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Sample records for quantitative liver function

  1. Quantitative PET of liver functions.

    Science.gov (United States)

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

    2018-01-01

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

  2. Quantitative PET of liver functions

    Science.gov (United States)

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

    2018-01-01

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

  3. Automatic quantitative analysis of liver functions by a computer system

    International Nuclear Information System (INIS)

    Shinpo, Takako

    1984-01-01

    In the previous paper, we confirmed the clinical usefulness of hepatic clearance (hepatic blood flow), which is the hepatic uptake and blood disappearance rate coefficients. These were obtained by the initial slope index of each minute during a period of five frames of a hepatogram by injecting sup(99m)Tc-Sn-colloid 37 MBq. To analyze the information simply, rapidly and accurately, we developed a automatic quantitative analysis for liver functions. Information was obtained every quarter minute during a period of 60 frames of the sequential image. The sequential counts were measured for the heart, whole liver, both left lobe and right lobes using a computer connected to a scintillation camera. We measured the effective hepatic blood flow, from the disappearance rate multiplied by the percentage of hepatic uptake as follows, (liver counts)/(tatal counts of the field) Our method of analysis automatically recorded the reappearance graph of the disappearance curve and uptake curve on the basis of the heart and the whole liver, respectively; and computed using BASIC language. This method makes it possible to obtain the image of the initial uptake of sup(99m)Tc-Sn-colloid into the liver by a small dose of it. (author)

  4. Scintigraphic assessment of liver function in patients requiring liver surgery

    NARCIS (Netherlands)

    Cieślak, K.P.

    2018-01-01

    This thesis addresses various aspects of assessment of liver function using a quantitative liver function test, 99mTc-mebrofenin hepatobiliary scintigraphy (HBS). HBS enables direct measurement of at least one of the liver’s true processes with minimal external interference and offers the

  5. Quantitative evaluation of liver function with MRI using Gd-EOB-DTPA

    International Nuclear Information System (INIS)

    Ryeom, Hun Kyu; Kim, Seong Hun; Kim, Jong Yeol; Kim, Hye Jeong; Lee, Jong Min; Chang, Yong Min; Kim, Yong Sun; Kang, Duk Sik

    2004-01-01

    Gadolinium ethoxybenzoyl diethylenetriaminepentaacetic acid Gd-EOB-DTPA) is a newly developed MR contrast agent. After intravenous injection Gd-EOB-DTPA is gradually taken up by the hepatocytes and eventually excreed via the biliary pathway without any change to its chemical structure. Because of these characteristics, it can be used as a tracer for quantitative liver function testing. The purpose of this study is to develop a noninvasive method of quantitation of the hepatic function using Gd-EOB-DTPA through the deconvolution analysis. Adult New Zealand white rabbits (n = 10, average body weight = 3.5 kg) were used in the present study. Hepatic injury was induced to by the intragastric administration of carbon tetrachloride (CCI4) three times a week for three weeks. Liver enzyme (aspartate aminotransferase, AST; alanine aminotransferase, ALT) levels and the plasma indocyanine green (ICG) retention rate 15 minutes after an intravenous injection of ICG (ICG R15), was checked before and after the three-week administration of CCI4. At the end of experimental period, an observer 'blinded' to the treatment given the rabbits performed the histological examination. MRI studies were performed before and after the three-week administration of CCI4 on a 1.5 T scanner using a human extremity coil. After intravenous bolus injection of Gd-EOB-DTPA (0.3 mL if Gd-EOB-DTPA freshly prepared in 2.7 mL of normal saline) through the ear vein, the 250 axial single level dynamic MR images were obtained using a fast low angle shot (FLASH, TR/TE = 11/4.2 msec, flip angle = 15, acquisition time 1 second, slice thickness = 5 mm, matrix = 128 x 128, field of view = 120 mm) sequence with 1.5 sec time intervals. The time-intensity curves were obtained at the abdominal aorta and the liver parenchyma that was devoid of blood vessels. Deconvolution analysis of the aortic (input function) and hepatic parenchymal (output function) time-intensity curves was performed with a modified Fourier

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

    Energy Technology Data Exchange (ETDEWEB)

    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. Shear wave elastography results correlate with liver fibrosis histology and liver function reserve.

    Science.gov (United States)

    Feng, Yan-Hong; Hu, Xiang-Dong; Zhai, Lin; Liu, Ji-Bin; Qiu, Lan-Yan; Zu, Yuan; Liang, Si; Gui, Yu; Qian, Lin-Xue

    2016-05-07

    To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve. Weekly subcutaneous injection of 60% carbon tetrachloride (1.5 mL/kg) was given to 12 canines for 24 wk to induce experimental liver fibrosis, with olive oil given to 2 control canines. At 24 wk, liver condition was evaluated using clinical biochemistry assays, SWE imaging, lidocaine metabolite monoethylglycine-xylidide (MEGX) test, and histologic fibrosis grading. Clinical biochemistry assays were performed at the institutional central laboratory for routine liver function evaluation. Liver stiffness was measured in triplicate from three different intercostal spaces and expressed as mean liver stiffness modulus (LSM). Plasma concentrations of lidocaine and its metabolite MEGX were determined using high-performance liquid chromatography repeated in duplicate. Liver biopsy samples were fixed in 10% formaldehyde, and liver fibrosis was graded using the modified histological activity index Knodell score (F0-F4). Correlations among histologic grading, LSM, and MEGX measures were analyzed with the Pearson linear correlation coefficient. At 24 wk liver fibrosis histologic grading was as follows: F0, n = 2 (control); F1, n = 0; F2, n = 3; F3, n = 7; and F4, n = 2. SWE LSM was positively correlated with histologic grading (r = 0.835, P function reserve in experimental severe fibrosis and cirrhosis.

  8. CT quantitative diagnosis in fatty liver: a clinical study

    International Nuclear Information System (INIS)

    He Wen; Qian Linxue; Zhao Jixue; Ma Daqing; Feng Jie; Hu Zhihai

    2001-01-01

    Objective: To establish the CT criteria of quantitative diagnosis for liver steatosis by means of studying the CT features of fatty liver cases proven histologically. Methods: Twenty-eight cases of fatty liver were underwent non-enhanced CT scan, and the attenuation of liver parenchyma was measured. To differentiate the degree of fatty liver, the mean CT value and the relative density of hepatic vessels were observed. The quantitative diagnosis was made according to the CT number threshold and the criteria of relative density of hepatic vessels, respectively. Results: Among the 28 cases, there were 17 cases of mild steatosis with mean CT number of 46 HU (32-65 HU), 7 cases of middle degree fatty liver with mean CT number of 28 HU (15-38 HU), and 4 cases of sever fatty liver with mean CT number of 0.2 HU (-7-11 HU). For the relative density of hepatic vessels, 16 of the 17 cases of mild fatty liver had a appearance of hepatic vessels immersion and 1 mild case had reverse hepatic vessels display, 6 of 7 middle degree cases had reverse hepatic vessels display with 1 case having the appearance of hepatic vessels immersion, and all the 4 case of sever steatosis had the appearance of reverse hepatic vessels display with sharp contrast between vessels and the liver parenchyma. The accuracy of quantitative diagnosis was 65.9% and 93.1% by means of criteria of CT number threshold and relative density of hepatic vessels, respectively (x 2 = 7.153, P < 0.01). Conclusion: The criteria of relative density of hepatic vessels is more reliable than that of CT number threshold in quantitative diagnosis of fatty liver

  9. 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.

  10. Electrical and optical spectroscopy for quantitative screening of hepatic steatosis in donor livers

    Energy Technology Data Exchange (ETDEWEB)

    McLaughlin, B L; Wilkinson, T D; Robertson, P A [Engineering Department, University of Cambridge, 9 JJ Thomson Avenue, Cambridge CB3 OFA (United Kingdom); Wells, A C; Watson, C J E [University Department of Surgery, Addenbrooke' s Hospital, Box 202, Level 9, Hills Road, Cambridge CB2 OCQ (United Kingdom); Virtue, S; Vidal-Puig, A, E-mail: mclaugb@gmail.co [Department of Clinical Biochemistry, University of Cambridge, Addenbrooke' s Hospital, Hills Road, Cambridge CB2 2QR (United Kingdom)

    2010-11-21

    Macro-steatosis in deceased donor livers is increasingly prevalent and is associated with poor or non-function of the liver upon reperfusion. Current assessment of the extent of steatosis depends upon the macroscopic assessment of the liver by the surgeon and histological examination, if available. In this paper we demonstrate electrical and optical spectroscopy techniques which quantitatively characterize fatty infiltration in liver tissue. Optical spectroscopy showed a correlation coefficient of 0.85 in humans when referenced to clinical hematoxylin and eosin (H and E) sections in 20 human samples. With further development, an optical probe may provide a comprehensive measure of steatosis across the liver at the time of procurement.

  11. Pituitary-testicular function in patients with alcoholic cirrhosis of the liver

    DEFF Research Database (Denmark)

    Bahnsen, M; Gluud, C; Johnsen, S G

    1981-01-01

    In forty-two patients with alcoholic liver cirrhosis and without recent alcohol ingestion the pituitary-testicular function was studied in an effort to relate the endocrine abnormalities with the degree of liver cell dysfunction, evaluated on a quantitative basis. Compared with values in twenty-o...

  12. Hepatic (Liver) Function Panel

    Science.gov (United States)

    ... Educators Search English Español Blood Test: Hepatic (Liver) Function Panel KidsHealth / For Parents / Blood Test: Hepatic (Liver) ... kidneys ) is working. What Is a Hepatic (Liver) Function Panel? A liver function panel is a blood ...

  13. Liver Function Tests

    Science.gov (United States)

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

  14. Initial study of quantitative analysis of fatty liver by 1H-MR spectroscopy imaging

    International Nuclear Information System (INIS)

    Liang Changhong; Liu Yubao; Zhang Zhonglin; Xie Shufei; Wang Qiushi

    2007-01-01

    Objective: To investigate the feasibility of 1 H-MR spectroscopy ( 1 H-MRS) imaging to quantitatively detect fatty liver. Methods: Twenty patients with fatty liver and 11 healthy volunteers underwent plain CT scan, conventional MR imaging and 1 H-MRS analysis. The blood lipid and liver function were tested on the same day as the MR examination. 1 H-MRS sequence measured the peaks of H 2 O and lipid, and the areas under the peaks. The relative contents of the lipid compound were calculated, and compared with the results of CT scan and liver function tests. Results: The CT values of the normal group and the fatty liver group were (59 ± 9) HU and (24 ± 11) HU respectively. On 1 H-MRS a protruding high H 2 O peak and a flat low lipid peak were observed in the normal group, while the protruding high H 2 O peak and a high lipid peak appeared in the fatty liver group. The values of lipid peak in the normal group and the fatty liver group were (0.05 ± 0.01) x l0 5 , (0.70 ± 0.24) x l0 5 respectively (t=4.32, P 5 , (1.85 ± 0.47) x l0 5 respectively (t=1.26, P>0.05), the areas under the lipid peak were (1.36 ± 0.73) x 10 9 , (2.35 ± 1.15) x 10 9 respectively (t=5.21, P 2 O peak were (4.33 ± 1.28) x 10 11 , (3.55 ± 0.94) x 10 11 respectively (t=2.04, P>0.05). Conclusion: 1 H-MRS imaging is feasible to quantitatively detect liver fat and is a non-invasive method for detecting early fatty liver. (authors)

  15. Liver Function Tests

    Science.gov (United States)

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

  16. Correlation with liver scintigram, reticuloendothelial function test, plasma endotoxin level and liver function tests in chronic liver diseases. Multivariate analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ohmoto, Kenji; Yamamoto, Shinichi; Ideguchi, Seiji and others

    1989-02-01

    Liver scintigrams with Tc-99m phytate were reviewed in a total of 64 consecutive patients, comprising 28 with chronic hepatitis and 36 with liver cirrhosis. Reticuloendothelial (RES) function, plasma endotoxin (Et) levels and findings of general liver function tests were used as reference parameters to determine the diagnostic ability of liver scintigraphy. Multivariate analyses revealed that liver scintigrams had a strong correlation with RES function and Et levels in terms of morphology of the liver and hepatic and bone marrow Tc-99m uptake. General liver function tests revealed gamma globulin to be correlated with hepatic uptake and the degree of splenogemaly on liver scintigrams; and ICG levels at 15 min to be correlated with bone marrow and splenic uptake. Accuracy of liver scintigraphy was 73% for chronic hepatitis, which was inferior to general liver function tests (83%). When both modalities were combined, diangostic accuracy increased to 95%. Liver scintigraphy seems to be useful as a complementary approach. (Namekawa, K).

  17. Tissue hepatic blood volume and liver function

    International Nuclear Information System (INIS)

    Masuyama, Mamoru

    1997-01-01

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

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

    Science.gov (United States)

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

    1999-08-01

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

  19. The utility of quantitative 99mTc-GSA liver scintigraphy in the evaluation of hepatic functional reserve

    International Nuclear Information System (INIS)

    Shuke, Noriyuki; Aburano, Tamio; Nakajima, Kenichi

    1992-01-01

    Using data from 17 patients with liver cirrhosis and 3 patients with fatty liver, we have compared the utility of 3 hepatic imaging agents in the evalution of hepatic functional reserve. Evaluated here were 99m Tc-galactosyl human serum albumin (GSA) which is a new ligand for hepatic binding protein, 99m Tc-N-pyridoxyl-5-methyl tryptophan (PMT) of a hepatobiliary agent, and 99m Tc-Sn colloid. In each patient, we performed these 3 imaging studies within a week and also examined hepatic function tests (indocyanine green test, hepaplastin test, choline-esterase, etc). In each imaging study, serial images and dynamic data were obtained after the injection of 99m Tc-GSA (185 MBq/3 mg), 99m Tc-PMT (185 MBq), or 99m Tc-Sn colloid (185 MBq). Using the dynamic data obtained, we analyzed the liver kinetics of the 3 agents based on 1 compartment model with 3 parameters (hepatic clearance, hepatic excretion rate, non-specific volume of distribution). From fitting the liver and heart data to this model, three unknown parameters were determined. Patlak plot was also applied in order to estimate liver uptake rate. Both curve fitting and Patlak plot could determine appropriate parameters in every study. In 99m Tc-GSA, a nonlinear 3 compartment model was also applied in order to estimate hepatic blood flow, liver receptor density, and affinity of receptor-GSA binding separately. Using the parameters obtained, we analyzed the correlations between the parameters and the results of hepatic function tests. In all of the parameters, those obtained from 99m Tc-GSA imaging showed the most significant statistical correlation with the results of hepatic function tests. From the present results, 99m Tc-GSA imaging was concluded to be the best for evaluation of hepatic functional reserve. (author)

  20. Sex Hormone-Related Functions in Regenerating Male Rat Liver

    Science.gov (United States)

    FRANCAVILLA, ANTONIO; EAGON, PATRICIA K.; DiLEO, ALFREDO; POLIMENO, LORENZO; PANELLA, CARMINE; AQUILINO, A. MARIA; INGROSSO, MARCELLO; Van THIEL, DAVID H.; STARZL, THOMAS E.

    2011-01-01

    Sex hormone receptors were quantitated in normal male rat liver and in regenerating liver at several different times after partial (70%) hepatectomy. Both estrogen and androgen receptor content were altered dramatically by partial hepatectomy. Total hepatic content and nuclear retention of estrogen receptors increased, with the zenith evident 2 days after partial hepatectomy, corresponding to the zenith of mitotic index. Serum estradiol increased after 1 day, and reached a maximum at 3 days after surgery. In contrast, total and nuclear androgen receptor content demonstrated a massive decline at 1, 2, and 3 days after resection. Serum testosterone displayed a parallel decline. In addition, hepatic content of two androgen-responsive proteins was reduced to 15% and 13% of normal values during this period. The activity of these various proteins during regeneration of male rat liver is comparable to that observed in the liver of normal female rats. Taken together, these results indicate that partial hepatectomy induces a feminization of certain sexually dimorphic aspects of liver function in male rats. Furthermore, these data provide evidence that estrogens, but not androgens, may have an important role in the process of liver regeneration. PMID:3758617

  1. How to interpret liver function tests

    Directory of Open Access Journals (Sweden)

    Christina Levick

    2017-05-01

    Full Text Available Careful interpretation of liver function tests within the clinical context can help elucidate the cause and severity of the underlying pathology. Predominantly raised alkaline phosphatase represents the cholestatic pattern of biliary pathology, whilst predominantly raised alanine aminotransferase and aspartate aminotransferase represent the hepatocellular pattern of hepatocellular pathology. The severity of liver dysfunction or biliary obstruction is reflected in the bilirubin level and the degree of liver synthetic function can also be indicated by the albumin level. Beyond the liver function tests, prothrombin time provides another marker of liver synthetic function and a low platelet count suggests portal hypertension.

  2. Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors

    International Nuclear Information System (INIS)

    Jansen, P.L.M.; Chamuleau, R.A.F.; Leeuwen, D.J. van; Schippor, H.G.; Busemann-Sokole, E.; Heyde, M.N. van der

    1990-01-01

    Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single photon computed tomography (SPECT), using 99m Tc-colloid as tracer. The method was assessed in 11 patients by comparing the pre- and post-operative volume measurement with the volume of the resected liver mass. Liver function was determined by measuring the galactose elimination capacity and the caffeine clearance. After a postoperative follow-up period of 50 days, the liver had regenerated maximally to a volume of 75 ± 2% of the preoperative liver mass. Maximal restoration of liver function was achieved 120 days after operation and amounted to 75 ± 10% for the caffeine clearance and to 100 ± 25% for the galactose elimination capacity. This study shows that SPECT is a useful method for assessing liver regeneration in patients after partial hepatectomy. The study furthermore shows that caffeine clearance correlates well with total liver volume, whereas the galactose elimination capacity overestimates total liver volume after partial hepatectomy. 22 refs

  3. 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.

  4. Liver Function Tests in Tuberculoid Leprosy

    Directory of Open Access Journals (Sweden)

    R V Korane

    1979-01-01

    Full Text Available A total of 24 patients with untreated tuberculoid leprosy were taken up for study, They were the same group of patients in whom the authors have earlier reported involvement of liver in 85 % cases. Five healthy controls, studied also belonged to the same series. Liver function tests included prothrombin time, serum bilirubin, zinc sulphate turbidity, serum proteins and serum transaminases. No significant alterations in the liver function were observed. This is because the changes in the liver were so minimal and focal that they were not reflected in the various liver function tests.

  5. FT-IR imaging for quantitative determination of liver fat content in non-alcoholic fatty liver.

    Science.gov (United States)

    Kochan, K; Maslak, E; Chlopicki, S; Baranska, M

    2015-08-07

    In this work we apply FT-IR imaging of large areas of liver tissue cross-section samples (∼5 cm × 5 cm) for quantitative assessment of steatosis in murine model of Non-Alcoholic Fatty Liver (NAFLD). We quantified the area of liver tissue occupied by lipid droplets (LDs) by FT-IR imaging and Oil Red O (ORO) staining for comparison. Two alternative FT-IR based approaches are presented. The first, straightforward method, was based on average spectra from tissues and provided values of the fat content by using a PLS regression model and the reference method. The second one – the chemometric-based method – enabled us to determine the values of the fat content, independently of the reference method by means of k-means cluster (KMC) analysis. In summary, FT-IR images of large size liver sections may prove to be useful for quantifying liver steatosis without the need of tissue staining.

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

    Science.gov (United States)

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

    2014-10-01

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

  7. 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.)

  8. Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors

    NARCIS (Netherlands)

    Jansen, P. L.; Chamuleau, R. A.; van Leeuwen, D. J.; Schipper, H. G.; Busemann-Sokole, E.; van der Heyde, M. N.

    1990-01-01

    Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single-photon computed tomography (SPECT), using 99mTc-colloid as tracer. The method was

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

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Poulsen, H.E.; 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....

  10. Efficacy of liver parenchymal enhancement and liver volume to standard liver volume ratio on Gd-EOB-DTPA-enhanced MRI for estimation of liver function

    Energy Technology Data Exchange (ETDEWEB)

    Yoneyama, Tomohide; Fukukura, Yoshihiko; Kamimura, Kiyohisa; Takumi, Koji; Umanodan, Aya; Nakajo, Masayuki [Kagoshima University Graduate School of Medical and Dental Sciences, Department of Radiology, Kagoshima City (Japan); Ueno, Shinichi [Kagoshima University Graduate School of Medical and Dental Sciences, Department of Surgical Oncology and Digestive Surgery, Kagoshima City (Japan)

    2014-04-15

    We aimed to develop and assess the efficacy of a liver function index that combines liver enhancement and liver volume to standard liver volume (LV/SLV) ratio on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. In all, 111 patients underwent a Gd-EOB-DTPA-enhanced MRI, including T1 mapping, before and 20 min after Gd-EOB-DTPA administration. We calculated the following Gd-EOB-DTPA-enhanced MRI-based liver function indices: relative enhancement of the liver, corrected enhancement of the liver-to-spleen ratio, LSC{sub N}20, increase rate of the liver-to-muscle ratio, reduction rate of T1 relaxation time of the liver, ΔR1 of the liver and K{sub Hep}; the indices were multiplied by the LV/SLV ratio. We calculated the correlations between an indocyanine green (ICG) clearance and the Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio, by using Pearson correlation analysis. There were significant correlations between all Gd-EOB-DTPA-enhanced MRI-based liver function indices and ICG clearance (r = -0.354 to -0.574, P < 0.001). All Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio (r = -0.394 to -0.700, P < 0.001) were more strongly correlated with the ICG clearance than those without multiplication by the LV/SLV ratio. Gd-EOB-DTPA-enhanced MRI-based liver function indices that combine liver enhancement and the LV/SLV ratio may more reliably estimate liver function. (orig.)

  11. 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.

  12. 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

  13. Liver Function Study using {sup 131}I-BSP

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Hideo; Lio, Masahiro; Chibe, Kazuo; Kameda, Haruo; Ueda, Hideo [Tokyo University Hospital, Tokyo (Japan); Luchi, Masahiko; Ishiwa, Mamoru [Kofu Municipal Hospital, Kofu (Japan)

    1971-03-15

    Liver function tests are indispensable for diagnosis of liver diseases. It is desirable to conduct several kinds of test for over-all evaluation of liver function, considering the various aspects of metabolism performed in the liver. Diagnosis of the existence and severity of liver diseases, especially in cases without jaundice and judgment of prognosis and effects of treatment must be made by various liver function tests. So far, the BSP loading test has been widely used as the most sensitive index of liver function, since BSP greatly contributes to the diagnosis of liver disease without jaundice and evaluation of prognosis. However, the clinical use of the BSP test seems to be decreasing, because side effects, such as pain and anaphylaxis-like shock, occasionally causing death, have been reported (1). Indocyanine-Green (ICG) appears to be replacing the BSP test as a safer dye for the dye excretion test (2,3), but it has not yet been widely used for clinical purpose because of problems of product stability and measurement procedures. The authors previously used {sup 35}S-BSP to analyze the mechanism of liver uptake of the dye and determined maximum hepatic uptake capacity of BSP in normal controls and for various liver diseases (4). At the same time it was noted that, in the presence of function disturbance, the liver cannot adequately handle even a tracer dose of BSP, and blood clearance of a tracer dose of BSP is not exclusively dependent on hepatic blood flow, but is also dependent on the hepatocellular function of dye uptake (5). BSP and ICG have been also used as a bilirubin analogue for analysis of clearance after a single intravenous injection (6) and to biliary excretion of the dye under continuous infusion in normal subjects as well as in various liver diseases (7). A clinical test must be safe and simple for routine use. The measurement of {sup 35}S-BSP is rather complicated while {sup 131}I-BSP, the basic properties of which were intensively studied (8

  14. Real-time elastography with a novel quantitative technology for assessment of liver fibrosis in chronic hepatitis B

    International Nuclear Information System (INIS)

    Wang Juan; Guo Long; Shi Xiuying; Pan Wenqian; Bai Yunfei; Ai Hong

    2012-01-01

    Background: The accurate evaluation of liver fibrosis stage is important in determining the treatment strategy. The limitations of percutaneous liver biopsy as the gold standard are obvious for invasion. Real-time elastography with conventional ultrasound probes and a new quantitative technology for diffuse histological lesion is a novel approach for staging of liver fibrosis. Purpose: This study aimed to evaluate the value of real-time tissue elastography with a new quantitative technology for the assessment of liver fibrosis stage. Materials and methods: Real-time elastography was performed in 55 patients with liver fibrosis and chronic hepatitis B and in 20 healthy volunteers. Eleven parameters for every patient in colorcode image obtained from the real-time elastography were analyzed with principal components analysis. We analyzed the correlation between elasticity index and liver fibrosis stage and the accuracy of real-time elastography for liver fibrosis staging. Additionally, aspartate transaminase-to-platelet ratio index was also included in the analysis. Results: The Spearman's correlation coefficient between the elasticity index and the histologic fibrosis stage was 0.81, which is highly significant (p 0.05), respectively. Conclusions: Real-time elastography with a new quantitative technology for diffuse histological lesion is a new and promising sonography-based noninvasive method for the assessment of liver fibrosis in patients with chronic hepatitis B.

  15. Assessment of adrenal function in liver diseases

    Directory of Open Access Journals (Sweden)

    Sandeep Kharb

    2013-01-01

    Full Text Available Background: In recent times, there are reports of adrenal dysfunction in whole spectrum of liver disease. Adrenal insufficiency (AI has been shown to correlate with progression of liver disease. Hence this study was conducted to assess adrenal function in subjects with acute liver disease (ALD, chronic liver disease (CLD and post liver transplantation (LT. Material and Methods: This study included 25 healthy controls, 25 patients of ALD, 20 subjects of CLD with Child-Pugh stage A (CLD-1 and 30 with Child-Pugh stage B or C (CLD-2, and 10 subjects with LT. All subjects were assessed clinically, biochemically and for adrenal functions. Results: AI was present in 9 (34.6% patients with ALD, 20 (40% patients with CLD and 4 (40% in subjects with LT. AI was more common in CLD-2 (18 patients - 60% than CLD-1 (2 patients - 10%. All patients with chronic liver disease had significantly lower basal cortisol (8.8±4.8, P=0.01, stimulated cortisol (18.2±6.3, P <0.00001 and incremental cortisol (9.4±4.6, P <0.00001 as compared to controls. There was increase in percentage of subjects with adrenal dysfunction with progression of liver disease as assessed by Child-Pugh staging. AI was predicted by lower levels of serum protein, serum albumin, total cholesterol and HDL cholesterol and higher levels of serum bilirubin and INR. Adrenal functions showed recovery following liver transplantation. Conclusions: AI forms important part of spectrum of acute and chronic liver disease. Deterioration of synthetic functions of liver disease predicts presence of AI, and these patients should be evaluated for adrenal dysfunction periodically.

  16. Evaluation of regeneration of liver function in pig model of auxiliary partial liver transplantation

    International Nuclear Information System (INIS)

    Li Jiaxin; Chen Xiaopeng; Rui Ging; Shong Qun; Chen Fangman; Lu Meijing; Chen Yongquan

    2010-01-01

    Objective: To establish a pig model of auxiliary partial liver transplantation and observe the liver function regeneration of host liver and graft. Methods: The portal vein providing for the host liver were gradually contracted; the donor hepatic veins were eng-to-side anastomosed to inferior vena cava in host caudal; graft was transplanted into the space under the host liver, part of receivers relieved portal vein angiography and color Doppler flow imaging was performed 3 days after surgery. Liver function of double livers in relievers was checked up, 3 days and 1 week after surgery respectively. Results: After surgery 10 relievers survived over 1 week, blood enzymology from hepatic vein of grafts 1 week after surgery were not ameliorative significantly compared with those 3 days after surgery (P > 0.05). Blood enzymology indexes from hepatic veins of grafts 1 week after surgery were were improved significantly compared with 3 days after surgery (P < 0.05). The graft did not reveal atrophic and gained favorable function. Conclusion: Favorable regeneration in the auxiliary partial liver transplantation model has achieved. Ideal foundation has been established for simulating and investigating human auxiliary liver transplantation. (authors)

  17. Local and Global Function Model of the Liver

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hesheng, E-mail: hesheng@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Feng, Mary [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Jackson, Andrew [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Ten Haken, Randall K.; Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States)

    2016-01-01

    Purpose: To develop a local and global function model in the liver based on regional and organ function measurements to support individualized adaptive radiation therapy (RT). Methods and Materials: A local and global model for liver function was developed to include both functional volume and the effect of functional variation of subunits. Adopting the assumption of parallel architecture in the liver, the global function was composed of a sum of local function probabilities of subunits, varying between 0 and 1. The model was fit to 59 datasets of liver regional and organ function measures from 23 patients obtained before, during, and 1 month after RT. The local function probabilities of subunits were modeled by a sigmoid function in relating to MRI-derived portal venous perfusion values. The global function was fitted to a logarithm of an indocyanine green retention rate at 15 minutes (an overall liver function measure). Cross-validation was performed by leave-m-out tests. The model was further evaluated by fitting to the data divided according to whether the patients had hepatocellular carcinoma (HCC) or not. Results: The liver function model showed that (1) a perfusion value of 68.6 mL/(100 g · min) yielded a local function probability of 0.5; (2) the probability reached 0.9 at a perfusion value of 98 mL/(100 g · min); and (3) at a probability of 0.03 [corresponding perfusion of 38 mL/(100 g · min)] or lower, the contribution to global function was lost. Cross-validations showed that the model parameters were stable. The model fitted to the data from the patients with HCC indicated that the same amount of portal venous perfusion was translated into less local function probability than in the patients with non-HCC tumors. Conclusions: The developed liver function model could provide a means to better assess individual and regional dose-responses of hepatic functions, and provide guidance for individualized treatment planning of RT.

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

    International Nuclear Information System (INIS)

    Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs; Lunsing, Roelineke J.; Spronsen, Francjan J. van; 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) 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, γ-glutamyl transpeptidase, alkaline phosphatase). (orig.)

  19. 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

    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.......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...

  20. 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.

  1. 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...

  2. 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.)

  3. 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.)

  4. Liver function tests using the stable istope 15N

    International Nuclear Information System (INIS)

    Faust, H.; Jung, K.; Hirschberg, K.; Krumbiegel, P.; Junghans, P.; Reinhardt, R.; Teichmann, B.

    1988-01-01

    Several liver function tests using oral application of a nitrogen compound labelled with 15 N and the subsequent determination of 15 N in a certain fraction of urine or in the total urine by emission spectrometry are described. Because of the key function of the liver in the metabolism of nitrogen compounds, the results of these tests allow conclusions concerning some disturbances of liver functions. (author)

  5. [Perioperative changes of coagulation functions in the local advanced liver cancer patients receiving liver transplantation].

    Science.gov (United States)

    Wang, Hao-Yuan; Zhao, Qing-Yu; Yuan, Yun-Fei

    2008-07-01

    Liver transplantation is widely accepted as an effective therapy of hepatoma. Perioperative dynamic observation of coagulation function is important for graft-receivers. This study was to explore perioperative changes of coagulation functions in the local advanced liver cancer patients who received liver transplantation. Clinical data of 31 local advanced liver cancer patients, underwent liver transplantation from Sep. 2003 to Jan. 2007, were analyzed. Platelet (PLT) counting, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib) and international normalized ratio (INR) before operation, at anhepatic phase and the first week after operation were analyzed to evaluate congulation function. The coagulation functions of most patients were normal before operation. The six parameters varied significantly at anhepatic phase and on most days of the first week after operation when compared with the preoperative levels (Pfunctions of local advanced liver cancer patients shift from hypocoagulatory to hypercoagulatory or normal in perioperative period, therefore, prevention of bleeding should be focused on at anhepatic phase and on 1-2 days after operation while prevention of thrombosis should be focused on after the first week after operation. The degree of liver cirrhosis and Child-Pugh level could help to evaluate postoperative coagulation disorder.

  6. Liver protein expression in dairy cows with high liver triglycerides in early lactation

    DEFF Research Database (Denmark)

    Sejersen, Henrik; Sørensen, Martin Tang; Larsen, Torben

    2012-01-01

    Fatty liver is a frequent subclinical health disorder in dairy cows that may lead to disorders related to the liver function. However, the effect of triglyceride (TG) accumulation on liver metabolic pathways is still unclear. The objective was, therefore, to characterize quantitative differences...... in the liver proteome between early lactation dairy cows with a low or high liver TG content. The liver proteome analysis indicated that a high liver TG content in early lactation dairy cows is associated with increased oxidation of saturated fatty acids, oxidative stress, and urea synthesis...... and decreasedoxidation of unsaturated fatty acids. Furthermore, liver gluconeogenesis is apparently not impaired by an increased liver TG content. Based on correlations between liver proteins and plasma components, we suggest that future studies investigate the sensitivity and specificity of plasma aspartate...

  7. 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

  8. Hepatic encephalopathy in a liver transplant recipient with stable liver function.

    Science.gov (United States)

    Arab, Juan Pablo; Meneses, Luis; Pérez, Rosa M; Arrese, Marco; Benítez, Carlos

    2013-04-01

    Postshunt hepatic encephalopathy after liver transplantation (LT) is an infrequent condition and is commonly associated with portal occlusion or stenosis and the presence of a patent portosystemic shunt. Portal vein stenosis (PVS) or thrombosis (PVT) are uncommon complications after LT. The overall frequency of both complications is reported to be less than 3%. When PVS or PVT develop early after LT, the occlusion of the portal vein can have catastrophic consequences to the graft including acute liver failure and graft loss. Late PVT/PVS are asymptomatic in approximately 50% of the cases and mainly diagnosed by a routine ultrasound. Symptomatic postshunt hepatic encephalopathy (HE) is a very infrequent condition after LT that has been scarcely reported in the literature. We present here the case of a liver recipient with normal graft function who presented with hepatic encephalopathy 3 months after LT with stable liver function but a severe portal stenosis and the presence of a spontaneous portosystemic shunt whose successful endovascular treatment was followed by the complete resolution of the HE.

  9. Diurnal variation in glycogen phosphorylase activity in rat liver. A quantitative histochemical study

    NARCIS (Netherlands)

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

    1987-01-01

    The diurnal variations of the glycogen content and of glycogen phosphorylase activity in periportal and pericentral areas of rat liver parenchyma have been analyzed in periodic acid Schiff (PAS)-stained cryostat sections using quantitative microdensitometry. Glycogen content and phosphorylase

  10. 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.

  11. Liver function tests using the stable isotope /sup 15/N

    Energy Technology Data Exchange (ETDEWEB)

    Faust, H; Jung, K; Hirschberg, K; Krumbiegel, P; Junghans, P; Reinhardt, R; Matkowitz, R; Teichmann, B

    1988-01-01

    Several liver function tests using oral application of a nitrogen compound labelled with /sup 15/N and the subsequent determination of /sup 15/N in a certain fraction of urine or in the total urine by emission spectrometry are described. Because of the key function of the liver in the metabolism of nitrogen compounds, the results of these tests allow conclusions concerning some disturbances of liver functions.

  12. Liver Function in the Pig

    African Journals Online (AJOL)

    1974-06-12

    Jun 12, 1974 ... The assessment of function of the isolated perfused liver remains complex. Much of this problem relates to an inability to compare function in vitro with that in vivo, because of a lack of knowledge of hepatic blood flow. This article documents measurement of total hepatic and portal blood flow in vivo in pigs, ...

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

    International Nuclear Information System (INIS)

    Elsharkawy, Wafaa B.; Elshemey, Wael M.

    2013-01-01

    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 (R 2 >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. - Highlights: • A method for the quantification of NAFLD is suggested. • Fatty liver tissue has characteristic x-ray scattering profile. • Profile characterization parameters show differences between normal and fatty liver. • Monte Carlo simulated x-ray scattering profiles are compared to measured

  14. A new liver function test using the asialoglycoprotein-receptor system on the liver cell membrane, 3

    International Nuclear Information System (INIS)

    Hazama, Hiroshi; Kawa, Soukichi; Kubota, Yoshitsugu

    1986-01-01

    We evaluated the vilidity of a new liver function test using liver scintigraphy based on the asialoglycoprotein (ASGP) receptor system on the liver cell membrane in rats with galactosamine-induced acute liver disorder and those with carbon tetra-chloride-induced chronic liver disorder. Neoglycoprotein (GHSA) produced by combining human serum albumin with 32 galactose units was labeled with 99m Tc and administered (50 μg/100 g body weight) to rats with acute or chronic liver disorder. Clearance curves were produced based on liver scintigrams and analysed using the two-compartment model to obtain parameters. In acute liver disorder, the prolongation of 99m Tc-GHSA clearance and the decrease in ASGP receptor activities correlated well to the increase in serum GOT and the decrease in the esterified to total cholesterol ratio (E/T ratio); in chronic liver disorder, they correlated significantly to the increase in the content of liver hydroxyproline (Hyp) which increased in proportion to the severity of liver fibrosis studied histologically, and to the decrease in the contents of cytochrome P-450 and cytochrome b 5 in liver microsomes. Significant correlation was observed between the prolongation of 99m Tc-GHSA clearance and the decrease in ASGP receptor activities in both acute and chronic liver disorders. These findings indicate that the measurement of 99m Tc-GHSA clearance can be a new liver function test sensitively reflecting the severity of liver damage. (author)

  15. 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.

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

    Science.gov (United States)

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

    2014-03-01

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

  17. 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.

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

    Science.gov (United States)

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

    2004-01-01

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

  19. Markers of liver function and inflammatory cytokines modulation by ...

    African Journals Online (AJOL)

    Conclusion: Aerobic exercise training modulates inflammatory cytokine levels and markers of liver function in patients with nonalcoholic ... and is associated with over nutrition and under activity, ... of these subjects with leptin reduced liver fat and liver enzyme ... tissue, muscle-released interleukin-6 inhibition of tumor.

  20. HEPATIC FUNCTION AFTER GENETICALLY-ENGINEERED PIG LIVER TRANSPLANTATION IN BABOONS

    Science.gov (United States)

    Ekser, Burcin; Echeverri, Gabriel J.; Hassett, Andrea Cortese; Yazer, Mark H.; Long, Cassandra; Meyer, Michael; Ezzelarab, Mohamed; Lin, Chih Che; Hara, Hidetaka; van der Windt, Dirk J.; Dons, Eefje M.; Phelps, Carol; Ayares, David; Cooper, David K.C.; Gridelli, Bruno

    2010-01-01

    Background If ‘bridging’ to allotransplantation is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured. Methods We have studied hepatic function in baboons after transplantation of livers from α1,3-galactosyltransferase gene-knockout (GTKO,n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46,n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In 4 baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs. Results Recipient baboons died or were euthanized after 4-7 days following internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed. Conclusions After the transplantation of genetically-engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near-normal; (2) there was evidence for production of pig proteins, including coagulation factors, and (3) these appeared to function adequately in baboons, though inter-species compatibility of such proteins remains to be confirmed. PMID:20606605

  1. 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...

  2. Visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging.

    NARCIS (Netherlands)

    Ploemen, I.H.J.; Prudencio, M.; Douradinha, B.G.; Ramesar, J.; Fonager, J.; Gemert, G.J.A. van; Luty, A.J.F.; Hermsen, C.C.; Sauerwein, R.W.; Baptista, F.G.; Mota, M.M.; Waters, A.P.; Que, I.; Lowik, C.W.G.M.; Khan, S.M.; Janse, C.J.; Franke-Fayard, B.

    2009-01-01

    The quantitative analysis of Plasmodium development in the liver in laboratory animals in cultured cells is hampered by low parasite infection rates and the complicated methods required to monitor intracellular development. As a consequence, this important phase of the parasite's life cycle has been

  3. The emerging role of transport systems in liver function tests

    NARCIS (Netherlands)

    Stieger, Bruno; Heger, Michal; de Graaf, Wilmar; Paumgartner, Gustav; van Gulik, Thomas

    2012-01-01

    Liver function tests are of critical importance for the management of patients with severe or terminal liver disease. They are also used as prognostic tools for planning liver resections. In recent years many transport systems have been identified that also transport substances employed in liver

  4. 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

    ). 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...... 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...... groups of patients. Dexamethasone suppression did not change the concentration of testosterone significantly, but oestrone and oestradiol concentrations decreased significantly (P less than 0.01) in controls and patients. In patients, but not in controls, a significant (P less than 0.01) increase in FSH...

  5. Extraction and quantitation of total cholesterol, dolichol and dolichyl phosphate from mammalian liver

    International Nuclear Information System (INIS)

    Crick, D.C.; Carroll, K.K.

    1987-01-01

    A procedure is described for the determination of total cholesterol, dolichol and dolichyl phosphate (Dol-P) in mammalian liver. It is based on extraction of these compounds into diethyl ether after alkaline saponification of the tissue. Extractability is affected by the length of saponification and concentration of potassium hydroxide (KOH) in the saponification mixture. After extraction, total cholesterol and dolichol are quantitated directly by reverse-phase high pressure liquid chromatography (HPLC) on C18. Dol-P requires further purification before quantitation by HPLC, this is accomplished by chromatography on silicic acid. These methods gave recoveries of over 90% for cholesterol and dolichol and about 60% for Dol-P, using [4- 14 C]cholesterol, a polyprenol containing 15 isoprene units, and [1- 14 C]Dol-P as recovery standards. Concentrations of total cholesterol, dolichol and Dol-P in livers from one month-old-CBA mice were found to be 5.7 +/- 0.7 mg/g, 66.3 +/- 1.2 micrograms/g and 3.7 +/- 0.3 micrograms/g, respectively

  6. Liver function test with 99mTc-labelled bilirubin in children

    International Nuclear Information System (INIS)

    Teichmann, B.; Kaempfer, I.; Schneider, G.

    1989-01-01

    Because of central role of bilirubin in the metabolism of liver it is well suited for liver function tests. Different parameters of hepatocellular partial function and histological findings were studied in patients suffering from functional hyperbilirubinaemia (n = 15), liver cirrhosis (n = 7) and 6 patients recovering from acute hepatitis. After intravenous injection of 99m Tc-bilirubin blood clearance and intestinal excretion in percentages of bilirubin were determined. In patients with cirrhosis the initial phase as well as the intestinal excretion of bilirubin were delayed. This liver function test is useful in the pediatric special diagnosis for investigations during the course of the illness and for assessment of therapeutic activities. (author)

  7. 15N liver function tests - concept, validity, clinical use

    International Nuclear Information System (INIS)

    Faust, H.; Jung, K.; Krumbiegel, P.; Hirschberg, K.; Reinhardt, R.; Junghans, P.

    1987-01-01

    Several liver function tests using the oral application of a nitrogen compound labelled with 15 N and the subsequent determination of 15 N in a certain fraction of urine by emission spectrometry are described. Because of the key position of the liver in the metabolism of nitrogen compounds the results of these tests allow conclusions concerning disturbances of special liver functions. Instructions for the clinical use of the '[ 15 N]Ammonium Test', '[ 15 N]Hippurate Test' the '[ 15 N]Methacetin Test', and the '[ 15 N]Glycine Test' are given. (author)

  8. A new liver function test using the asialoglycoprotein-receptor system on the liver cell membrane, 2

    International Nuclear Information System (INIS)

    Kawa, Soukichi; Hazama, Hiroshi; Kojima, Michimasa

    1986-01-01

    We produced labeled neoglycoprotein (GHSA) that is physiologically equivalent to ASGP, and quantitatively examined whether its uptake by the liver is dose-related using the following methods: 1) binding assay between GHSA and ASGP receptors, 2) measurement of the liver extraction ratio in the initial circulation following administration into the portal vein, and 3) measurement of clearance in normal rats and rats with galacosamine-induced acute liver disorder. The binding assay showed a linear relationship between the concentration of 125 I-GHSA and the amount of ASGP receptors obtained from the rat liver. A membrane assay using 125 I-GHSA and the liver cell membrane revealed similar results. The liver extraction ratio in the initial circulation following the administration into the portal vein of normal rabbits was highly dose-dependent (r = -0.95 in the range of 5 - 100 μg GHSA). Serial imaging of 99m Tc-GHSA during two-hour period after administration into the peripheral blood showed specific accumulation in the liver beginning immediately after the intravenous injection and subsequent transport mainly via the biliary system into the small intestine in the normal rat and mainly into the urine in the bile duct ligated rat. As a dynamic model of 99m Tc-GHSA, its circulation through the heart and liver and inactivated release from the liver was used, and two-compartment analysis was made on measurement curves in the heart and liver to obtain clearance parameters. The concentration of administered 99m Tc-GHSA (50 - 100 μg/100 g body weight) showed a positive linear relationship with clearance. Administration of 50 μg/100 g body weight of 99m Tc-GHSA revealed a significant correlation (p < 0.001) between clearance and ASGP receptor activity in normal rats and rats with galactosamine-induced acute liver disorder. (J.P.N.)

  9. Recellularization via the bile duct supports functional allogenic and xenogenic cell growth on a decellularized rat liver scaffold.

    Science.gov (United States)

    Hassanein, Wessam; Uluer, Mehmet C; Langford, John; Woodall, Jhade D; Cimeno, Arielle; Dhru, Urmil; Werdesheim, Avraham; Harrison, Joshua; Rivera-Pratt, Carlos; Klepfer, Stephen; Khalifeh, Ali; Buckingham, Bryan; Brazio, Philip S; Parsell, Dawn; Klassen, Charlie; Drachenberg, Cinthia; Barth, Rolf N; LaMattina, John C

    2017-01-02

    Recent years have seen a proliferation of methods leading to successful organ decellularization. In this experiment we examine the feasibility of a decellularized liver construct to support growth of functional multilineage cells. Bio-chamber systems were used to perfuse adult rat livers with 0.1% SDS for 24 hours yielding decellularized liver scaffolds. Initially, we recellularized liver scaffolds using a human tumor cell line (HepG2, introduced via the bile duct). Subsequent studies were performed using either human tumor cells co-cultured with human umbilical vein endothelial cells (HUVECs, introduced via the portal vein) or rat neonatal cell slurry (introduced via the bile duct). Bio-chambers were used to circulate oxygenated growth medium via the portal vein at 37C for 5-7 days. Human HepG2 cells grew readily on the scaffold (n = 20). HepG2 cells co-cultured with HUVECs demonstrated viable human endothelial lining with concurrent hepatocyte growth (n = 10). In the series of neonatal cell slurry infusion (n = 10), distinct foci of neonatal hepatocytes were observed to repopulate the parenchyma of the scaffold. The presence of cholangiocytes was verified by CK-7 positivity. Quantitative albumin measurement from the grafts showed increasing albumin levels after seven days of perfusion. Graft albumin production was higher than that observed in traditional cell culture. This data shows that rat liver scaffolds support human cell ingrowth. The scaffold likewise supported the engraftment and survival of neonatal rat liver cell slurry. Recellularization of liver scaffolds thus presents a promising model for functional liver engineering.

  10. Quantitative hepatosplenic scintiscanning. Experimental and clinical studies to determine the contents of radioactivity in liver and spleen following administration of 99mTc sulfur colloid

    International Nuclear Information System (INIS)

    Feuchtinger, T.

    1983-01-01

    Hepatosplenic scintiscans were obtained from 78 patients following administration of 99mTc sulfur colloid using a double-head scanner and subjected to quantitative analysis. It was the aim of the study to assess the practicability of quantitative scintiscanning of liver and spleen, to define the range of generally acceptable, normal values for the concentration of 99mTc sulfur colloid in liver and spleen as well as to evaluate the clinical relevance of this method. The following values were determined to be normal: 4.7±1.5 for the liver: Spleen ratio; 31±3% for the proportion of the left hepatic lobe in total liver concentration; 68.7±5.4% and 17.4±3.6% for the active contents of liver and spleen, respectively. Quantitative scintiscanning constitutes a very sensitive method to detect transformation processes in the liver that are associated with a decreased liver: Spleen ratio and an increased ratio between the left hepatic lobe and the total organ. The method is unsuitable to assess pathological accumulation of the tracer substances. The question as to whether the use of the more time-consuming procedure of quantitative scintiscanning is justified by the additional diagnostic information gained remains to be investigated in further studies. (TRV) [de

  11. Thyroid function and some related biochemical parameters in bilharzial liver disease

    International Nuclear Information System (INIS)

    Ibrahim, W. Abdel Massih

    1983-01-01

    Bilharziasis in its different forms is estimated to affect at least 200 million people in the world (W.H.O., 1973). In egypt, it affects 60 - 70% of the rural population (WcMullen, 1963). Bilharzial ova reaches the liver with the portal blood stream causing a fibro - cellular reaction in and around the portal tract resulting in hepatic periportal fibrosis with various clinical stages (Abdalla et al., 1978 b). The effect of liver disease on thyroid function is still a subject of controversy and contradiction. While some reports are published on the effect of non-bilharzial liver disease on thyroid function, there is scanty studies as regards to bilharzial liver diseases . Most of the studies carried out to evaluate thyroid function in bilharzial liver disease, were focused on the estimation of one or two parameters of thyroid function e.g., T 3 and TSH. The available review of literature was focused on some parameters of thyroid function ignoring the others thyroid function tests and not considering the hormone carrier proteins. Thus resulting inconsistent and contradictory results (Ghareeb, 1962; El Haieg and Ibrahim, 1977)

  12. Noninvasive Diagnosis of Nonalcoholic Fatty Liver Disease and Quantification of Liver Fat Using a New Quantitative Ultrasound Technique.

    Science.gov (United States)

    Lin, Steven C; Heba, Elhamy; Wolfson, Tanya; Ang, Brandon; Gamst, Anthony; Han, Aiguo; Erdman, John W; O'Brien, William D; Andre, Michael P; Sirlin, Claude B; Loomba, Rohit

    2015-07-01

    Liver biopsy analysis is the standard method used to diagnose nonalcoholic fatty liver disease (NAFLD). Advanced magnetic resonance imaging is a noninvasive procedure that can accurately diagnose and quantify steatosis, but is expensive. Conventional ultrasound is more accessible but identifies steatosis with low levels of sensitivity, specificity, and quantitative accuracy, and results vary among technicians. A new quantitative ultrasound (QUS) technique can identify steatosis in animal models. We assessed the accuracy of QUS in the diagnosis and quantification of hepatic steatosis, comparing findings with those from magnetic resonance imaging proton density fat fraction (MRI-PDFF) analysis as a reference. We performed a prospective, cross-sectional analysis of a cohort of adults (N = 204) with NAFLD (MRI-PDFF, ≥5%) and without NAFLD (controls). Subjects underwent MRI-PDFF and QUS analyses of the liver on the same day at the University of California, San Diego, from February 2012 through March 2014. QUS parameters and backscatter coefficient (BSC) values were calculated. Patients were assigned randomly to training (n = 102; mean age, 51 ± 17 y; mean body mass index, 31 ± 7 kg/m(2)) and validation (n = 102; mean age, 49 ± 17 y; body mass index, 30 ± 6 kg/m(2)) groups; 69% of patients in each group had NAFLD. BSC (range, 0.00005-0.25 1/cm-sr) correlated with MRI-PDFF (Spearman ρ = 0.80; P hepatic steatosis, based on a cross-sectional analysis that used MRI-PDFF as the reference. With further validation, QUS could be an inexpensive, widely available method to screen the general or at-risk population for NAFLD. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. 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.

