Regensburg (Germany); Barreiros, A. [University Hospital Regensburg, Department of Gastroenterology, Regensburg (Germany); Loss, M. [University Hospital Regensburg, Department of Surgery, Regensburg (Germany)

    2014-05-15

    The purpose of this study was to evaluate the usefulness of Gd-EOB-DTPA-enhanced 3-T MRI to determine the hepatic functional reserve expressed by the model for end-stage liver disease (MELD) score. A total of 121 patients with normal liver function (NLF; MELD score ≤ 10) and 29 patients with impaired liver function (ILF; MELD score > 10) underwent contrast-enhanced MRI with a hepatocyte-specific contrast agent at 3T. T1-weighted volume interpolated breath-hold examination (VIBE) sequences with fat suppression were acquired before and 20 min after contrast injection. Relative enhancement (RE) between plain signal intensity and contrast-enhanced signal intensity was calculated and was used to determine Gd-EOB-DTPA uptake into the liver parenchyma for patients with different MELD scores. RE differed significantly (p ≤ 0.001) between patients with NLF (87.2 ± 29.5 %) and patients with ILF (45.4 ± 26.5 %). The optimal cut-off value for RE to differentiate NLF from ILF was 47.7 % (AUC 0.87). This cut-off value showed a sensitivity of 82.8 % and a specificity of 92.7 % for the differentiation of the analysed groups. Gd-EOB-DTPA uptake in hepatocytes is strongly affected by liver function. Gd-EOB-DTPA-enhanced MRI and assessment of RE during the hepatobiliary phase (HBP) may serve as a useful image-based test in liver imaging for determining regional and global liver function. (orig.)

  13. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers.

    Science.gov (United States)

    Op den Dries, Sanna; Karimian, Negin; Westerkamp, Andrie C; Sutton, Michael E; Kuipers, Michiel; Wiersema-Buist, Janneke; Ottens, Petra J; Kuipers, Jeroen; Giepmans, Ben N; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J

    2016-07-01

    Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD.

  14. A study on the quantitative evaluation of skin barrier function

    Science.gov (United States)

    Maruyama, Tomomi; Kabetani, Yasuhiro; Kido, Michiko; Yamada, Kenji; Oikaze, Hirotoshi; Takechi, Yohei; Furuta, Tomotaka; Ishii, Shoichi; Katayama, Haruna; Jeong, Hieyong; Ohno, Yuko

    2015-03-01

    We propose a quantitative evaluation method of skin barrier function using Optical Coherence Microscopy system (OCM system) with coherency of near-infrared light. There are a lot of skin problems such as itching, irritation and so on. It has been recognized skin problems are caused by impairment of skin barrier function, which prevents damage from various external stimuli and loss of water. To evaluate skin barrier function, it is a common strategy that they observe skin surface and ask patients about their skin condition. The methods are subjective judgements and they are influenced by difference of experience of persons. Furthermore, microscopy has been used to observe inner structure of the skin in detail, and in vitro measurements like microscopy requires tissue sampling. On the other hand, it is necessary to assess objectively skin barrier function by quantitative evaluation method. In addition, non-invasive and nondestructive measuring method and examination changes over time are needed. Therefore, in vivo measurements are crucial for evaluating skin barrier function. In this study, we evaluate changes of stratum corneum structure which is important for evaluating skin barrier function by comparing water-penetrated skin with normal skin using a system with coherency of near-infrared light. Proposed method can obtain in vivo 3D images of inner structure of body tissue, which is non-invasive and non-destructive measuring method. We formulate changes of skin ultrastructure after water penetration. Finally, we evaluate the limit of performance of the OCM system in this work in order to discuss how to improve the OCM system.

  15. Alterations in the molecular species of rat liver lecithin by corn-oil feeding to essential fatty acid-deficient rats as a function of time

    NARCIS (Netherlands)

    Golde, L.M.G. van; Pieterson, W.A.; Deenen, L.L.M. van

    1968-01-01

    The present paper describes, as a function of time, the qualitative and quantitative alterations in the molecular species pattern of rat liver lecithin which are observed when corn oil is fed to essential fatty acid-deficient rats. One of the most important changes observed was a very rapid

  16. Functional mapping imprinted quantitative trait loci underlying developmental characteristics

    Directory of Open Access Journals (Sweden)

    Li Gengxin

    2008-03-01

    Full Text Available Abstract Background Genomic imprinting, a phenomenon referring to nonequivalent expression of alleles depending on their parental origins, has been widely observed in nature. It has been shown recently that the epigenetic modification of an imprinted gene can be detected through a genetic mapping approach. Such an approach is developed based on traditional quantitative trait loci (QTL mapping focusing on single trait analysis. Recent studies have shown that most imprinted genes in mammals play an important role in controlling embryonic growth and post-natal development. For a developmental character such as growth, current approach is less efficient in dissecting the dynamic genetic effect of imprinted genes during individual ontology. Results Functional mapping has been emerging as a powerful framework for mapping quantitative trait loci underlying complex traits showing developmental characteristics. To understand the genetic architecture of dynamic imprinted traits, we propose a mapping strategy by integrating the functional mapping approach with genomic imprinting. We demonstrate the approach through mapping imprinted QTL controlling growth trajectories in an inbred F2 population. The statistical behavior of the approach is shown through simulation studies, in which the parameters can be estimated with reasonable precision under different simulation scenarios. The utility of the approach is illustrated through real data analysis in an F2 family derived from LG/J and SM/J mouse stains. Three maternally imprinted QTLs are identified as regulating the growth trajectory of mouse body weight. Conclusion The functional iQTL mapping approach developed here provides a quantitative and testable framework for assessing the interplay between imprinted genes and a developmental process, and will have important implications for elucidating the genetic architecture of imprinted traits.

  17. Quantitative comparison of PET and Bremsstrahlung SPECT for imaging the in vivo yttrium-90 microsphere distribution after liver radioembolization.

    Directory of Open Access Journals (Sweden)

    Mattijs Elschot

    Full Text Available BACKGROUND: After yttrium-90 ((90Y microsphere radioembolization (RE, evaluation of extrahepatic activity and liver dosimetry is typically performed on (90Y Bremsstrahlung SPECT images. Since these images demonstrate a low quantitative accuracy, (90Y PET has been suggested as an alternative. The aim of this study is to quantitatively compare SPECT and state-of-the-art PET on the ability to detect small accumulations of (90Y and on the accuracy of liver dosimetry. METHODOLOGY/PRINCIPAL FINDINGS: SPECT/CT and PET/CT phantom data were acquired using several acquisition and reconstruction protocols, including resolution recovery and Time-Of-Flight (TOF PET. Image contrast and noise were compared using a torso-shaped phantom containing six hot spheres of various sizes. The ability to detect extra- and intrahepatic accumulations of activity was tested by quantitative evaluation of the visibility and unique detectability of the phantom hot spheres. Image-based dose estimates of the phantom were compared to the true dose. For clinical illustration, the SPECT and PET-based estimated liver dose distributions of five RE patients were compared. At equal noise level, PET showed higher contrast recovery coefficients than SPECT. The highest contrast recovery coefficients were obtained with TOF PET reconstruction including resolution recovery. All six spheres were consistently visible on SPECT and PET images, but PET was able to uniquely detect smaller spheres than SPECT. TOF PET-based estimates of the dose in the phantom spheres were more accurate than SPECT-based dose estimates, with underestimations ranging from 45% (10-mm sphere to 11% (37-mm sphere for PET, and 75% to 58% for SPECT, respectively. The differences between TOF PET and SPECT dose-estimates were supported by the patient data. CONCLUSIONS/SIGNIFICANCE: In this study we quantitatively demonstrated that the image quality of state-of-the-art PET is superior over Bremsstrahlung SPECT for the

  18. Quantitative analysis of the dual-energy CT virtual spectral curve for focal liver lesions characterization

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qi, E-mail: wq20@hotmail.com; Shi, Gaofeng, E-mail: gaofengs62@sina.com; Qi, Xiaohui, E-mail: qixiaohui1984@163.com; Fan, Xueli, E-mail: 407849960@qq.com; Wang, Lijia, E-mail: 893197597@qq.com

    2014-10-15

    Highlights: • We establish a feasible method using the virtual spectral curves (VSC) to differentiate focal liver lesions using DECT. • Our study shows the slope of the VSC can be used to differentiate between hemangioma, HCC, metastasis and cyst. • Importantly, the diagnostic specificities associated with using the slope to diagnose both hemangioma and cysts were 100%. - Abstract: Objective: To assess the usefulness of the spectral curve slope of dual-energy CT (DECT) for differentiating between hepatocellular carcinoma (HCC), hepatic metastasis, hemangioma (HH) and cysts. Methods: In total, 121 patients were imaged in the portal venous phase using dual-energy mode. Of these patients, 23 patients had HH, 28 patients had HCC, 40 patients had metastases and 30 patients had simple cysts. The spectral curves of the hepatic lesions were derived from the 40–190 keV levels of virtual monochromatic spectral imaging. The spectral curve slopes were calculated from 40 to 110 keV. The slopes were compared using the Kruskal–Wallis test. Receiver operating characteristic curves (ROC) were used to determine the optimal cut-off value of the slope of the spectral curve to differentiate between the lesions. Results: The spectral curves of the four lesion types had different baseline levels. The HH baseline level was the highest followed by HCC, metastases and cysts. The slopes of the spectral curves of HH, HCC, metastases and cysts were 3.81 ± 1.19, 1.49 ± 0.57, 1.06 ± 0.76 and 0.13 ± 0.17, respectively. These values were significantly different (P < 0.008). Based on ROC analysis, the respective diagnostic sensitivity and specificity were 87% and 100% for hemangioma (cut-off value ≥ 2.988), 82.1% and 65.9% for HCC (cut-off value 1.167–2.998), 65.9% and 59% for metastasis (cut-off value 0.133–1.167) and 44.4% and 100% for cysts (cut-off value ≤ 0.133). Conclusion: Quantitative analysis of the DECT spectral curve in the portal venous phase can be used to

  19. Clinical implications of non-steatotic hepatic fat fractions on quantitative diffusion-weighted imaging of the liver.

    Directory of Open Access Journals (Sweden)

    Hildebrand Dijkstra

    Full Text Available Diffusion-weighted imaging (DWI is an important diagnostic tool in the assessment of focal liver lesions and diffuse liver diseases such as cirrhosis and fibrosis. Quantitative DWI parameters such as molecular diffusion, microperfusion and their fractions, are known to be affected when hepatic fat fractions (HFF are higher than 5.5% (steatosis. However, less is known about the effect on DWI for HFF in the normal non-steatotic range below 5.5%, which can be found in a large part of the population. The aim of this study was therefore to evaluate the diagnostic implications of non-steatotic HFF on quantitative DWI parameters in eight liver segments. For this purpose, eleven healthy volunteers (2 men, mean-age 31.0 were prospectively examined with DWI and three series of in-/out-of-phase dual-echo spoiled gradient-recalled MRI sequences to obtain the HFF and T2*. DWI data were analyzed using the intravoxel incoherent motion (IVIM model. Four circular regions (ø22.3 mm were drawn in each of eight liver segments and averaged. Measurements were divided in group 1 (HFF ≤ 2.75%, group 2 (2.755.5%. DWI parameters and T2* were compared between the three groups and between the segments. It was observed that the molecular diffusion (0.85, 0.72 and 0.49 × 10(-3 mm(2/s and T2* (32.2, 27.2 and 21.0 ms differed significantly between the three groups of increasing HFF (2.18, 3.50 and 19.91%. Microperfusion and its fraction remained similar for different HFF. Correlations with HFF were observed for the molecular diffusion (r = -0.514, p<0.001 and T2* (-0.714, p<0.001. Similar results were obtained for the majority of individual liver segments. It was concluded that fat significantly decreases molecular diffusion in the liver, also in absence of steatosis (HFF ≤ 5.5%. Also, it was confirmed that fat influences T2*. Determination of HFF prior to quantitative DWI is therefore crucial.

  20. Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Wei-Xing Chen; You-Ming Li; Chao-Hui Yu; Wei-Min Cai; Min Zheng; Feng Chen

    2002-01-01

    AIM: To investigate the expression of the transforminggrowth factor beta 1 (TGF- beta 1 ) mRNA in different stagesof alcoholic liver disease (ALD) and its clinical value.METHODS: One hundred and seven male alcoholics weregrouped by clinical findings into four groups: alcoholabusers without liver impairment (n=22 ), alcoholicsteatosis ( n = 30 ); alcoholic hepatitis ( n = 31 ); andalcoholic cirrhosis ( n = 24 ) Using peripheral bloodmononuclear cells(PBMC) as samples the gene expressionof TGF-beta 1 was examined quantitatively by reversetranscription polymerase chain reaction (RT-PCR) and dotblot. There are 34 healthy subjects served as control.RESULTS: The expression of TGF-beta 1 from all ALDpatients was significantly greater than that in controls ( 1. 320± 1.162 vs 0.808±0.276, P<0.001). The differences of theexpressions were significant between the patients from eachgroups ( alcoholic steatosis, alcoholic hepatitis andalcoholic cirrhosis) and the controls ( 1. 168 ± 0.852, 1.462 ±1.657, 1.329± 0.610 vs 0.808 ± 0.276, P< 0.050). Nosignificant differences of TGF -beta 1 mRNA expression wereobserved between alcohol abusers without liver impairmentand controls. The expressions in patients with alcoholichepatitis and alcoholic cirrhosis were significantly greaterthan that in alcohol abusers respectively (1.462 ± 1. 657, 1.329 ± 0. 610 vs 0. 841 ± 0. 706, P < 0. 050). No significantdifferences of TGF -beta 1 mRNA expression were observedbetween alcoholic fatty liver men and alcohol abusers.CONCLUSION: TGF-beta 1 expression level can be a riskfactor for alcoholic liver disease and might be related to theinflammatory activity and fibrosis of the liver in patients .

  1. Expression of liver-specific functions in rat hepatocytes following sublethal and lethal acetaminophen poisoning

    DEFF Research Database (Denmark)

    Tygstrup, N; Jensen, S A; Krog, B

    1996-01-01

    AIM: In order to study the short-term effect of moderate and severe reduction of liver function by acetaminophen poisoning of different severity on gene expression for liver-specific functions, rats were given 3.75 and 7.5 g per kg body weight acetaminophen intragastrically. The lower dose...

  2. [Antitoxic function of the liver and the effect of zixorin in patients with diabetes mellitus].

    Science.gov (United States)

    Geller, L I; Griaznova, M V

    1987-01-01

    A study of 79 patients with insulin dependent and insulin independent types of diabetes mellitus showed a significant decrease in antitoxic liver function according to the criteria of the antipyrine test. A 10-day course with zixorin (an inductor of the oxidase enzymatic system of the hepatocytic microsomal fraction improved considerably antitoxic liver function indices in the patients with both types of diabetes mellitus.

  3. TH-A-9A-04: Incorporating Liver Functionality in Radiation Therapy Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Wu, V; Epelman, M; Feng, M; Cao, Y; Wang, H; Romeijn, E; Matuszak, M [University of Michigan, Ann Arbor, MI (United States)

    2014-06-15

    Purpose: Liver SBRT patients have both variable pretreatment liver function (e.g., due to degree of cirrhosis and/or prior treatments) and sensitivity to radiation, leading to high variability in potential liver toxicity with similar doses. This work aims to explicitly incorporate liver perfusion into treatment planning to redistribute dose to preserve well-functioning areas without compromising target coverage. Methods: Voxel-based liver perfusion, a measure of functionality, was computed from dynamic contrast-enhanced MRI. Two optimization models with different cost functions subject to the same dose constraints (e.g., minimum target EUD and maximum critical structure EUDs) were compared. The cost functions minimized were EUD (standard model) and functionality-weighted EUD (functional model) to the liver. The resulting treatment plans delivering the same target EUD were compared with respect to their DVHs, their dose wash difference, the average dose delivered to voxels of a particular perfusion level, and change in number of high-/low-functioning voxels receiving a particular dose. Two-dimensional synthetic and three-dimensional clinical examples were studied. Results: The DVHs of all structures of plans from each model were comparable. In contrast, in plans obtained with the functional model, the average dose delivered to high-/low-functioning voxels was lower/higher than in plans obtained with its standard counterpart. The number of high-/low-functioning voxels receiving high/low dose was lower in the plans that considered perfusion in the cost function than in the plans that did not. Redistribution of dose can be observed in the dose wash differences. Conclusion: Liver perfusion can be used during treatment planning potentially to minimize the risk of toxicity during liver SBRT, resulting in better global liver function. The functional model redistributes dose in the standard model from higher to lower functioning voxels, while achieving the same target EUD

  4. N-nitrosodimethylamine (NDMA, Liver Function Enzymes, Renal Function Parameters and Oxidative Stress Parameters: A Review

    Directory of Open Access Journals (Sweden)

    Usunobun Usunomena

    2012-08-01

    Full Text Available The aim of this study is to review a procarcinogen, the N-Nitrosodimethylamine (NDMA, liver and kidney functional enzymes (in assessing action of toxicants such as NDMA as well as oxidative stress parameters (in assessing the extent of free radical damage and scavenging. Catalase and hydro peroxidase enzymes convert hydrogen peroxide and hydro peroxides to non-radical forms and functions as natural antioxidant in human body. Enzymes like Superoxide Dismutase (SOD and Catalase (CAT and compounds such as tocopherol and ascorbic acid can protect organisms against free radical damage. Lipid peroxidation is a mechanism generally recognized as being the most important in the pathogenesis of liver injury by a number of toxic compounds including NDMA.

  5. Functional study on two artificial liver bioreactors with collagen gel

    Directory of Open Access Journals (Sweden)

    XU Bing

    2014-10-01

    Full Text Available ObjectiveTo improve the hollow fiber bioreactor of artificial liver. MethodsRat hepatocytes mixed with collagen solution were injected into the external cavity of a hollow fiber reactor to construct a bioreactor of hepatocytes suspended in collagen gel (group Ⅰ. Other rat hepatocytes suspended in solution were injected into the external cavity of a hollow fiber reactor with a layer of collagen on the wall of the external cavity to construct a bioreactor of collagen layer and hepatocytes (group Ⅱ. For each group, the culture solution circulated through the internal cavity of the hollow fiber bioreactor; the bioreactor was put in a culture box for 9 d, and the culture solution in the internal cavity was exchanged for new one every 24 h; the concentrations of albumin (Alb, urea, and lactate dehydrogenase (LDH in the culture solution samples were measured to examine the hepatocyte function of the bioreactor. Statistical analysis was performed using SPSS 130. Continuous data were expressed as mean±SD, and comparison between groups was made by paired t test. ResultsFor groups Ⅰ and Ⅱ, Alb levels reached peak values on day 3 of culture (1.41±0.08 g/L and 0.65±0.05 g/L; from day 3 to 9, group I had a significantly higher Alb level than group Ⅱ (t>7.572, P<0.01. For groups Ⅰ and Ⅱ, urea levels reached peak values on days 3 and 5 of culture (1.73±0.14 mmol/L and 1.56±0.18 mmol/L; from days 5 to 9, group I had a significantly higher urea level than group Ⅱ (t>8.418, P<0.01. For groups Ⅰ and Ⅱ, LDH levels reached peak values on day 9 of culture (32.03±9.13 U/L and 70.17±25.28 U/L; from days 1 to 9, group I had a significantly lower LDH level than group Ⅱ(t>5.633, P<0.01. Therefore, the bioreactor of hepatocytes suspended in collagen gel (group Ⅰ showed a better hepatocyte function and less hepatic enzyme leakage compared with the bioreactor of collagen layer and hepatocytes (group Ⅱ. Conclusion

  6. Quantitative detection of liver-relevant biomarkers by SERS-immunolabeled gold nanoparticles

    Science.gov (United States)

    Payne, William Mark

    Lab-on-a-chip technology has the potential to rapidly change the way experiments are conducted in a variety of fields ranging from medicine to environmental science. Specifically, sensors, detectors, and monitoring devices are increasingly being miniaturized to perform many experiments or measurements on a single chip. In this research, we develop an immunolabeled gold nanoparticle complex capable of detecting liver organoid biomarkers intended for use in a microfluidic device. Human Serum Albumin (HSA) and alpha-Glutathione S-Transferase (alpha-GST) are liver biomarkers that indicate liver health and damage respectively. Herein we demonstrate detection of the liver organoid biomarkers at nanomolar concentrations. Through plasmonic coupling induced by aggregation in the presence of analyte, the SERS signal obtained from the nanoparticles is dramatically increased. Furthermore, detection is demonstrated in a simple fluidic device to show the feasibility of implementing an optimized SERS-immunolabeled nanoparticle for translational application.

  7. Results of radiation therapy for primary liver cancer. Long-term influence of irradiation on liver function

    Energy Technology Data Exchange (ETDEWEB)

    Wadasaki, Kouichi; Kimura, Fumi; Oomae, Tadayuki; Urashima, Masaki; Mori, Masaki [Hiroshima Atomic Bomb Hospital (Japan)

    1995-06-01

    During the period from June 1991 through May 1993, 6 patients (3 males and 3 females) were treated with radiation therapy of 60 Gy or more for hepatomas complicated with liver cirrhosis type C. They ranged in age from 62 to 76 years with a mean of 70. Tumor size was examined on CT before and 2 months after irradiation. In addition, changes in liver function following irradiation were examined. In 4 of the 6 patients, tumor decreased by 27-90% at 11 to 43 months after irradiation. Although liver function was irreversibly aggravated in one patient, it was slight and recovered 6 months after irradiation in the other 5 patients. High dose irradiation to the limited fields is considered useful in the treatment of hepatoma. (S.Y.).

  8. Identification of quantitative trait transcripts for growth traits in the large scales of liver and muscle samples.

    Science.gov (United States)

    Xiong, Xinwei; Yang, Hui; Yang, Bin; Chen, Congying; Huang, Lusheng

    2015-07-01

    Growth-related traits are economically important traits to the pig industry. Identification of causative gene and mutation responsible for growth-related QTL will facilitate the improvement of pig growth through marker-assisted selection. In this study, we applied whole genome gene expression and quantitative trait transcript (QTT) analyses in 497 liver and 586 longissimus dorsi muscle samples to identify candidate genes and dissect the genetic basis of pig growth in a white Duroc × Erhualian F2 resource population. A total of 20,108 transcripts in liver and 23,728 transcripts in muscle with expression values were used for association analysis between gene expression level and phenotypic value. At the significance threshold of P growth-related traits in liver and muscle, respectively. We also found that some QTTs were correlated to more than one trait. The QTTs identified here showed high tissue specificity. We did not identify any QTTs that were associated with one trait in both liver and muscle. Through an integrative genomic approach, we identified SDR16C5 as the important candidate gene in pig growth trait. These findings contribute to further identification of the causative genes for porcine growth traits and facilitate improvement of pig breeding.

  9. Systems genetics of liver fibrosis: identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population.

    Directory of Open Access Journals (Sweden)

    Rabea A Hall

    Full Text Available The progression of liver fibrosis in response to chronic injury varies considerably among individual patients. The underlying genetics is highly complex due to large numbers of potential genes, environmental factors and cell types involved. Here, we provide the first toxicogenomic analysis of liver fibrosis induced by carbon tetrachloride in the murine 'genetic reference panel' of recombinant inbred BXD lines. Our aim was to define the core of risk genes and gene interaction networks that control fibrosis progression. Liver fibrosis phenotypes and gene expression profiles were determined in 35 BXD lines. Quantitative trait locus (QTL analysis identified seven genomic loci influencing fibrosis phenotypes (pQTLs with genome-wide significance on chromosomes 4, 5, 7, 12, and 17. Stepwise refinement was based on expression QTL mapping with stringent selection criteria, reducing the number of 1,351 candidate genes located in the pQTLs to a final list of 11 cis-regulated genes. Our findings demonstrate that the BXD reference population represents a powerful experimental resource for shortlisting the genes within a regulatory network that determine the liver's vulnerability to chronic injury.

  10. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients.

    Science.gov (United States)

    Zhang, Zheng; Lin, Hu; Shi, Ming; Xu, Ruonan; Fu, Junliang; Lv, Jiyun; Chen, Liming; Lv, Sa; Li, Yuanyuan; Yu, Shuangjie; Geng, Hua; Jin, Lei; Lau, George K K; Wang, Fu-Sheng

    2012-03-01

    Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC.

  11. Quantitative Analysis of the Effective Functional Structure in Yeast Glycolysis

    Science.gov (United States)

    De la Fuente, Ildefonso M.; Cortes, Jesus M.

    2012-01-01

    The understanding of the effective functionality that governs the enzymatic self-organized processes in cellular conditions is a crucial topic in the post-genomic era. In recent studies, Transfer Entropy has been proposed as a rigorous, robust and self-consistent method for the causal quantification of the functional information flow among nonlinear processes. Here, in order to quantify the functional connectivity for the glycolytic enzymes in dissipative conditions we have analyzed different catalytic patterns using the technique of Transfer Entropy. The data were obtained by means of a yeast glycolytic model formed by three delay differential equations where the enzymatic rate equations of the irreversible stages have been explicitly considered. These enzymatic activity functions were previously modeled and tested experimentally by other different groups. The results show the emergence of a new kind of dynamical functional structure, characterized by changing connectivity flows and a metabolic invariant that constrains the activity of the irreversible enzymes. In addition to the classical topological structure characterized by the specific location of enzymes, substrates, products and feedback-regulatory metabolites, an effective functional structure emerges in the modeled glycolytic system, which is dynamical and characterized by notable variations of the functional interactions. The dynamical structure also exhibits a metabolic invariant which constrains the functional attributes of the enzymes. Finally, in accordance with the classical biochemical studies, our numerical analysis reveals in a quantitative manner that the enzyme phosphofructokinase is the key-core of the metabolic system, behaving for all conditions as the main source of the effective causal flows in yeast glycolysis. PMID:22393350

  12. Protective Effects of Functional Chicken Liver Hydrolysates against Liver Fibrogenesis: Antioxidation, Anti-inflammation, and Antifibrosis.

    Science.gov (United States)

    Chen, Po-Ju; Tseng, Jung-Kai; Lin, Yi-Ling; Wu, Yi-Hsieng Samuel; Hsiao, Yi-Tse; Chen, Jr-Wei; Chen, Yi-Chen

    2017-06-21

    Via an assay using an Amino Acid Analyzer, pepsin-digested chicken liver hydrolysates (CLHs) contain taurine (365.57 ± 39.04 mg/100 g), carnosine (14.03 ± 1.98 mg/100 g), and anserine (151.58 ± 27.82 mg/100 g). This study aimed to evaluate whether CLHs could alleviate thioacetamide (TAA)-induced fibrosis. A dose of 100 mg TAA/kg BW significantly increased serum liver damage indices and liver cytokine contents. Cell infiltration and monocytes/macrophages in livers of TAA-treated rats were illustrated by the H&E staining and immunohistochemical analysis of cluster of differentiation 68 (CD68, ED1), respectively. A significantly increased hepatic collagen accumulation was also observed and quantified under TAA treatment. A significant up-regulation of transforming growth factor-beta (TGF-β) and SMAD family member 4 (SMAD4) caused by TAA treatment further enhanced alpha smooth muscle actin (αSMA) gene and protein expressions. The liver antioxidant effects under TAA treatment were significantly amended by 200 and 600 mg CLHs/kg BW. Hence, the ameliorative effects of CLHs on liver fibrogenesis could be attributed by antioxidation and anti-inflmmation.

  13. Critical appraisal of 13C breath tests for microsomal liver function: aminopyrine revisited.

    Science.gov (United States)

    Pijls, Kirsten E; de Vries, Hanne; Nikkessen, Suzan; Bast, Aalt; Wodzig, Will K W H; Koek, Ger H

    2014-04-01

    As liver diseases are a major health problem and especially the incidence of metabolic liver diseases like non-alcoholic fatty liver disease (NAFLD) is rising, the demand for non-invasive tests is growing to replace liver biopsy. Non-invasive tests such as carbon-labelled breath tests can provide a valuable contribution to the evaluation of metabolic liver function. This review aims to critically appraise the value of the (13) C-labelled microsomal breath tests for the evaluation of metabolic liver function, and to discuss the role of cytochrome P450 enzymes in the metabolism of the different probe drugs, especially of aminopyrine. Although a number of different probe drugs have been used in breath tests, the perfect drug to assess the functional metabolic capacity of the liver has not been found. Data suggest that both the (13) C(2) -aminopyrine and the (13) C-methacetin breath test can play a role in assessing the capacity of the microsomal liver function and may be useful in the follow-up of patients with chronic liver diseases. Furthermore, CYP2C19 seems to be an important enzyme in the N-demethylation of aminopyrine, and polymorphisms in this gene may influence breath test values, which should be kept in mind when performing the (13) C(2) -aminopyrine breath test in clinical practice.

  14. Effect on liver function, immune function and inflammatory factors of laparoscopic and open cholecystectomy in patients

    Institute of Scientific and Technical Information of China (English)

    Lun Yu; Jun Zhang; Yong Jiao; Peng Yong

    2016-01-01

    Objective:To observe the effect on liver function, immune function and inflammatory factors of laparoscopic and open cholecystectomy in patients.Methods:A total of 113 patients who would experience cholecystectomy were chosen as research objects. According to their own willingness, these patients were randomly divided into LC group (67 cases) and OC group (46 cases). LC group was treated with laparoscopic cholecystectomy (LC). OC group was treated with traditional open cholecystectomy (OC). Changes of liver function (ALT, AST,γ-GT, ALP, TBIL), immune function (IgA, IgM, CD3, CD4, CD8) and inflammatory factors (CRP, IL-6, IL-8) were observed 1 and 7 d after surgery.Results: Comparison of liver function: exceptγ-GT showed no significant difference before and after surgery, the levels of ALT, AST and TBIL were significantly increased, while the level of ALP was significantly decreased 1 d after surgery in the two groups (P<0.05); the levels of ALT, AST, TBIL and ALP 7 d after surgery were comparable with preoperative levels in the two groups; furthermore, there were no significant differences referring to these indexes between the two groups at the same time points, say, 1 and 7 d after surgery. Comparison of immune function: the levels of CD3 and CD4 were significantly decreased 1 d after surgery compared with before surgery in the two groups (P<0.05); but 7 d after surgery, the levels of CD3 and CD4 were comparable with preoperative levels in the two groups; furthermore, there were no significant differences referring to the levels of CD3 and CD4 between the two groups at the same time points; As for the levels of IgA, IgM and CD8, no significant changes were observed in the two groups before and after surgery. Comparison of inflammatory factors: the levels of CRP, IL-6 and IL-8 were significantly increased 1 d after surgery compared with before surgery in the two groups (P<0.05); these mentioned levels of inflammatory factors 7 d after surgery were still higher

  15. Pulmonary alveolar proteinosis: Quantitative CT and pulmonary functional correlations

    Energy Technology Data Exchange (ETDEWEB)

    Guan, Yubao, E-mail: yubaoguan@163.com [Department of Radiology, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120 (China); State Key Laboratory of Respiratory Disease, Guangzhou 510120 (China); Zeng, Qingsi [Department of Radiology, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120 (China); Yang, Haihong; Zheng, Jinping; Li, Shiyue; Gao, Yi [State Key Laboratory of Respiratory Disease, Guangzhou 510120 (China); Deng, Yu [Department of Radiology, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120 (China); Mei, Jiang [State Key Laboratory of Respiratory Disease, Guangzhou 510120 (China); He, Jianxing, E-mail: jianxing63@163.com [State Key Laboratory of Respiratory Disease, Guangzhou 510120 (China); Zhong, Nanshan, E-mail: nanshan@vip.163.com [State Key Laboratory of Respiratory Disease, Guangzhou 510120 (China)

    2012-09-15

    Objective: We assessed the relationship between quantitative computer tomography (qCT) and the pulmonary function test (PFT) or blood gas analysis in pulmonary alveolar proteinosis (PAP) patients, as well as the utility of these analyses to monitor responses to whole lung lavage (WLL) therapy. Methods: Thirty-eight PAP patients simultaneously received a CT scan and PFT. Fifteen of these patients, undergoing sequential WLL for a total of 20 lavages, also underwent chest CT scans and blood gas analysis before and after WLL, and 14 of 15 patients underwent simultaneous PFT analysis. Differences between the qCT and PFT results were analyzed by canonical correlation. Results: PAP patients with low predicted values for FVC, FEV1, D{sub LCO} and D{sub LCO}/VA indicated small airspace volume and mean lung inflation, low airspace volume/total lung volume ratio and high mean lung density. Correlation and regression analysis revealed a strong correlation between D{sub LCO} and PaO{sub 2} values with CT results. The qCT results indicated that WLL significantly decreased lung weights and mean lung densities, and improved the total airspace volume/total lung volume ratios and mean lung inflations. Conclusion: Quantitative CT may be a sensitive tool for measuring the response of PAP patients to medical interventions such as WLL.

  16. Liver function of Streptozotocin- Induced Diabetic Rats Orally ...

    African Journals Online (AJOL)

    phytochemicals (especially saponins), carbohydrate and food energy ... The role of the liver in metabolism, including detoxification ... in lipid metabolism and increased gluconeogenesis and ..... Hypoglycemic Activities in Rats and Rabbits.

  17. Fused 99m-Tc-GSA SPECT/CT imaging for the preoperative evaluation of postoperative liver function: can the liver uptake index predict postoperative hepatic functional reserve?

    Science.gov (United States)

    Yoshida, Morikatsu; Shiraishi, Shinya; Sakaguchi, Fumi; Utsunomiya, Daisuke; Tashiro, Kuniyuki; Tomiguchi, Seiji; Okabe, Hirohisa; Beppu, Toru; Baba, Hideo; Yamashita, Yasuyuki

    2012-04-01

    To evaluate the role of hepatic asialoglycoprotein receptor analysis in the preoperative estimation of postoperative hepatic functional reserve. We obtained technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin (99mTc-GSA) SPECT/CT fusion images in 256 patients with liver disease scheduled for hepatic resection. The liver uptake value corrected for body surface area [LUV(BSA)] and liver uptake ratio (LUR) of the remnant were preoperatively estimated based on the fused images. These values were compared with the postoperative hepatic functional reserve. Significant correlations were observed between LUV(BSA), LUR, and most conventional indicators of hepatic functional reserve. Postoperatively, nonpreserved liver functional reserve was observed in 15 of the 256 patients (5.8%). Remnant LUV(BSA) showed better correlation than remnant LUR or the other indicators. No patients with remnant LUV(BSA) above 28.0 manifested poor nonpreserved functional reserve. Using a LUV(BSA) of 27.0, it was possible to predict postoperative poor hepatic functional reserve at a sensitivity of 91%, specificity of 81%, and accuracy of 81% postoperatively. According to multivariate analysis, a low remnant LUV(BSA) was the only significant independent predictor of poor hepatic functional reserve. Our 99mTc-GSA SPECT/CT fusion imaging method was clinically useful for evaluating regional hepatic function and for predicting postoperative hepatic functional reserve.

  18. What Is Liver Cancer?

    Science.gov (United States)

    ... Research? Liver Cancer About Liver Cancer What Is Liver Cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  19. In-vivo quantitative proteomics reveals a key contribution of post-transcriptional mechanisms to the circadian regulation of liver metabolism.

    Directory of Open Access Journals (Sweden)

    Maria S Robles

    2014-01-01

    Full Text Available Circadian clocks are endogenous oscillators that drive the rhythmic expression of a broad array of genes, orchestrating metabolism and physiology. Recent evidence indicates that post-transcriptional and post-translational mechanisms play essential roles in modulating temporal gene expression for proper circadian function, particularly for the molecular mechanism of the clock. Due to technical limitations in large-scale, quantitative protein measurements, it remains unresolved to what extent the circadian clock regulates metabolism by driving rhythms of protein abundance. Therefore, we aimed to identify global circadian oscillations of the proteome in the mouse liver by applying in vivo SILAC mouse technology in combination with state of the art mass spectrometry. Among the 3000 proteins accurately quantified across two consecutive cycles, 6% showed circadian oscillations with a defined phase of expression. Interestingly, daily rhythms of one fifth of the liver proteins were not accompanied by changes at the transcript level. The oscillations of almost half of the cycling proteome were delayed by more than six hours with respect to the corresponding, rhythmic mRNA. Strikingly we observed that the length of the time lag between mRNA and protein cycles varies across the day. Our analysis revealed a high temporal coordination in the abundance of proteins involved in the same metabolic process, such as xenobiotic detoxification. Apart from liver specific metabolic pathways, we identified many other essential cellular processes in which protein levels are under circadian control, for instance vesicle trafficking and protein folding. Our large-scale proteomic analysis reveals thus that circadian post-transcriptional and post-translational mechanisms play a key role in the temporal orchestration of liver metabolism and physiology.

  20. MR imaging of the biliary tract with Gd-EOB-DTPA: Effect of liver function on signal intensity

    Energy Technology Data Exchange (ETDEWEB)

    Takao, Hidemasa, E-mail: takaoh-tky@umin.ac.jp [Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Akai, Hiroyuki; Tajima, Taku [Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Kiryu, Shigeru [Department of Radiology, Institute of Medical Science, University of Tokyo, 74-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Watanabe, Yasushi [Department of Radiological Technology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Imamura, Hiroshi [Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-8431 (Japan); Akahane, Masaaki; Yoshioka, Naoki [Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Kokudo, Norihiro [Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Ohtomo, Kuni [Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan)

    2011-02-15

    Objective: To quantitatively evaluate the signal intensity of the biliary tract in gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging and to investigate the effect of liver function on the signal intensity of the biliary tract. Materials and methods: A total of 32 patients with and without chronic liver disease (normal liver group, n = 15; chronic liver disease group, n = 17) were included in this study. All patients were prospectively enrolled for evaluation of known or suspected focal liver lesions. In the chronic liver disease group, the etiologies were chronic hepatitis C virus infection (n = 12) and chronic hepatitis B virus infection (n = 5). The median Child-Pugh score was 5 (range, 5-7). Each patient received the standard dose of Gd-EOB-DTPA (0.025 mmol/kg of body weight). Post-contrast T1-weighted MR images were obtained at 5, 10, 15, 20, 25, and 30 min after administration of Gd-EOB-DTPA. Maximum signal intensities (SIs) of the right and left hepatic ducts, common hepatic duct, and common bile duct were measured. Relative signal intensity was calculated as follows: relative SI = maximum SI{sub bileduct}/mean SI{sub muscle}. Serum albumin level, serum total bilirubin level, prothrombin time, indocyanine green retention rate at 15 min (ICG-R15), and estimated glomerular filtration rate were entered into regression analysis. Results: The signal intensity of the bile duct reached a peak 30 min after administration of Gd-EOB-DTPA. The mean relative signal intensity of the right and left hepatic ducts at the peak time point was not significantly different between the two groups, while increase in signal intensity was delayed in the chronic liver disease group. The mean relative signal intensity of the common hepatic duct and that of the common bile duct at the peak time point were significantly different between the two groups (Wilcoxon rank-sum test, P = 0.03, respectively). Stepwise regression

  1. Application of computer-assisted three-dimensional quantitative assessment and a surgical planning tool for living donor liver transplantation

    Institute of Scientific and Technical Information of China (English)

    WEI Lin; ZHU Zhi-jun; L(U) Yi; JIANG Wen-tao; GAO Wei; ZENG Zhi-gui; SHEN Zhong-yang

    2013-01-01

    Background Precise evaluation of the live donor's liver is the most important factor for the donor's safety and the recipient's prognosis in living donor liver transplantation (LDLT).Our study assessed the clinical value of computer-assisted three-dimensional quantitative assessment and a surgical planning tool for donor evaluation in LDLT.Methods Computer-assisted three-dimensional (3D) quantitative assessment was used to prospectively provide quantitative assessment of the graft volume for 123 consecutive donors of LDLT and its accuracy and efficiency were compared with that of the standard manual-traced method.A case of reduced monosegmental LDLT was also assessed and a surgical planning tool displayed the precise surgical plan to avoid large-for-size syndrome.Results There was no statistically significant difference between the detected graft volumes with computer-assisted 3D quantitative assessment and manual-traced approaches ((856.76±162.18) cm3 vs.(870.64±172.54) cm3,P=0.796).Estimated volumes by either method had good correlation with the actual graft weight (r-manual-traced method:0.921,r-3D quantitative assessment method:0.896,both P <0.001).However,the computer-assisted 3D quantitative assessment approach was significantly more efficient taking half the time of the manual-traced method ((16.91±1.375) minutes vs.(39.27±2.102) minutes,P <0.01) to estimate graft volume.We performed the reduced monosegmental LDLT,a pediatric case,with the surgical planning tool (188 g graft in the operation,which was estimated at 208 cm3 pre-operation).The recipient recovered without large-for-size syndrome.Conclusions Computer-assisted 3D quantitative assessment provided precise evaluation of the graft volume.It also assisted surgeons with a better understanding of the hepatic 3D anatomy and was useful for the individual surgical planning tool.

  2. The quantitative distinction of hyperplasia from hypertrophy in hepatomegaly induced in the rat liver by phenobarbital.

    Science.gov (United States)

    Carthew, P; Edwards, R E; Nolan, B M

    1998-07-01

    A histological method utilizing the optical dissector principle has been developed for determining the absolute numbers of rat hepatocytes in the liver after treatment with phenobarbital (PB). The optical dissector is a technique derived from the "new stereology" used to measure the number of features, in this case hepatocyte nuclear profiles, that are present in a reference volume of tissue. The method has been applied to distinguish between the hepatomegaly that commonly occurs in rodents after treatment with chemicals, due to an increase in the number of cells caused by cell division (hyperplasia), rather than the size of cells (hypertrophy). In the case of PB treatment, the hepatomegaly was found to be partly due to hypertrophy and partly to hyperplasia after 2 weeks of treatment. While the increase in the absolute number of hepatocytes was not significant after 2 weeks, after 12 weeks of treatment with PB the number of hepatocytes was significantly increased, compared to the controls at that time point. PCNA labeling index measurements of liver hepatocytes confirmed that there was a significant increase in the growth fraction of hepatocytes during PB treatment. The induction of hyperplasia can be associated with an increased risk of eventual liver tumor formation, and the distinction of hyperplasia from hypertrophy, using a purely histological method, for the determination of increases in absolute hepatocyte cell numbers, will be useful in assessing whether treatment-related sustained hyperplasia is occurring in the liver, although this methodology could be applied to any organ.

  3. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression

    NARCIS (Netherlands)

    Nantasanti, Sathidpak; Toussaint, Mathilda J. M.; Youssef, Sameh A.; Tooten, Peter C. J.; de Bruin, Alain

    2016-01-01

    The tumor suppressors Retinoblastoma (Rb) and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC) or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver f

  4. Liver haemodynamics and function in alcoholic cirrhosis. Relation to testosterone treatment and ethanol consumption

    DEFF Research Database (Denmark)

    Gluud, C; Henriksen, J H

    1987-01-01

    Liver haemodynamics and liver function were measured in 34 alcoholic cirrhotic men before entry and after 12 months (median) in a double-blind, placebo-controlled study on the effect of oral testosterone treatment (200 mg t.i.d.). Comparing data at entry with those at follow-up in the total patie...

  5. Liver haemodynamics and function in alcoholic cirrhosis. Relation to testosterone treatment and ethanol consumption

    DEFF Research Database (Denmark)

    Gluud, C; Henriksen, Jens Henrik Sahl

    1987-01-01

    , testosterone-treated patients did not differ significantly from placebo-treated patients regarding any of the measured variables. No significant relationships could be demonstrated between ethanol consumption and liver haemodynamics and liver function, but the number of patients consuming more than 100 g......, the improvement may be due to reduced ethanol consumption....

  6. Management of Liver Cancer Argon-helium Knife Therapy with Functional Computer Tomography Perfusion Imaging.

    Science.gov (United States)

    Wang, Hongbo; Shu, Shengjie; Li, Jinping; Jiang, Huijie

    2016-02-01

    The objective of this study was to observe the change in blood perfusion of liver cancer following argon-helium knife treatment with functional computer tomography perfusion imaging. Twenty-seven patients with primary liver cancer treated with argon-helium knife and were included in this study. Plain computer tomography (CT) and computer tomography perfusion (CTP) imaging were conducted in all patients before and after treatment. Perfusion parameters including blood flows, blood volume, hepatic artery perfusion fraction, hepatic artery perfusion, and hepatic portal venous perfusion were used for evaluating therapeutic effect. All parameters in liver cancer were significantly decreased after argon-helium knife treatment (p liver tissue, but other parameters kept constant. CT perfusion imaging is able to detect decrease in blood perfusion of liver cancer post-argon-helium knife therapy. Therefore, CTP imaging would play an important role for liver cancer management followed argon-helium knife therapy.

  7. Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis

    Science.gov (United States)

    Patel, Janki; Bettencourt, Ricki; Cui, Jeffrey; Salotti, Joanie; Hooker, Jonathan; Bhatt, Archana; Hernandez, Carolyn; Nguyen, Phirum; Aryafar, Hamed; Valasek, Mark; Haufe, William; Hooker, Catherine; Richards, Lisa; Sirlin, Claude B.; Loomba, Rohit

    2016-01-01

    Background: Magnetic resonance imaging-estimated proton-density-fat-fraction (MRI-PDFF) has been shown to be a noninvasive, accurate and reproducible imaging-based biomarker for assessing steatosis and treatment response in nonalcoholic steatohepatitis (NASH) clinical trials. However, there are no data on the magnitude of MRI-PDFF reduction corresponding to histologic response in the setting of a NASH clinical trial. The aim of this study was to quantitatively compare the magnitude of MRI-PDFF reduction between histologic responders versus histologic nonresponders in NASH patients. Methods: This study is a secondary analysis of the MOZART trial, which included 50 patients with biopsy-proven NASH randomized to ezetimibe 10 mg/day orally or placebo for 24 weeks. The primary aim was to perform a head-to-head comparative analysis of histologic responders [defined as a ⩾2-point reduction in the nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) without worsening fibrosis] versus nonresponders, and the corresponding quantitative change in liver fat content measured via MRI-PDFF. Results: Of the 35 patients who underwent paired liver biopsy and MRI-PDFF assessment at the beginning and end of treatment, 10 demonstrated a histologic response. Compared with histologic nonresponders, histologic responders had a statistically significant reduction in MRI-PDFF of −4.1% ± 4.9 versus −0.6 ± 4.1 (p < 0.04) with a mean relative percent change of −29.3% ± 33.0 versus +2.0% ± 24.0 (p < 0.004), respectively. Conclusions: Utilizing paired MRI-PDFF and liver histology data, we demonstrate that a relative reduction of 29% in liver fat on MRI-PDFF is associated with a histologic response in NASH. After external validation by independent research groups, these results can be incorporated into designing future NASH clinical trials, especially those utilizing change in hepatic fat quantified by MRI-PDFF, as a treatment endpoint. PMID:27582882

  8. Assessment of liver circulation by quantitative scintiangiography: Evaluation of the relative contribution of the hepatic arterial and portal venous blood flows to liver perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Molino, G.; Squadrone, E.; Baccegal, M.; Magnani, C.

    1989-04-01

    Quantitative hepatic scintiangiography was previously used for evaluating the relative contribution of hepatic arterial and portal venous blood flows to the hepatic circulation. The present study compares 3 different procedures (automatic and manual integration, and slope fitting methods) for analyzing the hepatic time activity curves obtained after bolus i.v. injection of 370 MBq /sup 99m/Tc-diethylentriaminopentacetic acid. Twenty five subjects were studied: Five controls, ten cirrhotics, and ten portal hypertensive patients previously submitted to side to side portacaval anastomosis. The correspondence between results given by the different methods was satisfactory only in shunted patients, and the reproducibility of computed parameters was quite poor for all procedures. Accordingly, none of the methods can be considered as supporting reliable quantitative pathophysiological evaluations. However, the hepatic arterial/portal venous flow ratio was found to be increased in liver cirrhosis and in shunted patients and therefore, in spite of the limitations underlined before and of the absence of data on the reproducibility of consecutive injections, hepatic scintiangiography may be of some clinical utility.

  9. Quantitative evaluation of scintillation camera imaging characteristics of isotopes used in liver radioembolization

    National Research Council Canada - National Science Library

    Elschot, Mattijs; Nijsen, Johannes Franciscus Wilhelmus; Dam, Alida Johanna; de Jong, Hugo Wilhelmus Antonius Maria

    2011-01-01

    .... The aim of this study is to quantitatively evaluate and compare the imaging characteristics of these three isotopes, in order that imaging protocols can be optimized and RE studies with varying isotopes can be compared...

  10. Functional Relationships between Lipid Metabolism and Liver Regeneration

    Directory of Open Access Journals (Sweden)

    David A. Rudnick

    2012-01-01

    Full Text Available The regenerative capacity of the liver is well known, and the mechanisms that regulate this process have been extensively studied using experimental model systems including surgical resection and hepatotoxin exposure. The response to primary mitogens has also been used to investigate the regulation of hepatocellular proliferation. Such analyses have identified many specific cytokines and growth factors, intracellular signaling events, and transcription factors that are regulated during and necessary for normal liver regeneration. Nevertheless, the nature and identities of the most proximal events that initiate hepatic regeneration as well as those distal signals that terminate this process remain unknown. Here, we review the data implicating acute alterations in lipid metabolism as important determinants of experimental liver regeneration and propose a novel metabolic model of regeneration based on these data. We also discuss the association between chronic hepatic steatosis and impaired regeneration in animal models and humans and consider important areas for future research.

  11. Occupational coke oven emissions exposure and risk of abnormal liver function: modifications of body mass index and hepatitis virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Y. Hu; B. Chen; J. Qian; L. Jin; T. Jin; D. Lu [Fudan University, Shanghai (China). Department of Occupational and Environmental Health

    2010-03-15

    Occupational coke oven emissions (COEs) have been considered an important health issue. However, there are no conclusive data on human hepatic injury due to COE exposure. The association of COE exposure with liver function was explored and the effects of modification of potential non-occupational factors were assessed. 705 coke oven workers and 247 referents were investigated. Individual cumulative COE exposure was quantitatively estimated. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), {gamma}-glutamyl transferase, alkaline phosphatase, hepatitis B surface antigen and anti-hepatitis C antibody were measured. Among those with high COE exposure, the adjusted ORs of abnormal ALT and AST were 5.23 (95% CI 2.66 to 10.27) and 1.95 (95% CI 1.18 to 3.52), respectively. Overweight individuals (body mass index (BMI) {>=}25 kg/m{sup 2}) with high COE exposure had elevated risks of abnormal ALT (adjusted OR 23.93, 95% CI 8.73 to 65.62) and AST (adjusted OR 5.18, 95% CI 2.32 to 11.58). Risk of liver damage in hepatitis B virus- or hepatitis C virus-positive individuals with COE exposure was also elevated. Long-term exposure to COE increases the risk of liver dysfunction, which is more prominent among those with higher BMI and hepatitis virus infection. The risk assessment of liver damage associated with COE exposure should take BMI and hepatitis virus infection into consideration.

  12. Immunochemical quantitation of 3-(cystein-S-yl)acetaminophen adducts in serum and liver proteins of acetaminophen-treated mice.

    Science.gov (United States)

    Pumford, N R; Hinson, J A; Potter, D W; Rowland, K L; Benson, R W; Roberts, D W

    1989-01-01

    Using a recently developed enzyme-linked immunosorbent assay specific for 3-(cystein-S-yl)acetaminophen adducts we have quantitated the formation of these specific adducts in liver and serum protein of B6C3F1 male mice dosed with acetaminophen. Administration of acetaminophen at doses of 50, 100, 200, 300, 400 and 500 mg/kg to mice resulted in evidence of hepatotoxicity (increase in serum levels of alanine aminotransferase and aspartate aminotransferase) at 4 hr in the 300, 400 and 500 mg/kg treatment groups only. The formation of 3-(cystein-S-yl)acetaminophen adducts in liver protein was not observed in the groups receiving 50, 100 and 200 mg/kg doses, but was observed in the groups receiving doses above 300 mg/kg of acetaminophen. Greater levels of adduct formation were observed at the higher doses. 3-(Cystein-S-yl)acetaminophen protein adducts were also observed in serum of mice receiving hepatotoxic doses of acetaminophen. After a 400 mg/kg dose of acetaminophen, 3-(cystein-S-yl)acetaminophen adducts in the liver protein reached peak levels 2 hr after dosing. By 12 hr the levels decreased to approximately 10% of the peak level. In contrast, 3-(cystein-S-yl)acetaminophen adducts in serum protein were delayed, reaching a sustained peak 6 to 12 hr after dosing. The dose-response correlation between the appearance of serum aminotransferases and 3-(cystein-S-yl)acetaminophen adducts in serum protein and the temporal correlation between the decrease in 3-(cystein-S-yl)acetaminophen adducts in liver protein and the appearance of adducts in serum protein are consistent with a hepatic origin of the adducts detected in serum protein.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Functional MR imaging of the liver; Funktionelle MR-Tomographie der Leber

    Energy Technology Data Exchange (ETDEWEB)

    Wibmer, A.; Nolz, R.; Ba-Ssalamah, A. [Medizinische Universitaet Wien, Allgemeines Krankenhaus der Stadt Wien, Universitaetsklinik fuer Radiodiagnostik und Nuklearmedizin, Wien (Austria); Trauner, M. [Medizinische Universitaet Wien, Universitaetsklinik fuer Innere Medizin III, Klinische Abteilung fuer Gastroenterologie und Hepatologie, Wien (Austria)

    2015-12-15

    The diagnostics of diffuse liver disease traditionally rely on liver biopsies and histopathological analysis of tissue specimens. However, a liver biopsy is invasive and carries some non-negligible risks, especially for patients with decreased liver function and those requiring repeated follow-up examinations. Over the last decades, magnetic resonance imaging (MRI) has developed into a valuable tool for the non-invasive characterization of focal liver lesions and diseases of the bile ducts. Recently, several MRI methods have been developed and clinically evaluated that also allow the diagnostics and staging of diffuse liver diseases, e. g. non-alcoholic fatty liver disease, hepatitis, hepatic fibrosis, liver cirrhosis, hemochromatosis and hemosiderosis. The sequelae of diffuse liver diseases, such as a decreased liver functional reserve or portal hypertension, can also be detected and quantified by modern MRI methods. This article provides the reader with the basic principles of functional MRI of the liver and discusses the importance in a clinical context. (orig.) [German] Die Diagnostik diffuser Lebererkrankungen stuetzt sich klassisch auf die Leberbiopsie und deren histopathologische Analyse. Dieses Verfahren ist allerdings fuer die Patienten unangenehm und schmerzhaft, birgt v. a. bei Patienten mit Lebererkrankungen ein gewisses Risiko und eignet sich daher nur sehr eingeschraenkt zur Verlaufskontrolle bei chronischen Erkrankungen. Die Magnetresonanztomographie (MRT) der Leber nimmt schon jetzt eine zentrale Stellung in der Diagnostik von Raumforderungen der Leber und von Erkrankungen der Gallenwege ein. Darueber hinaus bietet dieses nichtinvasive Verfahren Moeglichkeiten, diffuse Erkrankungen des Leberparenchyms zu diagnostizieren und ihren Schweregrad abzuschaetzen, z. B. bei nichtalkoholischer Leberverfettung, Hepatitis, Leberfibrose, Zirrhose, Haemochromatose und Siderose und anderen. Folgen einer parenchymatoesen Lebererkrankung, wie die portale

  14. Evaluation of liver functional reserve by combining D-sorbitol clearance rate and CT measured liver volume

    Institute of Scientific and Technical Information of China (English)

    Yi-Ming Li; Fan Lv; Xin Xu; Hong Ji; Wen-Tao Gao; Tuan-Jie Lei; Gui-Bing Ren; Zhi-Lan Bai; Qiang Li

    2003-01-01

    AIM: Our research attempted to evaluate the overall functional reserve of cirrhotic liver by combination of hepatic functional blood flow, liver volume, and ChildPugh′s classification, and to discuss its value of clinical application.METHODS: Ninety two patients with portal hypertension due to hepatic cirrhosis were investigated. All had a historyof haematemesis and hematochezia, esophageal and gastric fundus varices, splenomegaly and hypersplenia.A 2-year follow-up was routinely performed and no one was lost. Twenty two healthy volunteers were used as control group. Blood and urine samples were collected 4times before and after intravenous D-sorbitol infusion.The hepatic clearance (CLH) of D-sorbitol was then calculated according to enzymatic spectrophotometric method while the total blood flow (QToTAL) and intrahepatic shunt (RINs) were detected by multicolor Doppler ultrasound, and the liver volume was measured by spiral CT. Data were estimated by t-test, variance calculation and chi-squared test. The relationships between all these parameters and different groups were investigated according to Child-Pugh classification and postoperative complications respectively.RESULTS: Steady blood concentration was achieved 120 mins after D-sorbitol intravenous infusion, which was (0.358±0.064) mmoⅠ@L-1 in cirrhotic group and (0.189±0.05)mmol@L-1 in control group (P<0.01). CLH=(812.7±112.4) ml@min-1,QTOTAL=(1280.6±131.4) ml@min-1, and RINS=(36.54±10.65)%in cirrhotic group and CLH=(1248.3±210.5) ml.min-1, QTOTAL=(1362.4-±126.9) ml@min-1, and RINS=(8.37±3.32) % in control group (P<0.01). The liver volume of cirrhotic group was 1057±249 cm3, 851±148 cm3 and 663±77 cm3 in Child A, B and C group respectively with significant difference (P<0.001).The average volume of cirrhotic liver in Child B, C group was significantly reduced in comparison with that in control group (P<0.001). The patient, whose liver volume decreased by 40 % with the CLH below 600 ml

  15. Quantitative liver proteomics identifies FGF19 targets that couple metabolism and proliferation

    OpenAIRE

    Massafra, Vittoria; Milona, Alexandra; VOS, HARMJAN R.; Burgering, Boudewijn M. T.; van Mil, Saskia W. C.

    2017-01-01

    Fibroblast growth factor 19 (FGF19) is a gut-derived peptide hormone that is produced following activation of Farnesoid X Receptor (FXR). FGF19 is secreted and signals to the liver, where it contributes to the homeostasis of bile acid (BA), lipid and carbohydrate metabolism. FGF19 is a promising therapeutic target for the metabolic syndrome and cholestatic diseases, but enthusiasm for its use has been tempered by FGF19-mediated induction of proliferation and hepatocellular carcinoma. To infor...

  16. Epistasis analysis for quantitative traits by functional regression model.

    Science.gov (United States)

    Zhang, Futao; Boerwinkle, Eric; Xiong, Momiao

    2014-06-01

    The critical barrier in interaction analysis for rare variants is that most traditional statistical methods for testing interactions were originally designed for testing the interaction between common variants and are difficult to apply to rare variants because of their prohibitive computational time and poor ability. The great challenges for successful detection of interactions with next-generation sequencing (NGS) data are (1) lack of methods for interaction analysis with rare variants, (2) severe multiple testing, and (3) time-consuming computations. To meet these challenges, we shift the paradigm of interaction analysis between two loci to interaction analysis between two sets of loci or genomic regions and collectively test interactions between all possible pairs of SNPs within two genomic regions. In other words, we take a genome region as a basic unit of interaction analysis and use high-dimensional data reduction and functional data analysis techniques to develop a novel functional regression model to collectively test interactions between all possible pairs of single nucleotide polymorphisms (SNPs) within two genome regions. By intensive simulations, we demonstrate that the functional regression models for interaction analysis of the quantitative trait have the correct type 1 error rates and a much better ability to detect interactions than the current pairwise interaction analysis. The proposed method was applied to exome sequence data from the NHLBI's Exome Sequencing Project (ESP) and CHARGE-S study. We discovered 27 pairs of genes showing significant interactions after applying the Bonferroni correction (P-values < 4.58 × 10(-10)) in the ESP, and 11 were replicated in the CHARGE-S study.

  17. Noninvasive quantitation of human liver steatosis using magnetic resonance and bioassay methods

    Energy Technology Data Exchange (ETDEWEB)

    D' Assignies, Gaspard; Ruel, Martin; Khiat, Abdesslem; Lepanto, Luigi; Kauffmann, Claude; Tang, An [Centre Hospitalier de l' Universite de Montreal (CHUM), Departement de Radiologie, Montreal, Quebec (Canada); Chagnon, Miguel [Universite de Montreal (UDEM), Departement de Mathematiques et de Statistique, Montreal, Quebec (Canada); Gaboury, Louis [Centre Hospitalier de l' Universite de Montreal (CHUM), Departement d' Anatomo-Pathologie, Montreal, Quebec (Canada); Boulanger, Yvan [Centre Hospitalier de l' Universite de Montreal (CHUM), Departement de Radiologie, Montreal, Quebec (Canada); Hopital Saint-Luc du CHUM, Departement de Radiologie, Montreal, Quebec (Canada)

    2009-08-15

    The purpose was to evaluate the ability of three magnetic resonance (MR) techniques to detect liver steatosis and to determine which noninvasive technique (MR, bioassays) or combination of techniques is optimal for the quantification of hepatic fat using histopathology as a reference. Twenty patients with histopathologically proven steatosis and 24 control subjects underwent single-voxel proton MR spectroscopy (MRS; 3 voxels), dual-echo in phase/out of phase MR imaging (DEI) and diffusion-weighted MR imaging (DWI) examinations of the liver. Blood or urine bioassays were also performed for steatosis patients. Both MRS and DEI data allowed to detect steatosis with a high sensitivity (0.95 for MRS; 1 for DEI) and specificity (1 for MRS; 0.875 for DEI) but not DWI. Strong correlations were found between fat fraction (FF) measured by MRS, DEI and histopathology segmentation as well as with low density lipoprotein (LDL) and cholesterol concentrations. A Bland-Altman analysis showed a good agreement between the FF measured by MRS and DEI. Partial correlation analyses failed to improve the correlation with segmentation FF when MRS or DEI data were combined with bioassay results. Therefore, FF from MRS or DEI appear to be the best parameters to both detect steatosis and accurately quantify fat liver noninvasively. (orig.)

  18. Fibronectin: Functional character and role in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Razia S Aziz-Seible; Carol A Casey

    2011-01-01

    Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions with cell surface receptors that suggest a role for these proteins beyond the structural considerations of the extracellular matrix. These interactions implicate fibronectin in the regulation of mechanisms that also determine cell behavior and activity. The two major forms, plasma fibronectin (pFn) and cellular fibronectin (cFn), exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. The accumulating cFn, in addition to being a consequence of prolonged tissue damage, may in fact stimulate cellular events that promote further damage. In this review, we summarize what is known regarding such interactions between fibronectin and cells that may influence the biological response to injury. We elaborate on the effects of cFn in the liver, specifically under a condition of chronic alcohol-induced injury. Studies have revealed that chronic alcohol consumption stimulates excess production of cFn by sinusoidal endothelial cells and hepatic stellate cells while impairing its clearance by other cell types resulting in the build up of this glycoprotein throughout the liver and its consequent increased availability to influence cellular activity that could promote the development of alcoholic liver disease. We describe recent findings by our laboratory that support a plausible role for cFn in the promotion of liver injury under a condition of chronic alcohol abuse and the implications of cFn stimulation on the pathogenesis of alcoholic liver disease. These findings suggest an effect of cFn in regulating cell behavior in the alcohol-injured liver that is worth further characterizing not only to gain a more comprehensive understanding of the role this

  19. Quantitative evaluation of statistical inference in resting state functional MRI.

    Science.gov (United States)

    Yang, Xue; Kang, Hakmook; Newton, Allen; Landman, Bennett A

    2012-01-01

    Modern statistical inference techniques may be able to improve the sensitivity and specificity of resting state functional MRI (rs-fMRI) connectivity analysis through more realistic characterization of distributional assumptions. In simulation, the advantages of such modern methods are readily demonstrable. However quantitative empirical validation remains elusive in vivo as the true connectivity patterns are unknown and noise/artifact distributions are challenging to characterize with high fidelity. Recent innovations in capturing finite sample behavior of asymptotically consistent estimators (i.e., SIMulation and EXtrapolation - SIMEX) have enabled direct estimation of bias given single datasets. Herein, we leverage the theoretical core of SIMEX to study the properties of inference methods in the face of diminishing data (in contrast to increasing noise). The stability of inference methods with respect to synthetic loss of empirical data (defined as resilience) is used to quantify the empirical performance of one inference method relative to another. We illustrate this new approach in a comparison of ordinary and robust inference methods with rs-fMRI.

  20. Analysis of liver connexin expression using reverse transcription quantitative real-time polymerase chain reaction

    Science.gov (United States)

    Maes, Michaël; Willebrords, Joost; Crespo Yanguas, Sara; Cogliati, Bruno; Vinken, Mathieu

    2016-01-01

    Summary Although connexin production is mainly regulated at the protein level, altered connexin gene expression has been identified as the underlying mechanism of several pathologies. When studying the latter, appropriate methods to quantify connexin mRNA levels are required. The present chapter describes a well-established reverse transcription quantitative real-time polymerase chain reaction procedure optimized for analysis of hepatic connexins. The method includes RNA extraction and subsequent quantification, generation of complementary DNA, quantitative real-time polymerase chain reaction and data analysis. PMID:27207283

  1. Deferasirox, deferiprone and desferrioxamine treatment in thalassemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging

    Science.gov (United States)

    Pepe, Alessia; Meloni, Antonella; Capra, Marcello; Cianciulli, Paolo; Prossomariti, Luciano; Malaventura, Cristina; Putti, Maria Caterina; Lippi, Alma; Romeo, Maria Antonietta; Bisconte, Maria Grazia; Filosa, Aldo; Caruso, Vincenzo; Quarta, Antonella; Pitrolo, Lorella; Missere, Massimiliano; Midiri, Massimo; Rossi, Giuseppe; Positano, Vincenzo; Lombardi, Massimo; Maggio, Aurelio

    2011-01-01

    Background Oral deferiprone was suggested to be more effective than subcutaneous desferrioxamine for removing heart iron. Oral once-daily chelator deferasirox has recently been made commercially available but its long-term efficacy on cardiac iron and function has not yet been established. Our study aimed to compare the effectiveness of deferasirox, deferiprone and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients by means of quantitative magnetic resonance imaging. Design and Methods From the first 550 thalassemia subjects enrolled in the Myocardial Iron Overload in Thalassemia network, we retrospectively selected thalassemia major patients who had been receiving one chelator alone for longer than one year. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferiprone and 89 treated with desferrioxamine. Myocardial iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron concentrations were measured by T2* multiecho technique. Results The global heart T2* value was significantly higher in the deferiprone (34±11ms) than in the deferasirox (21±12 ms) and the desferrioxamine groups (27±11 ms) (P=0.0001). We found higher left ventricular ejection fractions in the deferiprone and the desferrioxamine versus the deferasirox group (P=0.010). Liver iron concentration, measured as T2* signal, was significantly lower in the desferrioxamine versus the deferiprone and the deferasirox group (P=0.004). Conclusions The cohort of patients treated with oral deferiprone showed less myocardial iron burden and better global systolic ventricular function compared to the patients treated with oral deferasirox or subcutaneous desferrioxamine. PMID:20884710

  2. Magnetic Resonance Elastography of the Liver: Qualitative and Quantitative Comparison of Gradient Echo and Spin Echo Echoplanar Imaging Sequences.

    Science.gov (United States)

    Wagner, Mathilde; Besa, Cecilia; Bou Ayache, Jad; Yasar, Temel Kaya; Bane, Octavia; Fung, Maggie; Ehman, Richard L; Taouli, Bachir

    2016-09-01

    The aim of this study was to compare 2-dimensional (2D) gradient recalled echo (GRE) and 2D spin echo echoplanar imaging (SE-EPI) magnetic resonance elastography (MRE) sequences of the liver in terms of image quality and quantitative liver stiffness (LS) measurement. This prospective study involved 50 consecutive subjects (male/female, 33/17; mean age, 58 years) who underwent liver magnetic resonance imaging at 3.0 T including 2 MRE sequences, 2D GRE, and 2D SE-EPI (acquisition time 56 vs 16 seconds, respectively). Image quality scores were assessed by 2 independent observers based on wave propagation and organ coverage on the confidence map (range, 0-15). A third observer measured LS on stiffness maps (in kilopascal). Mean LS values, regions of interest size (based on confidence map), and image quality scores between SE-EPI and GRE-MRE were compared using paired nonparametric Wilcoxon test. Reproducibility of LS values between the 2 sequences was assessed using intraclass coefficient correlation, coefficient of variation, and Bland-Altman limits of agreement. T2* effect on image quality was assessed using partial Spearman correlation. There were 4 cases of failure with GRE-MRE and none with SE-EPI-MRE. Image quality scores and region of interest size were significantly higher using SE-EPI-MRE versus GRE-MRE (P < 0.0001 for both measurements and observers). Liver stiffness measurements were not significantly different between the 2 sequences (3.75 ± 1.87 kPa vs 3.55 ± 1.51 kPa, P = 0.062), were significantly correlated (intraclass coefficient correlation, 0.909), and had excellent reproducibility (coefficient of variation, 10.2%; bias, 0.023; Bland-Altman limits of agreement, -1.19; 1.66 kPa). Image quality scores using GRE-MRE were significantly correlated with T2* while there was no correlation for SE-EPI-MRE. Our data suggest that SE-EPI-MRE may be a better alternative to GRE-MRE. The diagnostic performance of SE-EPI-MRE for detection of liver fibrosis needs

  3. Lifelong maintenance of composition, function and cellular/subcellular distribution of proteasomes in human liver.

    Science.gov (United States)

    Bellavista, Elena; Martucci, Morena; Vasuri, Francesco; Santoro, Aurelia; Mishto, Michele; Kloss, Alexander; Capizzi, Elisa; Degiovanni, Alessio; Lanzarini, Catia; Remondini, Daniel; Dazzi, Alessandro; Pellegrini, Sara; Cescon, Matteo; Capri, Miriam; Salvioli, Stefano; D'Errico-Grigioni, Antonia; Dahlmann, Burkhardt; Grazi, Gian Luca; Franceschi, Claudio

    2014-01-01

    Owing to organ shortage, livers from old donors are increasingly used for transplantation. The function and duration of such transplanted livers are apparently comparable to those from young donors, suggesting that, despite some morphological and structural age-related changes, no major functional changes do occur in liver with age. We tested this hypothesis by performing a comprehensive study on proteasomes, major cell organelles responsible for proteostasis, in liver biopsies from heart-beating donors. Oxidized and poly-ubiquitin conjugated proteins did not accumulate with age and the three major proteasome proteolytic activities were similar in livers from young and old donors. Analysis of proteasomes composition showed an age-related increased of β5i/α4 ratio, suggesting a shift toward proteasomes containing inducible subunits and a decreased content of PA28α subunit, mainly in the cytosol of hepatocytes. Thus our data suggest that, proteasomes activity is well preserved in livers from aged donors, concomitantly with subtle changes in proteasome subunit composition which might reflect the occurrence of a functional remodelling to maintain an efficient proteostasis. Gender differences are emerging and they deserve further investigations owing to the different aging trajectories between men and women. Finally, our data support the safe use of livers from old donors for transplantation.

  4. Biochemical and Cytological Aspects of Liver Cell Function During Infection

    Science.gov (United States)

    1981-01-01

    liver (Pekarek et al., 1972a), iron into ferritin (Konijn and Hershko, 1977), and zinc, at least in part, into metallothioneins (Sobocinski et al., 1978...corre- sponds to the same point in time as the change in the concentration of the acute- phase serum proteins. This suggests that the accelerated rate of... serum protein concentration . The isotopic label- ing of the albumin fraction, on the other hand, decreases by 50% (Williams et .- . ... ... 115 r 22

  5. Quantitative proteomics analysis reveals perturbation of lipid metabolic pathways in the liver of Atlantic cod (Gadus morhua) treated with PCB 153.

    Science.gov (United States)

    Yadetie, Fekadu; Oveland, Eystein; Døskeland, Anne; Berven, Frode; Goksøyr, Anders; Karlsen, Odd André

    2017-04-01

    PCB 153 is one of the most abundant PCB congeners detected in biological samples. It is a persistent compound that is still present in the environment despite the ban on production and use of PCBs in the late 1970s. It has strong tendencies to bioaccumulate and biomagnify in biota, and studies have suggested that it is an endocrine and metabolic disruptor. In order to study mechanisms of toxicity, we exposed Atlantic cod (Gadus morhua) to various doses of PCB 153 (0, 0.5, 2 and 8mg/kg body weight) for two weeks and examined the effects on expression of liver proteins using label-free quantitative proteomics. Label-free liquid chromatography-mass spectrometry analysis of the liver proteome resulted in the quantification of 1272 proteins, of which 78 proteins were differentially regulated in the PCB 153-treated dose groups compared to the control group. Functional enrichment analysis showed that pathways significantly affected are related to lipid metabolism, cytoskeletal remodeling, cell cycle and cell adhesion. Importantly, the main effects appear to be on lipid metabolism, with up-regulation of enzymes in the de novo fatty acid synthesis pathway, consistent with previous transcriptomics results. Increased plasma triglyceride levels were also observed in the PCB 153 treated fish, in agreement with the induction of the lipogenic genes and proteins. The results suggest that PCB 153 perturbs lipid metabolism in the Atlantic cod liver. Elevated levels of lipogenic enzymes and plasma triglycerides further suggest increased synthesis of fatty acids and triglycerides. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?

    Science.gov (United States)

    Ehler, Johannes; Wagner, Nana-Maria

    2017-01-01

    Purpose. Liver dysfunction and failure are severe complications of sepsis and result in poor outcome and increased mortality. The underlying pathologic mechanisms of hepatocyte dysfunction and necrosis during sepsis are only incompletely understood. Here, we investigated whether procalcitonin, a biomarker of sepsis, modulates liver cell function and viability. Materials and Methods. Employing a previously characterized and patented biosensor system evaluating hepatocyte toxicity in vitro, human hepatocellular carcinoma cells (HepG2/C3A) were exposed to 0.01–50 ng/mL procalcitonin for 2 × 72 h and evaluated for proliferation, necrosis, metabolic activity, cellular integrity, microalbumin synthesis, and detoxification capacity. Acetaminophen served as positive control. For further standardization, procalcitonin effects were confirmed in a cellular toxicology assay panel employing L929 fibroblasts. Data were analyzed using ANOVA/Tukey's test. Results. Already at concentrations as low as 0.25 ng/mL, procalcitonin induced HepG2/C3A necrosis (P < 0.05) and reduced metabolic activity, cellular integrity, synthesis, and detoxification capacity (all P < 0.001). Comparable effects were obtained employing L929 fibroblasts. Conclusion. We provide evidence for procalcitonin to directly impair function and viability of human hepatocytes and exert general cytotoxicity in vitro. Therapeutical targeting of procalcitonin could thus display a novel approach to reduce incidence of liver dysfunction and failure during sepsis and lower morbidity and mortality of septic patients. PMID:28255555

  7. Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Cao Yue, E-mail: yuecao@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Wang Hesheng [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Johnson, Timothy D. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Pan, Charlie [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Hussain, Hero [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Balter, James M.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-01-01

    Purpose: To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. Methods and Materials: Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation between mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. Results: There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. Conclusions: This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which

  8. In vivo quantitative visualization of hypochlorous acid in the liver using a novel selective two-photon fluorescent probe

    Science.gov (United States)

    Wang, Haolu; Jayachandran, Aparna; Gravot, Germain; Liang, Xiaowen; Thorling, Camilla A.; Zhang, Run; Liu, Xin; Roberts, Michael S.

    2016-11-01

    Hypochlorous acid (HOCl) plays a vital role in physiological events and diseases. During hepatic ischemia-reperfusion (I/R) injury, HOCl is generated by neutrophils and diffuses into hepatocytes, causing oxidant stress-mediated injury. Although many probes have been developed to detect HOCl, most were difficult to be distinguished from endogenous fluorophores in intravital imaging and only can be employed under one-photon microscopy. A novel iridium(III) complex-based ferrocene dual-signaling chemosensor (Ir-Fc) was designed and synthesized. Ir-Fc exhibited a strong positive fluorescent response only in the presence of HOCl, whereas negligible fluorescent signals were observed upon the additions of other reactive oxygen/nitrogen species and metal ions. There was a good linear relationship between probe responsive fluorescent intensity and HOCl concentration. Ir-Fc was then intravenously injected into BALB/c mice at the final concentration of 50 μM and the mouse livers were imaged using multiphoton microscopy (MPM). In the I/R liver, reduced autofluorescence was detected by MPM, indicating the hepatocyte necrosis. Remarkable enhancement of red fluorescence was observed in hepatocytes with decreased autofluorescence, indicating the reaction of Ir-Fc with endogenous HOCl molecules. The cellular concentration of HOCl was first calculated based on the intensity of MPM images. No obvious toxic effects were observed in histological examination of major organs after Ir-Fc injection. In summary, Ir-Fc has low cytotoxicity, high specificity to HOCl, and rapid "off-on" fluorescence. It is suitable for dynamic quantitatively monitoring HOCl generation using MPM at the cellular level. This technique can be readily extended to examination of liver diseases and injury.

  9. Abnormal liver function tests as predictors of adverse maternal outcomes in women with preeclampsia.

    Science.gov (United States)

    Kozic, Jennifer R; Benton, Samantha J; Hutcheon, Jennifer A; Payne, Beth A; Magee, Laura A; von Dadelszen, Peter

    2011-10-01

    To evaluate whether (1) the absolute magnitude of liver function test values, (2) the percentage change in liver function test values over time, or (3) the rate of change in liver function test values over time predicts adverse maternal outcomes in women with preeclampsia. We used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a prospective multicentre cohort study assessing predictors of adverse maternal outcomes in women with preeclampsia. Women with at least one liver function test performed at the time of hospital admission were included. Liver functions were tested by serum concentrations of aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), albumin, total bilirubin, and the international normalized prothrombin time ratio. Parameters investigated were absolute levels, change within 48 hours of hospital admission, change from admission to delivery or outcome, and rate of change from admission to delivery or outcome of each liver function test. The ability of these parameters to predict adverse outcomes was assessed using logistic regression analyses and by calculating the receiver operating characteristic (ROC) area under the curve (AUC). Of the 2008 women, 1056 (53%) had at least one abnormal liver function test result. The odds of having an adverse maternal outcome were higher in women with any abnormal liver function test than in women with normal results. When test results were stratified into quartiles, women with results in the highest quartile (lowest quartile for albumin) were at higher risk of adverse outcomes than women in the lowest quartile for all parameters (highest for albumin). The absolute magnitude of AST, ALT, and LDH predicted adverse maternal outcomes (AST: ROC AUC 0.73 [95% CI 0.67 to 0.97]; ALT: ROC AUC 0.73 [95% CI 0.67 to 0.79]; LDH: ROC AUC 0.74 [95% CI 0.68 to 0.81]). Neither change of liver function test results, within 48 hours of admission or from admission to

  10. Impact of PET/CT image reconstruction methods and liver uptake normalization strategies on quantitative image analysis.

    Science.gov (United States)

    Kuhnert, Georg; Boellaard, Ronald; Sterzer, Sergej; Kahraman, Deniz; Scheffler, Matthias; Wolf, Jürgen; Dietlein, Markus; Drzezga, Alexander; Kobe, Carsten

    2016-02-01

    In oncological imaging using PET/CT, the standardized uptake value has become the most common parameter used to measure tracer accumulation. The aim of this analysis was to evaluate ultra high definition (UHD) and ordered subset expectation maximization (OSEM) PET/CT reconstructions for their potential impact on quantification. We analyzed 40 PET/CT scans of lung cancer patients who had undergone PET/CT. Standardized uptake values corrected for body weight (SUV) and lean body mass (SUL) were determined in the single hottest lesion in the lung and normalized to the liver for UHD and OSEM reconstruction. Quantitative uptake values and their normalized ratios for the two reconstruction settings were compared using the Wilcoxon test. The distribution of quantitative uptake values and their ratios in relation to the reconstruction method used were demonstrated in the form of frequency distribution curves, box-plots and scatter plots. The agreement between OSEM and UHD reconstructions was assessed through Bland-Altman analysis. A significant difference was observed after OSEM and UHD reconstruction for SUV and SUL data tested (p < 0.0005 in all cases). The mean values of the ratios after OSEM and UHD reconstruction showed equally significant differences (p < 0.0005 in all cases). Bland-Altman analysis showed that the SUV and SUL and their normalized values were, on average, up to 60 % higher after UHD reconstruction as compared to OSEM reconstruction. OSEM and HD reconstruction brought a significant difference for SUV and SUL, which remained constantly high after normalization to the liver, indicating that standardization of reconstruction and the use of comparable SUV measurements are crucial when using PET/CT.

  11. Impact of PET/CT image reconstruction methods and liver uptake normalization strategies on quantitative image analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kuhnert, Georg; Sterzer, Sergej; Kahraman, Deniz; Dietlein, Markus; Drzezga, Alexander; Kobe, Carsten [University Hospital of Cologne, Department of Nuclear Medicine, Cologne (Germany); Boellaard, Ronald [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Scheffler, Matthias; Wolf, Juergen [University Hospital of Cologne, Lung Cancer Group Cologne, Department I of Internal Medicine, Center for Integrated Oncology Cologne Bonn, Cologne (Germany)

    2016-02-15

    In oncological imaging using PET/CT, the standardized uptake value has become the most common parameter used to measure tracer accumulation. The aim of this analysis was to evaluate ultra high definition (UHD) and ordered subset expectation maximization (OSEM) PET/CT reconstructions for their potential impact on quantification. We analyzed 40 PET/CT scans of lung cancer patients who had undergone PET/CT. Standardized uptake values corrected for body weight (SUV) and lean body mass (SUL) were determined in the single hottest lesion in the lung and normalized to the liver for UHD and OSEM reconstruction. Quantitative uptake values and their normalized ratios for the two reconstruction settings were compared using the Wilcoxon test. The distribution of quantitative uptake values and their ratios in relation to the reconstruction method used were demonstrated in the form of frequency distribution curves, box-plots and scatter plots. The agreement between OSEM and UHD reconstructions was assessed through Bland-Altman analysis. A significant difference was observed after OSEM and UHD reconstruction for SUV and SUL data tested (p < 0.0005 in all cases). The mean values of the ratios after OSEM and UHD reconstruction showed equally significant differences (p < 0.0005 in all cases). Bland-Altman analysis showed that the SUV and SUL and their normalized values were, on average, up to 60 % higher after UHD reconstruction as compared to OSEM reconstruction. OSEM and HD reconstruction brought a significant difference for SUV and SUL, which remained constantly high after normalization to the liver, indicating that standardization of reconstruction and the use of comparable SUV measurements are crucial when using PET/CT. (orig.)

  12. Gallbladder Function and Hepatic Structural Changes in Children with Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    N.Yu. Zavgorodnya

    2016-06-01

    Full Text Available During the last decade, pediatric nonalcoholic liver disease has reached epidemic proportions, becoming one of the most frequent chronic liver diseases in the global child population. Purpose: to study the relationship of the functional state of the gallbladder with structural changes in the liver in children with nonalcoholic fatty liver disease. Materials and methods. We examined 34 children aged from 8 to 17 years old. Hepatic steatosis was determined using the FibroScan® 502 touch with controlled attenuation parameter (CAP. According to the results of transient elastometry and ultrasound of the abdomen with the gallbladder function study, patients were divided into 4 groups: the 1st group consisted of 7 patients with steatosis and hypofunction of gallbladder (20.5 %, group 2 included 6 patients with steatosis and gallbladder normofunction (17.65 %, group 3 consisted of 11 patients without hepatic steatosis with hypofunction of gallbladder (32.35 %, group 4 included 10 patients without hepatic steatosis with gallbladder normofunction (29.4 %. Results. The sonographic studies demonstrated children of the 1st group (steatosis with gallbladder hypokinesia to have significantly larger sizes of liver lobes compared to group 4 (children without steatosis with gallbladder normofunction. Also, the stiffness of the liver parenchyma was highest in patients with hepatic steatosis and gallbladder hypokinesia. Discussion. The combination of hepatic steatosis and hypokinesia of the gallbladder in children is accompanied by a significant increase in liver size, increased stiffness of the liver parenchyma and increasing degree of steatosis. The data indicate the relationship of the gallbladder function and the liver structural changes.

  13. Toxicity Effect of Nigella Sativa on the Liver Function of Rats

    Directory of Open Access Journals (Sweden)

    Mohamad Hafanizam Bin Hassan

    2013-02-01

    Full Text Available Purpose: The aim of this study was to determine the toxic effect of Nigella sativa powder on the liver function which was evaluated by measuring liver enzymes and through histopathological examination of liver tissue. Methods: Twenty four male Sprague Dawley rats were allotted randomly to four groups including: control (taking normal diet; low dose (supplemented with 0.01 g/kg/day Nigella sativa; normal dose (supplemented with 0.1 g/kg/day Nigella sativa and high dose (supplemented with 1 g/kg/day Nigella sativa. All of supplements administered in powder form mixed with rats’ pellet for 28 days. To assess liver toxicity, liver enzymes measurement and histological study were done at the end of supplementation. Results: The finding revealed that there was no significant change in serum alanine aminotransferase (ALT and aspartate aminotransferase (AST between treatment groups. Histopathological study showed very minimal and mild changes in fatty degeneration in normal and high doses of Nigella sativa treated group. Inflammation and necrosis were absent. Conclusion: The study showed that supplementation of Nigella sativa up to the dose of 1 g/kg supplemented for a period of 28 days resulted no changes in liver enzymes level and did not cause any toxicity effect on the liver function.

  14. The ileum as a determinant organ of the functional liver cell mass in rats

    Directory of Open Access Journals (Sweden)

    Aldo Cunha Medeiros

    2013-03-01

    Full Text Available PURPOSE: To evaluate if the ileum resection changes the functioning liver cell mass, the hepatic metabolism and the biodistribution of radiopharmaceutical in rats. METHODS: Twelve Wistar rats weighing 285g±34g were randomly divided into the ileum resection group (n = 6 and sham group rats (n = 6. After 30 days, they were anesthetized and 0.1mL of 99m-Tc-phytate (0.66MBq was injected via femoral vein. After 30 minutes, blood samples were collected for red blood cells radioactive labeling and serum ALT, AST and gammaGT. Liver samples were used for 99m-Tc-phytate percentage of radioactivity/gram of tissue and histopathology. Student 's t test was used with significance 0.05. RESULTS: There was a higher uptake of 99m-Tc-phytate in the liver of sham rats, compared to the ileum resection group (p<0.05. GammaGT, ALT and AST were increased in ileum resection rats compared to sham (p<0.05. The he patocytes count was significantly lower in ileum resection group than in sham (p<0.05. Liver: body mass ratio was lower in experimental animals than in sham group (p<0.05. CONCLUSION: These data support that the ileum has important role in liver function and liver mass regulation, and they have potential clinical implications regarding the pathogenesis of liver injury following lower bowel resection.

  15. The effect of clofazimine on liver function tests in lepra reaction (ENL).

    Science.gov (United States)

    Bulakh, P M; Kowale, C N; Ranade, S M; Burte, N P; Chandorkar, A G

    1983-10-01

    Twenty patients with suspected DDS resistance and repeated attacks of lepra reactions were selected for the study. Clofazimine was administered in different doses over a period of 12 months. Elevated levels of transaminases and Alkaline phosphatase prior therapy attained values to near normalcy. Progressive fall in serum Bilirubin and Proteins with normal A/G ratio at the end of therapy was also observed. Clofazimine by its anti-inflammatory and antibacterial action could inhibit the process of liver damage and happened to have minimal deleterious effect on liver by studying the liver function tests.

  16. Data on body weight and liver functionality in aged rats fed an enriched strawberry diet

    Directory of Open Access Journals (Sweden)

    Francesca Giampieri

    2017-08-01

    Full Text Available Here, we present new original data on the effects of strawberry consumption on body weight and liver status of aged rats. Wistar rats aged 19–21 months were fed a strawberry enriched diet prepared by substituting 15% of the total calories with freeze-dried strawberry powder for two months. Body weight, plasma biomarkers of liver injury (alanine transferase, aspartate aminotransferase and alkaline phosphatase and liver histological analysis were assessed. These data indicate that strawberry supplementation did not interfere with normal animal maintenance and with liver structure and functionality. For further details and experimental findings please refer to the article “Strawberry consumption improves aging-associated impairments, mitochondrial biogenesis and functionality through the AMP-Activated Protein Kinase signaling cascade” in FOOD CHEMISTRY (Giampieri et al., 2017 [1].

  17. The Evaluation of Adrenal Function in Two Cases of Hypocortisolism Accompanied by Liver Cirrhosis.

    Science.gov (United States)

    Yamashita, Maki; Kageyama, Kazunori; Murakami, Hiroshi; Sugiyama, Aya; Yanagimachi, Miyuki; Sato, Eri; Murasawa, Shingo; Matsui, Jun; Tamasawa, Naoki; Daimon, Makoto

    2016-01-01

    Adrenal insufficiency may occur in patients with liver cirrhosis. The assessment of hypothalamus-pituitary-adrenal function is important in such patients, but there is no consensus as to how it should be performed. We herein report the results of our evaluation of the adrenal function in two patients with hypocortisolism accompanied by liver cirrhosis. The patients lacked the typical features of hypocortisolism. One was diagnosed with hypocortisolism accompanied by liver cirrhosis while the other had secondary adrenal insufficiency caused by a hypothalamic disorder. Hypocortisolism accompanied by liver cirrhosis should be evaluated by endocrine tests to determine its pathogenesis. A low-dose adrenocorticotropic hormone test may be appropriate for non-critically ill cirrhotic patients.

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

    Science.gov (United States)

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

    2013-03-01

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

  19. Quantitative Portal Vein Velocity of Liver Cancer Patients with Transcatheter Arterial Chemoembolization on Angiography

    Directory of Open Access Journals (Sweden)

    Yung-Jen Ho

    2012-01-01

    Full Text Available Objective. We applied optical flow method (OFM to quantify relative velocities of blood flow using digital subtraction angiography (DSA in the vascular analysis of hepatocellular carcinoma (HCC patients who underwent transarterial chemoembolization (TACE treatment. Methods. A total of 40 HCC patients treated by TACE were analyzed in this study. DSA imaging with a 12-inch field of view, 1024 × 1024 pixels and 4 frames/second was acquired. OFM developed for motion estimation is applied for blood flow estimation. Two acrylic phantoms were built to validate the method. Results. The relationship between the OFM and Doppler measurements was found linear with R2=0.99 for both straight and curved tube phantoms. Quantitative blood flow distribution images of the portal vein region were presented. After TACE, the minimum, maximum and mean velocities in the portal vein all decreased (P<0.05. Additionally, the velocity in the portal vein is significantly lower with a higher Child-Pugh score (P<0.01. Conclusions. The present technique provides add-on quantitative information of flows to DSA and the hemodynamic analysis in relative quantifications of blood flow in portal vein of hepatocellular carcinoma patients using DSA.

  20. In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

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    Sarada Devi Ramachandran

    Full Text Available In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process. Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs and mesenchymal stem cells (MSCs was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.

  1. Effect of Compound Glycyrrhizin Injection on Liver Function and Cellular Immunity of Children with Infectious Mononucleosis Complicated Liver Impairment

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To investigate the effects of Compound Glycyrrhizin Injection (CGI) on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment (IM-LI) and to explore its clinical therapeutic effect. Methods: Forty-two patients with IM-LI were randomly assigned, according to the randomizing number table, to two groups, 20 in the control group and 22 in the treated group.All the patients were treated with conventional treatment, but to those in the treated group, CGI was given additionally once a day, at the dosage of 10 ml for children aged below 2 years, 20 ml for 2-4 years old, 30 ml for 5-7 years old and 40 ml for 8- 12 years old, in 100-200 ml of 5% glucose solution by intravenous dripping. The treatment lasted for 2 weeks. T lymphocyte subsets and serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) were detected before and after treatment. Besides, a normal control group consisting of 20 healthy children was also set up. Results: Baseline of the percentage of CD3 + , CD8 + lymphocyte and serum levels of ALT, AST, TBiL in the children with IM-LI were markedly higher, while the percentage of CD4 + lymphocyte and the CD4 +/CD8 + ratio was markedly lower in IM-LI children as compared with the corresponding indices in the healthy children ( P<0.01 ). These indices were improved after treatment in both groups of patients, but the improvement in the treated group was better than that in the control group (P<0.01). Conclusion: Cellular immunity dysfunction often occurs in patients with IM-LI, and CGI treatment can not only obviously promote the recovery of liver function, but also regulate the immune function in organism.

  2. Quantitative evaluation of six graph based semi-automatic liver tumor segmentation techniques using multiple sets of reference segmentation

    Science.gov (United States)

    Su, Zihua; Deng, Xiang; Chefd'hotel, Christophe; Grady, Leo; Fei, Jun; Zheng, Dong; Chen, Ning; Xu, Xiaodong

    2011-03-01

    Graph based semi-automatic tumor segmentation techniques have demonstrated great potential in efficiently measuring tumor size from CT images. Comprehensive and quantitative validation is essential to ensure the efficacy of graph based tumor segmentation techniques in clinical applications. In this paper, we present a quantitative validation study of six graph based 3D semi-automatic tumor segmentation techniques using multiple sets of expert segmentation. The six segmentation techniques are Random Walk (RW), Watershed based Random Walk (WRW), LazySnapping (LS), GraphCut (GHC), GrabCut (GBC), and GrowCut (GWC) algorithms. The validation was conducted using clinical CT data of 29 liver tumors and four sets of expert segmentation. The performance of the six algorithms was evaluated using accuracy and reproducibility. The accuracy was quantified using Normalized Probabilistic Rand Index (NPRI), which takes into account of the variation of multiple expert segmentations. The reproducibility was evaluated by the change of the NPRI from 10 different sets of user initializations. Our results from the accuracy test demonstrated that RW (0.63) showed the highest NPRI value, compared to WRW (0.61), GWC (0.60), GHC (0.58), LS (0.57), GBC (0.27). The results from the reproducibility test indicated that GBC is more sensitive to user initialization than the other five algorithms. Compared to previous tumor segmentation validation studies using one set of reference segmentation, our evaluation methods use multiple sets of expert segmentation to address the inter or intra rater variability issue in ground truth annotation, and provide quantitative assessment for comparing different segmentation algorithms.

  3. Real-time elastography in the assessment of liver fibrosis: a review of qualitative and semi-quantitative methods for elastogram analysis.

    Science.gov (United States)

    Paparo, Francesco; Corradi, Francesco; Cevasco, Luca; Revelli, Matteo; Marziano, Andrea; Molini, Lucio; Cenderello, Giovanni; Cassola, Giovanni; Rollandi, Gian Andrea

    2014-09-01

    Despite its invasiveness, liver biopsy is still considered the gold standard for the assessment of hepatic fibrosis. Non-invasive ultrasound-based techniques are increasingly employed to assess parenchymal stiffness and the progression of chronic diffuse liver diseases. Real-time elastography is a rapidly evolving technique that can reveal the elastic properties of tissues. This review examines qualitative and semi-quantitative methods developed for analysis of real-time liver elastograms, to estimate parenchymal stiffness and, indirectly, the stage of fibrosis. Qualitative analysis is the most immediate approach for elastogram analysis, but this method increases intra- and inter-observer variability, which is seen as a major limitation of real-time elastography. Semi-quantitative methods include analysis of the histogram derived from color-coded maps, as well as calculation of the elastic ratio and fibrosis index.

  4. Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy

    Institute of Scientific and Technical Information of China (English)

    Koichi; Honda; Masataka; Seike; Junya; Oribe; Mizuki; Endo; Mie; Arakawa; Hiroki; Syo; Masao; Iwao; Masanori; Tokoro; Junko; Nishimura; Tetsu; Mori; Tsutomu; Yamashita; Satoshi; Fukuchi; Toyokichi; Muro; Kazunari; Murakami

    2016-01-01

    AIM:To identify factors that influence long-term liver function following radiofrequency ablation(RFA)in patients with viral hepatitis-related hepatocellular carcinoma.METHODS:A total of 123 patients with hepatitis B virus-or hepatitis C virus-related hepatocellular carcinoma(HCC)(n=12 and n=111,respectively)were enrolled.Cumulative rates of worsening Child-Pugh(CP)scores(defined as a 2-point increase)were examined.RESULTS:CP score worsening was confirmed in 22patients over a mean follow-up period of 43.8±26.3mo.Multivariate analysis identified CP class,platelet count,and aspartate aminotransferase levels as significant predictors of a worsening CP score(P=0.000,P=0.011 and P=0.024,respectively).In contrast,repeated RFA was not identified as a risk factor for liver function deterioration.CONCLUSION:Long-term liver function following RFA was dependent on liver functional reserve,the degreeof fibrosis present,and the activity of the hepatitis condition for this cohort.Therefore,in order to maintain liver function for an extended period following RFA,suppression of viral hepatitis activity is important even after the treatment of HCC.

  5. Quantitative Reasoning and the Sine Function: The Case of Zac

    Science.gov (United States)

    Moore, Kevin C.

    2014-01-01

    A growing body of literature has identified quantitative and covariational reasoning as critical for secondary and undergraduate student learning, particularly for topics that require students to make sense of relationships between quantities. The present study extends this body of literature by characterizing an undergraduate precalculus…

  6. Quantitative Reasoning and the Sine Function: The Case of Zac

    Science.gov (United States)

    Moore, Kevin C.

    2014-01-01

    A growing body of literature has identified quantitative and covariational reasoning as critical for secondary and undergraduate student learning, particularly for topics that require students to make sense of relationships between quantities. The present study extends this body of literature by characterizing an undergraduate precalculus…

  7. Feasibility of Preoperative FDG PET/CT Total Hepatic Glycolysis in the Remnant Liver for the Prediction of Postoperative Liver Function.

    Science.gov (United States)

    Cho, Arthur; Chung, Yong Eun; Choi, Jin Sub; Kim, Kyung Sik; Choi, Gi Hong; Park, Young Nyun; Kim, Myeong-Jin

    2017-03-01

    The objective of our study was to investigate the prognostic value of total glycolysis of the remnant liver, which reflects both metabolic and anatomic liver function, for predicting postoperative hepatic insufficiency. Patients who underwent (18)F-FDG PET/CT and abdominal CT within 1 month of major hepatectomy were retrospectively analyzed. Total liver volume, remnant liver volume, the ratio of the remnant hepatic volume to the preoperative hepatic volume (RFRHV), and mean standardized uptake value (SUVmean) were measured, and total glycolysis of the remnant liver was calculated. Clinical hepatic function reserve values, including the indocyanine green retention rate at 15 minutes, the model for end-stage liver disease (MELD) score, and aspartate aminotransferase to platelet ratio index (APRI), were calculated. Univariate and multivariate analyses were performed, and an optimal model for predicting hepatic insufficiency was developed. ROC curves were used to compare diagnostic performance. Of 149 patients, seven patients had hepatic insufficiency. The SUVmean showed the highest sensitivity (100%; specificity, 31.7%) for predicting hepatic insufficiency, and total glycolysis of the remnant liver showed the highest specificity (96.5%; sensitivity, 57.1%) for predicting hepatic insufficiency. On multivariate analysis, the odds ratio of APRI (> 5.4) and total glycolysis of the remnant liver (≤ 625.6) was 46.3 and 82.9, respectively, for predicting hepatic insufficiency. On ROC curve analysis, a new model composed of APRI and total glycolysis of the remnant liver showed a higher area under the ROC curve (Az) value (Az = 0.899) than SUVmean (0.659), MELD score (0.618), APRI (0.693), RFRHV (0.797), and remnant liver volume (0.762). The total glycolysis of the remnant liver has moderate sensitivity and high specificity for predicting hepatic insufficiency. Combining the total glycolysis of the remnant liver and APRI yielded the best diagnostic performance for predicting

  8. Study of Abnormal Liver Function Test during Pregnancy in a Tertiary Care Hospital in Chhattisgarh.

    Science.gov (United States)

    Mishra, Nalini; Mishra, V N; Thakur, Parineeta

    2016-10-01

    Abnormal liver function tests (LFTs) in pregnancy require proper interpretation in order to avoid pitfalls in the diagnosis. The underlying disorder can have a significant effect on the outcome of both mother and foetus. The present study was done with the objective to study the clinical profile, incidence and possible causes of derangements of liver function tests. Eighty pregnant women with abnormal liver dysfunction were studied prospectively. Women with chronic liver disease and drug-induced abnormal liver function test were excluded. All available LFTs including LDH were studied along with some more definitive tests to aid identification of underlying cause. Foetomaternal outcome was noted in all. The incidence of abnormal LFT was 0.9 %. 13/80 (16.75 %) women had liver disorder not specific to pregnancy, whereas 67/80 (83.25 %) women had pregnancy-specific liver dysfunction. Of these, 65(81.25 %) women with liver dysfunction had pre-eclampsia including 11 (13.75 %) with HELLP and six women with eclampsia. 48/65 (60 %) women had pre-eclampsia in the absence of HELLP syndrome or eclampsia. The mean value for bilirubin (mg %) in hypertensive disorders of pregnancy ranged from 1.64 to 3.8, between 5 and 10 for ICP and AFLP and >10 in infective hepatitis. Transaminases were highest in infective hepatitis, whereas alkaline phosphate was highest in ICP. Total 27 (33.75 %) women suffered from adverse outcome with four (5 %) maternal deaths and 23 (28.75 %) major maternal morbidities. 33/80 (41.25 %) women had intrauterine death. 26.25 % babies were small for date. Pregnancy-specific disorders are the leading cause of abnormal liver function test during pregnant state particularly in the third trimester. Pre-eclampsia-related disorder is the commonest. Gestational age of pregnancy and relative values of various liver function tests in different pregnancy-specific and pregnancy nonspecific disorders appear to be the best guide to clinch the diagnosis.