    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)

  14. EFFECTS OF RESVERATROL ON LIVER FUNCTION OF OBESE FEMALE WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Nádia Araújo Miguel

    2016-07-01

    Full Text Available Resveratrol has antioxidant, anti-inflammatory, lipolytic, and antifibrotic properties, which may be useful in supplementation of obese patients and with liver problems. This study evaluated the effects of 6-week resveratrol supplementation on the lipid profile and liver function of female Wistar rats fed a high-fat diet to induce obesity. Sixty-four Wistar rats were divided into 4 groups (n = 16: the control group (C; the control obese group (CO; the resveratrol group (R; and the resveratrol obese group (RO. At the end of the experiment, the animals were anesthetized for blood collection and subsequent euthanasia for collection of liver biopsy. The parameters for body weight, liver weight, retroperitoneal fat weight, serum lipid and liver profiles and histopathological analysis were evaluated. The 6-week resveratrol administration did not induce weight loss nor did it reduce the lipid profile; however, it decreased the liver enzymes aspartate aminotransferase (AST and alkaline phosphatase (ALP and reduced the incidence of steatosis (75.0% in group RO compared with group CO (81.2%. Thus, we concluded that resveratrol supplementation for the short period of six weeks had a beneficial effect on liver function by reducing hepatic steatosis and the liver enzymes AST and ALP in obese female rats. Keywords: liver function; obesity; rats; resveratrol.

  15. Liver Function Status in some Nigerian Children with Protein Energy ...

    African Journals Online (AJOL)

    Objective: To ascertain functional status of the liver in Nigeria Children with Protein energy malnutrition. Materials and Methods: Liver function tests were performed on a total of 88 children with protein energy malnutrition (PEM). These were compared with 22 apparently well-nourished children who served as controls.

  16. 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.

  17. UPF2 is a critical regulator of liver development, function and regeneration

    DEFF Research Database (Denmark)

    Thoren, Lina A; Nørgaard, Gitte A; Weischenfeldt, Joachim

    2010-01-01

    regulatory potential of the NMD pathway in mammals will require the functional assessment of NMD in different tissues. METHODOLOGY/PRINCIPAL FINDINGS: Here we use mouse genetics to address the role of UPF2, a core NMD component, in the development, function and regeneration of the liver. We find that loss....... CONCLUSION/SIGNIFICANCE: Collectively, our data demonstrate the critical role of the NMD pathway in liver development, function and regeneration and highlights the importance of NMD for mammalian biology....... of NMD during fetal liver development is incompatible with postnatal life due to failure of terminal differentiation. Moreover, deletion of Upf2 in the adult liver results in hepatosteatosis and disruption of liver homeostasis. Finally, NMD was found to be absolutely required for liver regeneration...

  18. Quantitative Shear-Wave Elastography of the Liver in Preterm Neonates with Intra-Uterine Growth Restriction.

    Directory of Open Access Journals (Sweden)

    Marianne Alison

    Full Text Available The feasibility and reproducibility of liver stiffness measurements using Supersonic Shear-wave Imaging (SSI in preterm neonate have not been reported. Our aim was to determine if liver stiffness differs between intra-uterine growth restriction (IUGR and appropriate for gestational age (AGA preterm infants with/without cholestasis. We measured liver stiffness (in kPa in 45 AGA and 18 IUGR preterm infants, and assessed reproducibility in 26 preterms using Intraclass Correlation Coefficients (ICC and Bland-Altman tests. Liver stiffness values were compared between AGA and IUGR with and without cholestasis and correlated with birth weight. Measurements showed high reproducibility (ICC = 0.94-0.98 for intra-operator, 0.86 for inter-operator with good agreement (95% limits: -1.24 to 1.24 kPa. During the first postnatal week, liver stiffness was higher in IUGR (7.50 ±1.53 kPa than in AGA infants (5.11 ±0.80 kPa, p<0.001. After day 8, liver stiffness remained unchanged in AGA but increased progressively in IUGR infants (15.57 ±6.49 kPa after day 21. Liver stiffness was higher in IUGR neonates with cholestasis (19.35 ± 9.80 kPa than without cholestasis (7.72 ± 1.27 kPa, p<0.001. In conclusion, quantitative liver SSI in preterms is feasible and reproducible. IUGR preterms who will develop cholestasis present high liver stiffness even at birth, before biological cholestasis occurs.

  19. Volumetric and functional recovery of the remnant liver after major liver resection with prior portal vein embolization : recovery after PVE and liver resection

    NARCIS (Netherlands)

    van den Esschert, J.W.; de Graaf, W.; van Lienden, K.P.; Busch, O.R.; Heger, M.; van Delden, O.M.; Gouma, D.J.; Bennink, R.J.; Laméris, J.S.; van Gulik, T.M.

    2009-01-01

    INTRODUCTION: Portal vein embolization is an accepted method to increase the future remnant liver preoperatively. The aim of this study was to assess the effect of preoperative portal vein embolization on liver volume and function 3 months after major liver resection. MATERIALS AND METHODS: This is

  20. Changes of plasma VEGF levels and liver function in patients with liver cancer before and after interventional treatment

    International Nuclear Information System (INIS)

    Li Jia; Qi Jun; Gao Jia

    2011-01-01

    To explore the effect of the interventional treatment for the angiogenesis and liver function in patients with liver cancer within short time, enzyme linked immunosorbent assay was used to determine the level of VEGF in plasma. The level of liver function was measured through automatic biochemistry analyzer. The results indicated that the level of VEGF in patients with liver cancer decreased after interventional treatment than that of before treatment (P<0.05). The level of total protein, albumin, alkaline phosphatase and total bile acid decreased after interventional treatment (P<0.05). The level of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin and indirect bilirubin were increased than before (P<0.05). The interventional treatment inhibit the expression of the VEGF in the tumor tissue and limited the angiogenesis within short time, but to some extent may caused the injury of the hepatocytes and the synthetic and excremental function in patients with liver cancer. (authors)

  1. 131I-BSP liver function test by BSP tolerance

    International Nuclear Information System (INIS)

    Kanda, Koichi

    1974-01-01

    131 I-BSP liver function test after BSP intravenous tolerance was discussed, assuming that the reason why measurements of 131 I-BSP retention rate at 30 minutes and 131 I-BSP disappearance rate in blood showed respectable overlapping between normal group and group with slight liver disorders as compared with BSP test and the reason why differential diagnosis was difficult were due to underestimate of tolerance volume of 131 I-BSP. 131 I-BSP was observed with time as to 70 persons with normal liver function and 257 cases of liver diseases, using 5, 3 and 2 mg of non-radioactive BSP tolerance volume per kilogram of body weight. 131 I-BSP retention rate at 30 minutes and 131 I-BSP disappearance rate in blood are possible to separate overlapping over control in each measurement value at 3-5 mg/kg of tolerance, and in comparison of 3 mg and 5 mg, the latter showed a little excellent result. So, it was decided that tolerance of 3 mg/kg was a proper dose, considering tolerance to liver cells. 131 I-BSP retention rate at 30 minutes was a little excellent in accuracy and disappearance rate in blood after BSP tolerance is simple and profitable for practical use because collection of blood was only one time and measurement could be made with whole blood. As mentioned above, this method is seemed to be useful to practice of liver function test. (Kanao, N.)

  2. Quantitative assessment of hepatic and splenic blood flow detected by Tc-99m-Sn colloid liver scintigraphy

    International Nuclear Information System (INIS)

    Narabayashi, Isamu; Nishiyama, Shoji; Sugimura, Kazuro

    1983-01-01

    Quantitative assessment of hepatic and splenic blood flow detected by injecting Tc-99m-Sn colloid as a bolus was performed on 75 patients who were suspected of having liver disease. Using a computer, the hepatic and splenic time-activity curves were analyzed. Hepatic index was calculated as the ratio of arterial to portal blood flow. The peak time of the right kidney was corresponded to the junction of the arterial and portal phases of the hepatic curve. Splenic index was calculated as the ratio of splenic arterial to liver arterial blood flow. Hepatic and splenic indices had elevated in cases of liver cirrhosis and hepatoma than those of normal controls. There was no significant difference in the hepatic and splenic indices among chronic hepatitis, liver metastasis and normal subject. These noninvasive tests for the hepatic and splenic blood flow may be useful in writing a report of liver scintigram because of the added information of the liver. (author)

  3. Two quantitative methods for assessment of [Tc-99m]-MAA in the lung in the treatment of liver metastases: a case study

    International Nuclear Information System (INIS)

    Willowson, Kathy P.; Bailey, Dale L.; Baldock, Clive

    2009-01-01

    Full text: Objective: The use of Y-90 microspheres to treat metastatic liver cancer is becoming widely utilized. Despite the fact that the microspheres are delivered directly to the liver, some activity may bypass the liver capillaries and be shunted to the lungs. To evaluate the percentage of pulmonary breakthrough, a pre-therapy test is performed using Tc- 9 9 m labeled spheres. The aim of this project was to compare two quantitative methods for assessing lung uptake, and consider the possibility of organ specific quantification. Method: A previously validated method for achieving CT-based quantitative SPECTI was compared to a simple planar approach. A 44 year old man suffering from metastatic liver sarcoma was referred to the clinic for pre-therapy evaluation. After injection of Tc- 9 9 m labeled microspheres and routine imaging, a SPECT/CT was acquired and specific organ uptake values calculated. A further calibrated injection of [Tc- 9 9 m ]-MAA was then given as a simplified alternative to quantify lung uptake by comparing pre and post counts. Results: The quantitative SPECT/CT method correctly accounted for all injected activity and found 80% of the dose was retained in the liver and 4% in the lungs. The planar method found -4% of the dose in the lungs. Conclusion: The quantitative technique we have developed allows for accurate calculation of organ specific uptake, which has important implications for treatment. The additional MAA injection offers a simplified but accurate method to quantify lung uptake. I. K Willow son, D.L Bailey and C Baldock (2008) Quantitative SPECT reconstructions using CT-derived corrections Phys Med Bioi 53:3099-3112.

  4. 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

    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 signi......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...... 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...

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

    International Nuclear Information System (INIS)

    Zhang, Long Jiang; Wu, Shengyong; Wang, Mei; Lu, Li; Chen, Bo; Jin, Lixin; Wang, Jiandong; Larson, Andrew C.; Lu, Guang Ming

    2012-01-01

    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.

  6. Isotopic study of liver function after narcosis in small animals

    International Nuclear Information System (INIS)

    Le Qui Cuong; Kiss, Bela; Jakab, Tivadar; Szilvasi, Istvan; Spett, Borbala

    1984-01-01

    Dinamic functional study of the liver was performed by sup(99m)Tc-TECHIDA in narcotized (Halothane) mice and rabbits. Hepatic uptake of the radiopharmaceutical decreased in narcotized group significantly. Excretion also decreased but statistically insignificantly. These alterations in the liver function could be attributed to the hypotensive effect of Halothane. (author)

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

    International Nuclear Information System (INIS)

    Wu, V; Epelman, M; Feng, M; Cao, Y; Wang, H; Romeijn, E; Matuszak, M

    2014-01-01

    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

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

    International Nuclear Information System (INIS)

    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.

    2015-01-01

    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- 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- 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 68 Ga-DOTATOC PET is

  9. Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

    Science.gov (United States)

    Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

    2016-09-01

    Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Quality of Liver and Kideny Function Test

    African Journals Online (AJOL)

    GB

    results for kidney functions and liver functions in. HIV diagnostic and monitoring laboratory are extremely important for decision making with patients under ART programs, and the consequences of erroneous results are huge (8, 9). 1University of Bahir Dar, Biological Inorganic Chemistry, P.O.Box-79, Bahir Dar, Ethiopia.

  11. 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.)

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

    Science.gov (United States)

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

    2017-06-02

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

  13. Characterization of genetically engineered mouse hepatoma cells with inducible liver functions by overexpression of liver-enriched transcription factors.

    Science.gov (United States)

    Yamamoto, Hideaki; Tonello, Jane Marie; Sambuichi, Takanori; Kawabe, Yoshinori; Ito, Akira; Kamihira, Masamichi

    2018-01-01

    New cell sources for the research and therapy of organ failure could significantly alleviate the shortage of donor livers that are available to patients who suffer from liver disease. Liver carcinoma derived cells, or hepatoma cells, are the ideal cells for developing bioartificial liver systems. Such cancerous liver cells are easy to prepare in large quantities and can be maintained over long periods under standard culture conditions, unlike primary hepatocytes. However, hepatoma cells possess only a fraction of the functions of primary hepatocytes. In a previous study, by transducing cells with liver-enriched transcription factors that could be inducibly overexpressed-hepatocyte nuclear factor (HNF)1α, HNF1β, HNF3β [FOXA2], HNF4α, HNF6, CCAAT/enhancer binding protein (C/EBP)α, C/EBPβ and C/EBPγ-we created mouse hepatoma cells with high liver-specific gene expression called the Hepa/8F5 cell line. In the present study, we performed functional and genetic analyses to characterize the Hepa/8F5 cell line. Further, in three-dimensional cultures, the function of these cells improved significantly compared to parental cells. Ultimately, these cells might become a new resource that can be used in basic and applied hepatic research. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. Contrast-enhanced ultrasound for quantitative assessment of portal pressure in canine liver fibrosis.

    Science.gov (United States)

    Zhai, Lin; Qiu, Lan-Yan; Zu, Yuan; Yan, Yan; Ren, Xiao-Zhuan; Zhao, Jun-Feng; Liu, Yu-Jiang; Liu, Ji-Bin; Qian, Lin-Xue

    2015-04-21

    To explore the feasibility of non-invasive quantitative estimation of portal venous pressure by contrast-enhanced ultrasound (CEUS) in a canine model. Liver fibrosis was established in adult canines (Beagles; n = 14) by subcutaneous injection of carbon tetrachloride (CCl4). CEUS parameters, including the area under the time-intensity curve and intensity at portal/arterial phases (Qp/Qa and Ip/Ia, respectively), were used to quantitatively assess the blood flow ratio of the portal vein/hepatic artery at multiple time points. The free portal venous pressures (FPP) were measured by a multi-channel baroreceptor using a percutaneous approach at baseline and 8, 16, and 24 wk after CCl4 injections in each canine. Liver biopsies were obtained at the end of 8, 16, and 24 wk from each animal, and the stage of the fibrosis was assessed according to the Metavir scoring system. A Pearson correlation test was performed to compare the FPP with Qp/Qa and Ip/Ia. Pathologic examination of 42 biopsies from the 14 canines at weeks 8, 16, and 24 revealed that liver fibrosis was induced by CCl4 and represented various stages of liver fibrosis, including F0 (n = 3), F1 (n = 12), F2 (n = 14), F3 (n = 11), and F4 (n = 2). There were significant differences in the measurements of Qp/Qa (19.85 ± 3.30 vs 10.43 ± 1.21, 9.63 ± 1.03, and 8.77 ± 0.96) and Ip/Ia (1.77 ± 0.37 vs 1.03 ± 0.12, 0.83 ± 0.10, and 0.69 ± 0.13) between control and canine fibrosis at 8, 16, and 24 wk, respectively (all P fibrosis model. Prediction of elevated FPP based on Qp/Qa and Ip/Ia was highly sensitive, as assessed by the area under the receiver operating curve (0.866 and 0.895, respectively). CEUS is a potential method to accurately, but non-invasively, estimate portal venous pressure through measurement of Qp/Qa and Ip/Ia parameters.

  15. 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...... with wedged-to-free hepatic vein pressure (r = +0.54; P less than 0.01). The increase of testosterone after the load did not correlate significantly with sex hormone-binding globulin (r = +0.35; P greater than 0.05). It is concluded that the hepatic extraction of testosterone is significantly decreased...

  16. Liver-resident NK cells and their potential functions.

    Science.gov (United States)

    Peng, Hui; Sun, Rui

    2017-09-18

    Natural killer (NK) cells represent a heterogeneous population of innate lymphocytes with phenotypically and functionally distinct subsets. In particular, recent studies have identified a unique subset of NK cells residing within the liver that are maintained as tissue-resident cells, confer antigen-specific memory responses and exhibit different phenotypical and developmental characteristics compared with conventional NK (cNK) cells. These findings have encouraged researchers to uncover tissue-resident NK cells at other sites, and detailed analyses have revealed that these tissue-resident NK cells share many similarities with liver-resident NK cells and tissue-resident memory T cells. Here, we present a brief historical perspective on the discovery of liver-resident NK cells and discuss their relationship to cNK cells and other emerging NK cell subsets and their potential functions.Cellular &Molecular Immunology advance online publication, 18 September 2017; doi:10.1038/cmi.2017.72.

  17. Liver Function Tests

    Science.gov (United States)

    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now Diagnosing Liver Disease – Liver ...

  18. Well Preserved Renal Function in Children With Untreated Chronic Liver Disease.

    Science.gov (United States)

    Berg, Ulla B; Németh, Antal

    2018-04-01

    On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD. In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. Hyperfiltration (>+2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%), and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% < -2 SD). Increased GFR and ERPF was found in patients with elevated transaminases, low prothrombin level, high bile acid concentration, and high aspartate-aminotransferase-to-platelet ratio. Most children with CLD had surprisingly well preserved renal function and certain groups had even hyperfiltration. The finding that children with decompensated liver disease and ongoing liver failure had stable kidney function suggests that no prognostic markers of threatening hepatorenal syndrome were at hand. Moreover, estimation of GFR based on serum creatinine fails to reveal hyperfiltration.

  19. 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

  20. Determination of liver and spleen perfusion by quantitative sequential scintigraphy: results in normal subjects and in patients with portal hypertension

    International Nuclear Information System (INIS)

    Biersack, H.J.; Torres, J.; Thelen, M.; Monzon, O.; Winkler, C.

    1981-01-01

    Quantitative sequential hepatosplenic scintigraphy was performed to determine the arterial and portal components of the total liver circulation in 135 patients (no liver disease in 20, liver cirrhosis and portal ;hypertension in 115). Portal circulation in healthy patients is calculated to be 70.4 +/- 6.2% of the total liver blood flow, whereas patients with portal hypertension showed a clear reduction of portal perfusion to 20.2 +/- 10.9%. Thirteen of 20 patients having portosystemic shunt surgery showed no portal perfusion. This new, noninvasive diagnostic technique yields vital information particularly useful in ;the surgical evaluation of portal hypertension. Other indications are also discussed

  1. Liver receptor homolog-1 is a critical determinant of methyl-pool metabolism

    Science.gov (United States)

    Balance of labile methyl groups (choline, methionine, betaine, and folate) is important for normal liver function. Quantitatively, a significant use of labile methyl groups is in the production of phosphatidylcholines (PCs), which are ligands for the nuclear liver receptor homolog-1 (LRH-1). We stud...

  2. Chronological evaluation of liver enhancement in patients with chronic liver disease at Gd-EOB-DTPA-enhanced 3-T MR imaging. Does liver function correlate with enhancement?

    International Nuclear Information System (INIS)

    Nakamura, Shinichi; Utsunomiya, Daisuke; Namimoto, Tomohiro; Yamashita, Yasuyuki; Awai, Kazuo; Nakaura, Takeshi; Morita, Kosuke

    2012-01-01

    The purpose of this study was to investigate the chronological relationship between scan delay and liver enhancement for the hepatobiliary phase on Gd-EOB-DTPA-enhanced MRI and evaluate the effects of liver function on liver enhancement. Hepatobiliary-phase images were retrospectively evaluated in 125 patients with chronic liver disease. Hepatobiliary phase images were obtained at 5, 10, 15, and 20 min after injection. We calculated relative liver enhancement (RLE) at t min after injection by dividing the signal intensity (SI) of the liver at t min by precontrast SI. We compared RLE values at 5, 10, 15, and 20 min and evaluated the detectability of focal hepatic lesions. We analyzed the effect of liver function on RLE with the generalized linear model. There was not significant difference in RLE and lesion detectability at 15 and 20 min. RLE in the Child-Pugh C group was significantly lower than in the Child-Pugh A and B groups. The serum albumin level and prothrombin time were significantly correlated with the liver enhancement. A delay time of 15 min for the hepatobiliary phase was thought to be adequate in patients with mild liver dysfunction. The serum albumin level and prothrombin time would be predictive of liver enhancement in the hepatobiliary phase. (author)

  3. Quantitative Proteome Analysis of Mouse Liver Lysosomes Provides Evidence for Mannose 6-phosphate-independent Targeting Mechanisms of Acid Hydrolases in Mucolipidosis II.

    Science.gov (United States)

    Markmann, Sandra; Krambeck, Svenja; Hughes, Christopher J; Mirzaian, Mina; Aerts, Johannes M F G; Saftig, Paul; Schweizer, Michaela; Vissers, Johannes P C; Braulke, Thomas; Damme, Markus

    2017-03-01

    The efficient receptor-mediated targeting of soluble lysosomal proteins to lysosomes requires the modification with mannose 6-phosphate (M6P) residues. Although the absence of M6P results in misrouting and hypersecretion of lysosomal enzymes in many cells, normal levels of lysosomal enzymes have been reported in liver of patients lacking the M6P-generating phosphotransferase (PT). The identity of lysosomal proteins depending on M6P has not yet been comprehensively analyzed. In this study we purified lysosomes from liver of PT-defective mice and 67 known soluble lysosomal proteins were identified that illustrated quantitative changes using an ion mobility-assisted data-independent label-free LC-MS approach. After validation of various differentially expressed lysosomal components by Western blotting and enzyme activity assays, the data revealed a small number of lysosomal proteins depending on M6P, including neuraminidase 1, cathepsin F, Npc2, and cathepsin L, whereas the majority reach lysosomes by alternative pathways. These data were compared with findings on cultured hepatocytes and liver sinusoid endothelial cells isolated from the liver of wild-type and PT-defective mice. Our findings show that the relative expression, targeting efficiency and lysosomal localization of lysosomal proteins tested in cultured hepatic cells resemble their proportion in isolated liver lysosomes. Hypersecretion of newly synthesized nonphosphorylated lysosomal proteins suggest that secretion-recapture mechanisms contribute to maintain major lysosomal functions in liver. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. 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

  5. Quantitative evaluation of 99mTc-GSA for fatty liver and ischemia-reperfusion injury in rats

    International Nuclear Information System (INIS)

    Kimoto, Mitsunori

    1996-01-01

    99m Tc-GSA (GSA) liver scintigraphy was performed in rats with fatty liver and ischemia-reperfusion injury to study the usefulness of GSA in evaluating these pathological processes. Fatty liver was produced by feeding rats a choline-deficient diet. The rats with fatty liver were divided into five groups according to the length of the diet (controls, two weeks, six weeks, 10 weeks, and 12 weeks). In the rats dieted for two weeks and six weeks, regional hepatic ischemia was also induced by clamping the left hepatic artery and the left portal vein for 10 minutes, then reperfusion was performed for 15 minutes. GSA was administered via the IVC. t 90 , or the time at which the liver time activity curve reached ninety percent of its peak value, was used as an index of GSA hepatic uptake, Ku and Kd, determined by two compartment analysis, were also used as indices. In rats of the fatty liver group, we confirmed microscopically that various degrees of fatty infiltration existed according to the diet period, and t 90 became significantly longer according to the severity of fatty infiltration. Ku and Kd also decreased according to the severity of fatty infiltration. In the rats with fatty infiltration and ischemia-reperfusion injury, t 90 also increased according to the severity of fatty infiltration, becoming longer than in the rats without ischemia-reperfusion injury. Quantitative analysis of GSA liver scintigraphy was useful for evaluating fatty liver and ischemia-reperfusion injury. (author)

  6. [Effects of an oxacephem antibiotic on liver function in orthopedic surgery].

    Science.gov (United States)

    Kuroyama, M; Otori, K; Yokota, S; Aoto, H; Sawada, M; Yago, K; Fujita, T; Kumagai, Y

    1999-07-01

    The subjects were 531 patients who underwent orthopedic surgery. Flomoxef was administered, and liver function was examined before and after administration. Abnormal liver function after administration of flomoxef was found in 14.3% of patients. In male patients, a high rate of 18.8% was observed. A particularly high rate of 37.0% was obtained among patients who showed GOT values of more than 40 U/L before treatment with flomoxef. The prevalence of abnormal GOT and GPT values after administration of flomoxef was 3.6% and 13.2%, respectively. These values were significantly higher than those obtained with other cephem antibiotics. These rates of occurrence of abnormally high GOT and GPT are obviously higher than those submitted at the time of approval and reported in the drug use investigation. The prevalence of abnormal liver function values was high in patients receiving flomoxef, and particularly high in male patients and patients whose GOT was high before administration of flomoxef. Therefore, sufficient check of liver function appears important when administration of flomoxef to these types of patients is intended.

  7. Evaluation of liver function tests of HIV positive patients on ...

    African Journals Online (AJOL)

    Liver enzymes-alanine and aspartate aminotransferases and alkaline phosphatase (AST, ALT and ALP), bilirubin and serum proteins were determined using standard laboratory methods and these parameters were used to evaluate the liver function of human immunodeficiency virus (HIV)- positive patients receiving ...

  8. /sup 131/I-BSP liver function test by BSP tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Kanda, K [Minami Osaka Hospital (Japan)

    1974-11-01

    /sup 131/I-BSP liver function test after BSP intravenous tolerance was discussed, assuming that the reason why measurements of /sup 131/I-BSP retention rate at 30 minutes and /sup 131/I-BSP disappearance rate in blood showed respectable overlapping between normal group and group with slight liver disorders as compared with BSP test and the reason why differential diagnosis was difficult were due to underestimate of tolerance volume of /sup 131/I-BSP. /sup 131/I-BSP was observed with time as to 70 persons with normal liver function and 257 cases of liver diseases, using 5, 3 and 2 mg of non-radioactive BSP tolerance volume per kilogram of body weight. /sup 131/I-BSP retention rate at 30 minutes and /sup 131/I-BSP disappearance rate in blood are possible to separate overlapping over control in each measurement value at 3 to 5 mg/kg of tolerance, and in comparison of 3 mg and 5 mg, the latter showed a little excellent result. So, it was decided that tolerance of 3 mg/kg was a proper dose, considering tolerance to liver cells. /sup 131/I-BSP retention rate at 30 minutes was a little excellent in accuracy and disappearance rate in blood after BSP tolerance is simple and profitable for practical use because collection of blood was only one time and measurement could be made with whole blood. As mentioned above, this method is seemed to be useful to practice of liver function test.

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

    International Nuclear Information System (INIS)

    Zhao Hong; Li Binxiang; Zhang Lizhong; Liang Jianfang

    1997-01-01

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

  10. 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

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

    Science.gov (United States)

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2016-09-14

    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 blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

  12. The microRNA Expression Profile in Donation after Cardiac Death (DCD Livers and Its Ability to Identify Primary Non Function.

    Directory of Open Access Journals (Sweden)

    Shirin Elizabeth Khorsandi

    Full Text Available Donation after cardiac death (DCD livers are marginal organs for transplant and their use is associated with a higher risk of primary non function (PNF or early graft dysfunction (EGD. The aim was to determine if microRNA (miRNA was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7, good functional outcome (n=7 peak aspartate transaminase (AST ≤ 1000 IU/L and EGD (n=9 peak AST ≥ 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR. The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p<0.05. On RT-qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical groups. Only one miRNA, miR-22, was validated with marginal significance, to have differential expression between the three groups (p=0.049. From computational biology miR-22 was predicted to affect signalling pathways that impact protein turnover, metabolism and apoptosis/cell cycle. In conclusion, microRNA expression patterns have a low diagnostic potential clinically in discriminating DCD liver quality and outcome.

  13. Hepatitis B and C virus infections and liver function in AIDS patients ...

    African Journals Online (AJOL)

    Background: Impaired liver function tests and co-infection with hepatitis viruses in AIDS patients are common in western countries. Objective: To assess liver function and prevalence of co-infection with hepatitis B and hepatitis C viruses in AIDS patients at Chris Hani Baragwanath Hospital. Design: A prospective study.

  14. Effect of 6-Month Calorie Restriction and Exercise on Serum and Liver Lipids and Markers of Liver Function

    Science.gov (United States)

    Larson-Meyer, D. Enette; Newcomer, Bradley R.; Heilbronn, Leonie K.; Volaufova, Julia; Smith, Steven R.; Alfonso, Anthony J.; Lefevre, Michael; Rood, Jennifer C.; Williamson, Donald A.; Ravussin, Eric

    2009-01-01

    objective Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. Methods and Procedures Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m2) were randomized to “control (CO)” = 100% energy requirements; “CR” = 25%; “caloric restriction and increased structured exercise (CR+EX)”= 12.5% CR + 12.5% increase in energy expenditure through exercise; or “low-calorie diet (LCD)” = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. Results At baseline, increased liver lipid content (by MRS) correlated (P triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. Discussion CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD. PMID:18421281

  15. Muscular exercise can cause highly pathological liver function tests in healthy men.

    Science.gov (United States)

    Pettersson, Jonas; Hindorf, Ulf; Persson, Paula; Bengtsson, Thomas; Malmqvist, Ulf; Werkström, Viktoria; Ekelund, Mats

    2008-02-01

    The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. Physical exercise can result in transient elevations of liver function tests. There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. Liver function tests are significantly increased for at least 7 days after weightlifting. It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10-12 days postexercise. Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.

  16. 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.

  17. Quantitative proton magnetic resonance spectroscopy of the normal liver and malignant hepatic lesions at 3.0 Tesla

    International Nuclear Information System (INIS)

    Fischbach, F.; Thormann, M.; Ricke, J.; Schirmer, T.; Freund, T.; Bruhn, H.

    2008-01-01

    This comparative study of tumour patients and volunteers aimed at differentiating liver parenchyma from neoplastic lesions by using localised 1 H MRS at 3.0 T as an adjunct to MRI. In total 186 single-voxel proton spectra of the liver were acquired at 3.0 T using the body transmit receive coil. Consecutive stacks of breath-hold spectra were acquired in the PRESS technique at a short echo time of 35 ms and a repetition time of 2,000 ms. Processing of the spectra included spectral alignment with the software package SAGE and quantitative processing with LCModel. The resulting metabolite concentrations were presented in arbitrary units relative to the internal water. In general, the spectra showed four main groups of resonances originating from the methyl protons (0.8-1.1 ppm) and methylene protons of the lipids (1.1-1.5 ppm; 2.0-2.2 ppm) as well as the methyl protons of choline-containing compounds (CCC) at 3.2 ppm. Overall, the CCC and lipid values in malignant liver tumours showed no significant differences to liver parenchyma. On average, total lipid measurements in normal liver parenchyma increased with age, while those of the CCC did not show pertinent changes. Significant differences between the contents of CCC in malignant liver tumours and normal liver parenchyma were not observed, because in patients and volunteers normal liver tissue showed a large variability in the content of CCC. (orig.)

  18. Assessment of biochemical liver function tests in relation to age ...

    African Journals Online (AJOL)

    Background and Objective: Multiorgan failure including liver dysfunction is a common finding in sickle cell anemia (SCA) patients, the cause of which is multifactorial with advancing age said to be a major determinant. There is a paucity of data on liver function among SCA patients in relation to age in northern Nigerian ...

  19. 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.

  20. Elasticity-based development of functionally enhanced multicellular 3D liver encapsulated in hybrid hydrogel.

    Science.gov (United States)

    Lee, Ho-Joon; Son, Myung Jin; Ahn, Jiwon; Oh, Soo Jin; Lee, Mihee; Kim, Ansoon; Jeung, Yun-Ji; Kim, Han-Gyeul; Won, Misun; Lim, Jung Hwa; Kim, Nam-Soon; Jung, Cho-Rock; Chung, Kyung-Sook

    2017-12-01

    Current in vitro liver models provide three-dimensional (3-D) microenvironments in combination with tissue engineering technology and can perform more accurate in vivo mimicry than two-dimensional models. However, a human cell-based, functionally mature liver model is still desired, which would provide an alternative to animal experiments and resolve low-prediction issues on species differences. Here, we prepared hybrid hydrogels of varying elasticity and compared them with a normal liver, to develop a more mature liver model that preserves liver properties in vitro. We encapsulated HepaRG cells, either alone or with supporting cells, in a biodegradable hybrid hydrogel. The elastic modulus of the 3D liver dynamically changed during culture due to the combined effects of prolonged degradation of hydrogel and extracellular matrix formation provided by the supporting cells. As a result, when the elastic modulus of the 3D liver model converges close to that of the in vivo liver (≅ 2.3 to 5.9 kPa), both phenotypic and functional maturation of the 3D liver were realized, while hepatic gene expression, albumin secretion, cytochrome p450-3A4 activity, and drug metabolism were enhanced. Finally, the 3D liver model was expanded to applications with embryonic stem cell-derived hepatocytes and primary human hepatocytes, and it supported prolonged hepatocyte survival and functionality in long-term culture. Our model represents critical progress in developing a biomimetic liver system to simulate liver tissue remodeling, and provides a versatile platform in drug development and disease modeling, ranging from physiology to pathology. We provide a functionally improved 3D liver model that recapitulates in vivo liver stiffness. We have experimentally addressed the issues of orchestrated effects of mechanical compliance, controlled matrix formation by stromal cells in conjunction with hepatic differentiation, and functional maturation of hepatocytes in a dynamic 3D

  1. Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships (MCBIOS)

    Science.gov (United States)

    Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships Jie Liu1,2, Richard Judson1, Matthew T. Martin1, Huixiao Hong3, Imran Shah1 1National Center for Computational Toxicology (NCCT), US EPA, RTP, NC...

  2. Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients

    Science.gov (United States)

    Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen

    2012-01-01

    Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. PMID:23197664

  3. A liver-function test using 15N-labelled ammonium chloride

    International Nuclear Information System (INIS)

    Jung, K.; Hirscherg, K.; Faust, H.; Matkowitz, R.

    1985-01-01

    Malfunction of the liver involves disturbances of urea synthesis and ammonia detoxification. These phenomena became apparent, especially during ammonia loading of patients. The functional state of the liver can be assessed by oral administration of 15 NH 4 Cl and subsequent analysis of 15 N-urea and 15 N-ammonia in urine by emission spectrometry. Clinical tests based on the ratio of the excess abundances (see Appendix) of 15 N-ammonia to 15 N-urea excreted in urine 3 h after oral administration gave values for patients with liver disease which differed significantly from those for healthy subjects. Absorption disturbances, which often accompany liver diseases, do not influence the effectiveness of the method. (orig.)

  4. Liver-function test using /sup 15/N-labelled ammonium chloride

    Energy Technology Data Exchange (ETDEWEB)

    Jung, K; Hirscherg, K; Faust, H; Matkowitz, R

    1985-08-01

    Malfunction of the liver involves disturbances of urea synthesis and ammonia detoxification. These phenomena became apparent, especially during ammonia loading of patients. The functional state of the liver can be assessed by oral administration of /sup 15/NH/sub 4/Cl and subsequent analysis of /sup 15/N-urea and /sup 15/N-ammonia in urine by emission spectrometry. Clinical tests based on the ratio of the excess abundances (see Appendix) of /sup 15/N-ammonia to /sup 15/N-urea excreted in urine 3 h after oral administration gave values for patients with liver disease which differed significantly from those for healthy subjects. Absorption disturbances, which often accompany liver diseases, do not influence the effectiveness of the method.

  5. 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

  6. Evaluation of usefulness of Tc-99m-GSA liver scintigraphy in chronic liver diseases

    International Nuclear Information System (INIS)

    Fukui, Hiroyuki; Kashiwagi, Toru; Kasahara, Akinori

    1991-01-01

    Liver scintigraphy was performed using a newly developed radiopharmaceutical, Tc-99m-DTPA-galactosyl-human-serum-albumin (Tc-99m-GSA), which binds specifically to the receptors on the hepatic cell surface, in 15 patients with chronic liver disease. The scintigraphy was evaluated qualitatively and quantitatively, and the results were compared with those obtained from the Tc-99m-PMT or Tc-99m-sn-phytate scintigraphy, and the liver function tests. The Tc-99m-GSA scintigraphy showed clear liver images in chronic hepatitis. However, in liver cirrhosis, the liver images were not clear and the cardiac images still existed 40 minutes after administration of Tc-99m-GSA, suggesting that the image quality of the Tc-99m-GSA scintigrams may be inferior to that of Tc-99m-sn-phytate or Tc-99m-PMT in some cases of severe liver dysfunction. The time-activity curves of the heart and liver were analyzed by non-linear regression analysis. The clearance rate from plasma (Kd) were obtained from the time-activity curve of the heart, and the hepatic uptake rate (Ku), hepatic excretion rate (Ke) and peak time of hepatic uptake-excretion curve (PT) were obtained from the time-activity curve of the liver. Kd, Ku, and PT values were more significantly decreased or prolonged in the patients with chronic hepatitis. Kd, Ku, and PT values had positive correlations with the result of the serum liver function tests, ICG-R15 and ICG-K. Ku and PT values had also correlations with the histological degree of hepatic fibrosis. On the other hand, the indices obtained using Tc-99m-PMT or Tc-99m-sn-phytate did not have correlations with the histological degrees of hepatic fibrosis. It is concluded that the liver scintigraphy using Tc-99m-GSA may be useful and give different information from those with conventional liver scintigraphies in evaluating chronic liver diseases. (author)

  7. 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

    International Nuclear Information System (INIS)

    Yan Weili; Fudan Univ., Shanghai; Lin Xiangtong; Jiang Yibin; Sun Su; Sun Dayu

    2005-01-01

    The aims of this study are to investigate the feasibility and validity of the L-[1- 13 C] phenylalanine breath test ( 13 C-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- 13 C] phenylalanine ( 13 C-Phe) was administered orally to all subjects. Breath samples were taken before and different intervals within 360 min after administration. The 13 CO 2 / 12 CO 2 enrichment was assessed by isotope ratio mass spectrometer( The parameter percentage 13 C excretion rate 13 CERt (% 13 C dose/h) all peaked within 10-30 min after oral 13 C-Phe application)The parameters such as maximum value of 13 C excretion rate, 13 CER max (% 13 C 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), 13 C excretion rate at 30 min, 13 CER 30 (% 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), 13 C cumulative excretion of first 60 min, 13 C cum60 (% 13 C 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 13 C excretion rate, T 1 / 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); T 1/2 was also useful for distinguishing mild HBV-related liver injure. (authors)

  8. 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

    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 patient......, 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...... ethanol per day decreased significantly (P less than 0.001) from 22 (65%) before entry to one (3%) during follow-up. In conclusion, oral testosterone treatment of men with alcoholic cirrhosis does not explain the significant improvement of liver haemodynamics and function observed in this study. However...

  9. Quantitative evaluation of fatty liver by computed tomography in rabbits

    International Nuclear Information System (INIS)

    Kawata, R.; Sakata, K.; Kunieda, T.; Saji, S.; Doi, H.; Nozawa, Y.

    1984-01-01

    Biochemical, histologic, and computed tomographic (CT) examinations of the liver were performed in 32 rabbits in which fatty liver was induced by prolonged intravenous fat infusion. In two groups of rabbits, in which 2 and 4 g/kg/day of fat emulsion was administered, respectively, posttreatment reduction in CT value of mild degree was observed. In the group that received 8 g/kg/day of fat emulsion, posttreatment change in CT value was sufficient for a diagnosis of fatty liver of moderate degree. Reduction in CT value in fatty liver might be due largely to accumulation of triglyceride and cholesterol in the liver cells. Significant correlation was found between changes in CT value of the liver and degrees of histological fat accumulation in the liver cells. Consecutive measurement of CT values of the liver during prolonged intravenous hyperalimentation is a nonagressive method of diagnosing fatty liver

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

    Science.gov (United States)

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

    2011-02-01

    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 cirrhotic liver disease by this fast imaging method. 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. 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 value of HBF at the tumor

  11. Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems.

    Science.gov (United States)

    Lee-Montiel, Felipe T; George, Subin M; Gough, Albert H; Sharma, Anup D; Wu, Juanfang; DeBiasio, Richard; Vernetti, Lawrence A; Taylor, D Lansing

    2017-10-01

    This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS). In addition, the oxygen tension was measured using a ratiometric imaging method with the oxygen sensitive dye, Tris(2,2'-bipyridyl) dichlororuthenium(II) hexahydrate (RTDP) and the oxygen insensitive dye, Alexa 488. The Zone 1 biased functions of oxidative phosphorylation, albumin and urea secretion and Zone 3 biased functions of glycolysis, α1AT secretion, Cyp2E1 expression and acetaminophen toxicity were demonstrated in the respective Zone 1 and Zone 3 MicroPhysiology System. Further improvements in the Liver Acinus MicroPhysiology System included improved performance of selected nonparenchymal cells, the inclusion of a porcine liver extracellular matrix to model the Space of Disse, as well as an improved media to support both hepatocytes and non-parenchymal cells. In its current form, the Liver Acinus MicroPhysiology System is most amenable to low to medium throughput, acute through chronic studies, including liver disease models, prioritizing compounds for preclinical studies, optimizing chemistry in structure activity relationship (SAR) projects, as well as in rising dose studies for initial dose ranging. Impact statement Oxygen zonation is a critical aspect of liver functions. A human microphysiology system is needed to investigate the impact of zonation on a wide range of liver functions that can be experimentally manipulated. Because oxygen zonation has such diverse physiological effects in the liver, we

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

    Directory of Open Access Journals (Sweden)

    N.Yu. Zavgorodnya

    2016-04-01

    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. Quantitative evaluation of enhancement patterns in focal solid liver lesions with Gd-EOB-DTPA-enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Michael Haimerl

    Full Text Available PURPOSE: The objective was to investigate the dynamic enhancement patterns in focal solid liver lesions after the administration of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA by means of dynamic magnetic resonance imaging (MRI including hepatobiliary phase (HP images 20 min after Gd-EOB-DTPA administration. MATERIALS AND METHODS: Non-enhanced T1/T2-weighted as well as dynamic magnetic resonance (MR images during the arterial phase (AP, the portal venous phase (PVP, the late phase (LP, and the HP (20 min were obtained from 83 patients (54 male, 29 female, mean age 62.01 years with focal solid liver lesions. MRI was conducted by means of a 1.5-T system for 63 patients with malignant liver lesions (HCCs: n = 34, metastases: n = 29 and for 20 patients with benign liver lesions (FNH lesions: n = 14, hemangiomas: n = 3, adenomas: n = 3. For quantitative analysis, signal-to-noise ratios (SNR, contrast enhancement ratios (CER, lesion-to-liver contrast ratios (LLC, and signal intensity (SI ratios were measured. RESULTS: The SNR of liver parenchyma significantly increased in each dynamic phase after Gd-EOB-DTPA administration compared to the SNR of non-enhanced images (p<0.001. The CER of HCCs and metastases significantly decreased between LP and HP images (p = 0.0011, p<0.0001. However, FNH lesions did not show any significant difference, whereas an increased CER was found in hemangiomas. The mean LLCs of FNH lesions were significantly higher than those of HCCs and metastases. The LLC values of hemangiomas remained negative during the entire time course, whereas the LLC of adenomas indicated hyperintensity from the AP to the LP. Furthermore, adenomas showed hypointensity in HP images. CONCLUSION: Gd-EOB-DTPA-enhanced MRI may help diagnose focal solid liver lesions by evaluating their enhancement patterns.

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

    Directory of Open Access Journals (Sweden)

    S. V. Gautier

    2017-01-01

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

  15. THE COMPARATIVE ANALYSIS OF RENAL FUNCTION IN LIVER DISEASES USING COCKCROFT-GAULT FORMULAE AND CREATININE CLEARANCE

    Directory of Open Access Journals (Sweden)

    Karem Ravi Teja

    2018-01-01

    Full Text Available BACKGROUND Kidney dysfunction in liver disease can be due to different aetiologies and can have diverse manifestations. Most of the abnormalities of kidney function in cirrhosis are of functional origin namely, sodium retention, impaired free water excretion and renal vasoconstriction with decrease in renal perfusion and glomerular filtration rate. Renal dysfunction in chronic liver disease usually follows a progressive course- the final phase being Hepatorenal Syndrome (HRS. MATERIALS AND METHODS This study included patients with chronic liver disease being treated as inpatients in the Department of General Medicine, Konaseema Institute of Medical Sciences, Amalapuram. Evidence for chronic liver disease being defined by a compatible clinical profile (signs of liver cell failure or reduced liver span along with biochemical (altered liver function tests, reversal of albuminglobulin ratio or sonographic evidence (altered echotexture of liver or tissue diagnosis (positive liver biopsy for cirrhosis. RESULTS Eighteen percent, i.e. 5 out of the 28 patients with creatinine clearance more than 60 mL/minute by Cockcroft-Gault formula were found to have creatinine clearance values less than 40 mL/minute when done by timed urine collection P value calculated was found to be less than 0.0001, which is statistically significant. CONCLUSION In chronic liver disease, serum creatinine alone is not a reliable marker to assess renal dysfunction. Calculating creatinine clearance by using Cockcroft-Gault formula overestimates renal function in cirrhotics. Creatinine clearance measured by timed urine collections should be done routinely to assess renal reserve in advanced liver disease. Alcoholism appears to have adverse effect on renal function when compared with other aetiologies of cirrhosis.

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

    Energy Technology Data Exchange (ETDEWEB)

    Dohan, Anthony, E-mail: anthony.dohan@lrb.aphp.fr [Department of Body and Interventional Imaging, Hôpital Lariboisière, AP-HP, 2 Rue Ambroise Paré, 75475 Paris Cedex 10 (France); Université Paris-Diderot, Sorbonne Paris Cité, 10 Rue de Verdun, 75010 Paris (France); UMR INSERM 965, Hôpital Lariboisière, 2 Rue Amboise Paré, 75010 Paris (France); Gavini, Jean-Philippe, E-mail: jpgavini@gmail.com [Department of Body and Interventional Imaging, Hôpital Lariboisière, AP-HP, 2 Rue Ambroise Paré, 75475 Paris Cedex 10 (France); Université Paris-Diderot, Sorbonne Paris Cité, 10 Rue de Verdun, 75010 Paris (France); Placé, Vinciane, E-mail: vinciane.place@gmail.com [Department of Body and Interventional Imaging, Hôpital Lariboisière, AP-HP, 2 Rue Ambroise Paré, 75475 Paris Cedex 10 (France); Sebbag, Delphine, E-mail: delphinesebbag@gmail.com [Department of Body and Interventional Imaging, Hôpital Lariboisière, AP-HP, 2 Rue Ambroise Paré, 75475 Paris Cedex 10 (France); Université Paris-Diderot, Sorbonne Paris Cité, 10 Rue de Verdun, 75010 Paris (France); Vignaud, Alexandre, E-mail: alexandre.vignaud@cea.fr [LRMN, Neurospin, CEA-SACLAY, Bâtiment 145, 91 191 Gif-sur-Yvette Cedex (France); and others

    2013-11-01

    Objective: 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. Materials and methods: 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. Results: SPACE MR imaging showed significantly greater CNR for focal liver lesions (median = 22.82) than TSE MR imaging (median = 14.15) (P < .001). No differences were found for SNR of hepatic parenchyma (P = .097), main focal hepatic lesions (P = .35), and splenic parenchyma (P = .25). SPACE sequence showed less artifacts than TSE sequence (vascular, P < .001; respiratory motion, P < .001; cardiac, P < .001) but needed a longer acquisition time (228.4 vs. 162.1 s; P < .001). Conclusion: SPACE MR imaging provides a significantly increased CNR for focal liver lesions and less artifacts by comparison 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.

  17. Evaluation of Factors Influencing Liver Function Test in On-Pump Coronary Artery Bypass Graft Surgery

    Directory of Open Access Journals (Sweden)

    Shahrbano Shahbazi

    2013-12-01

    Full Text Available Background: Liver dysfunction during on-pump coronary artery bypass graft surgery (CABG is a rare complication but is associated with significant morbidity and mortality. The ability to identify high-risk patients may be helpful in planning appropriate management strategies. We aimed to evaluate the factors influencing liver function tests during on-pump CABG. Methods: In 146 patients scheduled for on-pump CABG, the liver function test was done preoperatively and on the first postoperative day. Some preoperative and intraoperative risk factors were checked and then the postoperative liver function tests were compared with the preoperative ones. Probable relationships between these changes and the preoperative and intraoperative risk factors were studied. Results: A medical history of diabetes had a significant relationship with the changes in direct bilirubin. Preoperative central venous pressure had a significant relationship with the changes in aspartate aminotransferase and alanine aminotransferase. Use of intra-aortic balloon pump and duration of aortic cross-clamp were significantly related to the changes in the liver function tests except for alanine aminotransferase and alkaline phosphatase. Conclusion: It seems that the techniques for the reduction of cardiopulmonary bypass and aortic cross-clamp duration may be useful to protect liver function. We recommend that a larger population of patients be studied to confirm these findings.

  18. Nuclear medicine liver-function tests for pregnant women and children. Pt. 2

    International Nuclear Information System (INIS)

    Krumbiegel, P.; Hirschberg, K.; Faust, H.; Guenther, K.; Schneider, G.

    1985-01-01

    A simple, non-invasive, non-radiaoactive liver-function test is proposed. After an oral dose of 3 mg methacetin per kilogram body mass, the kinetics of 15 N excretion via urine were characterized by the quotient of the 15 N amounts of excreted in two successive urine samples (Q value). The stable nitrogen isotope 15 N, was found to be an excellent and easily detectable indicator of the sum of all methacetin metabolites present in urine. Alterations in the nature or ratio of methacetin metabilites due to liver diseases could not be found. From the investigation of 11 men 3 pregnant women and 156 children, a clear difference was observed in Q values of healthy persons and patients suffering from liver-cell-activity diseases. The discriminating power of our new liver-function test is shown to be equivalent to that of the 14 CO 2 breath test. (orig.)

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

    Science.gov (United States)

    Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P; Walles, Heike; Braspenning, Joris; Breitkopf-Heinlein, Katja

    2015-01-01

    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.

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

    International Nuclear Information System (INIS)

    Takao, Hidemasa; Akai, Hiroyuki; Tajima, Taku; Kiryu, Shigeru; Watanabe, Yasushi; Imamura, Hiroshi; Akahane, Masaaki; Yoshioka, Naoki; Kokudo, Norihiro; Ohtomo, Kuni

    2011-01-01

    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 bileduct /mean SI 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 analysis

  2. Liver insulinase and insulin-like activity of the blood plasma in irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhikhareva, A I; Dokshina, G A [Tomskij Gosudarstvennyj Univ. (USSR)

    1975-05-01

    Comparative quantitative analysis of the functional effect of radiation on the activity of liver insulinase of irradiated rats has shown that the insulinase activity of the blood plasma decreases (21-45%) one to three days after the exposure at betatron. Insulinase activity of the liver extracts is also inhibited (16-22%) as compared to intact liver extracts. Twelve days after the exposure and later, insulin-like activity of the plasma and the enzyme activity increase up to 37 per cent.

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

    Science.gov (United States)

    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 assessment of liver fat, is invasive and has sampling errors, and is not optimal for screening, monitoring, clinical decision making, or well-suited for many types of research studies. Non-invasive methods that accurately and objectively quantify liver fat are needed. Ultrasound (US) and computed tomography (CT) can be used to assess liver fat but have limited accuracy as well as other limitations. Magnetic resonance (MR) techniques can decompose the liver signal into its fat and water signal components and therefore assess liver fat more directly than CT or US. Most magnetic resonance (MR) techniques measure the signal fat-fraction (the fraction of the liver MR signal attributable to liver fat), which may be confounded by numerous technical and biological factors and may not reliably reflect fat content. By addressing the factors that confound the signal fat-fraction, advanced MR techniques measure the proton density fat-fraction (the fraction of the liver proton density attributable to liver fat), which is a fundamental tissue property and a direct measure of liver fat content. These advanced techniques show promise for accurate fat quantification and are likely to be commercially available soon. PMID:22025886

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  5. Quantitation: clinical applications

    International Nuclear Information System (INIS)

    Britton, K.E.

    1982-01-01

    Single photon emission tomography may be used quantitatively if its limitations are recognized and quantitation is made in relation to some reference area on the image. Relative quantitation is discussed in outline in relation to the liver, brain and pituitary, thyroid, adrenals, and heart. (U.K.)

  6. Liver Function Testing with Nuclear Medicine Techniques Is Coming of Age

    NARCIS (Netherlands)

    Bennink, Roelof J.; Tulchinsky, Mark; de Graaf, Wilmar; Kadry, Zakiyah; van Gulik, Thomas M.

    2012-01-01

    Liver function is a broad term, as the organ participates in a multitude of different physiological and biochemical processes, including metabolic, synthetic, and detoxifying functions. However, it is the function of the hepatocyte that is central to sustaining normal life and dealing with disease

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

    Science.gov (United States)

    Deng, Jie; Fishbein, Mark H; Rigsby, Cynthia K; Zhang, Gang; Schoeneman, Samantha E; Donaldson, James S

    2014-11-01

    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*W) and fat (T2*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 fat fraction, T2*W (27.9 ± 3.5 ms) decreased, whereas T2*F (20.3 ± 5.5 ms) increased; and T2*W and T2*F became increasingly more similar when fat fraction was higher than 15-20%. Histological fat

  8. 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

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

    International Nuclear Information System (INIS)

    Yazdani, Farshad; Fattahi, Bahare; Azizi, Najmodin

    2016-01-01

    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, Fe_3O_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_3O_4–SiO_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_2 relaxivity of the coated functional nanoparticles.

  10. Liver Function in Patients With Nonalcoholic Fatty Liver Disease Randomized to Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: A Secondary Analysis of a Randomized Clinical Trial.

    Science.gov (United States)

    Kalinowski, Piotr; Paluszkiewicz, Rafał; Ziarkiewicz-Wróblewska, Bogna; Wróblewski, Tadeusz; Remiszewski, Piotr; Grodzicki, Mariusz; Krawczyk, Marek

    2017-11-01

    The aim of the study was to compare the influence of sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB) on liver function in bariatric patients with non-alcoholic fatty liver disease (NAFLD) in a randomized clinical trial (NCT01806506). Rapid weight loss and malabsorption after bariatric surgery in patients with NAFLD or steatohepatitis (NASH) may impair liver function. Sixty-six morbidly obese patients randomized to SG or RYGB were included in a secondary outcome analysis. Intraoperative liver biopsies were categorized with NAFLD Activity Score (NAS) and liver function tests were done before surgery and after 1, 6 and 12 months. NASH was present in 54.5% RYGB and 51.5% SG patients (P > 0.05). At 12 months excess weight loss was 68.7 ± 19.7% after SG and 62.8 ± 18.5% after RYGB (P > 0.05). At 1 month international normalized ratio (INR) increased after RYGB (0.98 ± 0.05 vs 1.14 ± 0.11; P liver function than after SG.

  11. Investigation of impairment of liver function in local residents of Miaofeng Village, Wushan County, China

    Directory of Open Access Journals (Sweden)

    YANG Zhongxia

    2015-06-01

    Full Text Available ObjectiveTo assess the impairment of liver function and investigate possible causes in local residents in Miaofeng Village, Mali Town, Wushan County, Gansu Province, China, and to provide a basis for the etiological study of idiopathic liver damage. MethodsThe residents in Miaofeng Village were screened for liver function and an epidemiological study was conducted. Serological testing was performed for those with abnormal screening results. Trace elements in drinking water and soil such as arsenic, chromium, and selenium were also tested. ResultsOf all residents, 23.8% and 10.7% showed abnormal levels of alanine aminotransferase and aspartate aminotransferase, respectively. Positivity of HBsAg was detected in 11 cases, fatty liver was identified in 3 cases, and absence of selenium in soil was also confirmed. ConclusionA proportion of local residents in Miaofeng Village have impaired liver function and the absence of selenium in soil may be a contributing factor to this phenomenon.

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

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    Lan-Ping Yang

    2016-12-01

    Full Text Available 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, and α-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, and α-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, CKMB, LDH, and α-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.

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

    OpenAIRE

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

  16. Value of Gd-EOB-DTPA-enhanced MRI in assessing liver function

    Directory of Open Access Journals (Sweden)

    WANG Lili

    2015-05-01

    Full Text Available ObjectiveTo explore the value of magnetic resonance imaging (MRI specifically enhanced with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA in assessing the liver function in general population. MethodsUpper abdominal MRI images and Gd-EOB-DTPA-enhanced images, as well as some clinical information, were collected from 41 cases meeting the inclusion and exclusion criteria. Taking the spleen as the control organ, liver-spleen signal intensity contrast (SIliver/spleen and relative liver enhancement (RLE were calculated at 10 min and 20 min after injecting Gd-EOB-DTPA. Differences were evaluated using the independent-samples t-test or Mann-Whitney U test. Corrections were analyzed via Spearman’s rank correlation. ResultsBoth SIliver/spleen at 10 min and 20 min after injection of contrast agent were correlated with Child classification (P<0.05. SIliver/spleen at 20 min had a greater correlation coefficient (r=-0.526 than that at 10 min. The SIliver/spleen with plain scan had no significant correlation with Child classification (P>0.05. RLE at 20 min, but not at 10 min, was correlated with Child classification (r=-0.362, P=0049. Between the cirrhotic and non-cirrhotic groups, SIliver/spleen showed no significant difference (P>0.05. However, SIliver/spleen at 10 min and 20 min, as well as RLE20 min, showed significant differences between the cirrhotic and non-cirrhotic groups (P<0.05. SIliver/spleen at 20 min also exhibited a significant difference between the elevated and normal ALT and TBil groups (both P<0.05. ConclusionGd-EOB-DTPA-enhanced MRI can monitor liver function changes, and SIliver/spleen at 20 min may have an important value in assessing the liver function in general population.

  17. Prevalence of abnormal liver function tests in rheumatoid arthritis ...

    African Journals Online (AJOL)

    Objective: To determine the prevalence of Abnormal Liver Function Tests (LFTs) in patients with rheumatoid arthritis at the rheumatology out-patient clinic, Kenyatta National Hospital (KNH). Design: Cross-sectional descriptive study. Setting: Rheumatology out-patient clinic at KNH. Participants: One hundred and seven RA ...

  18. Administration of multipotent mesenchymal stromal cells restores liver regeneration and improves liver function in obese mice with hepatic steatosis after partial hepatectomy.

    Science.gov (United States)

    Ezquer, Fernando; Bahamonde, Javiera; Huang, Ya-Lin; Ezquer, Marcelo

    2017-01-28

    The liver has the remarkable capacity to regenerate in order to compensate for lost or damaged hepatic tissue. However, pre-existing pathological abnormalities, such as hepatic steatosis (HS), inhibits the endogenous regenerative process, becoming an obstacle for liver surgery and living donor transplantation. Recent evidence indicates that multipotent mesenchymal stromal cells (MSCs) administration can improve hepatic function and increase the potential for liver regeneration in patients with liver damage. Since HS is the most common form of chronic hepatic illness, in this study we evaluated the role of MSCs in liver regeneration in an animal model of severe HS with impaired liver regeneration. C57BL/6 mice were fed with a regular diet (normal mice) or with a high-fat diet (obese mice) to induce HS. After 30 weeks of diet exposure, 70% hepatectomy (Hpx) was performed and normal and obese mice were divided into two groups that received 5 × 10 5 MSCs or vehicle via the tail vein immediately after Hpx. We confirmed a significant inhibition of hepatic regeneration when liver steatosis was present, while the hepatic regenerative response was promoted by infusion of MSCs. Specifically, MSC administration improved the hepatocyte proliferative response, PCNA-labeling index, DNA synthesis, liver function, and also reduced the number of apoptotic hepatocytes. These effects may be associated to the paracrine secretion of trophic factors by MSCs and the hepatic upregulation of key cytokines and growth factors relevant for cell proliferation, which ultimately improves the survival rate of the mice. MSCs represent a promising therapeutic strategy to improve liver regeneration in patients with HS as well as for increasing the number of donor organs available for transplantation.

  19. The impact of longitudinal intestinal lengthening and tailoring on liver function in short bowel syndrome.

    Science.gov (United States)

    Reinshagen, K; Zahn, K; Buch, C von; Zoeller, M; Hagl, C I; Ali, M; Waag, K-L

    2008-08-01

    Short bowel syndrome is a functional or anatomic loss of major parts of the small bowel leading to severe malnutrition. The limiting factor for the survival of these patients remains parenteral nutrition-related liver damage leading to end-stage liver failure. Longitudinal intestinal lengthening and tailoring (LILT) has been proven to enhance peristalsis, to decrease bacterial overgrowth and to extend the mucosal contact time for the absorption of nutrients. The aim of this study was to show the impact of LILT on the development of parenteral nutrition-related liver damage. A cohort of 55 patients with short bowel syndrome managed with LILT in our institution between 1987 and 2007 was retrospectively reviewed. LILT was performed at a mean age of 24 months (range 4 - 150 months). Mean follow-up time was 83.76 months (range 5 - 240 months). We obtained reliable data from 31 patients with regard to liver enzymes and function parameters in blood samples before LILT and at the present time. Liver biopsy was performed in 14 patients prior to LILT. Liver enzymes ALAT (mean 121 U/l), ASAT (mean 166 U/l) and bilirubin (mean 2.49 mg/dl) were elevated preoperatively in 27/31 children. After the lengthening procedure, ALAT (mean 50 U/l), ASAT (mean 63 U/l) and bilirubin (mean 1.059 mg/dl) normalized except in 5 of 8 patients who could not be weaned from parenteral nutrition after LILT. Liver function parameters such as the international normal ratio (INR) were slightly elevated in 5/31 patients. Albumin was generally low, probably due to parenteral nutrition. Liver biopsy was performed in 14 patients preoperatively, showing 4 patients with low-grade, 6 patients with intermediate and 4 patients with high-grade fibrosis. End-stage liver disease with cirrhosis was an exclusion criterion for LILT. All patients with liver fibrosis showed a normalization of liver enzymes when they were weaned from parenteral nutrition. But patients with higher grade liver fibrosis tend to develop

  20. Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis

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    Chai Ryoung Eun

    2014-03-01

    Full Text Available Pheochromocytoma is a rare neuroendocrine tumor arising from the medulla of the adrenal glands, which causes an overproduction of catecholamines. The common symptoms are headache, palpitations, and sweating; however, various other clinical manifestations might also be present. Accurate diagnosis of pheochromocytoma is important because surgical treatment is usually successful, and associated clinical problems are reversible if treated early. A 49-year-old man with a history of uncontrolled hypertension and diabetes mellitus presented with chest pain, fever, and sweating. His liver function tests and white blood cell counts were markedly increased and his echocardiography results suggested stress-induced cardiomyopathy. His abdominal computed tomography showed a 5×5-cm-sized tumor in the left adrenal gland, and laboratory tests confirmed catecholamine overproduction. After surgical resection of the left adrenal gland, his liver function tests and white blood cell counts normalized, and echocardiography showed normal cardiac function. Moreover, his previous antihypertensive regimen was deescalated, and his previously uncontrolled blood glucose levels normalized without medication.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-01-01

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

  2. The utility of liver function tests for mortality prediction within one year in primary care using the algorithm for liver function investigations (ALFI.

    Directory of Open Access Journals (Sweden)

    David J McLernon

    Full Text Available BACKGROUND: Although liver function tests (LFTs are routinely measured in primary care, raised levels in patients with no obvious liver disease may trigger a range of subsequent expensive and unnecessary management plans. The aim of this study was to develop and validate a prediction model to guide decision-making by general practitioners, which estimates risk of one year all-cause mortality in patients with no obvious liver disease. METHODS: In this population-based historical cohort study, biochemistry data from patients in Tayside, Scotland, with LFTs performed in primary care were record-linked to secondary care and prescription databases to ascertain baseline characteristics, and to mortality data. Using this derivation cohort a survival model was developed to predict mortality. The model was assessed for calibration, discrimination (using the C-statistic and performance, and validated using a separate cohort of Scottish primary care practices. RESULTS: From the derivation cohort (n = 95 977, 2.7% died within one year. Predictors of mortality included: age; male gender; social deprivation; history of cancer, renal disease, stroke, ischaemic heart disease or respiratory disease; statin use; and LFTs (albumin, transaminase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase. The C-statistic for the final model was 0.82 (95% CI 0.80-0.84, and was similar in the validation cohort (n = 11 653 0.86 (0.79-0.90. As an example of performance, for a 10% predicted probability cut-off, sensitivity = 52.8%, specificity = 94.0%, PPV = 21.0%, NPV = 98.5%. For the model without LFTs the respective values were 43.8%, 92.8%, 15.6%, 98.1%. CONCLUSIONS: The Algorithm for Liver Function Investigations (ALFI is the first model to successfully estimate the probability of all-cause mortality in patients with no apparent liver disease having LFTs in primary care. While LFTs added to the model's discrimination and sensitivity, the

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

    Science.gov (United States)

    Audebert, Chloe; Vignon-Clementel, Irene E

    2018-03-30

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

  4. Effects of hyperthermia on the normal liver using scintigraphic methods. Functional changes of the rabbit whole-liver by local hyperthermia

    International Nuclear Information System (INIS)

    Ryu, Kiyotaka; Shinotsuka, Akira; Takenaka, Hiroki; Hirono, Yoshisada

    1995-01-01

    An experimental study was conducted to investigate effect of hyperthermia to the liver in rabbits. The whole liver was heated at 43degC for 30 min by a RF capacitive heating device, and subsequent changes were observed by scintigraphy using 99m Tc-EHIDA and 99m Tc-Sn-colloid. The excretory ratio (Ke value) of 99m Tc-EHIDA and the uptake ratio (K value) of 99m Tc-Sn-colloid were measured to estimate hyperthermia induced hepatic injury for a month. Blood chemistry analysis was also conducted during this period. Also, the uptake of 3 H-methyl-thymidine into the DNA of hepatocyted was assayed 2 and 5 days after heating. Concurrently, histopathological changes were observed. The Ke value showed a transient increase and returned to the level prior to heating after approximately one week. A distinct increase in GPT was observed. The uptake of 3 H-methyl-thymidine showed a marked rise 2 days after hyperthermia, which demonstrated regeneration of the previously damaged hepatocytes. Pathologically, overall liver congestion and hepatocytes necrosis were noted. Also, both enlargement of the nuclei and binuclear hepatocytes were present, pathologically proving hepatocytes regeneration. The K value showed a transient decrease, showing that the reticuloendothelial function and blood flow of the liver were temporarily reduced. These results indicate the whole liver function damaged by hyperthermia is reversible. (author)

  5. Liver Transplant

    Science.gov (United States)

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

  6. Quantification of liver fat: A comprehensive review.

    Science.gov (United States)

    Goceri, Evgin; Shah, Zarine K; Layman, Rick; Jiang, Xia; Gurcan, Metin N

    2016-04-01

    Fat accumulation in the liver causes metabolic diseases such as obesity, hypertension, diabetes or dyslipidemia by affecting insulin resistance, and increasing the risk of cardiac complications and cardiovascular disease mortality. Fatty liver diseases are often reversible in their early stage; therefore, there is a recognized need to detect their presence and to assess its severity to recognize fat-related functional abnormalities in the liver. This is crucial in evaluating living liver donors prior to transplantation because fat content in the liver can change liver regeneration in the recipient and donor. There are several methods to diagnose fatty liver, measure the amount of fat, and to classify and stage liver diseases (e.g. hepatic steatosis, steatohepatitis, fibrosis and cirrhosis): biopsy (the gold-standard procedure), clinical (medical physics based) and image analysis (semi or fully automated approaches). Liver biopsy has many drawbacks: it is invasive, inappropriate for monitoring (i.e., repeated evaluation), and assessment of steatosis is somewhat subjective. Qualitative biomarkers are mostly insufficient for accurate detection since fat has to be quantified by a varying threshold to measure disease severity. Therefore, a quantitative biomarker is required for detection of steatosis, accurate measurement of severity of diseases, clinical decision-making, prognosis and longitudinal monitoring of therapy. This study presents a comprehensive review of both clinical and automated image analysis based approaches to quantify liver fat and evaluate fatty liver diseases from different medical imaging modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. 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.

  8. Chronic liver injury in mice promotes impairment of skin barrier function via tumor necrosis factor-alpha.

    Science.gov (United States)

    Yokoyama, Satoshi; Hiramoto, Keiichi; Koyama, Mayu; Ooi, Kazuya

    2016-09-01

    Alcohol is frequently used to induce chronic liver injury in laboratory animals. Alcohol causes oxidative stress in the liver and increases the expression of inflammatory mediators that cause hepatocellular damage. However, during chronic liver injury, it is unclear if/how these liver-derived factors affect distal tissues, such as the skin. The purpose of this study was to evaluate skin barrier function during chronic liver injury. Hairless mice were administered 5% or 10% ethanol for 8 weeks, and damages to the liver and skin were assessed using histological and protein-analysis methods, as well as by detecting inflammatory mediators in the plasma. After alcohol administration, the plasma concentration of the aspartate and alanine aminotransferases increased, while albumin levels decreased. In mice with alcohol-induced liver injury, transepidermal water loss was significantly increased, and skin hydration decreased concurrent with ceramide and type I collagen degradation. The plasma concentrations of [Formula: see text]/[Formula: see text] and tumor necrosis factor-alpha (TNF-α) were significantly increased in mice with induced liver injury. TNF receptor (TNFR) 2 expression was upregulated in the skin of alcohol-administered mice, while TNFR1 levels remained constant. Interestingly, the impairment of skin barrier function in mice administered with 10% ethanol was ameliorated by administering an anti-TNF-α antibody. We propose a novel mechanism whereby plasma TNF-α, via TNFR2 alone or with TNFR1, plays an important role in skin barrier function during chronic liver disease in these mouse models.

  9. 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.

  10. 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.

  11. Clinical availability of cholescintigraphy in evaluating diffuse liver parenchymal diseases

    International Nuclear Information System (INIS)

    Itoh, Hisao; Shimono, Reiko; Hamamoto, Ken; Ohshima, Kanji; Akamatsu, Koichi

    1988-01-01

    Technetium-99m N-pyridoxyl-5-methyltryptophan (PMT) cholescintigraphy has been performed in 46 consecutive patients with diffuse liver parenchymal diseases, including acute hepatitis (9), chronic hepatitis (17), and liver cirrhosis (20), and 18 controls. Blood clearance rate, liver uptake rate, liver excretion rate, and half time (T1/2) were determined from cardiac and hepatic time-activity curves. Regarding the four parameters, there were statistically significant differences between the control group and the groups of acute hepatitis and liver cirrhosis. Both blood clearance rate and liver uptake rate were well correlated with ICG-k values (r = 0.874 and r = 0.791, respectively). Liver excretion rate was most highly correlated with total serum bilirubin levels (r = 0.763), followed by ICG-k values. T1/2 was well correlated as well with total serum bilirubin levels. During the process where liver excretory ability was lowered in association with elevated serum bilirubin levels, threshold values for liver excretion rate appeared to be established. Cholescintigraphy may be of value in evaluating the pathophysiology of diffuse liver parenchymal diseases in that it is capable of quantitatively determining excretory function of hepatic cells. (Namekawa, K.)

  12. Early graft function and carboxyhemoglobin level in liver transplanted patients.

    Science.gov (United States)

    Ali, Yasser; Negmi, H; Elmasry, N; Sadek, M; Riaz, A; Al Ouffi, H; Khalaf, H

    2007-10-01

    Heme-Oxygenase-1 catalyzes hemoglobin into bilirubin, iron, and carbon monoxide, a well known vasodilator. Heme-Oxygenase-1 expression and carbon monoxide production as measured by blood carboxyhemoglobin levels, increase in end stage liver disease patients. We hypothesized that there may be a correlation between carboxyhemoglobin level and early graft function in patients undergoing liver transplant surgeries. In a descriptive retrospective study, 39 patients who underwent liver transplantation between the year 2005 and 2006 at KFSH&RC, are included in the study. All patients received general anesthesia with isoflurane in 50% oxygen and air. Levels of oxyhemoglobin, carboxyhemoglobin and methemoglobin concentration in percentage were recorded at preoperative time, anhepatic phase, end of surgery, ICU admission and 24 hr after surgery. The level of lactic acid, prothrombin time (PT), partial thrombin time (PTT), serum total bilirubin and ammonia were also recorded at ICU admission and 24 hr after surgery. The numbers of blood units transfused were recorded. 39 patients were included in the study with 13/39 for living donor liver transplant (LDLT) compared to 26/39 patients scheduled for deceased donor liver transplant (DDLT). The mean age was 35.9 +/- 16.9 years while the mean body weight was 60.3 +/- 20.9 Kg. Female to male ratio was 21/18. The median packed red blood cell (PRBC) units was 4 (Rang 0-40). There was a significant increase in carboxyhemoglobin level during the anhepatic phase, end of surgery and on ICU admission compared with preoperative value (pcarboxyhemoglobin level on ICU admission and 24 hrs postoperatively were positively correlated with the changes in serum total bilirubin and prothrombin time (R = 0.35, 0.382, 0.325 and 0.31) respectively pcarboxyhemoglobin concentration and PT and total bilirubin while still the correlation with lactic acid was weak. There was no correlation between average perioperative carboxyhemoglobin concentration

  13. 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...... is associated with low mortality; after the higher dose, most rats die at between 12 and 24 h. METHODS: In the morning, 1 1/2, 3, 6, 9, and 12 h after the injection, the rats were killed and RNA was extracted from liver tissue. By slot-blot hybridization mRNA steady-state levels were determined for enzymes...

  14. 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.

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  16. Evaluation of Lung Function in Liver Transplant Candidates.

    Science.gov (United States)

    Roque, L; Sankarankutty, A K; Silva, O C; Mente, E D

    2018-04-01

    A wide variety of pulmonary conditions are found in cirrhotic patients and may compromise the pleura, diaphragm, parenchyma, and pulmonary vasculature, influencing the results of liver transplantation. To evaluate the pulmonary function (lung capacities, volumes, and gasometric study) of patients with liver cirrhosis awaiting liver transplantation. Cirrhotic patients, subdivided into 3 groups stratified by liver disease severity using the Child-Pugh-Turcotte score, were compared with a control group of healthy volunteers. In spirometry, the parameters evaluated were total lung capacity, forced volume in the first second, and the relationship between forced volume in the first minute and forced vital capacity. Blood gas analysis was performed. In the control group, arterial oxygenation was evaluated by peripheral oxygen saturation by pulse oximetry. Of the 55 patients (75% men, 51 ± 12.77 years), 11 were Child A (73% men, 52 ± 14.01 years), 23 were Child B (75% men, 51 ± 12.77 years), and 21 were Child C (95% men, 50 ± 12.09 years). The control group had 20 individuals (50% men, 47 ± 8.15 years). Pulmonary capacities and volumes by the parameters evaluated were within the normal range. Arterial blood gas analysis detected no hypoxemia, but a tendency to low partial gas pressure was noted. In this population of cirrhotic patients the parameters of spirometry were normal in relation to the lung capacities and volumes in the different groups. No hypoxemia was detected, but a tendency to hypocapnia in the blood gas was noted. Copyright © 2018. Published by Elsevier Inc.

  17. 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 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. © 2016 American Association for the Study of Liver Diseases.

  18. Liver Function Indicators Performed Better to Eliminate Cardioembolic Stroke than to Identify It from Stroke Subtypes.

    Science.gov (United States)

    Tan, Ge; Yuan, Ruozhen; Hao, Zilong; Lei, Chunyan; Xiong, Yao; Xu, Mangmang; Liu, Ming

    2017-01-01

    Identifying the etiology of ischemic stroke is essential to acute management and secondary prevention. The value of liver function indicators in differentiating stroke subtypes remains to be evaluated. A total of 1333 acute ischemic stroke patients were included. Liver function indicators collected within 24 hours from stroke onset, including alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and bilirubin (BILI), were collapsed into quartiles (Q) and also dichotomized by Q1. Multivariate regression analysis was conducted to identify the independent association between liver function indicators and cardioembolic stroke (SCE). Area under the curve (AUC) of receiver operating characteristic analysis was conducted, and sensitivity (Sen), specificity (Spe), positive prospective value (PPV), and negative prospective value (NPV) were determined to evaluate the predictive value of liver function indicators for SCE. AST, GGT, and BILI were associated with SCE. After adjustment, only AST was related to SCE independently. The incidence of SCE in the Q1 of AST, GGT, and BILI, particularly in the Q1 of AST, was quite low. The ability of AST, GGT, and BILI to identify SCE was poor, with low AUC, Sen, and PPV. The value of AST, GGT, and BILI in eliminating SCE from stroke subtypes was good, with high Spe and moderate NPV, and was enhanced after combining each liver function indicator. Results of present study demonstrated that AST, GGT, and BILI, particularly AST, had a potential to eliminate SCE from stroke subtypes, and the ability of eliminating SCE would be strengthened after combining each liver function indicator together. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. Liver Function In Patients With Homozygous Sickle Cell Disease ...

    African Journals Online (AJOL)

    Using the sensitive ELISA technique, 213 patients with sickle cell anemia (112 males and 101 females) aged 6 months to 18 years were screened for Hepatitis B infection using Hepatitis B surface antigen (HBsAg) and antibody to Hepatitis B core antigen. A biochemical evaluation of liver function was carried out on all ...

  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. 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.

  2. Correlation of hepatic 18F-fluorodeoxyglucose uptake with fatty liver

    International Nuclear Information System (INIS)

    An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam

    2006-01-01

    Liver demonstrates heterogeneous FDG uptake and sometimes it shows abnormally increased uptake even though there is no malignant tissue. However, there was no previous study to correlate these various pattern of hepatic FDG uptake with benign liver disease. Therefore, we evaluated the significance of hepatic FDG uptake associated with various clinical factors including fatty liver, liver function tests and lipid profiles. We reviewed a total of 188 patients (male/female: 120/68, mean age: 50 ± 9) who underwent PET/CT for screening of malignancy. Patients with DM, impaired glucose tolerance, previous severe hepatic disease or long-term medication history were excluded. The FDG uptake in liver was analyzed semi-quantitatively using ROI on transaxial images (segment 8) and we compared mean standardized uptake value (SUV) between fatty liver and non-fatty liver group. We also evaluated the correlation between hepatic FDG uptake and various clinical factors including serum liver function test (ALT, AST), γ -GT, total cholesterol and triglyceride concentration. The effect of alcoholic history and body mass index on hepatic FDG uptake was analyzed within the fatty liver patients. The hepatic FDG uptake of fatty liver group was significantly higher than that of non-fatty liver group. Serum total cholesterol and triglyceride concentration showed significant correlation with hepatic FDG uptake. However, there was no significant correlation between other factors (ALT, AST, and γ -GT) and FDG uptake. Also there was no difference of mean SUV between normal and abnormal groups on the basis of alcoholic history and body mass index within fatty liver patients. Fatty liver and high serum triglyceride concentration were the independent factors affecting hepatic FDG uptake according to multivariate analysis. In conclusion, hepatic FDG uptake was strongly correlated with fatty liver and serum triglyceride concentration

  3. 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].

  4. Hepatic stellate cell and myofibroblast-like cell gene expression in the explanted cirrhotic livers of patients undergoing liver transplantation.

    Science.gov (United States)

    Estep, J Michael; O'Reilly, Linda; Grant, Geraldine; Piper, James; Jonsson, Johann; Afendy, Arian; Chandhoke, Vikas; Younossi, Zobair M

    2010-02-01

    Hepatic stellate cells (HSC) are involved in hepatic fibrogenesis. Cell signaling associated with an insult to the liver affects an HSC transdifferentiation to fibrogenic myofibroblast-like cells. To investigate the transcriptional expression distinguishing HSC and myofibroblast-like cells between livers with and without cirrhosis. Tissue from ten cirrhotic livers (undergoing transplant) and four non-cirrhotic livers from the National Disease Research Interchange underwent cell separation to extract HSC and myofibroblast-like cell populations. Separated cell types as well as LI-90 cells were subjected to microarray analysis. Selected microarray results were verified by quantitative real-time PCR. Differential expression of some genes, such as IL-1beta, IL-1alpha, and IL-6, was associated with both transdifferentiation and disease. Other genes, such as fatty acid 2-hydroxylase only show differential expression in association with disease. Functional analysis supported these findings, indicating some signal transduction pathways (IL-6) are involved in disease and activation, whereas retinoid X receptor signaling in HSC from cirrhotic and non-cirrhotic livers varies in scope and quality. These findings indicate distinct phenotypes for HSC from cirrhotic and non-cirrhotic livers. Furthermore, coordinated differential expression between genes involved in the same signal transduction pathways provides some insight into the mechanisms that may control the balance between fibrogenesis and fibrolysis.

  5. 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.

  6. Study of liver function and expression of some detoxification genes ...

    African Journals Online (AJOL)

    Ahmad Ali Badr

    2015-10-19

    Oct 19, 2015 ... In this study we investigate the effect(s) of MTBE on liver function indices and ... Methyl-tertiary butyl ether (MTBE), a well known gasoline oxygenate, is added to ..... ether (MTBE) in CD-1 mice and F-344 rats. J Appl Toxicol.

  7. 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

  8. 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

  9. Benign Liver Tumors

    Science.gov (United States)

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

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

    International Nuclear Information System (INIS)

    Valletta, Daniela; Czech, Barbara; Thasler, Wolfgang E.; Müller, Martina; Bosserhoff, Anja-Katrin; Hellerbrand, Claus

    2012-01-01

    Highlights: ► The expression of the atypical cadherin FAT1 is increased in chronic liver disease. ► FAT1 expression goes up during the activation of hepatic stellate cells (HSCs). ► Activated HSCs are the cellular source of enhanced FAT1 expression in diseased livers. ► FAT1 enhanced NFkB activity and resistance to apoptosis in activated HSCs. ► 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 cells by siRNA. We newly found that FAT1 suppression in activated HSCs caused a downregulation of NFκB activity. This

  11. 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

  12. Functional Budd-Chiari Syndrome Associated With Severe Polycystic Liver Disease

    Directory of Open Access Journals (Sweden)

    Precil Diego Miranda de Menezes Neves

    2017-06-01

    Full Text Available A 50-year-old woman with end-stage renal disease secondary to autosomal dominant polycystic kidney disease was referred to a quaternary care center due to significantly increased abdominal girth. Her physical examination revealed tense ascites and abdominal collateral veins. A 10-L paracentesis improved abdominal discomfort and disclosed a transudate, suggestive of portal hypertension. A computed tomographic scan revealed massive hepatomegaly caused by multiple cysts of variable sizes, distributed throughout all hepatic segments. Contrast-enhanced imaging uncovered extrinsic compression of hepatic and portal veins, resulting in functional Budd-Chiari syndrome and portal hypertension. Although image-guided drainage followed by sclerosis of dominant cysts could potentially lead to alleviation of the extrinsic compression, the associated significant risk of cyst hemorrhage and infection precluded this procedure. In this scenario, the decision was to submit the patient to a liver-kidney transplantation. After 1 year of this procedure, the patient maintains normal liver and kidney function and refers significant improvement in quality of life.

  13. Optimisation of graft function in liver transplantation: functional and metabolic aspects

    NARCIS (Netherlands)

    J. de Jonge (Jeroen)

    2002-01-01

    textabstractPart one of this thesis contains the general introduction to partial and whole liver transplantation. Chapter 2 addresses the concept of auxiliary partial liver transplantation. Auxiliary partial heterotopic liver transplantation was first introduced as a less invasive procedure for

  14. Biliary tract enhancement in gadoxetic acid-enhanced MRI correlates with liver function biomarkers

    International Nuclear Information System (INIS)

    Noda, Yoshifumi; Goshima, Satoshi; Kajita, Kimihiro; Kawada, Hiroshi; Kawai, Nobuyuki; Koyasu, Hiromi; Matsuo, Masayuki; Bae, Kyongtae T.

    2016-01-01

    Purpose: To evaluate the association between gadoxetic-acid-enhanced magnetic resonance (MR) imaging measurements and laboratory and clinical biomarkers of liver function and fibrosis. Materials and methods: One hundred thirty nine consecutive patients with suspected liver disease or liver tumor underwent gadoxetic-acid-enhanced MR imaging. MR imaging measurements during the hepatobiliary phase included biliary tract structure-to-muscle signal intensity ratio (SIR). These measurements were compared with Child-Pugh classification, end-stage liver disease (MELD) score, and aspartate aminotransferase-to-platelet ratio index (APRI). Results: The SIRs of cystic duct and common bile duct were significantly correlated with Child-Pugh classification (P = 0.012 for cystic duct and P < 0.0001 for common bile duct), MELD score (P = 0.0016 and P = 0.0033), and APRI (P = 0.0022 and P = 0.0015). The sensitivity, specificity, and area under the receiver-operating-characteristic curve were: (74%, 88%, 0.86) with the SIR of common bile duct for the detection of patients with Child-Pugh class B or C; (100%, 87%, 0.94) with the SIR of cystic duct for MELD score (>10); (65%, 76%, 0.70) with the SIR of common bile duct for APRI (>1.5). Conclusion: Gadoxetic-acid contrast enhancement of cystic duct and common bile duct could be used as biomarkers to assess liver function.

  15. Biliary tract enhancement in gadoxetic acid-enhanced MRI correlates with liver function biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Yoshifumi [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194 (Japan); Goshima, Satoshi, E-mail: gossy@par.odn.ne.jp [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194 (Japan); Kajita, Kimihiro [Radiology Services, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1194 (Japan); Kawada, Hiroshi; Kawai, Nobuyuki; Koyasu, Hiromi; Matsuo, Masayuki [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194 (Japan); Bae, Kyongtae T. [Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

    2016-11-15

    Purpose: To evaluate the association between gadoxetic-acid-enhanced magnetic resonance (MR) imaging measurements and laboratory and clinical biomarkers of liver function and fibrosis. Materials and methods: One hundred thirty nine consecutive patients with suspected liver disease or liver tumor underwent gadoxetic-acid-enhanced MR imaging. MR imaging measurements during the hepatobiliary phase included biliary tract structure-to-muscle signal intensity ratio (SIR). These measurements were compared with Child-Pugh classification, end-stage liver disease (MELD) score, and aspartate aminotransferase-to-platelet ratio index (APRI). Results: The SIRs of cystic duct and common bile duct were significantly correlated with Child-Pugh classification (P = 0.012 for cystic duct and P < 0.0001 for common bile duct), MELD score (P = 0.0016 and P = 0.0033), and APRI (P = 0.0022 and P = 0.0015). The sensitivity, specificity, and area under the receiver-operating-characteristic curve were: (74%, 88%, 0.86) with the SIR of common bile duct for the detection of patients with Child-Pugh class B or C; (100%, 87%, 0.94) with the SIR of cystic duct for MELD score (>10); (65%, 76%, 0.70) with the SIR of common bile duct for APRI (>1.5). Conclusion: Gadoxetic-acid contrast enhancement of cystic duct and common bile duct could be used as biomarkers to assess liver function.

  16. Pulmonary dysfunction in advanced liver disease: frequent occurrence of an abnormal diffusing capacity

    International Nuclear Information System (INIS)

    Hourani, J.M.; Bellamy, P.E.; Tashkin, D.P.; Batra, P.; Simmons, M.S.

    1991-01-01

    Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation. We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations. The most commonly affected test of lung function was the single-breath diffusing capacity for carbon monoxide (DLCO), which was abnormal in 48%, 45%, and 71% of patients who never smoked, former smokers, and current smokers, respectively. Ventilatory restriction was noted in 25% of all patients, airflow obstruction (reduced ratio of forced expiratory volume in 1 second to forced vital expiratory volume in 1 second to forced vital capacity) in only 3%, and a widened alveolar-arterial oxygen gradient in 45%. Diffusion impairment was accompanied by a restrictive defect in only 35% of the patients and by an abnormally widened alveolar-arterial oxygen gradient in 60%. When diffusion impairment was accompanied by an oxygenation defect, it was also associated with a significantly increased right-to-left shunt fraction (mean 24.9%) assessed from quantitative whole-body perfusion imaging

  17. Clinical and CT evaluation of hepatic reserve function in patients with cirrhosis and liver cancer undergoing interventional therapy

    International Nuclear Information System (INIS)

    Ji Changxue; Tu Rong

    2011-01-01

    Objective: To determine the value of clinical and CT assessment of hepatic reserve function in patients with cirrhosis and liver cancer undergoing transcatheter arterial chemoembolization (TACE). Methods: Sixty consecutive patients with cirrhosis and primary liver cancer treated using TACE were studied prospectively. The hepatic reserve function was evaluated using Child-Pugh classification and modified Child-Pugh classification before and after TACE respectively. The modified Child-Pugh classification was an integration of Child-Pugh classification, morphological evaluation of the cirrhotic liver and measurement of tumor-free liver volume by CT. Agreement rates of the two methods for assessing the hepatic reserve function peri-operatively and the survival time were calculated. Results: The agreement rates of Child-Pugh classification and modified Child-Pugh classification for assessing the postoperative hepatic reserve function were 55.6% and 83.3% respectively in well-compensated cases (P 2 =11.2, 8.7, 13.5, P<0.001) shorter than that of patients in modified Child-Pugh classes A (71 months), B (46 months) and C (7.6 months). Conclusion: Modified Child-Pugh classification is better than Child-Pugh classification for assessing the hepatic reserve function in patients with cirrhosis and liver cancer undergoing TACE. (authors)

  18. Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.

    Science.gov (United States)

    Avraham, Y; Grigoriadis, Nc; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, Em

    2011-04-01

    Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  19. Correlation of hepatic {sup 18}F-fluorodeoxyglucose uptake with fatty liver

    Energy Technology Data Exchange (ETDEWEB)

    An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam [Ajou University School of Medicine, Suwon (Korea, Republic of)

    2006-10-15

    Liver demonstrates heterogeneous FDG uptake and sometimes it shows abnormally increased uptake even though there is no malignant tissue. However, there was no previous study to correlate these various pattern of hepatic FDG uptake with benign liver disease. Therefore, we evaluated the significance of hepatic FDG uptake associated with various clinical factors including fatty liver, liver function tests and lipid profiles. We reviewed a total of 188 patients (male/female: 120/68, mean age: 50 {+-} 9) who underwent PET/CT for screening of malignancy. Patients with DM, impaired glucose tolerance, previous severe hepatic disease or long-term medication history were excluded. The FDG uptake in liver was analyzed semi-quantitatively using ROI on transaxial images (segment 8) and we compared mean standardized uptake value (SUV) between fatty liver and non-fatty liver group. We also evaluated the correlation between hepatic FDG uptake and various clinical factors including serum liver function test (ALT, AST), {gamma} -GT, total cholesterol and triglyceride concentration. The effect of alcoholic history and body mass index on hepatic FDG uptake was analyzed within the fatty liver patients. The hepatic FDG uptake of fatty liver group was significantly higher than that of non-fatty liver group. Serum total cholesterol and triglyceride concentration showed significant correlation with hepatic FDG uptake. However, there was no significant correlation between other factors (ALT, AST, and {gamma} -GT) and FDG uptake. Also there was no difference of mean SUV between normal and abnormal groups on the basis of alcoholic history and body mass index within fatty liver patients. Fatty liver and high serum triglyceride concentration were the independent factors affecting hepatic FDG uptake according to multivariate analysis. In conclusion, hepatic FDG uptake was strongly correlated with fatty liver and serum triglyceride concentration.

  20. CT Perfusion Characteristics Identify Metastatic Sites in Liver

    Directory of Open Access Journals (Sweden)

    Yuan Wang

    2015-01-01

    Full Text Available Tissue perfusion plays a critical role in oncology because growth and migration of cancerous cells require proliferation of new blood vessels through the process of tumor angiogenesis. Computed tomography (CT perfusion is an emerging functional imaging modality that measures tissue perfusion through dynamic CT scanning following intravenous administration of contrast medium. This noninvasive technique provides a quantitative basis for assessing tumor angiogenesis. CT perfusion has been utilized on a variety of organs including lung, prostate, liver, and brain, with promising results in cancer diagnosis, disease prognostication, prediction, and treatment monitoring. In this paper, we focus on assessing the extent to which CT perfusion characteristics can be used to discriminate liver metastases from neuroendocrine tumors from normal liver tissues. The neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow (BF, blood volume (BV, mean transit time (MTT, permeability (PS, and hepatic arterial fraction (HAF, for tumor and normal liver. The result reveals the potential of CT perfusion as a tool for constructing biomarkers from features of the hepatic vasculature for guiding cancer detection, prognostication, and treatment selection.

  1. Quality of Liver and Kidney Function Tests among Public Medical ...

    African Journals Online (AJOL)

    The aim of this study is to assess the accuracy and precision of clinical chemistry laboratories in western region of Amhara national regional state of Ethiopia in testing liver and kidney functions. Methods: Eight laboratories in hospitals and a Regional Health Research Laboratory Center participated in this study from ...

  2. Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study.

    Science.gov (United States)

    Salihovic, Samira; Stubleski, Jordan; Kärrman, Anna; Larsson, Anders; Fall, Tove; Lind, Lars; Lind, P Monica

    2018-08-01

    While it is known that perfluoroalkyl substances (PFASs) induce liver toxicity in experimental studies, the evidence of an association in humans is inconsistent. The main aim of the present study was to examine the association of PFAS concentrations and markers of liver function using panel data. We investigated 1002 individuals from Sweden (50% women) at ages 70, 75 and 80 in 2001-2014. Eight PFASs were measured in plasma using isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). Bilirubin and hepatic enzymes alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) were determined in serum using an immunoassay methodology. Mixed-effects linear regression models were used to examine the relationship between the changes in markers of liver function and changes in PFAS levels. The changes in majority of PFAS concentrations were positively associated with the changes in activity of ALT, ALP, and GGT and inversely associated with the changes in circulating bilirubin after adjustment for gender and the time-updated covariates LDL- and HDL-cholesterol, serum triglycerides, BMI, statin use, smoking, fasting glucose levels and correction for multiple testing. For example, changes in perfluorononanoic acid (PFNA) were associated with the changes liver function markers β BILIRUBIN  = -1.56, 95% confidence interval (CI) -1.93 to -1.19, β ALT  = 0.04, 95% CI 0.03-0.06, and β ALP  = 0.11, 95% CI 0.06-0.15. Our longitudinal assessment established associations between changes in markers of liver function and changes in plasma PFAS concentrations. These findings suggest a relationship between low-dose background PFAS exposure and altered liver function in the general population. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Effects of Catha edulis on kidney and liver function among chewing ...

    African Journals Online (AJOL)

    Effects of Catha edulis on kidney and liver function among chewing adults in Meru ... socio-cultural tradition in Kenya and as such poses a public health problem. ... Objective: To investigate the possible effects of Catha edulis on the levels of ...

  4. Use of triton-WR-1339 (TWR) for a quantitative determination of the lysosomal binding of transuranium elements in the rat liver

    International Nuclear Information System (INIS)

    Gruner, K.R.

    1978-01-01

    The subcellular localisation of 239 Pu and 241 Am in the rat liver was investigated. A biochemical separation method with modified lysosomes was applied for the first time; the method permitted unique statements on the mitochondrial or lysosomal association of transuranium elements. Lysosomal association of 239 Pu and 241 Am between days 4 and 6 after radionuclide injection was most easily detected by follow-up treatment with TWR, i.e. the nonionic detergent was applied 2 days after injection of the radionuclide and 4 days before the onset of the analytical procedure. Extracellular transuranium depots could not be proved to exist neither by comparing absolute retention figures in perfused and nonperfused livers nor by subcellular distribution studies. A quantitative relation between the DTPA mobilisation efficiency in the total liver and the subcellular distribution patterns obtained for americium could be estimated for the period between the first and 18th day after radionuclide injection. It suggests on intracellular effect of DTPA. (orig./MG) [de

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

    International Nuclear Information System (INIS)

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

    1989-01-01

    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 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. (orig.)

  6. American Liver Foundation

    Science.gov (United States)

    ... Cirrhosis Clinical Trials Galactosemia Gilbert Syndrome Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Hepatocellular Carcinoma Lysosomal Acid Lipase Deficiency(LALD) Intrahepatic Cholestasis of Pregnancy (ICP) Liver Biopsy Liver Cancer Liver Cysts Liver Function Tests ...

  7. 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.)

  8. Quantitative and Functional Requirements for Bioluminescent Cancer Models.

    Science.gov (United States)

    Feys, Lynn; Descamps, Benedicte; Vanhove, Christian; Vermeulen, Stefan; Vandesompele, J O; Vanderheyden, Katrien; Messens, Kathy; Bracke, Marc; De Wever, Olivier

    2016-01-01

    Bioluminescent cancer models are widely used but detailed quantification of the luciferase signal and functional comparison with a non-transfected control cell line are generally lacking. In the present study, we provide quantitative and functional tests for luciferase-transfected cells. We quantified the luciferase expression in BLM and HCT8/E11 transfected cancer cells, and examined the effect of long-term luciferin exposure. The present study also investigated functional differences between parental and transfected cancer cells. Our results showed that quantification of different single-cell-derived populations are superior with droplet digital polymerase chain reaction. Quantification of luciferase protein level and luciferase bioluminescent activity is only useful when there is a significant difference in copy number. Continuous exposure of cell cultures to luciferin leads to inhibitory effects on mitochondrial activity, cell growth and bioluminescence. These inhibitory effects correlate with luciferase copy number. Cell culture and mouse xenograft assays showed no significant functional differences between luciferase-transfected and parental cells. Luciferase-transfected cells should be validated by quantitative and functional assays before starting large-scale experiments. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Plasma exchange combining with plasma bilirubin adsorption effectively removes toxic substances and improves liver functions of hepatic failure patients.

    Science.gov (United States)

    Che, X-Q; Li, Z-Q; Chen, Z; Guo, D; Jia, Q-Y; Jiang, S-C; Cai, J

    2018-02-01

    Hepatic failure (HF) is a kind of complex disease characterizing with liver dysfunction and a few clinical complications. Artificial liver support system (ALSS) has been applied to HF patients to improve dysfunctional liver in recent years. This study aims to evaluate therapeutic effects of ALSS approaches, including plasma exchange (PE), plasma diafiltration (PDF) and plasma bilirubin adsorption (PBA), on liver function of HF patients. This study is a retrospective analysis involving 516 patients diagnosed as HF between February 2014 and February 2015. Patients were randomly divided into PE, PDF, PE plus PBA, and PDF plus PBA group. Meanwhile, single-drug group and combined-drug group were also divided. The liver functions, capability of removing toxic substances and coagulation functions were evaluated both pre-treatment and post-treatment. The side effects and hospital improvement rate were also observed post-treatment. Hospital improvement rate achieves to 69.6%. TBIL levels and MELD scores were significantly decreased post-treatment compared to pre-treatment (phigher compared to PE and PDF group (p=0.002, 0.002, respectively). MELD scores were significantly decreased post-treatment compared to pre-treatment in each group (pbetter role in removing toxic substances, improving liver functions of HF patients.

  10. Evaluation of selected parameters of rat liver and kidney function ...

    African Journals Online (AJOL)

    The effects of administration of yohimbine, an aphrodisiac on some functional parameters of rat liver and kidney were investigated. White male albino rats weighing between 200-250g were grouped into two such that one group was orally administered with 14mg/kg body weight on daily basis for 15days while the control ...