  9. Functional renal failure (FRF) in cirrhosis of the liver and liver carcinoma

    Science.gov (United States)

    Vesin, P.; Traverso, H.

    1975-01-01

    The term ‘functional renal failure’ has been used to describe the renal failure developing in advanced cirrhosis in which tubular function and structure remain intact. It may develop spontaneously, in which case prognosis is poor, but may be secondary to gastro-intestinal haemorrhage or excessive use of diuretics, in which case correction of the precipitating factor leads to improvement in renal function. It is suggested that the renal failure is due to a reduction in effective circulating plasma volume. PMID:1234327

  10. Regulation and antimetastatic functions of liver-associated natural killer cells.

    Science.gov (United States)

    Wiltrout, R H

    2000-04-01

    The liver is a complex organ composed of hepatic parenchymal cells and a variety of non-parenchymal cells that consist of endothelial cells, Kupffer cells, and several subsets of resident lymphocytes, including natural killer (NK), T, and NK1.1+/CD3+ (NK/T) cells. The regulation of these various lymphoid subpopulations and their relative contributions to antiviral, antitumor and pathogenic inflammatory responses in the liver remain topics of much interest. Studies from our laboratory have shown that various immune stimulants and cytokines can augment liver-associated NK activity at least partially through the mobilization of NK cells from the bone marrow to the liver. The mobilization process can be dependent on the induction of interferon (IFN)-gamma and/or tumor necrosis factor-alpha and on very late activation antigen-4/vascular cell adhesion molecule-1 interaction. The induction of IFN-gamma by cytokines such as interleukin (IL)-12 also rapidly triggers the induction of chemokine genes in parenchymal cells that may contribute to the localization of NK and T cells. Both IL-2 and IL-12 trigger changes in the number and functions of liver-associated leukocyte subsets, and induce antimetastatic effects that are likely mediated through several direct and indirect mechanisms. The overall goal of these studies is to understand the interactions and functions of liver-associated NK1.1+ cells in the context of innate and adaptive immune responses to neoplasia.

  11. Assessment of the sexual functions of males with chronic liver disease in South West Nigeria.

    Science.gov (United States)

    Adekanle, Olusegun; Ndububa, Dennis A; Orji, Ernest O; Ijarotimi, Oluwasegun

    2014-01-01

    Patients with chronic liver disease (CLD) have been reported to have sexual dysfunction irrespective of etiology. There is little or no report from Nigeria on this disorder. This study looked at sexual dysfunction among male patients with CLD. Patients with chronic viral hepatitis B, liver cirrhosis (LC) and hepatocellular carcinoma (HCC) were interviewed using the international index of erectile function questionnaire. Their responses were compared with an age and sex matched healthy controls. Bio-data and body mass index were obtained for both groups and liver disease severity was graded for patients using the Child-Pugh score. Analysis was done using SPSS (SPSS Inc., Chicago, IL, USA, 2004) for frequencies and means while comparison of means was done using Student's t-test. Significance level was put at P Sexual dysfunctions were seen in patients with HCC and LC in the domains of sexual desire and sexual satisfaction respectively when compared with controls. When patients were divided into the various liver disease severities, patients in Child-Pugh Grade B scored low in the domain of arousal, whereas the domains of erectile functions, orgasm, resolution and satisfaction were affected in patients in Grade C when compared with controls. Male patients with CLD have significant sexual dysfunctions when compared with controls. The dysfunctions are more pronounced in those with Grade C liver disease. Sexual concerns of CLD should be inquired of in those with advanced liver disease.

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

    Science.gov (United States)

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

    2016-12-01

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

  13. Accuracy of indocyanine green pulse spectrophotometry clearance test for liver function prediction in transplanted patients

    Institute of Scientific and Technical Information of China (English)

    Chung-Bao Hsieh; Chung-Jueng Chen; Teng-Wei Chen; Jyh-Cherng Yu; Kuo-Liang Shen; Tzu-Ming Chang; Yao-Chi Liu

    2004-01-01

    AIM: To investigate whether the non-invasive real-time Indocynine green (ICG) clearance is a sensitive index of liver viability in patients before, during, and after liver transplantation.METHODS: Thirteen patients were studied, two before,three during, and eight following liver transplantation, with two patients suffering acute rejection. The conventional invasive ICG clearance test and ICG pulse spectrophotometry non-invasive real-time ICG clearance test were performed simultaneously. Using linear regression analysis we tested the correlation between these two methods. The transplantation condition of these patients and serum total bilirubin (T. Bil), alanine aminotransferase (ALT), and platelet count were also evaluated.RESULTS: The correlation between these two methods was excellent (r2=0.977).CONCLUSION: ICG pulse spectrophotometry clearance is a quick, non-invasive, and reliable liver function test in transplantation patients.

  14. Effect of commonly used vehicles on gastrointestinal, renal, and liver function in rats.

    Science.gov (United States)

    Pestel, Sabine; Martin, Hans-Juergen; Maier, Gerd-Michael; Guth, Brian

    2006-01-01

    Solubility is often a limiting factor when testing new compounds in animal experiments. Various solubilizing agents may be used, but each have their own pharmacological effects. We investigated the effects of selected vehicles having different chemical characteristics on gastrointestinal, renal, and liver function. Rats were treated orally, intravenously or intraperitoneally and gastric emptying, intestinal transit, renal, and liver function were investigated. Gastrointestinal motility was influenced by hydroxyethylcellulose, hydroxypropyl-beta-cyclodextrin (HPbetaCD), HPgammaCD, DMSO, polyethylene glycol 400 (PEG 400), fat emulsion, and the corresponding emulsifier. Liver function was affected by HPbetaCD, HPgammaCD, DMSO, PEG 400, Polysorbate 80, Cremophor RH 40, and fat emulsion. An increase in liver enzymes was observed after PEG 400 and Polysorbate 80. DMSO interfered with clinical chemistry measurements in serum. Urinary function was modified by HPgammaCD, DMSO, PEG 400, and Polysorbate 80, while enhanced urine enzyme excretion was observed after HPbetaCD, HPgammaCD, DMSO, PEG 400, and Polysorbate 80. Most of the investigated vehicles changed gastrointestinal, renal, and/or liver parameters after application of a certain threshold dose for each assay. No "best" vehicle could be identified that may be used in each test system. Thus, vehicles must be selected not only on their chemical characteristics but also on their potential pharmacological activity in a given test system.

  15. HISTOPATHOLOGICAL STUDIES OF LIVER FUNCTION IN RATS FED ON GINGER LILLY CORM MEAL

    Directory of Open Access Journals (Sweden)

    UGWU OKECHUKWU P.C

    2013-01-01

    Full Text Available The effect of feeding Gladiolus unguiculata corm on a few liver function markers were evaluated in this study using albino Wistar rats. Twenty rats were randomly divided into four groups of five rats each. Various concentration of G. unguiculata formulations were fed to the test groups excluding the negative control which received normal feed for the 28 days of analysis. At the end of the feeding period the levels of the serum liver function markers of Aspartate aminotransferase (AST, Alanine aminotransferase (ALT, Alkaline phosphatase (ALP and Protein were determined. Mean serum liver function markers were all increased when compared with the control with only AST liver marker deviating. The ALT activity increased from 36.0 + 3.16 in the control to 38.0 + 3.16 in 20%. The AST significantly increased (p<0.05 from 66.0 + 3.16 in the 20% to 88.0 + 3.16 in the control group. ALP significantly increased from 47.0 +3.16 in the control group to 56.0 + 3.16 in 20%. Protein also increased from 7.0 +0.316 in the control group to 7.8 +0.316 in 20%. The results emanating from this study suggest that Gladiolus unguiculata corm formulations might have some deleterious effects on the liver function.

  16. Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE

    Directory of Open Access Journals (Sweden)

    Sullivan Frank M

    2007-04-01

    Full Text Available Abstract Background Liver function tests (LFTs are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs. Methods/Design A population-based retrospective cohort study will follow up all those who have had an incident liver function test (LFT in primary care to subsequent liver disease or mortality over a period of 15 years (approx. 2.3 million tests in 99,000 people. The study is set in Primary Care in the region of Tayside, Scotland (pop approx. 429,000 between 1989 and 2003. The target population consists of patients with no recorded clinical signs or symptoms of liver disease and registered with a GP. The health technologies being assessed are LFTs, viral and auto-antibody tests, ultrasound, CT, MRI and liver biopsy. The study will utilise the Epidemiology of Liver Disease In Tayside (ELDIT database to determine the outcomes of liver disease. These are based on hospital admission data (Scottish Morbidity Record 1, dispensed medication records, death certificates, and examination of medical records from Tayside hospitals. A sample of patients (n = 150 with recent initial ALF tests or invitation to biopsy will complete questionnaires to obtain quality of life data and anxiety measures. Cost-effectiveness and cost utility Markov model analyses will be performed from health service and patient perspectives using standard NHS costs. The findings will also be used to develop a computerised clinical decision

  17. Changes and clinical significance of liver function and myocardial zymogram in children with rotavirus enteritis

    Institute of Scientific and Technical Information of China (English)

    Lan-Ping Yang

    2016-01-01

    Objective:To explore the changes and clinical significance of liver function and myocardial zymogram in children with rotavirus (RV) enteritis.Methods:A total of 70 children with RV enteritis who were admitted in our hospital were included in the study and served as the observation group. The liver function and myocardial zymogram before and after treatment were detected. The proportion of RV enteritis children with liver and myocardial damage was calculated. The effect of dehydration on the liver function and myocardial zymogram in children with RV enteritis was analyzed. A total of 65 children with non-RV enteritis who were admitted in our hospital at the same stage were served as the control group.Results:The serum ALT, AST, CK, CK-MB, LDH, andα-HBDH levels, and liver myocardial damage children proportion in the observation group were significantly higher than those in the control group (P<0.05). The serum ALT, AST, CK, CK-MB, LDH, andα-HBDH levels in the observation group were significantly elevated with the acceleration of dehydration degree (P<0.05). In the observation group, 45 children had liver and myocardial damage, whose ALT, AST, CK, CK-MB, LDH, andα-HBDH levels after treatment were significantly reduced when compared with before treatment (P<0.05).Conclusions:Early detection of liver function and myocardial zymogram can accurately reflect the condition in children with RV enteritis, which can provide an evidence for the formulation of clinical treatment protocol.

  18. Effect of pulmonary surfactant combined with mucosolvan on immune function, liver and kidney function in neonatal respiratory distress syndrome

    Institute of Scientific and Technical Information of China (English)

    Juan Ma; Xiao-Lei Wang; Zheng-Ying Li; Tao-Ying Chen

    2016-01-01

    Objective:To explore the pulmonary surfactant combined with mucosolvan on immune function, liver and kidney function in neonatal respiratory distress syndrome, provide help for the treatment.Methods:A total of 160 cases of neonatal respiratory distress syndrome in our hospital were selected and randomly divided into observation group and control group according to the random number table method, 80 cases in each group, the control group was given conventional therapy, the observation group was given pulmonary surfactant combined with mucosolvan treatment on the basis of conventional therapy, before treatment and 3 days after treatment, the arterial blood gas correlation indexes, respiratory distress syndrome related factors, immune related factors, liver and kidney function indexes were detected in the 2 groups.Results:Compared with before treatment, in the observation group and the control group after treatment, arterial blood gas indexes PaO2, TCO2, SaO2 significantly increased, while PaCO2 significantly decreased, related cytokines KL-6, MIF-1 and HMGB-1 significantly decreased, immunologic factors IFN-γ and IL-4 significantly increased, while IL-10 and TNF-α significantly decreased, liver function indexes AST, ALT and renal function indexes BUN, CRE decreased significantly, the differences had statistically significant; compared with the control group after treatment, in the observation group after combined treatment, arterial blood gas indexes PaO2, TCO2, SaO2 significantly increased, PaCO2 significantly decreased, related cytokines KL-6, MIF-1 and HMGB-1 significantly decreased, immunologic factors IL-10 and IL-4 significantly increased, IFN-γ and TNF-α significantly decreased, liver function indexes AST, ALT and renal function indexes BUN, CRE decreased significantly; the differences had statistically significant.Conclusion:Pulmonary surfactant combined with mucosolvan can improve the respiratory distress syndrome related factors, immune function, liver

  19. Imaging-based liver function tests. Past, present and future; Bildgestuetzte Leberfunktionstests. Stand der Technik und zukuenftige Entwicklungen

    Energy Technology Data Exchange (ETDEWEB)

    Geisel, D.; Hamm, B.; Denecke, T. [Charite, Campus Virchow-Klinikum, Berlin (Germany). Dept. of Diagnostic and Interventional Radiology; Luedemann, L. [Essen University Hospital (Germany). Dept. of Medical Physics

    2015-10-15

    Preoperative assessment of liver function and prediction of postoperative functional reserve are important in patients scheduled for liver resection. While determination of absolute liver function currently mostly relies on laboratory tests and clinical scores, postoperative remnant liver function is estimated volumetrically using imaging data obtained with computed tomography (CT) or magnetic resonance imaging (MRI). Accurate estimation of hepatic function is also relevant for intensive care patients, oncologic patients, and patients with diffuse liver disease. The indocyanine green (ICG) test is still the only established test for estimating true global liver function. However, more recent tools such as the LiMAx test also allow global assessment of hepatic function. These tests are limited when liver function is inhomogeneously distributed, which is the case in such conditions as unilateral cholestasis or after portal vein embolization. Imaging-based liver function tests were first developed in nuclear medicine and, compared with laboratory tests, have the advantage of displaying the spatial distribution of liver function. Nuclear medicine scans are obtained using tracers such as 99mTc galactosyl and 99mTc mebrofenin. Liver function is typically assessed using planar scintigraphy. However, three-dimensional volumetry is possible with single-photon emission computed tomography (SPECT-CT). Another technique for image-based liver function estimation is Gd-EOB-enhanced MRI. While metabolization of Gd-EOB in the body is similar to that of ICG and mebrofenin, its distribution in the liver can be displayed by MRI with higher temporal and spatial resolution. Moreover, MRI-based determination of liver function can be integrated into routine preoperative imaging. This makes MRI an ideal candidate for preoperative determination of liver function, though the best pulse sequence and the parameter to be derived from the image information remain to be identified. Another

  20. Quantitative assessment of regional right ventricular function with color kinesis.

    Science.gov (United States)

    Vignon, P; Weinert, L; Mor-Avi, V; Spencer, K T; Bednarz, J; Lang, R M

    1999-06-01

    We used color kinesis, a recent echocardiographic technique that provides regional information on the magnitude and timing of endocardial wall motion, to quantitatively assess regional right ventricular (RV) systolic and diastolic properties in 76 subjects who were divided into five groups, as follows: normal (n = 20), heart failure (n = 15), pressure/volume overload (n = 14), pressure overload (n = 12), and RV hypertrophy (n = 15). Quantitative segmental analysis of color kinesis images was used to obtain regional fractional area change (RFAC), which was displayed in the form of stacked histograms to determine patterns of endocardial wall motion. Time curves of integrated RFAC were used to objectively identify asynchrony of diastolic endocardial motion. When compared with normal subjects, patients with pressure overload or heart failure exhibited significantly decreased endocardial motion along the RV free wall. In the presence of mixed pressure/volume overload, the markedly increased ventricular septal motion compensated for decreased RV free wall motion. Diastolic endocardial wall motion was delayed in 17 of 72 segments (24%) in patients with RV pressure overload, and in 31 of 90 segments (34%) in patients with RV hypertrophy. Asynchrony of diastolic endocardial wall motion was greater in the latter group than in normal subjects (16% versus 10%: p kinesis images allows quantitative assessment of regional RV systolic and diastolic properties.

  1. Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome.

    Science.gov (United States)

    Vootla, Vamshidhar R; Daniel, Myrta

    2015-01-01

    Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome.

  2. Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome

    Directory of Open Access Journals (Sweden)

    Vamshidhar R. Vootla

    2015-07-01

    Full Text Available Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome.

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

    Directory of Open Access Journals (Sweden)

    Ryuta Shigefuku

    2016-09-01

    Full Text Available 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 NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC was significantly lower than that in hepatitis C virus (C-LC (p = 0.014. Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05. It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

  4. Shape-based motion correction in dynamic contrast-enhanced MRI for quantitative assessment of renal function.

    Science.gov (United States)

    Liu, Wenyang; Sung, Kyunghyun; Ruan, Dan

    2014-12-01

    11.7 within two manually selected regions of interest, respectively. The developed motion compensation method has demonstrated its ability to facilitate quantitative MRU functional analysis, with improved accuracy of pharmacokinetic modeling and quantitative parameter estimations. Future work will consider performing more intensive clinical verifications with sophisticated pharmacokinetic models and generalizing the proposed method to other quantitative DCE analysis, such as on liver or prostate function.

  5. The ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers.

    Science.gov (United States)

    Takeshita, T; Yang, X; Morimoto, K

    2000-06-01

    A highly prevalent, atypical genotype in low Km aldehyde dehydrogenase (ALDH2) may influence alcohol-induced liver injury because of higher production of acetaldehyde in the liver. In the present study, we examined relationships between the ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers. Study subjects were 385 male workers in a metal plant in Japan, who were free from hepatic viruses and did not have higher aminotransferase activities (alcohol drinking habits and other lifestyles. The ALDH2 genotype was determined by the PCR method followed by restriction-enzyme digestion. In the moderately and heavily drinking groups, those with ALDH2*1/*2 exhibited significantly lower levels than those with ALDH2*1/*1 for all three parameters of liver function, whereas no such differences were observed in the least-drinking group. Multiple linear-regression analysis, adjusting for age, obesity, and smoking habits, revealed that aspartate aminotransferase activity was positively associated with alcohol intake only in those with ALDH2*1/*1. On the other hand, alanine transferase activity was negatively associated with alcohol intake only in those with ALDH2*1/*2. The present study indicates that effects of alcohol intake on liver-function biomarkers are likely to be modified by the ALDH2 genotype in adult males.

  6. Liver function in rats acclimatized to a simulated altitude of 5500 m.

    Science.gov (United States)

    Ou, Lo Chang; Faulkner, Charles; Tam, Vincent; Leiter, James C

    2013-12-01

    We examined the functional and morphological characteristics of the liver in rats acclimatized to a simulated altitude of 5500 m. We examined the metabolic activity and cytoplasmic distribution of liver mitochondria and the capacity of the liver to regenerate after partial hepatectomy. Mitochondrial respiration, oxidative phosphorylation, the respiratory control ratio (RCR), and the morphological characteristics of mitochondria in liver sections were studied after 3 months acclimatization to high altitude (HA). Partial hepatectomy was performed in a subset of animals after 30 days acclimatization to 5500 m. The rate of hepatic regeneration, induction of ornithine decarboxylase and uridine diphosphate glucuronyltransferase (UGT1a1), and plasma bilirubin were measured 24, 48, 72, and 96 hours after hepatectomy. Acclimatization to 5500 m did not affect the mitochondrial respiratory capacity or oxidative phosphorylation. The RCR decreased and acid phosphatase activity increased, which suggests that there were subtle changes in mitochondrial integrity. In addition, mitochondria were distributed more homogeneously in hepatocytes. Hepatic regeneration, which was associated with 25-fold induction of the ornithine decarboxylase, did not differ between controls and the altitude-exposed animals. Plasma bilirubin levels rose markedly 24 hours after hepatectomy, but returned to control levels 48 hours after the operation in the altitude-exposed animals. Thus, the remarkable functional capacity of the liver was retained at simulated HA. Redistribution of hepatic mitochondria seems to play an important role in maintaining hepatic function despite severe cellular hypoxia.

  7. Effects of gomisin A on liver functions in hepatotoxic chemicals-treated rats.

    Science.gov (United States)

    Maeda, S; Takeda, S; Miyamoto, Y; Aburada, M; Harada, M

    1985-08-01

    The effects of gomisin A, which is a lignan component of schizandra fruits, on liver functions in various experimental liver injuries and on bile secretion in CCl4-induced liver injury were studied. Gomisin A weakly accelerated the disappearance of plasma ICG by itself at a high dose (100 mg/kg, i.p.). All of the hepatotoxic chemicals used in this study inhibited the excretion of ICG from plasma. Gomisin A showed a tendency to prevent the delays of the disappearance of plasma ICG induced by CCl4, d-galactosamine and orotic acid, but not that by ANIT. Bile flow and biliary outputs of total bile acids and electrolytes (Na+, K+, Cl- and HCO3-) were decreased in CCl4-treated rats. Gomisin A maintained bile flow and biliary output of each electrolyte nearly to the level of the vehicle-treated group, but did not affect biliary output of total bile acids. These findings suggest that gomisin A possesses a liver function-facilitating property in normal and liver injured rats and that its preventive action on CCl4-induced cholestasis is due to maintaining the function of the bile acids-independent fraction.

  8. T2-weighted MR imaging of the liver: qualitative and quantitative comparison of SPACE MR imaging with turbo spin-echo MR imaging.

    Science.gov (United States)

    Dohan, Anthony; Gavini, Jean-Philippe; Placé, Vinciane; Sebbag, Delphine; Vignaud, Alexandre; Herbin, Christine; Hamzi, Lounis; Boudiaf, Mourad; Soyer, Philippe

    2013-11-01

    To qualitatively and quantitatively compare T2-weighted MR imaging of the liver using volumetric spin-echo with sampling perfection with application-optimized contrast using different flip angle evolutions (SPACE) with conventional turbo spin-echo (TSE) sequence for fat-suppressed T2-weighted MR imaging of the liver. Thirty-three patients with suspected focal liver lesions had SPACE MR imaging and conventional fat-suppressed TSE MR imaging. Images were analyzed quantitatively by measuring the lesion-to-liver contrast-to-noise ratio (CNR), and the signal-to-noise ratio (SNR) of main focal hepatic lesions, hepatic and splenic parenchyma and qualitatively by evaluating the presence of vascular, respiratory motion and cardiac artifacts. Wilcoxon signed rank test was used to search for differences between the two sequences. SPACE MR imaging showed significantly greater CNR for focal liver lesions (median=22.82) than TSE MR imaging (median=14.15) (Pcomparison with the conventional TSE sequence. These results should stimulate further clinical studies with a surgical standard of reference to compare the two techniques in terms of sensitivity for malignant lesions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Functional role of monocytes and macrophages for the inflammatory response in acute liver injury

    Directory of Open Access Journals (Sweden)

    Henning W Zimmermann

    2012-10-01

    Full Text Available Different etiologies such as drug toxicity, acute viral hepatitis B or acetaminophen poisoning can cause acute liver injury (ALI or even acute liver failure (ALF. Excessive cell death of hepatocytes in the liver is known to result in a strong hepatic inflammation. Experimental murine models of liver injury highlighted the importance of hepatic macrophages, so-called Kupffer cells, for initiating and driving this inflammatory response by releasing proinflammatory cytokines and chemokines including tumor necrosis factor (TNF, interleukin-6 (IL-6, IL-1-beta or monocyte chemoattractant protein 1 (MCP-1, CCL2 as well as activating other non-parenchymal liver cells, e.g. endothelial or hepatic stellate cells (HSC. Many of these proinflammatory mediators can trigger hepatocytic cell death pathways, e.g. via caspase activation, but also activate protective signaling pathways, e.g. via nuclear factor kappa B (NF-kB. Recent studies in mice demonstrated that these macrophage actions largely depend on the recruitment of monocytes into the liver, namely of the inflammatory Ly6c+ (Gr1+ monocyte subset as precursors of tissue macrophages. The chemokine receptor CCR2 and its ligand MCP-1/CCL2 promote monocyte subset infiltration upon liver injury. In contrast, the chemokine receptor CX3CR1 and its ligand fractalkine (CX3CL1 are important negative regulators of monocyte infiltration by controlling their survival and differentiation into functionally diverse macrophage subsets upon injury. The recently identified cellular and molecular pathways for monocyte subset recruitment, macrophage differentiation and interactions with other hepatic cell types in the injured liver may therefore represent interesting novel targets for future therapeutic approaches in ALF.

  10. Deferasirox, deferiprone and desferrioxamine treatment in thalassemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging

    National Research Council Canada - National Science Library

    Alessia Pepe; Antonella Meloni; Marcello Capra; Paolo Cianciulli; Luciano Prossomariti; Cristina Malaventura; Maria Caterina Putti; Alma Lippi; Maria Antonietta Romeo; Maria Grazia Bisconte; Aldo Filosa; Vincenzo Caruso; Antonella Quarta; Lorella Pitrolo; Massimiliano Missere; Massimo Midiri; Giuseppe Rossi; Vincenzo Positano; Massimo Lombardi; Aurelio Maggio

    2011-01-01

    .... Our study aimed to compare the effectiveness of deferasirox, deferiprone and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients...

  11. Two- and Three-Dimensional Quantitative Structure-Activity Relationships Studies on a Series of Liver X Receptor Ligands

    Science.gov (United States)

    Honório, Káthia M; Salum, Lívia B; Garratt, Richard C; Polikarpov, Igor; Andricopulo, Adriano D

    2008-01-01

    Liver X receptor (LXR) is an attractive drug target for the development of novel therapeutic agents for the treatment of dyslipidaemia and cholestasis. In the present work, comparative molecular field analysis (CoMFA) and hologram quantitative structure-activity relationship (HQSAR) studies were conducted on a series of potent LXR ligands. Significant correlation coefficients (CoMFA, r2 = 0.98 and q2 = 0.69; HQSAR, r2 = 0.99 and q2 = 0.85) were obtained, indicating the potential of the models for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values obtained from the 2D and 3D models were in good agreement with the experimental results. The final QSAR models, along with the information obtained from 3D steric and electrostatic contour maps and 2D contribution maps should be useful for the design of novel LXR ligands having improved potency. PMID:19696872

  12. Characterization of liver-specific structure and function during hepatocyte spheroid self-assembly: Implications for a bioartificial liver device

    Science.gov (United States)

    Friend, Julie Renee

    A hollow fiber bioreactor containing collagen-entrapped hepatocytes has been developed as a bioartificial liver device. For clinical application, further scale-up of the device is desirable. This may be achieved through the use of hepatocyte spheroids, which are compacted aggregates that exhibit prolonged viability, higher liver-specific function and a more tissue-like ultrastructure compared to hepatocytes cultured as monolayers. In order to gain a better understanding of structural changes in spheroids over the course of their self-assembly, confocal microscopy was used to optically section spheroids and monitor changes in situ. Channels within spheroids hypothesized to be bile canaliculi were first evaluated by monitoring the diffusion of a fluorescent tracer, FITC-dextran, into spheroids. Three-dimensional reconstruction of spheroids showed that a continuous network of channels was forming within spheroids. Functionality of these channels as bile canaliculi was demonstrated by monitoring secretion of a fluorescently tagged bile acid, FITC-glycocholate, by hepatocytes in spheroids. Secretion of FITC-glycocholate could be seen in both rat and porcine hepatocyte spheroids. To elucidate changes in metabolism occurring during spheroid self-assembly, metabolic flux analysis was applied to hepatocyte spinner cultures. Glucose, lactate, amino acid, albumin and urea concentration in culture medium were measured and used to estimate intracellular fluxes within hepatocytes. Metabolism before and after spheroid formation was compared. Overall, little difference was seen in metabolism before and after spheroid self-assembly. As the BAL approaches clinical trials, methods of bioreactor storage for shipping and inventory purposed need to be developed. Storage conditions were tested in various hepatocyte culture systems. A protocol for storing reactors for 24 hours without significant loss in function was developed. Further optimization will be necessary for storage for longer

  13. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression.

    Directory of Open Access Journals (Sweden)

    Sathidpak Nantasanti

    Full Text Available The tumor suppressors Retinoblastoma (Rb and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver for metabolizing therapeutic drugs or toxins. We demonstrate that Rb and p53 cooperate to metabolize the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC. DDC is metabolized mainly by cytochrome P450 (Cyp3a enzymes resulting in inhibition of heme synthesis and accumulation of protoporphyrin, an intermediate of heme pathway. Protoporphyrin accumulation causes bile injury and ductular reaction. We show that loss of Rb and p53 resulted in reduced Cyp3a expression decreased accumulation of protoporphyrin and consequently less ductular reaction in livers of mice fed with DDC for 3 weeks. These findings provide strong evidence that synergistic functions of Rb and p53 are essential for metabolism of DDC. Because Rb and p53 functions are frequently disabled in liver diseases, our results suggest that liver patients might have altered ability to remove toxins or properly metabolize therapeutic drugs. Strikingly the reduced biliary injury towards the oxidative stress inducer DCC was accompanied by enhanced hepatocellular injury and formation of HCCs in Rb and p53 deficient livers. The increase in hepatocellular injury might be related to reduce protoporphyrin accumulation, because protoporphrin is well known for its anti-oxidative activity. Furthermore our results indicate that Rb and p53 not only function as tumor suppressors in response to carcinogenic injury, but also in response to non-carcinogenic injury such as DDC.

  14. Use of magnetic resonance elastography for assessing liver functional reserve: A clinical study.

    Science.gov (United States)

    Li, Bin; Min, Jie; Liang, Wei-Ren; Zhang, Guang-Qiang; Wu, Jian-Jun; Jin, Kai; Huang, Wei; Ying, Cai-Yu; Chao, Ming

    2015-06-28

    To investigate the value of magnetic resonance elastography (MRE) with regard to assessing liver functional reserve. Data from inpatients diagnosed with a liver tumor at an interventional radiology department from July 2013 to June 2014 were analyzed. A 3.0 Tesla magnetic resonance unit was used to scan 32 patients with confirmed diagnoses of hepatocellular carcinoma (HCC); an MRE sequence was added to the protocol, and the data were reconstructed and analyzed by two attending radiologists. Regions of interest were identified in different slices of the non-tumor liver parenchyma to measure average stiffness. In addition, the indocyanine green (ICG) test was performed no more than 1 wk before or after the magnetic resonance examination for all 32 patients; the ICG retention rate at 15 min (ICGR-15) and the ICG plasma clearance rate (ICG-K) were recorded. Correlational analyses were performed between the liver stiffness values and the ICGR-15 as well as between the liver stiffness values and the ICG-K. Magnetic resonance imaging, including an MRE sequence and the ICG test, was performed successfully in all 32 enrolled patients. None of the patients developed complications. The mean ± SD of the elasticity values measured by the two attending radiologists were 4.7 ± 2.2 kPa and 4.7 ± 2.1 kPa, respectively. The average liver stiffness value of the non-tumor parenchyma measured using MRE in HCC patients was 4.7 ± 2.2 kPa. The average ICGR-15 was 0.089 ± 0.077, and the average ICG-K was 0.19 ± 0.07. We found that the liver stiffness value of the non-tumor parenchyma was significantly and positively related to the ICGR-15 (r = 0.746, P functional reserve of HCC patients.

  15. Expression and function of the atypical cadherin FAT1 in chronic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Valletta, Daniela; Czech, Barbara [Department of Internal Medicine I, University Hospital Regensburg, Regensburg (Germany); Thasler, Wolfgang E. [Grosshadern Tissue Bank and Center for Liver Cell Research, Department of Surgery, Ludwig-Maximilians-University Munich (Germany); Mueller, Martina [Department of Internal Medicine I, University Hospital Regensburg, Regensburg (Germany); Bosserhoff, Anja-Katrin [Institute of Pathology, University of Regensburg, Regensburg (Germany); Hellerbrand, Claus, E-mail: claus.hellerbrand@ukr.de [Department of Internal Medicine I, University Hospital Regensburg, Regensburg (Germany)

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer The expression of the atypical cadherin FAT1 is increased in chronic liver disease. Black-Right-Pointing-Pointer FAT1 expression goes up during the activation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Activated HSCs are the cellular source of enhanced FAT1 expression in diseased livers. Black-Right-Pointing-Pointer FAT1 enhanced NFkB activity and resistance to apoptosis in activated HSCs. Black-Right-Pointing-Pointer FAT1 is a new therapeutic target for prevention and treatment of hepatic fibrosis. -- Abstract: Hepatic fibrosis can be considered as wound healing process in response to hepatocellular injury. Activation of hepatic stellate cells (HSCs) is a key event of hepatic fibrosis since activated HSCs are the cellular source of enhanced extracellular matrix deposition, and reversion of liver fibrosis is accompanied by clearance of activated HSCs by apoptosis. The atypical cadherin FAT1 has been shown to regulate diverse biological functions as cell proliferation and planar cell polarity, and also to affect wound healing. Here, we found increased FAT1 expression in different murine models of chronic liver injury and in cirrhotic livers of patients with different liver disease. Also in hepatic tissue of patients with non-alcoholic steatohepatitis FAT1 expression was significantly enhanced and correlated with collagen alpha I(1) expression. Immunohistochemistry revealed no significant differences in staining intensity between hepatocytes in normal and cirrhotic liver tissue but myofibroblast like cells in fibrotic septa of cirrhotic livers showed a prominent immunosignal. Furthermore, FAT1 mRNA and protein expression markedly increased during in vitro activation of primary human and murine HSCs. Together, these data indicated activated HSCs as cellular source of enhanced FAT1 expression in diseased livers. To gain insight into the functional role of FAT1 in activated HSCs we suppressed FAT1 in these

  16. Bile acids are "homeotrophic" sensors of the functional hepatic capacity and regulate adaptive growth during liver regeneration.

    Science.gov (United States)

    Geier, Andreas; Trautwein, Christian

    2007-01-01

    Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor-dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth.

  17. Effect of laparoscopic cholecystectomy and open cholecystectomy on liver function and immune function in patients

    Institute of Scientific and Technical Information of China (English)

    Sheng-Bing Huang; Shi-Lian Chen

    2016-01-01

    Objective:To investigate the effect of laparoscopic cholecystectomy and open cholecystectomy on liver function and immune function in patients.Methods:The clinical data of 100 cases of cholecystectomy in our hospital from November 2013 to November 2015 were retrospectively analyzed. According to the operation method was divided into OC group (laparoscopic cholecystectomy) and LC group (laparoscopic cholecystectomy), two groups were in general anesthesia, tracheal intubation, 1D, 1D, 5D fasting peripheral venous blood collection, serum total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (GGT), IgA, IgG, IgM, CD4+, CD8+, CD3+, and calculated CD4+/CD8+ ratio AST.Results:preoperative TBIL, ALT, GGT, AST no statistical significance (1D), postoperative indicators were significantly higher than preoperative levels, the index basically recovered to preoperative level, but the two groups were not statistically significant (1D) IgG two groups IgM each index level were lower than preoperative OC group, postoperative 5D indicators have recovered, LC group, CD8+, 1D, CD4+, two groups CD3+, 1D, 5D groups, 1D, 1D groups, OC, 1D two groups, IgA LC, CD4+/CD8+ no statistical significance, postoperative 1D two group CD3+, CD4+, CD4+/CD8+ compared with preoperative 1D decreased, CD8+ increased, there was statistical significance (P<0.05), postoperative 5D index LC There was no statistical significance between the group and the preoperative 1D, but the OC group had statistical significance.Conclusion:LC cholecystectomy is a minimally invasive surgery with little trauma, little impact on the body, fast recovery and so on, which reflects the advantages of minimally invasive surgery, it is worthy of clinical application.

  18. The Groningen hypothermic liver perfusion pump : Functional evaluation of a new machine perfusion system

    NARCIS (Netherlands)

    van der Plaats, A.; Maathuis, M. H. J.; Hart, N. A. 't; Bellekom, A. A.; Hofker, H. S.; van der Houwen, E. B.; Verkerke, G. J.; Leuvenink, H. G. D.; Verdonck, P.; Ploeg, R. J.; Rakhorst, G.

    2006-01-01

    To improve preservation of donor livers, we have developed a portable hypothermic machine perfusion (HMP) system as an alternative for static cold storage. A prototype of the system was built and evaluated on functionality. Evaluation criteria included 24 h of adequate pressure controlled perfusion,

  19. "CONGENTIAL PANHYPOPITUITARISM ASSOCIATED WITH IMPAIRED LIVER FUNCTION TESTS AND CONGENITAL HEART DISEASE"

    Directory of Open Access Journals (Sweden)

    Z. Khalili-Matinzadeh

    2006-06-01

    Full Text Available The term congenital hypopituitarism defines deficiency of all of the pituitary hormones. Hypoglycemia and microphallus (in males are common findings, and some infants have shown evidence of the neonatal hepatitis syndrome. We report a case of congenital panhypopituitarism with deficiency of six major hormones and association with severe hypoglycemia, impaired liver function tests and congenital heart disease.

  20. Effect of canagliflozin on liver function tests in patients with type 2 diabetes.

    Science.gov (United States)

    Leiter, L A; Forst, T; Polidori, D; Balis, D A; Xie, J; Sha, S

    2016-02-01

    To report changes in liver function tests observed with canagliflozin, a sodium glucose co-transporter 2 inhibitor, across phase 3 studies in patients with type 2 diabetes, and to examine the relationship between changes in liver function tests and the weight loss and glycaemic improvements observed with canagliflozin. Data were pooled from four 26-week, placebo-controlled studies of canagliflozin 100 and 300mg (n=2313) and two 52-week, active-controlled studies of canagliflozin 300mg versus sitagliptin 100mg (n=1488). Analysis of covariance was performed to determine the contribution of changes in body weight and HbA1c to the changes in liver function tests. Reductions in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transferase, and increases in bilirubin were seen with canagliflozin 100 and 300mg versus placebo (nominal Pcanagliflozin 300mg only]) at week 26 and with canagliflozin 300mg versus sitagliptin 100mg (nominal PCanagliflozin provided improvements in liver function tests versus either placebo or sitagliptin treatments that were fully explained by the combined effects of HbA1c and body weight reductions with canagliflozin. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Comparison of five incubation systems for rat liver slices using functional and viability parameters

    NARCIS (Netherlands)

    Olinga, P; Groen, K; Hof, IH; DeKanter, R; Leeman, WR; Rutten, AAJJL; VanTwillert, K; Groothuis, GMM; Koster, H

    1997-01-01

    Precision-cut liver slices are presently used for various research objects, e.g. to study metabolism, transport, and toxicity of xenobiotics. Various incubation systems are presently employed, but a systematic comparison between these incubation systems with respect to preservation of slice function

  2. Effects of Job categories on Some Biomarkers of Liver Function in ...

    African Journals Online (AJOL)

    Dr Olaleye

    Sub-clinical impairment of liver function has been reported in textile dye workers in ... used in the manufacture of various vat and disperse dyes. BA ..... Cancer 54 (3): 381-383 ... The inhalation toxicity of two commercial dyes: solvent yellow 33.

  3. LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX THERAPY

    Directory of Open Access Journals (Sweden)

    Ashraf Tawfik Soliman

    2014-04-01

    Conclusions: Some impairment of liver function can occur in hepatitis negative BMT patients with iron overload. The use of DFX was associated with mild but significant reduction of ALT, AST and ALP and increase in IGF-I levels. The negative correlation between IGF-I and ALT concentrations suggest that preventing hepatic dysfunction may improve the growth potential in these patients.

  4. Comparison of five incubation systems for rat liver slices using functional and viability parameters

    NARCIS (Netherlands)

    Olinga, P; Groen, K; Hof, IH; DeKanter, R; Leeman, WR; Rutten, AAJJL; VanTwillert, K; Groothuis, GMM; Koster, H

    1997-01-01

    Precision-cut liver slices are presently used for various research objects, e.g. to study metabolism, transport, and toxicity of xenobiotics. Various incubation systems are presently employed, but a systematic comparison between these incubation systems with respect to preservation of slice function

  5. Quantitative assessment of renal function with magnetic resonance imaging; Quantitative Erfassung der renalen Funktion mit der Magnetresonanztomographie

    Energy Technology Data Exchange (ETDEWEB)

    Schoenberg, S.O.; Bock, M.; Aumann, S.; Essig, M.; Floemer, F.; Knopp, M.V.; Kaick, G. van [Deutsches Krebsforschungszentrum Heidelberg (Germany). Abt. Radiologische Diagnostik und Therapie; Just, A. [Heidelberg Univ. (Germany). 1. Physiologisches Inst.

    2000-10-01

    Aim. To show the potential of various methods in magnetic resonance imaging for the evaluation of renal function. Material and Methods. A combined assessment of renal morphology, renal hemodynamics and function is proposed. Various techniques are explained, including multiphasic 3D gadolinium MR angiography, MR phase-contrast flow measurements, quantitative perfusion measurements with intravascular contrast agents, and MR renography and MR urography. The use of these techniques is demonstrated for renovascular diseases. Results. The combined use of these techniques allows renal artery stenosis to be accurately detected and evaluation of renal blood flow, perfusion, glomerular filtration rate, and renal excretion. Based on true quantitative parameters, the hemodynamic and functional significance of the stenosis can be assessed. Renovascular diseases can be differentiated from renoparenchymal disease. Conclusion. For the assessment of renal function, functional magnetic resonance imaging techniques are an important alternative to nuclear medicine. The predictive value regarding the effect of revascularization is currently under investigation. (orig.) [German] Fragestellung. Verschiedene Methoden der Magnetresonanztomographie zur quantitativen Erfassung der Nierenfunktion sollen aufgezeigt werden. Methodik. Es werden MR-Techniken zur kombinierten Beurteilung der renalen Morphologie, Haemodynamik und Funktion der Niere vorgestellt. Zur Anwendung kommen hierbei die multiphasische 3-D-Gadolinium-MR-Angiographie, die MR-Phasenkontrastflussmessung, die quantitative Perfusionsmessung mit intravasalen Kontrastmitteln sowie die MR-Renographie/MR-Urographie. Die Methoden werden exemplarisch am Beispiel renovaskulaerer Erkrankungen demonstriert. Ergebnisse. Mit den vorgestellten Methoden lassen sich Nierenarterienstenosen akkurat detektieren sowie Aenderungen des renalen Blutflusses, der Nierenperfusion, der Filtrationsleistung sowie der renalen Ausscheidung erfassen. Auf der

  6. Kidney function and mortality post-liver transplant in the Model for End-Stage Liver Disease era

    Directory of Open Access Journals (Sweden)

    Sethi A

    2011-11-01

    Full Text Available Aastha Sethi1, Michelle M Estrella1, Richard Ugarte2, Mohamed G Atta1 1Johns Hopkins University School of Medicine, Department of Medicine, Baltimore, MD, USA; 2University of Maryland Medical Center, Department of Medicine, Baltimore, MD, USA Abstract: The Model for End-Stage Liver Disease (MELD score incorporates serum creatinine and was introduced to facilitate allocation of orthotopic liver transplantation (LT. The objective is to determine the impact of MELD and kidney function on all-cause mortality. Among LTs performed in a tertiary referral hospital between 1995 and 2009, 419 cases were studied. Cox proportional hazards models were constructed to estimate the hazard ratios (HR and 95% confidence intervals (CI for death. Over mean follow-ups of 8.4 and 3.1 years during the pre-MELD and MELD era, 57 and 63 deaths were observed, respectively. Those transplanted during the MELD era had a higher likelihood of hepatorenal syndrome (8% vs 2%, P < 0.01, lower kidney function (median estimated glomerular filtration rate [eGFR] 77.8 vs 92.6 mL/min/1.73 m2, P < 0.01, and more pretransplantation renal replacement therapy (RRT (5% vs 1%; P < 0.01. All-cause mortality risk was similar in the MELD vs the pre-MELD era (HR: 0.98, 95% CI: 0.58–1.65. The risk of death, however, was nearly 3-fold greater (95% CI: 1.14–6.60 among those requiring pre-transplant RRT. Similarly, eGFR < 60 mL/min/1.73 m2 post-transplant was associated with a 2.5-fold higher mortality (95% CI: 1.48–4.11. The study suggests that MELD implementation had no impact on all-cause mortality post-LT. However, the need for pre-transplant RRT and post-transplant kidney dysfunction was associated with a more than 2-fold greater risk of subsequent death. Keywords: eGFR, mortality, MELD, liver transplant

  7. Genome-wide quantitative analysis of histone H3 lysine 4 trimethylation in wild house mouse liver: environmental change causes epigenetic plasticity.

    Directory of Open Access Journals (Sweden)

    Angelika G Börsch-Haubold

    Full Text Available In mammals, exposure to toxic or disease-causing environments can change epigenetic marks that are inherited independently of the intrauterine environment. Such inheritance of molecular phenotypes may be adaptive. However, studies demonstrating molecular evidence for epigenetic inheritance have so far relied on extreme treatments, and are confined to inbred animals. We therefore investigated whether epigenomic changes could be detected after a non-drastic change in the environment of an outbred organism. We kept two populations of wild-caught house mice (Mus musculus domesticus for several generations in semi-natural enclosures on either standard diet and light cycle, or on an energy-enriched diet with longer daylight to simulate summer. As epigenetic marker for active chromatin we quantified genome-wide histone-3 lysine-4 trimethylation (H3K4me3 from liver samples by chromatin immunoprecipitation and high-throughput sequencing as well as by quantitative polymerase chain reaction. The treatment caused a significant increase of H3K4me3 at metabolic genes such as lipid and cholesterol regulators, monooxygenases, and a bile acid transporter. In addition, genes involved in immune processes, cell cycle, and transcription and translation processes were also differently marked. When we transferred young mice of both populations to cages and bred them under standard conditions, most of the H3K4me3 differences were lost. The few loci with stable H3K4me3 changes did not cluster in metabolic functional categories. This is, to our knowledge, the first quantitative study of an epigenetic marker in an outbred mammalian organism. We demonstrate genome-wide epigenetic plasticity in response to a realistic environmental stimulus. In contrast to disease models, the bulk of the epigenomic changes we observed were not heritable.

  8. Quantitative targeted bile acid profiling as new markers for DILI in a model of methapyrilene-induced liver injury in rats.

    Science.gov (United States)

    Slopianka, Markus; Herrmann, Anne; Pavkovic, Mira; Ellinger-Ziegelbauer, Heidrun; Ernst, Rainer; Mally, Angela; Keck, Matthias; Riefke, Bjoern

    2017-07-01

    Recently, bile acids (BAs) were reported as promising markers for drug-induced liver injury (DILI). BAs have been suggested to correlate with hepatocellular and hepatobiliary damage; however a clear connection of BA patterns with different types of DILI remains to be established. To investigate if BAs can improve the assessment of liver injury, 20 specific BAs were quantitatively profiled via LC-MS/MS in plasma and liver tissue in a model of methapyrilene-induced liver injury in rats. Methapyrilene, a known hepatotoxin was dosed daily over 14-days at doses of 30 and 80mg/kg, followed by a recovery phase of 10days. Conventional preclinical safety endpoints were related to BA perturbations and to hepatic gene expression profiling for a mechanistic interpretation of effects. Histopathological signs of hepatocellular and hepatobiliary damage with significant changes of clinical chemistry markers were accompanied by significantly increased levels of indivdual BAs in plasma and liver tissue. BA perturbations were already evident at the earliest time point after 30mg/kg treatment, and thereby indicating better sensitivity than clinical chemistry parameters. Furthermore, the latter markers suggested recovery of liver injury, whereas BA levels in plasma and liver remained significantly elevated during the recovery phase, in line with persistent histopathological findings of bile duct hyperplasia (BDH) and bile pigment deposition. Gene expression profiling revealed downregulation of genes involved in BA synthesis (AMACR, BAAT, ACOX2) and hepatocellular uptake (NTCP, OATs), and upregulation for efflux transporters (MRP2, MRP4), suggesting an adaptive hepatocellular protection mechanism against cytotoxic bile acid accumulation. In summary, our data suggests that specific BAs with high reliability such as cholic acid (CA) and chenodeoxycholic acid (CDCA) followed by glycocholic acid (GCA), taurocholic acid (TCA) and deoxycholic acid (DCA) can serve as additional biomarkers for

  9. Functional hepatic flow in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Zheng Pan; Xing-Jiang Wu; Jie-Shou Li; Fang-Nan Liu; Wei-Su Li; Jian-Ming Han

    2004-01-01

    AIM: To evaluate hepatic reserve function by investigating the change of functional hepatic flow and total hepatic flow in cirrhotic patients with portal hypertension. METHODS: HPLC method was employed for the determination of concentration of D-sorbitol in human plasma and urine. The functional hepatic flow (FHF) and total hepatic flow (THF) were determined by means of modified hepatic clearance of D-sorbitol combined with duplex doppler color sonography in 20 patients with cirrhosis and 10 healthy volunteers. RESULTS: FHF, evaluated by means of bhe D-sorbitol dearance, was significantly reduced in patients wibh cirrhosis in comparison to controls (764.74±167.91 vs 1 195.04±242.97 mL/min, P<0.01). While THF was significantly increased in patients with cirrhosis in comparison to controls (1 605.23±279.99 vs 1 256.12±198.34 mL/min, P<0.01). Portal blood flow and hepatic artery flow all were increased in cirrhosis compared to controls (P<0.05 and P<0.01). D-sorbitol total clearance was significantly reduced in cirrhosis compared to control (P<0.01), while D-sorbitol renal clearance was significantly increased in cirrhosis (P<0.05). In controls FHF was similar to THF (1 195.05±242.97 vs1 256.12±198.34 mL/min, P=0.636), while FHF was significantly reduced compared with THF incirrhosis (764.74±167.91 vs 1 605.23±279.99 mL/min, P<0.01). CONCLUSION: Our method that combined modified hepatic clearance of D-sorbitol with duplex doppler color sonography is effective in the measurement of FHF and THF. FHF can be used to estimate hepatic reserve function.

  10. Total Hepatitis B Core Antigen Antibody, a Quantitative Non-Invasive Marker of Hepatitis B Virus Induced Liver Disease.

    Directory of Open Access Journals (Sweden)

    Quan Yuan

    Full Text Available Non invasive immunologic markers of virus-induced liver disease are unmet needs. We tested the clinical significance of quantitative total and IgM-anti-HBc in well characterized chronic-HBsAg-carriers. Sera (212 were obtained from 111 HBsAg-carriers followed-up for 52 months (28-216 during different phases of chronic-HBV-genotype-D-infection: 10 HBeAg-positive, 25 inactive-carriers (HBV-DNA≤2000IU/ml, ALT<30U/L, 66 HBeAg-negative-CHB-patients and 10 with HDV-super-infection. In 35 patients treated with Peg-IFN±nucleos(tide-analogues (NUCs sera were obtained at baseline, end-of-therapy and week-24-off-therapy and in 22 treated with NUCs (for 60 months, 42-134m at baseline and end-of-follow-up. HBsAg and IgM-anti-HBc were measured by Architect-assays (Abbott, USA; total-anti-HBc by double-antigen-sandwich-immune-assay (Wantai, China; HBV-DNA by COBAS-TaqMan (Roche, Germany. Total-anti-HBc were detectable in all sera with lower levels in HBsAg-carriers without CHB (immune-tolerant, inactive and HDV-superinfected, median 3.26, range 2.26-4.49 Log10 IU/ml versus untreated-CHB (median 4.68, range 2.76-5.54 Log10 IU/ml, p<0.0001. IgM-anti-HBc positive using the chronic-hepatitis-cut-off" (0.130-S/CO were positive in 102 of 212 sera (48.1%. Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r=0.417. Total-anti-HBc declined significantly in CHB patients with response to Peg-IFN (p<0.001 and in NUC-treated patients (p<0.001; the lowest levels (median 2.68, range 2.12-3.08 Log10 IU/ml were found in long-term responders who cleared HBsAg subsequently. During spontaneous and therapy-induced fluctuations of CHB (remissions and reactivations total- and IgM-anti-HBc correlated with ALT (p<0.001, r=0.351 and p=0.008, r=0.185 respectively. Total-anti-HBc qualifies as a useful marker of HBV-induced-liver-disease that might help to discriminate major phases of chronic HBV infection and to predict sustained response to antivirals.

  11. Non-Alcoholic Fatty Liver Disease in Subjects with Non-functioning Adrenal Adenomas

    Directory of Open Access Journals (Sweden)

    Serkan Yener

    2011-12-01

    Full Text Available Objectives: The relation between non-functioning adrenal adenoma and unfavorable metabolic status has been a debate so far. We aimed to demonstrate the prevalence of non-alcoholic fatty liver disease (NAFLD in subjects with silent adrenal adenomas.Materials and Methods: 130 consecutive subjects with non-functioning adrenal adenomas, 170 age-, gender- and BMI-matched individuals without adrenal gland disorders, and 20 patients with Cushing’s syndrome were included in the study. Fatty liver disease was diagnosed by ultrasonography and the severity was scored semiquantitatively. Liver function tests were performed. Cushing’s syndrome and non-functioning adrenal adenoma were diagnosed using appropriate tests of hypothalamus-pituitary-adrenal function.Results: The prevalence of NAFLD was 30.7%, 65.0% and 39.4% in adenoma group, Cushing’s syndrome group and control group, respectively. There was no significant difference in terms of Type 2 diabetes mellitus, hypertension and NAFLD prevalence between adenoma group and controls. NAFLD was not only more common in subjects with Cushing’s syndrome but was also more severe. Hypercortisolemia strongly predicted the development of metabolic syndrome (OR: 10.571, p=0.004. When age, gender, hypercortisolemia and metabolic syndrome were assessed, metabolic syndrome remained as the sole independent predictor of fatty liver development (OR: 9.162, p<0.001.Conclusion: Comparable prevalence between adenoma and control group was likely to be associated with similar rates of metabolic derangements and similar BMI. Cortisol excess seemed to be related with fatty liver development mainly through its unfavorable metabolic effects. Türk Jem 2011; 15: 116-20

  12. Quantitative evaluation of the reticuloendothelial system function with dynamic MRI.

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    Ting Liu

    Full Text Available PURPOSE: To evaluate the reticuloendothelial system (RES function by real-time imaging blood clearance as well as hepatic uptake of superparamagnetic iron oxide nanoparticle (SPIO using dynamic magnetic resonance imaging (MRI with two-compartment pharmacokinetic modeling. MATERIALS AND METHODS: Kinetics of blood clearance and hepatic accumulation were recorded in young adult male 01b74 athymic nude mice by dynamic T2* weighted MRI after the injection of different doses of SPIO nanoparticles (0.5, 3 or 10 mg Fe/kg. Association parameter, Kin, dissociation parameter, Kout, and elimination constant, Ke, derived from dynamic data with two-compartment model, were used to describe active binding to Kupffer cells and extrahepatic clearance. The clodrosome and liposome were utilized to deplete macrophages and block the RES function to evaluate the capability of the kinetic parameters for investigation of macrophage function and density. RESULTS: The two-compartment model provided a good description for all data and showed a low sum squared residual for all mice (0.27±0.03. A lower Kin, a lower Kout and a lower Ke were found after clodrosome treatment, whereas a lower Kin, a higher Kout and a lower Ke were observed after liposome treatment in comparison to saline treatment (P<0.005. CONCLUSION: Dynamic SPIO-enhanced MR imaging with two-compartment modeling can provide information on RES function on both a cell number and receptor function level.

  13. Direct, quantitative clinical assessment of hand function: usefulness and reproducibility.

    Science.gov (United States)

    Goodson, Alexander; McGregor, Alison H; Douglas, Jane; Taylor, Peter

    2007-05-01

    Methods of assessing functional impairment in arthritic hands include pain assessments and disability scoring scales which are subjective, variable over time and fail to take account of the patients' need to adapt to deformities. The aim of this study was to evaluate measures of functional strength and joint motion in the assessment of the rheumatoid (RA) and osteoarthritic (OA) hand. Ten control subjects, ten RA and ten OA patients were recruited for the study. All underwent pain and disability scoring and functional assessment of the hand using measures of pinch/grip strength and range of joint motion (ROM). Functional assessments including ROM analyses at interphalangeal (IP), metacarpophalangeal (MCP) and wrist joints along with pinch/grip strength clearly discriminated between patient groups (RA vs. OA MCP ROM P<0.0001), pain and disability scales were unable to. In the RA there were demonstrable relationships between ROM measurements and disability (R2=0.31) as well as disease duration (R2=0.37). Intra-patient measures of strength were robust whereas inter-patient comparisons showed variability. In conclusion, pinch/grip strength and ROM are clinically reproducible assessments that may more accurately reflect functional impairment associated with arthritis.

  14. Synthesis of functionalized magnetite nanoparticles to use as liver targeting MRI contrast agent

    Science.gov (United States)

    Yazdani, Farshad; Fattahi, Bahare; Azizi, Najmodin

    2016-05-01

    The aim of this research was the preparation of functionalized magnetite nanoparticles to use as a liver targeting contrast agent in magnetic resonance imaging (MRI). For this purpose, Fe3O4 nanoparticles were synthesized via the co-precipitation method. The synthesized nanoparticles were coated with silica via the Stober method and finally the coated nanoparticles were functionalized with mebrofenin. Formation of crystalline magnetite particles was confirmed by X-ray diffraction (XRD) analysis. The Fourier transform infrared spectroscopy (FTIR) and energy dispersive X-ray analyzer (EDX) of the final product showed that silica had been effectively bonded onto the surface of the magnetite nanoparticles and the coated nanoparticles functionalized with mebrofenin. The magnetic resonance imaging of the functional nanoparticles showed that the Fe3O4-SiO2-mebrofenin composite is an effective MRI contrast agent for liver targeting.

  15. Accuracy of liver function tests for predicting adverse maternal and fetal outcomes in women with preeclampsia: a systematic review

    NARCIS (Netherlands)

    S. Thangaratinam; C.M. Koopmans; S. Iyengar; J. Zamora; K.M.K. Ismail; B.W.J. Mol; K.S. Khan

    2011-01-01

    Background. Liver function tests are routinely performed in women as part of a battery of investigations to assess severity at admission and later to guide appropriate management. Objective. To determine the accuracy with which liver function tests predict complications in women with preeclampsia by

  16. Accuracy of liver function tests for predicting adverse maternal and fetal outcomes in women with preeclampsia : a systematic review

    NARCIS (Netherlands)

    Thangaratinam, Shakila; Koopmans, Corine M.; Iyengar, Shalini; Zamora, Javier; Ismail, Khaled M. K.; Mol, Ben W. J.; Khan, Khalid S.

    2011-01-01

    Background. Liver function tests are routinely performed in women as part of a battery of investigations to assess severity at admission and later to guide appropriate management. Objective. To determine the accuracy with which liver function tests predict complications in women with preeclampsia by

  17. Three Perspectives in Research on Functions: Multi-Representational, Quantitative, and Phenomenological.

    Science.gov (United States)

    Lobato, Joanne; Bowers, Janet

    Much research on student understanding of functions has been characterized by a "multi-representational" perspective that investigates students' efforts to make connections among conventionally accepted mathematical representations such as graphs, tables, and equations. In contrast, a "quantitative" perspective explores…

  18. An in vivo and in vitro comparison of CYP induction in rat liver and intestine using slices and quantitative RT-PCR.

    Science.gov (United States)

    Martignoni, Marcella; de Kanter, Ruben; Grossi, Pietro; Mahnke, Axel; Saturno, Grazia; Monshouwer, Mario

    2004-12-30

    Xenobiotics, including drugs, can influence cytochrome P450 (CYP) activity by upregulating the transcription of CYP genes. To minimize potential drug interactions, it is important to ascertain whether a compound will be an inducer of CYP enzymes early in the development of new therapeutic agents. In vivo and in vitro studies are reported that demonstrate the use of liver and intestinal slices as an in vitro model to predict potential CYP induction in vivo. Rat liver slices and intestinal slices were incubated, for 24 h and 6 h, respectively, with beta-naphthoflavone (betaNF), phenobarbital (PB) or dexamethasone (DEX). In an in vivo study, rats were treated with the same compounds for 3 days. In vivo and in vitro CYP mRNA levels were measured by using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). In addition, CYP enzyme activities were determined in rat liver slices after 48 h incubation. In both rat liver and intestinal slices, betaNF significantly induced CYP1A1, CYP1A2 and CYP2B1 mRNA levels. PB significantly induced CYP2B1. In liver slices a minor induction of CYP1A1 and CYP3A1 by PB was observed, whereas DEX significantly induced CYP3A1, CYP2B1 and CYP1A2 mRNA levels. The induction profiles (qualitative and quantitative) observed in vivo and in vitro are quite similar. All together, these data demonstrate that liver and intestinal slices are a useful and predictive tool to study CYP induction.

  19. Establishment of steady-state metabolism of ethanol in perfused rat liver: the quantitative analysis using kinetic mechanism-based rate equations of alcohol dehydrogenase.

    Science.gov (United States)

    Yao, Chung-Tay; Lai, Ching-Long; Hsieh, Hsiu-Shan; Chi, Chin-Wen; Yin, Shih-Jiun

    2010-09-01

    Alcohol dehydrogenase (ADH) catalyzes oxidation of ingested ethanol to acetaldehyde, the first step in hepatic metabolism. The purpose of this study was to establish an ex vivo rat liver perfusion system under defined and verified steady states with respect to the metabolites and the metabolic rates, and to quantitatively correlate the observed rates with simulations based on the kinetic mechanism-based rate equations of rat liver ADH. Class I ADH1 was isolated from male Sprague-Dawley rats and characterized by steady-state kinetics in the Krebs-Ringer perfusion buffer with supplements. Nonrecirculating liver perfusion with constant input of ethanol at near physiological hepatic blood flow rate was performed in situ. Ethanol and the related metabolites acetaldehyde, acetate, lactate, and pyruvate in perfusates were determined. Results of the initial velocity, product, and dead-end inhibition studies showed that rat ADH1 conformed to the Theorell-Chance Ordered Bi Bi mechanism. Steady-state metabolism of ethanol in the perfused liver maintained up to 3h as evidenced by the steady-state levels of ethanol and metabolites in the effluent, and the steady-state ethanol disappearance rates and acetate production rates. The changes of the metabolic rates were qualitatively and in general quantitatively correlated to the results from simulations with the kinetic rate equations of ADH1 under a wide range of ethanol, in the presence of competitive inhibitor 4-methylpyrazole and of uncompetitive inhibitor isobutyramide. Preliminary flux control analysis estimated that apparent C(ADH)(J) in the perfused liver may approximate 0.7 at constant infusion with 1-2 mM ethanol, suggesting that ADH plays a major but not the exclusive role in governing hepatic ethanol metabolism. The reported steady-state rat liver perfusion system may potentially be applicable to other drug or drug-ethanol interaction studies.

  20. Impact of Hyperbaric Oxygenation on the Phagocytosis-Stimulating Function of the Operated Liver

    Directory of Open Access Journals (Sweden)

    P. N. Savilov

    2008-01-01

    Full Text Available Objective: to study the ability of hyperbaric oxygenation (HBO to eliminate impaired phagocytosis-stimulating hepatic function caused by hepatectomy (HE. Material and methods. Experiments were conducted on 82 outbred female albino rats exposed to HE (15—20% of the organ mass and HBO at 3 ata for 50 min once daily three times within the first three days after surgery. The capacities of neutrophils and monocytes of arterial (aorta and venous (portal vein, hepatic veins blood to ingest and digest S.aureus were investigated. Results: Under HBO, the inhibitory impact of HE on the phagocytosis-stimulating ability of the liver to S.aureus was limited for neutrophils and completely precluded for monocytes. In the posthyperoxic period, the phagocytosis-stimulating function of the operated liver was found to be active against the microbe being examined for both types of phagocytes. This was attended by inhibition of the anhepatic mechanisms responsible for the amplified phagocytic activity of neutrophils and monocytes, which were triggered in HE. HBO selectively regulated the arterial and venous blood content of neutrophils, by ingesting and digesting S.aureus as much as possible. HBO prevented the post-HE delay of the neutrophils and monocytes which actively englobed S.aureus in the operated organ. Conclusion: HBO eliminates HE-induced impairment of phagocytosis-stimulating function of the liver and creates conditions for its delayed activation by day 11 posthy-peroxia. Key words: hyperoxia, phagocytosis, regulation, liver, resection.

  1. Apolipoprotein O expression in mouse liver enhances hepatic lipid accumulation by impairing mitochondrial function.

    Science.gov (United States)

    Tian, Feng; Wu, Chen-Lu; Yu, Bi-Lian; Liu, Ling; Hu, Jia-Rui

    2017-09-09

    Apolipoprotein O (ApoO) was recently observed in the cellular mitochondrial inner membrane, which plays a role in mitochondrial function and is associated with myocardiopathy. Empirical information on the physiological functions of apoO is therefore limited. In this study, we aimed to elucidate the effect of apoO on hepatic fatty acid metabolism. An adenoviral vector expressing hApoO was constructed and introduced into chow diet and high-fat diet induced mice and the L02 human hepatoma cell line. High levels of hApoO mRNA and protein were detected in the liver, and the expression of lipid metabolism genes was significantly altered compared with negative controls. The liver function indices (serum ALT and AST) were clearly elevated, and the ultrastructure of cellular mitochondria was distinctly altered in the liver after apoO overexpression. Further, mitochondrial membrane potential decreased with hApoO treatment in L02 cells. These results establish a link between apoO and lipid accumulation and could suggest a new pathway for regulating non-alcoholic fatty liver disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

    Science.gov (United States)

    Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2014-01-01

    Nitric oxide, when combined with superoxide, produces peroxynitrite, which is known to be an important mediator for a number of diseases including various liver diseases. Peroxynitrite can modify tyrosine residue(s) of many proteins resulting in protein nitration, which may alter structure and function of each target protein. Various proteomics and immunological methods including mass spectrometry combined with both high pressure liquid chromatography and 2D PAGE have been employed to identify and characterize nitrated proteins from pathological tissue samples to determine their roles. However, these methods contain a few technical problems such as low efficiencies with the detection of a limited number of nitrated proteins and labor intensiveness. Therefore, a systematic approach to efficiently identify nitrated proteins and characterize their functional roles is likely to shed new insights into understanding of the mechanisms of hepatic disease pathophysiology and subsequent development of new therapeutics. The aims of this review are to briefly describe the mechanisms of hepatic diseases. In addition, we specifically describe a systematic approach to efficiently identify nitrated proteins to study their causal roles or functional consequences in promoting acute and chronic liver diseases including alcoholic and nonalcoholic fatty liver diseases. We finally discuss translational research applications by analyzing nitrated proteins in evaluating the efficacies of potentially beneficial agents to prevent or treat various diseases in the liver and other tissues. PMID:24876909

  3. Measurement of serum paraoxonase-1 activity in the evaluation of liver function

    Institute of Scientific and Technical Information of China (English)

    Jordi Camps; Judit Marsillach; Jorge Joven

    2009-01-01

    Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxidized cholesteryl esters and oxidized phospholipids in lipoproteins and cell membranes. PON1 is, therefore, an antioxidant enzyme. Alterations in circulating PON1 levels have been reported in a variety of diseases involving oxidative stress including chronic liver diseases. Measurement of serum PON1 activity has been proposed as a potential test for the evaluation of liver function. However, this measurement is still restricted to research and has not been extensively applied in routine clinical chemistry laboratories. The reason for this restriction is due to the problem that the substrate commonly used for PON1 measurement,paraoxon, is toxic and unstable. The recent development of new assays with non-toxic substrates makes this proposal closer to a practical development. The present editorial summarizes PON1 biochemistry and function,its involvement with chronic liver impairment, and some aspects related to the measurement of PON1 activity in circulation.

  4. Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Mohamed A. Abdelmegeed

    2014-01-01

    Full Text Available Nitric oxide, when combined with superoxide, produces peroxynitrite, which is known to be an important mediator for a number of diseases including various liver diseases. Peroxynitrite can modify tyrosine residue(s of many proteins resulting in protein nitration, which may alter structure and function of each target protein. Various proteomics and immunological methods including mass spectrometry combined with both high pressure liquid chromatography and 2D PAGE have been employed to identify and characterize nitrated proteins from pathological tissue samples to determine their roles. However, these methods contain a few technical problems such as low efficiencies with the detection of a limited number of nitrated proteins and labor intensiveness. Therefore, a systematic approach to efficiently identify nitrated proteins and characterize their functional roles is likely to shed new insights into understanding of the mechanisms of hepatic disease pathophysiology and subsequent development of new therapeutics. The aims of this review are to briefly describe the mechanisms of hepatic diseases. In addition, we specifically describe a systematic approach to efficiently identify nitrated proteins to study their causal roles or functional consequences in promoting acute and chronic liver diseases including alcoholic and nonalcoholic fatty liver diseases. We finally discuss translational research applications by analyzing nitrated proteins in evaluating the efficacies of potentially beneficial agents to prevent or treat various diseases in the liver and other tissues.

  5. Changes in platelet functional parameters and CD62 P expression in liver cirrhosis.

    Science.gov (United States)

    Xianghong, G; Guanping, C; Fenghua, Y; Jiayin, W

    2013-12-01

    Hepatic impairment, portal hypertension, and multi-systemic damage could occur during liver cirrhosis's late stage. Bleeding is a complication of hepatic cirrhosis along with several changes including blood platelet count (BPC), mean platelet volume (MPV), platelet crit (PCT) and expression of platelet CD62P. Blood platelet count (BPC), mean platelet volume (MPV), platelet distribution width, and other indices are indirect reflections of CD62P parameters. To investigate the changes in platelet functional parameters and CD62 P expression in liver cirrhosis as a possible guide in clinical treatments and prognoses of liver cirrhosis. CD62P was tested by flow cytometry in liver cirrhosis. BPC, MPV, and PCT in peripheral blood were tested using an auto blood cell analyzer. Data were analyzed using SPSS11.0. The values of CD62P and MPV in patients was significantly higher than those of healthy donors (PPP, BPC, MPV, and platelet crit (PCT) show several changes in liver cirrhosis. It is useful to understand the relationship between hepatic cirrhosis severity and CD62P, BPC, MPV, PCT, timely monitoring of CD62P for treatment of hepatic cirrhosis in clinical treatment and prognosis.

  6. Function and Regulation of MicroRNAs and Their Potential as Biomarkers in Paediatric Liver Disease

    Directory of Open Access Journals (Sweden)

    Diego A. Calvopina

    2016-10-01

    Full Text Available MicroRNAs (miRNAs are short non-coding RNAs involved in biological and pathological processes of every cell type, including liver cells. Transcribed from specific genes, miRNA precursors are processed in the cytoplasm into mature miRNAs and as part of the RNA-induced silencing complex (RISC complex binds to messenger RNA (mRNA by imperfect complementarity. This leads to the regulation of gene expression at a post-transcriptional level. The function of a number of different miRNAs in fibrogenesis associated with the progression of chronic liver disease has recently been elucidated. Furthermore, miRNAs have been shown to be both disease-and tissue-specific and are stable in the circulation, which has led to increasing investigation on their utility as biomarkers for the diagnosis of chronic liver diseases, including those in children. Here, we review the current knowledge on the biogenesis of microRNA, the mechanisms of translational repression and the use of miRNA as circulatory biomarkers in chronic paediatric liver diseases including cystic fibrosis associated liver disease, biliary atresia and viral hepatitis B.

  7. Why and how to measure renal function in patients with liver disease.

    Science.gov (United States)

    Piano, Salvatore; Romano, Antonietta; Di Pascoli, Marco; Angeli, Paolo

    2017-01-01

    Patients with advanced liver disease frequently have impaired renal function. Both acute kidney injury (AKI) and chronic kidney disease (CKD) are quite common in patients with cirrhosis and both are associated with a worse prognosis in these patients. A careful assessment of renal function is highly important in these patients to help physicians determine their diagnosis, prognosis and therapeutic management and to define transplantation strategies (liver transplantation alone vs simultaneous liver and kidney transplantation). Although they are still widely used in clinical practice, conventional biomarkers of renal function such as serum creatinine have several limitations in these patients. Recent progress has been made in the evaluation of renal function and new diagnostic criteria for AKI have been proposed. However, certain issues such as the noninvasive assessment of the glomerular filtration rate and/or improvement in the differential diagnosis between hepatorenal syndrome and acute tubular necrosis must still be addressed. The purposes of this paper are: (i) to highlight the importance of the evaluation of renal function in patients with cirrhosis; (ii) to review the state of the art in the assessment of renal function in these patients as well as advances that we expect will be made to improve the accuracy of available tools. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Synthesis of functionalized magnetite nanoparticles to use as liver targeting MRI contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Yazdani, Farshad, E-mail: fyazdani@ccerci.ac.ir; Fattahi, Bahare; Azizi, Najmodin

    2016-05-15

    The aim of this research was the preparation of functionalized magnetite nanoparticles to use as a liver targeting contrast agent in magnetic resonance imaging (MRI). For this purpose, Fe{sub 3}O{sub 4} nanoparticles were synthesized via the co-precipitation method. The synthesized nanoparticles were coated with silica via the Stober method and finally the coated nanoparticles were functionalized with mebrofenin. Formation of crystalline magnetite particles was confirmed by X-ray diffraction (XRD) analysis. The Fourier transform infrared spectroscopy (FTIR) and energy dispersive X-ray analyzer (EDX) of the final product showed that silica had been effectively bonded onto the surface of the magnetite nanoparticles and the coated nanoparticles functionalized with mebrofenin. The magnetic resonance imaging of the functional nanoparticles showed that the Fe{sub 3}O{sub 4}–SiO{sub 2}-mebrofenin composite is an effective MRI contrast agent for liver targeting. - Highlights: • Superparamagnetic magnetite nanoparticles have been synthesized by simple and economical method. • Preperation of functional MNPs as a MRI contrast agent for liver targeting. • Gaining a good r{sub 2} relaxivity of the coated functional nanoparticles.

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

    Science.gov (United States)

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

    2004-01-01

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

  10. The use of DWI to assess spleen and liver quantitative ADC changes in the detection of liver fibrosis stages in chronic viral hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Cece, Hasan, E-mail: hasan_cece@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Ercan, Abdulbasit, E-mail: abdulbasitercan@hotmail.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Yıldız, Sema, E-mail: drsemayildiz@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Karakas, Ekrem, E-mail: karakasekrem@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Karakas, Omer, E-mail: dromerkarakas@hotmail.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Boyacı, Fatıma Nurefsan, E-mail: drnurefsan@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Aydogan, Timucin, E-mail: drtaydogan@yahoo.com.tr [Harran University, Faculty of Medicine, Department of Gastroenterology, Sanliurfa (Turkey); Karakas, Emel Yigit, E-mail: e.ygtkarakas@yahoo.com.tr [Sanliurfa Training and Research Hospital, Department of İnternal Medicine, Sanliurfa (Turkey); Cullu, Nesat, E-mail: nesatcullu77@gmail.com [Muğla Sıtkı Koçman University, Faculty of Medicine, Department of Radiology, Mugla (Turkey); Ulas, Turgay, E-mail: turgayulas@yahoo.com [Harran University, Faculty of Medicine, Department of İnternal Medicine, Sanliurfa (Turkey)

    2013-08-15

    This study aimed to evaluate the changes in spleen and liver diffusion-weighted magnetic resonance imaging (DWI) in chronic viral hepatitis patients. The study comprised 47 patients and 30 healthy volunteers. DWIs were obtained. Apparent Diffusion Coefficient (ADC) measurements were made by transferring the images to the workstation. The measurements of value b 1000 were made from a total of five points of the liver and three points of the spleen. Liver biopsy was performed on the 47 patients. The fibrosis stages of the patients were defined according to the METAVIR scoring system. Student's t-test was used in the comparison of mean ages, liver and spleen ADC values between the patient and the control group. Kruskal–Wallis followed by Mann–Whitney U Test with Bonferroni adjustment was performed in the comparison of mean ADC values of the patients at different stages and the control group. A statistically significant difference was determined between the patient and control group in respect of liver and spleen mean ADC values (P < 0.05). F3 group showed a significant difference compared to control and F1 and F4 group showed a significant difference compared to control, F1, F2 and F3 group in terms of the mean liver ADC value (P < 0.01). F3 and F4 group showed a significant difference compared to control and F1 group in terms of the mean spleen ADC value (P < 0.01). As a result we believe that the measurement of liver and spleen ADC values may be an indicator in the determination of the level of fibrosis.

  11. Measurement of hepatic functional mass by means of 13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease: Comparison with Child-Pugh score and serum bile acid levels

    Institute of Scientific and Technical Information of China (English)

    D. Festi; P. Portincasa; E. Roda; A. Colecchia; S. Capodicasa; L. Sandri; L. Colaiocco-Ferrante; T. Staniscia; E. Vitacolonna; A. Vestito; P. Simoni; G. Mazzella

    2005-01-01

    AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels.METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated.RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids.Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test.CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.

  12. Evaluation of quantitative contrast harmonic imaging to assess malignancy of liver tumors: A prospective controlled two-center study

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To establish the extent to which contrast enhancement with SonoVue in combination with quantitative evaluation of contrast-medium dynamics facilitates the detection of hepatic tumors.METHODS: One hundred patients with histologically confirmed malignant or benign hepatic tumor (maximum size 5 cm) were analyzed. Contrast-enhanced ultrasound (bolus injection 2.5 mL SonoVue) was carried out with intermittent breath-holding technique using a multifrequency transducer (2.5-4 MHz). Native vascularization was analyzed with power Doppler. The contrast-enhanced dynamic ultrasound investigation was carried out with contrast harmonic imaging in true detection mode during the arterial, portal venous and late phases. Mechanical index was set at 0.15. Perfusion analysis was performed by post-processing of the raw data [time intensity curve (TIC) analysis]. The cutoff of the gray value differences between tumor and normal liver tissue was established using Receiver Operating Characteristic (ROC) analysis 64-line multislice computed tomography served as reference method in all cases. Magnetic resonance tomography was used additionally in 19 cases.RESULTS: One hundred patients with 59 malignant (43 colon, 5 breast, 2 endocrine metastases, 7 hepatocellular carcinomas and 2 kidney cancers) and 41 benign (15 hemangiomas, 7 focal nodular hyperplasias, 5 complicated cysts, 2 abscesses and 12 circumscribed fatty changes) tumors were included. The late venous phase proved to be the most sensitive for classification of the tumor type. Fifty-eight of the 59 malignant tumors were classified as true positive, and one as false negative. This resulted in a sensitivity of 98.3%. Of the 41 benign tumors, 37 were classified as true negative and 4 as false negative, which corresponds to a specificity of 90.2%. Altogether, 95.0% of the diagnoses were classified as correct on the basis of the histological classification. No investigator-dependency (P = 0.23) was noted.CONCLUSION: The results show

  13. [Morpho-functional changes of liver and its regional lymph nodes after exposure to magnetic field of industrial frequency].

    Science.gov (United States)

    Michurina, S V; Efremov, A V; Shurlygina, A V; Belkin, A D; Vakulin, G M; Verbitskaia, L V; Larionov, P M

    2005-01-01

    The aim of this research was to study the morpho-functional organization of liver and its regional lymph nodes, as well as of other organs of immune system, in animals exposed for 14 days to a magnetic field of industrial frequency (MFIF) with aperiodic oscillations of amplitude of magnetic induction in the range of 5-10 _Ts. The methods of light and electron microscopy were used. Damage to DNA in hepatocyte nuclei was determined using ethidium bromide. Quantitative analysis of the cells in the organs of immune system was performed, blood leukocyte formula was calculated and the activity of oxidative enzymes in blood cells was determined. It was found that MFIF caused micro- and ultrastructural changes in animal liver and its regional lymph nodes, which included the disturbances of hemo- and lymphocirculation, destruction of cellular membranes in some cells, dilation of rough endoplasmic reticulum cisterns, appearance of degenerate mitochondrial forms, glycogen depletion, that collectively indicated the development of tissue hypoxia. The increase in the activity of nuclear endonucleases was detected. Response of organs of immune system to MFIF was manifested by shifts of blast forms/ mature lymphocytes ratio in hepatic regional lymph nodes and by the changes of energy metabolism of blood lymphocytes.

  14. Effect of increased intra-abdominal pressure due to pneumoperitoneum on liver functions and liver histopathology in a rat model with intra-abdominal sepsis.

    Science.gov (United States)

    Youssef, Youssef Farouk; Noseer, Mona

    2008-04-01

    Intra-abdominal sepsis was induced by open cecal ligation and puncture (OCLP) technique. Sixty rats were randomly divided into three equal groups each of 20. G1 was used as a control. G2 were subjected to laparotomy and closure after 12 hours from (OCLP) via the same incision. In G3, pneumoperitoneum was induced 12 hours after OCLP and maintained at 12 mmHg for about 30 minutes. Blood samples were taken for liver functions after 12 & 24 hours from OCLP procedure, and Liver biopsies were taken for histopathological examination after 24 hours. The results showed that liver functions were markedly increased in G3 after pneumoperitoneum, compared to Gs 1 & 2. The histopathological changes in liver biopsies due to sepsis were more marked in cases exposed to pneumoperitoneum than that exposed to conventional laparotomy. The intra-abdominal sepsis affected liver functions and caused pathogenesis. The increased intra-abdominal pressure induced more liver insults, compared to that gained after open surgery.

  15. Functional Maps of Protein Complexes from Quantitative Genetic Interaction Data

    OpenAIRE

    Sourav Bandyopadhyay; Ryan Kelley; Krogan, Nevan J.; Trey Ideker

    2008-01-01

    Recently, a number of advanced screening technologies have allowed for the comprehensive quantification of aggravating and alleviating genetic interactions among gene pairs. In parallel, TAP-MS studies (tandem affinity purification followed by mass spectroscopy) have been successful at identifying physical protein interactions that can indicate proteins participating in the same molecular complex. Here, we propose a method for the joint learning of protein complexes and their functional relat...

  16. Quantitative amyloid imaging using image-derived arterial input function.

    Directory of Open Access Journals (Sweden)

    Yi Su

    Full Text Available Amyloid PET imaging is an indispensable tool widely used in the investigation, diagnosis and monitoring of Alzheimer's disease (AD. Currently, a reference region based approach is used as the mainstream quantification technique for amyloid imaging. This approach assumes the reference region is amyloid free and has the same tracer influx and washout kinetics as the regions of interest. However, this assumption may not always be valid. The goal of this work is to evaluate an amyloid imaging quantification technique that uses arterial region of interest as the reference to avoid potential bias caused by specific binding in the reference region. 21 participants, age 58 and up, underwent Pittsburgh compound B (PiB PET imaging and MR imaging including a time-of-flight (TOF MR angiography (MRA scan and a structural scan. FreeSurfer based regional analysis was performed to quantify PiB PET data. Arterial input function was estimated based on coregistered TOF MRA using a modeling based technique. Regional distribution volume (VT was calculated using Logan graphical analysis with estimated arterial input function. Kinetic modeling was also performed using the estimated arterial input function as a way to evaluate PiB binding (DVRkinetic without a reference region. As a comparison, Logan graphical analysis was also performed with cerebellar cortex as reference to obtain DVRREF. Excellent agreement was observed between the two distribution volume ratio measurements (r>0.89, ICC>0.80. The estimated cerebellum VT was in line with literature reported values and the variability of cerebellum VT in the control group was comparable to reported variability using arterial sampling data. This study suggests that image-based arterial input function is a viable approach to quantify amyloid imaging data, without the need of arterial sampling or a reference region. This technique can be a valuable tool for amyloid imaging, particularly in population where reference

  17. Quantitative amyloid imaging using image-derived arterial input function.

    Science.gov (United States)

    Su, Yi; Blazey, Tyler M; Snyder, Abraham Z; Raichle, Marcus E; Hornbeck, Russ C; Aldea, Patricia; Morris, John C; Benzinger, Tammie L S

    2015-01-01

    Amyloid PET imaging is an indispensable tool widely used in the investigation, diagnosis and monitoring of Alzheimer's disease (AD). Currently, a reference region based approach is used as the mainstream quantification technique for amyloid imaging. This approach assumes the reference region is amyloid free and has the same tracer influx and washout kinetics as the regions of interest. However, this assumption may not always be valid. The goal of this work is to evaluate an amyloid imaging quantification technique that uses arterial region of interest as the reference to avoid potential bias caused by specific binding in the reference region. 21 participants, age 58 and up, underwent Pittsburgh compound B (PiB) PET imaging and MR imaging including a time-of-flight (TOF) MR angiography (MRA) scan and a structural scan. FreeSurfer based regional analysis was performed to quantify PiB PET data. Arterial input function was estimated based on coregistered TOF MRA using a modeling based technique. Regional distribution volume (VT) was calculated using Logan graphical analysis with estimated arterial input function. Kinetic modeling was also performed using the estimated arterial input function as a way to evaluate PiB binding (DVRkinetic) without a reference region. As a comparison, Logan graphical analysis was also performed with cerebellar cortex as reference to obtain DVRREF. Excellent agreement was observed between the two distribution volume ratio measurements (r>0.89, ICC>0.80). The estimated cerebellum VT was in line with literature reported values and the variability of cerebellum VT in the control group was comparable to reported variability using arterial sampling data. This study suggests that image-based arterial input function is a viable approach to quantify amyloid imaging data, without the need of arterial sampling or a reference region. This technique can be a valuable tool for amyloid imaging, particularly in population where reference normalization may

  18. Functional changes of dendritic cells derived from allogeneic partial liver graft undergoing acute rejection in rats

    Institute of Scientific and Technical Information of China (English)

    Ming-Qing Xu; Zhen-Xiang Yao

    2003-01-01

    AIM: To investigate functional change of dendritic cells (DCs)derived from allogeneic partial liver graft undergoing acuterejection in rats.METHODS: Allogeneic (SD rat to LEW rat) whole and 50 %partial liver transplantation were performed. DCs from livergrafts 0 hr and 4 days after transplantation were isolated andpropagated in the presence of GM-CSFin vitro. Morphologicalcharacteristics of DCs propagated for 4 days and 10 dayswere observed by electron rmicroscopy. Phenotypical featuresof DCs propagated for 10 days were analyzed by flowcytometry. Expression of IL-12 protein and IL-12 receptormRNA in DCs propagated for 10 days was also measured byWestern blotting and semiquantitative RT-PCR, respectively.Histological grading of rejection were determined.RESULTS: Allogeneic whole liver grafts showed no featuresof rejection at day 4 after transplantation. In contrast,allogeneic partial liver grafts demonstrated moderate tosevere rejection at day 4 after transplantation. DCs derivedfrom allogeneic partial liver graft 4 days after transplantationexhibited typical morphological characteristics of DC after 4days' culture in the presence of GM-CSF. DCs from allogeneicwhole liver graft 0 hr and 4 days after transplantation didnot exhibit typical morphological characteristics of DC untilafter 10 days' culture in the presence of GM-CSF. After 10days' propagationin vitro, DCs derived from allogeneic wholeliver graft exhibited features of immature DC, with absenceof CD40, CD80 and CD86 surface expression, and low levelsof IL-12 proteins (IL-12 p35 and IL-12 p40) and IL-12receptor (IL-12Rβ1 and IL-12Rβ2) mRNA, whereas DCs fromallogeneic partial liver graft 4 days after transplantationdisplayed features of mature DC, with high levels of CD40,CD80 and CD86 surface expression, and as a consequence,higher expression of IL-12 proteins (IL-12 p35 and IL-12 p40)and IL-12 receptors (IL-12Rβ1 and IL-12Rβ2) mRNA thanthose of DCs both from partial liver graft 0 hr and whole livergraft

  19. Transplantation of mouse fetal liver cells for analyzing the function of hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Gudmundsson, Kristbjorn Orri; Stull, Steven W; Keller, Jonathan R

    2012-01-01

    Hematopoietic stem cells are defined by their ability to self-renew and differentiate through progenitor cell stages into all types of mature blood cells. Gene-targeting studies in mice have demonstrated that many genes are essential for the generation and function of hematopoietic stem and progenitor cells. For definitively analyzing the function of these cells, transplantation studies have to be performed. In this chapter, we describe methods to isolate and transplant fetal liver cells as well as how to analyze donor cell reconstitution. This protocol is tailored toward mouse models where embryonic lethality precludes analysis of adult hematopoiesis or where it is suspected that the function of fetal liver hematopoietic stem and progenitor cells is compromised.

  20. Quantitative imaging of fibrotic and morphological changes in liver of non-alcoholic steatohepatitis (NASH) model mice by second harmonic generation (SHG) and auto-fluorescence (AF) imaging using two-photon excitation microscopy (TPEM).

    Science.gov (United States)

    Yamamoto, Shin; Oshima, Yusuke; Saitou, Takashi; Watanabe, Takao; Miyake, Teruki; Yoshida, Osamu; Tokumoto, Yoshio; Abe, Masanori; Matsuura, Bunzo; Hiasa, Yoichi; Imamura, Takeshi

    2016-12-01

    Non-alcoholic steatohepatitis (NASH) is a common liver disorder caused by fatty liver. Because NASH is associated with fibrotic and morphological changes in liver tissue, a direct imaging technique is required for accurate staging of liver tissue. For this purpose, in this study we took advantage of two label-free optical imaging techniques, second harmonic generation (SHG) and auto-fluorescence (AF), using two-photon excitation microscopy (TPEM). Three-dimensional ex vivo imaging of tissues from NASH model mice, followed by image processing, revealed that SHG and AF are sufficient to quantitatively characterize the hepatic capsule at an early stage and parenchymal morphologies associated with liver disease progression, respectively.

  1. Quantitative imaging of basic functions in renal (patho)physiology.

    Science.gov (United States)

    Kang, Jung Julie; Toma, Ildiko; Sipos, Arnold; McCulloch, Fiona; Peti-Peterdi, Janos

    2006-08-01

    Multiphoton fluorescence microscopy offers the advantages of deep optical sectioning of living tissue with minimal phototoxicity and high optical resolution. More importantly, dynamic processes and multiple functions of an intact organ can be visualized in real time using noninvasive methods, and quantified. These studies aimed to extend existing methods of multiphoton fluorescence imaging to directly observe and quantify basic physiological parameters of the kidney including glomerular filtration rate (GFR) and permeability, blood flow, urinary concentration/dilution, renin content and release, as well as more integrated and complex functions like the tubuloglomerular feedback (TGF)-mediated oscillations in glomerular filtration and tubular flow. Streptozotocin-induced diabetes significantly increased single-nephron GFR (SNGFR) from 32.4 +/- 0.4 to 59.5 +/- 2.5 nl/min and glomerular permeability to a 70-kDa fluorophore approximately eightfold. The loop diuretic furosemide 2-fold diluted and increased approximately 10-fold the volume of distal tubular fluid, while also causing the release of 20% of juxtaglomerular renin content. Significantly higher speeds of individual red blood cells were measured in intraglomerular capillaries (16.7 +/- 0.4 mm/s) compared with peritubular vessels (4.7 +/- 0.2 mm/s). Regular periods of glomerular contraction-relaxation were observed, resulting in oscillations of filtration and tubular flow rate. Oscillations in proximal and distal tubular flow showed similar cycle times ( approximately 45 s) to glomerular filtration, with a delay of approximately 5-10 and 25-30 s, respectively. These innovative technologies provide the most complex, immediate, and dynamic portrayal of renal function, clearly depicting the components and mechanisms involved in normal physiology and pathophysiology.

  2. Postoperative Decrease in Platelet Counts Is Associated with Delayed Liver Function Recovery and Complications after Partial Hepatectomy.

    Science.gov (United States)

    Takahashi, Kazuhiro; Kurokawa, Tomohiro; Oshiro, Yukio; Fukunaga, Kiyoshi; Sakashita, Shingo; Ohkohchi, Nobuhiro

    2016-05-01

    Peripheral platelet counts decrease after partial hepatectomy; however, the implications of this phenomenon are unclear. We assessed if the observed decrease in platelet counts was associated with postoperative liver function and morbidity (complications grade ≤ II according to the Clavien-Dindo classification). We enrolled 216 consecutive patients who underwent partial hepatectomy for primary liver cancers, metastatic liver cancers, benign tumors, and donor hepatectomy. We classified patients as either low or high platelet percentage (postoperative platelet count/preoperative platelet count) using the optimal cutoff value calculated by a receiver operating characteristic (ROC) curve analysis, and analyzed risk factors for delayed liver functional recovery and morbidity after hepatectomy. Delayed liver function recovery and morbidity were significantly correlated with the lowest value of platelet percentage based on ROC analysis. Using a cutoff value of 60% acquired by ROC analysis, univariate and multivariate analysis determined that postoperative lowest platelet percentage ≤ 60% was identified as an independent risk factor of delayed liver function recovery (odds ratio (OR) 6.85; P decreased postoperative prothrombin time ratio and serum albumin level and increased serum bilirubin level when compared with patients with platelet percentage ≥ 61%. A greater than 40% decrease in platelet count after partial hepatectomy was an independent risk factor for delayed liver function recovery and postoperative morbidity. In conclusion, the decrease in platelet counts is an early marker to predict the liver function recovery and complications after hepatectomy.

  3. Role of Liver Function Enzymes in Diagnosis of Choledocholithiasis in Biliary Colic Patients

    Directory of Open Access Journals (Sweden)

    Mohammad Hussein Mirshamsi

    2011-10-01

    Full Text Available Liver functional tests due to inflammatory process which induced by cholecystitis might changed and some clinicians suggested that these changes might help us to stone prediction in common bile ducts and decrease hazards of performing ERCP and other invasive procedures. Present study was performed for assessment of role of liver functional test in diagnosis of common bile duct stone in patients with cholecystitis and help in their management. Present prospective study was performed between April 2010 and March 2011 on 350 patients who come to our hospital with cholecystitis or biliary colic diagnosis. Patients with cholesistitis diagnosis were underwent operation for removing gall bladder stone and retrograde cholangiopancreatography (ERCP was performed for patients with suspicious to biliary colic and common bile duct (CBD stones. Ultrasonography, Aspartate Aminotransferases (AST, Alanine Aminotransferases (ALT, Alkaline Phosphatase (ALP and direct and total serum bilirubin were measured for all of participated patients. Mean of AST. ALT, ALP and total and direct bilirubin were had no significant differences between two study groups. In logistic regression analysis, after entering into the model only CBD diameter (OR: 20; P=0.00 and elevated serum level of ALT (OR: 2; P=0.04 were remained into the model and were known as independent predictor of cholelithiasis. Elevated level of liver enzymes had not main role in CBD diagnosis and ERCP had no to perform for suspicious CBD stone only with elevated liver enzyme and even with normal ultrasonography findings. Endosonography as non invasive procedure recommend for patients before ERCP.

  4. The effect of cytoflavin on functional and metabolic parameters rat liver in pancreatonecrosis

    Directory of Open Access Journals (Sweden)

    M. S. Sukach

    2012-01-01

    Full Text Available Problem of diagnosis and treatment of patients with necrotizing pancreatitis is an urgent. So it is interesting to study the effectiveness of a multicomponent antihypoxant and antioxidant cytoflavin to reduce violations of the detoxifying properties of the liver in experimental pancreatitis and reduce the severity of pancreatic endotoxemia. Pancreatic modeled by introducing into the pancreas of autobile in a dose of 0,15 ml/kg. Cytoflavin was injected into animals of a comparison group in a dose 0,21 ml/kg in 5 minutes after the model of pancreatic necrosis. We determined the activity of enzymes: alanine transaminase, amylase, and gamma glutamyltransferase, the content of direct bilirubin, glucose, and urea. After modeling of pancreatic necrosis in two days, there are signs of acute liver failure, as evidenced by the differences in the studied parameters of blood and hepatic portal vein: increased alanine transaminase and gamma glutamyltransferase, the change in concentration of metabolic products, such as direct bilirubin and urea. In addition, decreased glucose levels. Introduction of cytoflavin approached the control values the basic biochemical parameters of liver function: decreased hyperenzymemia, exchange function of the liver was restored, which is probably due to antihypoxic, membrane and antioxidant effects of the drug.

  5. Multi-factor analysis of initial poor graft function after orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Hao Chen; Cheng-Hong Peng; Bai-Yong Shen; Xia-Xing Deng; Chuan Shen; Jun-Jie Xie; Wei Dong; Hong-Wei Li

    2007-01-01

    BACKGROUND: In the early period of orthotopic liver transplantation (OLT), initial poor graft function (IPGF) is one of the complications which leads to primary graft non-function (PGNF) in serious cases. This study set out to establish the clinical risk factors resulting in IPGF after OLT. METHODS: Eighty cases of OLT were analyzed. The IPGF group consisted of patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) above 1500 IU/L within 72 hours after OLT, while those in the non-IPGF group had values below 1500 IU/L. Recipient-associated factors before OLT analyzed were age, sex, primary liver disease and Child-Pugh classiifcation;factors analyzed within the peri-operative period were non-heart beating time (NHBT), cold ischemia time (CIT), rewarming ischemic time (RWIT), liver biopsy at the end of cold ischemia;and factors analyzed within 72 hours after OLT were ALT and/or AST values. A logistic regression model was applied to iflter the possible factors resulting in IPGF. RESULTS:Donor NHBT, CIT and RWIT were signiifcantly longer in the IPGF group than in the non-IPGF group;in the logistic regression model, NHBT was the risk factor leading to IPGF (P CONCLUSIONS:Longer NHBT is an important risk factor leading to IPGF, while serious steatosis in the donor liver, CIT and RWIT are potential risk factors.

  6. New Trends in Quantitative Assessment of the Corneal Barrier Function

    Directory of Open Access Journals (Sweden)

    Anton Guimerà

    2014-05-01

    Full Text Available The cornea is a very particular tissue due to its transparency and its barrier function as it has to resist against the daily insults of the external environment. In addition, maintenance of this barrier function is of crucial importance to ensure a correct corneal homeostasis. Here, the corneal epithelial permeability has been assessed in vivo by means of non-invasive tetrapolar impedance measurements, taking advantage of the huge impact of the ion fluxes in the passive electrical properties of living tissues. This has been possible by using a flexible sensor based in SU-8 photoresist. In this work, a further analysis focused on the validation of the presented sensor is performed by monitoring the healing process of corneas that were previously wounded. The obtained impedance measurements have been compared with the damaged area observed in corneal fluorescein staining images. The successful results confirm the feasibility of this novel method, as it represents a more sensitive in vivo and non-invasive test to assess low alterations of the epithelial permeability. Then, it could be used as an excellent complement to the fluorescein staining image evaluation.

  7. Assessment of the link between quantitative biexponential diffusion-weighted imaging and contrast-enhanced MRI in the liver

    NARCIS (Netherlands)

    Dijkstra, Hildebrand; Oudkerk, Matthijs; Kappert, Peter; Sijens, Paul E.

    Purpose: To investigate if intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) can be linked to contrast-enhanced (CE-)MRI in liver parenchyma and liver lesions. Methods: Twenty-five patients underwent IVIM-DWI followed by multiphase CE-MRI using Gd-EOB-DTPA (n = 20) or

  8. Impaired function of bone marrow-derived endothelial progenitor cells in murine liver fibrosis.

    Science.gov (United States)

    Shirakura, Katsuya; Masuda, Haruchika; Kwon, Sang-Mo; Obi, Syotaro; Ito, Rie; Shizuno, Tomoko; Kurihara, Yusuke; Mine, Tetsuya; Asahara, Takayuki

    2011-01-01

    Liver fibrosis (LF) caused by chronic liver damage has been considered as an irreversible disease. As alternative therapy for liver transplantation, there are high expectations for regenerative medicine of the liver. Bone marrow (BM)- or peripheral blood-derived stem cells, including endothelial progenitor cells (EPCs), have recently been used to treat liver cirrhosis. We investigated the biology of BM-derived EPC in a mouse model of LF. C57BL/6J mice were subcutaneously injected with carbon tetrachloride (CCl(4)) every 3 days for 90 days. Sacrificed 2 days after final injection, whole blood (WB) was collected for isolation of mononuclear cells (MNCs) and biochemical examination. Assessments of EPC in the peripheral blood and BM were performed by flow cytometry and EPC colony-forming assay, respectively, using purified MNCs and BM c-KIT(+), Sca-1(+), and Lin(-) (KSL) cells. Liver tissues underwent histological analysis with hematoxylin/eosin/Azan staining, and spleens were excised and weighed. CCl(4)-treated mice exhibited histologically bridging fibrosis, pseudolobular formation, and splenomegaly, indicating successful induction of LF. The frequency of definitive EPC-colony-forming-units (CFU) as well as total EPC-CFU at the equivalent cell number of 500 BM-KSL cells decreased significantly (p changes in primitive EPC-CFU occurred in LF mice. The frequency of WB-MNCs of definitive EPC-CFU decreased significantly (p < 0.01) in LF mice compared with control mice. Together, these findings indicated the existence of impaired EPC function and differentiation in BM-derived EPCs in LF mice and might be related to clinical LF.