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

    Science.gov (United States)

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

    2004-11-01

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

  12. Comparison of Deferasirox and deferoxamine treatment in iron-overloaded patients: liver iron concentration determined by quantitative MRI-R_2"*

    International Nuclear Information System (INIS)

    Peng Peng; Long Liling; Huang Zhongkui; Zhang Ling; Feng Xiao; Li Xiaohui; Yang Gaohui

    2013-01-01

    Objective: To explore the value of MRI-R_2"* and to compare clinical effect of two iron chelators (Deferasirox and deferoxamine) in iron-overloaded patients. Methods: By completely randomized balanced design, 24 iron-overloaded patients were randomly divided into 2 groups, which consisted of 12 patients treated with Deferasirox and 12 patients treated with deferoxamine. The planned Deferasirox dose was 40 mg · kg"-"1 · d"-"1, and the deferoxamine dose was no less than 50 mg · kg"-"1 · d"-"1. All patients underwent quantitative MRI at the time points of the primary screening, 6 months and 12 months. Pair Wilcoxon rank sum test was used to compare the differences of liver R_2"* values of the 2 groups at various time points respectively. Wilcoxon rank sum test was used to compare the differences of change rate of liver R_2"* values between the two groups at the time point of 6 months, 12 months, respectively. Results: Deferasirox group's liver R_2"* values of primary screening, 6 months and 12 months were 1081, 889 and 712 Hz, while deferoxamine group's liver R_2"* values were 1042, 838 and 488 Hz. There was no statistically significant difference between liver R_2"* values of two groups at primary screening (Z = -0.029, P > 0.05). The change rate of liver R_2"* of Deferasirox group at 12 month was -32%, while it was -58% for the deferoxamine group, and there was statistically significant difference between the two groups (Z = -3.060, P < 0.01). The change rate of serum ferritin of Deferasirox group at 12 month was -15%, while it was -55% for the deferoxamine group, and there was statistically significant difference between the two groups (Z = -2.945, P < 0.01). Conclusion: By using MRI-R_2"*, it suggest that both Deferasirox and deferoxamine can effectively remove liver iron and deferoxamine is superior to Deferasirox. (authors)

  13. A study on relationship between liver scintigram and various kinds of liver function tests

    International Nuclear Information System (INIS)

    Watanabe, Kazuo

    1975-01-01

    The relationship between GOT, γ-globulin, alkaline phosphatase, ICG-R 15 and liver scintigram (anterior view) was studied in 37 patients with miscellaneous liver diseases. The length of the splenic image and the difference between right side and left side widths of the liver were indicated as liver scintigraphic findings. 1. γ-globulin and alkaline phosphatase tended to be slightly higher with remarkable splenic image. 2. All three patients with over 35% of ICG-R 15 had atrophic type of the right lobe showing more than 13 cm of the spleen. At first sight, they were diagnosed as having liver cirrhosis. On the other hand, some of the patients who had normal or slightly abnormal ICG-R 15 were suspected of having liver cirrhosis because of the long splenic image, but all had remarkable swelling of the right lobe. 3. The patients whom the difference between the right side and the left side widths was below 3 cm contained many patients with liver cirrhosis acompanied by atrophic type of the right lobe and remarkably abnormal ICG-R 15 . (Namekawa, K.)

  14. Radionuclide assessment of the liver function changes in patients with phlegmonas in the facio-maxillary region

    Energy Technology Data Exchange (ETDEWEB)

    Yudin, L; Budkevich, I; Uskov, I; Minchev, D

    1991-01-01

    The effect of endogenic intoxication on the liver function in 171 patients with different severity of the inflammatory process is investigated. Static liver scintigraphy is made at different intervals after the surgical intervention. The scintigrams are analyzed by conventional methods. 12 healthy volunteers are examined for determination of the relative activity of the preparation ({sup 99m}Tc-labelled colloid Fiton) which was found to be 42.6{+-}0.3 pulses/cm{sup 2} (image area - 138{+-}5.5 cm{sup 2}). It was observed a reliable correlation between the body intoxication indices (leucocite intoxication index, paramecine test and mean molecules level) and the liver relative activity indices. The method is assessed as an trustworthy tool not only for evaluation of liver function changes in inflammatory diseases, but also for treatment efficiency determination and pathological process forecasting. 2 tabs., 11 refs.

  15. Early Quantitative Assessment of Non-Functional Requirements

    NARCIS (Netherlands)

    Kassab, M.; Daneva, Maia; Ormandjieva, O.

    2007-01-01

    Non-functional requirements (NFRs) of software systems are a well known source of uncertainty in effort estimation. Yet, quantitatively approaching NFR early in a project is hard. This paper makes a step towards reducing the impact of uncertainty due to NRF. It offers a solution that incorporates

  16. Increase in left liver lobe function after preoperative right portal vein embolisation assessed with gadolinium-EOB-DTPA MRI.

    Science.gov (United States)

    Geisel, Dominik; Lüdemann, Lutz; Keuchel, Thomas; Malinowski, Maciej; Seehofer, Daniel; Stockmann, Martin; Hamm, Bernd; Gebauer, Bernhard; Denecke, Timm

    2013-09-01

    To prospectively evaluate the early development of regional liver function after right portal vein embolisation (PVE) with Gd-EOB-DTPA-enhanced MRI in patients scheduled for extended right hemihepatectomy. Ten patients who received a PVE before an extended hemihepatectomy were examined before and 14 days after PVE using Gd-EOB-DTPA-enhanced MRI of the liver. In these sequences representative region of interest measurements were performed in the embolised right (RLL) and the non-embolised left liver lobe (LLL). The volume as well as hepatic uptake index (HUI) was calculated independently for each lobe. Relative enhancement 14 days after PVE decreased in the RLL and increased significantly in the LLL (P DTPA-enhanced MRI, which could reflect the redirected portal venous blood flow and the rapid utilisation of a hepatic functional reserve. • Preoperative portal vein embolisation (PVE) is widely performed before right-sided hepatic resection. • PVE increases intravenous contrast medium uptake in the left lobe of liver. • The hepatic uptake index for the left liver lobe increases rapidly after PVE. • Left liver lobe function increase may be visualised by Gd-EOB-DTPA-enhanced MRI.

  17. Computational Modeling in Liver Surgery

    Directory of Open Access Journals (Sweden)

    Bruno Christ

    2017-11-01

    Full Text Available The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery.

  18. A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro

    Science.gov (United States)

    Zhang, Xiaoqian; Lu, Juan; He, Bin; Tang, Lingling; Liu, Xiaoli; Zhu, Danhua; Cao, Hongcui; Wang, Yingjie; Li, Lanjuan

    2017-01-01

    Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotransformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two-dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases. PMID:27959388

  19. Long-term liver-specific functions of hepatocytes in electrospun chitosan nanofiber scaffolds coated with fibronectin.

    Science.gov (United States)

    Rajendran, Divya; Hussain, Ali; Yip, Derek; Parekh, Amit; Shrirao, Anil; Cho, Cheul H

    2017-08-01

    In this study, a new 3D liver model was developed using biomimetic nanofiber scaffolds and co-culture system consisting of hepatocytes and fibroblasts for the maintenance of long-term liver functions. The chitosan nanofiber scaffolds were fabricated by the electrospinning technique. To enhance cellular adhesion and spreading, the surfaces of the chitosan scaffolds were coated with fibronectin (FN) by adsorption and evaluated for various cell types. Cellular phenotype, protein expression, and liver-specific functions were extensively characterized by immunofluorescent and histochemical stainings, albumin enzyme-linked immunosorbent assay and Cytochrome p450 detoxification assays, and scanning electron microscopy. The electrospun chitosan scaffolds exhibited a highly porous and randomly oriented nanofibrous structure. The FN coating on the surface of the chitosan nanofibers significantly enhanced cell attachment and spreading, as expected, as surface modification with this cell adhesion molecule on the chitosan surface is important for focal adhesion formation and integrin binding. Comparison of hepatocyte mono-cultures and co-cultures in 3D culture systems indicated that the hepatocytes in co-cultures formed colonies and maintained their morphologies and functions for prolonged periods of time. The 3D liver tissue model developed in this study will provide useful tools toward the development of engineered liver tissues for drug screening and tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2119-2128, 2017. © 2017 Wiley Periodicals, Inc.

  20. Quantitative in vivo assessment of radiation injury of the liver using Gd-EOB-DTPA enhanced MRI: tolerance dose of small liver volumes

    Directory of Open Access Journals (Sweden)

    Pech Maciej

    2011-04-01

    Full Text Available Abstract Backround Hepatic radiation toxicity restricts irradiation of liver malignancies. Better knowledge of hepatic tolerance dose is favourable to gain higher safety and to optimize radiation regimes in radiotherapy of the liver. In this study we sought to determine the hepatic tolerance dose to small volume single fraction high dose rate irradiation. Materials and methods 23 liver metastases were treated by CT-guided interstitial brachytherapy. MRI was performed 3 days, 6, 12 and 24 weeks after therapy. MR-sequences were conducted with T1-w GRE enhanced by hepatocyte-targeted Gd-EOB-DTPA. All MRI data sets were merged with 3D-dosimetry data. The reviewer indicated the border of hypointensity on T1-w images (loss of hepatocyte function or hyperintensity on T2-w images (edema. Based on the volume data, a dose-volume-histogram was calculated. We estimated the threshold dose for edema or function loss as the D90, i.e. the dose achieved in at least 90% of the pseudolesion volume. Results At six weeks post brachytherapy, the hepatocyte function loss reached its maximum extending to the former 9.4Gy isosurface in median (i.e., ≥9.4Gy dose exposure led to hepatocyte dysfunction. After 12 and 24 weeks, the dysfunctional volume had decreased significantly to a median of 11.4Gy and 14Gy isosurface, respectively, as a result of repair mechanisms. Development of edema was maximal at six weeks post brachytherapy (9.2Gy isosurface in median, and regeneration led to a decrease of the isosurface to a median of 11.3Gy between 6 and 12 weeks. The dose exposure leading to hepatocyte dysfunction was not significantly different from the dose provoking edema. Conclusion Hepatic injury peaked 6 weeks after small volume irradiation. Ongoing repair was observed up to 6 months. Individual dose sensitivity may differ as demonstrated by a relatively high standard deviation of threshold values in our own as well as all other published data.

  1. 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 knife therapy. Therefore, CTP imaging would play an important role for liver cancer management followed argon-helium knife therapy. © The Author(s) 2014.

  2. Dual-Functional Nanoparticles Targeting CXCR4 and Delivering Antiangiogenic siRNA Ameliorate Liver Fibrosis.

    Science.gov (United States)

    Liu, Chun-Hung; Chan, Kun-Ming; Chiang, Tsaiyu; Liu, Jia-Yu; Chern, Guann-Gen; Hsu, Fu-Fei; Wu, Yu-Hsuan; Liu, Ya-Chi; Chen, Yunching

    2016-07-05

    The progression of liver fibrosis, an intrinsic response to chronic liver injury, is associated with hepatic hypoxia, angiogenesis, abnormal inflammation, and significant matrix deposition, leading to the development of cirrhosis and hepatocellular carcinoma (HCC). Due to the complex pathogenesis of liver fibrosis, antifibrotic drug development has faced the challenge of efficiently and specifically targeting multiple pathogenic mechanisms. Therefore, CXCR4-targeted nanoparticles (NPs) were formulated to deliver siRNAs against vascular endothelial growth factor (VEGF) into fibrotic livers to block angiogenesis during the progression of liver fibrosis. AMD3100, a CXCR4 antagonist that was incorporated into the NPs, served dual functions: it acted as a targeting moiety and suppressed the progression of fibrosis by inhibiting the proliferation and activation of hepatic stellate cells (HSCs). We demonstrated that CXCR4-targeted NPs could deliver VEGF siRNAs to fibrotic livers, decrease VEGF expression, suppress angiogenesis and normalize the distorted vessels in the fibrotic livers in the carbon tetrachloride (CCl4) induced mouse model. Moreover, blocking SDF-1α/CXCR4 by CXCR4-targeted NPs in combination with VEGF siRNA significantly prevented the progression of liver fibrosis in CCl4-treated mice. In conclusion, the multifunctional CXCR4-targeted NPs delivering VEGF siRNAs provide an effective antifibrotic therapeutic strategy.

  3. Liver Progenitor Cell Line HepaRG Differentiated in a Bioartificial Liver Effectively Supplies Liver Support to Rats with Acute Liver Failure

    NARCIS (Netherlands)

    Nibourg, Geert A. A.; Chamuleau, Robert A. F. M.; van der Hoeven, Tessa V.; Maas, Martinus A. W.; Ruiter, An F. C.; Lamers, Wouter H.; Oude Elferink, Ronald P. J.; van Gulik, Thomas M.; Hoekstra, Ruurdtje

    2012-01-01

    A major roadblock to the application of bioartificial livers is the need for a human liver cell line that displays a high and broad level of hepatic functionality. The human bipotent liver progenitor cell line HepaRG is a promising candidate in this respect, for its potential to differentiate into

  4. The influence of liver and pancreas surgery on the thyroid function

    Directory of Open Access Journals (Sweden)

    Wojciechowska-Durczynska Katarzyna

    2012-12-01

    Full Text Available Abstract Background Nowadays, the increasing number of oncologic patients with liver or pancreatic tumours are subjected to surgical treatment, as it can provide a long-term survival or sometimes cure. As a result, numerous new clinical questions regarding metabolic disturbances in these patients have been arisen. Among others, the impact of the pancreas and liver surgery extent in relation to the thyroid function remains to be elucidated. Materials and methods The study comprised 51 patients (25 men and 26 women, mean age ± SD 61.6 ± 10.4 yrs, mean ± SD with pancreatic or liver tumours, qualified for abdominal operation. Serum levels of FT3, FT4 and TSH were measured on the day before (time “0” and on the 1st, 3rd and 5th day after surgery in two (2 subgroups reflecting the extent of surgery: twenty seven (27 patients (14 men and 13 women, mean age ± SD 61.5 ± 11.8 yrs after major surgery (Whipple’s surgery, right and left hemihepatectomy, segmentectomy of the liver, distal pancreatectomy, total duodenopancreatectomy and twenty four (24 patients (11 men and 13 women, mean age ± SD 61.8 ± 8.9 yrs after minor, palliative surgery (exploratory laparotomy, gastroenterostomy, triple by-pass, liver tumour embolization, hepaticojejunostomy. Additionally, the obtained results were analyzed in relation to the type of the disease (pancreatic surgery vs liver surgery. Results Mean serum FT3 level decreased significantly during the study in major and minor surgery subgroups (prd and 5th day after major surgery was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.002, p=0.032, respectively. Similarly, mean FT3 concentration on the 3rd day in minor surgery subgroup was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.015. Discussion Our findings have confirmed essential reduction of FT3 values after abdominal surgery, independently of surgery extent. Additionally, pancreatic tumour

  5. Report of the methods for quantitative organ evaluation in nuclear medicine

    International Nuclear Information System (INIS)

    Nakata, Shigeru; Akagi, Naoki; Mimura, Hiroaki; Nagaki, Akio; Takahashi, Yasuyuki

    1999-01-01

    The group for the methods in the title herein reported the summary of their investigations on literatures concerning the brain, heart, liver and kidney evaluation. The report consisted of the history, kinetics of the agents, methods for quantitative evaluation and summary for each organ. As for the brain, the quantitative evaluation of cerebral blood flow scintigraphy with 123 I-IMP and 99m Tc-HMPAO or -ECD were reviewed to conclude that the present convenient methods are of problems in precision, for which a novel method and/or tracer should be developed. For cardiac functions, there is a method based either on the behavior of tracer in the blood which is excellent in reproducibility, or on the morphology of cardiac wall of which images can be analyzed alternatively by CT and MRI. For these, 131 I-albumin, 99m Tc-albumin, -red blood cells, -MIBI and -tetrofosmin have been used. For myocardium, 201 Tl has been used to evaluate the ischemic region and, with simultaneous use of 99m Tc-MIBI or -tetrofosmin, the viability. 123 I-BMIPP and -MIBG have been developed for myocardial fatty acid metabolism and for cardiac sympathetic nerve functions. Liver functions have been evaluated by the blood elimination rate, hepatic uptake, hepatic elimination and hepatic blood flow with use of 99m Tc-labeled colloids, -PMT and -GSA. Quantitative evaluation of renal functions is now well established with high precision since the kinetic behavior of the tracers, like 99m Tc-DTPA, -MAG3, -DMSA and 131 I-OIH, is simple. (K.H.)

  6. Progression of Liver Disease

    Science.gov (United States)

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

  7. Changes of liver function and serum hepatic fibrosis markers levels in patients with trichloroethylene induced drugrash-like dermatitis

    International Nuclear Information System (INIS)

    Li Senhua; Xie Guoqiang; Zeng Zeming

    2004-01-01

    Objective: To investigate the liver function damage and serum hepatic fibrosis markers levels changes in patients suffering from trichloroethylene induced drugrash-like dermatitis. Methods: Serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC III), type IV collagen ( IV C) levels (with RIA), mono-amine oxidase (MAO) activity (with chemo-colorimetry) and liver function tests (including ALT, AGT, total protein, albumin, total bile acid, with automated biochemical analysis system) were determined in 30 controls and 30 patients with trichloroethylene induced drugrash-like dermatitis. Results: Severe liver function damage was demonstrated in all the patients. The serum hepatic fibrosis markers levels were significantly increased (vs controls, P<0.01) and correlated well with the degree of hepatic damage. Conclusion: Liver damage occurred early in patients with trichloroethylene induced dermatitis, accompanied with laboratory evidence of hepatic fibrosis. (authors)

  8. Unacylated ghrelin does not alter mitochondrial function, redox state and triglyceride content in rat liver in vivo

    Directory of Open Access Journals (Sweden)

    Gianluca Gortan Cappellari

    2015-12-01

    Full Text Available Changes in liver mitochondrial function with more oxidized redox state and enhanced inflammation may contribute to the onset of obesity- and insulin resistance-associated hepatic complications, including non-alcoholic fatty liver disease and steato-hepatitis. Unacylated ghrelin (UnAG is a gastric hormone reported to be associated with lower oxidative stress in different cell types, but its potential effects on liver mitochondrial function, redox state and inflammation in vivo remains undetermined. We investigated the impact of chronic UnAG overexpression (Tg Myh6/Ghrl leading to systemic upregulation of circulating hormone on mitochondrial ATP production, redox state (oxidized-to-total glutathione and inflammation markers in lean mice. Compared to wild-type animals (wt, Tg Myh6/Ghrl had superimposable liver weight, triglyceride content and plasma lipid profile. Liver mitochondrial enzyme activities and ATP production as well as oxidized-to-total glutathione were also similar in the two groups. In addition, no differences were observed in tissue inflammation marker TNF-alpha between wild-type and Tg Myh6/Ghrl animals. Thus, chronic systemic UnAG upregulation does not alter liver triglyceride content, mitochondrial function, redox state and inflammation markers in lean mice. These findings do not support a major role of UnAG as a physiological modulator of in vivo liver oxidative-lipid metabolism and inflammation.

  9. Imaging of pharmacokinetic rates of indocyanine green in mouse liver with a hybrid fluorescence molecular tomography/x-ray computed tomography system.

    Science.gov (United States)

    Zhang, Guanglei; Liu, Fei; Zhang, Bin; He, Yun; Luo, Jianwen; Bai, Jing

    2013-04-01

    Pharmacokinetic rates have the potential to provide quantitative physiological and pathological information for biological studies and drug development. Fluorescence molecular tomography (FMT) is an attractive imaging tool for three-dimensionally resolving fluorophore distribution in small animals. In this letter, pharmacokinetic rates of indocyanine green (ICG) in mouse liver are imaged with a hybrid FMT and x-ray computed tomography (XCT) system. A recently developed FMT method using structural priors from an XCT system is adopted to improve the quality of FMT reconstruction. In the in vivo experiments, images of uptake and excretion rates of ICG in mouse liver are obtained, which can be used to quantitatively evaluate liver function. The accuracy of the results is validated by a fiber-based fluorescence measurement system.

  10. Liver Function in Areas of Hepatic Venous Congestion After Hepatectomy for Liver Cancer: 99mTc-GSA SPECT/CT Fused Imaging Study.

    Science.gov (United States)

    Yoshida, Morikatsu; Beppu, Toru; Shiraishi, Shinya; Tsuda, Noriko; Sakamoto, Fumi; Kuramoto, Kunitaka; Okabe, Hirohisa; Nitta, Hidetoshi; Imai, Katsunori; Tomiguchi, Seiji; Baba, Hideo; Yamashita, Yasuyuki

    2018-05-01

    Background/Aim: The sacrifice of a major hepatic vein can cause hepatic venous congestion (HVC). We evaluated the effects of HVC on regional liver function using the liver uptake value (LUV), that was calculated from 99m Tc-labeled-galactosyl-human-serum-albumin ( 99m Tc-GSA) single-photon emission computed tomography (SPECT) /contrast-enhanced computed tomography (CE-CT) fused images. Patients and Methods: Sixty-two patients underwent 99m Tc-GSA SPECT/CE-CT prior to hepatectomy for liver cancer and at 7 days after surgery were divided into groups with (n=8) and without HVC (n=54). In the HVC group, CT volume (CTv) and LUV were separately calculated in both congested and non-congested areas. Results: The remnant LUV/CTv of the HVC group was significantly smaller than that of the non-HVC group (pliver function per unit volume in the congested areas was approximately 40% of that in the non-congested areas. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. A Study on the Significance of the Colloidal Radiogold Disappearance Rate as a Simple Clinical Liver Function Test

    International Nuclear Information System (INIS)

    Hong, Chang Gi

    1969-01-01

    Liver function in diffuse parenchymal liver such as cirrhosis of the liver depend largely on the effective hepatic blood flow rather than on the individual cell functions. Clinical methods of measuring the hepatic blood flow were developed recently by the application of colloidal disappearance rate. In order to correlate the radiogold disappearance rate to conventional biochemical liver function tests, 21 normal subjects and 80 cases of cirrhosis of the liver were studied with both methods. The results are summarized as following: 1) The validity of external counting method to measure the blood disappearance rate of colloidal radiogold was confirmed by in vitro counting of the serial blood samples. 2) The blood disappearance rate of colloidal radiogold was essentially the same as the liver uptake rate of colloidal radiogold in normal and cirrhotic subjects with various degrees of functional disturbance. And it seemed there was no serious extrahepatic removal of the colloidal radiogold. 3) The disappearance rate of colloidal radiogold was not significant changed by the posture change, but was enhanced by ingestion of 500 ml of water. 4) The disappearance rate of colloidal radiogold was not influenced y single dose of Telepaque, while BSP retention was increased after Telepaque. 5) The mean disappearance half time of colloidal radiogold in normal subjects was 2.49±0.391 (S.D.) minutes. The mean normal disappearance rate constant (K value) was 0.285±0.0428 (S.D.)/minute. 6) The colloidal radiogold disappearance half time was abnormally prolonged (over 3.2 mm) in 87.7±3.68 (S.D.) % of cirrhotic subjects. 7) In patients of liver cirrhosis the blood disappearance rate of colloidal radiogold correlated well to serum albumin and globulin levels and BSP retention which were considered to reflect functions of hepatic parenchymal cells. There was, however, no correlation between colloidal disappearance rate and thymol turbidity test, serum glutamic pyruvic transaminase

  12. The efficacy of the Peginterferon treatment in chronic hepatitis HDV and compensate liver cirrhosis.

    Science.gov (United States)

    Tugui, Letitia; Dumitru, M; Iacob, Speranta; Gheorghe, Liana; Preda, Carmen; Dinu, Ioana; Becheanu, G; Dumbrava, Mona; Nicolae, Ioana; Andrei, Adriana; Lupu, A; Diculescu, M

    2014-01-01

    To evaluate the efficiency of the treatment with Peginterferon alfa 2a 180 mcg/week, 48 weeks in patients with chronic hepatitis or compensated liver cirrhosis HDV and predictive factors of response to treatment. Prospective study that enrolled 50 patients with chronic hepatitis or compensated cirrhosis HDV between the 1st of January 2011 - 3st of December 2011. The diagnosis of chronic HDV infection was made based on the presence of detectable anti HDV IgG antibodies and HDV-RNA. Patients were evaluated at baseline by CBC, liver function tests, HBV profile, HDV RNA, and by liver biopsy/Fibrotest for evaluating fibrosis and necroinflammatory activity. At 24 weeks CBC (count blood cells), liver function tests, quantitative HBsAg and at 48 and 72 weeks biochemical tests, HDV RNA, HBV DNA, quantitative HBsAg, were performed. Adverse reactions to the treatment were recorded. SVR (sustained virologic response) was recorded in 12 patients (24%) and biochemical response in 28 patients (56%). SVR was correlated with low-grade fibrosis, age, the aminotransferase value and the value of HBsAg at the beginning of the treatment. In week 48 HDV RNA was undetectable in 20 patients (40%). The therapy was well tolerated, except two patients for whom the discontinuation of the treatment was decided for severe exacerbation of cytolysis, respectively hepatic decompensation. In a representative group of patients, the treatment with Peginterferon once again proves its efficacy in treating chronic HDV.

  13. /sup 14/C-D-galactose breath test for evaluation of liver function in patients with chronic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Caspary, W F; Schaffer, J

    1978-01-01

    D-galactose metabolism and demethylation of aminopyrine by healthy controls and patients with chronic active hepatitis (CAH) and cirrhosis (Ci), were assessed by a breath analysis technique measuring /sup 14/CO2 exhalation after oral ingestion of /sup 14/C-D-galactose or /sup 14/C-aminopyrine. Patients with CAH and Ci exhibited decreased /sup 14/CO2-exhalation rates following /sup 14/-D-galactose or /sup 14/C-aminopyrine. D-galactose oxidation capacity of the liver can be assessed by a breath analysis technique in analogy to the demethylating function for aminopyrine. The ordinary oral D-galactose tolerance test seems, however, superior in comparison to the /sup 14/C-D-galactose tolerance test, in discriminating between healthy controls and patients with chronic liver disease.

  14. Implementation of an interactive liver surgery planning system

    Science.gov (United States)

    Wang, Luyao; Liu, Jingjing; Yuan, Rong; Gu, Shuguo; Yu, Long; Li, Zhitao; Li, Yanzhao; Li, Zhen; Xie, Qingguo; Hu, Daoyu

    2011-03-01

    Liver tumor, one of the most wide-spread diseases, has a very high mortality in China. To improve success rates of liver surgeries and life qualities of such patients, we implement an interactive liver surgery planning system based on contrastenhanced liver CT images. The system consists of five modules: pre-processing, segmentation, modeling, quantitative analysis and surgery simulation. The Graph Cuts method is utilized to automatically segment the liver based on an anatomical prior knowledge that liver is the biggest organ and has almost homogeneous gray value. The system supports users to build patient-specific liver segment and sub-segment models using interactive portal vein branch labeling, and to perform anatomical resection simulation. It also provides several tools to simulate atypical resection, including resection plane, sphere and curved surface. To match actual surgery resections well and simulate the process flexibly, we extend our work to develop a virtual scalpel model and simulate the scalpel movement in the hepatic tissue using multi-plane continuous resection. In addition, the quantitative analysis module makes it possible to assess the risk of a liver surgery. The preliminary results show that the system has the potential to offer an accurate 3D delineation of the liver anatomy, as well as the tumors' location in relation to vessels, and to facilitate liver resection surgeries. Furthermore, we are testing the system in a full-scale clinical trial.

  15. Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

    Science.gov (United States)

    Chen, T S; Ottenweller, J; Luke, A; Santos, S; Keeting, P; Cuy, R; Lea, M A

    1989-01-01

    A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

  16. Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community.

    Science.gov (United States)

    Darrow, Lyndsey A; Groth, Alyx C; Winquist, Andrea; Shin, Hyeong-Moo; Bartell, Scott M; Steenland, Kyle

    2016-08-01

    , Steenland K. 2016. Modeled perfluorooctanoic acid (PFOA) exposure and liver function in a Mid-Ohio Valley community. Environ Health Perspect 124:1227-1233; http://dx.doi.org/10.1289/ehp.1510391.

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

    Directory of Open Access Journals (Sweden)

    Magnus F Kaffarnik

    Full Text Available 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.

  18. Tc-99m GSA scintigraphy for evaluation of liver function. Correlations with histological grading and staging (new Inuyama classification)

    International Nuclear Information System (INIS)

    Endo, Ikuyo; Ohashi, Kenjirou; Fukui, Atsushi; Nikai, Akira; Maeyama, Shiro

    2001-01-01

    To evaluate the parameters of Tc-99m galactosyl human serum albumin (Tc-99m GSA) as indicators of residual liver function by comparing with laboratory data and histological grading and staging. The study population consists of 82 patients with liver diseases including chronic hepatitis (60), compensated liver cirrhosis (12) and decompensated liver cirrhosis (10). Five parameters of Tc-99m GSA (HH 15 , LHL 15 , LHL/HH, ncEI 5 and EI 5 ) were measured and correlated with laboratory data and histological grading, which indicates necro-inflammatory activity, and staging, which indicates fibrosis (New Inuyama Classification). All 5 parameters showed significant correlation with the laboratory data for liver function including serum albumin, platelet count, and prothrombin time. LHL 15 showed a particularly strong correlation with serum albumin, total bilirubin, TTT, ZTT, and prothrombin time. Regarding histological correlation, only LHL 15 showed a significant correlation with both histological grading and staging. HH 15 and LHL/HH revealed significant correlations with staging only. Extraction indexes were not correlated significantly with histological grading and staging. Among the five parameters we tested, LHL 15 is the most potent indicator of liver function. HH 15 , LHL 15 and LHL/HH appear-useful to non-invasive assess histological fibrosis of the liver non-invasively. (author)

  19. The effect of TACE plus PSE on the liver function of hepatic cancer with portal hypertension and hypersplenism

    International Nuclear Information System (INIS)

    Tao Zhenglong; Jin Hongxian; Cheng Yongde; Zhan Yingjiang

    2004-01-01

    Objective: To evaluate the effect of transcatheter arterial chemoembolization (TACE) plus partial spleen embolization (PSE) on the liver function in patients with hepatocellular carcinoma (HCC). Methods: 85 patients with HCC complicated with portal hypertension and hypersplenism, including group A 45 patients with treatment of TACE plus PSE and group B 40 patients with single TACE were observed. The liver function was evaluated with Child Pugh scores before and after the procedure. Results: There was no difference in the levels of TBIL, ALT, ALB and Child Pugh scores between groups A and B (P>0.05) but remarkable change after therapy was shown at one week later (P<0.05, P<0.01). The liver function tests showed remarkable improvement in the TACE plus PSE group. Conclusion: TACE combined with PSE is a safe and effective procedure for patients with HCC associated with liver cirrhosis, portal hypertension and hypersplenism. (authors)

  20. 99m technetium-labelled acetanilidoimino-diacetate to diagnose the functioning of the liver

    International Nuclear Information System (INIS)

    Molter, M.; Kloss, G.

    1979-01-01

    The proposed agent for liver function diagnosis has got a very low renal secretion. If is suited for scintigraphic representation of liver, gall-bladder and bile-ducts. To an aqueous solution of (2,3,4,5,6 penta-fluoracetanilido)-iminodiacetate and/or (4-n-pentylacetanilido)-iminodiacetate is admixed a tin (II) salt (pH between 4 and 9) and as a label 99m Tc pertechnetate in a physiological salt solution. Production and effect are described in detail. (RB) [de

  1. Quantitative radiology: automated CT liver volumetry compared with interactive volumetry and manual volumetry.

    Science.gov (United States)

    Suzuki, Kenji; Epstein, Mark L; Kohlbrenner, Ryan; Garg, Shailesh; Hori, Masatoshi; Oto, Aytekin; Baron, Richard L

    2011-10-01

    The purpose of this study was to evaluate automated CT volumetry in the assessment of living-donor livers for transplant and to compare this technique with software-aided interactive volumetry and manual volumetry. Hepatic CT scans of 18 consecutively registered prospective liver donors were obtained under a liver transplant protocol. Automated liver volumetry was developed on the basis of 3D active-contour segmentation. To establish reference standard liver volumes, a radiologist manually traced the contour of the liver on each CT slice. We compared the results obtained with automated and interactive volumetry with those obtained with the reference standard for this study, manual volumetry. The average interactive liver volume was 1553 ± 343 cm(3), and the average automated liver volume was 1520 ± 378 cm(3). The average manual volume was 1486 ± 343 cm(3). Both interactive and automated volumetric results had excellent agreement with manual volumetric results (intraclass correlation coefficients, 0.96 and 0.94). The average user time for automated volumetry was 0.57 ± 0.06 min/case, whereas those for interactive and manual volumetry were 27.3 ± 4.6 and 39.4 ± 5.5 min/case, the difference being statistically significant (p volumetry are accurate for measuring liver volume with CT, but automated volumetry is substantially more efficient.

  2. 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

  3. 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.

    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

  4. Evaluation of the liver scintigraphy with sup(99m)Tc-Sn-colloid, 2

    International Nuclear Information System (INIS)

    Kimura, Kazufumi; Nishimura, Tsunehiko; Takeda, Hiroshi; Furukawa, Toshiyuki; Kajiya, Fumihiko.

    1975-01-01

    Clinical significance of the liver scintigraphy with sup(99m)Tc-Sn-colloid was evaluated in comparison with those with 198 Au-colloid. The liver scintigrams with sup(99m)Tc-Sn-colloid and 198 Au-colloid were done in 36 cases of various hepatic diseases and RI accumulation curves in the liver and the spleen, and the blood disapearance curves were also obtained. The conclusions were as follows. The liver scintigrams with sup(99m)Tc-Sn-colloid proved to be more sensitive in the detection of tumors, especially, in the lower margin, left lobe and superficial layers of the liver than those with 198 Au-colloid. In all cases, including normal and cirrhotic subjects, visualizations of the spleen were seen on the scintigrams with sup(99m)Tc-Sn-colloid. In diffuse hepatic diseases, comparing both radiopharmaceuticals, the splenic accumulations were studied qualitatively and quantitatively. As a result, the ratio (spleen/liver) was thought to be useful for the differentiation of diffuse hepatic diseases concerned with splenic function and/or size. It was also shown that sup(99m)Tc-Sn-colloid was useful as a spleen scanning agent. The Tl/2 in the liver accumulation curves with sup(99m)Tc-Sn-colloid were not as clearly differentiated in the various hepatic diseases as those with 198 Au-colloid where those indexes were useful in the evaluation of liver functions. (auth.)

  5. Contrast-enhanced sonography for quantitative assessment of portal hypertension in patients with liver cirrhosis.

    Science.gov (United States)

    Qu, En-Ze; Zhang, Ying-Cai; Li, Zhi-Yan; Liu, Yang; Wang, Jin-Rui

    2014-11-01

    The clinical utility of contrast-enhanced sonography in portal hypertension remains unclear. We explored the feasibility of using contrast-enhanced sonography for noninvasive assessment of portal venous pressure. Twenty healthy individuals (control group; 9 men; mean age, 46.4 years) and 18 patients with portal hypertension (15 men; mean age, 46.2 years) were enrolled in this study. The portal hypertension group included patients who underwent splenectomy and pericardial blood vessel disarticulation at our hospital from October 2010 to March 2011. One week before surgery, patients with portal hypertension underwent preoperative liver contrast-enhanced sonography. Two-dimensional, Doppler, and contrast-enhanced sonographic parameters were compared between the groups. Portal venous pressure was measured intraoperatively by portal vein puncture in the portal hypertension group, and its relationship with the other parameters was analyzed. The 2-dimensional, Doppler, and contrast-enhanced sonographic parameters differed between the groups (P Portal venous pressure was inversely correlated with the area under the portal vein/hepatic artery time-intensity curve ratio (Qp/Qa), portal vein/hepatic artery strength ratio (Ip/Ia), and portal vein/hepatic artery wash-in perfusion slope ratio (βp/βa), with correlation coefficients of -0.701, -0.625, and -0.494, respectively. Measurement of the liver contrast-enhanced sonographic parameters Qp/Qa, Ip/Ia, and βp/βa could be used as a new quantitative method for noninvasively assessing portal venous pressure. © 2014 by the American Institute of Ultrasound in Medicine.

  6. Serum levels of DDT and liver function of malaria control personnel

    African Journals Online (AJOL)

    1991-03-16

    Mar 16, 1991 ... a carcinogen in animal models,7 no such effects have been. Research ... found in people with excessive exposure to DDT, such as pesticide-factory workers.8 However, impaired liver function,9 ... of cement dwellings, which were treated with a different DDT ..... Men with intensive occupational exposure to.

  7. Serial MR imaging evaluation of effects of radiation therapy on bone marrow and liver

    International Nuclear Information System (INIS)

    Yankelevitz, D.; Henschke, C.I.; Chu, F.; Hayt, D.B.; Whalen, J.P.; Cahill, P.T.

    1989-01-01

    This paper reports on baseline and serial MR imaging studies obtained on 20 patients (lung cancer and lymphoma) who were receiving radiation therapy as their only form of treatment. Quantitative and qualitative MR signal intensity measurement were made on bone marrow and liver. Additionally, changes in signal intensity were correlated with laboratory values including both complete blood count and liver function tests. The spine showed increased signal intensity on T1-weighted images. MR signal intensity increased rapidly in the first 6 weeks and continued to rise slowly thereafter. In three of 10 cases in which the liver was included in the radiotherapy field, areas of increased activity in the liver were seen on T2-weighted images. These areas were in the field of radiation and sharply demarcated from nonirradiated liver. This area of abnormality gradually returned to normal after completion of therapy

  8. Quantitative pre-surgical lung function estimation with SPECT/CT

    International Nuclear Information System (INIS)

    Bailey, D. L.; Willowson, K. P.; Timmins, S.; Harris, B. E.; Bailey, E. A.; Roach, P. J.

    2009-01-01

    Full text:Objectives: To develop methodology to predict lobar lung function based on SPECT/CT ventilation and perfusion (V/Q) scanning in candidates for lobectomy for lung cancer. Methods: This combines two development areas from our group: quantitative SPECT based on CT-derived corrections for scattering and attenuation of photons, and SPECT V/Q scanning with lobar segmentation from CT. Eight patients underwent baseline pulmonary function testing (PFT) including spirometry, measure of DLCO and cario-pulmonary exercise testing. A SPECT/CT V/Q scan was acquired at baseline. Using in-house software each lobe was anatomically defined using CT to provide lobar ROIs which could be applied to the SPECT data. From these, individual lobar contribution to overall function was calculated from counts within the lobe and post-operative FEV1, DLCO and VO2 peak were predicted. This was compared with the quantitative planar scan method using 3 rectangular ROIs over each lung. Results: Post-operative FEV1 most closely matched that predicted by the planar quantification method, with SPECT V/Q over-estimating the loss of function by 8% (range - 7 - +23%). However, post-operative DLCO and VO2 peak were both accurately predicted by SPECT V/Q (average error of 0 and 2% respectively) compared with planar. Conclusions: More accurate anatomical definition of lobar anatomy provides better estimates of post-operative loss of function for DLCO and VO2 peak than traditional planar methods. SPECT/CT provides the tools for accurate anatomical defintions of the surgical target as well as being useful in producing quantitative 3D functional images for ventilation and perfusion.

  9. [Liver transplantation].

    Science.gov (United States)

    Pompili, Maurizio; Mirante, Vincenzo Giorgio; Rapaccini, Gian Ludovico; Gasbarrini, Giovanni

    2004-01-01

    Liver transplantation represents the first choice treatment for patients with fulminant acute hepatitis and for patients with chronic liver disease and advanced functional failure. Patients in the waiting list for liver transplantation are classified according to the severity of their clinical conditions (evaluated using staging systems mostly based on hematochemical parameters related to liver function). This classification, together with the blood group and the body size compatibility, remains the main criterion for organ allocation. The main indications for liver transplantation are cirrhosis (mainly HCV-, HBV- and alcohol-related) and hepatocellular carcinoma emerging in cirrhosis in adult patients, biliary atresia and some inborn errors of metabolism in pediatric patients. In adults the overall 5-year survival ranges between 60 and 70%, in both American and European series. Even better results have been reported for pediatric patients: in fact, the 5-year survival rate for children ranges between 70 and 80% in the main published series. In this study we evaluated the main medical problems correlated with liver transplantation such as immunosuppressive treatment, acute and chronic rejection, infectious complications, the recurrence of the liver disease leading to transplantation, and cardiovascular and metabolic complications.

  10. Comparison of low-calorie diet with and without sibutramine on body weight and liver function of patients with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    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.

  11. Influence of Prescribed Herbal and Western Medicine on Patients with Abnormal Liver Function Tests: A Retrospective Quasi-Experimental Study

    Science.gov (United States)

    Lee, Ah-Ram; Yim, Je-Min; Kim, Won-Il

    2012-01-01

    Objectives: The aim of this study was to investigate the safety and the efficacy of Korean herbal, western and combination medicine use in patients with abnormal liver function tests. Methods: We investigated nerve disease patients with abnormal liver function tests who were treated with Korean herbal, western and combination medicine at Dong-Eui University Oriental Hospital from January 2011 to August 2011. We compared aspartic aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (T-bil) levels before and after taking medicine and excluded patients who had liver-related disease when admitted. Results: AST and ALT were decreased significantly in patients who had taken herbal, western medicine. AST, ALT and ALP were decreased significantly in patients who had taken combination medicine. Compare to herbal medicine, AST, ALT and ALP were decreased significantly in patients who had taken western medicine, and ALT and ALP were decreased significantly in patients who had taken combination medicine. There were no significant differences between western and combination medicine. Conclusions: This study suggests that prescribed Korean herbal medicine, at least, does not injure liver function for patients’, moreover, it was shown to be effective in patients with abnormal liver function tests. PMID:25780634

  12. Functional proteomic analysis of corticosteroid pharmacodynamics in rat liver: Relationship to hepatic stress, signaling, energy regulation, and drug metabolism.

    Science.gov (United States)

    Ayyar, Vivaswath S; Almon, Richard R; DuBois, Debra C; Sukumaran, Siddharth; Qu, Jun; Jusko, William J

    2017-05-08

    Corticosteroids (CS) are anti-inflammatory agents that cause extensive pharmacogenomic and proteomic changes in multiple tissues. An understanding of the proteome-wide effects of CS in liver and its relationships to altered hepatic and systemic physiology remains incomplete. Here, we report the application of a functional pharmacoproteomic approach to gain integrated insight into the complex nature of CS responses in liver in vivo. An in-depth functional analysis was performed using rich pharmacodynamic (temporal-based) proteomic data measured over 66h in rat liver following a single dose of methylprednisolone (MPL). Data mining identified 451 differentially regulated proteins. These proteins were analyzed on the basis of temporal regulation, cellular localization, and literature-mined functional information. Of the 451 proteins, 378 were clustered into six functional groups based on major clinically-relevant effects of CS in liver. MPL-responsive proteins were highly localized in the mitochondria (20%) and cytosol (24%). Interestingly, several proteins were related to hepatic stress and signaling processes, which appear to be involved in secondary signaling cascades and in protecting the liver from CS-induced oxidative damage. Consistent with known adverse metabolic effects of CS, several rate-controlling enzymes involved in amino acid metabolism, gluconeogenesis, and fatty-acid metabolism were altered by MPL. In addition, proteins involved in the metabolism of endogenous compounds, xenobiotics, and therapeutic drugs including cytochrome P450 and Phase-II enzymes were differentially regulated. Proteins related to the inflammatory acute-phase response were up-regulated in response to MPL. Functionally-similar proteins showed large diversity in their temporal profiles, indicating complex mechanisms of regulation by CS. Clinical use of corticosteroid (CS) therapy is frequent and chronic. However, current knowledge on the proteome-level effects of CS in liver and

  13. PREDICTION AND PREVENTION OF LIVER FAILURE AFTER MAJOR LIVER PRIMARY AND METASTATIC TUMORS RESECTION

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2016-01-01

    Full Text Available Abstract Purpose of the study. Improvement of results of treatment in patients with primary and metastatic liver cancer by decreasing the risk of post-resection liver failure on the basis of the evaluation of the functional reserves of the liver.Materials and Methods. The study included two independent samples of patients operated about primary or metastatic lesions of the liver at the Department of abdominal Oncology, P. A. Hertsen MORI. The first group included 53 patients who carried out 13C-breath test metallimovie and dynamic scintigraphy of the liver in the preoperative stage in addition to the standard algorithm of examination. Patients of the 2nd group (n=35 had a standard clinical and laboratory examination, the patients were not performed the preoperative evaluation of the functional reserve of the liver, the incidences of total bilirubin, albumin and prothrombin time did not reveal a reduction of liver function. Post-resection liver failure have been established on the basis of the 50/50 criterion in the evaluation on day 5 after surgery.Results. Analysis of operating characteristics of the functional tests showed the absolute methacin breath test sensitivity (SE≥100%, high specificity (SP≥67% of scintigraphy of the liver and the negative predictive value of outcome (VP≥100% at complex use of two diagnostic methods. The incidence of PROPS in the study group was significantly 2 times higher in the control group –15,1% and 26.8%, respectively (p<0.001.Conclusion. The combination of preoperative dynamic scintigraphy of the liver with carrying out 13C-breath methacin test allows you to conduct a comprehensive evaluation of the liver functional reserve and can significantly improve preoperative evaluation and postoperative results of anatomic resection in patients with primary and metastatic liver lesions.

  14. Determination of micro mineral Fe on cow meat and liver

    International Nuclear Information System (INIS)

    Natalia Adventini; Muhayatun; Syukria Kurniawati; Endang; Yuni Setyowat

    2010-01-01

    Fe deficiency is common in development countries. Fe deficiency could decreased the IQ level, immune function and work performance, impacts decreasing human resource quality. Beef and liver are Fe source which more easily absorbed compare to Fe found in plant products. Therefore, the Fe determination in beef and liver need to be carried out using INAA. Instrumental neutron activation analysis is a method for qualitative and quantitative determination of elements based on the measurement of characteristic radiation from radionuclide formed by neutron irradiation of the material. The Sixteen beef and liver from feed treatment cows were collected. Method validation using RM IAEAA-13 gave accuracy and precise were 99 % and 3,3 % respectively. Fe concentration in 16 beef and liver were obtained between 5.5-18.6 mg/kg wet weight with average value was 12.2±4.0 mg/kg and 22.9-4.7 mg/kg with average value was 35.2±8.7 mg/kg. Generally, this value gave the same result from other countries. Fe determination in beef and liver is not only expected to be a scientific based reference but also to update Indonesia food stuff composition data. (author)

  15. Effect of evacuation on liver function after the Fukushima Daiichi Nuclear Power Plant accident: The Fukushima Health Management Survey.

    Science.gov (United States)

    Takahashi, Atsushi; Ohira, Tetsuya; Hosoya, Mitsuaki; Yasumura, Seiji; Nagai, Masato; Ohira, Hiromasa; Hashimoto, Shigeatsu; Satoh, Hiroaki; Sakai, Akira; Ohtsuru, Akira; Kawasaki, Yukihiko; Suzuki, Hitoshi; Kobashi, Gen; Ozasa, Kotaro; Yamashita, Shunichi; Kamiya, Kenji; Abe, Masafumi

    2017-04-01

    The Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident caused residents to switch from their normal lives to lives focused on evacuation. We evaluated liver function before and after this disaster to elucidate the effects of evacuation on liver function. This study was a longitudinal survey of 26,006 Japanese men and women living near the Fukushima Daiichi Nuclear Power Plant. This study was undertaken using data from annual health checkups conducted for persons aged 40-90 years between 2008 and 2010. Follow-up examinations were conducted from June 2011 to the end of March 2013, with a mean follow up of 1.6 years. Changes in liver function before and after the disaster were compared among evacuees and non-evacuees. We also assessed groups according to alcohol drinking status. The prevalence of liver dysfunction significantly increased in all participants from 16.4% before to 19.2% after the disaster. The incidence of liver dysfunction was significantly higher in evacuees than in non-evacuees. Multivariate logistic regression analysis showed that evacuation was significantly associated with liver dysfunction among residents. This is the first study to show that evacuation due to the Fukushima Daiichi nuclear power plant disaster was associated with an increase in liver dysfunction. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  16. Lineage fate of ductular reactions in liver injury and carcinogenesis.

    Science.gov (United States)

    Jörs, Simone; Jeliazkova, Petia; Ringelhan, Marc; Thalhammer, Julian; Dürl, Stephanie; Ferrer, Jorge; Sander, Maike; Heikenwalder, Mathias; Schmid, Roland M; Siveke, Jens T; Geisler, Fabian

    2015-06-01

    Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function of DRs in liver injury are not entirely understood. It is widely believed that DRs contain bipotential liver progenitor cells (LPCs) that serve as an emergency cell pool to regenerate both cholangiocytes and hepatocytes and may eventually give rise to hepatocellular carcinoma (HCC). Here, we used a murine model that allows highly efficient and specific lineage labeling of the biliary compartment to analyze the histogenesis of DRs and their potential contribution to liver regeneration and carcinogenesis. In multiple experimental and genetic liver injury models, biliary cells were the predominant precursors of DRs but lacked substantial capacity to produce new hepatocytes, even when liver injuries were prolonged up to 12 months. Genetic modulation of NOTCH and/or WNT/β-catenin signaling within lineage-tagged DRs impaired DR expansion but failed to redirect DRs from biliary differentiation toward the hepatocyte lineage. Further, lineage-labeled DRs did not produce tumors in genetic and chemical HCC mouse models. In summary, we found no evidence in our system to support mouse biliary-derived DRs as an LPC pool to replenish hepatocytes in a quantitatively relevant way in injury or evidence that DRs give rise to HCCs.

  17. Quantification of Liver Fat with Magnetic Resonance Imaging

    Science.gov (United States)

    Reeder, Scott B.; Sirlin, Claude

    2010-01-01

    Intracellular fat accumulation is common feature of liver disease. Intracellular fat (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 article reviews emerging magnetic resonance imaging techniques that attempt to quantify liver fat. The content provides an overview of fatty liver disease and diseases where fat is an important disease feature. Also discussed is the current use and limitation of non-targeted biopsy in diffuse liver disease, and why quantitative non-invasive biomarkers of liver fat would be beneficial. PMID:21094444

  18. 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.

  19. A quantitative histochemical procedure for the demonstration of purine nucleoside phosphorylase activity in rat and human liver using Tetranitro BT and xanthine oxidase as auxiliary enzyme

    NARCIS (Netherlands)

    Frederiks, W. M.; Bosch, K. S.; van Gulik, T.

    1993-01-01

    A quantitative histochemical procedure was developed for the demonstration of purine nucleoside phosphorylase in rat liver using unfixed cryostat sections and the auxiliary enzyme xanthine oxidase. The optimum incubation medium contained 18% (w/v) poly(vinyl alcohol), 100 mM phosphate buffer, pH

  20. A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro.

    Science.gov (United States)

    Zhang, Xiaoqian; Lu, Juan; He, Bin; Tang, Lingling; Liu, Xiaoli; Zhu, Danhua; Cao, Hongcui; Wang, Yingjie; Li, Lanjuan

    2017-01-01

    Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotra-nsformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two‑dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases.

  1. Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver[S

    Science.gov (United States)

    Satapati, Santhosh; Sunny, Nishanth E.; Kucejova, Blanka; Fu, Xiaorong; He, Tian Teng; Méndez-Lucas, Andrés; Shelton, John M.; Perales, Jose C.; Browning, Jeffrey D.; Burgess, Shawn C.

    2012-01-01

    The manner in which insulin resistance impinges on hepatic mitochondrial function is complex. Although liver insulin resistance is associated with respiratory dysfunction, the effect on fat oxidation remains controversial, and biosynthetic pathways that traverse mitochondria are actually increased. The tricarboxylic acid (TCA) cycle is the site of terminal fat oxidation, chief source of electrons for respiration, and a metabolic progenitor of gluconeogenesis. Therefore, we tested whether insulin resistance promotes hepatic TCA cycle flux in mice progressing to insulin resistance and fatty liver on a high-fat diet (HFD) for 32 weeks using standard biomolecular and in vivo 2H/13C tracer methods. Relative mitochondrial content increased, but respiratory efficiency declined by 32 weeks of HFD. Fasting ketogenesis became unresponsive to feeding or insulin clamp, indicating blunted but constitutively active mitochondrial β-oxidation. Impaired insulin signaling was marked by elevated in vivo gluconeogenesis and anaplerotic and oxidative TCA cycle flux. The induction of TCA cycle function corresponded to the development of mitochondrial respiratory dysfunction, hepatic oxidative stress, and inflammation. Thus, the hepatic TCA cycle appears to enable mitochondrial dysfunction during insulin resistance by increasing electron deposition into an inefficient respiratory chain prone to reactive oxygen species production and by providing mitochondria-derived substrate for elevated gluconeogenesis. PMID:22493093

  2. Restoration of Liver Function and Portosystemic Pressure Gradient after TIPSS and Late TIPSS Occlusion

    International Nuclear Information System (INIS)

    Maedler, U.; Hansmann, J.; Duex, M.; Noeldge, G.; Sauer, P.; Richter, G.M.

    2002-01-01

    TIPSS (transjugular intrahepatic portosystemic shunt) may be indicated to control bleeding from esophageal and gastric varicose veins, to reduce ascites, and to treat patients with Budd-Chiari syndrome and veno-occlusive disease. Numerous measures to improve the safety and methodology of the procedure have helped to increase the technical and clinical success. Follow-up of TIPSS patients has revealed shunt stenosis to occur more often in patients with preserved liver function (Child A, Child B). In addition, the extent of liver cirrhosis is the main factor that determines prognosis in the long term. Little is known about the effects of TIPSS with respect to portosystemic hemodynamics. This report deals with a cirrhotic patient who stopped drinking 7 months prior to admission. He received TIPSS to control ascites and recurrent esophageal bleeding. Two years later remarkable hypertrophy of the left liver lobe and shunt occlusion was observed. The portosystemic pressure gradient dropped from 24 mmHg before TIPSS to 11 mmHg and remained stable after shunt occlusion. The Child's B cirrhosis prior to TIPSS turned into Child's A cirrhosis and remained stable during the follow-up period of 32 months. This indicates that liver function of TIPSS patients may recover due to hypertrophy of the remaining non-cirrhotic liver tissue. In addition the hepatic hemodynamics may return to normal. In conclusion, TIPSS cannot cure cirrhosis but its progress may be halted if the cause can be removed. This may result in a normal portosystemic gradient, leading consequently to shunt occlusion

  3. Liver transplantation in polycystic liver disease

    DEFF Research Database (Denmark)

    Krohn, Paul S; Hillingsø, Jens; Kirkegaard, Preben

    2008-01-01

    OBJECTIVE: Polycystic liver disease (PLD) is a rare, hereditary, benign disorder. Hepatic failure is uncommon and symptoms are caused by mass effects leading to abdominal distension and pain. Liver transplantation (LTX) offers fully curative treatment, but there is still some controversy about...... whether it is a relevant modality considering the absence of liver failure, relative organ shortage, perioperative risks and lifelong immunosuppression. The purpose of this study was to review our experience of LTX for PLD and to compare the survival with the overall survival of patients who underwent LTX...... from 1992 to 2005. MATERIAL AND METHODS: A retrospective study of the journals of 440 patients, who underwent 506 LTXs between 1992 and 2005, showed that 14 patients underwent LTX for PLD. All patients had normal liver function. Three were receiving haemodialysis and thus underwent combined liver...

  4. Liver Cell Culture Devices

    NARCIS (Netherlands)

    Andria, B.; Bracco, A.; Cirino, G.; Chamuleau, R. A. F. M.

    2010-01-01

    In the last 15 years many different liver cell culture devices, consisting of functional liver cells and artificial materials, have been developed. They have been devised for numerous different applications, such as temporary organ replacement (a bridge to liver transplantation or native liver

  5. Clinical value of acoustic radiation force impulse in quantitative prediction of the degree of esophageal varices in patients with liver cirrhosis

    Directory of Open Access Journals (Sweden)

    CHEN Min

    2018-01-01

    Full Text Available Objective To investigate the clinical value of acoustic radiation force impulse (ARFI in quantitative prediction of the degree of esophageal varices in patients with cirrhotic portal hypertension. Methods A total of 116 patients with liver cirrhosis who were admitted to 302 Hospital of PLA from October 2014 to February 2016 were enrolled. ARFI was used to measure real-time liver and spleen stiffness for all patients. With the degree of esophageal varices determined by gastroscopy as the gold standard for diagnosis, these patients were divided into non-varices group (EV0, 16 patients, mild varices group (EV1, 39 patients, moderate varices group (EV2, 26 patients, and severe varices group (EV3, 35 patients. The receiver operating characteristic (ROC curve was used to analyze the clinical value of liver/spleen ARFI in predicting the degree of esophageal varices. An analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the least significant difference Mann-Whitney U test was used for further comparison between any two groups; the chi-square test was used for comparison of categorical data between groups. The Spearman correlation analysis was used to investigate the correlation between the stiffness measured by ARFI and the degree of esophageal varices. Results The ARFI value of the spleen was 2.54±0.34 m/s for EV0 patients, 3.05±0.34 m/s for EV1 patients, 3.48±0.50 m/s for EV2 patients, and 3.69±0.33 m/s for EV3 patients (χ2=60.121,P<0.001. The ARFI value of the spleen was positively correlated with the grade of esophageal varices (r=0.713, P<0.001. The areas under the ROC curve for the ARFI value of the spleen in the diagnosis of ≥EV1, ≥EV2, or EV3 esophageal varices were 0.93, 0.88, and 0.83, respectively. There was no significant difference in the ARFI value of the liver between groups (P=0.085, and the ARFI value of the liver was not correlated with the degree of

  6. Evaluation of clinial usefulness of 11C-methionine positron emission tomography (11C-MET-PET) as a tool for liver functional imaging

    International Nuclear Information System (INIS)

    Enomoto, Kazuo; Matsui, Yoshifumi; Okazumi, Shinichi

    1994-01-01

    We studied 11 C-MET-PET in 17 clinical cases, 10 patients with obstructive jaundice and 7 normal volunteers, and analyzed its efficacy for the evaluation of hepatic functional reserve in major hepatectomy candidates. Differential absorption ratio (DAR) of 11 C was compared to the hepatic protein synthesis rate (HPS), which is measured as the incorporation rate of 3 H-labeled leucine in protein fraction, using needle biopsied liver specimen obtained from each hepatic segment. In the cases of normal liver function, DAR was well correlated with HPS. Also in jaundice cases with two exceptions, low HPS segment was demonstrated as low DAR segment. Consequently, MET-PET images could clearly provide functional liver imaging. After injection of 11 C-MET, the increase in rate of radioactivity of 11 C in plasma protein fraction was higher in jaundice cases than in normal volunteers, which is in accord with the results of our former study that cholestatic liver has accelerated protein synthesis rate. In summary, since 11 C-MET-PET could demonstrate liver functional imaging, it might be a possible tool for liver function assessment in major hepatectomy candidates. (author)

  7. [Study on liver targeted drug delivery system of the effective anticancer component from Bolbstemma paniculatum].

    Science.gov (United States)

    Sun, Yi-Yi; Ll, Tong-Hui; Tang, Chen-Kang; Zhu, Zi-Ping; Chi, Qun; Hou, Shi-Xiang

    2005-06-01

    To study the liver targeted drug delivery system of TBMS--the effective anticancer component from Bolbstemma paniculatum, and to discuss the system's function of decreasing toxicity. BCA was used as carrier material. The preparation through overall feedback dynamic techniques. The properties of preparation and toxicology were also technology of nanoparticles was optimized studied. Thenanoparticles' targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system. D50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t 1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much lower than injection. The TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.

  8. Nonparametric functional mapping of quantitative trait loci.

    Science.gov (United States)

    Yang, Jie; Wu, Rongling; Casella, George

    2009-03-01

    Functional mapping is a useful tool for mapping quantitative trait loci (QTL) that control dynamic traits. It incorporates mathematical aspects of biological processes into the mixture model-based likelihood setting for QTL mapping, thus increasing the power of QTL detection and the precision of parameter estimation. However, in many situations there is no obvious functional form and, in such cases, this strategy will not be optimal. Here we propose to use nonparametric function estimation, typically implemented with B-splines, to estimate the underlying functional form of phenotypic trajectories, and then construct a nonparametric test to find evidence of existing QTL. Using the representation of a nonparametric regression as a mixed model, the final test statistic is a likelihood ratio test. We consider two types of genetic maps: dense maps and general maps, and the power of nonparametric functional mapping is investigated through simulation studies and demonstrated by examples.

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

    Science.gov (United States)

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

    2014-04-01

    Liver transplantation is the ultimate treatment for severe hepatic failure to date. However, the limited supply of donor organs has severely hampered this treatment. So far, great potentials of using mesenchymal stem cells (MSCs) to replenish the hepatic cell population have been shown; nevertheless, there still is a lack of an optimal three-dimensional scaffold for generation of well-transplantable hepatic tissues. In this study, we utilized a cryo-chemical decellularization method which combines physical and chemical approach to generate acellular liver scaffolds (ALS) from the whole liver. The produced ALS provides a biomimetic three-dimensional environment to support hepatic differentiation of MSCs, evidenced by expression of hepatic-associated genes and marker protein, glycogen storage, albumin secretion, and urea production. It is also found that hepatic differentiation of MSCs within the ALS is much more efficient than two-dimensional culture in vitro. Importantly, the hepatic-like tissues (HLT) generated by repopulating ALS with MSCs are able to act as functional grafts and rescue lethal hepatic failure after transplantation in vivo. In summary, the cryo-chemical method used in this study is suitable for decellularization of liver and create acellular scaffolds that can support hepatic differentiation of MSCs and be used to fabricate functional tissue-engineered liver constructs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Adipokines in Liver Cirrhosis.

    Science.gov (United States)

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

    2017-06-29

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

  11. 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

  12. Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats

    NARCIS (Netherlands)

    Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P. J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a

  13. Metabolic liver function measured in vivo by dynamic (18)F-FDGal PET/CT without arterial blood sampling.

    Science.gov (United States)

    Horsager, Jacob; Munk, Ole Lajord; Sørensen, Michael

    2015-01-01

    Metabolic liver function can be measured by dynamic PET/CT with the radio-labelled galactose-analogue 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) in terms of hepatic systemic clearance of (18)F-FDGal (K, ml blood/ml liver tissue/min). The method requires arterial blood sampling from a radial artery (arterial input function), and the aim of this study was to develop a method for extracting an image-derived, non-invasive input function from a volume of interest (VOI). Dynamic (18)F-FDGal PET/CT data from 16 subjects without liver disease (healthy subjects) and 16 patients with liver cirrhosis were included in the study. Five different input VOIs were tested: four in the abdominal aorta and one in the left ventricle of the heart. Arterial input function from manual blood sampling was available for all subjects. K*-values were calculated using time-activity curves (TACs) from each VOI as input and compared to the K-value calculated using arterial blood samples as input. Each input VOI was tested on PET data reconstructed with and without resolution modelling. All five image-derived input VOIs yielded K*-values that correlated significantly with K calculated using arterial blood samples. Furthermore, TACs from two different VOIs yielded K*-values that did not statistically deviate from K calculated using arterial blood samples. A semicircle drawn in the posterior part of the abdominal aorta was the only VOI that was successful for both healthy subjects and patients as well as for PET data reconstructed with and without resolution modelling. Metabolic liver function using (18)F-FDGal PET/CT can be measured without arterial blood samples by using input data from a semicircle VOI drawn in the posterior part of the abdominal aorta.

  14. [Liver diseases in the elderly].

    Science.gov (United States)

    Bruguera, Miguel

    2014-11-01

    Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  15. New therapeutic strategies for canine liver disease; Growth factors and liver progenitor cells

    NARCIS (Netherlands)

    Arends, B.

    2008-01-01

    The liver has the unique capacity to regulate its mass after loss of functional liver cells due to liver disease, injury, and/or toxicity. Unfortunately, in the course of chronic liver disease this meticulously regulated regeneration process is imbalanced resulting in a decreased regenerative

  16. Quantitative Characterization of Major Hepatic UDP-Glucuronosyltransferase Enzymes in Human Liver Microsomes: Comparison of Two Proteomic Methods and Correlation with Catalytic Activity.

    Science.gov (United States)

    Achour, Brahim; Dantonio, Alyssa; Niosi, Mark; Novak, Jonathan J; Fallon, John K; Barber, Jill; Smith, Philip C; Rostami-Hodjegan, Amin; Goosen, Theunis C

    2017-10-01

    Quantitative characterization of UDP-glucuronosyltransferase (UGT) enzymes is valuable in glucuronidation reaction phenotyping, predicting metabolic clearance and drug-drug interactions using extrapolation exercises based on pharmacokinetic modeling. Different quantitative proteomic workflows have been employed to quantify UGT enzymes in various systems, with reports indicating large variability in expression, which cannot be explained by interindividual variability alone. To evaluate the effect of methodological differences on end-point UGT abundance quantification, eight UGT enzymes were quantified in 24 matched liver microsomal samples by two laboratories using stable isotope-labeled (SIL) peptides or quantitative concatemer (QconCAT) standard, and measurements were assessed against catalytic activity in seven enzymes ( n = 59). There was little agreement between individual abundance levels reported by the two methods; only UGT1A1 showed strong correlation [Spearman rank order correlation (Rs) = 0.73, P quantitative proteomic data should be validated against catalytic activity whenever possible. In addition, metabolic reaction phenotyping exercises should consider spurious abundance-activity correlations to avoid misleading conclusions. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Martin Sauer

    2017-01-01

    Full Text Available 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.

  19. Liver failure in total artificial heart therapy.

    Science.gov (United States)

    Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero; Spiliopoulos, Sotirios

    2016-07-01

    Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.

  20. Liver histology and follow up of 68 patients with ulcerative colitis and normal liver function tests.

    OpenAIRE

    Broomé, U; Glaumann, H; Hultcrantz, R

    1990-01-01

    Hepatobiliary disorders are well known complications in patients with ulcerative colitis but it is not possible to predict those patients with ulcerative colitis who will eventually develop liver disease. In this study, liver biopsies from 74 patients with ulcerative colitis have been reevaluated. None of the patients showed clinical or biochemical signs of liver disease at the time of biopsy. Thirty seven (50%) had a completely normal liver biopsy. The others showed minimal portal inflammati...

  1. Tc-99 m-GSA liver scintigraphy in alcoholic liver cirrhosis

    International Nuclear Information System (INIS)

    Itano, Satoshi; Harada, Masaru; Nagamatsu, Hiroaki

    2003-01-01

    We compared 15 alcoholic liver cirrhosis patients with 10 viral liver cirrhosis patients using technetium-99 m-galactosyl human serum albumin (Tc-99 m-GSA) liver scintigraphy and could clinically reveal the disorder of metabolism of asialoglycoprotein in alcoholic liver cirrhosis. Receptor index (LHL 15 = liver count divided by the sum of liver and heart counts at 15 minutes) was significantly (p <0.01) lower in patients with alcoholic cirrhosis (median: 0.821), compared with patients with viral cirrhosis (0.915). Grading score, which was an index showed by the difference in the isotope uptake patterns between liver and heart, was significantly (p <0.01) worse in patients with alcoholic cirrhosis, compared with patients with viral cirrhosis. These results suggested that alcoholic liver cirrhosis had a specific disorder of a metabolic function for asialoglycoprotein. (author)

  2. 肾移植术后的肝功能异常%The abnormality of liver function following renal transplantation

    Institute of Scientific and Technical Information of China (English)

    林荣禧; 欧良明; 陈子宣; 洪佳平; 林文洪; 吴卫真; 杨顺良

    1998-01-01

    为探讨肝功能异常对肾移植患者存活的影响,对48例肾移植前后发生肝功能异常的病例资料进行分析.术前乙型肝炎病毒表面抗原(HBsAg)阳性,伴或不伴丙氨酸转氨酶(ALT)升高者32例,术后肝功能正常者18例,肝功能异常但经治疗预后好者6例,预后差者8例;术前仅ALT升高者9例,术后肝功能正常者3例,肝功能异常但经治疗预后好者5例,预后差者1例;术前肝功能正常,术后发生肝功能异常者28例,大部分系药物的肝毒性所致,经治疗预后好者14例,预后差者14例.认为HBsAg阳性和ALT异常并非肾移植术的禁忌证;对药物的肝毒性应引起足够的重视.%In ordertoinvestigate the effects of the abnormality of liver function on the survival of the patients undergoing renal transplantation,the data of 48 patients having liver function abnormality pre-and post-transplantation of kidney were analyzed. After operation, 32 cases showed positive hepatitis B surface antigen(HBsAg)with or without an increase of ALT.After operation,liver function was normal in 18 cases.6 cases revealed abnormal liver function with favourable prognosis following treatment,while other 8 cases with unfavourable prognosis.Nine cases only showed an increase of ALT before operation.After operation.1iver function was normal in 3 cases;liver function was abnormal with good prognosis in 5,bad prognosis in one.28cases of preoperative normal liver function showed postoperative liver function abnormality mostly induced by the hepatoxication of the drugs.Of them,14 cases obtained good prognosis and 14 badprognosis after the treatment.It was suggested that positive HBsAg and ALT abnormality was not the controindications for renal transplantation and full attention should paytothe drug's hepatoxication.

  3. WE-EF-210-05: Diagnosis and Quantification of Liver Steatosis with Quantitative Ultrasound Backscatter Technique

    Energy Technology Data Exchange (ETDEWEB)

    Andre, M [VA Medical Center, Encinitas, CA (United States); University of California, San Diego, San Diego, CA (United States); Heba, E; Lin, S; Wolfson, T; Ang, B; Gamst, A; Sirlin, C; Loomba, R [University of California, San Diego, San Diego, CA (United States); Han, A; Erdman, J; O’Brien, W [University of Illinois, Urbana, IL (United States)

    2015-06-15

    Purpose: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States, affects 30% of adult Americans and may progress to more serious diseases. Liver biopsy is the standard method for diagnosing NAFLD. MRI can accurately diagnose and quantify hepatic steatosis but is expensive. Sonography with qualitative interpretation by radiologists is lower cost, more accessible but less sensitive for detection. The objective of this study, using MRI proton density fat fraction (PDFF) as reference, is to assess the accuracy for diagnosing and quantifying steatosis with two quantitative US parameters-- backscatter coefficient (BSC) and attenuation coefficient (AC)--derived from RF signals using the calibration phantom technique. Methods: We performed a prospective, cross-sectional analysis of a cohort of adults (n=204) with NAFLD (MRI-PDFF≥5%) and without NAFLD (controls). Subjects underwent MRI-PDFF and BSC and AC US analyses of the liver on the same day. Patients were randomly assigned to training (n=102, mean age 51±17 years, mean body mass index 31±7 kg/m{sup 2}) and validation (n=102, mean age 49±17 years, body mass index 30±6 kg/m{sup 2}) groups; 69% of patients in each group had NAFLD. Results: BSC provided AUC 0.98 (95% CI 0.95–1.00, p<0.0001) for diagnosis of NAFLD; the optimal BSC cut-off provided sensitivity, specificity, positive and negative predictive values (PPV, NPV) of 87%, 91%, 95%, and 76%, respectively. AC provided AUC 0.89 (95% CI 0.81–0.96, p<0.0001) for diagnosis of steatosis; the optimal AC cut-off provided sensitivity, specificity, PPV, NPV of 80%, 84%, 92%, and 66%, respectively. BSC and AC both correlated significantly with MRI-PDFF (P<0.0001). Conclusion: QUS BSC and AC can accurately diagnose and quantify hepatic steatosis, using MRI-PDFF as reference. With further validation, QUS may emerge as an inexpensive, widely available tool for NAFLD assessment. General support: NIH R01 CA111289, K

  4. 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.

  5. Quantitation of left ventricular dimensions and function by digital video subtraction angiography

    International Nuclear Information System (INIS)

    Higgins, C.B.; Norris, S.L.; Gerber, K.H.; Slutsky, R.A.; Ashburn, W.L.; Baily, N.

    1982-01-01

    Digital video subtraction angiography (DVSA) after central intravenous administration of contrast media was used in experimental animals and in patients with suspected coronary artery disease to quantitate left ventricular dimensions and regional and global contractile function. In animals, measurements of left ventricular (LV) volumes, wall thickness, ejection fraction, segmental contraction, and cardiac output correlated closely with sonocardiometry or thermodilution measurements. In patients, volumes and ejection fractions calculated from mask mode digital images correlated closely with direct left ventriculography. Global and segmental contractile function was displayed in patients by ejection shell images, stroke volume images, and time interval difference images. Central cardiovascular function was also quantitated by measurement of pulmonary transit time and calculation of pulmonary blood volume from digital fluoroscopic images. DVSA was shown to be useful and accurate in the quantitation of central cardiovascular physiology

  6. 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.

  7. The preliminary study of quantitative evaluation of salivary gland function by dynamic imaging

    International Nuclear Information System (INIS)

    Han Chunqi; Li Yaming; Li Deshun; Wang Guoli; Bai Jingming; Luo Xigui

    1999-01-01

    Objective: To evaluate the function of salivary gland by quantitative dynamic imaging. Methods: In thirty normals and twenty patients with Sjogren's syndrome (SS), absorption rate (15 min) and excretion rate (30 min) were calculated using two quantitative software. Results: Parotid and submandibular absorption rates in normal subjects were (0.26 +- 0.09)% and (0.15 +- 0.08)%, respectively; those of SS patients were (0.07 +- 0.03)% and (0.05 +- 0.04)%, t = 5.3 and 4.1, both were P < 0.01. There were markedly relativity between the two groups (r = 0.85). Conclusions: Quantitative methods of analyzing salivary function is simple, sensitive, practical reliable for evaluating salivary function and also has important clinical significance

  8. Suppression of Human Liver Cancer Cell Migration and Invasion via the GABAA Receptor

    International Nuclear Information System (INIS)

    Chen, Zhi-ao; Bao, Mei-yan; Xu, Yong-fen; Zha, Ruo-peng; Shi, Hai-bing; Chen, Tao-yang; He, Xiang-huo

    2012-01-01

    To investigate the roles of the γ-aminobutyric acid (GABA) in the metastasis of hepatocellular carcinoma (HCC) and to explore the potential of a novel therapeutic approach for the treatment of HCC. The expression levels of GABA receptor subunit genes in various HCC cell lines and patients‘ tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Transwell cell migration and invasion assays were carried out for functional analysis. The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining. And the effects of GABA on HCC metastasis in nude mice were evaluated using an in vivo orthotopic model of liver cancer. The mRNA level of GABA receptor subunits varied between the primary hepatocellular carcinoma tissue and the adjacent non-tumor liver tissue. GABA inhibited human liver cancer cell migration and invasion via the ionotropic GABA A receptor as a result of the induction of liver cancer cell cytoskeletal reorganization. Pretreatment with GABA also significantly reduced intrahepatic liver metastasis and primary tumor formation in vivo. These findings introduce a potential and novel therapeutic approach for the treatment of cancer patients based on the modulation of the GABAergic system

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

    Science.gov (United States)

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

    2013-09-01

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

  10. Regional metabolic liver function measured in patients with cirrhosis by 2-[¹⁸F]fluoro-2-deoxy-D-galactose PET/CT.

    Science.gov (United States)

    Sørensen, Michael; Mikkelsen, Kasper S; Frisch, Kim; Villadsen, Gerda E; Keiding, Susanne

    2013-06-01

    There is a clinical need for methods that can quantify regional hepatic function non-invasively in patients with cirrhosis. Here we validate the use of 2-[(18)F]fluoro-2-deoxy-d-galactose (FDGal) PET/CT for measuring regional metabolic function to this purpose, and apply the method to test the hypothesis of increased intrahepatic metabolic heterogeneity in cirrhosis. Nine cirrhotic patients underwent dynamic liver FDGal PET/CT with blood samples from a radial artery and a liver vein. Hepatic blood flow was measured by indocyanine green infusion/Fick's principle. From blood measurements, hepatic systemic clearance (Ksyst, Lblood/min) and hepatic intrinsic clearance (Vmax/Km, Lblood/min) of FDGal were calculated. From PET data, hepatic systemic clearance of FDGal in liver parenchyma (Kmet, mL blood/mL liver tissue/min) was calculated. Intrahepatic metabolic heterogeneity was evaluated in terms of coefficient-of-variation (CoV, %) using parametric images of Kmet. Mean approximation of Ksyst to Vmax/Km was 86% which validates the use of FDGal as PET tracer of hepatic metabolic function. Mean Kmet was 0.157 mL blood/mL liver tissue/min, which was lower than 0.274 mL blood/mL liver tissue/min, previously found in healthy subjects (pdynamic FDGal PET/CT with arterial sampling provides an accurate measure of regional hepatic metabolic function in patients with cirrhosis. This is likely to have clinical implications for the assessment of patients with liver disease as well as treatment planning and monitoring. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  11. Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model.

    Science.gov (United States)

    Rigo, Federica; De Stefano, Nicola; Navarro-Tableros, Victor; David, Ezio; Rizza, Giorgia; Catalano, Giorgia; Gilbo, Nicholas; Maione, Francesca; Gonella, Federica; Roggio, Dorotea; Martini, Silvia; Patrono, Damiano; Salizzoni, Mauro; Camussi, Giovanni; Romagnoli, Renato

    2018-05-01

    The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution. Livers were perfused for 4 hours without (control group, n = 10) or with HLSC-EV (treated group, n = 9). Bile production was quantified; perfusate samples were collected hourly to measure metabolic (pH, pO2, pCO2) and cytolysis parameters (AST, alanine aminotransferase, lactate dehydrogenase). At the end of perfusion, we assessed HLSC-EV engraftment by immunofluorescence, tissue injury by histology, apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, tissue hypoxia-inducible factor 1-α, and transforming growth factor-beta 1 RNA expression by quantitative reverse transcription-polymerase chain reaction. During hypoxic NMP, livers were able to maintain homeostasis and produce bile. In the treated group, AST (P = 0.018) and lactate dehydrogenase (P = 0.032) levels were significantly lower than those of the control group at 3 hours of perfusion, and AST levels persisted lower at 4 hours (P = 0.003). By the end of NMP, HLSC-EV had been uptaken by hepatocytes, and EV treatment significantly reduced histological damage (P = 0.030), apoptosis (P = 0.049), and RNA overexpression of hypoxia-inducible factor 1-α (P < 0.0001) and transforming growth factor-beta 1 (P = 0.014). HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-10-15

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

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

    Science.gov (United States)

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

    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 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. PMID:22073149

  15. Hepatic and renal extraction of circulating type I procollagen aminopropeptide in patients with normal liver function and in patients with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Schytte, S; Hansen, M; Møller, S

    1999-01-01

    40-65, palcoholic cirrhosis. Size-chromatography revealed no significant change in the ratio of the high and low molecular forms of PINP following extraction in liver and kidney......The circulating level and splanchnic and renal extraction of serum type I procollagen aminoterminal propeptide (PINP) was studied in 20 patients with normal liver function and in 15 patients with alcoholic liver cirrhosis. In patients with alcoholic cirrhosis, the concentration of PINP....... It is concluded that circulating PINP is extracted in the normal liver and kidney, and that the serum concentration of PINP is significantly higher in patients with alcoholic cirrhosis than in patients with normal liver function. Both the hepatic and the renal clearance of PINP are seriously impaired...

  16. 25 Ways to Love Your Liver

    Science.gov (United States)

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

  17. 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

  18. Long-Term and Short-Term Effects of Hemodialysis on Liver Function Evaluated Using the Galactose Single-Point Test

    Directory of Open Access Journals (Sweden)

    Yi-Chou Hou

    2014-01-01

    Full Text Available Aim. The galactose single-point (GSP test assesses functioning liver mass by measuring the galactose concentration in the blood 1 hour after its administration. The purpose of this study was to investigate the impact of hemodialysis (HD on short-term and long-term liver function by use of GSP test. Methods. Seventy-four patients on maintenance HD (46 males and 28 females, 60.38 ± 11.86 years with a mean time on HD of 60.77 ± 48.31 months were studied. The GSP values were compared in two groups: (1 before and after single session HD, and (2 after one year of maintenance HD. Results. Among the 74 HD patient, only the post-HD Cr levels and years on dialysis were significantly correlated with GSP values (r=0.280, P<0.05 and r=-0.240, P<0.05, resp.. 14 of 74 patients were selected for GSP evaluation before and after a single HD session, and the hepatic clearance of galactose was similar (pre-HD 410 ± 254 g/mL, post-HD 439 ± 298 g/mL, P=0.49. GSP values decreased from 420.20 ± 175.26 g/mL to 383.40 ± 153.97 g/mL after 1 year maintenance HD in other 15 patients (mean difference: 19.00 ± 37.66 g/mL, P<0.05. Conclusions. Patients on maintenance HD for several years may experience improvement of their liver function. However, a single HD session does not affect liver function significantly as assessed by the GSP test. Since the metabolism of galactose is dependent on liver blood flow and hepatic functional mass, further studies are needed.

  19. 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

  20. Preoperative detection of colorectal liver metastases in fatty liver: MDCT or MRI?

    International Nuclear Information System (INIS)

    Kulemann, Vanessa; Schima, Wolfgang; Tamandl, Dietmar; Kaczirek, Klaus; Gruenberger, Thomas; Wrba, Friedrich; Weber, Michael; Ba-Ssalamah, Ahmed

    2011-01-01

    Objective: To compare the diagnostic value of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the preoperative detection of colorectal liver metastases in diffuse fatty infiltration of the liver, associated with neoadjuvant chemotherapy. Materials and methods: Twenty preoperative tri-phasic MDCT (4-64-row, Siemens) and dynamic contrast-enhanced MRI (1.5 T or 3.0 T, Siemens) examinations of patients with colorectal cancer and liver metastases in diffuse steatosis were retrospectively evaluated. All patients underwent surgical resection for liver metastases (time interval 1-60 days). The amount of fatty infiltration of the liver was determined histopathologically by semi-quantitative percent-wise estimation and ranged from 25 to 75%. Results: Overall, 51 metastases were found by histopathology of the resected liver segments/lobes. The size of the metastases ranged from 0.4 to 13 cm, with 18 (35%) being up to 1 cm in diameter. In the overall rating, MDCT detected 33/51 lesions (65%), and MRI 45/51 (88%). For lesions up to 1 cm, MDCT detected only 2/18 (11%) and MRI 12/18 (66%). One false positive lesion was detected by MDCT. Statistical analysis showed that MRI is markedly superior to MDCT, with a statistically significant difference (p 1 cm. Conclusion: For the detection of colorectal liver metastases after neoadjuvant chemotherapy and consecutive diffuse fatty infiltration of the liver, MRI is superior to MDCT, especially for the detection of small lesions.

  1. Liver function assessment using 99mTc-GSA single-photon emission computed tomography (SPECT)/CT fusion imaging in hilar bile duct cancer: A retrospective study.

    Science.gov (United States)

    Sumiyoshi, Tatsuaki; Shima, Yasuo; Okabayashi, Takehiro; Kozuki, Akihito; Hata, Yasuhiro; Noda, Yoshihiro; Kouno, Michihiko; Miyagawa, Kazuyuki; Tokorodani, Ryotaro; Saisaka, Yuichi; Tokumaru, Teppei; Nakamura, Toshio; Morita, Sojiro

    2016-07-01

    The objective of this study was to determine the utility of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin ((99m)Tc-GSA) single-photon emission computed tomography (SPECT)/CT fusion imaging for posthepatectomy remnant liver function assessment in hilar bile duct cancer patients. Thirty hilar bile duct cancer patients who underwent major hepatectomy with extrahepatic bile duct resection were retrospectively analyzed. Indocyanine green plasma clearance rate (KICG) value and estimated KICG by (99m)Tc-GSA scintigraphy (KGSA) and volumetric and functional rates of future remnant liver by (99m)Tc-GSA SPECT/CT fusion imaging were used to evaluate preoperative whole liver function and posthepatectomy remnant liver function, respectively. Remnant (rem) KICG (= KICG × volumetric rate) and remKGSA (= KGSA × functional rate) were used to predict future remnant liver function; major hepatectomy was considered unsafe for values liver were significantly higher than volumetric rates (median: 0.54 vs 0.46; P liver failure and mortality did not occur in the patients for whom hepatectomy was considered unsafe based on remKICG. remKGSA showed a stronger correlation with postoperative prothrombin time activity than remKICG. (99m)Tc-GSA SPECT/CT fusion imaging enables accurate assessment of future remnant liver function and suitability for hepatectomy in hilar bile duct cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. A double isotope technique for the detection of diffuse liver disease

    International Nuclear Information System (INIS)

    McCready, V.R.; Seelentag, W.W.; Lillicrap, S.C.; Royal Mardsen Hospital, Sutton, Surrey

    1978-01-01

    Radioisotope, ultrasound and CT X-ray scanning are all moderately successful in diagnosing focal abnormalities of the liver. However, the diagnosis of diffuse disease remains difficult or impossible in spite of recent advances in imaging and biochemical techniques. This paper investigates the possibility of using two radioactive compounds which detect different aspects of liver function to determine the presence of diffuse disease. Normal patients and patients with obvious metastases were studied after an injection of a mixture of Tc 99m sulphur colloid and Gallium 67 citrate. Measurements of the absolute and relative uptake in the liver were made within one hour and at 48 hours using a quantitative dual probe system and a collimated dual detector system. The Tc 99m:Ga-67 ratio was calculated. The ratio for abnormals ranged from 1.5-3.9 mean=2.5 and the normals ranged from 3.67-6.25 (mean=4.5). The technique shows promise in the detection of diffuse disease. (author)

  3. Generalized PSF modeling for optimized quantitation in PET imaging.

    Science.gov (United States)

    Ashrafinia, Saeed; Mohy-Ud-Din, Hassan; Karakatsanis, Nicolas A; Jha, Abhinav K; Casey, Michael E; Kadrmas, Dan J; Rahmim, Arman

    2017-06-21

    Point-spread function (PSF) modeling offers the ability to account for resolution degrading phenomena within the PET image generation framework. PSF modeling improves resolution and enhances contrast, but at the same time significantly alters image noise properties and induces edge overshoot effect. Thus, studying the effect of PSF modeling on quantitation task performance can be very important. Frameworks explored in the past involved a dichotomy of PSF versus no-PSF modeling. By contrast, the present work focuses on quantitative performance evaluation of standard uptake value (SUV) PET images, while incorporating a wide spectrum of PSF models, including those that under- and over-estimate the true PSF, for the potential of enhanced quantitation of SUVs. The developed framework first analytically models the true PSF, considering a range of resolution degradation phenomena (including photon non-collinearity, inter-crystal penetration and scattering) as present in data acquisitions with modern commercial PET systems. In the context of oncologic liver FDG PET imaging, we generated 200 noisy datasets per image-set (with clinically realistic noise levels) using an XCAT anthropomorphic phantom with liver tumours of varying sizes. These were subsequently reconstructed using the OS-EM algorithm with varying PSF modelled kernels. We focused on quantitation of both SUV mean and SUV max , including assessment of contrast recovery coefficients, as well as noise-bias characteristics (including both image roughness and coefficient of-variability), for different tumours/iterations/PSF kernels. It was observed that overestimated PSF yielded more accurate contrast recovery for a range of tumours, and typically improved quantitative performance. For a clinically reasonable number of iterations, edge enhancement due to PSF modeling (especially due to over-estimated PSF) was in fact seen to lower SUV mean bias in small tumours. Overall, the results indicate that exactly matched PSF

  4. Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model

    Energy Technology Data Exchange (ETDEWEB)

    Stefano, J.T.; Pereira, I.V.A.; Torres, M.M.; Bida, P.M. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Coelho, A.M.M. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Xerfan, M.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Cogliati, B. [Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Barbeiro, D.F. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mazo, D.F.C. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Kubrusly, M.S.; D' Albuquerque, L.A.C. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Souza, H.P. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carrilho, F.J.; Oliveira, C.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-02-24

    Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg{sup -1}·day{sup -1} by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.

  5. Primary non-function is frequently associated with fatty liver allografts and high mortality after re-transplantation.

    Science.gov (United States)

    Kulik, Ulf; Lehner, Frank; Klempnauer, Jürgen; Borlak, Jürgen

    2017-08-01

    The shortage of liver donations demands the use of suboptimal grafts with steatosis being a frequent finding. Although ≤30% macrovesicular steatosis is considered to be safe the risk for primary non-function (PNF) and outcome after re-transplantation (re-OLT) is unknown. Among 1205 orthotopic liver transplantations performed at our institution the frequency, survival and reason of re-OLT were evaluated. PNF (group A) cases and those with initial transplant function but subsequent need for re-OLT (group B) were analysed. Histopathology and clinical judgement determined the cause of PNF and included an assessment of hepatic steatosis. Additionally, survival of fatty liver allografts (group C) not requiring re-OLT was considered in Kaplan-Meier and multivariate regression analysis. A total of 77 high urgency re-OLTs were identified and included 39 PNF cases. Nearly 70% of PNF cases were due to primary fatty liver allografts. The 3-month in-hospital mortality for PNF cases after re-OLT was 46% and the mean survival after re-OLT was 0.5 years as compared to 5.2 and 5.1 years for group B, C, respectively, (Phepatic steatosis was associated with an inferior survival (HR 4.272, P=.002). The MELD score, donor BMI, age, cold ischaemic time, ICU stay, serum sodium and transaminases did not influence overall survival. Our study highlights fatty liver allografts to be a major cause for PNF with excessive mortality after re-transplantation. The findings demand the development of new methods to predict risk for PNF of fatty liver allografts. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Hyperintensity of basal ganglia on T1-weighted images in patients with liver cirrhosis. Correlation with hepatic encephalopathy and liver function

    International Nuclear Information System (INIS)

    Maeda, Hiroko; Kita, Keisuke; Mizobata, Toshiharu; Kimura, Masashi; Sonomura, Tetsuo; Kishi, Kazushi; Tanaka, Kayo; Sato, Morio; Yamada, Ryosaku

    1995-01-01

    Brain MR imaging was performed in 38 liver cirrhosis (LC) patients and 9 normal volunteers. On T 1 -weighted images, the signal intensity of globus pallidus (S1) and frontal white matter (S2) was measured and S1/S2 ratio was explored. We examined the relationship between S1/S2 ratio and liver function parameters. High signal intensity in bilateral globus pallidus was noted on T 1 W1 in 28 of 38 LC patients. The S1/S2 ratio of 1.186±0.097 in the 38 LC patients was significantly higher than 0.987±0.062 in the 9 normal volunteers (p 2 -weighted images showed no abnormal intensity. Compared with the LC patients with hepatic encephalopathy (HE) (n=7) and without HE (n=31), the former S1/S2 ratio (1.239±0.057) was significantly higher than the latter (1.174±0.097) (p 15 (r=0.501, p 1 -WI and the degree of liver dysfunction. (author)

  7. Dynamic PET of human liver inflammation: impact of kinetic modeling with optimization-derived dual-blood input function.

    Science.gov (United States)

    Wang, Guobao; Corwin, Michael T; Olson, Kristin A; Badawi, Ramsey D; Sarkar, Souvik

    2018-05-30

    The hallmark of nonalcoholic steatohepatitis is hepatocellular inflammation and injury in the setting of hepatic steatosis. Recent work has indicated that dynamic 18F-FDG PET with kinetic modeling has the potential to assess hepatic inflammation noninvasively, while static FDG-PET did not show a promise. Because the liver has dual blood supplies, kinetic modeling of dynamic liver PET data is challenging in human studies. The objective of this study is to evaluate and identify a dual-input kinetic modeling approach for dynamic FDG-PET of human liver inflammation. Fourteen human patients with nonalcoholic fatty liver disease were included in the study. Each patient underwent one-hour dynamic FDG-PET/CT scan and had liver biopsy within six weeks. Three models were tested for kinetic analysis: traditional two-tissue compartmental model with an image-derived single-blood input function (SBIF), model with population-based dual-blood input function (DBIF), and modified model with optimization-derived DBIF through a joint estimation framework. The three models were compared using Akaike information criterion (AIC), F test and histopathologic inflammation reference. The results showed that the optimization-derived DBIF model improved the fitting of liver time activity curves and achieved lower AIC values and higher F values than the SBIF and population-based DBIF models in all patients. The optimization-derived model significantly increased FDG K1 estimates by 101% and 27% as compared with traditional SBIF and population-based DBIF. K1 by the optimization-derived model was significantly associated with histopathologic grades of liver inflammation while the other two models did not provide a statistical significance. In conclusion, modeling of DBIF is critical for kinetic analysis of dynamic liver FDG-PET data in human studies. The optimization-derived DBIF model is more appropriate than SBIF and population-based DBIF for dynamic FDG-PET of liver inflammation. © 2018

  8. The heart and the liver

    DEFF Research Database (Denmark)

    Møller, Søren; Dümcke, Christine Winkler; Krag, Aleksander

    2009-01-01

    Cardiac failure affects the liver and liver dysfunction affects the heart. Chronic and acute heart failure can lead to cardiac cirrhosis and cardiogenic ischemic hepatitis. These conditions may impair liver function and treatment should be directed towards the primary heart disease and seek...... against the heart failure. Transjugular intrahepatic portosystemic shunt insertion and liver transplantation affect cardiac function in portal hypertensive patients and cause stress to the cirrhotic heart, with a risk of perioperative heart failure. The risk and prevalence of coronary artery disease...

  9. Role of functional imaging in treatment plan optimization of stereotactic body radiation therapy for liver cancer.

    Science.gov (United States)

    De Bari, Berardino; Jumeau, Raphael; Deantonio, Letizia; Adib, Salim; Godin, Sarah; Zeverino, Michele; Moeckli, Raphael; Bourhis, Jean; Prior, John O; Ozsahin, Mahmut

    2016-10-13

    We report the first known instance of the clinical use of 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) for the optimization of radiotherapy treatment planning and for the follow-up of acute toxicity in a patient undergoing stereotactic body radiation therapy for hepatocellular carcinoma. In our experience, HBS allowed the identification and the sparing of more functioning liver areas, thus potentially reducing the risk of radiation-induced liver toxicity.

  10. 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.

  11. Quantification of human hepatic binding protein (HBP) via 99mTc-galactosyl-neoglycoalbumin (NGA) liver scintigraphy

    International Nuclear Information System (INIS)

    Virgolini, I.; Hoebart, J.; Bergmann, H.; Sinzinger, H.; Mueller, C.; Angelberger, P.

    1991-01-01

    99m Tc-galactosyl-neoglycoalbumin ( 99m Tc-NGA) was synthesized by covalent coupling of 2-imino-2-methoxyethyl-1-thio-β-D-galactopyranoside to the primary amino groups of human serum albumin. Injections of 99m Tc-NGA (150 MBq; 3.5 mg (=50 nmol)/ml) demonstrated the liver to be the exclusive site of tracer-uptake. Simulation of 99m Tc-NGA-kinetics allowed quantification of binding to the hepatic binding protein (HBP). Using this model we studied 250 patients with various liver disease. In alcoholic liver cirrhosis such patients with Child B and Child C stage cirrhosis had a lower HBP-concentration in the liver compared to control individuals (0.85-1.2 μmol/l). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP-concentration (0.20-0.45 μmol/l) than Child A patients (0.60-0.85 μmol/l; p 99m Tc-galactosyl-neoglycoalbumin (NGA) scanning of the liver during the course of the disease. Return of liver function tests to normal values was associated with an increased hepatic imaging size as well as increase in HBP-concentration (up to a 3-fold of initial concentration). In patients exhibiting a prolonged course of the disease changes in NGA-kinetic data were borderline and the hepatic image size unchanged. The values obtained for HBP-concentration in the liver amounted to 0.30-0.50 μmol/l liver for patients with hepatoma, to 0.40-0.60 μmol/l in patients with liver metastasis and to 0.90-1.20 μmol/l in cancer patients without liver malignancy. It is concluded that scintigraphic evaluation of functional hepatic cell mass using the new receptor-tracer 99m Tc-NGA provides an in vivo diagnostic mean allowing quantitative data on liver function beside assessment of liver morphology. (Authors)

  12. Natural course of changes hepatic functional reserve in patients with chronic liver diseases evaluated by scintigraphy with GSA

    International Nuclear Information System (INIS)

    Susumu Shiomi; Etsushi Kawamura; Takehiro Hayashi; Ai Oe; Jin Kotani; Hirotaka Ishizu; Kenji Torii; Joji Kawabe; Takashi Tanaka; Daiki Habu; Shubei Nishiguchi

    2004-01-01

    Purpose: When evaluating the efficacy of therapies for cirrhosis such as branched-chain amino acid (BCAA), knowledge of the natural history of hepatic functional reserve in patients with chronic liver disease is essential. However, biochemical tests such as serum albumin level and prothrombin time do not faithfully reflect hepatic functional reserves since they are affected 'by the blood product supplementation used for treatment. On the other hand, hepatic receptor imaging with Tc-99m DTPA-galactosyl human serum albumin (Tc-99m GSA) allows objective evaluation of hepatic functional reserve since it is not affected by blood preparations. This method allows hepatic functional reserve to be estimated quantitatively on the basis of the receptor index and index of blood clearance. The natural course of chronic liver diseases has been reported in terms of changes in liver histology and development of hepatocellular carcinoma. However, there has been no report on the natural course of changes in hepatic functional reserve in patients with chronic liver disease. We monitored hepatic functional reserve in patients with chronic hepatitis and cirrhosis using scintigraphy with Tc-99m GSA. Materials and Methods: A cross-sectional study was performed for all subjects who underwent scintigraphy with Tc-99m GSA at our hospital. Of these, 324 were patients with chronic liver disease (86 with chronic hepatitis and 226 with cirrhosis) diagnosed at our hospital by examination of liver specimens obtained by laparoscopy or needle biopsy performed under ultrasonic guidance and 12 were subjects found to have a healthy liver when examined during the same period. Moreover, we selected for a longitudinal study all patients with underlying hepatic viral infection, without hepatocellular carcinoma, not treated by interferon, and not treated surgically or by sclerotherapy for varices, who agreed to return after discharge to our outpatient clinic for monitoring and who gave informed consent to

  13. [Liver and sport].

    Science.gov (United States)

    Watelet, J

    2008-11-01

    The liver is a vital organ and plays a central role in energy exchange, protein synthesis as well as the elimination of waste products from the body. Acute and chronic injury may disturb a variety of liver functions to different degrees. Over the last three decades, the effects of physical activity and competitive sport on the liver have been described by various investigators. These include viral hepatitis and drug-induced liver disorders. Herein, we review acute and chronic liver diseases potentially caused by sport. Team physicians, trainers and others, responsible for the health of athletes, should be familiar with the risk factors, clinical features, and consequences of liver diseases that occur in sports.

  14. Perfusion maps of the whole liver based on high temporal and spatial resolution contrast-enhanced MRI (4D THRIVE): Feasibility and initial results in focal liver lesions

    International Nuclear Information System (INIS)

    Coenegrachts, Kenneth; Ghekiere, Johan; Denolin, Vincent; Gabriele, Beck; Herigault, Gwen; Haspeslagh, Marc; Daled, Peter; Bipat, Shandra; Stoker, Jaap; Rigauts, Hans

    2010-01-01

    Purpose: To prospectively evaluate a new imaging sequence (4D THRIVE) for whole liver perfusion in high temporal and spatial resolution. Feasibility of parametric mapping and its potential for characterizing focal liver lesions (FLLs) are investigated. Materials and methods: Fifteen patients suspected for colorectal liver metastases (LMs) were included. Parametric maps were evaluated qualitatively (ring-enhancement and lesion heterogeneity) and compared to three-phased contrast-enhanced MRI. Quantitative analysis was based on average perfusion values of entire FLLs. Reference standard comprised surgery with histopathology or follow-up imaging. Fisher's exact test was used for qualitative and Kruskal-Wallis test for quantitative analysis. Results: In total 29 LMs, 17 hemangiomas and 4 focal nodular hyperplasias were evaluated. FLLs could be differentiated by qualitative assessment of parametric maps respectively three-phased contrast-enhanced MRI (Fisher's p < 0.001 for comparisons between LMs and hemangiomas and LMs and FNHs for both ring-enhancement and lesion heterogeneity) rather than by quantitative analysis of parametric maps (Chi-square for Kep = 0.33 (p = 0.847) and Chi-square for Kel = 1.35 (p = 0.509)). Conclusion: This preliminary study shows potential of 4D THRIVE for whole liver imaging enabling calculation of parametric maps. Qualitative rather than quantitative analysis was accurate for differentiating malignant and benign FLLs.

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  16. Impairment of liver and kidney functions in gamma irradiation rats suffering pesticide toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Roushdy, H M; Abdel-Hamid, F M; Abu-Ghadir, A R [Radiation biology department, National Centre for Radiation Research and Technology, Radio isotope Department, Nuclear Reseach Center, and atomic Energy, Authority, Cairo (Egypt)

    1995-10-01

    The effect of exposure to single whole body gamma irradiation dose at 6.5 Gy and/or either oral administration of 50 or 100 mg kelthane/kg kelthane/kg body weight/day for successively 3 days, or daily feeding with 200 mg kelthane/kg body weight for 3, 6, and 12 weeks has been studied on relative liver and kidney weights, certain serum and liver enzymes creatinine and inorganic phosphorous clearance, as well as percentage of tubular phosphorous reabsorption in male animals. The data obtained revealed that exposure to gamma-irradiation alone or combined with kelthane treatment caused significant increase in the relative spleen weight besides significant decrease in serum and liver alkaline phosphatase and serum cholinesterase. Exposure to gamma irradiation after orally administration of 100 mg or feeding dietary kelthane caused significant decrease in liver glucose-6-phosphatase. Non significant changes in aspartic and alanine transaminases could be recorded due to gamma-irradiation and/or kelthane treatment. Endogenous clearance of creatinine and phosphorous as well as tubular phosphorous reabsorption were determined to assess the glomerular filtration and tubular function. The data obtained revealed that exposure to gamma-irradiation either alone or after treatment with kelthane caused significant decrease in creatinine and phosphorous clearance while phosphorous reabsorption was not appreciably affected. 4 tabs.