  9. Pattern of liver function tests in morbidly obese Saudi patients undergoing bariatric surgery

    Directory of Open Access Journals (Sweden)

    Ahmad Al Akwaa

    2011-01-01

    Full Text Available Background/Aim: Morbidly obese patients have a high prevalence of fatty liver disease and its serious complications, and high prevalence of abnormal liver function tests (LFT. The LFT can give a clue to the liver damage and correlate with activity. We aim to study the pattern of LFT in morbidly obese Saudi patients undergoing bariatric surgery in Eastern region. Patients and Methods: Medical records of patients undergoing bariatric surgery were reviewed. Demographic data, comorbid conditions, and medications taken were recorded. Intraoperative liver appearance was noted. Patients with alcohol intake or without LFT were excluded. Results: Out of 113 patients, 15 patients were excluded, and of the remaining 98 patients analyzed, 58.2% were females. Mean age was 33.1 ± 8.87 years. Mean body mass index (BMI was 53.7 ± 1.27 kg/m 2 . Abnormal LFT (alanine aminotransaminase (ALT, aspartate aminotransaminase (AST alkaline phosphatase (ALK, and Gamma glutamyl transpeptidase (GTT were observed in 17.3%, with 1.5 to 2 times the upper limit of normal. ALT was most elevated in 12.2%. Abdominal ultrasonography was done in 67 (68.4% patients, of whom 51 (76% had fatty liver. Comorbid conditions including diabetes mellitus, hypertension, hyperlipidemia, bronchial asthma, and obstructive sleep apnea were observed in 51 (51.50% patients, eight of them (16.3% had abnormal LFT. No intraoperative changes of cirrhosis were observed. Conclusion: The prevalence of abnormal LFT is low in morbidly obese patients from the eastern region of Saudi Arabia. A prospective study with a larger sample and liver biopsy, is needed to clarify the findings.

  10. Prevalence of Fatty Liver Disease and Hepatic Iron Overload in a Northeastern German Population by Using Quantitative MR Imaging.

    Science.gov (United States)

    Kühn, Jens-Peter; Meffert, Peter; Heske, Christian; Kromrey, Marie-Luise; Schmidt, Carsten O; Mensel, Birger; Völzke, Henry; Lerch, Markus M; Hernando, Diego; Mayerle, Julia; Reeder, Scott B

    2017-09-01

    Purpose To quantify liver fat and liver iron content by measurement of confounder-corrected proton density fat fraction (PDFF) and R2* and to identify clinical associations for fatty liver disease and liver iron overload and their prevalence in a large-scale population-based study. Materials and Methods From 2008 to 2013, 2561 white participants (1336 women; median age, 52 years; 25th and 75th quartiles, 42 and 62 years) were prospectively recruited to the Study of Health in Pomerania (SHIP). Complex chemical shift-encoded magnetic resonance (MR) examination of the liver was performed, from which PDFF and R2* were assessed. On the basis of previous histopathologic calibration, participants were stratified according to their liver fat and iron content as follows: none (PDFF, ≤5.1%; R2*, ≤41.0 sec(-1)), mild (PDFF, >5.1%; R2*, >41 sec(-1)), moderate (PDFF, >14.1%; R2*, >62.5 sec(-1)), high (PDFF: >28.0%; R2*: >70.1 sec(-1)). Prevalence of fatty liver diseases and iron overload was calculated (weighted by probability of participation). Clinical associations were identified by using boosting for generalized linear models. Results Median PDFF was 3.9% (range, 0.6%-41.5%). Prevalence of fatty liver diseases was 42.2% (1082 of 2561 participants); mild, 28.5% (730 participants); moderate, 12.0% (307 participants); high content, 1.8% (45 participants). Median R2* was 34.4 sec(-1) (range, 14.0-311.8 sec(-1)). Iron overload was observed in 17.4% (447 of 2561 participants; mild, 14.7% [376 participants]; moderate, 0.8% [20 participants]; high content, 2.0% [50 participants]). Liver fat content correlated with waist-to-height ratio, alanine transaminase, uric acid, serum triglycerides, and blood pressure. Liver iron content correlated with mean serum corpuscular hemoglobin, male sex, and age. Conclusion In a white German population, the prevalence of fatty liver diseases and liver iron overload is 42.2% (1082 of 2561) and 17.4% (447 of 2561). Whereas liver fat is associated

  11. A computer-assisted morphometric quantitative analysis of iron overload in liver biopsies. A comparison with histological and biochemical methods.

    Science.gov (United States)

    Ortega, Luis; Ladero, José M; Carreras, María P; Alvarez, Teresa; Taxonera, Carlos; Oliván, María P; Sanz-Esponera, Julián; Díaz-Rubio, Manuel

    2005-01-01

    The aim of this study was to evaluate a new method of image analysis used to quantify the iron load in routinely processed liver biopsies. Sixty-four liver biopsies from the same number of patients were studied. Both biochemical determination of iron concentration and histopathological semiquantification and quantification were performed. The latter was performed on Perls-stained liver sections by a semiautomatic system of image analysis that yields the percentage of stained liver tissue. In 43 samples with an hepatic iron content higher than 2000microg/mg of dry tissue, this morphometric index was compared to the liver iron load measured biochemically, showing a significant correlation (Spearman's test) between both variables (rho = 0.686, pgrading systems, such as the one described by Deugnier, since the morphometric method shows a closer correlation with the hepatic iron concentration determined biochemically.

  12. Quantitative Assessment of Liver Fat in an Obese Patient Population Using Non-contrast CT Fat Percent Index

    Science.gov (United States)

    Jon, Ali F.; Cheema, Ahmad R.; Khan, Atif N.; Raptopoulos, V.; Hauser, T.; Nasser, I.; Welty, F.K.; Karellas, A.; Clouse, Melvin E.

    2014-01-01

    Objective To develop a simplified method to quantify liver fat using CT fat % index (CTFPI) compared to liver spleen method (CTL/S, CTL-S) Methods Non-contrast CT of the liver was performed in 89 patients (overweight, obese, severely obese) to quantify fat, using: CTFPI= [(65-patient HU)/65] ×100, normal liver =65 HU. Results There was strong linear correlation between CTFPI and the standard method of assessing liver fat using CTL/S (r = −0.901), CTL-S (r = −0.911). Hepatic HU and CTFPI were significantly different in the severely obese group compared to other two groups(p<0.05). Conclusion Significant correlation indicates equal diagnostic accuracy of the two methods in appropriately calibrated scanners. PMID:24559751

  13. Assessment of functional integrity of liver among workers exposed to soluble nickel compounds during nickel plating

    Directory of Open Access Journals (Sweden)

    Kalahasthi Ravi Babu

    2006-01-01

    Full Text Available The present study investigates the functional integrity of liver among workers exposed to nickel during nickel-plating process. The functional integrity of liver was assessed in 69 workers who are exposed to nickel during nickel plating and considered as nickel-exposed workers; and 50 administrative workers residing in same city, but away from the place of work of study group, were considered as control group. The level of urine nickel was measured by using a flameless atomic absorption spectrophotometer. Using kits supplied by Bayer Diagnostics, we determined serum markers of liver function tests. Results: The levels of urine nickel were significantly increased in high-and moderate-exposure groups as compared to control group. The levels of serum transaminases -viz, alanine transaminase and aspartate transaminase-were significantly increased in nickel-exposed workers, who had high urine nickel levels as compared to control group. The level of serum albumin was negatively correlated with urine nickel levels. The levels of serum transaminases and serum g- glutamyl- transpeptidase were positively and significantly correlated with urine nickel levels. Conclusion: Results indicate that workers who had high urine nickel levels had a consistent effect on hepatic inflammatory function.

  14. A quantitative confidence signal detection model: 1. Fitting psychometric functions.

    Science.gov (United States)

    Yi, Yongwoo; Merfeld, Daniel M

    2016-04-01

    Perceptual thresholds are commonly assayed in the laboratory and clinic. When precision and accuracy are required, thresholds are quantified by fitting a psychometric function to forced-choice data. The primary shortcoming of this approach is that it typically requires 100 trials or more to yield accurate (i.e., small bias) and precise (i.e., small variance) psychometric parameter estimates. We show that confidence probability judgments combined with a model of confidence can yield psychometric parameter estimates that are markedly more precise and/or markedly more efficient than conventional methods. Specifically, both human data and simulations show that including confidence probability judgments for just 20 trials can yield psychometric parameter estimates that match the precision of those obtained from 100 trials using conventional analyses. Such an efficiency advantage would be especially beneficial for tasks (e.g., taste, smell, and vestibular assays) that require more than a few seconds for each trial, but this potential benefit could accrue for many other tasks. Copyright © 2016 the American Physiological Society.

  15. Qualitative and quantitative image analysis of CT and MR imaging in patients with neuroendocrine liver metastases in comparison to (68)Ga-DOTATOC PET.

    Science.gov (United States)

    Flechsig, Paul; Zechmann, Christian M; Schreiweis, Julian; Kratochwil, Clemens; Rath, Daniel; Schwartz, Lawrence H; Schlemmer, Heinz-Peter; Kauczor, Hans-Ulrich; Haberkorn, Uwe; Giesel, Frederik L

    2015-08-01

    To compare lesion conspicuity in patients with liver metastases arising from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using MRI, PET and CT. 16 patients with GEP-NETs were evaluated using non-contrast MRI, contrast-enhanced (CE) MRI using Gd-EOB-DTPA and CE-(68)Ga-DOTATOC PET. Quantitative analyses were performed by two blinded readers using ROI-analyses quantifying contrast ratios (CR) between normal liver-tissue and GEP-NET-metastases. Qualitative analyses were performed evaluating primary visibility and spatial detectability of all lesions. 103 of the same liver metastases were detected on all modalities. Qualitatively, lesion conspicuity was superior on CE-MRI imaging compared to non-contrast MR-sequences (T2, DWI, fl2D, fl3D), as well as arterial- and portal-venous phase CT. Concerning detectability of lesions, CE-MRI was superior to all other modalities. The quantitative ROI-analysis demonstrated improved CR for DWI compared to all other non-contrast MR-sequences (p<0.001). CE-MRI presented with higher CR-values compared to CE-(68)Ga-DOTATOC PET/CT (p<0.001). Anatomic imaging using non contrast MRI with fl2D-and fl3D-sequences in combination with the molecular imaging modality (68)Ga-DOTATOC PET is optimal for the assessment of liver lesions in GEP-NET-patients. Even though CE-MRI was superior to non-contrast MRI, non-contrast MRI is sufficient to detect and quantify liver metastases in daily routine, especially in combination with DW-Imaging. Copyright © 2015. Published by Elsevier Ireland Ltd.

  16. Lipid profiling and transcriptomic analysis reveals a functional interplay between estradiol and growth hormone in liver

    DEFF Research Database (Denmark)

    Fernández-Pérez, Leandro; Santana-Farré, Ruymán; Mirecki-Garrido, Mercedes de

    2014-01-01

    fatty acid oxidation. Both E2 and GH replacements reduced hepatic CHO levels and increased the formation of cholesterol esters and triacylglycerols. Notably, the hepatic lipid profiles were endowed with singular fingerprints that may be used to segregate the effects of different hormonal replacements......, through its interaction with the estrogen receptor, exerts direct effects on liver. Hypothyroidism also affects endocrine and metabolic functions of the liver, rendering a metabolic phenotype with features that mimic deficiencies in E2 or GH. In this work, we combined the lipid and transcriptomic analysis......-differentiated functions. E2 influenced genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, immune, and male-specific responses. E2 induced a female-pattern of gene expression and inhibited GH-regulated STAT5b targeted genes. E2 did not prevent the inhibitory effects...

  17. The Src family kinases: distinct functions of c-Src, Yes, and Fyn in the liver.

    Science.gov (United States)

    Reinehr, Roland; Sommerfeld, Annika; Häussinger, Dieter

    2013-04-01

    The Src family kinases Yes, Fyn, and c-Src play a pivotal role in regulating diverse liver functions such as bile flow, proteolysis, apoptosis, and proliferation and are regulated by anisoosmotic cell volume changes, death receptor ligands, and bile acids. For example, cell swelling leads to an integrin-sensed and focal adhesion kinase-mediated activation of c-Src-triggering choleresis, proteolysis inhibition, regulatory volume decrease via p38MAPK and proliferation via the activation of the epidermal growth factor receptor and extracellular regulated kinases 1 and 2. In contrast, hepatocyte shrinkage generates an almost instantaneous oxidative stress response that triggers the activation of c-Jun N-terminal kinase and the Src family kinases Fyn and Yes. Whereas Fyn activation mediates cholestasis, Yes triggers CD95 activation and apoptosis. This review will discuss the role of Src family kinases in the regulation of liver function with emphasis on their role in osmo-signaling and bile acid signaling.

  18. Liver function

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008072 The correlation between nosocomial infections and the serum levels of interleukin-10, interleukin-13,interleukin-15 in patients with chronic hepatic failure. SU Zhijun(苏智军), et al. Dept Infect Dis, Quanzhou 1st Hosp, Fujian Med Univ, Quanzhou 362000. Chin J Infect Dis 2007;25(12):745-749. Objective To investigate the significance of the serum

  19. Longitudinal Study on Liver Functions in Patients with Thalassemia Major before and after Deferasirox (DFX) Therapy

    Science.gov (United States)

    Soliman, Ashraf; Yassin, Mohamed; Al Yafei, Fawzia; Al-Naimi, Lolwa; Almarri, Noora; Sabt, Aml; De Sanctis, Vincenzo

    2014-01-01

    By performing regular blood transfusion and iron chelation therapy, most patients with beta thalassemia major (BTM) now survive beyond the third decade of life. Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are both important causes of liver pathology. Iron chelation with desferrioxamine (DFO) reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox ( DFX ), an oral single dose therapy, has improved the compliance to chelation. Aims To study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX treatment in relation to ferritin level. Methods Only BTM patients with hepatitis negative screening (checked every year) and on treatment with DFO for at least five years and with DFX for four years were enrolled. Liver function tests including serum bilirubin, alanine transferase (ALT), aspartate transferase (AST), albumin, insulin-like growth factor – I (IGF-I) and serum ferritin concentrations were followed every six months in 40 patients with BTM. Results DFX treatment (20 mg/kg/day) significantly decreased serum ferritin level in patients with BTM; this was associated with a significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum ferritin concentrations ( r = 0.45 and 0.33 respectively, p < 0.05). IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels. The negative correlation between serum ferritin concentrations and ALT suggests that the impairment of hepatic function negatively affect IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis. Conclusions Some impairment of liver function can occur

  20. Determination of the integrated CT number of the whole liver in patients with severe hepatitis. As an indicator of the functional reserve of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Kumahara, Tadashi; Muto, Yasutoshi; Moriwaki, Hisataka; Yoshida, Takashi; Tomita, Eiichi (Gifu Univ. (Japan). Faculty of Medicine)

    1989-06-01

    A study was conducted to estimate the functional reserve of the liver of patients with severe hepatitis by computed tomography (CT), in particular employing the integrated CT number of the whole liver (ICTN). ICTN was calculated by integrating the product of 'area' times 'mean CT number' of the liver in each CT slice for the entire height of the liver. The following results were obtained: (1) In patients with fulminant hepatitis (FH) as well as those with subacute hepatitis (SAH), ICTN was found to be significantly lower as compared to that of patients with acute hepatitis (AH) or non-hepatic diseases. In addition, in FH and SAH patients, ICTN showed a larger degree of decrease when compared with such conventional parameters as either estimated liver volume or mean hepatic CT number. Thus, ICTN seems to more sensitively reflect the changes in functional reserve of the liver. (2) ICTN showed significant positive correlations with prothrombin time and plasma BCAA/AAA ratio, and a significant negative correlation with plasma methionine level. (3) Time course of changes in ICTN correlated well with the clinical features of severe hepatitis. In particular, patients with initial ICTN values above 20 lcenter dotHU/m/sup 2/ of body surface area showed significantly higher survival rate than those with initial ICTN below 20. In conclusion, ICTN well indicates the functional reserve of the liver, and is further suggested to be valuable as a parameter to predict the prognosis of patients with severe hepatitis. (author).

  1. Biochemical liver function test parameter levels in relation to treatment response in liver metastatic colorectal patients treated with FOLFOX4 with or without bevacizumab

    Directory of Open Access Journals (Sweden)

    Denić Kristina

    2016-01-01

    Full Text Available Introduction. Combined use of bevacizumab and conventional anticancer drugs leads to a significant improvement of treatment response in patients with metastatic colorectal carcinoma (CRC. Conventional treatment protocols exert undesired effects on the liver tissue. Hepatotoxic effects are manifested as a disturbance of liver function test parameters. The relation between clinical outcome and disorder of biochemical parameters has not been completely evaluated. Objective. The objective of our study was to examine whether clinical outcome in patients with liver metastatic CRC correlates with the level of liver function test parameters. Methods. The study included 96 patients with untreated liver metastatic CRC who received FOLFOX4 protocol with or without bevacizumab. Biochemical liver parameters were performed before and after the treatment completion. Treatment response was evaluated as disease regression, stable disease, and disease progression. The patients were divided into three groups according to the accomplished treatment response. Results. In the group of patients with disease regression the post-treatment levels of aspartate aminotransferase, alanine aminotransferase, and bilirubin were statistically significantly increased. In contrast to this, gamma-glutamyltransferase and protein post-treatment values were significantly lower in relation to initial values. In patients with stable disease, difference was found only in the level of proteins being lower after the treatment. In patients with disease progression, values of aspartate aminotransferase and bilirubin were significantly increased after completed treatment. Conclusion. Treatment responses are not completely associated with the level of liver function test parameters. The only parameter which correlated with treatment response is gamma-glutamyltransferase. Its decrease is accompanied with disease regression.

  2. Effects of Aqueous Stem Extract of Massularia Acuminata on Some Liver Function Indices of Male Rats

    Directory of Open Access Journals (Sweden)

    Musa Toyin Yakubu

    2012-09-01

    Full Text Available Background: Massularia acuminata has been claimed to be used in managingseveral ailments in folk medicine and in some instances substantiated withscientific data. This however has been without recourse to its safety. Therefore,aqueous stem extract of M. acuminata was evaluated for its effects on somefunction indices of the liver of male rats.Methods: Sixty, male rats were grouped into 4 (A, B, C and D such that Group A(control was orally administered 1cm3 of distilled water while those in groups B, Cand D received orally 1 cm3 of extract corresponding to 250, 500 and 1000 mg/kgbody weight respectively. Some biochemical parameters of liver function wereevaluated in the animals after 1, 7 and 21 daily doses.Results: The extract significantly decreased (P<0.05 the activity of alkalinephosphatase in the liver of rats throughout the experimental period. This decreasewas accompanied by corresponding increase in the serum enzyme. In contrast, allthe doses of the extract increased the activities of both the AST and ALT in the liverand serum aspartate aminotransferase and alanine aminotransferase as well asthe concentrations of serum total bilirubin, protein and albumin.Conclusion: This study has revealed that the aqueous stem extract of Massulariaacuminata at the doses of 250-1000 mg/kg body weight hampered the normalfunctioning of the liver of male rats and is therefore not safe for oral consumption atthe doses investigated.

  3. Dietary restriction reduces blood lipids and ameliorates liver function of mice with hyperlipidemia.

    Science.gov (United States)

    Gao, Hai-Tao; Cheng, Wen-Zhao; Xu, Qian; Shao, Lin-Xiang

    2017-02-01

    Dietary restriction (DR) can delay senescence, prolong lifespan of mammals and improve their learning-memory activity. The purpose of the study was to explore the effects of DR on hypolipidemic action and liver function of mice with hyperlipidemia. To investigate these effects, hyperlipidemia mouse models were established with high-fat diet (HFD) (34% of energy), then randomly divided into HFD group, DR30% group and DR50% group. Mice in DR30% and DR50% group were respectively supplied with HFD as much as about 70% and 50% of the consumption of HFD in the mice of HFD group. Rats in control group were fed routinely. After DR for 5 weeks, the average body weight, liver weight, liver index, serum lipids and glucose levels in both DR groups decreased significantly as compared with the HFD group (PLDH) levels and the ratio of LDL-C/HDL-C in the DR50% group (Pfunction. Western blotting showed that DR significantly increased the expression of silent mating type information regulation 2 homolog 1 (SIRT1) in liver and adipose, while notably decreased the expression of peroxisome proliferators-activated receptors-gamma (PPARγ) in adipose (Pfunction.

  4. [Biological function prediction of mir-210 in the liver of acute cold stress rat].

    Science.gov (United States)

    Guo, Wen-Jin; Lian, Shuai; Guo, Jing-Ru; Zhai, Jun-Fei; Zhang, Yu-Chen; Li, Yue; Zhen, Li; Ji, Hong; Yang, Huan-Min

    2016-04-25

    The study was aimed to observe mir-210 expression in liver tissue of acute cold stress rat and predict the function of mir-210 in cold stress. Thirty SPF Wistar male rats which were 12-week-old and weighed (340 ± 20) g were used. The rats were pre-fed in normal room temperature for one week, and then were randomly divided into acute cold stress group at (4 ± 0.1) °C and normal control group at (24 ± 0.1) °C. After the rats were treated with cold stress for 12 h, the liver tissue was extracted and the gene expression of mir-210 was assayed using qRT-PCR. The results demonstrated that the gene expression of mir-210 was significantly enhanced in acute cold stress group compared with that in normal control group (n = 3, P kinds of target genes such as E2F3, RAD52, ISCU and Ephrin-A3 are more relative with liver cold stress. ISCU regulates the cell respiratory metabolism and Ephrin-A3 is related with cell proliferation and apoptosis. On the other hand, up-regulated mir-210 affects the DNA repairing mechanism which usually leads to genetic instabilities. Our results suggest that cold stress-induced up-regulation of mir-210 in liver harmfully influences cell growth, energy metabolism and hereditary.

  5. The Evaluation of Liver Function Using Liver-Specific MR Contrast Agents%MR特异性对比剂肝功能评价研究

    Institute of Scientific and Technical Information of China (English)

    冯汝静; 黄仲奎

    2013-01-01

    Objective To evaluate the application value of liver-specific contrast agents in evaluating liver function. Methods Thirty six patients with liver dysfunction underwent MRI enhanced examination using liver specific contrast a-gent,including Gd BOPTA in 28 cases and Gd EOB DTPA in 12 cases, as well as MR conventional raulti phase enhanced scan. The liver function were evaluated with the biliary display in the hepatobiliary excretion phase. Results According to the visibility score of biliary in the hepatobiliary excretion phase images, 33 patients' liver function can be classified as grade A (grade > 16 points) in 17 cases,grade B (6 to 15 points) in 10 cases,grade C (6 to 15 points)in 6 cases. The consistency of image grading and clinical Child-pugh grading for liver function were good in the 33 patients (K = 0. 570, P = 0. 000). Especially, excellent consistency was presented in 10 cases using Gd EOB DTPA agent (K = 0. 804, P = 0.000). Conclusion The liver function could be evaluated by the liver-specific contrast agent enhanced MR images.%目的 探讨MRI特异性对比剂对肝功能评价的应用价值.方法 选择2011年至2012年行肝脏MRI检查的33例肝功能障碍患者资料.行肝脏常规MRI平扫、肝脏MRI特异性对比剂[钆贝葡胺(Gd-BOPTA)26例,钆塞酸二钠(Gd-EOB-DTPA) 10例]增强,对肝胆排泄期的各级胆管显示情况进行5级评分,再根据各级胆管显示总评分进行肝功能MRI分级.结果 33例患者的肝功能MR分级与临床Child-Pugh分级一致性良好(K=0.570,P=o.ooo),其中10例Gd-EOB-DTPA增强肝功能MR分级与临床Child-Pugh分级吻合程度极佳(K=0.804,P=0.000).结论 观察肝脏MRI特异性对比剂增强肝胆排泄期的胆管显示情况,可以评价整个肝脏肝功能情况.

  6. Biomarkers of fibrosis and impaired liver function in chronic hepatitis C: how well do they predict clinical outcomes?

    DEFF Research Database (Denmark)

    Peters, L.; Rockstroh, J.K.

    2010-01-01

    PURPOSE OF REVIEW: To review the recent literature on the prognostic value of biomarkers of liver fibrosis and impaired liver function in patients with chronic hepatitis C with or without HIV coinfection. RECENT FINDINGS: A combination of standard blood tests seems to be useful in identifying...

  7. Hepatocyte function within a stacked double sandwich culture plate cylindrical bioreactor for bioartificial liver system.

    Science.gov (United States)

    Xia, Lei; Arooz, Talha; Zhang, Shufang; Tuo, Xiaoye; Xiao, Guangfa; Susanto, Thomas Adi Kurnia; Sundararajan, Janani; Cheng, Tianming; Kang, Yuzhan; Poh, Hee Joo; Leo, Hwa Liang; Yu, Hanry

    2012-11-01

    Bioartificial liver (BAL) system is promising as an alternative treatment for liver failure. We have developed a bioreactor with stacked sandwich culture plates for the application of BAL. This bioreactor design addresses some of the persistent problems in flat-bed bioreactors through increasing cell packing capacity, eliminating dead flow, regulating shear stress, and facilitating the scalability of the bioreactor unit. The bioreactor contained a stack of twelve double-sandwich-culture plates, allowing 100 million hepatocytes to be housed in a single cylindrical bioreactor unit (7 cm of height and 5.5 cm of inner diameter). The serial flow perfusion through the bioreactor increased cell-fluid contact area for effective mass exchange. With the optimal perfusion flow rate, shear stress was minimized to achieve high and uniform cell viabilities across different plates in the bioreactor. Our results demonstrated that hepatocytes cultured in the bioreactor could re-establish cell polarity and maintain liver-specific functions (e.g. albumin and urea synthesis, phase I&II metabolism functions) for seven days. The single bioreactor unit can be readily scaled up to house adequate number of functional hepatocytes for BAL development.

  8. Cultivation of adult rat hepatocytes on 3T3 cells: expression of various liver differentiated functions.

    Science.gov (United States)

    Kuri-Harcuch, W; Mendoza-Figueroa, T

    1989-08-01

    Adult rat hepatocytes were maintained in culture for at least 1 month without losing the expression of their differentiated functions; they were cultured on lethally treated 3T3 fibroblasts inoculated at 35,000 cells/cm2 with medium containing 10-25 micrograms/ml hydrocortisone. Hepatocytes showed their typical morphology; they formed bile canaliculi, microvilli, and intercellular junctions with desmosomes and nexus; some formed structures that may resemble the perisinusoidal space of Disse. In addition, they showed DNA synthesis and expressed some liver-specific functions. They synthesized albumin and other proteins, which were exported to the culture medium. Like parenchymal liver cells in vivo, de novo fatty acid synthesis and esterification took place, and more than 80% of the lipids synthesized by the hepatocytes were secreted into the medium as triglycerides; they also showed cytochrome-P450 activity that was inducible with phenobarbital, suggesting that the hepatocytes have the capacity to metabolize drugs. These culture conditions allow the study of various hepatocyte differentiated functions, and they may provide the means to analyze the effect on liver of hormones, viruses and hepatotoxic chemicals and drugs; they may also indicate conditions adequate for serial growth of hepatocytes.

  9. Liver regeneration.

    Science.gov (United States)

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-04-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  10. Early changes of graft function, cytokines and superoxide dismutase serum levels after donor liver denervation and Kupffer cell depletion in a rat-to-rat liver transplantation model

    Institute of Scientific and Technical Information of China (English)

    Hong Zhu; Catena Marco; Ferla Gianfranco

    2009-01-01

    BACKGROUND:Hepatic reperfusion injury may cause acute inlfammatory damage, producing signiifcant organ dysfunction, and is an important problem in liver transplantation. This experiment aimed to study early changes of hepatic function after donor liver denervation and Kupffer cell depletion in rat-to-rat liver transplantation and to evaluate the effect of pre-treatment on liver reperfusion injury. METHODS:Donor rats were divided into four groups:control group; group G was pre-treated with gadolinium chloride (G), an inhibitor of Kupffer cells; group H with hexamethonium (H), a sympathetic ganglionic blocking agent; and group HG, with combined H and G pre-treatment. Under the same conditions, serum alanine aminotransferase (ALT), arterial ketone body ratio (AKBR), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and superoxide dismutase (SOD) of recipient rats were assessed at 4, 8, 16 and 24 hours after liver transplantation. Histological studies of the grafts were compared. RESULTS:HG pre-treatment signiifcantly decreased ALT, TNF-α, and IL-6 levels, increased AKBR and SOD levels, and demonstrated less pathological damage at 8, 16 and 24 hours compared with the control group. Similar trends were also found in the other groups (G and H). However, the differences among them were not signiifcant at 4 post-operative hours.CONCLUSIONS:Donor denervation and Kupffer cell depletion had preventive effect on liver reperfusion injury. HG pre-treatment is a feasible and reproducible method to protect grafts from reperfusion injury.

  11. Linking multidimensional functional diversity to quantitative methods: a graphical hypothesis--evaluation framework.

    Science.gov (United States)

    Boersma, Kate S; Dee, Laura E; Miller, Steve J; Bogan, Michael T; Lytle, David A; Gitelman, Alix I

    2016-03-01

    Functional trait analysis is an appealing approach to study differences among biological communities because traits determine species' responses to the environment and their impacts on ecosystem functioning. Despite a rapidly expanding quantitative literature, it remains challenging to conceptualize concurrent changes in multiple trait dimensions ("trait space") and select quantitative functional diversity methods to test hypotheses prior to analysis. To address this need, we present a widely applicable framework for visualizing ecological phenomena in trait space to guide the selection, application, and interpretation of quantitative functional diversity methods. We describe five hypotheses that represent general patterns of responses to disturbance in functional community ecology and then apply a formal decision process to determine appropriate quantitative methods to test ecological hypotheses. As a part of this process, we devise a new statistical approach to test for functional turnover among communities. Our combination of hypotheses and metrics can be applied broadly to address ecological questions across a range of systems and study designs. We illustrate the framework with a case study of disturbance in freshwater communities. This hypothesis-driven approach will increase the rigor and transparency of applied functional trait studies.

  12. Correlation between plasma endothelin-1 levels and severity of septic liver failure quantified by maximal liver function capacity (LiMAx test). A prospective study.

    Science.gov (United States)

    Kaffarnik, Magnus F; Ahmadi, Navid; Lock, Johan F; Wuensch, Tilo; Pratschke, Johann; Stockmann, Martin; Malinowski, Maciej

    2017-01-01

    To investigate the relationship between the degree of liver dysfunction, quantified by maximal liver function capacity (LiMAx test) and endothelin-1, TNF-α and IL-6 in septic surgical patients. 28 septic patients (8 female, 20 male, age range 35-80y) were prospectively investigated on a surgical intensive care unit. Liver function, defined by LiMAx test, and measurements of plasma levels of endothelin-1, TNF-α and IL-6 were carried out within the first 24 hours after onset of septic symptoms, followed by day 2, 5 and 10. Patients were divided into 2 groups (group A: LiMAx ≥100 μg/kg/h, moderate liver dysfunction; group B: LiMAx <100 μg/kg/h, severe liver dysfunction) for analysis and investigated regarding the correlation between endothelin-1 and the severity of liver failure, quantified by LiMAx test. Group B showed significant higher results for endothelin-1 than patients in group A (P = 0.01, d5; 0.02, d10). For TNF-α, group B revealed higher results than group A, with a significant difference on day 10 (P = 0.005). IL-6 showed a non-significant trend to higher results in group B. The Spearman's rank correlation coefficient revealed a significant correlation between LiMAx and endothelin-1 (-0.434; P <0.001), TNF-α (-0.515; P <0.001) and IL-6 (-0.590; P <0.001). Sepsis-related hepatic dysfunction is associated with elevated plasma levels of endothelin-1, TNF-α and IL-6. Low LiMAx results combined with increased endothelin-1 and TNF-α and a favourable correlation between LiMAx and cytokine values support the findings of a crucial role of Endothelin-1 and TNF-α in development of septic liver failure.

  13. The serum nT-proBnP in Patients with Cirrhosis:Relationship to Cardiac dysfunction and liver Function

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Objective To detect the values of NT-proBNP and evaluate its relationship with liver function, cardiac structure, and cardiac function which was evaluated by echocardiography in patients with liver cirrhosis. Methods A total of 50 liver cirrhotic patients and 11 healthy controls were studied by two dimensional Doppler echocardiography. Liver cirrhotic patients were divided into group A, B and C according to the Child-Pugh score. Cardiac dimensions and left and right ventricular functions were also evaluated. At the same time, the serum NT-proBNP of liver cirrhotic patients and healthy controls were detected, respectively. Results By Comparison between two groups, we found that the values of LVd, LAs, LVPW, AAO, A Wave, RVOTs, PV and NT-proBNP in liver cirrhosis group were higher than those in control group, whereas the value of E/A decreased. As for the value of LAs and serum NT-proBNP, A and B group were all lower than C group. With LAs>35 mm, the number of cases in liver cirrhosis group was higher than that in control group. So did that With E/A Conclusions The cardiac dysfunction confirmed the existence of cirrhotic cardiomyopathy. More clinical implications were found in liver cirrhotic patients with increased values of serum NT-proBNP.

  14. Effects of Shark Hepatic Stimulator Substance on the Function and Antioxidant Capacity of Liver Mitochondria in an Animal Model of Acute Liver Injury

    Institute of Scientific and Technical Information of China (English)

    Qiu-Ling FAN; Cai-Guo HUANG; Yan JIN; Bo FENG; Hui-Nan MIAO; Wen-Jie LI; Bing-Hua JIAO; Qin-Sheng YUAN

    2005-01-01

    This study was carried out to investigate whether shark hepatic stimulator substance (HSS) can prevent acute liver injury and affect mitochondrial function and antioxidant defenses in a rat model of thioacetamide (TAA)-induced liver injury. The acute liver injury was induced by two intraperitoneal injections of TAA (400 mg/kg) in a 24 h interval. In the TAA plus shark HSS group, rats were treated with shark HSS (80 mg/kg) 1 h prior to each TAA injection. In this group, serum liver enzyme activities were significantly lower than those in the TAA group. The mitochondrial respiratory control ratio was improved, and the mitochondrial respiratory enzyme activities were increased in the TAA plus shark HSS group. The mitochondrial antioxidant enzyme activities and glutathione level were higher in the TAA plus shark HSS group than in the TAA group. These results suggest that the protective effect of shark HSS against TAA-induced acute liver injury may be a result of the restoration of the mitochondrial respiratory function and antioxidant defenses and decreased oxygen stress.

  15. Transplantation of fetal liver tissue suspension into the spleens of adult syngenic rats: inducibility of cytochrome P450 dependent monooxygenase functions by beta-naphthoflavone, phenobarbital and dexamethasone.

    Science.gov (United States)

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

    1999-01-01

    EROD and ECOD were significantly increased after BNF or PB treatment at all three time points after surgery, and ECOD after DEX administration, but at 4 and 6 months after transplantation only. END was only induced after DEX treatment at 6 months after transplantation. With the livers of both transplant recipients and control rats EROD and ECOD were increased after BNF induction and EROD, ECOD, and END after PB treatment at all three time points after transplantation. After DEX administration END was significantly enhanced only at 2 and 4 months after transplantation, ECOD was decreased at 2 and 4 months, and EROD was diminished at all three time points after surgery. Transplantation of fetal liver tissue suspensions into the spleens did not influence monooxygenase functions and their inducibility within the respective livers of the animals. These results demonstrate that transplanted liver cells originating from syngenic fetal liver tissue suspensions display P450 dependent monooxygenase functions which are, simi lar to normal adult liver, inducible by BNF, PB and DEX. Both monooxygenase functions and their inducibility within the transplant containing spleens display quantitative and qualitative developmental changes.

  16. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    Energy Technology Data Exchange (ETDEWEB)

    Chapiro, Julius; Savic, Lynn Jeanette [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Charite Universitaetsmedizin, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Lin, MingDe [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); U/S Imaging and Interventions (UII), Philips Research North America, Briarcliff Manor, NY (United States); Lesage, David [Philips Research, Medisys, Suresnes (France)

    2015-07-15

    This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

  17. Lipid profiling and transcriptomic analysis reveals a functional interplay between estradiol and growth hormone in liver

    DEFF Research Database (Denmark)

    Fernández-Pérez, Leandro; Santana-Farré, Ruymán; Mirecki-Garrido, Mercedes de;

    2014-01-01

    17β-estradiol (E2) may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2......-differentiated functions. E2 influenced genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, immune, and male-specific responses. E2 induced a female-pattern of gene expression and inhibited GH-regulated STAT5b targeted genes. E2 did not prevent the inhibitory effects...

  18. In vitro gene regulatory networks predict in vivo function of liver

    Directory of Open Access Journals (Sweden)

    Ang Choo Y

    2010-11-01

    Full Text Available Abstract Background Evolution of toxicity testing is predicated upon using in vitro cell based systems to rapidly screen and predict how a chemical might cause toxicity to an organ in vivo. However, the degree to which we can extend in vitro results to in vivo activity and possible mechanisms of action remains to be fully addressed. Results Here we use the nitroaromatic 2,4,6-trinitrotoluene (TNT as a model chemical to compare and determine how we might extrapolate from in vitro data to in vivo effects. We found 341 transcripts differentially expressed in common among in vitro and in vivo assays in response to TNT. The major functional term corresponding to these transcripts was cell cycle. Similarly modulated common pathways were identified between in vitro and in vivo. Furthermore, we uncovered the conserved common transcriptional gene regulatory networks between in vitro and in vivo cellular liver systems that responded to TNT exposure, which mainly contain 2 subnetwork modules: PTTG1 and PIR centered networks. Interestingly, all 7 genes in the PTTG1 module were involved in cell cycle and downregulated by TNT both in vitro and in vivo. Conclusions The results of our investigation of TNT effects on gene expression in liver suggest that gene regulatory networks obtained from an in vitro system can predict in vivo function and mechanisms. Inhibiting PTTG1 and its targeted cell cyle related genes could be key machanism for TNT induced liver toxicity.

  19. In vitro gene regulatory networks predict in vivo function of liver

    Science.gov (United States)

    2010-01-01

    Background Evolution of toxicity testing is predicated upon using in vitro cell based systems to rapidly screen and predict how a chemical might cause toxicity to an organ in vivo. However, the degree to which we can extend in vitro results to in vivo activity and possible mechanisms of action remains to be fully addressed. Results Here we use the nitroaromatic 2,4,6-trinitrotoluene (TNT) as a model chemical to compare and determine how we might extrapolate from in vitro data to in vivo effects. We found 341 transcripts differentially expressed in common among in vitro and in vivo assays in response to TNT. The major functional term corresponding to these transcripts was cell cycle. Similarly modulated common pathways were identified between in vitro and in vivo. Furthermore, we uncovered the conserved common transcriptional gene regulatory networks between in vitro and in vivo cellular liver systems that responded to TNT exposure, which mainly contain 2 subnetwork modules: PTTG1 and PIR centered networks. Interestingly, all 7 genes in the PTTG1 module were involved in cell cycle and downregulated by TNT both in vitro and in vivo. Conclusions The results of our investigation of TNT effects on gene expression in liver suggest that gene regulatory networks obtained from an in vitro system can predict in vivo function and mechanisms. Inhibiting PTTG1 and its targeted cell cyle related genes could be key machanism for TNT induced liver toxicity. PMID:21073692

  20. Comparison of conventional PCR, quantitative PCR, bacteriological culture and the Warthin Starry technique to detect Leptospira spp. in kidney and liver samples from naturally infected sheep from Brazil.

    Science.gov (United States)

    Fornazari, Felipe; da Silva, Rodrigo Costa; Richini-Pereira, Virginia Bodelão; Beserra, Hugo Enrique Orsini; Luvizotto, Maria Cecília Rui; Langoni, Helio

    2012-09-01

    Leptospirosis is an infectious disease of worldwide importance. The development of diagnostic techniques allows sick animals to be identified, reservoirs to be eliminated and the disease prevented and controlled. The present study aimed to compare different techniques for diagnosing leptospirosis in sheep. Samples of kidney, liver and blood were collected from 465 animals that originated from a slaughterhouse. The sera were analyzed by the Microscopic Agglutination Test (MAT), and kidney and liver samples of seropositive animals were analyzed using four techniques: bacteriological culture, the Warthin Starry (WS) technique, conventional PCR (cPCR), and quantitative PCR (qPCR). With the MAT, 21 animals were positive (4.5%) to serovars Hardjo (n=12), Hebdomadis (n=5), Sentot (n=2), Wolfii (n=1) and Shermani (n=1). Titers were 100 (n=10), 200 (n=2), 400 (n=6) and 1600 (n=3). No animal was positive by bacteriological culture; four animals were positive by the WS technique in kidney samples; six animals were positive by cPCR in kidney samples; and 11 animals were positive by qPCR, eight of which in kidney samples and three in liver. The bacterial quantification revealed a median of 4.3 bacteria/μL in liver samples and 36.6 bacteria/μL in kidney samples. qPCR presented the highest sensitivity among the techniques, followed by cPCR, the WS technique and bacteriological culture. These results indicate that sheep can carry leptospires of the Sejroe serogroup, and demonstrate the efficiency of quantitative PCR to detect Leptospira spp. in tissue samples.

  1. Perioperative changes of ventricular function and three indicators of myocardial injury during orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    HEI Zi-qing; LIU De-zhao; LUO Chen-fang; LI Shang-rong; MA Wu-hua; LUO Gang-jian

    2006-01-01

    @@ Patients undergoing orthotopic liver transplantation may develop significant haemodynamic instability, especially during anhepatic phase and immediately after reperfusion of the graft. The haemodynamic instability may be caused directly by myocardial depression due to pathogenic substances released from the liver, or by acute blood loss.1 Creatine kinase(CK) and its MB fraction (CK-MB) are sensitive and specific indicators to reflect myocardial damage.2 Cardiac troponin I (cTnl) is a specific and sensitive marker of myocardial necrosis.3 This study assessed perioperative cardiac function using three indicators (CK,CK-MB,and CTnl) to evaluate perioperative myocardial damage.$4This study was supported by grants from the National Natural Science Foundation of China (No. 30271254) and Guangdong Medical Development Foundation (No. 2004B35001005).

  2. Lipid profiling and transcriptomic analysis reveals a functional interplay between estradiol and growth hormone in liver.

    Directory of Open Access Journals (Sweden)

    Leandro Fernández-Pérez

    Full Text Available 17β-estradiol (E2 may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2, through its interaction with the estrogen receptor, exerts direct effects on liver. Hypothyroidism also affects endocrine and metabolic functions of the liver, rendering a metabolic phenotype with features that mimic deficiencies in E2 or GH. In this work, we combined the lipid and transcriptomic analysis to obtain comprehensive information on the molecular mechanisms of E2 effects, alone and in combination with GH, to regulate liver functions in males. We used the adult hypothyroid-orchidectomized rat model to minimize the influence of internal hormones on E2 treatment and to explore its role in male-differentiated functions. E2 influenced genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, immune, and male-specific responses. E2 induced a female-pattern of gene expression and inhibited GH-regulated STAT5b targeted genes. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. The combination of E2 and GH decreased transcriptional immune responses. E2 decreased the hepatic content of saturated fatty acids and induced a transcriptional program that seems to be mediated by the activation of PPARα. In contrast, GH inhibited fatty acid oxidation. Both E2 and GH replacements reduced hepatic CHO levels and increased the formation of cholesterol esters and triacylglycerols. Notably, the hepatic lipid profiles were endowed with singular fingerprints that may be used to segregate the effects of different hormonal replacements. In summary, we provide in vivo evidence that E2 has a significant impact on lipid content and transcriptome in male liver and that E2 exerts a

  3. Liver and Kidney on Chips: Microphysiological Models to Understand Transporter Function.

    Science.gov (United States)

    Chang, S Y; Weber, E J; Ness, Kp Van; Eaton, D L; Kelly, E J

    2016-11-01

    Because of complex cellular microenvironments of both the liver and kidneys, accurate modeling of transport function has remained a challenge, leaving a dire need for models that can faithfully recapitulate both the architecture and cell-cell interactions observed in vivo. The study of hepatic and renal transport function is a fundamental component of understanding the metabolic fate of drugs and xenobiotics; however, there are few in vitro systems conducive for these types of studies. For both the hepatic and renal systems, we provide an overview of the location and function of the most significant phase I/II/III (transporter) of enzymes, and then review current in vitro systems for the suitability of a transporter function study and provide details on microphysiological systems that lead the field in these investigations. Microphysiological modeling of the liver and kidneys using "organ-on-a-chip" technologies is rapidly advancing in transport function assessment and has emerged as a promising method to evaluate drug and xenobiotic metabolism. Future directions for the field are also discussed along with technical challenges encountered in complex multiple-organs-on-chips development. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  4. Do kidney histology lesions predict long-term kidney function after liver transplantation?

    Science.gov (United States)

    Kamar, Nassim; Maaroufi, Chakib; Guilbeau-Frugier, Céline; Servais, Aude; Meas-Yedid, Vannary; Tack, Ivan; Thervet, Eric; Cointault, Olivier; Esposito, Laure; Guitard, Joelle; Lavayssière, Laurence; Panterne, Clarisse; Muscari, Fabrice; Bureau, Christophe; Rostaing, Lionel

    2012-01-01

    Histological renal lesions observed after liver transplantation are complex, multifactorial, and interrelated. The aims of this study were to determine whether kidney lesions observed at five yr after liver transplantation can predict long-term kidney function. Ninety-nine liver transplant patients receiving calcineurin inhibitor (CNI)-based immunosuppression, who had undergone a kidney biopsy at 60±48 months post-transplant, were included in this follow-up study. Kidney biopsies were scored according to the Banff classification. Estimated glomerular filtration rate (eGFR) was assessed at last follow-up, that is, 109±48 months after liver transplantation. eGFR decreased from 92±33 mL/min at transplantation to 63±19 mL/min after six months, to 57±17 mL/min at the kidney biopsy, to 54±24 mL/min at last follow-up (p<0.0001). At last follow-up, only three patients required renal replacement therapy. After the kidney biopsy, 13 patients were converted from CNIs to mammalian target of rapamycin inhibitors, but no significant improvement in eGFR was observed after conversion. Elevated eGFR at six months post-transplant and a lower fibrous intimal thickening score (cv) observed at five yr post-transplant were the two independent predictive factors for eGFR≥60 mL/min at nine yr post-transplant. Long-term kidney function seems to be predicted by the kidney vascular lesions.

  5. [Monoethylglycinexylidide--a metabolite of lidocaine--as an index of liver function in chronic hepatic parenchymal diseases].

    Science.gov (United States)

    Kupcová, V; Turecký, L; Szántová, M; Schmidtová, K

    1999-01-01

    The changes of biotransformation enzyme system (b.e.s.) activity and capacity in liver diseases significantly influence the metabolism of various xenobiotics. Lidocaine is metabolised through oxidative N-deethylation by b.e.s. resulting in the production of monoethylglycinexylide (MEGX). The aim of this study was the determination of serum MEGX concentration as a model substance for indirect evaluation of liver b.e.s. function in patients with liver steatofibrosis and cirrhosis and the assessment of the possibilities to use it as a quantitave test of liver functional state. The study group consisted of 53 patients, 36 of them with liver disease of different etiology (postviral, ethyltoxic, cryptogenic, liver cirrhosis on the basis of autoimmune hepatitis, liver cirrhosis induced by primary sclerosing cholangitis, primary biliary cirrhosis in the stage of cirrhosis, Wilson's disease in the stage of cirrhosis), 7 patients with liver steatofibrosis and 10 control persons. After intravenous administration of lidocaine (1 mg/kg of body weight), concentration of MEGX was assessed by fluorescence polarization immunoassay (FPIA) using Tdx system in venous blood. The concentration was assesed prior to administration of lidocaine and 15 and 30 minutes after. In the group of liver steatofibrosis the concentrations in the 15th minute after administration were lower comparing to controls, in the 30th minute the difference was less significant. The values of MEGX in cirrhosis group were significantly decreased 15 and 30 minutes after lidocaine administration in comparison with control group. The cirrhosis group was divided into two subgroups: compensated (Ci c) and decompensated (Ci d) and independently of this division into three parts according to score system of Child-Pugh classification (Ci A, Ci B, Ci C). The concentrations 15 and 30 minutes after lidocaine administration in patients with Ci c and Ci d were significantly different, similarly there were statistically

  6. Renal Function Improvement by Telbivudine in Liver Transplant Recipients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Wei-Chen Lee

    2017-01-01

    Full Text Available Chronic renal failure is a frequent complication in liver transplantation. Telbivudine, anti-hepatitis B virus (HBV nucleoside, can improve renal function. It is interesting if using telbivudine for prophylaxis of HBV recurrence has additional value on renal function improvement. 120 liver transplant recipients with lamivudine prophylaxis for HBV recurrence were 1 : 1 randomized into lamivudine-continuous (n=60 and telbivudine-replacement (n=60 groups. Fifty-eight patients in lamivudine-continuous group and 54 in telbivudine-replacement group completed the study. In telbivudine-replacement group, the estimated glomerular filtration rate (eGRF was improved from 63.0 ± 16.3 ml/min to 72.8 ± 21.1 ml/min at 12 months after telbivudine administration (p = 0.003. Stratifying the patients according to renal function staging, the eGRF was improved from 74.7 ± 6.9 ml/min to 84.2 ± 16.6 ml/min (p = 0.002 in 32 stage II patients and from 48.2 ± 7.3 ml/min to 59.7 ± 11.8 ml/min in 20 stage III patients after 12 months of telbivudine administration (p<0.001. Eleven (18.3% patients with telbivudine developed polyneuritis during the trial and post hoc following-up. In conclusion, renal function was improved by telbivudine in liver transplant recipients with long-term chronic kidney disease. However, the high incidence of polyneuritis induced by telbivudine has to be closely monitored. This trial is registered with ClinicalTrials NCT02447705.

  7. Quantitative ATP synthesis in human liver measured by localized 31P spectroscopy using the magnetization transfer experiment.