  17. Impairment of liver and kidney functions in gamma irradiation rats suffering pesticide toxicity

    International Nuclear Information System (INIS)

    Roushdy, H.M.; Abdel-Hamid, F.M.; Abu-Ghadir, A.R.

    1995-01-01

    The effect of exposure to single whole body gamma irradiation dose at 6.5 Gy and/or either oral administration of 50 or 100 mg kelthane/kg kelthane/kg body weight/day for successively 3 days, or daily feeding with 200 mg kelthane/kg body weight for 3, 6, and 12 weeks has been studied on relative liver and kidney weights, certain serum and liver enzymes creatinine and inorganic phosphorous clearance, as well as percentage of tubular phosphorous reabsorption in male animals. The data obtained revealed that exposure to gamma-irradiation alone or combined with kelthane treatment caused significant increase in the relative spleen weight besides significant decrease in serum and liver alkaline phosphatase and serum cholinesterase. Exposure to gamma irradiation after orally administration of 100 mg or feeding dietary kelthane caused significant decrease in liver glucose-6-phosphatase. Non significant changes in aspartic and alanine transaminases could be recorded due to gamma-irradiation and/or kelthane treatment. Endogenous clearance of creatinine and phosphorous as well as tubular phosphorous reabsorption were determined to assess the glomerular filtration and tubular function. The data obtained revealed that exposure to gamma-irradiation either alone or after treatment with kelthane caused significant decrease in creatinine and phosphorous clearance while phosphorous reabsorption was not appreciably affected. 4 tabs

  18. SET mediates TCE-induced liver cell apoptosis through dephosphorylation and upregulation of nucleolin.

    Science.gov (United States)

    Ren, Xiaohu; Huang, Xinfeng; Yang, Xifei; Liu, Yungang; Liu, Wei; Huang, Haiyan; Wu, Desheng; Zou, Fei; Liu, Jianjun

    2017-06-20

    Trichloroethylene (TCE) is an occupational and environmental chemical that can cause severe hepatotoxicity. While our previous studies showed that the phosphatase inhibitor SET is a key mediator of TCE-induced liver cell apoptosis, the molecular mechanisms remain elusive. Using quantitative phosphoproteomic analysis, we report here that nucleolin is a SET-regulated phosphoprotein in human liver HL-7702 cells. Functional analysis suggested that SET promoted dephosphorylation of nucleolin, decreased its binding to its transcriptional activator, c-myc, and upregulated nucleolin expression in TCE-treated cells. Importantly, TCE-induced hepatocyte apoptosis was significantly attenuated when nucleolin was downregulated with specific siRNAs. These findings indicate that TCE may induce hepatocyte apoptosis via SET-mediated dephosphorylation and overexpression of nucleolin.

  19. Loss of brain function - liver disease

    Science.gov (United States)

    Hepatic coma; Encephalopathy - hepatic; Hepatic encephalopathy; Portasystemic encephalopathy ... 2017:417-421. Nevah MI, Fallon MB. Hepatic encephalopathy, hepatorenal ... of liver disease. In: Feldman M, Friedman LS, Brandt LJ, ...

  20. Nuclear medicine liver function tests for pregnant women and children. Pt. 1

    International Nuclear Information System (INIS)

    Krumbiegel, P.; Faust, H.; Moebius, G.; Hirschberg, K.; Guenther, K.; Schneider, G.

    1985-01-01

    Stable isotopes, such as 13 C, should be substituted for the long-lived radionuclide 14 C in the 14 C breath test when doing liver function tests in children and pregnant women. For comparison 13 C, 15 N-methacetin and 14 C-methacetin were synthesized as suitable diagnostic agents. Methods are described for the measurement of 14 C and 13 C in the breath. After oral administration of labelled methacetin to healthy subjects and patients with liver diseases a good correspondence between 13 C- and 14 C-measurements in the same subject on the one hand, and a good discrimination between controls and patients on the other hand were shown. Findings with regard to 14 C measurements in urine are discussed supporting the supposed advantage of 13 C-methacetin over 14 C-methacetin application. (orig.)

  1. [Pharmacological analysis of the effect of natural double-helical nucleic acids on the detoxifying function of the liver].

    Science.gov (United States)

    Masycheva, V I; Morozova, E N; Nadolinnaia, I G

    1988-10-01

    The effect of interferon inductors i.e. double stranded RNAs from S. cerevisiae and phage F6 on the liver detoxicating function was studied on noninbred albino mice. The liver detoxicating function was tested by duration of hexenal sleep. It was shown that intraperitoneal administration of the yeast and phage RNAs in doses of 1/5 LD50 for three times led to increasing of the narcotic sleep duration in the animals by 65 and 207 per cent, respectively. The effect was of the dose-dependent nature. The doses not inducing reliable inhibition of hexenal metabolism were equal to 1/10 LD50 for the yeast dsRNA and 1/27 LD50 for the phage dsRNA. The inhibitory effect of the dsRNAs was retained for 2-3 days after discontinuation of the drug use. When the dsRNAs were administered simultaneously with nembutal, an inductor of the liver microsomal enzymes, the dsRNAs eliminated its inducing effect. Simultaneous administration of alpha-tocopherol lowered the dsRNA effect on hexenal metabolism. The findings suggested that the dsRNA inhibitory effect on the liver detoxicating function was grounded on the mechanisms associated with inhibition of syntheses and activation of lipid peroxidation specific of the monooxygenase system under the action of the dsRNAs.

  2. "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.

  3. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl4-induced liver fibrosis.

    Science.gov (United States)

    Wang, Ming-Jun; Ling, Wen-Wu; Wang, Hong; Meng, Ling-Wei; Cai, He; Peng, Bing

    2016-12-14

    To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. Liver stiffness was measured in sixty-eight rabbits with CCl 4 -induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. LSM by ElastPQ was significantly correlated with histologic fibrosis stage ( r = 0.85, P fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinal monitoring of the changes in liver stiffness by ElastPQ showed that early splenectomy (especially F1) may delay liver fibrosis progression. ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl 4 -induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy.

  5. Hepatocyte transplants improve liver function and encephalopathy in portacaval shunted rats.

    Science.gov (United States)

    Fogel, Wieslawa Agnieszka; Stasiak, Anna; Maksymowicz, Michał; Kobos, Jozef; Unzeta, Mercedes; Mussur, Miroslaw

    2014-07-01

    Rats with portacaval shunt (PCS) are useful experimental models of human hepatic encephalopathy in chronic liver dysfunction. We have previously shown that PCS modifies amine neurotransmitter systems in the CNS and increases voluntary alcohol intake by rats. Hepatocyte transplantation, used in acute liver failure, has recently also been applied to chronic liver diseases, which prompted us to investigate whether the altered brain amine system and the drinking behavior in long-term shunted rats could be normalized by hepatocyte transplants. Hepatocytes, isolated from syngeneic donors by collagenase digestion, were injected (3 × 10(6) cells/rat) into the pancreatic tail region, 6 months after PCS. Hepatic function was evaluated by measuring urine urea and plasma L-histidine concentrations. A free choice test with two bottles (tap water and 10% ethyl alcohol) was performed for 3 days to assess the rats' preference for alcohol. The rats were euthanized 2 months posttransplantation. Brain histamine and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured by radioenzymatic assay and by HPLC-EC, respectively, N-tele-methylhistamine by GC/MS while MAOA and MAOB activities by isotopic procedures. Portacaval shunt rats with hepatocyte transplants gave more urea than before transplantation, with lower plasma L-His levels and higher body weight versus the PCS counterparts. Also, those rats consumed less alcohol. The CNS amines and 5-HIAA concentrations, as well as MAO-B activity, being abnormally high in untreated PCS rats, significantly reduced after PCS hepatocyte treatment. The results support the therapeutic values of hepatocyte transplants in chronic liver diseases and the temporary character of PCS-exerted CNS dysfunctions. © 2014 John Wiley & Sons Ltd.

  6. Effects of x-rays or aseptic inflammatory reaction on the circadian rythm of tyrosine aminotransferase in mouse liver (TAT activity of mouse liver)

    International Nuclear Information System (INIS)

    Jungowska-Klin, B.

    1979-01-01

    The circadian rhythm of tyrosine aminotransferase (TAT) was investigated during 48 hours in the liver of mice subjected to: a/ subcutaneous inflammatory reaction, b/ ionizing radiation. The cyclic changes in the circadian enzyme activity were described with a harmonic function. In relation to the control mice in the experimental mice statistically significant changes were demonstrated in the activity of tyrosine aminotransferase associated with desynchronization of the circadian TAT rhythm, particularly evident in the first hours of the first day of the experiment. The functions of enzyme activity changed in the second 24-hours period showed, both qualitatively and quantitatively, a tendency for a gradual return of normal TAT activity in the 24-hour periods. (author)

  7. Thyroid hormones and thyroxine-binding globulin in relation to liver function and serum testosterone in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Becker, U; Gluud, C; Bennett, Patrick

    1988-01-01

    concentrations of triiodothyronine (T3) decreased significantly (p less than 0.05) and thyroid-stimulating hormone (TSH) increased with progressing liver dysfunction. Serum concentrations of tetraiodothyronine (T4), TBG and T4/TBG ratio did not correlate significantly with liver function. Serum T3 concentrations...

  8. Prediction of postoperative respiratory function of lung cancer patients using quantitative lung scans

    International Nuclear Information System (INIS)

    Konishi, Hiroshi

    1982-01-01

    Quantitative sup(99m)Tc-MISA inhalation scan and sup(99m)Tc-MAA perfusion scan were performed in 35 patients with lung cancer who underwent lobectomies. Quantitative 133 Xe ventilation-perfusion scans were also performed in 34 patients with lung cancer who underwent lobectomies. To predict functional loss after lobectomy, the proportion of the No. of segments in the lobe to be resected to the No. of entire segments of that lung was provided for the study. Postoperative FVC, FEVsub(1.0) and MVV were predicted in the study, and which were compared to the respiratory function at one month after operation and more than four months after operation. The predicted postoperative respiratory function was highly correlated with the actually observed postoperative respiratory function (0.7413 lt r lt 0.9278, p lt 0.001). In this study, the postoperative respiratory function was proven to be quite accurately predicted preoperatively with combination of quantitative lung scans and spirometric respiratory function. Therefore this method is useful not only for judgement of operative indication but also for choice of operative method and for counterplan of postoperative respiratory insufficiency. (J.P.N.)

  9. Quantitation of HBV cccDNA in anti-HBc-positive liver donors by droplet digital PCR: a new tool to detect occult infection.

    Science.gov (United States)

    Caviglia, Gian Paolo; Abate, Maria Lorena; Tandoi, Francesco; Ciancio, Alessia; Amoroso, Antonio; Salizzoni, Mauro; Saracco, Giorgio Maria; Rizzetto, Mario; Romagnoli, Renato; Smedile, Antonina

    2018-04-02

    The accurate diagnosis of occult HBV infection (OBI) requires the demonstration of HBV DNA in liver biopsies of HBsAg-negative subjects. However, in clinical practice a latent OBI is deduced by the finding of the antibody to the HB-core antigen (anti-HBc). We investigated the true prevalence of OBI and the molecular features of intrahepatic HBV in anti-HBc-positive subjects. The livers of 100 transplant donors (median age 68.2 years; 64 males, 36 females) positive for anti-HBc at standard serologic testing, were examined for total HBV DNA by nested-PCR and for the HBV covalently closed circular DNA (HBV cccDNA) with an in-house droplet digital PCR assay (ddPCR) (Linearity: R 2 = 0.9998; lower limit of quantitation and detection of 2.4 and 0.8 copies/10 5 cells, respectively). A true OBI status was found in 52% (52/100) of the subjects and cccDNA was found in 52% (27/52) of the OBI-positive, with a median 13 copies/10 5 cells (95% confidence interval 5-25). Using an assay specific for anti-HBc of IgG class, the median antibody level was significantly higher in HBV cccDNA-positive than negative donors (5.7 [3.6-9.7] vs. 17.0 [7.0-39.2] COI, p = 0.007). By multivariate analysis, an anti-HBc IgG value above a 4.4 cut-off index (COI) was associated with the finding of intrahepatic HBV cccDNA (OR = 8.516, p = 0.009); a lower value ruled out its presence with a negative predictive value of 94.6%. With a new in-house ddPCR-based method, intrahepatic HBV cccDNA was detectable in quantifiable levels in about half of the OBI cases examined. The titer of anti-HBc IgG may be a useful surrogate to predict the risk of OBI reactivation in immunosuppressed patients. The covalently closed circular DNA (cccDNA) form of the Hepatitis B virus (HBV) sustains the persistence of the virus even after decades of resolution of the florid infection (Occult HBV infection=OBI). In the present study we developed an highly sensitive method based on droplet digital PCR technology for the detection

  10. 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.

  11. Reproduction Does Not Adversely Affect Liver Mitochondrial Respiratory Function but Results in Lipid Peroxidation and Increased Antioxidants in House Mice.

    Science.gov (United States)

    Mowry, Annelise V; Kavazis, Andreas N; Sirman, Aubrey E; Potts, Wayne K; Hood, Wendy R

    2016-01-01

    Reproduction is thought to come at a cost to longevity. Based on the assumption that increased energy expenditure during reproduction is associated with increased free-radical production by mitochondria, oxidative damage has been suggested to drive this trade-off. We examined the impact of reproduction on liver mitochondrial function by utilizing post-reproductive and non-reproductive house mice (Mus musculus) living under semi-natural conditions. The age-matched post-reproductive and non-reproductive groups were compared after the reproductive females returned to a non-reproductive state, so that both groups were in the same physiological state at the time the liver was collected. Despite increased oxidative damage (p = 0.05) and elevated CuZnSOD (p = 0.002) and catalase (p = 0.04) protein levels, reproduction had no negative impacts on the respiratory function of liver mitochondria. Specifically, in a post-reproductive, maintenance state the mitochondrial coupling (i.e., respiratory control ratio) of mouse livers show no negative impacts of reproduction. In fact, there was a trend (p = 0.059) to suggest increased maximal oxygen consumption by liver mitochondria during the ADP stimulated state (i.e., state 3) in post-reproduction. These findings suggest that oxidative damage may not impair mitochondrial respiratory function and question the role of mitochondria in the trade-off between reproduction and longevity. In addition, the findings highlight the importance of quantifying the respiratory function of mitochondria in addition to measuring oxidative damage.

  12. Fatty infiltration of the liver: evaluation by proton spectroscopic imaging

    International Nuclear Information System (INIS)

    Heiken, J.P.; Lee, J.K.; Dixon, W.T.

    1985-01-01

    The reliability of proton spectroscopic imaging in evaluating fatty infiltration of the liver was investigated in 35 subjects (12 healthy volunteers and 23 patients with fatty livers). With this modified spin-echo technique, fatty liver could be separated from normal liver both visually and quantitatively. On the opposed image, normal liver had an intermediate signal intensity, greater than that of muscle, whereas fatty liver had a lower signal intensity, equal to or less than that of muscle. In normal livers, the lipid signal fraction was less than 10%, while in fatty livers it was greater than 10% and usually exceeded 20%. With this technique, nonuniform fatty infiltration of the liver can be differentiated from hepatic metastases, and the technique may prove useful in the differentiation of some hepatic disorders

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-01-01

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

  14. A variational approach to liver segmentation using statistics from multiple sources

    Science.gov (United States)

    Zheng, Shenhai; Fang, Bin; Li, Laquan; Gao, Mingqi; Wang, Yi

    2018-01-01

    Medical image segmentation plays an important role in digital medical research, and therapy planning and delivery. However, the presence of noise and low contrast renders automatic liver segmentation an extremely challenging task. In this study, we focus on a variational approach to liver segmentation in computed tomography scan volumes in a semiautomatic and slice-by-slice manner. In this method, one slice is selected and its connected component liver region is determined manually to initialize the subsequent automatic segmentation process. From this guiding slice, we execute the proposed method downward to the last one and upward to the first one, respectively. A segmentation energy function is proposed by combining the statistical shape prior, global Gaussian intensity analysis, and enforced local statistical feature under the level set framework. During segmentation, the shape of the liver shape is estimated by minimization of this function. The improved Chan-Vese model is used to refine the shape to capture the long and narrow regions of the liver. The proposed method was verified on two independent public databases, the 3D-IRCADb and the SLIVER07. Among all the tested methods, our method yielded the best volumetric overlap error (VOE) of 6.5 +/- 2.8 % , the best root mean square symmetric surface distance (RMSD) of 2.1 +/- 0.8 mm, the best maximum symmetric surface distance (MSD) of 18.9 +/- 8.3 mm in 3D-IRCADb dataset, and the best average symmetric surface distance (ASD) of 0.8 +/- 0.5 mm, the best RMSD of 1.5 +/- 1.1 mm in SLIVER07 dataset, respectively. The results of the quantitative comparison show that the proposed liver segmentation method achieves competitive segmentation performance with state-of-the-art techniques.

  15. 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,

  16. The relationship between heart and liver iron in thalassemia: a quantitative analysis using MRI

    International Nuclear Information System (INIS)

    Peng Peng; Huang Zhongkui; Long Liliang; Long Mei; Zhao Fanyu; Li Chunyan; Li Wenmei

    2012-01-01

    Objective: To quantify the heart and liver iron overload in thalassemia patients and discuss the relationship of iron deposition between them, and to evaluate the accuracy of using hepatic iron concentration > 15 mg/g dry tissue as an index to predict heart iron deposition as used in clinical practice. Methods: One hundred and three transfusion-dependent patients with thalassemia, who were older than 5 years, underwent MRI heart and liver measurement to obtain T 2 * values. The Spearman rank correlation was employed to analyze the relationship between cardiac T 2 * and liver T 2 * values. By using liver T 2 * =0.96 ms as standard setting, patients were divided into two groups, and the differences of cardiac T 2 * values between the two groups were compared by Wilcoxon rank sum test. Then by using cardiac T 2 * =10, 20 ms as standard setting, patients were divided into 3 groups, and the differences of liver T 2 * values among the 3 groups were compared by Wilcoxon rank sum test. The ROC curves were drawn to predict the possibility of using hepatic iron concentration > 15 mg/g dry tissue as an index of cardiac iron deposition. Results: The cardiac and liver T 2 * values of the 103 thalassemia patients showed low correlation (r=0.453, P=0.000). With the liver T 2 * value reduced, the cardiac T 2 * value did not decline proportionally. The cardiac T 2 * value range and median of 25 patients' group whose liver T 2 * < 0.96 ms were 4.70 to 41.70 ms and 12.10 ms, respectively. The cardiac T 2 * value range and the median of 78 patients' group whose liver T 2 * > 0.96 ms were 4.80 to 51.10 ms and 26.10 ms, respectively. There was statistically significant difference between those of the two groups (Z=-3.566, P=0.000). The liver T 2 * value range and the median of 20 patients' group whose cardiac T 2 * < 10 ms was 0.68 to 3.83 ms and 1.06 ms, respectively. The liver T 2 * value range and the median of 58 patients' group whose cardiac T 2 * ≥20 ms were

  17. Integrated analysis of microRNA and gene expression profiles reveals a functional regulatory module associated with liver fibrosis.

    Science.gov (United States)

    Chen, Wei; Zhao, Wenshan; Yang, Aiting; Xu, Anjian; Wang, Huan; Cong, Min; Liu, Tianhui; Wang, Ping; You, Hong

    2017-12-15

    Liver fibrosis, characterized with the excessive accumulation of extracellular matrix (ECM) proteins, represents the final common pathway of chronic liver inflammation. Ever-increasing evidence indicates microRNAs (miRNAs) dysregulation has important implications in the different stages of liver fibrosis. However, our knowledge of miRNA-gene regulation details pertaining to such disease remains unclear. The publicly available Gene Expression Omnibus (GEO) datasets of patients suffered from cirrhosis were extracted for integrated analysis. Differentially expressed miRNAs (DEMs) and genes (DEGs) were identified using GEO2R web tool. Putative target gene prediction of DEMs was carried out using the intersection of five major algorithms: DIANA-microT, TargetScan, miRanda, PICTAR5 and miRWalk. Functional miRNA-gene regulatory network (FMGRN) was constructed based on the computational target predictions at the sequence level and the inverse expression relationships between DEMs and DEGs. DAVID web server was selected to perform KEGG pathway enrichment analysis. Functional miRNA-gene regulatory module was generated based on the biological interpretation. Internal connections among genes in liver fibrosis-related module were determined using String database. MiRNA-gene regulatory modules related to liver fibrosis were experimentally verified in recombinant human TGFβ1 stimulated and specific miRNA inhibitor treated LX-2 cells. We totally identified 85 and 923 dysregulated miRNAs and genes in liver cirrhosis biopsy samples compared to their normal controls. All evident miRNA-gene pairs were identified and assembled into FMGRN which consisted of 990 regulations between 51 miRNAs and 275 genes, forming two big sub-networks that were defined as down-network and up-network, respectively. KEGG pathway enrichment analysis revealed that up-network was prominently involved in several KEGG pathways, in which "Focal adhesion", "PI3K-Akt signaling pathway" and "ECM

  18. Proteome analysis of a hepatocyte-specific BIRC5 (survivin)-knockout mouse model during liver regeneration.

    Science.gov (United States)

    Bracht, Thilo; Hagemann, Sascha; Loscha, Marius; Megger, Dominik A; Padden, Juliet; Eisenacher, Martin; Kuhlmann, Katja; Meyer, Helmut E; Baba, Hideo A; Sitek, Barbara

    2014-06-06

    The Baculoviral IAP repeat-containing protein 5 (BIRC5), also known as inhibitor of apoptosis protein survivin, is a member of the chromosomal passenger complex and a key player in mitosis. To investigate the function of BIRC5 in liver regeneration, we analyzed a hepatocyte-specific BIRC5-knockout mouse model using a quantitative label-free proteomics approach. Here, we present the analyses of the proteome changes in hepatocyte-specific BIRC5-knockout mice compared to wildtype mice, as well as proteome changes during liver regeneration induced by partial hepatectomy in wildtype mice and mice lacking hepatic BIRC5, respectively. The BIRC5-knockout mice showed an extensive overexpression of proteins related to cellular maintenance, organization and protein synthesis. Key regulators of cell growth, transcription and translation MTOR and STAT1/STAT2 were found to be overexpressed. During liver regeneration proteome changes representing a response to the mitotic stimulus were detected in wildtype mice. Mainly proteins corresponding to proliferation, cell cycle and cytokinesis were up-regulated. The hepatocyte-specific BIRC5-knockout mice showed impaired liver regeneration, which had severe consequences on the proteome level. However, several proteins with function in mitosis were found to be up-regulated upon the proliferative stimulus. Our results show that the E3 ubiquitin-protein ligase UHRF1 is strongly up-regulated during liver regeneration independently of BIRC5.

  19. 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

    International Nuclear Information System (INIS)

    Chapiro, Julius; Savic, Lynn Jeanette; Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois; Lin, MingDe; Lesage, David

    2015-01-01

    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.)

  20. 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.)

  1. Clinical observation on the treatment of acute liver failure by combined non-biological artificial liver.

    Science.gov (United States)

    Li, Maoqin; Sun, Jingxi; Li, Jiaqiong; Shi, Zaixiang; Xu, Jiyuan; Lu, Bo; Cheng, Shuli; Xu, Yanjun; Wang, Xiaomeng; Zhang, Xianjiang

    2016-12-01

    The clinical efficacy and safety of different combinations of non-bio artificial liver in the treatment of acute liver failure was examined. A total of 61 cases were selected under blood purification treatment from the patients with severe acute liver failure admitted to the severe disease department of the hospital from December, 2010 to December, 2015. Three types of artificial liver combinations were observed, i.e., plasma exchange plus hemoperfusion plus continuous venovenous hemodiafiltration (PE+HP+CVVHDF), PE+CVVHDF and HP+CVVHDF. The heart rate (HR), mean arterial pressure (MAP), respiratory index (PaO 2 /FiO 2 ), liver and kidney function indicator, as well as platelet and coagulation function were compared. A comparison before and after the treatment using the three methods, showed improvement in the HRs, MAPs, PaO 2 /FiO 2 , total bilirubins (TBIL) and alanine aminotransferases (ALT) (Prate of 62.3% (38/61), and a viral survival rate of 35.0% (7/20); with the non-viral survival rate being 75.6% (31/41). In conclusion, following the treatment of three types of artificial livers, the function was improved to varying degrees, with the PE+HP+CVVHDF and the PE+CVVHDF method being better. By contrast, after the treatment of non-viral liver failure, the survival rate was significantly higher than the patients with viral liver failure.

  2. Non-invasive assessment of the liver using imaging

    Science.gov (United States)

    Thorling Thompson, Camilla; Wang, Haolu; Liu, Xin; Liang, Xiaowen; Crawford, Darrell H.; Roberts, Michael S.

    2016-12-01

    Chronic liver disease causes 2,000 deaths in Australia per year and early diagnosis is crucial to avoid progression to cirrhosis and end stage liver disease. There is no ideal method to evaluate liver function. Blood tests and liver biopsies provide spot examinations and are unable to track changes in function quickly. Therefore better techniques are needed. Non-invasive imaging has the potential to extract increased information over a large sampling area, continuously tracking dynamic changes in liver function. This project aimed to study the ability of three imaging techniques, multiphoton and fluorescence lifetime imaging microscopy, infrared thermography and photoacoustic imaging, in measuring liver function. Collagen deposition was obvious in multiphoton and fluorescence lifetime imaging in fibrosis and cirrhosis and comparable to conventional histology. Infrared thermography revealed a significantly increased liver temperature in hepatocellular carcinoma. In addition, multiphoton and fluorescence lifetime imaging and photoacoustic imaging could both track uptake and excretion of indocyanine green in rat liver. These results prove that non-invasive imaging can extract crucial information about the liver continuously over time and has the potential to be translated into clinic in the assessment of liver disease.

  3. Galactosylated poly(ε-caprolactone) membrane promoted liver-specific functions of HepG2 cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan, E-mail: zhang_yan@ecust.edu.cn [The Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Zhang, Yi [The Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Chen, Min; Zhou, Yan [The State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai, 200237 (China); Lang, Meidong, E-mail: mdlang@ecust.edu.cn [The Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2014-08-01

    The lack of pendant functional groups on the PCL backbone has been a great challenge for surface bioactivation of poly(ε-caprolactone) (PCL). In the present study, covalently galactosylated PCL (GPCL) was developed through coupling between the amino-functionalized PCL (NPCL) and the lactobionic acid (LA) and its potential application in maintenance of physiological functions of HepG2 cells was further evaluated. The structure and properties of GPCL were explored by {sup 1}H NMR, FT-IR, GPC and DSC. Moreover, the incorporation of galactose ligands onto GPCL membranes not only promoted higher wettability, but also radically changed surface morphology in comparison with PCL and NPCL according to the contact angle measurement and atomic force microscopy. When HepG2 cells were seeded onto these membranes, the cells on GPCL membranes showed more pronounced cell adhesion and tended to form aggregates during the initial adhesion stage and then progressively grew into multi-layer structures compared to those without galactose ligands by the observation with fluorescence microscope and scanning electron microscopy. Furthermore, live–dead assay and functional tests demonstrated that HepG2 cells on GPCL membranes had superior viability and maintained better liver-specific functions. Collectively, GPCL has great potential for hepatic tissue engineering scaffolds. - Graphical abstract: The specific recognition between the galactose ligands on the galactosylated poly(ε-caprolactone) membrane and the ASGPR on the HepG2 cell surface. The galactosylated poly(ε-caprolactone) membranes improved the cell-matrix interaction. The galactosylated functionalized PCL scaffold is a potential candidate for liver tissue engineering. - Highlights: • The specific recognition between the galactose ligands on the galactosylated poly(ε-caprolactone) membrane and the ASGPR on the HepG2 cell surface. • The galactosylated poly(ε-caprolactone) membranes improved the cell-matrix interaction.

  4. Functional contribution of elevated circulating and hepatic non-classical CD14CD16 monocytes to inflammation and human liver fibrosis.

    Directory of Open Access Journals (Sweden)

    Henning W Zimmermann

    Full Text Available BACKGROUND: Monocyte-derived macrophages critically perpetuate inflammatory responses after liver injury as a prerequisite for organ fibrosis. Experimental murine models identified an essential role for the CCR2-dependent infiltration of classical Gr1/Ly6C(+ monocytes in hepatic fibrosis. Moreover, the monocyte-related chemokine receptors CCR1 and CCR5 were recently recognized as important fibrosis modulators in mice. In humans, monocytes consist of classical CD14(+CD16(- and non-classical CD14(+CD16(+ cells. We aimed at investigating the relevance of monocyte subpopulations for human liver fibrosis, and hypothesized that 'non-classical' monocytes critically exert inflammatory as well as profibrogenic functions in patients during liver disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed circulating monocyte subsets from freshly drawn blood samples of 226 patients with chronic liver disease (CLD and 184 healthy controls by FACS analysis. Circulating monocytes were significantly expanded in CLD-patients compared to controls with a marked increase of the non-classical CD14(+CD16(+ subset that showed an activated phenotype in patients and correlated with proinflammatory cytokines and clinical progression. Correspondingly, CD14(+CD16(+ macrophages massively accumulated in fibrotic/cirrhotic livers, as evidenced by immunofluorescence and FACS. Ligands of monocyte-related chemokine receptors CCR2, CCR1 and CCR5 were expressed at higher levels in fibrotic and cirrhotic livers, while CCL3 and CCL4 were also systemically elevated in CLD-patients. Isolated monocyte/macrophage subpopulations were functionally characterized regarding cytokine/chemokine expression and interactions with primary human hepatic stellate cells (HSC in vitro. CD14(+CD16(+ monocytes released abundant proinflammatory cytokines. Furthermore, CD14(+CD16(+, but not CD14(+CD16(- monocytes could directly activate collagen-producing HSC. CONCLUSIONS/SIGNIFICANCE: Our data

  5. Hepatic enhancement on Gd-BOPTA-enhanced MR imaging: comparison between cirrhotic and normal livers

    International Nuclear Information System (INIS)

    Shin, Sang Soo; Jeong, Yong Yeon; Kang, Heoung Keun; Lim, Hyo Soon; Yoon, Woong; Seo, Jeong Jin; Park, Jin Gyoon

    2004-01-01

    To compare the enhancement features of hepatic parenchyma between cirrhotic and normal liver, using Gd-BOPTA-enhanced delayed MR imaging. The 60 patients (35 with cirrhotic and 25 with normal liver) included in our study underwent Gd-BOPTA-enhanced MR imaging using a 1.5T system with a phase-array multicoil. In all cases, T1-weighted in-phase and opposed-phase gradient-echo MR imaging was performed before and 60 minutes after intravenous administration of a bolus of Gd-BOPTA. All images were quantitatively analysed by comparing the signal-to-noise ratio (SNR) and signal enhancement (SE) of cirrhotic and normal liver before and after contrast enhancement, and in cirrhotic patients, SNR and SE were also compared in terms of the Child-Pugh classification. For qualitative analysis, the hepatic enhancement patterns of cirrhotic and normal liver were classified as homogeneous or heterogeneous according to the consensual findings of two radiologists. At contrast-enhanced imaging, both cirrhotic (p<0.001) and normal liver (p<0.001) showed substantially increased SNR relative to unenhanced images, and the SNR of cirrhotic liver was significantly lower than that of normal livers at both in-phase (p<0.001) and opposed-phase (p<0.001) imaging. The SE of cirrhotic liver was significantly lower than that of normal liver (in-phase:p=0.002; opposed phase:p=0.011). Both Child-Pugh class A (p<0.001) and B (p<0.001) cirrhotic liver showed a substantial increase in SNR at contrast-enhanced imaging relative to unenhanced imaging and the SNR of Child-Pugh class A was significantly higher than that of Child-Pugh class B at both in-phase (p<0.001) and opposed-phase (p=0.022) imaging. In addition, the SE of class A was significantly higher than that of class B at in-phase imaging (p=0.004). Cirrhotic liver showed heterogeneous enhancement in 20 of 35 patients (57%), whereas normal liver showed homogeneous enhancement in all patients. At Gd-BOPTA-enhanced delayed MR imaging, cirrhotic liver

  6. Hepatic steatosis and non-alcoholic fatty liver disease are not associated with decline in renal function in people with Type 2 diabetes.

    Science.gov (United States)

    Jenks, S J; Conway, B R; Hor, T J; Williamson, R M; McLachlan, S; Robertson, C; Morling, J R; Strachan, M W J; Price, J F

    2014-09-01

    We aimed to determine whether the presence of hepatic steatosis and/or non-alcoholic fatty liver disease was associated with decline in renal function or onset of microalbuminuria in a cohort of people with Type 2 diabetes, including those managed in both primary and secondary care. Nine hundred and thirty-three patients from the Edinburgh Type 2 Diabetes Study, a cohort of Scottish men and women aged 60-74 years with Type 2 diabetes, underwent assessment for hepatic steatosis by liver ultrasonography 1 year after recruitment. Non-alcoholic fatty liver disease was defined as the presence of steatosis following exclusion of secondary causes of liver disease. Patients were followed for 4 years and decline in renal function was assessed by the change in estimated glomerular filtration rate over time. Of the 933 subjects, 530 had hepatic steatosis and, of those with hepatic steatosis, 388 had non-alcoholic fatty liver disease. Neither hepatic steatosis nor non-alcoholic fatty liver disease were significantly associated with rate of decline in renal function, with the mean rate of decline in estimated glomerular filtration rate being -1.55 ml min(-1) 1.73 m(-2) per year for participants with hepatic steatosis compared with -1.84 ml min(-1) 1.73 m(-2) for those without steatosis (P = 0.19). Similar results were obtained when the analysis was restricted to participants with and without non-alcoholic fatty liver disease (-1.44 vs. -1.64 ml min(-1) 1.73 m(-2) per year, respectively; P = 0.44). Additionally, neither hepatic steatosis nor non-alcoholic fatty liver disease were associated with the onset or regression of albuminuria during follow-up (all P ≥ 0.05). The presence of hepatic steatosis/non-alcoholic fatty liver disease was not associated with decline in renal function during a 4-year follow-up in our cohort of older people with Type 2 diabetes. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  7. New-onset diabetes mellitus after living-donor liver transplantation: association with graft synthetic function.

    Science.gov (United States)

    Yagi, Shintaro; Kaido, Toshimi; Iida, Taku; Yoshizawa, Atsushi; Okajima, Hideaki; Uemoto, Shinji

    2017-06-01

    It is now known that post-transplant graft function after deceased-donor liver transplantation and living-donor liver transplantation (LDLT) differ; however, there is no report assessing the relationship between graft function and the development of new-onset diabetes mellitus after transplantation (NODAT). We conducted this study to identify the predictive risk factors for NODAT, including graft function after LDLT. The subjects of this study were 175 adult recipients who underwent LDLT at Kyoto University Hospital between 2006 and 2010, and survived for more than 3 months (median observation period, 1046 days). The 1-, 2-, and 3-year incidences of NODAT after LDLT were 26.1, 32.0, and 33.4%, respectively. Pre-transplant diabetes was associated with poor survival (p = 0.0048), whereas NODAT was not associated with patient survival. In the multivariate analysis, recipient age ≥40, a tacrolimus trough level ≥8 ng/mL 3 months after LDLT, and cholinesterase (ChE) <185 IU/L 3 months after LDLT were the independent risk factors for NODAT. Poor graft synthetic function 3 months after LDLT as well as older age of the recipient and a higher tacrolimus concentration were strongly associated with NODAT development after LDLT.

  8. Carcinoembryonic Antigen Level in Liver Disease

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Kyoo Ok; Kim, Ki Whang; Park, Chang Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1978-09-15

    Carcinoembryonic antigen was initially known as tumor specific antigen and had a potential diagnostic value in the detection of digestive tract malignancies. However, subsequent studies showed CEA and CEA-like antigen present in benign disease, particularly in liver. We had collected sera from 58 patients who had liver scan and later were diagnosed clinically and histologically as liver disease. We estimated CEA values and correlations were made with liver function tests in liver cirrhosis cases. The results: 1) The raised plasma carcinoembryonic antigen level were found in 13 (68.4%) of 19 patients cirrhosis, 5 (27.8%) of 18 patients in hepatoma, 5 (71%) of 7 patients in chronic active hepatitis, all 3 patients in liver abscesses, 2 (66.7%) of 3 patients in liver abscesses, 2 (66.7%) of 3 patients in obstructive biliary disease and none in each one patient of traumatic liver hematoma, subphrenic abscess and clonorchiasis. 2) There is no linear correlation between carcinoembryonic antigen level and liver function tests including serum bilirubin, alkaline phosphatase, SGOT and prothrombin time in liver patients.

  9. Carcinoembryonic Antigen Level in Liver Disease

    International Nuclear Information System (INIS)

    Choi, Kyoo Ok; Kim, Ki Whang; Park, Chang Yun

    1978-01-01

    Carcinoembryonic antigen was initially known as tumor specific antigen and had a potential diagnostic value in the detection of digestive tract malignancies. However, subsequent studies showed CEA and CEA-like antigen present in benign disease, particularly in liver. We had collected sera from 58 patients who had liver scan and later were diagnosed clinically and histologically as liver disease. We estimated CEA values and correlations were made with liver function tests in liver cirrhosis cases. The results: 1) The raised plasma carcinoembryonic antigen level were found in 13 (68.4%) of 19 patients cirrhosis, 5 (27.8%) of 18 patients in hepatoma, 5 (71%) of 7 patients in chronic active hepatitis, all 3 patients in liver abscesses, 2 (66.7%) of 3 patients in liver abscesses, 2 (66.7%) of 3 patients in obstructive biliary disease and none in each one patient of traumatic liver hematoma, subphrenic abscess and clonorchiasis. 2) There is no linear correlation between carcinoembryonic antigen level and liver function tests including serum bilirubin, alkaline phosphatase, SGOT and prothrombin time in liver patients.

  10. Gut microbiome can control antitumor immune function in liver

    Science.gov (United States)

    An NCI study in mice that found a connection between gut bacteria and antitumor immune responses in the liver has implications for understanding mechanisms that lead to liver cancer and for potential treatments. The study was published in Science.

  11. Recellularization of rat liver: An in vitro model for assessing human drug metabolism and liver biology.

    Directory of Open Access Journals (Sweden)

    Matthew J Robertson

    Full Text Available Liver-like organoids that recapitulate the complex functions of the whole liver by combining cells, scaffolds, and mechanical or chemical cues are becoming important models for studying liver biology and drug metabolism. The advantages of growing cells in three-dimensional constructs include enhanced cell-cell and cell-extracellular matrix interactions and preserved cellular phenotype including, prevention of de-differentiation. In the current study, biomimetic liver constructs were made via perfusion decellularization of rat liver, with the goal of maintaining the native composition and structure of the extracellular matrix. We optimized our decellularization process to produce liver scaffolds in which immunogenic residual DNA was removed but glycosaminoglycans were maintained. When the constructs were recellularized with rat or human liver cells, the cells remained viable, capable of proliferation, and functional for 28 days. Specifically, the cells continued to express cytochrome P450 genes and maintained their ability to metabolize a model drug, midazolam. Microarray analysis showed an upregulation of genes involved in liver regeneration and fibrosis. In conclusion, these liver constructs have the potential to be used as test beds for studying liver biology and drug metabolism.

  12. Impact of future remnant liver volume on post-hepatectomy regeneration in non-cirrhotic livers

    Directory of Open Access Journals (Sweden)

    Duilio ePagano

    2014-04-01

    Full Text Available Objective: The purpose of the study is to detect if some parameters can be considered as predictors of liver regeneration in two different patient populations composed of in living donors for adult to adult living donor liver transplant and patients with hepatic malignancies within a single institution.Summary Background Data: Preoperative multi-detector computed tomography volumetry is an essential tool to assess the volume of the remnant liver. Methods: a retrospective analysis from an ongoing clinical study on 100 liver resections, between 2004 and 2010. 70 patients were right lobe living donors for liver transplantation and 30 patients were resected for treatment of tumors. Pre-surgical factors such as age, weight, height, body mass index (BMI, original liver volume, future remnant liver volume (FRLV, spleen volume, liver function tests, creatinine, platelet count, steatosis, portal vein embolization (PVE and number of resected segments were analyzed to evidence potential markers for liver regeneration. Results: Follow-up period did not influence the amount of liver regenerated: the linear regression evidenced that there is no correlation between percentage of liver regeneration and time of follow-up (p=0.88. The pre-surgical variables that resulted markers of liver regeneration include higher preoperative values of BMI (p=0.01, bilirubin(p=0.04, glucose (p=0.05 and GGT (p=0.014; the most important association was revealed regarding the lower FRLV (pConclusions: Liver regeneration follows similar pathway in living donor and in patients resected for cancer. Small FRLV tends to regenerate more and faster, confirming that a larger resections may lead to a greater promotion of liver regeneration in patients with optimal conditions in terms of body habitus, preoperative liver function tests and glucose level.

  13. Abnormal reticuloendothelial function in patients with active vasculitis and idiopathic membranous glomerulopathy

    Energy Technology Data Exchange (ETDEWEB)

    van der Woude, F J; Piers, D A; van der Giessen, M; Hoedemaeker, P J; Hauw The, T; van der Hem, G K

    1983-02-01

    Reticuloendothelial function was assessed in 11 patients with systemic lupus erythematosus, 8 patients with Wegener's granulomatosus, and 20 patients with idiopathic membranous sup(99m)Tc-labeled heat-damaged red blood cells. With this method organ uptake could be measured by quantitative scintigraphy. There was no relation between the Tsub(1/2) of the blood disappearance curve and the Tsub(1/2) of the splenic uptake curve. The Tsub(1/2) of the blood disappearance curve was normal in all the patient groups. However, there was a significant shift from spleen to liver uptake in patients with active systemic lupus erythematosus, active Wegener's granulomatosus, and membranous glomerulopathy in comparison with a control group. There was no relation with age, level of circulating immune complexes, complement level, kidney function, or immunosuppressive treatment. We conclude that an increase of the liver component of reticuloendothelial function may compensate abnormalities in splenic function. This stresses the importance of quantitative scanning to detect such abnormalities. The study provides evidence for disease related hyposplenism in patients with active systemical lupus erythematosus, active Wegener's granulamatosus, and membranous glomerulopathy.

  14. Abnormal reticuloendothelial function in patients with active vasculitis and idiopathic membranous glomerulopathy

    International Nuclear Information System (INIS)

    Woude, F.J. van der; Piers, D.A.; Giessen, M. van der; Hoedemaeker, P.J.; Hauw The, T.; Hem, G.K. van der; Rijksuniversiteit Groningen; Rijksuniversiteit Groningen

    1983-01-01

    Reticuloendothelial function was assessed in 11 patients with systemic lupus erythematosus, 8 patients with Wegener's granulomatosus, and 20 patients with idiopathic membranous sup(99m)Tc-labeled heat-damaged red blood cells. With this method organ uptake could be measured by quantitative scintigraphy. There was no relation between the Tsub(1/2) of the blood disappearance curve and the Tsub(1/2) of the splenic uptake curve. The Tsub(1/2) of the blood disappearance curve was normal in all the patient groups. However, there was a significant shift from spleen to liver uptake in patients with active systemic lupus erythematosus, active Wegener's granulomatosus, and membranous glomerulopathy in comparison with a control group. There was no relation with age, level of circulating immune complexes, complement level, kidney function, or immunosuppressive treatment. We conclude that an increase of the liver component of reticuloen-dothelial function may compensate abnormalities in splenic function. This stresses the importance of quantitative scanning to detect such abnormalities. The study provides evidence for disaase related hyposplenism in patients with active systemical lupus erythematosus, active Wegener's granulamatosus, and membranous glomerulopathy. (orig.)

  15. Gd-EOB-DTPA-enhanced MRI for monitoring future liver remnant function after portal vein embolization and extended hemihepatectomy: A prospective trial

    Energy Technology Data Exchange (ETDEWEB)

    Geisel, Dominik; Raabe, Philip; Hamm, Bernd; Denecke, Timm [Charite Campus Virchow-Klinikum, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Luedemann, Lutz [Essen University Hospital, Department of Medical Physics, Essen (Germany); Malinowski, Maciej; Stockmann, Martin; Seehofer, Daniel; Pratschke, Johann [Charite Campus Virchow-Klinikum, Department of General, Visceral and Transplantation Surgery, Berlin (Germany)

    2017-07-15

    To evaluate changes in liver function after right portal vein embolization (PVE) and extended right hemihepatectomy using gadolinium ethoxybenzyl-DTPA-enhanced (Gd-EOB-DTPA) MRI. In this prospective trial, 37 patients undergoing PVE were examined before and 14 and 28 days after PVE and 10 days after extended hemihepatectomy using Gd-EOB-DTPA-enhanced MRI. Lobar volume, kinetic growth rate (KGR), relative enhancement (RE) as well as hepatocellular uptake index (HUI) and fat signal fraction (FSF) were calculated for each lobe. RE of the left liver lobe (LLL) was steadily increasing after PVE and decreased to 0.48 ± 0.19 10 days after surgery, which is significantly lower than 14 days and 28 days post PVE (P < 0.05). KGR was 14.06 ± 9.82%/week for the period from PVE to 14 days after PVE. HUI of the LLL increased steadily after PVE and was significantly higher at both 14 and 28 days after PVE compared to pre PVE (P < 0.05). HUI of the residual liver after surgery was lower than before. Gd-EOB-DTPA-enhanced MRI may be used to monitor the functional increase in the FLR after PVE and to depict the intraoperative liver injury leading to a decrease in liver remnant function. (orig.)

  16. A quantitative assay measuring the function of lipase maturation factor 1

    Science.gov (United States)

    Yin, Fen; Doolittle, Mark H.; Péterfy, Miklós

    2009-01-01

    Newly synthesized lipoprotein lipase (LPL) and related members of the lipase gene family require an endoplasmic reticulum maturation factor for attainment of enzyme activity. This factor has been identified as lipase maturation factor 1 (Lmf1), and mutations affecting its function and/or expression result in combined lipase deficiency (cld) and hypertriglyceridemia. To assess the functional impact of Lmf1 sequence variations, both naturally occurring and induced, we report the development of a cell-based assay using LPL activity as a quantitative reporter of Lmf1 function. The assay uses a cell line homozygous for the cld mutation, which renders endogenous Lmf1 nonfunctional. LPL transfected into the mutant cld cell line fails to attain activity; however, cotransfection of LPL with wild-type Lmf1 restores its ability to support normal lipase maturation. In this report, we describe optimized conditions that ensure the detection of a complete range of Lmf1 function (full, partial, or complete loss of function) using LPL activity as the quantitative reporter. To illustrate the dynamic range of the assay, we tested several novel mutations in mouse Lmf1. Our results demonstrate the ability of the assay to detect and analyze Lmf1 mutations having a wide range of effects on Lmf1 function and protein expression. PMID:19471043

  17. Influence of thyroid hormones on biochemical parameters of liver ...

    African Journals Online (AJOL)

    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 ...

  18. Breath 14CO2 after intravenous administration of [14C]aminopyrine in liver diseases

    International Nuclear Information System (INIS)

    Pauwels, S.; Geubel, A.P.; Dive, C.; Beckers, C.

    1982-01-01

    The determination of of 14 CO2 in breath after oral administration of [ 14 C]aminopyrine has been proposed as a quantitative liver function test. In order to shorten the procedure and avoid misinterpretations related to variable rates of intestinal absorption, the [ 14 C]aminopyrine breath test (ABT) was performed after intravenous administration of [ 14 C]aminopyrine in 21 controls and 89 patients with biopsy-proven liver disease. The specific activity of the first hour sample corrected for body weight (SA1) was the most discriminant expression of breath data. The SA1 value, expressed as the percentage of the administered dose, was 0.86 +/- 0.1% (mean +/- SD) in controls and significantly less in patients (0.46 +/- 0.31%). Low values were observed in patients with untreated chronic active hepatitis (0.16 +/- 0.13%), alcoholic cirrhosis (0.2 +/ 0.15%0, and untreated postnecrotic cirrhosis (0.47 +/- 0.17%). In contrast, normal values were obtained in chronic persistent hepatitis (0.86 +/- 0.13%) and 58% of noncirrhotic alcoholic liver diseases (0.83 +/- 0.27%). The results of duplicate studies were reproducible and SA1 correlated with other conventional liver function tests, including 45-min BSP retention. Among these, ABT was the most sensitive screening test for the presence of cirrhosis, especially in alcoholic patients, where it allowed a sharp distinction between cirrhotic and noncirrhotic cases. The results obtained in chronic hepatitis suggested that ABT may provide a reliable index of the activity of the disease. In our hands, intravenous ABT, performed over a 1-hr period, was a fast, sensitive, and discriminant liver function test

  19. Quantification of human hepatic binding protein (HBP) via sup 99m Tc-galactosyl-neoglycoalbumin (NGA) liver scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Virgolini, I; Hoebart, J; Bergmann, H; Sinzinger, H [Vienna Univ. (Austria). Abt. fuer Nuklearmedizin; Mueller, C [Vienna Univ. (Austria). 2. Klinik fuer Gastroenterologie und Hepatologie; Angelberger, P [Oesterreichisches Forschungszentrum Seibersdorf GmbH (Austria). Inst. fuer Chemie

    1991-01-01

    {sup 99m}Tc-galactosyl-neoglycoalbumin ({sup 99m}Tc-NGA) was synthesized by covalent coupling of 2-imino-2-methoxyethyl-1-thio-{beta}-D-galactopyranoside to the primary amino groups of human serum albumin. Injections of {sup 99m}Tc-NGA (150 MBq; 3.5 mg (=50 nmol)/ml) demonstrated the liver to be the exclusive site of tracer-uptake. Simulation of {sup 99m}Tc-NGA-kinetics allowed quantification of binding to the hepatic binding protein (HBP). Using this model we studied 250 patients with various liver disease. In alcoholic liver cirrhosis such patients with Child B and Child C stage cirrhosis had a lower HBP-concentration in the liver compared to control individuals. The group with the most advanced cirrhosis had a significantly lower HBP-concentration (0.20-0.45 {mu}mol/l) than Child A patients (0.60-0.85 {mu}mol/l; p<0.01) and Child B patients (0.45-0.60 {mu}mol/l; p<0.05). In patients with biopsy proven liver fibrosis (0.80-1.22 {mu}mol/l) no difference in receptor concentration to normal individuals was estimated. Patients with recently diagnosed acute viral hepatitis underwent repeated {sup 99m}Tc-galactosyl-neoglycoalbumin (NGA) scanning of the liver during the course of the disease. Return of liver function tests to normal values was associated with an increased hepatic imaging size as well as increase in HBP-concentration. In patients exhibiting a prolonged course of the disease changes in NGA-kinetic data were borderline and the hepatic image size unchanged. The values obtained for HBP-concentration in the liver amounted to 0.30-0.50 {mu}mol/l liver for patients with hepatoma, to 0.40-0.60 {mu}mol/l in patients with liver metastasis and to 0.90-1.20 {mu}mol/l in cancer patients without liver malignancy. It is concluded that scintigraphic evaluation of functional hepatic cell mass using the new receptor-tracer {sup 99m}Tc-NGA provides an in vivo diagnostic mean allowing quantitative data on liver function beside assessment of liver morphology.

  20. 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 conju...

  1. Lead nitrate induced unallied expression of liver and kidney functions in male albino rats.

    Science.gov (United States)

    Chougule, Priti; Patil, Bhagyashree; Kanase, Aruna

    2005-06-01

    To determine the effects of lead where lead accumulates maximum (liver followed by kidney), liver and kidney functions were studied using low oral dose of lead nitrate for prolonged duration. Dose of 20 mg lead nitrate/kg body wt/day was used in male albino rats. AST and ALT levels altered independently. When ALT remained unaltered after 7 and 21 days of treatment, it is decreased by 13.21% after 14 days treatment. AST was marginally lowered after 7 days, increased after 14 days and increased marginally after 21 days. Bilirubin (conjugated, unconjugated and total) decreased after 7 and 14 days and increased after 21 days. Urea increase was directly proportional to duration. Creatinine remained unaltered.

  2. Functional linear models for association analysis of quantitative traits.

    Science.gov (United States)

    Fan, Ruzong; Wang, Yifan; Mills, James L; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao

    2013-11-01

    Functional linear models are developed in this paper for testing associations between quantitative traits and genetic variants, which can be rare variants or common variants or the combination of the two. By treating multiple genetic variants of an individual in a human population as a realization of a stochastic process, the genome of an individual in a chromosome region is a continuum of sequence data rather than discrete observations. The genome of an individual is viewed as a stochastic function that contains both linkage and linkage disequilibrium (LD) information of the genetic markers. By using techniques of functional data analysis, both fixed and mixed effect functional linear models are built to test the association between quantitative traits and genetic variants adjusting for covariates. After extensive simulation analysis, it is shown that the F-distributed tests of the proposed fixed effect functional linear models have higher power than that of sequence kernel association test (SKAT) and its optimal unified test (SKAT-O) for three scenarios in most cases: (1) the causal variants are all rare, (2) the causal variants are both rare and common, and (3) the causal variants are common. The superior performance of the fixed effect functional linear models is most likely due to its optimal utilization of both genetic linkage and LD information of multiple genetic variants in a genome and similarity among different individuals, while SKAT and SKAT-O only model the similarities and pairwise LD but do not model linkage and higher order LD information sufficiently. In addition, the proposed fixed effect models generate accurate type I error rates in simulation studies. We also show that the functional kernel score tests of the proposed mixed effect functional linear models are preferable in candidate gene analysis and small sample problems. The methods are applied to analyze three biochemical traits in data from the Trinity Students Study. © 2013 WILEY

  3. Encephalopathy and liver transplantation.

    Science.gov (United States)

    Chavarria, Laia; Cordoba, Juan

    2013-06-01

    Liver transplantation (LT) candidates experience frequently episodic or persistent hepatic encephalopathy. In addition, these patients can exhibit neurological comorbidities that contribute to cognitive impairment in the pre-transplant period. Assessment of the respective contribution of hepatic encephalopathy or comorbidities in the cognitive manifestations is critical to estimate the neurological benefits of restoring liver function. Magnetic resonance imaging and spectroscopy are useful to assess the impact of liver failure or comorbidities. This assessment is critical to decide liver transplant in difficult cases. In the early postoperative period, LT is commonly complicated by a confusional syndrome. The possible role of persisting hepatic encephalopathy in its development has not been clearly established. The origin is usually considered multifactorial and relates to complications following LT, such as infections, rejection, primary liver dysfunction, immunosuppressors, etc.… The diagnosis and treatment is based in the recognition of comorbidities and optimal care of metabolic disturbances. Several studies have demonstrated recovery of cognitive function after LT in patients that have exhibited hepatic encephalopathy. However, some deficits may persist specifically among patients with persistent HE. Other factors present before LT that contribute to a worse neuropsychological outcome after LT are diabetes mellitus and alcohol consumption. Long-term after LT, cognitive function may worsen in relation to vascular risk factors.

  4. Functional image-guided stereotactic body radiation therapy planning for patients with hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tsegmed, Uranchimeg [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Nakashima, Takeo [Division of Radiation Therapy, Hiroshima University Hospital, Hiroshima (Japan); Nakamura, Yuko; Higaki, Toru [Department of Diagnostic Radiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Imano, Nobuki; Doi, Yoshiko; Kenjo, Masahiro; Ozawa, Shuichi; Murakami, Yuji [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Awai, Kazuo [Department of Diagnostic Radiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Nagata, Yasushi [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan)

    2017-07-01

    The aim of the current planning study is to evaluate the ability of gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI)–guided stereotactic body radiation therapy (SBRT) planning by using intensity-modulated radiation therapy (IMRT) techniques in sparing the functional liver tissues during SBRT for hepatocellular carcinoma. In this study, 20 patients with hepatocellular carcinoma were enrolled. Functional liver tissues were defined according to quantitative liver-spleen contrast ratios ≥ 1.5 on a hepatobiliary phase scan. Functional images were fused with the planning computed tomography (CT) images; the following 2 SBRT plans were designed using a “step-and-shoot” static IMRT technique for each patient: (1) an anatomical SBRT plan optimization based on the total liver; and (2) a functional SBRT plan based on the functional liver. The total prescribed dose was 48 gray (Gy) in 4 fractions. Dosimetric parameters, including dose to 95% of the planning target volume (PTV D{sub 95%}), percentages of total and functional liver volumes, which received doses from 5 to 30 Gy (V5 to V30 and fV5 to fV30), and mean doses to total and functional liver (MLD and fMLD, respectively) of the 2 plans were compared. Compared with anatomical plans, functional image-guided SBRT plans reduced MLD (mean: plan A, 5.5 Gy; and plan F, 5.1 Gy; p < 0.0001) and fMLD (mean: plan A, 5.4 Gy; and plan F, 4.9 Gy; p < 0.0001), as well as V5 to V30 and fV5 to fV30. No differences were noted in PTV coverage and nonhepatic organs at risk (OARs) doses. In conclusion, EOB-MRI–guided SBRT planning using the IMRT technique may preserve functional liver tissues in patients with hepatocellular carcinoma (HCC).

  5. 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...

  6. Natural Killer cells and liver fibrosis

    Directory of Open Access Journals (Sweden)

    Frank eFasbender

    2016-01-01

    Full Text Available In the 40 years since the discovery of Natural Killer (NK cells it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. Additionally, tissue resident NK cells with distinct phenotypical and functional characteristics have been identified. Here we focus on the phenotype of different NK cell subpopulations that can be found in the liver and summarize the current knowledge about the functional role of these cells with a special emphasis on liver fibrosis. NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver fibrosis by killing hepatic stellate cell-derived myofibroblasts, which play a key role in this pathogenic process. Therefore, liver NK cells need to be tightly regulated in order to balance these beneficial and pathological effects.

  7. Imaging-based evaluation of liver function: comparison of {sup 99m}Tc-mebrofenin hepatobiliary scintigraphy and Gd-EOB-DTPA-enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Geisel, Dominik; Gebauer, Bernhard [Charite Campus Virchow-Klinikum, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Luedemann, Lutz [Essen University Hospital, Department of Medical Physics, Essen (Germany); Froeling, Vera; Denecke, Timm [Charite Campus Virchow-Klinikum, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Charite Campus Virchow-Klinikum, Department of Nuclear Medicine, Berlin (Germany); Malinowski, Maciej; Stockmann, Martin; Baron, Annekathrin; Seehofer, Daniel [Charite Campus Virchow-Klinikum, Department of General, Visceral and Thoracic Surgery, Berlin (Germany); Prasad, Vikas [Charite Campus Virchow-Klinikum, Department of Nuclear Medicine, Berlin (Germany)

    2015-05-01

    To compare Gd-EOB-enhanced MRI and {sup 99m}Tc-mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests for separate evaluation of right (RLL) and left liver lobe (LLL) function. Fourteen patients underwent Gd-EOB-enhanced MRI and {sup 99m}Tc-mebrofenin HBS after portal vein embolization within 24 h. Relative enhancement (RE) and hepatic uptake index (HUI) were determined from MRI; and T{sub max}, T{sub 1/2} and mebrofenin uptake were determined from HBS, all values separately for RLL and LLL. Mebrofenin uptake correlated significantly with HUI and RE for both liver lobes. There was strong correlation of mebrofenin uptake with HUI for RLL (r{sup 2} = 0.802, p = 0.001) and RE for LLL (r{sup 2} = 0.704, p = 0.005) and moderate correlation with HUI for LLL (r{sup 2} = 0.560, p = 0.037) and RE for RLL (r{sup 2} = 0.620, p = 0.018). Correlating the percentage share of RLL function derived from MRI (with HUI) with the percentage of RLL function derived from mebrofenin uptake revealed a strong correlation (r{sup 2} = 0.775, p = 0.002). Both RE and HUI correlate with mebrofenin uptake in HBS. The results suggest that Gd-EOB-enhanced MRI and {sup 99m}Tc-mebrofenin HBS may equally be used to separately determine right and left liver lobe function. (orig.)

  8. Frequency of worsening liver function in severe dengue hepatitis patients receiving paracetamol: A retrospective analysis of hospital data

    International Nuclear Information System (INIS)

    Syed, A.A.; Aslam, F.; Hakeem, H.; Siddiqui, F.; Nasir, N.

    2017-01-01

    To determine the frequency of worsening liver function among hospital in-patients with severe dengue hepatitis receiving paracetamol. Methods: This retrospective study was conducted at the Department of Medicine, Aga Khan University Hospital, Karachi, and comprised records of dengue patients with severe hepatitis who received paracetamol for control of fever between June 2007 and December 2014. Alanine aminotransferase at baseline and following paracetamol administration was noted, as well as dosage and duration of paracetamol, along with participants' demographic details. Frequency of patients who developed worsening or improvement of alanine aminotransferase was also noted. SPSS 19 was used for data analysis. Results: Of the 113 subjects, 73(64.6%) were male and 40(35.4%) were female. Overall improvement was observed in subsequent alanine aminotransferase levels (491 units per litre, IQR 356.5 TO 775 vs 151 units per litre, IQR 49.5 to 299.5). Most commonly prescribed dose of paracetamol was 2g (IQR 1 to 5 grams), which was taken for a median duration of 1 day (IQR 1 to 3 days). Moreover, 100(88.5 %) patients showed improvement in alanine aminotransferase. Only 13(11.5 %) patients developed worsening of alanine aminotransferase. Of those with worsening liver function, 8(61.5 %) were discharged home with no clinical deterioration and 5(38.5 %) deaths were observed. However, causes of deaths were unrelated to liver dysfunction. Conclusion: The frequency of worsening liver function following paracetamol administration in patients with severe dengue hepatitis was relatively low. (author)

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

    Directory of Open Access Journals (Sweden)

    Bauyrzhan Umbayev

    2014-12-01

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

  10. Enzyme immunoassay of oestrogen receptors in needle biopsies from human liver

    DEFF Research Database (Denmark)

    Becker, U; Andersen, J; Poulsen, H S

    1991-01-01

    For quantitative assessments of sex hormone receptors in liver tissue, ligand binding assays are inconvenient, as they require large biopsies (0.5-1.0 g). The present study shows that it is possible to measure oestrogen receptors (ER) quantitatively in needle biopsy specimens as small as 10 mg...... by modifications of a commercial enzyme immunoassay employing monoclonal antibodies. Sucrose gradient centrifugation and the dextran charcoal method served as reference methods. A consecutive series of needle biopsies from patients suspected of liver disease were investigated. The biopsies (n = 37) had a median...

  11. Recombinant high-density lipoprotein nanoparticles containing gadolinium-labeled cholesterol for morphologic and functional magnetic resonance imaging of the liver

    Directory of Open Access Journals (Sweden)

    Rui M

    2012-07-01

    Full Text Available Mengjie Rui,1 Wei Guo,2 Qian Ding,2 Xiaohui Wei,2 Jianrong Xu,3 Yuhong Xu21School of Life Science and Biotechnology, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China; 3Department of Radiology, Renji Hospital Affiliation with Medical School of Shanghai Jiao Tong University, Shanghai, People's Republic of ChinaBackground: Natural high-density lipoproteins (HDL possess important physiological functions to the transport of cholesterol from the peripheral tissues to the liver for metabolic degradation and excretion in the bile.Methods and results: In this work, we took advantage of this pathway and prepared two different gadolinium (Gd-DTPA-labeled cholesterol-containing recombinant HDL nanoparticles (Gd-chol-HDL and Gd-(chol2-HDL as liver-specific magnetic resonance imaging (MRI contrast agents. The reconstituted HDL nanoparticles had structural similarity to native HDL, and could be taken up by HepG2 cells via interaction with HDL receptors in vitro. In vivo MRI studies in rats after intravenous injections of 10 µmol gadolinium per kg of recombinant HDL nanoparticles indicated that both nanoparticles could provide signal enhancement in the liver and related organs. However, different T1-weighted image details suggested that they participated in different cholesterol metabolism and excretion pathways in the liver.Conclusion: Such information could be highly useful to differentiate functional changes as well as anatomic differences in the liver. These cholesterol-derived contrast agents and their recombinant HDL preparations may warrant further development as a new class of contrast agents for MRI of the liver and related organs.Keywords: magnetic resonance imaging, apolipoprotein, high-density lipoprotein, contrast agent, gadolinium, liver

  12. Monocytes with angiogenic potential are selectively induced by liver resection and accumulate near the site of liver regeneration.

    Science.gov (United States)

    Schauer, Dominic; Starlinger, Patrick; Zajc, Philipp; Alidzanovic, Lejla; Maier, Thomas; Buchberger, Elisabeth; Pop, Lorand; Gruenberger, Birgit; Gruenberger, Thomas; Brostjan, Christine

    2014-10-30

    Monocytes reportedly contribute to liver regeneration. Three subsets have been identified to date: classical, intermediate, non-classical monocytes. The intermediate population and a subtype expressing TIE2 (TEMs) were suggested to promote angiogenesis. In a clinical setting, we investigated which monocyte subsets are regulated after liver resection and correlate with postoperative liver function. In 38 patients monocyte subsets were evaluated in blood and subhepatic wound fluid by flow cytometry before and 1-3 days after resection of colorectal liver metastases. The monocyte-regulating cytokines macrophage colony stimulating factor (M-CSF), transforming growth factor beta 1 (TGFβ1), and angiopoietin 2 (ANG-2) were measured in patient plasma by ELISA. C-reactive protein (CRP) and liver function parameters were retrieved from routine hospital analyses. On post-operative day (POD) 1 blood monocytes shifted to significantly elevated levels of intermediate monocytes. In wound fluid, a delayed surge in intermediate monocytes was detected by POD 3. Furthermore, TEMs were highly enriched in wound fluid as compared to circulation. CRP and M-CSF levels were substantially increased in patient blood after surgery and correlated significantly with the frequency of intermediate monocytes. In addition, liver function parameters showed a significant association with intermediate monocyte levels on POD 3. The reportedly pro-angiogenic subsets of monocytes are selectively increased upon liver resection and accumulate next to the site of liver regeneration. As previously proposed by in vitro experiments, the release of CRP and M-CSF may trigger the induction of intermediate monocytes. The correlation with liver parameters points to a functional involvement of these monocyte populations in liver regeneration which warrants further investigation.

  13. Predictors of renal function recovery among patients undergoing renal replacement therapy following orthotopic liver transplantation.

    Science.gov (United States)

    Andreoli, Maria Claudia Cruz; Souza, Nádia Karina Guimarães de; Ammirati, Adriano Luiz; Matsui, Thais Nemoto; Carneiro, Fabiana Dias; Ramos, Ana Claudia Mallet de Souza; Iizuca, Ilson Jorge; Coelho, Maria Paula Vilela; Afonso, Rogério Carballo; Ferraz-Neto, Ben-Hur; Almeida, Marcio Dias de; Durão, Marcelino; Batista, Marcelo Costa; Monte, Julio Cesar; Pereira, Virgílio Gonçalves; Santos, Oscar Pavão Dos; Santos, Bento Cardoso Dos

    2017-01-01

    Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27-39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (prenal function after OLT, and those who were diagnosed with fulminant hepatic failure, had no pre-OLT hypertension, received a lower transfused volume of intraoperative FFP and did not undergo pre-OLT intermittent HD had a higher probability

  14. 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......) 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...

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

    Science.gov (United States)

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

    2017-02-01

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

  16. 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.

  17. Pathological assessment of liver fibrosis regression

    Directory of Open Access Journals (Sweden)

    WANG Bingqiong

    2017-03-01

    Full Text Available Hepatic fibrosis is the common pathological outcome of chronic hepatic diseases. An accurate assessment of fibrosis degree provides an important reference for a definite diagnosis of diseases, treatment decision-making, treatment outcome monitoring, and prognostic evaluation. At present, many clinical studies have proven that regression of hepatic fibrosis and early-stage liver cirrhosis can be achieved by effective treatment, and a correct evaluation of fibrosis regression has become a hot topic in clinical research. Liver biopsy has long been regarded as the gold standard for the assessment of hepatic fibrosis, and thus it plays an important role in the evaluation of fibrosis regression. This article reviews the clinical application of current pathological staging systems in the evaluation of fibrosis regression from the perspectives of semi-quantitative scoring system, quantitative approach, and qualitative approach, in order to propose a better pathological evaluation system for the assessment of fibrosis regression.

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

    Science.gov (United States)

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

    2017-01-01

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

  19. Fatty liver diagnostic from medical examination to analyze the accuracy between the abdominal ultrasonography and liver hounsfield units

    International Nuclear Information System (INIS)

    Oh, Wang Kyun; Kim, Sang Hyun

    2017-01-01

    In abdominal Ultrasonography, the fatty liver is diagnosed through hepatic parenchymal echo increased parenchymal density and unclear blood vessel boundary, and according to many studies, abdominal Ultrasonography has 60 ∼ 90% of sensitivity and 84 ∼ 95% of specificity in diagnosis of fatty liver, but the result of Ultrasonography is dependent on operators, so there can be difference among operators, and quantitative measurement of fatty infiltration is impossible. Among examinees who same day received abdominal Ultrasonography and chest computed tomography (CT), patients who were diagnosed with a fatty liver in the Ultrasonography were measured with liver Hounsfield Units (HU) of chest CT imaging to analyze the accuracy of the fatty liver diagnosis. Among 720 subject examinees, those who were diagnosed with a fatty liver through abdominal Ultrasonography by family physicians were 448, which is 62.2%. The result of Liver HU measurement in the chest CT imaging of those who were diagnosed with a fatty liver showed that 175 out of 720 had the measured value of less than 40 HU, which is 24.3%, and 173 were included to the 175 among 448 who were diagnosed through Ultrasonography, so 98.9% corresponded. This indicates that the operators' subjective ability has a great impact on diagnosis of lesion in Ultrasonography diagnosis of a fatty liver, and that in check up chest CT, under 40 HU in the measurement of Liver HU can be used for reference materials in diagnosis of a fatty liver

  20. Fatty liver diagnostic from medical examination to analyze the accuracy between the abdominal ultrasonography and liver hounsfield units

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Wang Kyun [Dept. of Radiology, Cheongju Medical Center, Cheongju (Korea, Republic of); Kim, Sang Hyun [Dept. of Radiological Science, Shinhan University, Uijeongbu (Korea, Republic of)

    2017-06-15

    In abdominal Ultrasonography, the fatty liver is diagnosed through hepatic parenchymal echo increased parenchymal density and unclear blood vessel boundary, and according to many studies, abdominal Ultrasonography has 60 ∼ 90% of sensitivity and 84 ∼ 95% of specificity in diagnosis of fatty liver, but the result of Ultrasonography is dependent on operators, so there can be difference among operators, and quantitative measurement of fatty infiltration is impossible. Among examinees who same day received abdominal Ultrasonography and chest computed tomography (CT), patients who were diagnosed with a fatty liver in the Ultrasonography were measured with liver Hounsfield Units (HU) of chest CT imaging to analyze the accuracy of the fatty liver diagnosis. Among 720 subject examinees, those who were diagnosed with a fatty liver through abdominal Ultrasonography by family physicians were 448, which is 62.2%. The result of Liver HU measurement in the chest CT imaging of those who were diagnosed with a fatty liver showed that 175 out of 720 had the measured value of less than 40 HU, which is 24.3%, and 173 were included to the 175 among 448 who were diagnosed through Ultrasonography, so 98.9% corresponded. This indicates that the operators' subjective ability has a great impact on diagnosis of lesion in Ultrasonography diagnosis of a fatty liver, and that in check up chest CT, under 40 HU in the measurement of Liver HU can be used for reference materials in diagnosis of a fatty liver.

  1. Human immunodeficiency virus infection and the liver.

    Science.gov (United States)

    Crane, Megan; Iser, David; Lewin, Sharon R

    2012-03-27

    Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries.

  2. The Role of Ischemia Modified Albumin as a Biomarker in Patients with Chronic Liver Disease.

    Science.gov (United States)

    Kumar, Prashanth Ashok; Subramanian, Kavitha

    2016-03-01

    Chronic Liver Disease (CLD) is characterised by gradual destruction of liver tissue over time. Ischemia Modified Albumin (IMA) is an upcoming biomarker shown to be elevated in conditions associated with ischemia and oxidative stress. Albumin levels are greatly reduced in patients with CLD and studying its alterations will provide essential information regarding the molecular changes occurring to it. The study aims to estimate IMA and IMA/Albumin ratio in patients with CLD and to correlate it with parameters assessing liver function and the Model for End Stage Liver Disease (MELD) score. The study consisted of 43 CLD patients as test subjects and 28 apparently healthy individuals as controls. Multiple parameters assessing liver function like albumin, bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), Gamma Glutamyl Transpeptidase (GGT), alkaline phosphatase (ALP), Prothrombin Time (PT) INR and creatinine were estimated and the MELD score calculated. Serum IMA expressed as Absorbance Units (ABSU) was estimated using the Albumin Cobalt Binding test (ABT). Student's t-test and correlation coefficient was used for statistical analysis. Serum IMA was significantly higher in CLD patients (0.5320 ± 0.1677) as compared to the control group (0.3203 ± 0.1257) with a p-value of CLD compared to control group (0.0714 ± 0.0283) with a p-value of CLD could indicate a qualitative change and not merely a quantitative reduction of albumin. IMA can serve as a biomarker to assess the disease severity and prognosis of CLD patients.

  3. Computer-aided diagnostic system of diffuse liver diseases using scintiscanning, 1. Application of linear discriminant function

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, T; Ogawa, F; Okabe, H; Murakami, K [Kyoto Prefectural Univ. of Medicine (Japan); Yoshida, S

    1976-07-01

    An approach to an automated diagnostic system for diffuse parenchymal diseases of the liver is made based on hepatic scintigraphy and an electronic computer. The findings of hepatic scintigram with /sup 198/Au-colloid were analysed for 7 items, various patterns of hepatic image on anterior view, various patterns of hepatic image on right lateral view, criteria for visualization of bone marrow on anterior view, criteria for visualization of bone marrow on right lateral view, criteria for visualization of spleen on anterior view, degree of splenomegaly, and value of effective hepatic blood flow (KL-value). Each item was subdivided into several categories. Multivariate discriminant analysis was used for differential diagnosis of liver diseases with a dummy variable, based on the 25 categories of the 7 item on 100 abnormal hepato-scintigrams confirmed histologically, and on 20 normal subjects. This study was 90.0% accurate in normal liver, 81.1% accurate in acute hepatitis, 71.1% in inactive chronic hepatitis, 78.2% in active chronic hepatitis, 93.3% in Ko-type of liver cirrhosis, and 77.8% in the Otu-type of liver cirrhosis. The final diagnostic accuracy was 81.7% in all cases for training group. The accuracy of hepatic scintigraphy was 13% and 19% higher than that of laboratory findings in differentiating two groups of liver cirrhosis and two groups of chronic hepatitis respectively. To obtain maximum diagnostic information for discriminating among etiologies, ranges of discriminant function coefficients in these items were compared with in each group of liver diseases. The most useful diagnostic finding were the configurations of the hepatic images on the anterior and the right lateral views. Visualization of the spleen and the degree of splenomegaly were also useful for differentiation in each group of chronic hepatitis and liver cirrhosis.

  4. A galactose-functionalized dendritic siRNA-nanovector to potentiate hepatitis C inhibition in liver cells

    Science.gov (United States)

    Lakshminarayanan, Abirami; Reddy, B. Uma; Raghav, Nallani; Ravi, Vijay Kumar; Kumar, Anuj; Maiti, Prabal K.; Sood, A. K.; Jayaraman, N.; Das, Saumitra

    2015-10-01

    A RNAi based antiviral strategy holds the promise to impede hepatitis C viral (HCV) infection overcoming the problem of emergence of drug resistant variants, usually encountered in the interferon free direct-acting antiviral therapy. Targeted delivery of siRNA helps minimize adverse `off-target' effects and maximize the efficacy of therapeutic response. Herein, we report the delivery of siRNA against the conserved 5'-untranslated region (UTR) of HCV RNA using a liver-targeted dendritic nano-vector functionalized with a galactopyranoside ligand (DG). Physico-chemical characterization revealed finer details of complexation of DG with siRNA, whereas molecular dynamic simulations demonstrated sugar moieties projecting ``out'' in the complex. Preferential delivery of siRNA to the liver was achieved through a highly specific ligand-receptor interaction between dendritic galactose and the asialoglycoprotein receptor. The siRNA-DG complex exhibited perinuclear localization in liver cells and co-localization with viral proteins. The histopathological studies showed the systemic tolerance and biocompatibility of DG. Further, whole body imaging and immunohistochemistry studies confirmed the preferential delivery of the nucleic acid to mice liver. Significant decrease in HCV RNA levels (up to 75%) was achieved in HCV subgenomic replicon and full length HCV-JFH1 infectious cell culture systems. The multidisciplinary approach provides the `proof of concept' for restricted delivery of therapeutic siRNAs using a target oriented dendritic nano-vector.A RNAi based antiviral strategy holds the promise to impede hepatitis C viral (HCV) infection overcoming the problem of emergence of drug resistant variants, usually encountered in the interferon free direct-acting antiviral therapy. Targeted delivery of siRNA helps minimize adverse `off-target' effects and maximize the efficacy of therapeutic response. Herein, we report the delivery of siRNA against the conserved 5'-untranslated

  5. Arrhythmia risk in liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ioana Mozos

    2015-01-01

    Interactions between the functioning of the heart andthe liver have been described, with heart diseasesaffecting the liver, liver diseases affecting the heart,and conditions that simultaneously affect both. Theheart is one of the most adversely affected organs inpatients with liver cirrhosis. For example, arrhythmiasand electrocardiographic changes are observed inpatients with liver cirrhosis. The risk for arrhythmia isinfluenced by factors such as cirrhotic cardiomyopathy,cardiac ion channel remodeling, electrolyte imbalances,impaired autonomic function, hepatorenal syndrome, metabolic abnormalities, advanced age, inflammatory syndrome, stressful events, impaired drug metabolism and comorbidities. Close monitoring of cirrhotic patients is needed for arrhythmias, particularly when QT intervalprolonging drugs are given, or if electrolyte imbalances or hepatorenal syndrome appear. Arrhythmia risk may persist after liver transplantation due to possible QT interval prolongation, persistence of the parasympathetic impairment, post-transplant reperfusion and chronic immunosuppression, as well as consideration of the fact that the transplant itself is a stressful event for the cardiovascular system. The aims of the present article were to provide a review of the most important data regarding the epidemiology, pathophysiology, and biomarkers of arrhythmia risk in patients with liver cirrhosis, to elucidate the association with long-term outcome, and to propose future research directions.

  6. Prolactin and liver disease

    NARCIS (Netherlands)

    A.G.C. Bauer (Alexander)

    1982-01-01

    textabstractCirrhosis of the liver is associated with profound endocrinological disturbances. Until recently it was thought that these disturbances were caused mainly by ineffective elimination of hormones by the diseased liver. It is now known that the pathogenesis of disturbed hormonal function in

  7. 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.

  8. The Influence of histamine H1-receptor on liver functions in immunized rabbits.

    Science.gov (United States)

    Tripathi, Trivendra; Shahid, Mohammad; Khan, Haris M; Khan, Rahat Ali; Siddiqui, Mashiatullah; Mahdi, Abbas Ali

    2011-10-01

    This study was designed to investigate the functional roles of histamine and histamine H1-receptor agonist and antagonist in the development of liver function impairment in immunized rabbits. The study comprised of six groups containing 18 rabbits each. Group III-VI received histamine (100 μg/kg, s.c.), H1R-agonist (HTMT, 10 μg/kg, s.c.), H1R-antagonist (pheniramine, 10 mg/kg, i.m.), and H1R-antagonist (pheniramine, 10 mg/kg, i.m.) plus histamine (100 μg/kg, s.c.), respectively, b.i.d. for 10 days. Group I (negative control) and group II (positive control) received sterile distilled water intramuscularly b.i.d. for 10 days. Groups II-VI were immunized on day 3 with intravenous injection of SRBC (1 × 10(9) cells/ml). Blood samples were collected on pre-immunization day 0, as well as on days 7-, 14-, 21-, 28-, and 58-post-immunization. Biochemical parameters AST, ALT, alkaline phosphatase and bilirubin [total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IB)] were determined. On each experimental day, the mean values of serum enzymes and bilirubin in group I and group II showed no significant changes while in group III, IV, V, and VI, these enzymes and bilirubin levels showed significant changes (p pheniramine, and combination of histamine + pheniramine cause hepatic function impairment in terms of altered serum enzymes and bilirubin levels. The present findings suggest that HTMT causes moderate liver function impairment while others show mild impairment.

  9. Effects of Oral L-Carnitine on Liver Functions after Transarterial Chemoembolization in Intermediate-Stage HCC Patients

    Directory of Open Access Journals (Sweden)

    Abeer Hassan

    2015-01-01

    Full Text Available Transarterial chemoembolization (TACE is usually followed by hepatic dysfunction. We evaluated the effects of L-carnitine on post-TACE impaired liver functions. Methods. 53 cirrhotic hepatocellular carcinoma patients at Osaka Medical College were enrolled in this study and assigned into either L-carnitine group receiving 600 mg oral L-carnitine daily or control group. Liver functions were evaluated at pre-TACE and 1, 4, and 12 weeks after TACE. Results. The L-carnitine group maintained Child-Pugh (CP score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (P<0.01. Conversely, the control group reported a significant CP score deterioration at 1 week (P<0.05 and 12 weeks after TACE (P<0.05. L-carnitine suppressed serum albumin deterioration at 1 week after TACE. There were significant differences between L-carnitine and control groups regarding mean serum albumin changes from baseline to 1 week (P<0.05 and 4 weeks after TACE (P<0.05. L-carnitine caused prothrombin time improvement from baseline to 1, 4 (P<0.05, and 12 weeks after TACE. Total bilirubin mean changes from baseline to 1 week after TACE exhibited significant differences between L-carnitine and control groups (P<0.05. The hepatoprotective effects of L-carnitine were enhanced by branched chain amino acids combination. Conclusion. L-carnitine maintained and improved liver functions after TACE.

  10. Hypoglycemic depression of hepatic phagocytosis in vivo and in the in situ perfused rat liver.

    Science.gov (United States)

    Kober, P M; Filkins, J P

    1981-01-01

    Depression of the phagocytic function of the reticuloendothelial system (RES) during endotoxic hypoglycemia has been implicated in the pathogenesis of endotoxin shock. The present study evaluated the in vivo effects of hypoglycemia on RES function and assessed the effects of an vivo bout of hypoglycemia on phagocytosis in the in situ perfused rat liver. Hypoglycemia was produced in male Holtzman rats using either 1 U of regular insulin (RI) (ILETIN, Lilly) or 0.75 U of long-acting insulin (LAI) (85% LENTE/15% ULTRALENTE, Lilly). RES function was quantitated by intravascular clearance of 8 mg/100 gm body weight colloidal carbon (CC). Two hr after RI and 2.5 hr after LAI, the intravascular halftimes of CC clearance were 19 +/- 2 min (N = 22) and 18 +/- 1 min (N = 19), respectively, as compared to control, 11.3 +/- 0.4 min (N = 53, P less than 0.001). The corresponding plasma glucose (PG) levels were 95 +/- 2 mg/dl in control, 14.4 +/- 0.9 for the RI group, and 17 +/- 1 for LAI. Two hr after RI, livers were perfused for 10 min in situ with 50 mg/liter CC in saline 5% rat serum. PG for control liver donors were 90 +/- 3 mg/dl, while those for hypoglycemic liver donors were 15 +/- 2. CC uptake was decreased from 22 micrograms/min/gm liver in the control (+ serum, n = 19) to 11 +/- 2 in hypoglycemia livers (N = 6); no effect of serum on hypoglycemic depression of the RES was seen. There were no differences in flow rates in the 2 groups. These results indicate that hypoglycemia directly impairs RES function and that the in vivo depression of intravascular clearance is not related to either the presence or absence of serum factors or total hepatic blood flow. Thus, the characteristic hypoglycemia of endotoxin shock may contribute to RES depression and the lethal shock syndrome.

  11. 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.

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

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  13. Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expressions in fatty liver rats.

    Science.gov (United States)

    Duan, Yun-Fei; An, Yong; Zhu, Feng; Jiang, Yong

    2017-08-15

    Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathway and microRNA expressions in this process. A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and real-time quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions. Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups, while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and inflammatory cell infiltration were found. Cell apoptosis number was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all Pfatty liver I/R injury by affecting the eNOS-NO pathway and liver microRNA expressions. Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.

  14. [EFFECT OF ACETYLCYSTEINE, CORVITIN AND THEIR COMBINATION ON THE FUNCTIONAL STATE OF LIVER IN RATS WITH PARACETAMOL INDUCED TOXIC HEPATITIS].

    Science.gov (United States)

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

    2017-02-01

    Nowadays drug-induced hepatotoxicity is urgent problem worldwide. Currently more than 1000 drugs are hepatotoxic and most often are the reason of acute fulminant hepatitis and hepatocellular failure, the states requiring liver transplantation. The paracetamol induced liver toxicity is related with accumulation of its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is the free radical and enhances peroxidation of lipids, disturbs the energy status and causes death of hepatocytes. During our research we investigated and assessed the efficacy of acetylcysteine, corvitin and their combination in rat model of paracetamol induced acute toxic hepatitis. The study was performed on mature white male Wistar rates with body mass 150-180 g. 50 rats were randomly divided into 5 groups (10 rats in each group). To get the model of acute toxic hepatitis single intraperitoneal injection of paracetamol solution was used (750 mg/kg). Toxic hepatitis was treated with intrapertoneal administration of 40mg/kg acetylcysteine or 100mg/kg corvitin, as well as with combination of these drugs. Monotherapy with acetylcysteine and corvitin of paracetamol induced toxic hepatitis improved the liver function, decreased relative mass of the liver and animal mortality. The treatment of toxic hepatitis was most effective in the case of simultaneous administration of acetylcysteine and corvitin. The normal value of laboratory tests (ALT, ACT, alkaline phosphatase, total and unconjugated bilirubin) was reached and mortality was not more observed. On the bases of obtained data was concluded that acetylcysteine and corvitin have almost equal hepatoprotective activity. The combination of two drugs actually improves the liver function. The most pronounced hepatoprotective effect may be due to synergic action of acetylcysteine and corvitin and such regime can be recommended for correction of liver function.

  15. Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver

    Directory of Open Access Journals (Sweden)

    Laghi Luigi

    2006-04-01

    Full Text Available Abstract Background Epigenetic changes during ageing and their relationship with cancer are under the focus of intense research. RASSF1A and NORE1A are novel genes acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A has not been previously investigated in the human liver, recent reports have suggested that RASSF1A is frequently epigenetically methylated not only in HCC but also in the cirrhotic liver. Methods To address whether epigenetic changes take place in connection to age and/or to the underlying disease, we investigated RASSF1A and NORE1A gene promoter methylation by conventional methylation specific PCR and Real-Time MSP in a series of hepatitic and non-hepatitic livers harboring regenerative/hyperplastic (cirrhosis/focal nodular hyperplasia, dysplastic (large regenerative, low and high grade dysplastic nodules and neoplastic (hepatocellular adenoma and carcinoma growths. Results In the hepatitic liver (chronic hepatitic/cirrhosis, hepatocellular nodules and HCC we found widespread RASSF1A gene promoter methylation with a methylation index that increased from regenerative conditions (cirrhosis to hepatocellular nodules (p RASSF1A gene promoter methylation, NORE1A gene was never found epigenetically alterated in both hepatitic and non-hepatitic liver. Conclusion We have shown that in non-lesional, regenerative and neoplastic liver the RASSF1A gene is increasingly methylated, that this condition takes place as an age-related phenomenon and that the early setting and spreading over time of an epigenetically methylated hepatocyte subpopulation, might be related to liver tumorigenesis.

  16. Effect of airplane transport of donor livers on post-liver transplantation survival.

    Science.gov (United States)

    Huang, Yi; MacQuillan, Gerry; Adams, Leon A; Garas, George; Collins, Megan; Nwaba, Albert; Mou, Linjun; Bulsara, Max K; Delriviere, Luc; Jeffrey, Gary P

    2016-11-07

    To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Australia from 1992 to 2012. Donor and recipient characteristics information were extracted from Western Australian liver transplantation service database. Patients were followed up for a mean of six years. Patient and graft survival were evaluated and compared between patients who received a local donor liver and those who received an airplane transported donor liver. Predictors of survival were determined by univariate and multivariate analysis using cox regression. One hundred and ninety-three patients received a local donor liver and 93 patients received an airplane transported donor liver. Airplane transported livers had a significantly lower alanine transaminase (mean: 45 U/L vs 84 U/L, P = 0.035), higher donor risk index (mean: 1.88 vs 1.42, P airplane transport retained significance for graft loss (HR = 1.92, 95%CI: 1.16-3.17). One year graft survival was 0.88 for those with a local liver and was 0.71 for those with an airplane transported liver. One year graft loss was due to primary graft non-function or associated with preservation injury in 20.8% of recipients of an airplane transported liver compared with 4.6% in those with a local liver ( P = 0.027). Airplane transport of donor livers was independently associated with reduced graft survival following liver transplantation.

  17. Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Schwimmer, Jeffrey B; Middleton, Michael S; Behling, Cynthia; Newton, Kimberly P; Awai, Hannah I; Paiz, Melissa N; Lam, Jessica; Hooker, Jonathan C; Hamilton, Gavin; Fontanesi, John; Sirlin, Claude B

    2015-06-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI-estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. Liver PDFF estimated by MRI was significantly (P steatosis grade. The correlation of MRI-estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly (P steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI-estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child. Advanced magnitude-based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus, magnitude-based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child. © 2015 by the American Association for the Study of Liver Diseases.

  18. Changes in Liver Function Enzymes of HIV/AIDS Patients Treated ...

    African Journals Online (AJOL)

    user

    on liver enzyme markers (Aspartate aminotransferase, Alanine aminotransferase ... the diagnosis and advanced infection of the liver cells by HIV. ... recommended guideline for the treatment of HIV ... HIV-positive patients not on treatment and.

  19. Liver involvement in Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Wong, Adelaine; Ortiz-Neira, Clara L.; Abou Reslan, Walid; Kaura, Deepak; Sharon, Raphael; Anderson, Ronald; Pinto-Rojas, Alfredo

    2006-01-01

    Liver involvement in Langerhans cell histiocytosis (LCH) typically presents with hepatomegaly and other signs of liver dysfunction. We present an 11-month-old child having only minimally elevated liver enzymes as an indication of liver involvement. Using sonography as the initial diagnostic tool followed by MRI, LCH of the liver was revealed. A review of sonographic, CT, MRI and MR cholangiopancreatography findings in liver LCH is presented. We recommend that physicians consider sonography and MRI screening for liver involvement in patients with newly diagnosed LCH, as periportal involvement may be present with little or no liver function abnormality present, as in this patient. (orig.)

  20. Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver

    Science.gov (United States)

    Di Gioia, Sonia; Bianchi, Paolo; Destro, Annarita; Grizzi, Fabio; Malesci, Alberto; Laghi, Luigi; Levrero, Massimo; Morabito, Alberto; Roncalli, Massimo

    2006-01-01

    Background Epigenetic changes during ageing and their relationship with cancer are under the focus of intense research. RASSF1A and NORE1A are novel genes acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A has not been previously investigated in the human liver, recent reports have suggested that RASSF1A is frequently epigenetically methylated not only in HCC but also in the cirrhotic liver. Methods To address whether epigenetic changes take place in connection to age and/or to the underlying disease, we investigated RASSF1A and NORE1A gene promoter methylation by conventional methylation specific PCR and Real-Time MSP in a series of hepatitic and non-hepatitic livers harboring regenerative/hyperplastic (cirrhosis/focal nodular hyperplasia), dysplastic (large regenerative, low and high grade dysplastic nodules) and neoplastic (hepatocellular adenoma and carcinoma) growths. Results In the hepatitic liver (chronic hepatitic/cirrhosis, hepatocellular nodules and HCC) we found widespread RASSF1A gene promoter methylation with a methylation index that increased from regenerative conditions (cirrhosis) to hepatocellular nodules (p < 0.01) to HCC (p < 0.001). In the non-hepatitic liver a consistent pattern of gene methylation was also found in both lesional (focal nodular hyperplasia and hepatocellular adenoma) and non-lesional tissue. Specifically, hepatocellular adenomas (HA) showed a methylation index significantly higher than that detected in focal nodular hyperplasia (FNH) (p < 0.01) and in non-lesional tissue (p < 0.001). In non-lesional liver also the methylation index gradually increased by ageing (p = 0.002), suggesting a progressive spreading of methylated cells over time. As opposed to RASSF1A gene promoter methylation, NORE1A gene was never found epigenetically alterated in both hepatitic and non-hepatitic liver. Conclusion We have shown that in non-lesional, regenerative and neoplastic liver the RASSF1A gene is increasingly

  1. 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

  2. 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

    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 A...

  3. Pancreatic fat and β-cell function in overweight/obese children with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Pacifico, Lucia; Di Martino, Michele; Anania, Caterina; Andreoli, Gian Marco; Bezzi, Mario; Catalano, Carlo; Chiesa, Claudio

    2015-04-21

    To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease (NAFLD). We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction (HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue (VAT), pancreatic fat fraction (PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance (HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index (WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either: (1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/dL to Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes (OR = 3.38; 95%CI: 1.10-10.4; P = 0.034). In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.

  4. Proteomic analysis of physiological function response to hot summer in liver from lactating dairy cows.

    Science.gov (United States)

    Wang, Qiangjun; Zhao, Xiaowei; Zhang, Zijun; Zhao, Huiling; Huang, Dongwei; Cheng, Guanglong; Yang, Yongxin

    2017-04-01

    Lactation performance of dairy cattle is susceptible to heat stress. The liver is one of the most crucial organs affected by high temperature in dairy cows. However, the physiological adaption by the liver to hot summer conditions has not been well elucidated in lactating dairy cows. In the present study, proteomic analysis of the liver in dairy cows in spring and hot summer was performed using a label-free method. In total, 127 differentially expressed proteins were identified; most of the upregulated proteins were involved in protein metabolic processes and responses to stimuli, whereas most of the downregulated proteins were related to oxidation-reduction. Pathway analysis indicated that 3 upregulated heat stress proteins (HSP90α, HSP90β, and endoplasmin) were enriched in the NOD-like receptor signaling pathway, whereas several downregulated NADH dehydrogenase proteins were involved in the oxidative phosphorylation pathway. The protein-protein interaction network indicated that several upregulated HSPs (HSP90α, HSP90β, and GRP78) were involved in more interactions than other proteins and were thus considered as central hub nodes. Our findings provide novel insights into the physiological adaption of liver function in lactating dairy cows to natural high temperature. Copyright © 2017. Published by Elsevier Ltd.

  5. Evaluation of liver hemodynamics using SPIO-enhanced dynamic MRI. Comparison between cirrhotic liver and normal liver

    International Nuclear Information System (INIS)

    Shimada, Kotaro; Kobayashi, Hisato; Furuta, Akihiro; Nunoura, T.; Takahashi, Takahiro; Ogasawara, Nobuhiko; Akuta, Keizo

    2006-01-01

    SPIO, ferucarbotran (Resovist), which enables rapid bolus injection is well suited for the evaluation of liver hemodynamics. Our study aimed to assess the difference of hemodynamics associated with progression of chronic liver disease using SPIO-enhanced dynamic MRI. Ten patients with normal liver function, 10 patients with chronic hepatitis, and 16 patients with liver cirrhosis were examined. The MR perfusion studies were performed by 1.5T MR system with a single-shot GRE-EPI with spectral presaturation inversion recovery (SPIR) and sensitivity encoding (SENSE) technique. After the bolus injection of SPIO (0.016 ml/kg) followed by a 20 ml saline flush, 30 sequential dynamic echo planar images were obtained under the condition of 30 seconds breath hold. From the ROI set in the right lobe of the liver, time-to-signal intensity curves (TICs) were obtained. TICs were converted to time-to-R2 * curves, and the slope at hepatic arterial phase (Sa) and at portal predominant phase (Sp) were calculated by the linear regression. Sp/Sa (portal/arterial ratio) of each group was analyzed statistically. (unpaired T-test) In comparing Sp/Sa of each group, there was a significant difference between normal liver and advanced liver cirrhosis. The decrease of Sp/Sa was seen in severe cirrhosis, but this change was unclear in chronic hepatitis and mild cirrhosis. In extremely severe cirrhosis, there was a bizarre phenomenon that Sp became minus number. In conclusion, SPIO-enhanced dynamic MRI was useful to assess the difference of liver hemodynamics associated with progression of chronic liver disease. (author)

  6. Influence of autologous blood transfusion in liver transplantation in patients with hepatitis B on the function and hemorheology of red blood cells

    OpenAIRE

    Liu, Xiangfu; Fan, Ruifang; Lu, Ying; Kuang, Lihua; Yuan, Qing; Chen, Yuchan; Lin, Zhesheng; Lin, Dongjun

    2017-01-01

    The present study aimed to characterize the function and hemorheology of red blood cells (RBCs) recovered during liver transplantation surgery in patients with hepatitis B and decompensation. A total of 15 hepatitis B patients with decompensation who underwent liver transplantation surgery were included in the present study. Blood samples were recovered during the liver transplantation surgery using an Autologous Blood Recovery System. The morphology and structure of RBCs were characterized a...

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

    Science.gov (United States)

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

    2005-05-01

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

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

    Science.gov (United States)

    Dave, M; Langbart, M M

    1994-03-01

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

  9. Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression

    Directory of Open Access Journals (Sweden)

    Francesco Bellanti

    2018-05-01

    Full Text Available The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury.

  10. Evaluation of Liver Fibrosis Using Texture Analysis on Combined-Contrast-Enhanced Magnetic Resonance Images at 3.0T

    Directory of Open Access Journals (Sweden)

    Takeshi Yokoo

    2015-01-01

    Full Text Available Purpose. To noninvasively assess liver fibrosis using combined-contrast-enhanced (CCE magnetic resonance imaging (MRI and texture analysis. Materials and Methods. In this IRB-approved, HIPAA-compliant prospective study, 46 adults with newly diagnosed HCV infection and recent liver biopsy underwent CCE liver MRI following intravenous administration of superparamagnetic iron oxides (ferumoxides and gadolinium DTPA (gadopentetate dimeglumine. The image texture of the liver was quantified in regions-of-interest by calculating 165 texture features. Liver biopsy specimens were stained with Masson trichrome and assessed qualitatively (METAVIR fibrosis score and quantitatively (% collagen stained area. Using L1 regularization path algorithm, two texture-based multivariate linear models were constructed, one for quantitative and the other for quantitative histology prediction. The prediction performance of each model was assessed using receiver operating characteristics (ROC and correlation analyses. Results. The texture-based predicted fibrosis score significantly correlated with qualitative (r=0.698, P<0.001 and quantitative (r=0.757, P<0.001 histology. The prediction model for qualitative histology had 0.814–0.976 areas under the curve (AUC, 0.659–1.000 sensitivity, 0.778–0.930 specificity, and 0.674–0.935 accuracy, depending on the binary classification threshold. The prediction model for quantitative histology had 0.742–0.950 AUC, 0.688–1.000 sensitivity, 0.679–0.857 specificity, and 0.696–0.848 accuracy, depending on the binary classification threshold. Conclusion. CCE MRI and texture analysis may permit noninvasive assessment of liver fibrosis.

  11. Abacavir-induced liver toxicity

    Directory of Open Access Journals (Sweden)

    Maria Diletta Pezzani

    2016-09-01

    Full Text Available Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine.

  12. Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Obayashi, Yoko, E-mail: youko_oobayashi@ajinomoto.com [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Campbell, Jean S.; Fausto, Nelson [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Yeung, Raymond S. [Department of Surgery, University of Washington School of Medicine, Seattle, WA (United States)

    2013-07-19

    Highlights: •Tuberin phosphorylation correlated with mTOR activation in early liver regeneration. •Liver regeneration in the Tsc2+/− mice was not enhanced. •The Tsc2+/− livers failed to accumulate lipid bodies during liver regeneration. •Mortality rate increased in Tsc2+/− mice after partial hepatectomy. •Tuberin plays a critical role in hepatic lipid accumulation to support regeneration. -- Abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/− mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/− mice was not enhanced. Instead, the Tsc2+/− livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation.