    Science.gov (United States)

    Schmid, A I; Chmelík, M; Szendroedi, J; Krssák, M; Brehm, A; Moser, E; Roden, M

    2008-06-01

    The liver plays a central role in intermediate metabolism. Accumulation of liver fat (steatosis) predisposes to various liver diseases. Steatosis and abnormal muscle energy metabolism are found in insulin-resistant and type-2 diabetic states. To examine hepatic energy metabolism, we measured hepatocellular lipid content, using proton MRS, and rates of hepatic ATP synthesis in vivo, using the 31P magnetization transfer experiment. A suitable localization scheme was developed and applied to the measurements of longitudinal relaxation times (T1) in six healthy volunteers and the ATP-synthesis experiment in nine healthy volunteers. Liver 31P spectra were modelled and quantified successfully using a time domain fit and the AMARES (advanced method for accurate, robust and efficient spectral fitting of MRS data with use of prior knowledge) algorithm describing the essential components of the dataset. The measured T1 relaxation times are comparable to values reported previously at lower field strengths. All nine subjects in whom saturation transfer was measured had low hepatocellular lipid content (1.5 +/- 0.2% MR signal; mean +/- SEM). The exchange rate constant (k) obtained was 0.30 +/- 0.02 s(-1), and the rate of ATP synthesis was 29.5 +/- 1.8 mM/min. The measured rate of ATP synthesis is about three times higher than in human skeletal muscle and human visual cortex, but only about half of that measured in perfused rat liver. In conclusion, 31P MRS at 3 T provides sufficient sensitivity to detect magnetization transfer effects and can therefore be used to assess ATP synthesis in human liver.

  8. Major influence of renal function on hyperlipidemia after living donor liver transplantation

    Science.gov (United States)

    Ling, Qi; Wang, Kai; Lu, Di; Guo, Hai-Jun; Jiang, Wen-Shi; He, Xiang-Xiang; Xu, Xiao; Zheng, Shu-Sen

    2012-01-01

    AIM: To investigate the impact of renal and graft function on post-transplant hyperlipidemia (PTHL) in living donor liver transplantation (LDLT). METHODS: A total of 115 adult patients undergoing LDLT from January 2007 to May 2009 at a single center were enrolled. Data were collected and analyzed by the China Liver Transplant Registry retrospectively. PTHL was defined as serum triglycerides ≥ 150 mg/dL or serum cholesterol ≥ 200 mg/dL or the need for pharmacologic treatment at the sixth month after LDLT. Early renal dysfunction (ERD) was defined as serum creatinine ≥ 2 mg/dL and/or the need for renal replacement therapy in the first post-transplant week. RESULTS: In 115 eligible patients, the incidence of PTHL was 24.3%. Recipients with PTHL showed a higher incidence of post-transplant cardiovascular events compared to those without PTHL (17.9% vs 4.6%, P = 0.037). Serum creatinine showed significant positive correlations with total serum triglycerides, both at post-transplant month 1 and 3 (P transplant serum creatinine levels (P transplant renal insufficiency (P transplant serum creatinine, graft-to-recipient weight ratio, graft volume/standard liver volume ratio, body mass index (BMI) and ERD were identified as risk factors for PTHL by univariate analysis. Furthermore, ERD [odds ratio (OR) = 9.593, P transplant renal dysfunction, which mainly results from pre-transplant renal insufficiency, contributes to PTHL. PMID:23323005

  9. Morphine Sulphate Toxicity on Liver Function Tests in Fructose-Induced Insulin Resistant Male Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Shahraki

    2014-02-01

    Full Text Available Background: Since liver is a gland which has an important role in drug metabolism, the present study was conducted to evaluate the effect of a single dose and repeated administration of morphine on LFT, blood sugar and fasting insulin resistance index in fructose- fed male rats. Materials and Methods: The experiment was performed on 36 Wistar-Albino male rats, which were divided into a control (A and three tests groups (B, C and D. The control group consumed tap water, but the test groups consumed fructose-enriched water (10%, w/v and received null, single, and repeated doses of morphine, respectively. At the end, animals were anesthetized and blood samples were collected. Liver enzymes, insulin and insulin resistance were measured. Data were analyzed by SPSS-11, using ANOVA and Tukey tests as post hoc test. Results were expressed as mean±SD and Statistical differences were recognized significant by p<0.05. Results: The results showed that all test groups were insulin resistant; alanine aminotransferase (ALT and asparatate aminotransferase (AST activity values in group D significantly increased compared to other groups while its plasma glucose and insulin values showed a significant decrease in comparison to other test groups. Conclusion: It seems that repeated morphine administration can affect liver function test (LFT and fasting Insulin resistance index (FIRI in fructose- fed male rats.

  10. Evaluation of Pistacia lentiscus fatty oil effects on glycemic index, liver functions and kidney functions of New Zealand rabbits.

    Science.gov (United States)

    Djerrou, Zouhir; Hamdi-Pacha, Y; Belkhiri, A M; Djaalab, H; Riachi, F; Serakta, M; Boukeloua, A; Maameri, Z

    2011-01-01

    Pistacia lentiscus fatty oil (PLFO) is a well known natural remedy in eastern Algeria folk medicine. It is widely used in the treatment of respiratory disorders and dermal burns. The present study has been carried out to investigate effects of this oil on fasting glucose and some functional parameters of the liver and kidney in white male New Zealand rabbits (Initial mean weight 1.95 Kg). PLFO was applied to tested rabbits (PLFO group) via rectal route, once daily 5-day per week, for six consecutive weeks at the dose of 1 ml/Kg body weight. The same number of animals (n=6) was not treated and served as control (CRL group). The results showed that PLFO was tolerated by rectal route. No significant differences were observed in body weights of the two groups. Biochemical analysis showed that aspartate transaminase (AST) and alanine transaminase (ALT) were significantly decreased in blood plasma at (P< 0.05) and (P< 0.01) respectively in PLFO group (Mann-Whitney test). On the other hand, the fasting glucose level (GLU) was significantly increased (Mann-Whitney test, P< 0.05), while the rest of the tested parameters (Albumin, total proteins, creatinine, urea) was not significantly affected. However, these variations have not biologic signification toxicity. The study concludes that PLFO is tolerable via rectal route; it is safe with no adverse effect on liver functions and renal functions with possible anti-glycogenesis activity.

  11. Whole genome scan to detect quantitative trait loci for conformation and functional traits in dairy cattle

    NARCIS (Netherlands)

    Schrooten, C.; Bovenhuis, H.; Coppieters, W.; Arendonk, van J.A.M.

    2000-01-01

    A granddaughter design was used to locate quantitative trait loci determining conformation and functional traits in dairy cattle. In this granddaughter design, consisting of 20 Holstein Friesian grandsires and 833 sons, genotypes were determined for 277 microsatellite markers covering the whole geno

  12. Ecosystem functioning and maximum entropyes production: a quantitative test of hypothes

    NARCIS (Netherlands)

    Meysman, F.J.R.; Bruers, S.

    2010-01-01

    The idea that entropy production puts a constraint on ecosystem functioning is quite popular in ecological thermodynamics. Yet, until now, such claims have received little quantitative verification. Here, we examine three ‘entropy production’ hypotheses that have been forwarded in the past. The firs

  13. 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

  14. Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver

    Directory of Open Access Journals (Sweden)

    Yang Bi

    2014-10-01

    Full Text Available Background/Aims: Liver is a vital organ and retains its regeneration capability throughout adulthood, which requires contributions from different cell populations, including liver precursors and intrahepatic stem cells. To overcome the mortality of hepatic progenitors (iHPs in vitro, we aim to establish reversibly immortalized hepatic progenitor cells from mouse embryonic liver. Methods and Results: Using retroviral system to stably express SV40 T antigen flanked with Cre/LoxP sites, we establish a repertoire of iHP clones with varied differentiation potential. The iHP cells maintain long-term proliferative activity and express varied levels of progenitor markers (Pou5f1/Oct4 and Dlk and hepatocyte markers (AFP, Alb and ApoB. Five representative iHP clones express hepatic/pancreatic transcription factors HNF3α/Foxa1, HNF3β/Foxa2, and HNF4α/MODY1. Dexamethasone is shown to promote the expression of hepatocyte markers AFP and TAT, along with ICG-uptake and glycogen storage functions in the iHP clones. Cre-mediated removal of SV40 T antigen reverses the proliferative activity of iHP cells. When iHP cells are subcutaneously implanted in athymic nude mice, no tumor formation is observed for up to 8 weeks. Conclusions: We demonstrate that the established iHP cells are stable, reversible, and non-tumorigenic hepatic progenitor-like cells, which should be valuable for studying liver organogenesis, metabolic regulations, and hepatic lineage-specific differentiation.

  15. Functional genomics bridges the gap between quantitative genetics and molecular biology.

    Science.gov (United States)

    Lappalainen, Tuuli

    2015-10-01

    Deep characterization of molecular function of genetic variants in the human genome is becoming increasingly important for understanding genetic associations to disease and for learning to read the regulatory code of the genome. In this paper, I discuss how recent advances in both quantitative genetics and molecular biology have contributed to understanding functional effects of genetic variants, lessons learned from eQTL studies, and future challenges in this field.

  16. Impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat

    Directory of Open Access Journals (Sweden)

    Jan Muhammad Shah

    2016-10-01

    Full Text Available Aim: The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Materials and Methods: Six mature, healthy goats (combine breed and sex with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w. and high doses (40 and 60 mg of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. Results: The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT and bilirubin on all timings, and increased (p<0.05 the serum glutamic oxaloacetic transaminase (SGOT and serum glutamate-pyruvate transaminase (SGPT levels for 48 h. Whereas the high doses of florfenicol (40 and 60 mg significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (p<0.01 increased at all timing points. Creatinine values were altered (p<0.01, <0.05 in increasing manner from 24 to 96 h. The high dose of 40 mg decreased the TP (p<0.05 for 72 h and 60 mg persisted same effect (p<0.01 up to 120 h. The indices of ALP, GGT, SGOT, and SGPT were raised (p<0.01, <0.05 at all timings. The bilirubin indexes also (p<0.05 elevated from 48 to 72. Conclusion: It was concluded that the high doses of florfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin.

  17. Clinical challenge: Deteriorating liver function in TB and HIV co-treatment

    Directory of Open Access Journals (Sweden)

    Francois Venter

    2013-06-01

    Full Text Available Editor’s note: In this section of the Journal, we present complex, real-world HIV medicine cases to two experienced clinicians working in very different environments, and ask them to describe the approach that they would take if they saw the case in their local hospital setting. In our first edition, a patient with deteriorating liver function is presented by Prof. Francois Venter and Dr Ntsakisi Masingi, and then discussed by Dr Sarah Stacey in Johannesburg and Dr Sarah Fidler in London.

  18. Comparison of yttrium-90 quantitative imaging by TOF and non-TOF PET in a phantom of liver selective internal radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Van Elmbt, Larry; Walrand, Stephan; Pauwels, Stanislas; Jamar, Francois [Department of Nuclear Medicine, Universite Catholique de Louvain, Brussels (Belgium); Vandenberghe, Stefaan, E-mail: Larry.vanElmbt@uclouvain.be [MEDISIP Research Group ELIS-IBITECH, University Hospital Ghent, Ghent University, Ghent (Belgium)

    2011-11-07

    The aim of this study is to determine the feasibility of achieving quantitative measurement in {sup 90}Y-microspheres liver selective internal radiotherapy (SIRT) by imaging {sup 90}Y with a conventional non-time of flight (TOF) PET device. Instead of the bremsstrahlung x-rays of the {beta}-decay, the low branch of e{sup -}- e{sup +} pair production in the {sup 90}Y-decay was used. The activity distribution in a phantom-simulated liver SIRT was obtained by direct {sup 90}Y-PET imaging. We tested a LYSO TOF PET and two GSO and BGO non-TOF PET scanners using a 3.6-l cylindrical phantom filled with the {sup 90}Y solution containing two sets of hot and cold spheres. The best hot contrast was obtained with the LYSO TOF. It was close to the expected value and remained constant, even for short acquisition times. The LYSO non-TOF was about 10% lower. The GSO performed similarly but degraded for shorter times whilst the BGO was the worst with 40% loss. For the cold spheres, the LYSO TOF and the GSO provided the best results, while the LYSO non-TOF and the BGO were the worst. {sup 90}Y PET imaging in liver SIRT is achievable with LYSO TOF. Conventional LYSO and GSO show a loss of contrast and require longer acquisition times. BGO imaging is not feasible for dosimetry calculation.

  19. An in vivo and in vitro comparison of CYP gene induction in mice using liver slices and quantitative RT-PCR.

    Science.gov (United States)

    Martignoni, Marcella; de Kanter, Ruben; Grossi, Pietro; Saturno, Grazia; Barbaria, Elena; Monshouwer, Mario

    2006-02-01

    The scope of this study was to compare in vitro and in vivo cytochrome P450 (CYP) gene induction in mice, using liver slices as an in vitro model. We have chosen to study mice to be able to better interpret CYP induction during long-term safety studies in this species. Mouse liver slices were incubated with beta-naphthoflavone (betaNF), phenobarbital (PB) or dexamethasone (DEX) for 24 h. In addition, in an in vivo study, mice were treated with the same compounds for three days. The mRNA expression of cyp1a1, cyp1a2, cyp2b10 and cyp3a11, which are important for drug metabolism and inducible by xenobiotics, were investigated in vivo and in vitro by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Both in mouse liver slices and in vivo, betaNF was found to be a potent inducer of cyp1a1 and to a lesser extent of cyp1a2. All three compounds induced cyp2b10 mRNA levels, while the cyp3a11 mRNA level was induced only by DEX. Overall, these data demonstrated a good predictive in vitro-in vivo correlation of CYP induction.

  20. Functional Human Liver Preservation and Recovery by Means of Subnormothermic Machine Perfusion

    NARCIS (Netherlands)

    Bruinsma, Bote G.; Avruch, James H.; Weeder, Pepijn D.; Sridharan, Gautham V.; Uygun, Basak E.; Karimian, Negin G.; Porte, Robert J.; Markmann, James F.; Yeh, Heidi; Uygun, Korkut

    2015-01-01

    There is currently a severe shortage of liver grafts available for transplantation. Novel organ preservation techniques are needed to expand the pool of donor livers. Machine perfusion of donor liver grafts is an alternative to traditional cold storage of livers and holds much promise as a modality

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

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    Pourhamzeh

    2016-06-01

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

  2. Effect of flow on the detoxification function of rat hepatocytes in a bioartificial liver reactor.

    Science.gov (United States)

    Roy, P; Washizu, J; Tilles, A W; Yarmush, M L; Toner, M

    2001-01-01

    Ethoxyresorufin-o-deethylation (EROD) can be used as a sensitive measure of hepatic detoxification function. In this study, we employed a fluorescence assay based on EROD to study the effect of varying Peclet number (or flow) on hepatic function in a microchannel flat-plate bioartificial liver (BAL) reactor containing a coculture of hepatocytes and fibroblasts. Static culture and reactor flow experiments established that: 1) a pseudo-steady-state detoxification rate could be attained at each Peclet number, 2) the steady-state detoxification rate increased nonlinearly with Peclet number (ranging from 167 to 2500), 3) the uptake rate of substrate was a linear function of cell surface substrate concentration (reactor for human application.

  3. Quantitative protein localization signatures reveal an association between spatial and functional divergences of proteins.

    Science.gov (United States)

    Loo, Lit-Hsin; Laksameethanasan, Danai; Tung, Yi-Ling

    2014-03-01

    Protein subcellular localization is a major determinant of protein function. However, this important protein feature is often described in terms of discrete and qualitative categories of subcellular compartments, and therefore it has limited applications in quantitative protein function analyses. Here, we present Protein Localization Analysis and Search Tools (PLAST), an automated analysis framework for constructing and comparing quantitative signatures of protein subcellular localization patterns based on microscopy images. PLAST produces human-interpretable protein localization maps that quantitatively describe the similarities in the localization patterns of proteins and major subcellular compartments, without requiring manual assignment or supervised learning of these compartments. Using the budding yeast Saccharomyces cerevisiae as a model system, we show that PLAST is more accurate than existing, qualitative protein localization annotations in identifying known co-localized proteins. Furthermore, we demonstrate that PLAST can reveal protein localization-function relationships that are not obvious from these annotations. First, we identified proteins that have similar localization patterns and participate in closely-related biological processes, but do not necessarily form stable complexes with each other or localize at the same organelles. Second, we found an association between spatial and functional divergences of proteins during evolution. Surprisingly, as proteins with common ancestors evolve, they tend to develop more diverged subcellular localization patterns, but still occupy similar numbers of compartments. This suggests that divergence of protein localization might be more frequently due to the development of more specific localization patterns over ancestral compartments than the occupation of new compartments. PLAST enables systematic and quantitative analyses of protein localization-function relationships, and will be useful to elucidate protein

  4. Quantitative protein localization signatures reveal an association between spatial and functional divergences of proteins.

    Directory of Open Access Journals (Sweden)

    Lit-Hsin Loo

    2014-03-01

    Full Text Available Protein subcellular localization is a major determinant of protein function. However, this important protein feature is often described in terms of discrete and qualitative categories of subcellular compartments, and therefore it has limited applications in quantitative protein function analyses. Here, we present Protein Localization Analysis and Search Tools (PLAST, an automated analysis framework for constructing and comparing quantitative signatures of protein subcellular localization patterns based on microscopy images. PLAST produces human-interpretable protein localization maps that quantitatively describe the similarities in the localization patterns of proteins and major subcellular compartments, without requiring manual assignment or supervised learning of these compartments. Using the budding yeast Saccharomyces cerevisiae as a model system, we show that PLAST is more accurate than existing, qualitative protein localization annotations in identifying known co-localized proteins. Furthermore, we demonstrate that PLAST can reveal protein localization-function relationships that are not obvious from these annotations. First, we identified proteins that have similar localization patterns and participate in closely-related biological processes, but do not necessarily form stable complexes with each other or localize at the same organelles. Second, we found an association between spatial and functional divergences of proteins during evolution. Surprisingly, as proteins with common ancestors evolve, they tend to develop more diverged subcellular localization patterns, but still occupy similar numbers of compartments. This suggests that divergence of protein localization might be more frequently due to the development of more specific localization patterns over ancestral compartments than the occupation of new compartments. PLAST enables systematic and quantitative analyses of protein localization-function relationships, and will be useful to

  5. Assessment of Liver Function in Patients With Hepatocellular Carcinoma: A New Evidence-Based Approach—The ALBI Grade

    Science.gov (United States)

    Johnson, Philip J.; Berhane, Sarah; Kagebayashi, Chiaki; Satomura, Shinji; Teng, Mabel; Reeves, Helen L.; O'Beirne, James; Fox, Richard; Skowronska, Anna; Palmer, Daniel; Yeo, Winnie; Mo, Frankie; Lai, Paul; Iñarrairaegui, Mercedes; Chan, Stephen L.; Sangro, Bruno; Miksad, Rebecca; Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori

    2015-01-01

    Purpose Most patients with hepatocellular carcinoma (HCC) have associated chronic liver disease, the severity of which is currently assessed by the Child-Pugh (C-P) grade. In this international collaboration, we identify objective measures of liver function/dysfunction that independently influence survival in patients with HCC and then combine these into a model that could be compared with the conventional C-P grade. Patients and Methods We developed a simple model to assess liver function, based on 1,313 patients with HCC of all stages from Japan, that involved only serum bilirubin and albumin levels. We then tested the model using similar cohorts from other geographical regions (n = 5,097) and other clinical situations (patients undergoing resection [n = 525] or sorafenib treatment for advanced HCC [n = 1,132]). The specificity of the model for liver (dys)function was tested in patients with chronic liver disease but without HCC (n = 501). Results The model, the Albumin-Bilirubin (ALBI) grade, performed at least as well as the C-P grade in all geographic regions. The majority of patients with HCC had C-P grade A disease at presentation, and within this C-P grade, ALBI revealed two classes with clearly different prognoses. Its utility in patients with chronic liver disease alone supported the contention that the ALBI grade was indeed an index of liver (dys)function. Conclusion The ALBI grade offers a simple, evidence-based, objective, and discriminatory method of assessing liver function in HCC that has been extensively tested in an international setting. This new model eliminates the need for subjective variables such as ascites and encephalopathy, a requirement in the conventional C-P grade. PMID:25512453

  6. Circulating vascular endothelial growth factor and its soluble receptors in patients with liver cirrhosis: possible association with hepatic function impairment.

    Science.gov (United States)

    Jaroszewicz, Jerzy; Januszkiewicz, Marcin; Flisiak, Robert; Rogalska, Magdalena; Kalinowska, Alicja; Wierzbicka, Iwona

    2008-10-01

    Recent studies provided in vivo evidences of an increased angiogenesis in animal model of portal hypertension and cirrhosis which was linked to increased expression of vascular endothelial growth factor. The aim of study was to evaluate the plasma concentration of VEGF and its receptors in liver cirrhosis and the possible association with the degree of liver insufficiency. Methods. Vascular endothelial growth factor (VEGF) and its soluble receptors: sVEGF-R1, sVEGF-R2 were measured in plasma of 78 patients with liver cirrhosis by ELISA. Results. The significant increase of plasma VEGF and sVEGF-R1 was observed in liver cirrhosis compared to healthy individuals (153.1+/-51.9 vs. 46.8+/-4.1pg/mL, P<0.05; 279.8+/-34.3 vs. 105.1+/-5.9pg/mL, P<0.001, respectively). Plasma VEGF and foremost sVEGF R1 showed significant associations with biochemical indices of liver function. Among clinical parameters, only ascites revealed significant association with plasma VEGR and sVEGF-R1. VEGF and sVEGF-R1 were increased respectively to the degree of liver insufficiency. It was demonstrated through a significant positive correlation with Child-Pugh score and MELD classification. In conclusion, our study suggests that serum VEGF and VEGF-R1 may reflect the hepatic function impairment in liver cirrhosis and seems to be associated with portal hypertension symptoms.

  7. Use of quantitative lung scintigraphy to predict postoperative pulmonary function in lung cancer patients undergoing lobectomy.

    Science.gov (United States)

    Win, Thida; Laroche, Clare M; Groves, Ashley M; White, Carol; Wells, Francis C; Ritchie, Andrew J; Tasker, Angela D

    2004-10-01

    In patients with non-small cell lung cancer, the only realistic chance of cure is surgical resection. However, in some of these patients there is such poor respiratory reserve that surgery can result in an unacceptable quality of life. In order to identify these patients, various pulmonary function tests and scintigraphic techniques have been used. The current American College of Physicians and British Thoracic Society guidelines do not recommend the use of quantitative ventilation-perfusion scintigraphy to predict postoperative function in lung cancer patients undergoing lobectomy. These guidelines may have been influenced by previous scintigraphic studies performed over a decade ago. Since then there have been advances in both surgical techniques and scintigraphic techniques, and the surgical population has become older and more female represented. We prospectively performed spirometry and quantitative ventilation-perfusion scintigraphy on 61 consecutive patients undergoing lobectomy for lung cancer. Spirometry was repeated one-month postsurgery. Both a simple segment counting technique alone and scintigraphy were used to predict the postoperative lung function. There was statistically significant correlation (p lung function using both the simple segment counting technique and the scintigraphic techniques. However, the correlation using simple segment counting was of negligible difference compared to scintigraphy. In keeping with current American Chest Physician and British Thoracic Society guidelines, our results suggest that quantitative ventilation-perfusion scintigraphy is not necessary in the preoperative assessment of lung cancer patients undergoing lobectomy. The simple segmenting technique can be used to predict postoperative lung function in lobectomy patients.

  8. Major influence of renal function on hyperlipidemia after living donor liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Qi Ling; Kai Wang; Di Lu; Hai-Jun Guo; Wen-Shi Jiang; Xiang-Xiang He; Xiao Xu

    2012-01-01

    AIM:To investigate the impact of renal and graft function on post-transplant hyperlipidemia (PTHL) in living donor liver transplantation (LDLT).METHODS:A total of 115 adult patients undergoing LDLT from January 2007 to May 2009 at a single center were enrolled.Data were collected and analyzed by the China Liver Transplant Registry retrospectively.PTHL was defined as serum triglycerides ≥ 150 mg/dL or serum cholesterol ≥ 200 mg/dL or the need for pharmacologic treatment at the sixth month after LDLT.Early renal dysfunction (ERD) was defined as serum creatinine ≥ 2 mg/dL and/or the need for renal replacement therapy in the first post-transplant week.RESULTS:In 115 eligible patients,the incidence of PTHL was 24.3%.Recipients with PTHL showed a higher incidence of post-transplant cardiovascular events compared to those without PTHL (17.9% vs 4.6%,P=0.037).Serum creatinine showed significant positive correlations with total serum triglycerides,both at posttransplant month 1 and 3 (P < 0.01).Patients with ERD had much higher pre-transplant serum creatinine levels (P < 0.001) and longer duration of pre-transplant renal insufficiency (P < 0.001) than those without ERD.Pretransplant serum creatinine,graft-to-recipient weight ratio,graft volume/standard liver volume ratio,body mass index (BMI) and ERD were identified as risk factors for PTHL by univariate analysis.Furthermore,ERD [odds ratio (OR) =9.593,P < 0.001] and BMI (OR =6.358,P =0.002) were identified as independent risk factors for PTHL by multivariate analysis.CONCLUSION:Renal function is closely associated with the development of PTHL in LDLT.Post-transplant renal dysfunction,which mainly results from pre-transplant renal insufficiency,contributes to PTHL.

  9. Vascular function in obese children with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Weghuber, Daniel; Roden, Michael; Franz, Carlo; Chmelik, Marek; Torabia, Sherin; Nowotny, Peter; Gruber, Stephan; Waldhäusl, Werner; Klingler, Anton; Bieglmayer, Christian; Bischof, Martin; Wolzt, Michael; Schaller, Georg; Widhalm, Kurt

    2011-04-01

    To test whether obese children with non-alcoholic fatty liver disease have impaired vascular function compared with obese children with normal liver fat content. Obese children (n = 28, 16 males, mean age 10.9 ± 0.7 years, body mass index [BMI] 31.9 ± 4.5 kg/m(2)) with normal (HCLn) and increased hepatocellular lipid content (HCLi, 2.6 ± 0.8 vs. 12.4 ± 8.2%) were recruited, outcome measures being flow-mediated dilation of the brachial artery [FMD] measured by ultrasound, biochemical markers of inflammation (hs-CRP, hs-IL6) and cell adhesion molecules [CAMs], hepatocellular lipids, visceral and subcutaneous fat quantified by nuclear magnetic resonance spectroscopy and imaging. HCLi and HCLn groups showed no significant differences in terms of age, gender, BMI, waist circumference and subcutaneous fat. Subjects in the HCLi group had significantly higher amounts of visceral fat and higher fasting glucose, insulin and triglyceride, but lower adiponectin levels and were more insulin resistant than their HCLn controls. Hepatic fat fraction (HFF) correlated positively with fasting plasma glucose, HOMA-IR, adiponectin, visceral fat, negatively with WBISI independent of BMI. HFF was not associated with subcutaneous fat, fasting insulin, FFA, HDL-C, TG, hs-CRP, hs-IL6, vCAM, iCAM, and FMD. HCLi patients had significantly higher serum levels of hs-CRP and hs-IL6 than HCLn controls. FMD and serum levels of vCAM and iCAM were comparable between groups. Obese children with simple steatosis rather than steatohepatitis seem to have intact vascular function. Further studies in obese children with different grades of NAFLD are warranted to elucidate the role of fatty liver as a marker of risk for future cardiovascular events.

  10. Assessment of Lifespan Functioning Attainment (ALFA) scale: A quantitative interview for self-reported current and functional decline in schizophrenia.

    Science.gov (United States)

    Joseph, Jamie; Kremen, William S; Glatt, Stephen J; Franz, Carol E; Chandler, Sharon D; Liu, Xiaohua; Johnson, Barbara K; Tsuang, Ming T; Twamley, Elizabeth W

    2015-06-01

    Schizophrenia has been characterized as a disorder with poor outcomes across various functional domains, especially social and occupational functioning. Although these outcomes have been investigated based on patients' current functioning, few studies have considered the assessment of functional outcomes across the lifespan in schizophrenia. We developed a novel and brief scale of adulthood lifespan functioning, the Assessment of Lifespan Functioning Attainment (ALFA). We assessed current functioning and percentage of pre- and post-psychosis onset engagement for five functional domains including paid employment, living independently, romantic partnerships, close friendships, and recreational engagement with others. Pre-to post-psychosis functional decline was observed for all domains, with paid employment having the greatest decline (d = 2.68) and living independently having the least decline (d = .59). Our exploratory factor analysis suggests that a single factor accounted for the most variance in Pre-Psychosis Functioning in ALFA domains. Two factors explain the majority of variance in Post-Psychosis Functioning and Pre-to-Post Psychosis Decline: a sociability factor (close friendships and recreational engagement with others) and an independence factor (paid employment, living independently, romantic relationships). To our knowledge, this is the first study to report on a self-reported quantitative assessment of adult lifespan functioning in schizophrenia. The ALFA scale may be a useful tool for future research on functional outcomes in schizophrenia.

  11. Zebrafish fgf10b has a complementary function to fgf10a in liver and pancreas development.

    Science.gov (United States)

    Yan, Chuan; Zheng, Weiling; Gong, Zhiyuan

    2015-04-01

    Fgf10 is a critical growth factor in mammals for development of endodermal organs such as the liver, pancreas, lung, and gut. Due to whole genome duplication, the zebrafish has two fgf10 orthologs, fgf10a and fgf10b. While fgf10a has a role in development of the esophagus and swimbladder, we found in the present study that fgf10b had a complementary expression pattern in the liver, pancreas, and gut. Morpholino knockdown of Fgf10b further confirmed its essential role in the normal development of liver and pancreas. Thus, our data provide another example of functional partition of two duplicated othologous genes during evolution.

  12. Quantitative study of liver magnetic resonance spectroscopy quality at 3T using body and phased array coils with physical analysis and clinical evaluation.

    Directory of Open Access Journals (Sweden)

    Li Xu

    Full Text Available This study aims to investigate the quality difference of short echo time (TE breathhold 1H magnetic resonance spectroscopy (MRS of the liver at 3.0T using the body and phased array coils, respectively. In total, 20 pairs of single-voxel proton spectra of the liver were acquired at 3.0T using the phased array and body coils as receivers. Consecutive stacks of breathhold spectra were acquired using the point resolved spectroscopy (PRESS technique at a short TE of 30 ms and a repetition time (TR of 1500 ms. The first spectroscopy sequence was "copied" for the second acquisition to ensure identical voxel positioning. The MRS prescan adjustments of shimming and water suppression, signal-to noise ratio (SNR, and major liver quantitative information were compared between paired spectra. Theoretical calculation of the SNR and homogeneity of the region of interest (ROI, 2 cm×2 cm×2 cm using different coils loaded with 3D liver electromagnetic model of real human body was implemented in the theoretical analysis. The theoretical analysis showed that, inside the ROI, the SNR of the phase array coil was 2.8387 times larger than that of body coil and the homogeneity of the phase array coil and body coil was 80.10% and 93.86%, respectively. The experimental results showed excellent correlations between the paired data (all r > 0.86. Compared with the body coil group, the phased array group had slightly worse shimming effect and better SNR (all P values 0.05. The theoretical analysis and clinical experiment showed that the phased array coil was superior to the body coil with respect to 3.0T breathhold hepatic proton MRS.

  13. Value of detection of myocardial enzymes, troponin T, liver and renal function in children with severe pneumonia

    Institute of Scientific and Technical Information of China (English)

    Zhen Wang; Bin Wang; Lin Fu; Xue Ren

    2016-01-01

    Objective:To analyze the significance of myocardial enzymes, cardiac troponin T (Troponin T, cTnT), liver and renal function in children with severe pneumonia. Methods:A total of 164 children with pneumonia who were admitted in our hospital from March, 2014 to March, 2015 were included in the study and divided into the severe pneumonia group (n=82) and the common pneumonia group (n=82). The myocardial enzymes (AST,α-HBDH, LD, CK-MB), troponin T, and liver and renal function indicators (UCr, Alb, ALT) in the two groups were observed and compared. According to the arterial partial pressure of oxygen, the children with severe pneumonia were divided into the varying degrees of hypoxia groups, i.e. mild hypoxia group, moderate hypoxia group, and severe hypoxia group. The myocardial enzymes, troponin T, and liver and renal function in the three groups were compared. The correlation of partial pressure of blood oxygen with myocardial enzymes, troponin T, and liver and renal function was analyzed. Results:In the severe pneumonia group, the myocardial enzymes AST, LD, CK, HBDH, CK-MB was significantly higher than that in the ordinary pneumonia group;UCr, Alb ALT troponin T was significantly higher than that in the ordinary pneumonia group;With the increasing hypoxia degree, the levels of myocardial enzymes, troponin T, and liver and renal function indicators in the mild hypoxia group, moderate hypoxia group, and severe hypoxia group were elevated. In the severe pneumonia group, the partial pressure of blood oxygen was negatively correlated with myocardial enzymes, troponin T, and liver and renal function. Conclusions:Timely monitoring of the levels of myocardial enzymes, troponin T, and liver and renal function indicators in the clinic is extremely crucial to evaluate the progression in children with severe pneumonia.

  14. Bactericidal/permeability-increasing protein preserves leukocyte functions after major liver resection.

    Science.gov (United States)

    Wiezer, M J; Meijer, C; Sietses, C; Prins, H A; Cuesta, M A; Beelen, R H; Meijer, S; van Leeuwen, P A

    2000-08-01

    To analyze postoperative leukocyte functions in patients undergoing hemihepatectomy, and to assess the effect of treatment with the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rBPI21). Extensive liver resection is associated with a high incidence of infectious complications. Because elimination of pathogenic microorganisms occurs mainly by leukocytes, this increased rate of infections is most likely due to an impaired function of these cells. Endotoxin, translocated from the gut into the systemic circulation as a result of increased gut permeability and reduced hepatic clearance function after major liver resection, may play an important role in the impairment of posthepatectomy leukocyte function. To investigate whether hemihepatectomy results in impaired leukocyte functions and to determine the role of endotoxin in this process, leukocyte oxidative burst and leukocyte antigen expression were studied in three groups of patients: patients undergoing a hemihepatectomy and receiving rBPI21 treatment, patients undergoing hemihepatectomy and receiving placebo, and as an extra control group patients undergoing other major abdominal surgeries. Blood samples were collected before surgery, 2 hours after surgery, and at days 1, 2, 5, and 7. Phorbol myristate acetate-stimulated oxidative burst was measured using dihydrorhodamine, and leukocyte surface expression of the antigens CD11b, CD16, and CD14 was investigated by indirect immunofluorescence. Both oxidative burst and membrane surface expression were quantified by flow cytometry. An indication of the antiendotoxin effect of rBPI21 treatment was provided by assessment of plasma lipopolysaccharide binding protein (LBP) levels by enzyme-linked immunosorbent assay. The oxidative burst in the hemihepatectomized patients receiving placebo and the controls increased 2 hours after surgery, whereas it decreased in the rBPI21-treated patients, resulting in significant differences between the groups

  15. Quantitative magnetic resonance methods for in vivo investigation of the human liver and spleen. Technical aspects and preliminary clinical results

    DEFF Research Database (Denmark)

    Thomsen, C

    1996-01-01

    This project was initiated with the introduction of magnetic resonance (MR) in Denmark in order to evaluate the possibilities of this technique as a diagnostic aid in non-focal liver and splenic diseases. The signal intensities in the MR image are sensitive to the longitudinal relaxation (T1...... sequences with different repetition times was chosen, because motion effects were partly refocused. Multi-acquisition was used to improve the signal-to-noise ratio in the heavily saturated experiments with short repetition times, to further reduce the sensitivity to motion. To test the quality of this pulse...... sequence, phantom experiments were performed, and sensitivity to motion was tested by measuring with and without respiratory synchronization. Respiratory synchronization gave a marked improvement in focal liver diseases, whereas no difference was found in non-focal diseases. Standard imaging sequences...

  16. Robust classification of functional and quantitative image data using functional mixed models.

    Science.gov (United States)

    Zhu, Hongxiao; Brown, Philip J; Morris, Jeffrey S

    2012-12-01

    This article introduces new methods for performing classification of complex, high-dimensional functional data using the functional mixed model (FMM) framework. The FMM relates a functional response to a set of predictors through functional fixed and random effects, which allows it to account for various factors and between-function correlations. The methods include training and prediction steps. In the training steps we train the FMM model by treating class designation as one of the fixed effects, and in the prediction steps we classify the new objects using posterior predictive probabilities of class. Through a Bayesian scheme, we are able to adjust for factors affecting both the functions and the class designations. While the methods can be used in any FMM framework, we provide details for two specific Bayesian approaches: the Gaussian, wavelet-based FMM (G-WFMM) and the robust, wavelet-based FMM (R-WFMM). Both methods perform modeling in the wavelet space, which yields parsimonious representations for the functions, and can naturally adapt to local features and complex nonstationarities in the functions. The R-WFMM allows potentially heavier tails for features of the functions indexed by particular wavelet coefficients, leading to a down-weighting of outliers that makes the method robust to outlying functions or regions of functions. The models are applied to a pancreatic cancer mass spectroscopy data set and compared with other recently developed functional classification methods. © 2012, The International Biometric Society.

  17. A quantitative analysis of the thermal properties of porcine liver with glycerol at subzero and cryogenic temperatures.

    Science.gov (United States)

    Choi, Jeung Hwan; Bischof, John C

    2008-10-01

    There is a lack of information on the effect of cryoprotective agents (CPAs) on the thermal properties of biomaterials at cryobiologically relevant temperatures (i.e. properties that are of most interest include: thermal conductivity, density, specific heat, and latent heat resulting from phase change in tissue systems. Availability of such information would be beneficial for accurate mathematical modeling of cryobiological applications. Recently, we reported these thermal properties in phosphate buffered saline (PBS) with varying concentrations of glycerol, a widely used cryoprotective agent. In this study we extend these results by assessing the effects of glycerol on the thermal properties of porcine liver at subzero temperatures. Differential scanning calorimeter (DSC) was used to measure the specific heat and the latent heat release of porcine liver immersed in PBS and varying concentrations of glycerol. The specific heat data obtained from the DSC experiments were also used to predict the bulk thermal conductivity. This was done using a transient heat transfer model with a thermistor probe technique. Results show that the introduction of glycerol significantly alters thermal properties from known values for H2O and non-treated liver. Therefore, inaccuracies in thermal predictions can be expected due to the application of measured vs. predicted thermal properties such as from weight averaging. This supports the need for these and other measurements of biomaterial thermal properties, with and without CPA addition, in the cryogenic regime.

  18. [Functional activity of peritonal macrophages in liver immune damage of cellular and antibody genesis in mice].

    Science.gov (United States)

    Martynova, T V; Aleksieieva, I M

    2009-01-01

    The aim of present work was to compare the functional activity of peritoneal macrophages (Mf) at T-cellular and antibody induced hepatitis in mice of CBA line. T-cellular hepatitis was caused by concanavalin A (ConA), antibody-induced hepatitis was caused by administration of xenogenic anti-liver antibodies: gamma-globulin fractions of antihepatocytotoxic serum (gamma-AHCS). It was found that single injection of ConA or gamma-AHCS caused damage of liver with cytolytic syndrome through 20 hours. Functional activity of Mf in these conditions was significantly different. Application of ConA resulted in the decrease in phagocytosis of latex particles and oxygen-dependent metabolism; application of gamma-AHCS--to increase of these processes. Weakening of Mf activity may be one of the reasons for the decrease of dead cell eliminations that results in the maintenance of inflammatory reaction. At the same time significant amplification of phagocytic Mf activity may be one of the pathways of free radical endogenic sources increase that causes cell alteration and plays its role as mediators at inflammation.

  19. Features of History, Anthropometric Data and Individual Functions of the Liver in Children with Prolonged Jaundice

    Directory of Open Access Journals (Sweden)

    O.V. Tyajka

    2017-02-01

    Full Text Available Background. Neonatal jaundice is one of the urgent problems in neonatology. There is a tendency to increase the incidence of prolonged jaundice. The aim of our study was to explore the features of history, anthropometric data and some liver functions in children with prolonged jaundice. Materials and methods. The study involved 111 children with prolonged jaundice aged from 3 weeks to 3 months. In all children with prolonged jaundice, we have examined complete blood count, urinalysis, blood chemistry (determination of total bilirubin and fractions, total protein, albumin, glucose and used instrumental methods of examination — ultrasound of the abdominal cavity and cranial ultrasonography, electrocardiography. Most children with prolonged jaundice were breastfed and were term infants. Results. Indicators of physical development at birth (body weight, body length, head circumference, chest circumference in children with prolonged jaundice and in healthy children had not statistically significant differences. Neonatal jaundice was prolonged in children, who were born from the first pregnancy, — 60 children (54.1 %. A high level of total and indirect bilirubin was accompanied by a low level of albumin in the blood serum of children with prolonged jaundice. Protein-synthesis function of the liver was reduced in children with prolonged jaundice.

  20. Optical nanoscopy to reveal structural and functional properties of liver cells (Presentation Recording)

    Science.gov (United States)

    McCourt, Peter; Huser, Thomas R.; Sørensen, Karen K.; Øie, Cristina I.; Mönkemöller, Viola; Ahluwalia, Balpreet S.

    2015-08-01

    The advent of optical nanoscopy has provided an opportunity to study fundamental properties of nanoscale biological functions, such as liver sinusoidal endothelial cells (LSEC) and their fenestrations. The fenestrations are nano-pores (50-200 nm) on the LSEC plasma membrane that allow free passage of molecules through cells. The fenestrated LSEC also hase a voracious appetite for waste molecules, viruses and nanoparticles. LSEC daily remove huge amounts of waste, nanoparticles and virus from the blood. Pharmaceuticals also need to pass through these fenestrations to be activated (e.g. cholesterol reducing statins) or detoxified by hepatocytes. And, when we age, our LSEC fenestrations become smaller and fewer. Today, we study these cells and structures using either conventional light microscopy on living cells, or high-resolution (but static) methods such as transmission and scanning electron microscopy on fixed (i.e. dead) tissue. Such methods, while very powerful, yield no real time information about the uptake of virus or nanoparticles, nor any information about fenestration dynamics. Therefore, to study LS-SEC, we are now using optical nanoscopy methods, and developing our own, to map their functions in 4 dimensions. Attaining this goal will shed new light on the cell biology of the liver and how it keeps us alive. This paper describes the challenges of studying LS-SEC with light microscopy, as well as current and potential solutions to this challenge using optical nanoscopy.

  1. Routine testing of liver function before and after elective laparoscopic cholecystectomy: is it necessary?

    LENUS (Irish Health Repository)

    Ahmad, Nasir Zaheer

    2012-01-31

    BACKGROUND AND OBJECTIVES: Liver function tests (LFTs) include alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and bilirubin. The role of routine testing before and after laparoscopic cholecystectomy was evaluated in this study. PATIENTS AND METHODS: A total of 355 patients were retrospectively analyzed by examining the LFTs the day before, the day after, and 3 weeks after the surgery. The Wilcoxon signed-rank test and Student t test were performed to determine statistical significance. RESULTS: Alterations in the serum AST, ALT, and GGT were seen on the first postoperative day. Minor changes were seen in bilirubin and ALP. An overall disturbance in the LFTs was seen in more than two-thirds of the cases. Repeat LFTs performed after 3 weeks on follow-up were found to be within normal limits. CONCLUSION: Mild-to-moderate elevation in preoperative LFTs may not be associated with any deleterious effect, and, in the absence of clinical indications, routine preoperative or postoperative liver function testing is unnecessary.

  2. Altered UDP-Glucuronosyltransferase and Sulfotransferase Expression and Function during Progressive Stages of Human Nonalcoholic Fatty Liver Disease

    OpenAIRE

    Hardwick, Rhiannon N.; Ferreira, Daniel W.; More, Vijay R.; Lake, April D.; Lu, Zhenqiang; Manautou, Jose E.; Slitt, Angela L.; Cherrington, Nathan J

    2013-01-01

    The UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) represent major phase II drug-metabolizing enzymes that are also responsible for maintaining cellular homeostasis by metabolism of several endogenous molecules. Perturbations in the expression or function of these enzymes can lead to metabolic disorders and improper management of xenobiotics and endobiotics. Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver damage ranging from steatosis to nonalcoholic...

  3. Influence of thyroid hormones on biochemical parameters of liver function: a case-control study in North Indian population

    Directory of Open Access Journals (Sweden)

    Jayashree Bhattacharjee

    2013-01-01

    Full Text Available Normal level of thyroid hormones is important for normal hepatic function and thyroid dysfunction may modulate metabolic function of liver. The purpose of this study is to determine whether liver function is associated with subclinical and overt hypothyroidism. Thyroid and liver function tests were evaluated in 47 patients with overt (TSH ≥10.0 mIU/L and 77 patients with subclinical hypothyroidism (TSH 6.0-9.9mIU/L and compared with 120 age-matched euthyroid controls. Subjects with overt hypothyroidism had significantly raised serum ALT, AST, ALP and total protein levels as compared to controls whereas subclinical hypothyroid patients had significantly increased levels of serum ALT, ALP and total protein. Further, TSH showed significant positive correlation with AST and ALP values whereas fT3 and fT4 had a negative correlation with AST in overt hypothyroidism. Thus, overt hypothyroid state is associated with significant derangement in biochemical parameters of liver function. Hence, liver function should be regularly monitored in hypothyroid patients.

  4. A new scoring system for assessment of liver function after successful hepatectomy in patients with hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zheng-GuiDu; BoLi; Yong-GangWei; JieYin; XiFeng; XiChen

    2011-01-01

    BACKGROUND: Whether a major liver resection is safe has been judged mainly from the patient's hepatic reserve. However, a safe limit for liver resection does not exist yet. This study aimed to construct a new scoring system as a guide to determine a safe limit for liver resection and avoid liver dysfunction after hepatectomy. METHODS: Eighty-six patients with hepatocellular carcinoma who had undergone hepatectomy in West China Hospital from March 2007 to June 2010 were reviewed. The patients were classified according to the levels of total bilirubin after hepatectomy and the parameters in the perioperative period were compared. Receiver operating characteristic (ROC) analysis was made to assess the liver function compensatory (LFC) value to predict liver dysfunction of the patients after hepatectomy. LFC value is defined as the preoperative KICG value×22.487+standard remnant liver volume (SRLV)×0.020. RESULTS: Patients were classified into group I (normal group, n=69) and group II (with total bilirubin >85.5 μmol/L for 7 days after hepatectomy, n=17) based on the levels of total bilirubin after hepatectomy. Group II was further divided into two subgroups: recovered subgroup (n=14) and fatal subgroup (n=3). There were no significant differences in preoperative data or intraoperative findings except the indocyanine green test parameters (KICG and ICG R15) and SRLV. ROC analysis showed that the sensitivity and specificity of an LFC value ≤13.01 were 94.1% and 82.6% respectively for predicting liver dysfunction of the patients after hepatectomy. CONCLUSIONS: The LFC value appears to be a good predictor of postoperative liver dysfunction in patients who undergo hepatectomy for HCC. An expected LFC value of 13.01 seems to be a safe limit for liver resection.

  5. Mapping Quantitative Trait Loci Underlying Function-Valued Traits Using Functional Principal Component Analysis and Multi-Trait Mapping

    Directory of Open Access Journals (Sweden)

    Il-Youp Kwak

    2016-01-01

    Full Text Available We previously proposed a simple regression-based method to map quantitative trait loci underlying function-valued phenotypes. In order to better handle the case of noisy phenotype measurements and accommodate the correlation structure among time points, we propose an alternative approach that maintains much of the simplicity and speed of the regression-based method. We overcome noisy measurements by replacing the observed data with a smooth approximation. We then apply functional principal component analysis, replacing the smoothed phenotype data with a small number of principal components. Quantitative trait locus mapping is applied to these dimension-reduced data, either with a multi-trait method or by considering the traits individually and then taking the average or maximum LOD score across traits. We apply these approaches to root gravitropism data on Arabidopsis recombinant inbred lines and further investigate their performance in computer simulations. Our methods have been implemented in the R package, funqtl.

  6. Liver and Kidney Functional Indices of Pregnant Rats Following the Administration of the Crude Alkaloids from Senna alata (Linn. Roxb Leaves

    Directory of Open Access Journals (Sweden)

    Musa Toyin Yakubu

    2012-05-01

    Full Text Available Background: Alkaloids from Senna alata leaves implicated as the active constituents of abortifacient are yet to be investigated for their effects on the normal functioning of the maternal liver and kidney. Therefore, the effects of crude alkaloids on some biochemical indices of kidney and liver damage were investigated in pregnant rats. Methods: Pregnant rats were randomized into 4 groups: A (control, B, C, and D and were orally administered 0.5 ml of distilled water, 250, 500 and 1000 mg/kg body weight of the alkaloids respectively once daily on days 10-18 post coitum. Results: Thin-layer chromatographic separation gave five spots with Rf values of 0.28, 0.33, 0.39, 0.47, and 0.55 that produced creamy precipitate and reddish-brown colour, respectively, with Mayer’s and Wagner’s reagents. Quantitative determination gave 0.30 g which corresponded to a percentage yield of 1.50 % of the alkaloids. The decreases in the activities of alkaline phosphatase (ALP, gamma glutamyl transferase (GGT, aspartate (AST and alanine transaminases in the liver and kidney of the animals by the alkaloids were accompanied by corresponding increases in the serum enzymes. The alkaloids reduced liver- and kidney-body weight ratios, serum globulin, urea, uric acid, and phosphate ions while the serum concentrations of albumin, bilirubin, creatinine, potassium ions, AST/ALT ratio, blood urea nitrogen: creatinine increased. The levels of sodium, calcium, and chloride ions did not change significantly (P>0.05. Conclusion: Overall, the alkaloid at doses of 250-1000 mg/kg body weight produced permeability changes in the plasma membrane of the organs and adversely affected the normal secretory, synthetic, and excretory functions of these organs.

  7. Comparison of low-calorie diet with and without sibutramine on body weight and liver function of patients with non-alcoholic fatty liver disease

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    Z bahmanabadi

    2011-06-01

    Full Text Available Introduction & Objective: Non-alcoholic fatty liver (NAFLD is defined as a spectrum of clinical scenarios which is pathological deposition of fat droplets in the liver of patients who have no history of alcohol use. This study compared the effect of low calorie diet with and without sibutramine on body weight and liver function in patients with NAFLD. Materials & Methods: This clinical trial study was conducted in 2010 at Tabriz University of Medical Sciences, on 40 obese patients with non-alcoholic fatty liver. Patients were randomly divided into two equal groups of intervention and control groups. Group one received 15 mg daily sibutramine capsules half an hour before lunch and a weight loss diet based on ideal body weight. The other group only had diet control for weight reduction. Before and after 3 months of intervention, weight changes, fasting glucose, glycosylated hemoglobin HbA1c, levels of liver enzymes and ultrasound evaluation was repeated. Data were analyzed using the SPSS software and the paired T test, Mann-Whitney and McNemar test. Results: The mean age of the subjects was 38.90 ± 7.00 in the sibutramine group and 36.55 ±7.87 for the control group. After three months, the average weight loss in sibutramine group was significantly more than the control group (sibutramine group13 kg and control group 4 kg (p<0.05. Improvement in liver echogenicity in sibutramine patients was 90% and 50% of diet group patients. ALT changes in the sibutramine group and control group was 7.50 ± 15.11 and 6.15 ± 28.23 respectively, which was statistically significant in the sibutramine group. AST changes were 4.38 ± 13.37 and 1.70 ± 18.37 in sibutramine and control group respectively. The changes were not statistically significant. Conclusion: Overall, findings of this study suggest that sibutramine is effective in liver function improvement and treatment of NAFLD patients.

  8. Discovering the cellular-localized functional modules and modular interactions in response to liver cancer

    Institute of Scientific and Technical Information of China (English)

    Zhu Jing; Guo Zheng; Yang Da; Zhang Min; Wang Jing; Wang Chenguang

    2008-01-01

    In this paper, we firstly identify the functional modules enriched with differentially expressed genes (DEGs) and characterized by biological processes in specific cellular locations, based on gene ontology (GO) and microarray data. Then, we further define and filter disease relevant signature modules according to the ranking of the disease discriminating abilities of the pre-selected functional modules. At last, we analyze the potential way by which they cooperate towards human disease. Application of the proposed method to the analysis of a liver cancer dataset shows that, using the same false discovery rate (FDR) threshold, we can find more biologically meaningful and detailed processes by using the cellular localization information. Some biological evidences support the relevancy of our biological modules to the disease mechanism.

  9. The influence of Enteral Nutrition in postoperative patients with poor liver function

    Institute of Scientific and Technical Information of China (English)

    Qing-Gang Hu; Qi-Chang Zheng

    2003-01-01

    AIM: To investigate the safety, rationality and the practicality of enteral nutritional (EN) support in the postoperative patients with damaged liver function and the protective effect of EN on the gut barrier.METHODS: 135 patients with liver function of Child B or C grade were randomly allocated to enteral nutrition group (EN, 65 cases), total parenteral nutrition group (TPN, 40cases) and control group (CON, 30 cases). Nutritional parameters, hepatic and kidney function indexes were measured at the day before operation, 5th and 10th day after the operation respectively. Comparison was made to evaluate the efficacy of different nutritional support. Urinary concentrations of lactulose(L) and mannitol(M) were measured by pulsed electrochemical detection(HPLC-PED)and the L/M ratio calculated to evaluate their effectiveness on protection of gut barrier.RESULTS: No significant damages in hepatic and kidney function were observed in both EN and TPN groups between pre- and postoperatively. EN group was the earliest one reaching the positive nitrogen balance after operation and with the lowest loss of body weight and there was no change in L/M ratio after the operation (0.026±0.004) at the day 1before operation, 0.030±0.004 at the day 5 postoperative and 0.027±0.005 at the day 10 postoperative), but the change in TPN group was significant at the day 5postoperative (0.027±0.003 vs 0.038±0.009,P<0.01).CONCLUSION: EN is a rational and effective method in patients with hepatic dysfunction after operation and has significant protection effect on the gut barrier.

  10. Liver in systemic disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Potential causes of abnormal liver function tests include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies or infection, gallstones and drug-induced liver injury. Moreover, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in patients without etiology of liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function test results might be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. However, some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

  11. Subclinical change of liver function could also provide a clue on prognosis for patients with spontaneous intracerebral hemorrhage.

    Science.gov (United States)

    Tan, Ge; Hao, Zilong; Lei, Chunyan; Chen, Yanchao; Yuan, Ruozhen; Xu, Mangmang; Liu, Ming

    2016-10-01

    Whether subclinical change of liver function is associated with outcome of spontaneous intracerebral hemorrhage remains to be an open question. A total of 639 patients of spontaneous intracerebral hemorrhage within 7 days from stroke onset were finally enrolled. Liver function indicators, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (BIL), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), albumin (ALB), and international normalized ratio (INR), were collected and collapsed into quartiles. The main outcomes were 30-day death, 90-day death, and 90-day poor outcome (modified Rankin Scale score of 3-6). Two adjusted model, Model 1 and Model 2 (Model 1 plus GCS score), were established to identify independent association between liver function indicators and ICH outcomes. The mortality rate was 19.9 % (127/639) at 30 days and 21.3 % (136/639) at 90 days. Rate of 90-day poor outcome was 51.5 % (329/639). Among liver function indicators, AST and ALP were associated with all the three outcomes, which did not alter significantly when adjusted by Model 1. After adjusted by Model 2, ALP was still associated with outcomes. Association between AST and outcomes was, however, weakened significantly by GCS score. In conclusions, among liver function indicators, AST and ALP were associated with outcomes after spontaneous intracerebral hemorrhage.

  12. Correlation between infection of herpes virus family and liver function parameters: a population-based cross-sectional study.

    Science.gov (United States)

    Cui, Yali; Huang, Xiaocui; Wang, Xia; Li, Yingying; Tang, Chao; Wang, Hong; Jiang, Yongmei

    2017-04-30

    To evaluate the relationship between seropositivity to herpes virus family and liver function parameters in children from southwest China. A 2-year cross-sectional retrospective study of 6,396 children aged 6 months to 12 years was performed. All participants underwent physical examination and liver function tests. Of the children, 622 were positive for EBV, HSV, or CMV IgM, with dramatic changes in liver function parameters. Aspartate aminotransferase and alanine aminotransferase levels were negatively correlated with EBV-IgM and hepatocellular injuries in children LDH) and EBV-IgM and hepatocellular injuries was documented in children LDH were observed in 85.71% of children simultaneously infected with CMV and HSV, 77.78% for CMV and EBV, 83.33% for EBV and HSV, and irregular levels of AST were noted in 69.19% of children infected with CMV and HSV, 77.78% for CMV and EBV, and 83.33% for EBV and HSV. Seropositivity to herpes virus family was correlated with abnormal liver function parameters across years of age. Clinicians should aim to protect the liver function of children infected with herpes viruses.

  13. Taurine treatment preserves brain and liver mitochondrial function in a rat model of fulminant hepatic failure and hyperammonemia.

    Science.gov (United States)

    Jamshidzadeh, Akram; Heidari, Reza; Abasvali, Mozhgan; Zarei, Mehdi; Ommati, Mohammad Mehdi; Abdoli, Narges; Khodaei, Forouzan; Yeganeh, Yasaman; Jafari, Faezeh; Zarei, Azita; Latifpour, Zahra; Mardani, Elnaz; Azarpira, Negar; Asadi, Behnam; Najibi, Asma

    2017-02-01

    Ammonia-induced mitochondrial dysfunction and energy crisis is known as a critical consequence of hepatic encephalopathy (HE). Hence, mitochondria are potential targets of therapy in HE. The current investigation was designed to evaluate the role of taurine treatment on the brain and liver mitochondrial function in a rat model of hepatic encephalopathy and hyperammonemia. The animals received thioacetamide (400mg/kg, i.p, for three consecutive days at 24-h intervals) as a model of acute liver failure and hyperammonemia. Several biochemical parameters were investigated in the serum, while the animals' cognitive function and locomotor activity were monitored. Mitochondria was isolated from the rats' brain and liver and several indices were assessed in isolated mitochondria. Liver failure led to cognitive dysfunction and impairment in locomotor activity in the rats. Plasma and brain ammonia was high and serum markers of liver injury were drastically elevated in the thioacetamide-treated group. An assessment of brain and liver mitochondrial function in the thioacetamide-treated animals revealed an inhibition of succinate dehydrogenase activity (SDA), collapsed mitochondrial membrane potential, mitochondrial swelling, and increased reactive oxygen species (ROS). Furthermore, a significant decrease in mitochondrial ATP was detected in the brain and liver mitochondria isolated from thioacetamide-treated animals. Taurine treatment (250, 500, and 1000mg/kg) decreased mitochondrial swelling, ROS, and LPO. Moreover, the administration of this amino acid restored brain and liver mitochondrial ATP. These data suggest taurine to be a potential protective agent with therapeutic capability against hepatic encephalopathy and hyperammonemia-induced mitochondrial dysfunction and energy crisis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. The Effects of Liver Transplantation on the Bone Metabolism and Gonadal Functions

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    Funda Atamaz

    2005-06-01

    Full Text Available The present study was designed to evaluate the effects of liver transplantation (LT on the bone mineral density (BMD, characteristics of bone turnover, mineral metabolism and sex hormons. Fifty one patients (34 men, 11 women aged 43.5 ± 12.1, who underwent LT were studied, assessing the following parameters: lumbar spine and proximal femur BMD, osteocalcin, deoxypyridinoline (DPD, parathyroid hormone (PTH, free testesterone (FT, gonadotropins (FSH, LH, tyroid hormones, growth hormone (GH and blood/ 24-hours urine Ca and P. All the measures were obtained at baseline and at 3rd month after LT. At baseline, 12 patients (%23.5 had osteoporosis, 22 patients (%43.1 had osteopenia and the mean BMD was 0.892 ± 0.1 for lumbar spine. Whereas, osteoporosis was seen less at femoral neck and total femur: 5 (%9.8 and 4 (%7.8, respectively. Three months after LT, 3.9% drop for lumbar spine, 5.3% drop for femur neck, 6.3% drop for total femur were observed, in BMD these decreases were statistically significant for all sites (p<0.05. The thyroid hormones, GH, PTH, blood Ca, P and osteocalcin levels and urinary DPD excretion were within normal range, while the levels of FSH and LH in women and level of FT in men were lower than normal range. After LT, statistically significant increases were observed in the PTH, osteocalcin, DPD, FSH, LH and FT levels (p<0.05. There was a highly significant negative correlation between duration of liver disease and all the BMD measures (p<0.01. Consequently, the increased osteoporosis ratio which was characterized by high bone turnover was found in patients who underwent LT in this study. The normalization of liver functions following LT was characterized by an early rise in sex hormones.

  15. Localized Quantitative Characterization of Chemical Functionalization Effects on Adhesion Properties of SWNT

    Directory of Open Access Journals (Sweden)

    Hao Lu

    2011-01-01

    Full Text Available Chemical modification of single-walled carbon nanotubes (SWNT has been found to be an excellent method to promote SWNT dispersion, and possibly to improve interaction with matrices via covalent bonding. It is thus a quite promising technique to enhance the mechanical properties of SWNT-reinforced nanocomposites. However, the underlying mechanism of SWNT chemical functionalization effects on interfacial strength is not quantitatively understood, limiting their usefulness in the design of nanocomposites. In this work, an atomic force microscopy (AFM- based adhesive force mapping technique combined with a statistical analysis method were developed and implemented to study adhesive interactions of small SWNT bundles functionalized by amino, epoxide, and hydroperoxide groups as compared to SDS-treated SWNT in controlled environment. Finally, the importance of such localized quantitative measurements in SWNT-reinforced nanocomposites design and fabrication was also discussed.

  16. Renal function in tyrosinaemia type I after liver transplantation : A long-term follow-up

    NARCIS (Netherlands)

    Pierik, LJWM; van Spronsen, FJ; Bijleveld, CMA; van Dael, CML

    2005-01-01

    Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine catabolism caused by a deficiency of the enzyme fumarylacetoacetase that results in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute intermittent porphyria. When treated with liver transplan

  17. Prospective association of liver function biomarkers with development of hepatobiliary cancers

    NARCIS (Netherlands)

    Stepien, Magdalena; Fedirko, Veronika; Duarte-Salles, Talita; Ferrari, Pietro; Freisling, Heinz; Trepo, Elisabeth; Trichopoulou, Antonia; Bamia, Christina; Weiderpass, Elisabete; Olsen, Anja; Tjønneland, Anne; Overvad, Kim; Boutron-Ruault, Marie Christine; Fagherazzi, Guy; Racine, Antoine; Kühn, Tilman; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Lagiou, Pagona; Benetou, Vassiliki; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Naccarati, Alessio; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Peeters, Petra H.; Lund, Eiliv; Quirós, J. Ramón; Nápoles, Osmel Companioni; Sánchez, María José; Dorronsoro, Miren; Huerta, José María; Ardanaz, Eva; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Nystrom, Hanna; Khaw, Kay Tee; Key, Timothy J.; Gunter, Marc; Cross, Amanda; Riboli, Elio; Romieu, Isabelle; Jenab, Mazda

    2016-01-01

    Introduction: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of

  18. Quantitative evaluation of interaction force between functional groups in protein and polymer brush surfaces.

    Science.gov (United States)

    Sakata, Sho; Inoue, Yuuki; Ishihara, Kazuhiko

    2014-03-18

    To understand interactions between polymer surfaces and different functional groups in proteins, interaction forces were quantitatively evaluated by force-versus-distance curve measurements using atomic force microscopy with a functional-group-functionalized cantilever. Various polymer brush surfaces were systematically prepared by surface-initiated atom transfer radical polymerization as well-defined model surfaces to understand protein adsorption behavior. The polymer brush layers consisted of phosphorylcholine groups (zwitterionic/hydrophilic), trimethylammonium groups (cationic/hydrophilic), sulfonate groups (anionic/hydrophilic), hydroxyl groups (nonionic/hydrophilic), and n-butyl groups (nonionic/hydrophobic) in their side chains. The interaction forces between these polymer brush surfaces and different functional groups (carboxyl groups, amino groups, and methyl groups, which are typical functional groups existing in proteins) were quantitatively evaluated by force-versus-distance curve measurements using atomic force microscopy with a functional-group-functionalized cantilever. Furthermore, the amount of adsorbed protein on the polymer brush surfaces was quantified by surface plasmon resonance using albumin with a negative net charge and lysozyme with a positive net charge under physiological conditions. The amount of proteins adsorbed on the polymer brush surfaces corresponded to the interaction forces generated between the functional groups on the cantilever and the polymer brush surfaces. The weakest interaction force and least amount of protein adsorbed were observed in the case of the polymer brush surface with phosphorylcholine groups in the side chain. On the other hand, positive and negative surfaces generated strong forces against the oppositely charged functional groups. In addition, they showed significant adsorption with albumin and lysozyme, respectively. These results indicated that the interaction force at the functional group level might be

  19. Comprehensive treatment of a functional pancreatic neuroendocrine tumor with multifocal liver metastases.

    Science.gov (United States)

    Wang, Wei; Seeruttun, Sharvesh Raj; Fang, Cheng; Zhou, Zhiwei

    2014-08-01

    A 64-year-old man was admitted to the Sun Yat-Sen University Cancer Center with chief complaints of recurrent abdominal pain and diarrhea for about 3 years and with a history of surgical repair for intestinal perforation owing to stress ulcer. Positron emission tomography (PET)/computed tomography (CT) demonstrated a primary tumor on the pancreatic tail with multifocal liver metastases. Pathological and immunohistochemistry staining revealed the lesion to be a pancreatic neuroendocrine tumor (pNET). According to the latest World Health Organization (WHO, 2013) classification, the tumor was classified as stage IV functional G1 pNET. After referral to the multidisciplinary treatment board (MDT), the patient was started on periodic dose of omeprazole, somatostatin analogues and Interferon α (IFNα) and had scanning follow-ups. Based upon the imaging results, CT-guided radioactive iodine-125 ((125)I) seeds implantation therapy, radiofrequency ablation therapy (RFA) or microwave ablation technique were chosen for the treatment of the primary tumor. Transarterial chemoembolization (TACE), RFA and microwave ablation techniques were decided upon for liver metastases. The patient showed beneficial response to the treatment with clinically manageable low-grade side effects and attained partial remission (RECIST criteria) with a good quality of life.

  20. Liver function evaluation in leptospirosis with colloidal gold 1 9 8 Au

    Directory of Open Access Journals (Sweden)

    Walber Miranda Silva

    1977-12-01

    Full Text Available Eight patients with leptospirosis were studied with colloidal gold 1 9 8 Au. The radiocolloidal hepatic distribution was altered, presenting a non-homogeneous tiver concentration in seven cases, and a minute to moderate splenic visualization in five. Two patients presented doubtful splenic image, and one seemed to be normal. Liver scanning with colloidal gold 1 9 8 Au is demonstra ted to be a good liver function test.Oito pacientes com Leptospirose foram investigados com ouro coloidal radioativo (1 9 8 Au. A distribuição intrahepática do radiocoloide era alterada, apresentando uma concentração hepática não-homogênea em 7 casos, e visualização esp/ênica de mínima a moderada em 5. Dois tinham dúvida quanto à imagem do baço, e um parecia normal. A cintigrafia hepática com ouro coloidai radioativo (1 9 8 Au é demonstrada ser um bom teste de função hepática.

  1. Tributyltin chloride leads to adiposity and impairs metabolic functions in the rat liver and pancreas.

    Science.gov (United States)

    Bertuloso, Bruno D; Podratz, Priscila L; Merlo, Eduardo; de Araújo, Julia F P; Lima, Leandro C F; de Miguel, Emilio C; de Souza, Leticia N; Gava, Agata L; de Oliveira, Miriane; Miranda-Alves, Leandro; Carneiro, Maria T W D; Nogueira, Celia R; Graceli, Jones B

    2015-05-19

    Tributyltin chloride (TBT) is an environmental contaminant used in antifouling paints of boats. Endocrine disruptor effects of TBT are well established in animal models. However, the adverse effects on metabolism are less well understood. The toxicity of TBT in the white adipose tissue (WAT), liver and pancreas of female rats were assessed. Animals were divided into control and TBT (0.1 μg/kg/day) groups. TBT induced an increase in the body weight of the rats by the 15th day of oral exposure. The weight gain was associated with high parametrial (PR) and retroperitoneal (RP) WAT weights. TBT-treatment increased the adiposity, inflammation and expression of ERα and PPARγ proteins in both RP and PR WAT. In 3T3-L1 cells, estrogen treatment reduced lipid droplets accumulation, however increased the ERα protein expression. In contrast, TBT-treatment increased the lipid accumulation and reduced the ERα expression. WAT metabolic changes led to hepatic inflammation, lipid accumulation, increase of PPARγ and reduction of ERα protein expression. Accordingly, there were increases in the glucose tolerance and insulin sensitivity tests with increases in the number of pancreatic islets and insulin levels. These findings suggest that TBT leads to adiposity in WAT specifically, impairing the metabolic functions of the liver and pancreas.

  2. Recent insights into the biological functions of liver fatty acid binding protein 1.

    Science.gov (United States)

    Wang, GuQi; Bonkovsky, Herbert L; de Lemos, Andrew; Burczynski, Frank J

    2015-12-01

    Over four decades have passed since liver fatty acid binding protein (FABP)1 was first isolated. There are few protein families for which most of the complete tertiary structures, binding properties, and tissue occurrences are described in such detail and yet new functions are being uncovered for this protein. FABP1 is known to be critical for fatty acid uptake and intracellular transport and also has an important role in regulating lipid metabolism and cellular signaling pathways. FABP1 is an important endogenous cytoprotectant, minimizing hepatocyte oxidative damage and interfering with ischemia-reperfusion and other hepatic injuries. The protein may be targeted for metabolic activation through the cross-talk among many transcriptional factors and their activating ligands. Deficiency or malfunction of FABP1 has been reported in several diseases. FABP1 also influences cell proliferation during liver regeneration and may be considered as a prognostic factor for hepatic surgery. FABP1 binds and modulates the action of many molecules such as fatty acids, heme, and other metalloporphyrins. The ability to bind heme is another cytoprotective property and one that deserves closer investigation. The role of FABP1 in substrate availability and in protection from oxidative stress suggests that FABP1 plays a pivotal role during intracellular bacterial/viral infections by reducing inflammation and the adverse effects of starvation (energy deficiency).

  3. Innate functions of immunoglobulin M lessen liver gene transfer with helper-dependent adenovirus.

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    Carmen Unzu

    Full Text Available The immune system poses obstacles to viral vectors, even in the first administration to preimmunized hosts. We have observed that the livers of B cell-deficient mice were more effectively transduced by a helper-dependent adenovirus serotype-5 (HDA vector than those of WT mice. This effect was T-cell independent as shown in athymic mice. Passive transfer of the serum from adenovirus-naïve WT to Rag1KO mice resulted in a reduction in gene transfer that was traced to IgM purified from serum of adenovirus-naïve mice. To ascribe the gene transfer inhibition activity to either adenoviral antigen-specific or antigen-unspecific functions of IgM, we used a monoclonal IgM antibody of unrelated specificity. Both the polyclonal and the irrelevant monoclonal IgM inhibited gene transfer by the HDA vector to either cultured hepatocellular carcinoma cells or to the liver of mice in vivo. Adsorption of polyclonal or monoclonal IgMs to viral capsids was revealed by ELISAs on adenovirus-coated plates. These observations indicate the existence of an inborn IgM mechanism deployed against a prevalent virus to reduce early post-infection viremia. In conclusion, innate IgM binding to adenovirus serotype-5 capsids restrains gene-transfer and offers a mechanism to be targeted for optimization of vector dosage in gene therapy with HDA vectors.

  4. Stiffness of hyaluronic acid gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology.

    Science.gov (United States)

    Deegan, Daniel B; Zimmerman, Cynthia; Skardal, Aleksander; Atala, Anthony; Shupe, Thomas D

    2015-03-01

    Tissue engineering and cell based liver therapies have utilized primary hepatocytes with limited success due to the failure of hepatocytes to maintain their phenotype in vitro. In order to overcome this challenge, hyaluronic acid (HA) cell culture substrates were formulated to closely mimic the composition and stiffness of the normal liver cellular microenvironment. The stiffness of the substrate was modulated by adjusting HA hydrogel crosslinking. Additionally, the repertoire of bioactive molecules within the HA substrate was bolstered by supplementation with normal liver extracellular matrix (ECM). Primary human hepatocyte viability and phenotype were determined over a narrow physiologically relevant range of substrate stiffnesses from 600 to 4600Pa in both the presence and absence of liver ECM. Cell attachment, viability, and organization of the actin cytoskeleton improved with increased stiffness up to 4600Pa. These differences were not evident in earlier time points or substrates containing only HA. However, gene expression for the hepatocyte markers hepatocyte nuclear factor 4 alpha (HNF4α) and albumin significantly decreased on the 4600Pa stiffness at day 7 indicating that cells may not have maintained their phenotype long-term at this stiffness. Function, as measured by albumin secretion, varied with both stiffness and time in culture and peaked at day 7 at the 1200Pa stiffness, slightly below the stiffness of normal liver ECM at 3000Pa. Overall, gel stiffness affected primary human hepatocyte cell adhesion, functional marker expression, and morphological characteristics dependent on both the presence of liver ECM in gel substrates and time in culture.

  5. Analysis of common and specific mechanisms of liver function affected by nitrotoluene compounds.

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    Youping Deng

    Full Text Available BACKGROUND: Nitrotoluenes are widely used chemical manufacturing and munitions applications. This group of chemicals has been shown to cause a range of effects from anemia and hypercholesterolemia to testicular atrophy. We have examined the molecular and functional effects of five different, but structurally related, nitrotoluenes on using an integrative systems biology approach to gain insight into common and disparate mechanisms underlying effects caused by these chemicals. METHODOLOGY/PRINCIPAL FINDINGS: Sprague-Dawley female rats were exposed via gavage to one of five concentrations of one of five nitrotoluenes [2,4,6-trinitrotoluene (TNT, 2-amino-4,6-dinitrotoluene (2ADNT 4-amino-2,6-dinitrotoulene (4ADNT, 2,4-dinitrotoluene (2,4DNT and 2,6-dinitrotoluene (2,6DNT] with necropsy and tissue collection at 24 or 48 h. Gene expression profile results correlated well with clinical data and liver histopathology that lead to the concept that hematotoxicity was followed by hepatotoxicity. Overall, 2,4DNT, 2,6DNT and TNT had stronger effects than 2ADNT and 4ADNT. Common functional terms, gene expression patterns, pathways and networks were regulated across all nitrotoluenes. These pathways included NRF2-mediated oxidative stress response, aryl hydrocarbon receptor signaling, LPS/IL-1 mediated inhibition of RXR function, xenobiotic metabolism signaling and metabolism of xenobiotics by cytochrome P450. One biological process common to all compounds, lipid metabolism, was found to be impacted both at the transcriptional and lipid production level. CONCLUSIONS/SIGNIFICANCE: A systems biology strategy was used to identify biochemical pathways affected by five nitroaromatic compounds and to integrate data that tie biochemical alterations to pathological changes. An integrative graphical network model was constructed by combining genomic, gene pathway, lipidomic, and physiological endpoint results to better understand mechanisms of liver toxicity and

  6. Effects of thrombin inhibition with melagatran on renal hemodynamics and function and liver integrity during early endotoxemia

    DEFF Research Database (Denmark)

    Nitescu, Nicoletta; Grimberg, Elisabeth; Ricksten, Sven-Erik

    2007-01-01

    in thiobutabarbital-anesthetized rats by an intravenous bolus dose of lipopolysaccharide (LPS; 6 mg/kg). Sham-Saline, LPS-Saline, and LPS-Melagatran study groups received isotonic saline or melagatran immediately before (0.75 micromol/kg iv) and continuously during (0.75 micromol.kg(-1).h(-1) iv) 4.5 h of endotoxemia....... Kidney function, renal blood flow (RBF), and intrarenal cortical and outer medullary perfusion (OMLDF) measured by laser-Doppler flowmetry were analyzed throughout. Markers of liver injury and tumor necrosis factor (TNF)-alpha were measured in plasma after 4.5 h of endotoxemia. In addition, liver....... Melagatran did not diminish histological abnormalities in the liver or the elevated hepatic gene expression of TNF-alpha, intercellular adhesion molecule-1, and inducible nitric oxide synthase in endotoxemic rats. In summary, thrombin inhibition with melagatran preserved renal OMLDF, attenuated liver...

  7. Effects of endurance and endurance-strength exercise on biochemical parameters of liver function in women with abdominal obesity.

    Science.gov (United States)

    Skrypnik, Damian; Ratajczak, Marzena; Karolkiewicz, Joanna; Mądry, Edyta; Pupek-Musialik, Danuta; Hansdorfer-Korzon, Rita; Walkowiak, Jarosław; Jakubowski, Hieronim; Bogdański, Paweł

    2016-05-01

    Obesity is a risk factor of nonalcoholic fatty liver disease. Although the standard therapy for obesity involves physical exercise, well-planned studies of the changes in liver function in response to different exercise intensities in obese subjects are scarce. The aim of the present study was to examine a question of how does exercise mode affect the liver function. 44 women with abdominal obesity were randomized into two exercise groups: endurance (group A) and endurance-strength (group B). Women in each group exercised for 60min 3 times/week for a 3-month period. Markers of liver function: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) activities, and bilirubin levels were quantified. We found significant differences in ALT (pexercise. Blood ALT and AST tended to decrease in group B, increase in group A. Significant reduction in serum GGT level after exercise in both groups was observed (pexercise led to changes in serum ALP activity and total or direct bilirubin level. However, endurance-strength training resulted in significant decreases in serum indirect bilirubin (pexercise (group B). The mode of exercise does matter: endurance-strength exercise led to a greater improvement, compared to endurance exercise, in the liver function in women with abdominal obesity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Quantitative assessment of p-glycoprotein expression and function using confocal image analysis.

    Science.gov (United States)

    Hamrang, Zahra; Arthanari, Yamini; Clarke, David; Pluen, Alain

    2014-10-01

    P-glycoprotein is implicated in clinical drug resistance; thus, rapid quantitative analysis of its expression and activity is of paramout importance to the design and success of novel therapeutics. The scope for the application of quantitative imaging and image analysis tools in this field is reported here at "proof of concept" level. P-glycoprotein expression was utilized as a model for quantitative immunofluorescence and subsequent spatial intensity distribution analysis (SpIDA). Following expression studies, p-glycoprotein inhibition as a function of verapamil concentration was assessed in two cell lines using live cell imaging of intracellular Calcein retention and a routine monolayer fluorescence assay. Intercellular and sub-cellular distributions in the expression of the p-glycoprotein transporter between parent and MDR1-transfected Madin-Derby Canine Kidney cell lines were examined. We have demonstrated that quantitative imaging can provide dose-response parameters while permitting direct microscopic analysis of intracellular fluorophore distributions in live and fixed samples. Analysis with SpIDA offers the ability to detect heterogeniety in the distribution of labeled species, and in conjunction with live cell imaging and immunofluorescence staining may be applied to the determination of pharmacological parameters or analysis of biopsies providing a rapid prognostic tool.

  9. Systematic Discovery of Archaeal Transcription Factor Functions in Regulatory Networks through Quantitative Phenotyping Analysis.

    Science.gov (United States)

    Darnell, Cynthia L; Tonner, Peter D; Gulli, Jordan G; Schmidler, Scott C; Schmid, Amy K

    2017-01-01

    Gene regulatory networks (GRNs) are critical for dynamic transcriptional responses to environmental stress. However, the mechanisms by which GRN regulation adjusts physiology to enable stress survival remain unclear. Here we investigate the functions of transcription factors (TFs) within the global GRN of the stress-tolerant archaeal microorganism Halobacterium salinarum. We measured growth phenotypes of a panel of TF deletion mutants in high temporal resolution under heat shock, oxidative stress, and low-salinity conditions. To quantitate the noncanonical functional forms of the growth trajectories observed for these mutants, we developed a novel modeling framework based on Gaussian process regression and functional analysis of variance (FANOVA). We employ unique statistical tests to determine the significance of differential growth relative to the growth of the control strain. This analysis recapitulated known TF functions, revealed novel functions, and identified surprising secondary functions for characterized TFs. Strikingly, we observed that the majority of the TFs studied were required for growth under multiple stress conditions, pinpointing regulatory connections between the conditions tested. Correlations between quantitative phenotype trajectories of mutants are predictive of TF-TF connections within the GRN. These phenotypes are strongly concordant with predictions from statistical GRN models inferred from gene expression data alone. With genome-wide and targeted data sets, we provide detailed functional validation of novel TFs required for extreme oxidative stress and heat shock survival. Together, results presented in this study suggest that many TFs function under multiple conditions, thereby revealing high interconnectivity within the GRN and identifying the specific TFs required for communication between networks responding to disparate stressors. IMPORTANCE To ensure survival in the face of stress, microorganisms employ inducible damage repair

  10. Application of postoperative Model for End-Stage Liver Disease scoring system for evaluating liver graft function after living donor liver transplantation.

    Science.gov (United States)

    Toshima, T; Ikegami, T; Kimura, K; Harimoto, N; Yamashita, Y; Yoshizumi, T; Soejima, Y; Ikeda, T; Shirabe, K; Maehara, Y

    2014-01-01

    The Model for End-Stage Liver Disease (MELD) score has been validated to predict the mortality rate of patients with various chronic liver diseases on the waiting list for liver transplantation (LT). The aim of this study was to assess the value of the postoperative MELD scoring system as an early postoperative predictor of outcome in patients undergoing living donor LT (LDLT). A retrospective analysis of 217 adult-to-adult LDLT patients was performed. The values of the MELD score on various postoperative days (PODs) as predictors of graft loss within 6 months after LDLT were examined by calculating the areas under the receiver operating characteristic (AUROC) curves. The 6-months graft survival rates were compared between patients with (n = 22) and without (n = 195) graft loss. Univariate and multivariate analyses were performed to identify the factors associated with mortality. The MELD score on POD2 was a predictor of graft loss, with an AUROC c-statistic of 0.779, a specificity of 79.5%, and a sensitivity of 68.2% at optimal cutoff, whereas the preoperative MELD score c-statistic was 0.605 with 44.6% sensitivity. Multivariate analyses for postoperative mortality revealed MELD-POD2 ≥19 (odds ratio, 5.601; 95% confidence interval [CI], 1.395-4.508; P = .0009) as an independent predictor of short-term graft loss following LDLT, in addition to preoperative hospitalization status. Later MELD POD scores were also predictive of graft loss. The early postoperative MELD scoring system is feasible as an index for prediction of postoperative mortality following LDLT. Published by Elsevier Inc.

  11. The revised human liver cytochrome P450 "Pie": absolute protein quantification of CYP4F and CYP3A enzymes using targeted quantitative proteomics.

    Science.gov (United States)

    Michaels, Scott; Wang, Michael Zhuo

    2014-08-01

    The CYP4F subfamily of enzymes has been identified recently to be involved in the metabolism of endogenous compounds (arachidonic acid and leukotriene B4), nutrients (vitamins K1 and E), and xenobiotics (pafuramidine and fingolimod). CYP4F2 and CYP4F3B are reported to be expressed in the human liver. However, absolute concentrations of these enzymes in human liver microsomes (HLMs) and their interindividual variability have yet to be determined because of the lack of specific antibodies. Here, an liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based targeted quantitative proteomic approach was employed to determine the absolute protein concentrations of CYP4F2 and CYP4F3B compared with CYP3A in two panels of HLMs (n = 31). As a result, the human hepatic cytochrome P450 (P450) "pie" has been revised to include the contribution of CYP4F enzymes, which amounts to 15% of the total hepatic cytochrome P450 enzymes. CYP4F3B displayed low interindividual variability (3.3-fold) in the HLM panels whereas CYP4F2 displayed large variability (21-fold). However, CYP4F2 variability decreased to 3.4-fold if the two donors with the lowest expression were excluded. In contrast, CYP3A exhibited 29-fold interindividual variability in the same HLM panels. The proposed marker reaction for CYP4F enzymes pafuramidine/DB289 M1 formation did not correlate with CYP4F protein content, suggesting alternate metabolic pathways for DB289 M1 formation in HLMs. In conclusion, CYP4F enzymes are highly expressed in the human liver and their physiologic and pharmacologic roles warrant further investigation.

  12. High-resolution micro-CT for morphologic and quantitative assessment of the sinusoid in human cavernous hemangioma of the liver.

    Directory of Open Access Journals (Sweden)

    Jinghao Duan

    Full Text Available Hepatic sinusoid plays a vital role in human cavernous hemangioma of the liver (CHL, and its morphologic investigation facilitates the understanding of microcirculation mechanism and pathological change of CHL. However, precise anatomical view of the hepatic sinusoid has been limited by the resolution and contrast available from existing imaging techniques. While liver biopsy has traditionally been the reliable method for the assessment of hepatic sinusoids, the invasiveness and sampling error are its inherent limitations. In this study, imaging of CHL samples was performed using in-line phase-contrast imaging (ILPCI technique with synchrotron radiation. ILPCI allowed clear visualization of soft tissues and revealed structural details that were invisible to conventional radiography. Combining the computed tomography (CT technique, ILPCI-CT was used to acquire the high-resolution micro-CT images of CHL, and three dimensional (3D microstructures of hepatic sinusoids were provided for the morphologic depiction and quantitative assessment. Our study demonstrated that ILPCI-CT could substantially improve the radiographic contrast of CHL tissues in vitro with no contrast agent. ILPCI-CT yielded high-resolution micro-CT image of CHL sample at the micron scale, corresponding to information on actual structures revealed at histological section. The 3D visualization provided an excellent view of the hepatic sinusoid. The accurate view of individual hepatic sinusoid was achieved. The valuable morphological parameters of hepatic sinusoids, such as thrombi, diameters, surface areas and volumes, were measured. These parameters were of great importance in the evaluation of CHL, and they provided quantitative descriptors that characterized anatomical properties and pathological features of hepatic sinusoids. The results highlight the high degree of sensitivity of the ILPCI-CT technique and demonstrate the feasibility of accurate visualization of hepatic

  13. Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

    DEFF Research Database (Denmark)

    Karsdal, Morten A; Manon-Jensen, Tina; Genovese, Federica

    2015-01-01

    Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essent......Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing......) explore key structural and functional components of the ECM as exemplified by monogenetic disorders leading to severe pathologies, 2) discuss selected pathological posttranslational modifications of ECM proteins resulting in altered functional (signaling) properties from the original structural proteins......, and 3) discuss how these findings support the novel concept that an increasing number of components of the ECM harbor signaling functions that can modulate fibrotic liver disease. The ECM entails functions in addition to anchoring cells and modulating their migratory behavior. Key ECM components...

  14. [Early identification of impaired renal function in obese children with non-alcoholic fatty liver disease].

    Science.gov (United States)

    Lin, Hu; Fu, Junfen; Chen, Xuefeng; Huang, Ke; Wu, Wei; Liang, Li

    2013-07-01

    To early assess the impaired renal function in the obese children with non-alcoholic fatty liver disease (NAFLD) and to identify the relationship between NAFLD and impairment of renal function. Three hundred and eighty-six obese children were enrolled and divided into NAFLD group and simple obesity group (control) according to the diagnostic criteria. Clinical biochemical parameters and early impaired renal functions were evaluated and compared. Among all patients 234 obese children aged over 10 y were subdivided into 3 groups: NAFLD combined with metabolic syndrome (NAFLD+MS) group, NAFLD group and simple obesity group (control), and the above indexes were compared among 3 groups. The urinary microalbumin levels in NAFLD, NAFLD+MS (>10y) and NAFLD groups (>10y) were significantly higher than those in controls. Additionally, the positive correlations of urinary microalbumin with systolic pressure, triglyceride and 2h-postprandial blood glucose were found. There is early renal dysfunction in children with NAFLD and those accompanied with MS, which may be associated with hypertension and glucose-lipid metabolic disorder. The results indicate that NAFLD is not only an early sign of early impaired renal function but also an early stage of chronic kidney disease (CKD) in obese children.

  15. ADH1B and ADH1C Genotype, Alcohol Consumption and Biomarkers of Liver Function

    DEFF Research Database (Denmark)

    Lawlor, Debbie A; Benn, Marianne; Zuccolo, Luisa;

    2014-01-01

    1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on alanine aminotransferase (ALT), γ-glutamyl-transferase (γ-GT), alkaline phosphatase (ALP), bilirubin and prothrombin action. Analyses were undertaken on 58,313 Danes (mean age 56). RESULTS......BACKGROUND: The effect of alcohol consumption on liver function is difficult to determine because of reporting bias and potential residual confounding. Our aim was to determine this effect using genetic variants to proxy for the unbiased effect of alcohol. METHODS: We used variants in ADH1B and ADH......: In both confounder adjusted multivariable and genetic-IV analyses greater alcohol consumption, amongst those who drank any alcohol, was associated with higher ALT [mean difference per doubling of alcohol consumption: 3.4% (95% CI: 3.1, 3.7) from multivariable analyses and 3.7% (-4.5, 11.9) from genetic...

  16. CHANGES IN SERUM ENZYMES LEVELS ASSOCIATED WITH LIVER FUNCTIONS IN STRESSED MARWARI GOAT

    Directory of Open Access Journals (Sweden)

    Kataria N.

    2011-03-01

    Full Text Available Serum enzyme levels were determined in goats of Marwari breed belonging to farmers’ stock of arid tract of Rajasthan state, India. The animals were grouped into healthy and stressed comprising of gastrointestinal parasiticised, pneumonia affected, and drought affected. The serum enzymes determined were sorbitol dehydrogenase, malate dehydrogenase, glucose-6-phosphate dehydrogenase, glutamate dehydrogenase, ornithine carbamoyl transferase, gamma-glutamayl transferase, 5’nucleotidase, glucose-6-phosphatase, arginase, and aldolase. In stressed group the mean values of all the enzymes increased significantly (p≤0.05 as compared to respective healthy mean value. All the enzymes showed highest values in the gastrointestinal parasiticised animals and least values in the animals having pneumonia. In gastrointestinal parasiticised animals maximum change was observed in G-6-Pase activity and minimum change was observed in malate dehydrogenase mean value. It was concluded that Increased activity of all the serum enzymes was due to modulation of liver functions directly or indirectly.

  17. Protective effects of Spirulina on the liver function and hyperlipidemia of rats and human

    Directory of Open Access Journals (Sweden)

    Mostafa Mohamed El-Sheekh

    2014-02-01

    Full Text Available In the present study, the effects of Spirulina on subchronic treatments (two weeks of hyperlipidemia and liver function of the rats and humans were investigated. The hyperlipidemia was induced in the rats using 25% of soya bean oil and 25% butter. The butter induced more hyperlipidemia than soya bean oil. Spirulina was used at the concentrations of 0, 2.5, 5.0 and 10 % of diet weight of the rats. The decrease in hyperlipidemia by Spirulina was dependent on its concentration in the diet. In case of human studies, about four g/day of Spirulina was taken via oral administration by Egyptian volunteers patients with hyperlipidemia. Spirulina decreased the levels of hyperlipidemia in these patients. The effects were dependent on the amount and number of administered dose of Sprirulina. The results suggested that the Spirulina treatment could induce marked reduction of aminotransferase through correcting lipid profile and increasing high density lipoprotein.

  18. Training signaling pathway maps to biochemical data with constrained fuzzy logic: quantitative analysis of liver cell responses to inflammatory stimuli.

    Directory of Open Access Journals (Sweden)

    Melody K Morris

    2011-03-01

    Full Text Available Predictive understanding of cell signaling network operation based on general prior knowledge but consistent with empirical data in a specific environmental context is a current challenge in computational biology. Recent work has demonstrated that Boolean logic can be used to create context-specific network models by training proteomic pathway maps to dedicated biochemical data; however, the Boolean formalism is restricted to characterizing protein species as either fully active or inactive. To advance beyond this limitation, we propose a novel form of fuzzy logic sufficiently flexible to model quantitative data but also sufficiently simple to efficiently construct models by training pathway maps on dedicated experimental measurements. Our new approach, termed constrained fuzzy logic (cFL, converts a prior knowledge network (obtained from literature or interactome databases into a computable model that describes graded values of protein activation across multiple pathways. We train a cFL-converted network to experimental data describing hepatocytic protein activation by inflammatory cytokines and demonstrate the application of the resultant trained models for three important purposes: (a generating experimentally testable biological hypotheses concerning pathway crosstalk, (b establishing capability for quantitative prediction of protein activity, and (c prediction and understanding of the cytokine release phenotypic response. Our methodology systematically and quantitatively trains a protein pathway map summarizing curated literature to context-specific biochemical data. This process generates a computable model yielding successful prediction of new test data and offering biological insight into complex datasets that are difficult to fully analyze by intuition alone.

  19. Training signaling pathway maps to biochemical data with constrained fuzzy logic: quantitative analysis of liver cell responses to inflammatory stimuli.

    Science.gov (United States)

    Morris, Melody K; Saez-Rodriguez, Julio; Clarke, David C; Sorger, Peter K; Lauffenburger, Douglas A

    2011-03-01

    Predictive understanding of cell signaling network operation based on general prior knowledge but consistent with empirical data in a specific environmental context is a current challenge in computational biology. Recent work has demonstrated that Boolean logic can be used to create context-specific network models by training proteomic pathway maps to dedicated biochemical data; however, the Boolean formalism is restricted to characterizing protein species as either fully active or inactive. To advance beyond this limitation, we propose a novel form of fuzzy logic sufficiently flexible to model quantitative data but also sufficiently simple to efficiently construct models by training pathway maps on dedicated experimental measurements. Our new approach, termed constrained fuzzy logic (cFL), converts a prior knowledge network (obtained from literature or interactome databases) into a computable model that describes graded values of protein activation across multiple pathways. We train a cFL-converted network to experimental data describing hepatocytic protein activation by inflammatory cytokines and demonstrate the application of the resultant trained models for three important purposes: (a) generating experimentally testable biological hypotheses concerning pathway crosstalk, (b) establishing capability for quantitative prediction of protein activity, and (c) prediction and understanding of the cytokine release phenotypic response. Our methodology systematically and quantitatively trains a protein pathway map summarizing curated literature to context-specific biochemical data. This process generates a computable model yielding successful prediction of new test data and offering biological insight into complex datasets that are difficult to fully analyze by intuition alone.

  20. Prediction of poor graft function by means of gastric tonometry in patients undergoing liver transplantation.

    Science.gov (United States)

    Perilli, Valter; Aceto, Paola; Modesti, Cristina; Vitale, Francesca; Ciocchetti, Pierpaolo; Sacco, Teresa; Adduci, Alessia; Lai, Carlo; Avolio, Alfonso W; Sollazzi, Liliana

    INTRODUCTION. Splanchnic hypoperfusion appears to play a key role in the failure of functional recovery of the graft after orthotopic liver transplantation (LT). The aim of this study was to determine if alterations of tonometric parameters, which are related to splanchnic perfusion, could predict poor graft function in patients undergoing LT. After Ethics Committee approval, 68 patients undergoing LT were enrolled. In all the patients, regional-arterial CO2 gradient (Pr-aCO2) was recorded; in addition, the difference between Pr-aCO2 recorded at anhepatic phase (T1) and at the end of surgery (T2) (T2- T1 = ΔPr-aCO2) was calculated. Poor graft function was determined on the basis of Toronto's classification 72 hours after LT. Student t-test and logistic regression analysis were used for statistical purpose. Results. ΔPr-aCO2 was significantly greater in patients with poor graft function (3.5 ± 13.2) compared to patients with good graft function (-5.8 ± 12.3) (p = 0.014). The logistic regression analysis showed that the ΔPr-aCO2 was able to predict the onset of poor graft function (p = 0.037). A value of ΔPr-aCO2 ≥ -4 was associated with poor graft function with a sensibility of 93.3% and a specificity of 42.3%. CONCLUSION. Our study suggests that the change of Pr-aCO2 may be a valuable index of graft dysfunction. Gastric tonometry might give early prognostic information on the graft outcome, and it may aid clinicians in planning a more strict follow-up and proper interventions in order to improve graft survival.

  1. Prospective Randomized Trial Comparing Hepatic Venous Outflow and Renal Function after Conventional versus Piggyback Liver Transplantation.

    Directory of Open Access Journals (Sweden)

    Marília D'Elboux Guimarães Brescia

    Full Text Available This randomized prospective clinical trial compared the hepatic venous outflow drainage and renal function after conventional with venovenous bypass (n = 15 or piggyback (n = 17 liver transplantation.Free hepatic vein pressure (FHVP and central venous pressure (CVP measurements were performed after graft reperfusion. Postoperative serum creatinine (Cr was measured daily on the first week and on the 14th, 21st and 28th postoperative days (PO. The prevalence of acute renal failure (ARF up to the 28th PO was analyzed by RIFLE-AKIN criteria. A Generalized Estimating Equation (GEE approach was used for comparison of longitudinal measurements of renal function.FHVP-CVP gradient > 3 mm Hg was observed in 26.7% (4/15 of the patients in the conventional group and in 17.6% (3/17 in the piggyback group (p = 0.68. Median FHVP-CVP gradient was 2 mm Hg (0-8 mmHg vs. 3 mm Hg (0-7 mm Hg in conventional and piggyback groups, respectively (p = 0.73. There is no statistically significant difference between the conventional (1/15 and the piggyback (2/17 groups regarding massive ascites development (p = 1.00. GEE estimated marginal mean for Cr was significantly higher in conventional than in piggyback group (2.14 ± 0.26 vs. 1.47 ± 0.15 mg/dL; p = 0.02. The conventional method presented a higher prevalence of severe ARF during the first 28 PO days (OR = 3.207; 95% CI, 1.010 to 10.179; p = 0.048.Patients submitted to liver transplantation using conventional or piggyback methods present similar results regarding venous outflow drainage of the graft. Conventional with venovenous bypass technique significantly increases the harm of postoperative renal dysfunction.ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01707810.

  2. INHIBITION OF BILE ACID ACCUMULATION DECREASED THE EXCESSIVE HEPATOCYTE APOPTOSIS AND IMPROVED THE LIVER SECRETION FUNCTIONS ON OBSTRUCTIVE JAUNDICE PATIENTS

    Directory of Open Access Journals (Sweden)

    Akmal Taher

    2011-06-01

    Full Text Available Excessive hepatocyte apoptosis induced by bile acid accumulation occurred in severe obstructive jaundice, and impair the liver secretion function. The objective of this study is to determine whether the inhibition of bile acid accumulation through bile duct decompression affect the excessive hepatocyte apoptosis and caused improvement the liver secretion functions on human model. In this study we use a before and after study on severe obstructive jaundice patients due to extra hepatic bile duct tumor was decompressed. Bile duct decompression was performed as a model of the role of inhibition of bile acid accumulation inhibition bile acid accumulation and excessive hepatocyte apoptosis. Bile acid and marker of liver secretion functions were serially measured. Liver biopsy pre and post decompression was performed for Hepatocyte apoptosis pathologic examination by TUNEL fluorescing, which measured by 2 people in double blinded system. Total bile acid, and liver secretion functions were measured by automated chemistry analyzer. The result of this study shows that twenty one severe obstructive jaundice patients were included. After decompression the hepatocyte apoptosis index decreased from an average of 53.1 (SD 105 to 11.7 (SD 13.6 (p < 0.05. Average of bile acid serum decreased from 96.4 (SD 53.8 to 19.9 (SD 39.5 until 13.0 (SD 12.6 μmol/L (p < 0.05 Total ilirubin decreased from 20.0 (SD 8.9 to 13.3 (SD 5.0 until 6.2 (SD 4.0 mg/dL (p < 0.05, while the phosphates alkaline (ALP and γ-glutamil transpeptidase (γ-GT activities also decreased ignificantly. In conclusion, bile acids accumulation and excessive hepatocyte poptosis through bile duct decompression improve the liver secretion functions by inhibition mechanism.

  3. The impact of pelvic floor surgery on female sexual function: a mixed quantitative and qualitative study.

    Science.gov (United States)

    Roos, A M; Thakar, R; Sultan, A H; de Leeuw, J W; Paulus, A T G

    2014-01-01

    To assess whether the current condition-specific sexual function questionnaire provides full insight into sexual function following pelvic floor surgery. Prospective, mixed quantitative and qualitative study. Urogynaecology clinic in a large university hospital. Thirty-seven women undergoing surgery for pelvic organ prolapse (POP) and/or stress urinary incontinence (SUI). Women were seen before surgery and 3 months postoperatively. At both visits the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ) was completed and a qualitative face-to-face semi-structured interview was conducted. PISQ total and domain scores, as well as the change in the preoperative and postoperative score, were calculated and analysed using Wilcoxon signed rank test and one-sample t-test. The qualitative data were systematically analysed using data-matrices. The impact of pelvic floor surgery on female sexual function. Significant improvement was seen for PISQ total score (P = 0.003) as well as Physical (P qualitative data showed that improvement in sexual function was a result of cure of POP and SUI symptoms. Deterioration of sexual function was due to dyspareunia, fear of causing damage to the surgical result, new symptoms and a disappointing result of surgery. Our qualitative data show that PISQ is limited in the assessment of sexual function after pelvic floor surgery as it does not assess most surgery-specific negative effects on sexual function. © 2013 Royal College of Obstetricians and Gynaecologists.

  4. Effects of crystalloids and colloids on liver and intestine microcirculation and function in cecal ligation and puncture induced septic rodents

    Science.gov (United States)

    2012-01-01

    Background Septic acute liver and intestinal failure is associated with a high mortality. We therefore investigated the influence of volume resuscitation with different crystalloid or colloid solutions on liver and intestine injury and microcirculation in septic rodents. Methods Sepsis was induced by cecal ligation and puncture (CLP) in 77 male rats. Animals were treated with different crystalloids (NaCl 0.9% (NaCl), Ringer’s acetate (RA)) or colloids (Gelafundin 4% (Gel), 6% HES 130/0.4 (HES)). After 24 h animals were re-anesthetized and intestinal (n = 6/group) and liver microcirculation (n = 6/group) were obtained using intravital microscopy, as well as macrohemodynamic parameters were measured. Blood assays and organs were harvested to determine organ function and injury. Results HES improved liver microcirculation, cardiac index and DO2-I, but significantly increased IL-1β, IL-6 and TNF-α levels and resulted in a mortality rate of 33%. Gel infused animals revealed significant reduction of liver and intestine microcirculation with severe side effects on coagulation (significantly increased PTT and INR, decreased haemoglobin and platelet count). Furthermore Gel showed severe hypoglycemia, acidosis and significantly increased ALT and IL-6 with a lethality of 29%. RA exhibited no derangements in liver microcirculation when compared to sham and HES. RA showed no intestinal microcirculation disturbance compared to sham, but significantly improved the number of intestinal capillaries with flow compared to HES. All RA treated animals survided and showed no severe side effects on coagulation, liver, macrohemodynamic or metabolic state. Conclusions Gelatine 4% revealed devastated hepatic and intestinal microcirculation and severe side effects in CLP induced septic rats, whereas the balanced crystalloid solution showed stabilization of macro- and microhemodynamics with improved survival. HES improved liver microcirculation, but exhibited significantly

  5. The effect of Jinlong capsule on the immune function for intervened patients with primary liver cancer

    Institute of Scientific and Technical Information of China (English)

    Chunsheng Zeng; Lianming Cai; Zuochao Huang; Qingyun Xu

    2014-01-01

    Objective:The aim of this study was to evaluate the ef ect of Jinlong capsule on the immune function for inter-vened patients with primary liver cancer. Methods:Matched the inclusion criteria, 60 patients were selected and randomly divided into two groups. The treatment group had 30 cases treated with Jinlong capsule combined with the transcatheter arterial chemoembolization (TACE);the control group had 30 cases treated with TACE. Each group was treated 30 days as a cycle, which had completed at least two cycles. Indicators of cellular immune function about the activity of CD3, CD4, CD8, CD4/CD8 and natural kil er (NK) cellwere detected before and after treatment, then to compare and analysis with each other. Results:Before treatment, the activity of peripheral blood CD3, CD4, CD8, CD4/CD8 and NK cellin the two groups was no significant dif erence (P>0.05);after treatment, the activity of CD3, CD4 and NK cellin the treatment group was significantly increased, the ratio of CD4/CD8 increased, and the value of CD8 decreased (P0.05), the dif erence between the two groups indicated the statistical significance (P0.05). Conclusion:Jinlong capsule with hepatic arterial infusion chemotherapy can improve the patients’ immune function, and reduce the adverse reactions of interventional chemotherapy. Hence,it deserves to be promoted in clinical y.

  6. Quantitative secondary electron imaging for work function extraction at atomic level and layer identification of graphene.

    Science.gov (United States)

    Zhou, Yangbo; Fox, Daniel S; Maguire, Pierce; O'Connell, Robert; Masters, Robert; Rodenburg, Cornelia; Wu, Hanchun; Dapor, Maurizio; Chen, Ying; Zhang, Hongzhou

    2016-02-16

    Two-dimensional (2D) materials usually have a layer-dependent work function, which require fast and accurate detection for the evaluation of their device performance. A detection technique with high throughput and high spatial resolution has not yet been explored. Using a scanning electron microscope, we have developed and implemented a quantitative analytical technique which allows effective extraction of the work function of graphene. This technique uses the secondary electron contrast and has nanometre-resolved layer information. The measurement of few-layer graphene flakes shows the variation of work function between graphene layers with a precision of less than 10 meV. It is expected that this technique will prove extremely useful for researchers in a broad range of fields due to its revolutionary throughput and accuracy.

  7. [Liver function of workers occupationally exposed to mixed organic solvents in a petrochemical industry].

    Science.gov (United States)

    Fernández-D'Pool, J; Oroño-Osorio, A

    2001-06-01

    A descriptive and cross sectional study was conducted to determine whether hepatic function changes in workers occupationally exposed to a mixture of organic solvents, were due to the exposure or confusing factors. A non random sample of 77 workers, operators and supervisors of the Olefin Plant I and II of a petrochemical industry in Maracaibo, Venezuela, was used. Their mean age was 29 +/- 7 years, and had at least one year of exposure to the solvents. This sample was compared with a group of employees of the administrative offices or control panel workers, with a mean age of 36 +/- 8 year and with similar anthropometric characteristics. Workers with a known history of liver disease, blood transfusions and diabetes mellitus were excluded of the study. In addition to a complete occupational disease medical history and a physical examination, serum samples were obtained to determine the activity of the aspartato aminotransferase (AST), alanin aminotransferase (ALT), gamma glutamiltransferase (GGT), alkaline phosphatase (AF), the concentration of the total bile acids (BAS), the surface antigen of hepatitis B(HbsAg) and the hepatitis A virus antibodies: AntiHAV-IgG and the AntiHAV-IgM. An urine sample was taken and analyzed by standard methodology to determine urinary phenols. The air concentrations of benzene, ethylbenzene, toluene and xylene were analyzed by gas chromathography. The serum activities of the liver enzymes, the concentration of bile acids and urinary phenols were not influenced by the exposure to the solvents. The increase of the activity of GGT was associated with obesity and alcohol consumption. The antibodies of the surface antigen of hepatitis A-IgM were normal in both groups and the antibodies for the antigen of hepatitis A-IgG presented a prevalence of 6% in the exposed group and 9% in the non exposed not being associated with liver abnormalities. The individual air concentrations of the solvents were below the environmentally permissible

  8. 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.

  9. Functional Analysis of the Unique Cytochrome P450 of the Liver Fluke Opisthorchis felineus

    Science.gov (United States)

    Pakharukova, Mariya Y.; Vavilin, Valentin A.; Sripa, Banchob; Laha, Thewarach; Brindley, Paul J.; Mordvinov, Viatcheslav A.

    2015-01-01

    The basic metabolic cytochrome P450 (CYP) system is essential for biotransformation of sterols and xenobiotics including drugs, for synthesis and degradation of signaling molecules in all living organisms. Most eukaryotes including free-living flatworms have numerous paralogues of the CYP gene encoding heme monooxygenases with specific substrate range. Notably, by contrast, the parasitic flatworms have only one CYP gene. The role of this enzyme in the physiology and biochemistry of helminths is not known. The flukes and tapeworms are the etiologic agents of major neglected tropical diseases of humanity. Three helminth infections (Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium) are considered by the International Agency for Research on Cancer (IARC) as definite causes of cancer. We focused our research on the human liver fluke Opisthorchis felineus, an emerging source of biliary tract disease including bile duct cancer in Russia and central Europe. The aims of this study were (i) to determine the significance of the CYP activity for the morphology and survival of the liver fluke, (ii) to assess CYP ability to metabolize xenobiotics, and (iii) to localize the CYP activity in O. felineus tissues. We observed high constitutive expression of CYP mRNA (Real-time PCR) in O. felineus. This enzyme metabolized xenobiotics selective for mammalian CYP2E1, CYP2B, CYP3A, but not CYP1A, as determined by liquid chromatography and imaging analyses. Tissue localization studies revealed the CYP activity in excretory channels, while suppression of CYP mRNA by RNA interference was accompanied by morphological changes of the excretory system and increased mortality rates of the worms. These results suggest that the CYP function is linked to worm metabolism and detoxification. The findings also suggest that the CYP enzyme is involved in vitally important processes in the organism of parasites and is a potential drug target. PMID:26625139

  10. The utility of pulmonary function testing in predicting outcomes following liver transplantation.

    Science.gov (United States)

    Kia, Leila; Cuttica, Michael J; Yang, Amy; Donnan, Erica N; Whitsett, Maureen; Singhvi, Ajay; Lemmer, Alexander; Levitsky, Josh

    2016-06-01

    Although pulmonary function tests (PFTs) are routinely performed in patients during the evaluation period before liver transplantation (LT), their utility in predicting post-LT mortality and morbidity outcomes is not known. The aim of this study was to determine the impact of obstructive and/or restrictive lung disease on post-LT outcomes. We conducted a retrospective analysis of patients who had pre-LT PFTs and underwent a subsequent LT (2007-2013). We used statistical analyses to determine independent associations between PFT parameters and outcomes (graft/patient survival, time on ventilator, and hospital/intensive care unit [ICU] length of stay [LOS]). A total of 415 LT recipients with available PFT data were included: 65% of patients had normal PFTs; 8% had obstructive lung disease; and 27% had restrictive lung disease. There was no difference in patient and graft survival between patients with normal, obstructive, and restrictive lung disease. However, restrictive lung disease was associated with longer post-LT time on ventilator and both ICU and hospital LOS (P < 0.05). More specific PFT parameters (diffusing capacity of the lungs for carbon monoxide, total lung capacity, and residual volume) were all significant predictors of ventilator time and both ICU and hospital LOS (P < 0.05). Although pre-LT PFT parameters may not predict post-LT mortality, restrictive abnormalities correlate with prolonged post-LT ventilation and LOS. Efforts to identify and minimize the impact of restrictive abnormalities on PFTs might improve such outcomes. Liver Transplantation 22 805-811 2016 AASLD.

  11. Correlation between liver function tests and metabolic syndrome in hepatitis-free elderly

    Directory of Open Access Journals (Sweden)

    Hung-Sheng Shang

    2015-01-01

    Full Text Available Background: We aimed to investigate the relationship between liver function tests (LFTs and metabolic syndrome (MetS as several studies have shown positive correlations between some of the LFTs, including alanine aminotransferase (ALT and γ-glutamyl transpeptidase (γ-GT, and MetS but have not fully explored the same in the elderly. Owing to the progress in public health, the aging of the general population becomes a major issue. Design: We enrolled subjects aged over 60 years who underwent routine health checkups in a Health Screening Center after excluding subjects with a history of hepatitis B or C infection, excessive alcohol consumption, liver fibrosis, cirrhosis, acute hepatitis, diabetes, hypertension, dyslipidemia, cardiovascular disease, or receiving medications for these diseases. Finally, 9,282 participants were eligible for analysis. Statistical Analysis: All data were tested for normal distribution with the Kolmogorov-Smirnov test and for homogeneity of variances with the Levene′s test. A t-test was used to evaluate the differences between the two groups. Univariate and multivariate regressions were used to observe correlations between different parameters. Receiver operating characteristic curves of each LFT were used to predict MetS. Areas under curves and 95% confidence interval were also estimated and compared. Results: With the exception of aspartate aminotransferase and α-fetal protein, the results of LFTs, including total and direct bilirubin, alkaline phosphatase (ALP, ALT, and γ-GT, were altered in the group with MetS. Furthermore, the levels of γ-GT in men and ALP in women were independently associated with all MetS components and had the highest areas under receiver operating characteristic curves. Conclusion: Abnormal LFTs are highly correlated with MetS in the hepatitis-free elderly, with levels of γ-GT in men and ALP in women being the most important factors. LFTs may represent an auxiliary tool for the

  12. Functional Analysis of the Unique Cytochrome P450 of the Liver Fluke Opisthorchis felineus.

    Directory of Open Access Journals (Sweden)

    Mariya Y Pakharukova

    2015-12-01

    Full Text Available The basic metabolic cytochrome P450 (CYP system is essential for biotransformation of sterols and xenobiotics including drugs, for synthesis and degradation of signaling molecules in all living organisms. Most eukaryotes including free-living flatworms have numerous paralogues of the CYP gene encoding heme monooxygenases with specific substrate range. Notably, by contrast, the parasitic flatworms have only one CYP gene. The role of this enzyme in the physiology and biochemistry of helminths is not known. The flukes and tapeworms are the etiologic agents of major neglected tropical diseases of humanity. Three helminth infections (Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium are considered by the International Agency for Research on Cancer (IARC as definite causes of cancer. We focused our research on the human liver fluke Opisthorchis felineus, an emerging source of biliary tract disease including bile duct cancer in Russia and central Europe. The aims of this study were (i to determine the significance of the CYP activity for the morphology and survival of the liver fluke, (ii to assess CYP ability to metabolize xenobiotics, and (iii to localize the CYP activity in O. felineus tissues. We observed high constitutive expression of CYP mRNA (Real-time PCR in O. felineus. This enzyme metabolized xenobiotics selective for mammalian CYP2E1, CYP2B, CYP3A, but not CYP1A, as determined by liquid chromatography and imaging analyses. Tissue localization studies revealed the CYP activity in excretory channels, while suppression of CYP mRNA by RNA interference was accompanied by morphological changes of the excretory system and increased mortality rates of the worms. These results suggest that the CYP function is linked to worm metabolism and detoxification. The findings also suggest that the CYP enzyme is involved in vitally important processes in the organism of parasites and is a potential drug target.

  13. Should we look for celiac disease among all patients with liver function test abnormalities?

    Directory of Open Access Journals (Sweden)

    Mohammad Hassan Emami

    2012-01-01

    Full Text Available Background: Celiac disease (CD has been found in up to 10% of the patients presenting with unexplained abnormal liver function tests (LFT. As there is no precise data from our country in this regard, we investigated the prevalence of CD in patients presenting with abnormal LFT. Methods: From 2003 to 2008, we measured IgA anti-tissue transglutaminase (t-TG antibody (with ELISA technique within the first-level screening steps for all patients presenting with abnormal LFT to three outpatient gastroenterology clinics in Isfahan, IRAN. All subjects with an IgA anti-tTG antibody value of >10 μ/ml (seropositive were undergone upper gastrointestinal endoscopy and duodenal biopsy. Histopathological changes were assessed according to the Marsh classification. CD was defined as being seropositive with Marsh I or above in histopathology and having a good response to gluten free diet (GFD. Results: During the study, 224 patients were evaluated, out of which, 10 patients (4.4% were seropositive for CD. Duodenal biopsies were performed in eight patients and revealed six (2.7% cases of Marsh I or above (four Marsh IIIA, two Marsh I, all of them had good response to GFD. The overall prevalence of CD among patients with hypertransaminasemia, autoimmune hepatitis, and cryptogenic cirrhosis was determined as 10.7% (3/28, 3.4% (2/59, and 5.3% (1/19, respectively. Conclusion: Serological screening with IgA anti-tTG antibody test should be routinely performed in patients presenting with abnormal LFT and especially those with chronic liver diseases including hypertransaminasemia, autoimmune hepatitis, and cryptogenic cirrhosis.

  14. Morphological, functional and metabolic imaging biomarkers: assessment of vascular-disrupting effect on rodent liver tumours

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huaijun; Li, Junjie; Keyzer, Frederik De; Yu, Jie; Feng, Yuanbo; Marchal, Guy; Ni, Yicheng [University Hospitals, University of Leuven, Department of Radiology, Leuven (Belgium); Chen, Feng [University Hospitals, University of Leuven, Department of Radiology, Leuven (Belgium); Southeast University, Department of Radiology, Zhongda Hospital, Nanjing (China); Nuyts, Johan [University Hospitals, University of Leuven, Department of Nuclear Medicine, Leuven (Belgium)

    2010-08-15

    To evaluate effects of a vascular-disrupting agent on rodent tumour models. Twenty rats with liver rhabdomyosarcomas received ZD6126 intravenously at 20 mg/kg, and 10 vehicle-treated rats were used as controls. Multiple sequences, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) with the microvascular permeability constant (K), were acquired at baseline, 1 h, 24 h and 48 h post-treatment by using 1.5-T MRI. [{sup 18}F]fluorodeoxyglucose micro-positron emission tomography ({sup 18}F-FDG {mu}PET) was acquired pre- and post-treatment. The imaging biomarkers including tumour volume, enhancement ratio, necrosis ratio, apparent diffusion coefficient (ADC) and K from MRI, and maximal standardised uptake value (SUV{sub max}) from FDG {mu}PET were quantified and correlated with postmortem microangiography and histopathology. In the ZD6126-treated group, tumours grew slower with higher necrosis ratio at 48 h (P < 0.05), corresponding well to histopathology; tumour K decreased from 1 h until 24 h, and partially recovered at 48 h (P < 0.05), parallel to the evolving enhancement ratios (P < 0.05); ADCs varied with tumour viability and perfusion; and SUV{sub max} dropped at 24 h (P < 0.01). Relative K of tumour versus liver at 48 h correlated with relative vascular density on microangiography (r = 0.93, P < 0.05). The imaging biomarkers allowed morphological, functional and metabolic quantifications of vascular shutdown, necrosis formation and tumour relapse shortly after treatment. A single dose of ZD6126 significantly diminished tumour blood supply and growth until 48 h post-treatment. (orig.)

  15. The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity

    Directory of Open Access Journals (Sweden)

    Lucia Pacifico

    2016-07-01

    Full Text Available The association between nonalcoholic fatty liver disease (NAFLD and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m2. Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m2 was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001. The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001. Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16–5.57; p < 0.05 independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease.

  16. Thyroid function in obese children with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Bilgin, Hüseyin; Pirgon, Özgür

    2014-09-01

    To investigate the relationships between thyroid function and metabolic risk factors in obese adolescents with non-alcoholic fatty liver disease (NAFLD). One hundred sixty obese adolescents and 40 control subjects were enrolled in the study. The obese subjects were divided into two groups based on presence or absence of liver steatosis (NAFLD group and non-NAFLD group). Serum samples were assayed for glucose, insulin, cholesterol, alanine aminotransferase, aspartate aminotransferase, free thyroxine (fT4), free triiodothyronine (fT3) and thyroid-stimulating hormone (TSH). The ratio of fT3 to fT4 was evaluated as an indirect index of deiodinase activity. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples. NAFLD and non-NAFLD groups had slightly higher fasting blood glucose values than the control group. Fasting insulin levels in the NAFLD group were significantly higher than those in the non-NAFLD and control groups. The NAFLD group had significantly greater HOMA-IR values compared with the non-NAFLD group and also with the control group. The NAFLD group had significantly higher fT3/fT4 ratio values compared to both non-NAFLD and control groups. fT3/fT4 was positively correlated with serum insulin levels in the NAFLD group. This study showed that obese adolescents with hepatosteatosis had elevated values for fT3/fT4 ratio. This finding suggested a high conversion of T4 to T3 due to increased deiodinase activity as a compensatory mechanism for fat accumulation.

  17. Functional and genetic deconstruction of the cellular origin in liver cancer

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B; Thorgeirsson, Snorri S

    2015-01-01

    During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation......, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance...... of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution...

  18. Supplementation with selenium can influence nausea, fatigue, physical, renal, and liver function of children and adolescents with cancer.

    Science.gov (United States)

    Vieira, Maria Luiza Dos Santos; Fonseca, Fernando Luiz Affonso; Costa, Larissa Grossi; Beltrame, Registila Libania; Chaves, Carolina Machado de Sousa; Cartum, Jairo; Alves, Sarah Isabel P M do N; Azzalis, Ligia Ajaime; Junqueira, Virginia Berlanga Campos; Pereria, Edimar Cristiano; Rocha, Katya Cristina

    2015-01-01

    The drugs used in chemotherapy treatments have little specificity, attack tumor cells, and also injure proliferative tissues. Knowledge of the functions of micronutrients has greatly increased, especially of Selenium (Se) that presents immunomodulatory and antitumor functions. The present study evaluated the health-related quality of life of patients undergoing chemotherapy for the treatment of leukemias and lymphomas (LL) and solid tumors (ST) while receiving Selenium (Se) supplementation. This is a randomized, double-blind, crossover study that evaluated the quality of life (EORTC-QLQ-C30 questionnaire), renal and liver functions of patients supplemented with Se. There was no statistically significant alteration in LL patients. However, the fatigue and nausea scores after 30 days did decrease in this group as well as in the ST group. After 1 year supplementation with Selenium, a more noticeable decrease in the scores concerning fatigue and nausea could be observed in the ST group, when compared with the beginning of the study. The LL patients also presented a decrease in the fatigue scores and physical functions. The kidney function as well as liver function has improved after Selenium supplementation when compared with the placebo intake in LL and ST patients, more remarkably in the LL group. Supplementation with Selenium promotes the reduction of chemotherapy side effects in cancer patients, especially by improving the conditions of patients with fatigue, nausea, and impaired physical function. Renal and liver functions have also improved.

  19. Multi-institutional Quantitative Evaluation and Clinical Validation of Smart Probabilistic Image Contouring Engine (SPICE) Autosegmentation of Target Structures and Normal Tissues on Computer Tomography Images in the Head and Neck, Thorax, Liver, and Male Pelvis Areas

    NARCIS (Netherlands)

    Zhu, Mingyao; Bzdusek, Karl; Brink, Carsten; Eriksen, Jesper Grau; Hansen, Olfred; Jensen, Helle Anita; Gay, Hiram A.; Thorstad, Wade; Widder, Joachim; Brouwer, Charlotte L.; Steenbakkers, Roel J. H. M.; Vanhauten, Hubertus A. M.; Cao, Jeffrey Q.; McBrayne, Gail; Patel, Salil H.; Cannon, Donald M.; Hardcastle, Nicholas; Tome, Wolfgang A.; Guckenberg, Matthias; Parikh, Parag J.

    2013-01-01

    Purpose: Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE). Methods and Materials: CT images of 125 treated patients (32 head and neck [HN], 40 thorax, 23 liver, and 30 prostate) in 7 independe

  20. The impact of chronic carrier of hepatitis B virus on liver function in a 7-day ultramarathon race

    Directory of Open Access Journals (Sweden)

    Shang-Lin Chou

    2016-04-01

    Conclusion: Compared to their counterparts, runners who are HBV carriers had significantly greater increases in levels of ALT, AST, and T-BIL during a 7-day ultramarathon, indicating that the liver function of carriers is more highly impacted in these races.

  1. Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury

    NARCIS (Netherlands)

    Olthof, Pim B.; Golen, van Rowan F.; Meijer, Ben; Beek, van Adriaan A.; Bennink, Roelof J.; Verheij, Joanne; Gulik, van Thomas M.; Heger, Michal

    2017-01-01

    Background

    Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used mouse I/R models are too severe and poorly reflect the clinical injury profile. The aim was to establish a mouse

  2. Quantitative analysis of PEG-functionalized colloidal gold nanoparticles using charged aerosol detection.

    Science.gov (United States)

    Smith, Mackensie C; Crist, Rachael M; Clogston, Jeffrey D; McNeil, Scott E

    2015-05-01

    Surface characteristics of a nanoparticle, such as functionalization with polyethylene glycol (PEG), are critical to understand and achieve optimal biocompatibility. Routine physicochemical characterization such as UV-vis spectroscopy (for gold nanoparticles), dynamic light scattering, and zeta potential are commonly used to assess the presence of PEG. However, these techniques are merely qualitative and are not sensitive enough to distinguish differences in PEG quantity, density, or presentation. As an alternative, two methods are described here which allow for quantitative measurement of PEG on PEGylated gold nanoparticles. The first, a displacement method, utilizes dithiothreitol to displace PEG from the gold surface. The dithiothreitol-coated gold nanoparticles are separated from the mixture via centrifugation, and the excess dithiothreitol and dissociated PEG are separated through reversed-phase high-performance liquid chromatography (RP-HPLC). The second, a dissolution method, utilizes potassium cyanide to dissolve the gold nanoparticles and liberate PEG. Excess CN(-), Au(CN)2 (-), and free PEG are separated using RP-HPLC. In both techniques, the free PEG can be quantified against a standard curve using charged aerosol detection. The displacement and dissolution methods are validated here using 2-, 5-, 10-, and 20-kDa PEGylated 30-nm colloidal gold nanoparticles. Further value in these techniques is demonstrated not only by quantitating the total PEG fraction but also by being able to be adapted to quantitate the free unbound PEG and the bound PEG fractions. This is an important distinction, as differences in the bound and unbound PEG fractions can affect biocompatibility, which would not be detected in techniques that only quantitate the total PEG fraction.

  3. An MRM-based workflow for absolute quantitation of lysine-acetylated metabolic enzymes in mouse liver.

    Science.gov (United States)

    Xu, Leilei; Wang, Fang; Xu, Ying; Wang, Yi; Zhang, Cuiping; Qin, Xue; Yu, Hongxiu; Yang, Pengyuan

    2015-12-07

    As a key post-translational modification mechanism, protein acetylation plays critical roles in regulating and/or coordinating cell metabolism. Acetylation is a prevalent modification process in enzymes. Protein acetylation modification occurs in sub-stoichiometric amounts; therefore extracting biologically meaningful information from these acetylation sites requires an adaptable, sensitive, specific, and robust method for their quantification. In this work, we combine immunoassays and multiple reaction monitoring-mass spectrometry (MRM-MS) technology to develop an absolute quantification for acetylation modification. With this hybrid method, we quantified the acetylation level of metabolic enzymes, which could demonstrate the regulatory mechanisms of the studied enzymes. The development of this quantitative workflow is a pivotal step for advancing our knowledge and understanding of the regulatory effects of protein acetylation in physiology and pathophysiology.

  4. Rainbow trout peptidoglycan recognition protein has an anti-inflammatory function in liver cells.

    Science.gov (United States)

    Jang, Ju Hye; Kim, Hyun; Cho, Ju Hyun

    2013-12-01

    Peptidoglycan recognition proteins (PGRPs) are innate immune molecules that are structurally conserved through evolution in both invertebrate and vertebrate animals. PGRPs exert diverse host-defense functions both through direct antibacterial activity and through indirect effects, including the induction of antimicrobial peptides and the modulation of inflammation and immune responses. In this study, we identified the gene encoding a long form of PGRP (OmPGRP-L1) from the rainbow trout, Oncorhynchus mykiss, and investigated whether it has immunomodulating activity in a rainbow trout hepatoma cell line RTH-149 challenged with fish pathogenic bacteria. OmPGRP-L1 contains the conserved PGRP domain and the four Zn(2+)-binding amino acid residues required for amidase activity. In RTH-149 cells, OmPGRP-L1 expression was increased by bacterial stimulation. Loss-of-function and gain-of-function experiments indicated that OmPGRP-L1 is involved in the expression of pro-inflammatory cytokines. Silencing of OmPGRP-L1 in RTH-149 cells challenged with Edwardsiella tarda dramatically increased the expression of IL-1β and TNF-α. In contrast, overexpression of OmPGRP-L1 or its amidase-inactive mutant OmPGRP-L1(C472S) resulted in down-regulation of IL-1β and TNF-α expression. When overexpressed in RTH-149 cells, OmPGRP-L1 inhibited NF-κB activity with or without bacterial stimulation. Collectively, these findings suggest that OmPGRP-L1 has an anti-inflammatory function, independent of its amidase activity, possibly via NF-κB inhibition in liver cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Phenotypic and functional analysis of human fetal liver hematopoietic stem cells in culture.

    Science.gov (United States)

    Rollini, Pierre; Faes-Van't Hull, Eveline; Kaiser, Stefan; Kapp, Ursula; Leyvraz, Serge

    2007-04-01

    Steady-state hematopoiesis and hematopoietic transplantation rely on the unique potential of stem cells to undergo both self-renewal and multilineage differentiation. Fetal liver (FL) represents a promising alternative source of hematopoietic stem cells (HSCs), but limited by the total cell number obtained in a typical harvest. We reported that human FL nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulating cells (SRCs) could be expanded under simple stroma-free culture conditions. Here, we sought to further characterize FL HSC/SRCs phenotypically and functionally before and following culture. Unexpanded or cultured FL cell suspensions were separated into various subpopulations. These were tested for long-term culture potential and for in vivo repopulating function following transplantation into NOD/SCID mice. We found that upon culture of human FL cells, a tight association between classical stem cell phenotypes, such as CD34(+) /CD38(-) and/or side population, and NOD/SCID repopulating function was lost, as observed with other sources. Although SRC activity before and following culture consistently correlated with the presence of a CD34(+) cell population, we provide evidence that, contrary to umbilical cord blood and adult sources, stem cells present in both CD34(+) and CD34(-) FL populations can sustain long-term hematopoietic cultures. Furthermore, upon additional culture, CD34-depleted cell suspensions, devoid of SRCs, regenerated a population of CD34(+) cells possessing SRC function. Our studies suggest that compared to neonatal and adult sources, the phenotypical characteristics of putative human FL HSCs may be less strictly defined, and reinforce the accumulated evidence that human FL represents a unique, valuable alternative and highly proliferative source of HSCs for clinical applications.

  6. Influence of adefovir dipivoxil versus telbivudine combined with entecavir on liver function and serum virology in hepatitis B patients with decompensated liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Wei ZHANG

    2017-02-01

    Full Text Available Objective To investigate the influence of adefovir dipivoxil (ADV versus telbivudine (LdT combined with entecavir (ETV on liver function and serum virology of hepatitis B patients with decompensated liver cirrhosis (DLC. Methods Eighty DLC patients in our hospital from February 2014 to April 2015 were selected and divided into two groups (40 in each group. Observation group was given LdT combined with ETV, control group was given ADV. The liver function and serum virology were observed 12, 24, 48 weeks after treatment in the two groups. Results Before treatment, the expression level and Child-pugh score between observation group [ALT(156.3±50.2U/L, ALB (30.5±3.8g/L, TBil (60.4±23.1µmol/L, PTA (40.3%±7.8%, and Child-pugh score (11.3±1.5 points] and control group [ALT (154.1±51.4U/L, ALB (31.3±4.2g/L, TBil (58.9±24.3µmol/L, PTA (42.1%±8.4%, and the score (11.2±2.0 points] were compared with no statistically significant difference between the two groups (P>0.05; after a period of treatment, ALT, TBil and Child-pugh score decreased gradually, while ALB and PTA increased gradually in the two groups, and the difference was statistically significant compared to the pretreatment (P<0.05. With the passage of time, ALT, TBil and Child-Pugh score were lower, while ALB and PTA higher in the observation group than in control group, and the difference was statistically significant (P<0.05. At the same period after treatment, the negative conversion rates of HBV-DNA and HBeAg were obviously higher in the observation group than in the control group (P<0.05. Conclusion LDT combined with ETV in treating decompensated hepatitic cirrhosis has better effect than ADV does. Liver function recovered quicker, negative conversion ratio is higher, adverse reaction is less and LDT plus ETV is worthy of wide application. DOI: 10.11855/j.issn.0577-7402.2016.12.14

  7. Non-functioning pancreatic neuroendocrine tumor accompanied with multiple liver metastases: remorseful case and literature review.

    Science.gov (United States)

    Hori, Tomohide; Takaori, Kyoichi; Kawaguchi, Michiya; Ogawa, Kohei; Masui, Toshihiko; Ishii, Takamichi; Nagata, Hiromitsu; Narita, Masato; Kodama, Yuzo; Uza, Norimitsu; Uemoto, Shinji

    2014-11-28

    Pancreatic neuroendocrine tumor (P-NET) is a rare and slow-growing tumor. Unfortunately, there is no clear consensus on the role and timing of surgery for primary tumor and liver metastases, although current reports refer to liver surgery including LT for unresectable liver metastases. A thirty-nine-year-old man was diagnosed with nonfunctioning pancreatic neuroendocrine tumor (P-NET) in the pancreatic head, with multiple liver metastases. The tumor was 2.5 cm in diameter and he was asymptomatic. Small but multiple metastases were detected in the liver, and no extrahepatic metastases were observed. We initially intended to control the liver metastases before resection of the primary tumor. To begin with, transarterial chemoembolization (TACE) and transcatheter arterial infusion (TAI) were repeated. Thereafter, systemic chemotherapy and biotherapy were introduced according to follow-up assessments. Unfortunately, imaging assessment at about 10 months later revealed that liver metastases were partially enlarged, although some were successfully treated. Therefore, these therapies were switched to other regimens, and TACE/TAI, systemic chemotherapies and biotherapies were repeated. Although liver metastases seemed to be stable for a while, the primary tumor was enlarged even after therapy. At 3.5 years after initial diagnosis, the primary tumor became symptomatic (pain and jaundice). Liver metastases enlarged and massive swelling of the para-aortic lymph nodes was observed. Thereafter, palliative therapy was the main course of action. He died at 4.3 years after initial diagnosis. Our young patient could have been a candidate for initial surgery for primary tumor and might have had a chance of subsequent liver transplantation for unresectable metastases. Surgeons still face questions in deciding the best surgical scenario in patients with P-NET with liver metastases.

  8. Low-dose interleukin-2 promotes STAT-5 phosphorylation, Treg survival and CTLA-4-dependent function in autoimmune liver diseases.

    Science.gov (United States)

    Jeffery, H C; Jeffery, L E; Lutz, P; Corrigan, M; Webb, G J; Hirschfield, G M; Adams, D H; Oo, Y H

    2017-02-08

    CD4(+) CD25(high) CD127(low) forkhead box protein 3 (FoxP3(+) ) regulatory T cells (Treg ) are essential for the maintenance of peripheral tolerance. Impaired Treg function and an imbalance between effector and Tregs contribute to the pathogenesis of autoimmune diseases. We reported recently that the hepatic microenvironment is deficient in interleukin (IL)-2, a cytokine essential for Treg survival and function. Consequently, few liver-infiltrating Treg demonstrate signal transducer and activator of transcription-5 (STAT-5) phosphorylation. To establish the potential of IL-2 to enhance Treg therapy, we investigated the effects of very low dose Proleukin (VLDP) on the phosphorylation of STAT-5 and the subsequent survival and function of Treg and T effector cells from the blood and livers of patients with autoimmune liver diseases. VLDP, at less than 5 IU/ml, resulted in selective phosphorylation of STAT-5 in Treg but not effector T cells or natural killer cells and associated with increased expression of cytotoxic T lymphocyte antigen-4 (CTLA-4), FoxP3 and CD25 and the anti-apoptotic protein Bcl-2 in Treg with the greatest enhancement of regulatory phenotype in the effector memory Treg population. VLDP also maintained expression of the liver-homing chemokine receptor CXCR3. VLDP enhanced Treg function in a CTLA-4-dependent manner. These findings open new avenues for future VLDP cytokine therapy alone or in combination with clinical grade Treg in autoimmune liver diseases, as VLDP could not only enhance regulatory phenotype and functional property but also the survival of intrahepatic Treg .

  9. Poor initial graft function after orthotopic liver transplantation : can it be predicted and does it affect outcome? An analysis of 125 adult primary transplantations

    NARCIS (Netherlands)

    Maring, JK; Klompmaker, IJ; Zwaveling, JH; Kranenburg, K; TenVergert, EM; Slooff, MJH

    1997-01-01

    Donor liver shortage is a persistent problem in liver transplantation. A more liberal donor acceptance policy may be a possible solution. However, this might put recipients at risk for initial poor function or even non-function of the graft. Therefore risk factors for initial graft dysfunction shoul

  10. DMPD: Functions of anaphylatoxin C5a in rat liver: direct and indirect actions onnonparenchymal and parenchymal cells. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11367531 Functions of anaphylatoxin C5a in rat liver: direct and indirect actions onnon...rect and indirect actions onnonparenchymal and parenchymal cells. PubmedID 113675...31 Title Functions of anaphylatoxin C5a in rat liver: direct and indirect actions onnonparenchymal and paren

  11. Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings

    Science.gov (United States)

    Verstuyft, Céline; Corruble, Emmanuelle; Perlemuter, Gabriel; Colle, Romain

    2016-01-01

    Background Concerning the risk of antidepressant induced liver injury, it is not clear whether psychiatrists perform a liver function test (LFT) and whether an increase in aminotransferase levels should contraindicate antidepressant treatment. Aim To evaluate LFT availability, the prevalence of LFT abnormalities and the probable cause of an altered LFT in patients with a major depressive episode (MDE) requiring an antidepressant drug. Methods We studied LFT evaluation in a real world psychiatric setting, in a sample of 321 consecutive patients with a current major depressive episode (MDE) requiring an antidepressant drug treatment, but without current alcohol or drug dependence or unstable medical disease. Results An LFT is performed in 36.1% (116/321) of depressed patients. One fifth of antidepressant-treated patients who had an LFT evaluation had abnormal results. The most frequent causes of LFT abnormalities were: NAFLD (nonalcoholic fatty liver disease) (7/321; 2.1%), acute alcohol consumption (4/321; 1.2%), antidepressant-induced liver injury (3/321; 0.9%), hepatitis C virus infection (2/321; 0.6%) and heart failure (1/321; 0.3%). The cause of LFT abnormalities was unknown in 32% of patients (8/25) due to the absence of etiological investigations. Conclusion These results demonstrate that an LFT is infrequently performed by psychiatrists in depressed patients requiring an antidepressant drug. Baseline LFT assessment and observations during the first six months of antidepressant treatment may be useful for detection of patients with pre-existing liver disease such as NAFLD, and early identification of cases of antidepressant-induced liver injury. An increase in aminotransferase levels may be related to an underlying liver disease, but does not contraindicate antidepressant treatment. PMID:27171561

  12. Gene Level Meta-Analysis of Quantitative Traits by Functional Linear Models.

    Science.gov (United States)

    Fan, Ruzong; Wang, Yifan; Boehnke, Michael; Chen, Wei; Li, Yun; Ren, Haobo; Lobach, Iryna; Xiong, Momiao

    2015-08-01

    Meta-analysis of genetic data must account for differences among studies including study designs, markers genotyped, and covariates. The effects of genetic variants may differ from population to population, i.e., heterogeneity. Thus, meta-analysis of combining data of multiple studies is difficult. Novel statistical methods for meta-analysis are needed. In this article, functional linear models are developed for meta-analyses that connect genetic data to quantitative traits, adjusting for covariates. The models can be used to analyze rare variants, common variants, or a combination of the two. Both likelihood-ratio test (LRT) and F-distributed statistics are introduced to test association between quantitative traits and multiple variants in one genetic region. Extensive simulations are performed to evaluate empirical type I error rates and power performance of the proposed tests. The proposed LRT and F-distributed statistics control the type I error very well and have higher power than the existing methods of the meta-analysis sequence kernel association test (MetaSKAT). We analyze four blood lipid levels in data from a meta-analysis of eight European studies. The proposed methods detect more significant associations than MetaSKAT and the P-values of the proposed LRT and F-distributed statistics are usually much smaller than those of MetaSKAT. The functional linear models and related test statistics can be useful in whole-genome and whole-exome association studies.

  13. Synthetically quantitative evaluation function of characteristic parameters on CO2 arc welding process

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The statistical probability and their variation regularity of the measurable characteristic parameters in the CO2 arc welding droplet short-circuiting transfer process have been studied. The statistical analysis shows that the sensitivity of each characteristic parameter with regard to the variation of the short-circuiting transfer process is different. The sensitivity of 4 kinds among these characteristic parameters is more intense than that of the short-circuiting transfer frequency. In order to take account of the synthetic influence of these characteristic parameters, by means of the characteristic parameters synthetic value, a quantitative evaluation function is built up to describe and evaluate the short-circuiting transfer process of CO2 arc welding in real time. The testing shows that the evaluation function can give a suitable synthetic valuation for the short-circuiting transfer process with a variety of welding variables.

  14. Quantitative Analysis of Lithium-Ion Battery Capacity Prediction via Adaptive Bathtub-Shaped Function

    Directory of Open Access Journals (Sweden)

    Shaomin Wu

    2013-06-01

    Full Text Available Batteries are one of the most important components in many mechatronics systems, as they supply power to the systems and their failures may lead to reduced performance or even catastrophic results. Therefore, the prediction analysis of remaining useful life (RUL of batteries is very important. This paper develops a quantitative approach for battery RUL prediction using an adaptive bathtub-shaped function (ABF. ABF has been utilised to model the normalised battery cycle capacity prognostic curves, which attempt to predict the remaining battery capacity with given historical test data. An artificial fish swarm algorithm method with a variable population size (AFSAVP is employed as the optimiser for the parameter determination of the ABF curves, in which the fitness function is defined in the form of a coefficient of determination (R2. A 4 x 2 cross-validation (CV has been devised, and the results show that the method can work valuably for battery health management and battery life prediction.

  15. Development of {sup 68}Ga-labelled DTPA galactosyl human serum albumin for liver function imaging

    Energy Technology Data Exchange (ETDEWEB)

    Haubner, Roland [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Medizinische Universitaet Innsbruck, Universitaetsklinik fuer Nuklearmedizin, Innsbruck (Austria); Vera, David R.; Farshchi-Heydari, Salman [University of California, Department of Radiology, School of Medicine, and the UCSD Molecular Imaging Program, San Diego, CA (United States); Helbok, Anna; Rangger, Christine; Putzer, Daniel; Virgolini, Irene J. [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria)

    2013-08-15

    The hepatic asialoglycoprotein receptor is responsible for degradation of desialylated glycoproteins through receptor-mediated endocytosis. It has been shown that imaging of the receptor density using [{sup 99m}Tc]diethylenetriamine pentaacetic acid (DTPA) galactosyl human serum albumin ([{sup 99m}Tc]GSA) allows non-invasive determination of functional hepatocellular mass. Here we present the synthesis and evaluation of [{sup 68}Ga]GSA for the potential use with positron emission tomography (PET). Labelling of GSA with {sup 68}Ga was carried out using a fractionated elution protocol. For quality control thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and size exclusion chromatography (SEC) techniques were evaluated. Stability of [{sup 68}Ga]GSA was studied in phosphate-buffered saline (PBS) and human serum. For in vivo evaluation [{sup 68}Ga]GSA distribution in Lewis rats was compared with [{sup 99m}Tc]GSA by using a dual isotope protocol. PET and planar imaging studies were performed using the same scaled molar dose of [{sup 68}Ga]GSA and [{sup 99m}Tc]GSA. Time-activity curves (TAC) for heart and liver were generated and corresponding parameters calculated (t50, t90). [{sup 68}Ga]GSA can be produced with high radiochemical purity. The best TLC methods for determining potential free {sup 68}Ga include 0.1 M sodium citrate as eluent. None of the TLC methods tested were able to determine potential colloids. This can be achieved by SEC. HPLC confirmed high radiochemical purity (>98 %). Stability after 120 min incubation at 37 C was high in PBS (>95 % intact tracer) and low in human serum ({proportional_to}27 % intact tracer). Biodistribution studies simultaneously injecting both tracers showed comparable liver uptake, whereas activity concentration in blood was higher for [{sup 68}Ga]GSA compared to [{sup 99m}Tc]GSA. The [{sup 99m}Tc]GSA TACs exhibited a small degree of hepatic metabolism compared to the [{sup 68}Ga]GSA curves. The mean

  16. Organotypic functional cultures of human liver cells for long-term maintenance and assessment of drug-induced metabolome effects

    OpenAIRE

    MÜLLER Daniel

    2011-01-01

    The goals of this thesis were (i) to establish and improve organotypic liver cell culture techniques for long-term pharmacological studies and (ii) to develop and apply a metabolomics based approach for the assessment of drug-induced effects. As first model, a 3D bioreactor system was characterized in terms of cell physiology and functionality. Primary human hepatocytes could be kept viable and functional for more than 2 weeks in this system. Optimization of the system allowed determination o...

  17. Normothermic Machine Perfusion Reduces Bile Duct Injury and Improves Biliary Epithelial Function in Rat Donor Livers

    NARCIS (Netherlands)

    Op den Dries, Sanna; Karimian, Negin; Westerkamp, Andrie C; Sutton, Michael E; Kuipers, Michiel; Wiersema-Buist, Janneke; Ottens, Petra J; Kuipers, Jeroen; Giepmans, Ben N; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J

    BACKGROUND: Bile duct injury may occur during liver procurement and transplantation, especially in livers donated after circulatory death (DCD). Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury, compared to static cold storage (SCS). However, it is unknown whether NMP

  18. Puerarin improves metabolic function leading to hepatoprotective effects in chronic alcohol-induced liver injury in rats.

    Science.gov (United States)

    Chen, Xu; Li, Rong; Liang, Tao; Zhang, Kefeng; Gao, Ya; Xu, Lingyuan

    2013-07-15

    Puerarin (PR), an active component extracted from the kudzu root, has been widely used as an ethno-medicine to treat hepatopathy in China. Therefore, the aim of the present study was to investigate the hepatoprotective action of PR in chronic alcohol-induced liver injury in rats. Data showed that the serum levels of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were elevated following PR administration. In addition, the levels of endogenous CYP2E1, CYP1A2, and CYP3A proteins in liver tissue were also gradually decreased following PR treatment. Histopathological examinations suggested that alcohol-induced hepatocellular lesions were mitigated by PR treatment. Collectively, these data indicate that PR contributes to cytoprotection against alcohol-induced liver lesions through improving metabolic function. Copyright © 2013 Elsevier GmbH. All rights reserved.

  19. Effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients infected with hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Lei Pan; Zhan-Sheng Jia; Lin Chen; En-Qing Fu; Guang-Yu Li

    2005-01-01

    AIM: To observe the effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients with hepatitis B virus (HBV) infection, and to compare the differences of liver function by two treatments of antituberculosis.METHODS: Forty-seven TB patients with HBV infection and 170 TB patients without HBV infection were divided into HPBE(S) and HLAMKO treatment groups. Liver function tests before and after the treatments were performed once in 2 wk or monthly, and their clinical manifestations were recorded.RESULTS: The rate of hepatotoxicity occurred in 26 (59%)TB patients with HBV during anti-TB treatment, higher than that in 40 (24%) TB patients without HBV. Hepatotoxicity occurred in 66 out of 217 patients, and the incidence of liver dysfunction was 46.1% in HPBE(S) group, significantly higher than that in HLAMKO group (12.7%) (P<0.01).CONCLUSION: TB patients with HBV should choose HLAMKO treatment because of fewer hepatotoxicity.

  20. Quantitative estimation of brain atrophy and function with PET and MRI two-dimensional projection images

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Reiko; Uemura, Koji; Uchiyama, Akihiko [Waseda Univ., Tokyo (Japan). School of Science and Engineering; Toyama, Hinako; Ishii, Kenji; Senda, Michio

    2001-05-01

    The purpose of this paper is to estimate the extent of atrophy and the decline in brain function objectively and quantitatively. Two-dimensional (2D) projection images of three-dimensional (3D) transaxial images of positron emission tomography (PET) and magnetic resonance imaging (MRI) were made by means of the Mollweide method which keeps the area of the brain surface. A correlation image was generated between 2D projection images of MRI and cerebral blood flow (CBF) or {sup 18}F-fluorodeoxyglucose (FDG) PET images and the sulcus was extracted from the correlation image clustered by K-means method. Furthermore, the extent of atrophy was evaluated from the extracted sulcus on 2D-projection MRI and the cerebral cortical function such as blood flow or glucose metabolic rate was assessed in the cortex excluding sulcus on 2D-projection PET image, and then the relationship between the cerebral atrophy and function was evaluated. This method was applied to the two groups, the young and the aged normal subjects, and the relationship between the age and the rate of atrophy or the cerebral blood flow was investigated. This method was also applied to FDG-PET and MRI studies in the normal controls and in patients with corticobasal degeneration. The mean rate of atrophy in the aged group was found to be higher than that in the young. The mean value and the variance of the cerebral blood flow for the young are greater than those of the aged. The sulci were similarly extracted using either CBF or FDG PET images. The purposed method using 2-D projection images of MRI and PET is clinically useful for quantitative assessment of atrophic change and functional disorder of cerebral cortex. (author)

  1. 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 ...

  2. Synthesis, characterization and liver targeting evaluation of self-assembled hyaluronic acid nanoparticles functionalized with glycyrrhetinic acid.

    Science.gov (United States)

    Wang, Xiaodan; Gu, Xiangqin; Wang, Huimin; Sun, Yujiao; Wu, Haiyang; Mao, Shirui

    2017-01-01

    Recently, polymeric materials with multiple functions have drawn great attention as the carrier for drug delivery system design. In this study, a series of multifunctional drug delivery carriers, hyaluronic acid (HA)-glycyrrhetinic acid (GA) succinate (HSG) copolymers were synthesized via hydroxyl group modification of hyaluronic acid. It was shown that the HSG nanoparticles had sub-spherical shape, and the particle size was in the range of 152.6-260.7nm depending on GA graft ratio. HSG nanoparticles presented good short term and dilution stability. MTT assay demonstrated all the copolymers presented no significant cytotoxicity. In vivo imaging analysis suggested HSG nanoparticles had superior liver targeting efficiency and the liver targeting capacity was GA graft ratio dependent. The accumulation of DiR (a lipophilic, NIR fluorescent cyanine dye)-loaded HSG-6, HSG-12, and HSG-20 nanoparticles in liver was 1.8-, 2.1-, and 2.9-fold higher than that of free DiR. The binding site of GA on HA may influence liver targeting efficiency. These results indicated that HSG copolymers based nanoparticles are potential drug carrier for improved liver targeting. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver.

    Science.gov (United States)

    Duarte, Filipe V; Amorim, João A; Varela, Ana T; Teodoro, João S; Gomes, Ana P; Cunha, Rodrigo A; Palmeira, Carlos M; Rolo, Anabela P

    2016-11-15

    Although adenosine A1 receptors (A1R) have been associated to ischemic preconditioning (IPC), direct evidence for their ability to preserve mitochondrial function upon hepatic preconditioning is still missing and could represent a novel strategy to boost the quality of liver transplants. We tested if the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) prevented IPC in the liver and if the A1R agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) might afford a pharmacological preconditioning. Livers underwent a 120 min of 70% wa