  13. Study of functional liver scintiscanning with sup(99m)technetium diethyl iminodiacetate in different hepatobiliary diseases

    International Nuclear Information System (INIS)

    Stickel, R.

    1981-01-01

    In 46 patients with five different affections, liver scintiscanning with sup(99m)technetium diethyl aminodiacetate was carried through. From the time/activity curves of different parts of the camera matrix picture the evaluation program of a camera process computer system calculated 25 function parameters, 8 of which were more closely described. The group with affections of the liver parenchyma showed a characteristic prolongation of the half-life period above the cardiac ragion of interest, a gentler curve rise and a retardation of Tsub(max) of the parenchyma curve as well as reduced evidence of activity of the intestine. For patients with extrahepatic cholostasis, prolonged and retarded accumulation of activity above the region of interest of the bibe duct, and reduced emission of activity from the intestine were characteristic, with the liver parenchyma parameters deviating only slightly from normal. In the groups with vascular stasis liver and nuclear findings the computation parameters did not permit to recognize a typical behaviour. The correlation of the serum bilirubin level with the half-life period above the cardiac region gave a correlation coefficient of r = 0.695. (orig./MG) [de

  14. Timed function tests, motor function measure, and quantitative thigh muscle MRI in ambulant children with Duchenne muscular dystrophy: A cross-sectional analysis.

    Science.gov (United States)

    Schmidt, Simone; Hafner, Patricia; Klein, Andrea; Rubino-Nacht, Daniela; Gocheva, Vanya; Schroeder, Jonas; Naduvilekoot Devasia, Arjith; Zuesli, Stephanie; Bernert, Guenther; Laugel, Vincent; Bloetzer, Clemens; Steinlin, Maja; Capone, Andrea; Gloor, Monika; Tobler, Patrick; Haas, Tanja; Bieri, Oliver; Zumbrunn, Thomas; Fischer, Dirk; Bonati, Ulrike

    2018-01-01

    The development of new therapeutic agents for the treatment of Duchenne muscular dystrophy has put a focus on defining outcome measures most sensitive to capture treatment effects. This cross-sectional analysis investigates the relation between validated clinical assessments such as the 6-minute walk test, motor function measure and quantitative muscle MRI of thigh muscles in ambulant Duchenne muscular dystrophy patients, aged 6.5 to 10.8 years (mean 8.2, SD 1.1). Quantitative muscle MRI included the mean fat fraction using a 2-point Dixon technique, and transverse relaxation time (T2) measurements. All clinical assessments were highly significantly inter-correlated with p muscle MRI values significantly correlated with all clinical assessments with the extensors showing the strongest correlation. In contrast to the clinical assessments, quantitative muscle MRI values were highly significantly correlated with age. In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of nonalcoholic fatty liver disease

    Science.gov (United States)

    Obesity is often associated with a cluster of increased health risks collectively known as "Metabolic Syndrome" (MS). MS is often accompanied by development of fatty liver. Sometimes fatty liver results in damage leading to reduced liver function, and need for a transplant. This condition is known...

  16. Improved hepatocyte function of future liver remnant of cirrhotic rats after portal vein ligation: a bonus other than volume shifting.

    Science.gov (United States)

    Lin, Kun-Ju; Liao, Chien-Hung; Hsiao, Ing-Tsung; Yen, Tzu-Chen; Chen, Tse-Ching; Jan, Yi-Yin; Chen, Miin-Fu; Yeh, Ta-Sen

    2009-02-01

    Preoperative portal vein embolization is increasingly employed for those with hepatocellular carcinoma and cirrhosis to gain a volume-shifting effect. However, the alterations of histologic architecture and hepatocyte function of future liver remnant (FLR) remain unexplored. Portal vein ligation (PVL) was performed in cirrhotic and noncirrhotic rats. Regeneration indices that include the DNA synthesis index, restituted liver mass, and the redistributed volume ratio were measured. The indocyanine green 15' retention test (ICG-R15), histologic changes, total Knodell score, and activated hepatic stellate cells (HSCs) were measured before and after PVL. Tc-99m sulfur-colloid liver single photon emission computed tomography (SPECT) and diisopropyl iminoacetic acid (DISIDA) SPECT were conducted. The redistributed volume ratio of cirrhotic rats was less than noncirrhotic rats (63% vs 80%, P baseline (6.0 +/- 4.1% vs 15.8 +/- 4.6%, P baseline. The redistributed volume ratio of noncirrhotic and cirrhotic rats based on 99mTc sulfur-colloid SPECT were 79% and 64%, respectively. The clearance T(1/2) of FLR in cirrhotic rats based on DISIDA SPECT was decreased compared with baseline (5.2 +/- 1.9 min vs 8.6 +/- 3.1 min). The regenerated functional liver mass of cirrhotic rats after PVL is less than noncirrhotic rats, whereas the hepatocyte function of FLR in cirrhotic rats is improved relevant to tissue remodeling.

  17. Evolution of association between renal and liver functions while awaiting heart transplant: An application using a bivariate multiphase nonlinear mixed effects model.

    Science.gov (United States)

    Rajeswaran, Jeevanantham; Blackstone, Eugene H; Barnard, John

    2018-07-01

    In many longitudinal follow-up studies, we observe more than one longitudinal outcome. Impaired renal and liver functions are indicators of poor clinical outcomes for patients who are on mechanical circulatory support and awaiting heart transplant. Hence, monitoring organ functions while waiting for heart transplant is an integral part of patient management. Longitudinal measurements of bilirubin can be used as a marker for liver function and glomerular filtration rate for renal function. We derive an approximation to evolution of association between these two organ functions using a bivariate nonlinear mixed effects model for continuous longitudinal measurements, where the two submodels are linked by a common distribution of time-dependent latent variables and a common distribution of measurement errors.

  18. Ultrasound versus liver function tests for diagnosis of common bile duct stones.

    Science.gov (United States)

    Gurusamy, Kurinchi Selvan; Giljaca, Vanja; Takwoingi, Yemisi; Higgie, David; Poropat, Goran; Štimac, Davor; Davidson, Brian R

    2015-02-26

    Ultrasound and liver function tests (serum bilirubin and serum alkaline phosphatase) are used as screening tests for the diagnosis of common bile duct stones in people suspected of having common bile duct stones. There has been no systematic review of the diagnostic accuracy of ultrasound and liver function tests. To determine and compare the accuracy of ultrasound versus liver function tests for the diagnosis of common bile duct stones. We searched MEDLINE, EMBASE, Science Citation Index Expanded, BIOSIS, and Clinicaltrials.gov to September 2012. We searched the references of included studies to identify further studies and systematic reviews identified from various databases (Database of Abstracts of Reviews of Effects, Health Technology Assessment, Medion, and ARIF (Aggressive Research Intelligence Facility)). We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We included studies that provided the number of true positives, false positives, false negatives, and true negatives for ultrasound, serum bilirubin, or serum alkaline phosphatase. We only accepted studies that confirmed the presence of common bile duct stones by extraction of the stones (irrespective of whether this was done by surgical or endoscopic methods) for a positive test result, and absence of common bile duct stones by surgical or endoscopic negative exploration of the common bile duct, or symptom-free follow-up for at least six months for a negative test result as the reference standard in people suspected of having common bile duct stones. We included participants with or without prior diagnosis of cholelithiasis; with or without symptoms and complications of common bile duct stones, with or without prior treatment for common bile duct stones; and before or after cholecystectomy. At least two authors screened abstracts and selected studies for inclusion independently. Two authors independently collected data from

  19. A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma with poor liver function

    Directory of Open Access Journals (Sweden)

    Hyun Yang

    2017-06-01

    Full Text Available Background/Aims Metronomic chemotherapy (MET is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. The aim of this study was to evaluate the feasibility and overall survival (OS of MET compared to sorafenib for advanced hepatocellular carcinoma (HCC patients with portal vein tumor thrombosis (PVTT. Methods A total of 54 patients with advanced HCC and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53 patients who had undergone sorafenib therapy were analyzed as the control group. The primary endpoint of this study was OS. Results The median number of MET cycles was two (1-15. The OS values for the MET group and sorafenib group were 158 days (132-184 and 117 days (92-142, respectively (P=0.029. The Cox proportional-hazard model showed that a higher risk of death was correlated with higher serum alpha fetoprotein level (≥400 mg/dL, hazard ratio [HR]=1.680, P=0.014 and Child-Pugh class B (HR=1.856, P=0.008. Conclusions MET was associated with more favorable outcomes in terms of overall survival than was sorafenib in patients with advanced HCC with PVTT, especially in patients with poor liver function. Therefore, MET can be considered as a treatment option in patients with advanced HCC with PVTT and poor liver function.

  20. Nonalcoholic fatty liver disease is associated with cognitive function in adults.

    Science.gov (United States)

    Seo, Sang Won; Gottesman, Rebecca F; Clark, Jeanne M; Hernaez, Ruben; Chang, Yoosoo; Kim, Changsoo; Ha, Kyoung Hwa; Guallar, Eliseo; Lazo, Mariana

    2016-03-22

    We hypothesized that nonalcoholic fatty liver disease (NAFLD) is independently associated with cognitive impairment in a representative sample of the general US population regardless of the presence of cardiovascular disease (CVD) or its risk factors. This was a cross-sectional study of 4,472 adults aged 20-59 years who participated in the Third National Health and Nutritional Examination Survey. The participants underwent assessment of liver enzyme activity and hepatic steatosis by ultrasound, and underwent cognitive evaluation using the following computer-administered tests: the Simple Reaction Time Test (SRTT), the Symbol-Digit Substitution Test (SDST), and the Serial Digit Learning Test (SDLT). We defined NAFLD as moderate/severe steatosis as determined by ultrasound in the absence of hepatitis B or C or excessive alcohol consumption. We used multiple linear regression models to examine the association between NAFLD and cognitive function while controlling for potential confounders. Participants with NAFLD showed lower overall performance on the SDLT (β = 0.726, 95% confidence interval [CI] 0.105-1.347), while associations with SRTT and SDST did not reach significance. Increased activity of the liver enzymes alanine aminotransferase (β = 0.018, 95% CI 0.006-0.030) and aspartate aminotransferase (β = 0.021, 95% CI 0.005-0.037) correlated with lower performance on the SDLT, while increased alanine aminotransferase was also correlated with lower performance in the SDST (β = 0.002, 95% CI 0.0001-0.004). NAFLD was independently associated with lower cognitive performance independent of CVD and its risk factors. Given the scarcity of risk factors associated with age-related cognitive decline, these findings may have significant implications. © 2016 American Academy of Neurology.

  1. Towards a new therapy protocol for liver metastases. Effect of boron compounds and BNCT on normal liver regeneration

    International Nuclear Information System (INIS)

    Cardoso, Jorge E.; Heber, Elisa M.; Trivillin, Veronica A.

    2006-01-01

    The Taormina project developed a new method for BNCT treatment of multifocal unresectable liver metastases based on whole liver autograft. The Roffo Institute liver surgeons propose a new technique based on partial liver autograft that would pose less risk to the patient but would require significant healthy liver regeneration following BNCT. The aim of the present study was to assess the effect of BPA, GB-10 (Na 2 10 B 10 H 10 ) and (GB-10 + BPA) and of BNCT mediated by these boron compounds on normal liver regeneration in the Wistar rat. Normal liver regeneration, body weight, hemogram, liver and kidney function were assessed following partial hepatectomy post administration of BPA, GB-10 or (GB-10 + BPA) and post in vivo BNCT at the RA-6 Reactor. These end-points were evaluated 9 days following partial hepatectomy, the time at which complete liver regeneration occurs in untreated controls. The corresponding biodistribution studies were conducted to perform dosimetric calculations. BPA, GB-10 and (GB-10 + PBA) and in vivo BNCT mediated by these boron compounds in dose ranges compatible with therapy did not cause alterations in the outcome of normal liver regeneration, and did not induce alterations in body weight, hemogram, liver or kidney function. The experimental data available to date support the development of a new BNCT protocol for the treatment of liver metastases that requires the regeneration of normal liver past-BNCT. (author)

  2. [Exposure to toxic dose of adrenaline on the functional state of the liver].

    Science.gov (United States)

    Kopylova, S V; Vlasova, K M; Anashkina, A A

    2017-01-01

    The blood biochemical parameters characterizing the functional state of the liver, and the morphological profile of the body after a single exposure to a toxic dose of adrenaline were studied. Studies were conducted on 60 adult rats (female) weighing 0.15-0.2 kg, were divided into groups: intact animals; experience - animals, injected with epinephrine hydrochloride intraperitoneally in a dose of 0.5 mg/kg. All kinds of Biological material (blood, liver) were collected out through one and ten days after the start of the experiment. The degree of influence of high doses of epinephrine were evaluated in terms of lipid peroxidation (LPO) and protein (PSP) in liver homogenates, the concentration of average weight molecules (MSM), the activity of ALT, AST, alkaline phosphatase, LDH, total protein concentration, glucose and lactate in the blood plasma, as well as the determination of the prothrombin time (PTT) with the counting on the basis thereof of international normalized ration (INR). Histology of the liver was studied by light microscopy. It was found that throughout the experiment, there was an increased in the concentration of lipid peroxidation products and protein in liver homogenates, there was an increase in the concentration of MSM 1.7. Twenty-four hours after the administration of a toxic dose of adrenaline observed hyperenzymemia that manifested an increase in the activity of ALT and AST, was an increase in LDH. After 10-day five after the start of the experiment established the presence hyperenzymemia activity decreased ALT and AST, LDH activity remained elevated, total protein level was higher than in the group of animal in which investigations were conducted one day after the start of the experiment, PTV also continued to decline. In histological sections of the development of a pathological condition characterized by circulatory disturbance - plasmatization, both in central and in small vessels. From the hepatocytes both in the center and the periphery

  3. Gd-EOB-DTPA-enhanced MRI for monitoring future liver remnant function after portal vein embolization and extended hemihepatectomy: A prospective trial.

    Science.gov (United States)

    Geisel, Dominik; Raabe, Philip; Lüdemann, Lutz; Malinowski, Maciej; Stockmann, Martin; Seehofer, Daniel; Pratschke, Johann; Hamm, Bernd; Denecke, Timm

    2017-07-01

    To evaluate changes in liver function after right portal vein embolization (PVE) and extended right hemihepatectomy using gadolinium ethoxybenzyl-DTPA-enhanced (Gd-EOB-DTPA) MRI. In this prospective trial, 37 patients undergoing PVE were examined before and 14 and 28 days after PVE and 10 days after extended hemihepatectomy using Gd-EOB-DTPA-enhanced MRI. Lobar volume, kinetic growth rate (KGR), relative enhancement (RE) as well as hepatocellular uptake index (HUI) and fat signal fraction (FSF) were calculated for each lobe. RE of the left liver lobe (LLL) was steadily increasing after PVE and decreased to 0.48 ± 0.19 10 days after surgery, which is significantly lower than 14 days and 28 days post PVE (P DTPA-enhanced MRI may be used to monitor the functional increase in the FLR after PVE and to depict the intraoperative liver injury leading to a decrease in liver remnant function. • The most significant FLR volume increase happens within the first 14 days. • No MRI parameter was able to predict the success of FLR growth. • Our data suggest an early resection about 14 days after PVE. • Routine Gd-EOB-DTPA-enhanced MRI might be suitable to replace ICG-test.

  4. Nutrition and Liver Health.

    Science.gov (United States)

    Jackson, Alan A

    2017-01-01

    Good clinical practice is based on a secure and accurate diagnosis. Poor nutrition is frequently associated with disorders of the liver, and a specific nutrition diagnosis is needed for providing best care and experiencing successful outcome. There is opportunity for better-structured approaches to making secure and consistent nutritional diagnoses in patients with liver disease. Nutrition is the set of integrated processes by which cells, tissues, organs and the whole body acquire the energy and nutrients to retain normal structure and perform the required functions. At the level of the whole body, this is achieved through dietary supply and the capacity of the body to transform the substrates and cofactors necessary for metabolism. All of these domains (diet, metabolic capacity, activity of the microbiome, body composition and the level of demand for energy and nutrients) are influenced by levels of physical activity and can vary according to physiological and pathological disease states. The liver plays a central role in establishing and maintaining these regulated processes. Its capacity to achieve and maintain these functional capabilities is established during one's early life. When these capabilities are exceeded and the ability to maintain the milieu interieur is compromised, ill-health supervenes. Stress tests that assess flow through gateway pathways can be used to determine the maximal capacity and functional reserve for critical functions. The inability of the liver to reliably integrate body lipid metabolism and the accumulation of abnormal lipid are obvious manifestations of impaired regulation both in situations of weight loss, for example, the fatty liver of severe malnutrition, and in situations of energy excess, as in non-alcoholic fatty liver disease. The use of stable isotopic probes and the more recent definition of the variability in the metabolome in different nutritional and pathological states indicate the great potential for clinical tools

  5. 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.

  6. Interactions of the heart and the liver

    DEFF Research Database (Denmark)

    Møller, Søren; Bernardi, Mauro

    2013-01-01

    There is a mutual interaction between the function of the heart and the liver and a broad spectrum of acute and chronic entities that affect both the heart and the liver. These can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting...... the heart and the liver at the same time. In chronic and acute cardiac hepatopathy, owing to cardiac failure, a combination of reduced arterial perfusion and passive congestion leads to cardiac cirrhosis and cardiogenic hypoxic hepatitis. These conditions may impair the liver function and treatment should...... be directed towards the primary heart disease and seek to secure perfusion of vital organs. In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities termed cirrhotic...

  7. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.**

    Science.gov (United States)

    We have previously shown that the conazole fungicides triadimefon and propiconazole, which are tumorigenic in mouse liver, are in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses. The nontumorigenic conazole myclo...

  8. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.

    Science.gov (United States)

    We have previously shown that the conazole fungicides triadimefon and propiconazole, which are tumorigenic in mouse liver, are in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses. The nontumorigenic conazole myclo...

  9. 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.)

  10. Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway

    International Nuclear Information System (INIS)

    Drakaki, Alexandra; Hatziapostolou, Maria; Polytarchou, Christos; Vorvis, Christina; Poultsides, George A.; Souglakos, John; Georgoulias, Vassilis; Iliopoulos, Dimitrios

    2015-01-01

    Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths, reflecting the aggressiveness of this type of cancer and the absence of effective therapeutic regimens. MicroRNAs have been involved in the pathogenesis of different types of cancers, including liver cancer. Our aim was to identify microRNAs that have both functional and clinical relevance in HCC and examine their downstream signaling effectors. MicroRNA and gene expression levels were measured by quantitative real-time PCR in HCC tumors and controls. A TargetScan algorithm was used to identify miR-9 downstream direct targets. A high-throughput screen of the human microRNAome revealed 28 microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR-224 were the top inducers of HCC invasiveness and also their expression was increased in HCC relative to control liver tissues. Integration of the microRNA screen and expression data revealed miR-9 as the top microRNA, having both functional and clinical significance. MiR-9 levels correlated with HCC tumor stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth, invasiveness and their ability to form colonies in soft agar. Bioinformatics and 3′UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome proliferator-activated receptor alpha (PPARA) as direct downstream effectors of miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that miR-9 regulates CDH1 expression directly through binding in its 3′UTR and indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were decreased in HCC relative to controls and were inversely correlated with miR-9 levels. Taken together, this study revealed the involvement of the miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis. The online version of this article (doi:10.1186/s12885-015-1562-9) contains supplementary material, which is

  11. The liver in regulation of iron homeostasis.

    Science.gov (United States)

    Rishi, Gautam; Subramaniam, V Nathan

    2017-09-01

    The liver is one of the largest and most functionally diverse organs in the human body. In addition to roles in detoxification of xenobiotics, digestion, synthesis of important plasma proteins, gluconeogenesis, lipid metabolism, and storage, the liver also plays a significant role in iron homeostasis. Apart from being the storage site for excess body iron, it also plays a vital role in regulating the amount of iron released into the blood by enterocytes and macrophages. Since iron is essential for many important physiological and molecular processes, it increases the importance of liver in the proper functioning of the body's metabolism. This hepatic iron-regulatory function can be attributed to the expression of many liver-specific or liver-enriched proteins, all of which play an important role in the regulation of iron homeostasis. This review focuses on these proteins and their known roles in the regulation of body iron metabolism. Copyright © 2017 the American Physiological Society.

  12. The impact of intrahepatic microcapsule transplantation on the liver function and liver blood flow: a comparative study of different transplantation approaches

    International Nuclear Information System (INIS)

    Ai Zhaodong; Wang Wei; Gao Feng; Rong Pengfei; Zheng Wei; Dong Qiong; Liu Sheng

    2011-01-01

    Objective: to compare the impact of intrahepatic microcapsule transplantation on the liver function and liver blood flow between via portal vein approach and via hepatic artery approach. Methods: Twenty healthy male dogs were randomly and equally divided into four groups: A1, A2, V1 and V2. For group V1 and group V2, the microcapsules were implanted into portal vein through percultaneous transhepatic approach under ultrasonographic guidance, while for group A1 and group A2, the microcapsules were implanted into hepatic artery through hepatic artery catheterization. The quantity of microcapsules implanted into group A1 and group A2 was 32000 microcapsule/Kg and 48000 microcapsule/Kg respectively, while for group V1 and group V2 was 16000 microcapsule/Kg and 32000 microcapsule/Kg respectively. Before, during and after the microcapsule transplantation ultrasonography was performed to determine the hepatic blood flow rate as well as the diameter of the portal vein. ALT, AST and the main serum liver fibrosis indexes were measured before and after the transplantation. Samples of the livers were pathologically examined before and after the operation. The results were compared between each group. Results: No significant changes in blood flow rate of main portal vein was found after the transplantation in both group A1 and group A2. In both group V1 and group V2 the blood flow of main portal vein became slow during the procedure but recovered quickly. No significant difference in portal blood flow rate existed between each group one week after the operation (P>0.05). Shortly after the transplantation the ALT and AST levels showed an increase of different degree in all dogs, which reached its peak at 24 hours after the operation. The increase in ALT and AST levels was most sharp in group V2 while most minor in group A1. The ALT and AST levels gradually returned to normal two weeks later. The difference in ALT and AST levels between every group was significant (P<0

  13. PROTECTIVE EFFECTS OF HYPOTHALAMIC BETA-ENDORPHIN NEURONS AGAINST ALCOHOL-INDUCED LIVER INJURIES AND LIVER CANCERS IN RAT ANIMAL MODELS

    Science.gov (United States)

    Murugan, Sengottuvelan; Boyadjieva, Nadka; Sarkar, Dipak K.

    2014-01-01

    Background Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods Male rats received either BEP neuron transplants or control transplants in the hypothalamus and randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results Alcohol-feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased protein levels of triglyceride, hepatic stellate cell activation factors and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocelluar carcinoma, collagen deposition, numbers of preneoplastic foci, levels of hepatic stellate cell activation factors and catecholamines, as well as inflammatory milieu and the levels of NK cell cytotoxic factors in the liver. Conclusion These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and hepatocellular carcinoma formation possibly via influencing the immune function. PMID:25581653

  14. Structure and function of the liver in conditions of chrome-isoniazid-rifampicin affection of rats after applying of sorbex

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    N. I. Burmas

    2014-09-01

    Full Text Available The aim of this research was to assess the activity of marker enzymes of the liver and its biliary formation function in conditions of the affection of animals by hexavalent chromium compounds, isoniazid and rifampicin, after applying of sorbex. The experimental affection of rats of different age was carried in the conditions of combined injection of hexavalent chromium compounds (solution of potassium dichromate, 3 mg/kg, isoniazid (0.05 g/kg and rifampicin (0.25 g/kg during the 7th and 14th days, and sorbex enterosorbent was introduced in quantity of 150 mg/kg. The activity of marker enzymes of the liver was evaluated by the activity of alanine and aspartate aminotransferases (ALT and AST and alkaline phosphatase (ALP. The state of biliary formation function of the liver was evaluated by the content of total bilirubin (TB and bile acids (BA in blood. The most significant changes in ALT activity were observed in the liver of old animals by the combined effects of the abovementioned xenobiotics – the activity of ALT was decreased by the end of the experiment by 58% compared with the animals of intact control. Using of sorbex led to decreasing in blood serum and increasing in the liver of affected animals of the different age of ALT activity throughout the experiment. AST activity in blood serum increased, and it was the highest in old animals upon chrome-isoniazid-rifampicin affection on the 14th day of the research. With the use of sorbex, there was a tendency to normalization of this index in blood serum and liver of affected animals on the 7th day from the beginning of the experiment. It was found that the largest increase in ALP took place in blood serum of immature animals by the combined effects of toxicants. In the liver of affected animals the activity of ALP decreased throughout the experiment in all age groups of animals. Maximum corrective effect on the activity of ALP was shown by the enterosorbent in the liver of mature animals on

  15. Bioengineered Liver Models for Drug Testing and Cell Differentiation Studies

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    Gregory H. Underhill

    2018-01-01

    Full Text Available In vitro models of the human liver are important for the following: (1 mitigating the risk of drug-induced liver injury to human beings, (2 modeling human liver diseases, (3 elucidating the role of single and combinatorial microenvironmental cues on liver cell function, and (4 enabling cell-based therapies in the clinic. Methods to isolate and culture primary human hepatocytes (PHHs, the gold standard for building human liver models, were developed several decades ago; however, PHHs show a precipitous decline in phenotypic functions in 2-dimensional extracellular matrix–coated conventional culture formats, which does not allow chronic treatment with drugs and other stimuli. The development of several engineering tools, such as cellular microarrays, protein micropatterning, microfluidics, biomaterial scaffolds, and bioprinting, now allow precise control over the cellular microenvironment for enhancing the function of both PHHs and induced pluripotent stem cell–derived human hepatocyte-like cells; long-term (4+ weeks stabilization of hepatocellular function typically requires co-cultivation with liver-derived or non–liver-derived nonparenchymal cell types. In addition, the recent development of liver organoid culture systems can provide a strategy for the enhanced expansion of therapeutically relevant cell types. Here, we discuss advances in engineering approaches for constructing in vitro human liver models that have utility in drug screening and for determining microenvironmental determinants of liver cell differentiation/function. Design features and validation data of representative models are presented to highlight major trends followed by the discussion of pending issues that need to be addressed. Overall, bioengineered liver models have significantly advanced our understanding of liver function and injury, which will prove useful for drug development and ultimately cell-based therapies.

  16. Effect of gemcitabine chemotherapy on immune function and VEGF in patients with middle and advanced liver cancer

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    Ling Zuo

    2016-09-01

    Full Text Available Objective: To observe the effect of gemcitabine chemotherapy on the immune function and VEGF in patients with middle and advanced liver cancer. Methods: A total of 90 patients with middle and advanced liver cancer who were admitted in our hospital from June, 2014 to July, 2015 were included in the study and randomized into the observation group and the control group with 45 cases in each group. The patients in the control group were given adriamycin, and the patients in the observation group were given gemcitabine chemotherapy. The efficacy, immunological function indicators, VEGF level, and the occurrence of adverse reactions in the two groups were compared. Results: IL-6 and TNF-毩 levels after treatment in the two groups were significantly elevated, and the increased degree in the observation group was significantly greater than that in the control group (P0.05. VEGF level after treatment in the two groups was significantly reduced, and the reduced degree in the observation group was significantly greater than that in the control group (P<0.05. The improvement of T cell subsets after treatment in the observation group was significantly superior to that in the control group (P<0.05. The occurrence rate of adverse reactions in the observation group was significantly lower than that in the control group (P<0.05. Conclusions: Gemcitabine chemotherapy on patients with middle and advanced liver cancer can effectively improve the immunological function, and enhance the efficacy, with a higher safety.

  17. Liver function tests and risk prediction of incident type 2 diabetes : evaluation in two independent cohorts

    NARCIS (Netherlands)

    Abbasi, Ali; Bakker, Stephan J. L.; Corpeleijn, Eva; van der A, Daphne L.; Gansevoort, Ron T.; Gans, Rijk O. B.; Peelen, Linda M.; van der Schouw, Yvonne T.; Stolk, Ronald P.; Navis, Gerjan; Spijkerman, Annemieke M. W.; Beulens, Joline W. J.

    2012-01-01

    Background: Liver function tests might predict the risk of type 2 diabetes. An independent study evaluating utility of these markers compared with an existing prediction model is yet lacking. Methods and Findings: We performed a case-cohort study, including random subcohort (6.5%) from 38,379

  18. Evaluation of the liver scintigraphy with /sup 99m/Tc-Sn-colloid. II. C Clinical studies by comparison with /sup 198/Au-colloid

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, K; Nishimura, T; Takeda, H; Furukawa, T [Osaka Univ. (Japan). Faculty of Medicine; Kajiya, Fumihiko

    1975-08-01

    Clinical significance of the liver scintigraphy with sup(99m)Tc-Sn-colloid was evaluated in comparison with those with /sup 198/Au-colloid. The liver scintigrams with sup(99m)Tc-Sn-colloid and /sup 198/Au-colloid were done in 36 cases of various hepatic diseases and RI accumulation curves in the liver and the spleen, and the blood disapearance curves were also obtained. The conclusions were as follows. The liver scintigrams with sup(99m)Tc-Sn-colloid proved to be more sensitive in the detection of tumors, especially, in the lower margin, left lobe and superficial layers of the liver than those with /sup 198/Au-colloid. In all cases, including normal and cirrhotic subjects, visualizations of the spleen were seen on the scintigrams with sup(99m)Tc-Sn-colloid. In diffuse hepatic diseases, comparing both radiopharmaceuticals, the splenic accumulations were studied qualitatively and quantitatively. As a result, the ratio (spleen/liver) was thought to be useful for the differentiation of diffuse hepatic diseases concerned with splenic function and/or size. It was also shown that sup(99m)Tc-Sn-colloid was useful as a spleen scanning agent. The Tl/2 in the liver accumulation curves with sup(99m)Tc-Sn-colloid were not as clearly differentiated in the various hepatic diseases as those with /sup 198/Au-colloid where those indexes were useful in the evaluation of liver functions.

  19. Toxicological Aspects of Carbaryl on liver functions, lipid profile and thyroid hormones in male rats

    International Nuclear Information System (INIS)

    Afifi, E.A.A.

    2003-01-01

    The present study was undertaken to show the toxicological effects of daily oral doses of carbaryl on different metabolic activities through biochemical determinations in male rats by feeding diet treated with 28 mg/kg for four consecutive weeks, followed by one and two weeks of recovery periods. Results revealed disturbance in liver functions which were elucidated through marked increases of serum glutamic oxalacetic (SGOT), glutamic pyruvic (SGPT) transaminases and alkaline phosphatase (SALP). Carbaryl also induced hypoglycemia, increase in liver glycogen content, decrease in kidney and brain glycogen, decrease in serum bilirubin and total lipids, reduction in blood cholesterol, increase in serum calcium with decrease in serum inorganic phosphorus. Thyroxine hormone(T 4 ) was increased while triiodothyronine (T 3 ) was decreased

  20. Hepatocyte nuclear factor 4A improves hepatic differentiation of immortalized adult human hepatocytes and improves liver function and survival.

    Science.gov (United States)

    Hang, Hua-Lian; Liu, Xin-Yu; Wang, Hai-Tian; Xu, Ning; Bian, Jian-Min; Zhang, Jian-Jun; Xia, Lei; Xia, Qiang

    2017-11-15

    Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH. Cells were analyzed for telomerase activity, proliferative capacity, hepatocyte markers, and tumorigenicity (c-myc) expression. Hepatocyte markers, hepatocellular functions, and morphology were studied in the HNF4A-overexpressing IHH. Hepatocyte markers and karyotype analysis were completed in the primary hepatocytes using shRNA knockdown of HNF4A. Nuclear translocation of β-catenin was assessed. Rat models of ALF were treated with encapsulated IHH or HNF4A-overexpressing IHH. A HNF4A-positive IHH line was established, which was non-tumorigenic and conserved properties of primary hepatocytes. HNF4A overexpression significantly enhanced mRNA levels of genes related to hepatic differentiation in IHH. Urea levels were increased by the overexpression of HNF4A, as measured 24h after ammonium chloride addition, similar to that of primary hepatocytes. Chromosomal abnormalities were observed in primary hepatocytes transfected with HNF4A shRNA. HNF4α overexpression could significantly promote β-catenin activation. Transplantation of HNF4A overexpressing IHH resulted in better liver function and survival of rats with ALF compared with IHH. HNF4A improved hepatic differentiation of IHH. Transplantation of HNF4A-overexpressing IHH could improve the liver function and survival in a rat model of ALF. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats

    International Nuclear Information System (INIS)

    Imaeda, Masumi; Yoshida, Yukari; Ohkubo, Yu; Musha, Atsushi; Komachi, Mayumi; Nakano, Takashi; Ishikawa, Hitoshi; Takahashi, Takeo; Nakazato, Yoichi

    2014-01-01

    Radiation therapy (RT) has become particularly important recently for treatment of liver tumors, but there are few experimental investigations pertaining to radiation-induced liver injuries over long-term follow-up periods. Thus, the present study examined pathological liver features over a 10-month period using an intraoperative whole-liver irradiation model. Liver function tests were performed in blood samples, whereas cell death, cell proliferation, and fibrotic changes were evaluated pathologically in liver tissues, which were collected from irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function, increased hepatocyte number, and decreased apoptotic cell proportion observed in the 15 Gy group, but not the 30 Gy group, returned to control group levels after 40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than those in the control group after 40 weeks. Azan staining showed a fibrotic pattern in the irradiated liver in the 30 Gy group only, but the expression levels of alpha smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) in both the 15 and 30 Gy groups were significantly higher than those in the control group (P < 0.05). There were differences in the pathological features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF-β1 and α-SMA expression patterns supported the gradual progression of radiation-induced liver fibrosis in both groups. These findings will be useful in the future development of protective drugs for radiation-induced liver injury. (author)

  2. Polyploidization in liver tissue.

    Science.gov (United States)

    Gentric, Géraldine; Desdouets, Chantal

    2014-02-01

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

  3. Liver function in workers exposed of the cosmetics industry.

    Science.gov (United States)

    Casale, T; Caciari, T; Rosati, M V; Biagi, M; De Sio, S; Andreozzi, G; Schifano, M P; Capozzella, A; Pimpinella, B; Tomei, G; Tomei, F

    2013-01-01

    The purpose of this study is to assess whether occupational exposure to substances used in the cosmetic factories may cause effects on the liver and blood counts in exposed workers. The study included 48 exposed workers and 86 unexposed controls. All workers included in the study underwent blood count, white blood count, total, direct and indirect bilirubin, transaminases, alkaline phosphatase and cholinesterase. The differences between the means and frequencies were compared using the Student's t-test and chi-square test with Yates correction and were considered significant when the p value was cosmetics industry had liver test values above the range. We noted a statistically significant higher prevalence of GPT (p cosmetics industry compared with the control group. The results obtained suggest that occupational exposure to low doses of substances used in the cosmetic industry is able to influence some liver parameters in occupationally exposed workers.

  4. Mitochondrial-related proteomic changes during obesity and fasting in mice are greater in the liver than skeletal muscles.

    Science.gov (United States)

    Nesteruk, Monika; Hennig, Ewa E; Mikula, Michal; Karczmarski, Jakub; Dzwonek, Artur; Goryca, Krzysztof; Rubel, Tymon; Paziewska, Agnieszka; Woszczynski, Marek; Ledwon, Joanna; Dabrowska, Michalina; Dadlez, Michal; Ostrowski, Jerzy

    2014-03-01

    Although mitochondrial dysfunction is implicated in the pathogenesis of obesity, the molecular mechanisms underlying obesity-related metabolic abnormalities are not well established. We performed mitochondrial quantitative proteomic and whole transcriptome analysis followed by functional annotations within liver and skeletal muscles, using fasted and non-fasted 16- and 48-week-old high-fat diet (HFD)-fed and normal diet-fed (control group) wild-type C56BL/6J mice, and hyperphagic ob/ob and db/db obese mice. Our study identified 1,675 and 704 mitochondria-associated proteins with at least two peptides in liver and muscle, respectively. Of these, 221 liver and 44 muscle proteins were differentially expressed (adjusted p values ≤ 0.05) between control and all obese mice, while overnight fasting altered expression of 107 liver and 35 muscle proteins. In the liver, we distinguished a network of 27 proteins exhibiting opposite direction of expression changes in HFD-fed and hyperphagic mice when compared to control. The network centered on cytochromes P450 3a11 (Cyp3a11) and 4a14 (Cyp4a14), and fructose-bisphosphate aldolase B (Aldob) proteins which bridged proteins cluster involved in Metabolism of xenobiotics with proteins engaged in Fatty acid metabolism and PPAR signaling pathways. Functional annotations revealed that most of the hepatic molecular alterations, which characterized both obesity and fasting, related to different aspects of energy metabolism (such as Fatty acid metabolism, Peroxisome, and PPAR signaling); however, only a limited number of functional annotations could be selected from skeletal muscle data sets. Thus, our comprehensive molecular overview revealed that both obesity and fasting states induce more pronounced mitochondrial proteome changes in the liver than in the muscles.

  5. TAM receptor tyrosine kinase function and the immunopathology of liver disease.

    Science.gov (United States)

    Mukherjee, S K; Wilhelm, A; Antoniades, C G

    2016-06-01

    Tyro3, Axl, MERTK (TAM) receptor tyrosine kinases are implicated in the regulation of the innate immune response through clearance of apoptotic cellular debris and control of cytokine signaling cascades. As a result they are pivotal in regulating the inflammatory response to tissue injury. Within the liver, immune regulatory signaling is employed to prevent the overactivation of innate immunity in response to continual antigenic challenge from the gastrointestinal tract. In this review we appraise current understanding of the role of TAM receptor function in the regulation of both innate and adaptive immunity, with a focus on its impact upon hepatic inflammatory pathology. Copyright © 2016 the American Physiological Society.

  6. Xenotransplantation of neonatal porcine liver cells.

    Science.gov (United States)

    Garkavenko, O; Emerich, D F; Muzina, M; Muzina, Z; Vasconcellos, A V; Ferguson, A B; Cooper, I J; Elliott, R B

    2005-01-01

    Xenotransplantation of porcine liver cell types may provide a means of overcoming the shortage of suitable donor tissues to treat hepatic diseases characterized by inherited inborn errors of metabolism or protein production. Here we report the successful isolation, culture, and xenotransplantation of liver cells harvested from 7- to 10-day-old piglets. Liver cells were isolated and cultured immediately after harvesting. Cell viability was excellent (>90%) over the duration of the in vitro studies (3 weeks) and the cultured cells continued to significantly proliferate. These cells also retained their normal secretory and metabolic capabilities as determined by continued release of albumin, factor 8, and indocyanin green (ICG) uptake. After 3 weeks in culture, porcine liver cells were loaded into immunoisolatory macro devices (Theracyte devices) and placed into the intraperitoneal cavity of immunocompetant CD1 mice. Eight weeks later, the devices were retrieved and the cells analyzed for posttransplant determinations of survival and function. Post mortem analysis confirmed that the cell-loaded devices were biocompatible, and were well-tolerated without inducing any notable inflammatory reaction in the tissues immediately surrounding the encapsulated cells. Finally, the encapsulated liver cells remained viable and functional as determined by histologic analyses and ICG uptake/release. The successful harvesting, culturing, and xenotransplantation of functional neonatal pig liver cells support the continued development of this approach for treating a range of currently undertreated or intractable hepatic diseases.

  7. Multi-detector row helical CT of the liver. Quantitative assessment of iodine concentration of intravenous contrast material on multiphasic CT. A prospective randomized study

    International Nuclear Information System (INIS)

    Tsurusaki, Masakatsu; Sugimoto, Koji; Fujii, Masahiko; Sugimura, Kazuro

    2004-01-01

    The purpose of this study was to assess the quantitative effects of contrast material concentration on hepatic parenchymal and vascular enhancement in multiphasic computed tomography (CT), using multi-detector row helical CT. We designed a prospective randomized study to test two different concentrations of contrast material on five phasic scans of the liver. One hundred patients were randomly assigned to two groups: an iodine concentration of 300 mg/mL in group A and 370 mg/mL in group B. All patients received a fixed volume of 100 mL at a 4 mL/sec injection rate. Enhancement values for the hepatic parenchyma and aorta at three levels (upper, middle, and lower level of the liver), and values for portal and hepatic veins were statistically compared between the two groups. Hepatic parenchymal enhancement values at all levels of the liver in portal phase (PP) and equilibrium phase (EP) were significantly higher in group B than in group A (p<0.01). Aortic enhancement values at two levels of the liver (middle and lower) in early hepatic arterial phase (EAP) were significantly higher in group B than in group A (p<0.05), however, there was no significant difference between groups A and B in aortic enhancement during the delayed hepatic arterial phase (DAP). Portal and hepatic venous enhancement values in PP and EP were significantly higher in group B than in group A (p<0.01). On multiphasic dynamic CT, the use of a higher iodine concentration of contrast material results in higher hepatic parenchymal enhancement and aortic enhancement, as well as higher portal and hepatic venous enhancement. (author)

  8. Propylthiouracil-induced liver failure and artificial liver support systems: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Wu DB

    2017-01-01

    Full Text Available Dong-Bo Wu,1,2 En-Qiang Chen,1,2 Lang Bai,1,2 Hong Tang1,2 1Center of Infectious Diseases, West China Hospital of Sichuan University, 2Division of Molecular Biology of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People’s Republic of China Background: Antithyroid drugs carry a potential risk of hepatotoxicity. Propylthiouracil (PTU is commonly prescribed for patients with hyperthyroidism. PTU, however, can induce liver injury, ranging from mild asymptomatic elevation of aminotransferases to acute liver failure (ALF.Case presentation: This case reports on a 16-year-old Chinese girl with hyperthyroidism, who was admitted to our hospital for jaundice, nausea, and fatigue associated with severe hyperbilirubinemia and coagulopathy. She had been prescribed PTU 5 months earlier. There was no history of hypersensitivity to drugs, viral liver diseases, blood transfusion, or surgery. On the basis of her symptoms and the clinical data, she was diagnosed with PTU-induced ALF. Due to the limited number of available donor organs for liver transplantation, she was started on treatment with artificial liver support system (ALSS. After four sessions of ALSS, her clinical signs and symptoms were found to be markedly improved, and she was discharged 25 days after admission. Four months later, her liver function normalized.Conclusion: Although PTU-induced liver failure is rare in clinical practice, liver function should be appropriately monitored during treatment with PTU. PTU-induced ALF in this patient was successfully managed with an ALSS, suggesting that the latter may be an alternative to liver transplantation. Keywords: propylthiouracil, liver injury, acute liver failure, artificial liver support systems 

  9. Quantitation and histochemical localization of galectin-1 and galectin-1-reactive glycoconjugates in fetal development of bovine organs.

    Science.gov (United States)

    Kaltner, H; Lips, K S; Reuter, G; Lippert, S; Sinowatz, F; Gabius, H J

    1997-10-01

    , kidney and liver demonstrate that the localization of the galectin and of lectin-reactive epitopes can show a similar distribution, as seen in liver and heart, with organ-typical quantitative changes of a rather similar staining profile (heart, kidney) or notable changes in the spatial distribution (liver) in the course of development. This report emphasizes the potential value of combined monitoring of the lectin and its potential in vivo ligands to contribute to eventually unravel organ-related function(s) of a tissue lectin.

  10. Quantification of liver fat with respiratory-gated quantitative chemical shift encoded MRI.

    Science.gov (United States)

    Motosugi, Utaroh; Hernando, Diego; Bannas, Peter; Holmes, James H; Wang, Kang; Shimakawa, Ann; Iwadate, Yuji; Taviani, Valentina; Rehm, Jennifer L; Reeder, Scott B

    2015-11-01

    To evaluate free-breathing chemical shift-encoded (CSE) magnetic resonance imaging (MRI) for quantification of hepatic proton density fat-fraction (PDFF). A secondary purpose was to evaluate hepatic R2* values measured using free-breathing quantitative CSE-MRI. Fifty patients (mean age, 56 years) were prospectively recruited and underwent the following four acquisitions to measure PDFF and R2*; 1) conventional breath-hold CSE-MRI (BH-CSE); 2) respiratory-gated CSE-MRI using respiratory bellows (BL-CSE); 3) respiratory-gated CSE-MRI using navigator echoes (NV-CSE); and 4) single voxel MR spectroscopy (MRS) as the reference standard for PDFF. Image quality was evaluated by two radiologists. MRI-PDFF measured from the three CSE-MRI methods were compared with MRS-PDFF using linear regression. The PDFF and R2* values were compared using two one-sided t-test to evaluate statistical equivalence. There was no significant difference in the image quality scores among the three CSE-MRI methods for either PDFF (P = 1.000) or R2* maps (P = 0.359-1.000). Correlation coefficients (95% confidence interval [CI]) for the PDFF comparisons were 0.98 (0.96-0.99) for BH-, 0.99 (0.97-0.99) for BL-, and 0.99 (0.98-0.99) for NV-CSE. The statistical equivalence test revealed that the mean difference in PDFF and R2* between any two of the three CSE-MRI methods was less than ±1 percentage point (pp) and ±5 s(-1) , respectively (P liver PDFF and R2* and are as valid as the standard breath-hold technique. © 2015 Wiley Periodicals, Inc.

  11. MR Fingerprinting for Rapid Quantitative Abdominal Imaging.

    Science.gov (United States)

    Chen, Yong; Jiang, Yun; Pahwa, Shivani; Ma, Dan; Lu, Lan; Twieg, Michael D; Wright, Katherine L; Seiberlich, Nicole; Griswold, Mark A; Gulani, Vikas

    2016-04-01

    To develop a magnetic resonance (MR) "fingerprinting" technique for quantitative abdominal imaging. This HIPAA-compliant study had institutional review board approval, and informed consent was obtained from all subjects. To achieve accurate quantification in the presence of marked B0 and B1 field inhomogeneities, the MR fingerprinting framework was extended by using a two-dimensional fast imaging with steady-state free precession, or FISP, acquisition and a Bloch-Siegert B1 mapping method. The accuracy of the proposed technique was validated by using agarose phantoms. Quantitative measurements were performed in eight asymptomatic subjects and in six patients with 20 focal liver lesions. A two-tailed Student t test was used to compare the T1 and T2 results in metastatic adenocarcinoma with those in surrounding liver parenchyma and healthy subjects. Phantom experiments showed good agreement with standard methods in T1 and T2 after B1 correction. In vivo studies demonstrated that quantitative T1, T2, and B1 maps can be acquired within a breath hold of approximately 19 seconds. T1 and T2 measurements were compatible with those in the literature. Representative values included the following: liver, 745 msec ± 65 (standard deviation) and 31 msec ± 6; renal medulla, 1702 msec ± 205 and 60 msec ± 21; renal cortex, 1314 msec ± 77 and 47 msec ± 10; spleen, 1232 msec ± 92 and 60 msec ± 19; skeletal muscle, 1100 msec ± 59 and 44 msec ± 9; and fat, 253 msec ± 42 and 77 msec ± 16, respectively. T1 and T2 in metastatic adenocarcinoma were 1673 msec ± 331 and 43 msec ± 13, respectively, significantly different from surrounding liver parenchyma relaxation times of 840 msec ± 113 and 28 msec ± 3 (P < .0001 and P < .01) and those in hepatic parenchyma in healthy volunteers (745 msec ± 65 and 31 msec ± 6, P < .0001 and P = .021, respectively). A rapid technique for quantitative abdominal imaging was developed that allows simultaneous quantification of multiple tissue

  12. 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.

  13. A quantitative phase field model for hydride precipitation in zirconium alloys: Part I. Development of quantitative free energy functional

    International Nuclear Information System (INIS)

    Shi, San-Qiang; Xiao, Zhihua

    2015-01-01

    A temperature dependent, quantitative free energy functional was developed for the modeling of hydride precipitation in zirconium alloys within a phase field scheme. The model takes into account crystallographic variants of hydrides, interfacial energy between hydride and matrix, interfacial energy between hydrides, elastoplastic hydride precipitation and interaction with externally applied stress. The model is fully quantitative in real time and real length scale, and simulation results were compared with limited experimental data available in the literature with a reasonable agreement. The work calls for experimental and/or theoretical investigations of some of the key material properties that are not yet available in the literature

  14. Digital liver biopsy: Bio-imaging of fatty liver for translational and clinical research.

    Science.gov (United States)

    Mancini, Marcello; Summers, Paul; Faita, Francesco; Brunetto, Maurizia R; Callea, Francesco; De Nicola, Andrea; Di Lascio, Nicole; Farinati, Fabio; Gastaldelli, Amalia; Gridelli, Bruno; Mirabelli, Peppino; Neri, Emanuele; Salvadori, Piero A; Rebelos, Eleni; Tiribelli, Claudio; Valenti, Luca; Salvatore, Marco; Bonino, Ferruccio

    2018-02-27

    The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a "digital biopsy" for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver.

  15. 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...... levels of the fibrosis marker hyaluronic acid are a strong predictor of clinical complications. A smaller study found hyaluronic acid and two other fibrosis tests, aspartate aminotransferase-to-platelet ratio index (APRI) and Fib-4, to be independent predictors of mortality when included in models...

  16. 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

    Sepsis is associated with an activation of the coagulation system and multiorgan failure. The aim of the study was to examine the effects of selective thrombin inhibition with melagatran on renal hemodynamics and function, and liver integrity, during early endotoxemia. Endotoxemia was induced...

  17. Liver diseases and aging : friends or foes?

    NARCIS (Netherlands)

    Sheedfar, Fareeba; Di Biase, Stefano; Koonen, Debby; Vinciguerra, Manlio

    2013-01-01

    The liver is the only internal human organ capable of natural regeneration of lost tissue, as little as 25% of a liver can regenerate into a whole liver. The process of aging predisposes to hepatic functional and structural impairment and metabolic risk. Therefore, understanding how aging could

  18. Traditional Chinese medicine treatment of liver diseases

    Directory of Open Access Journals (Sweden)

    WANG Rongbing

    2015-01-01

    Full Text Available Traditional Chinese medicine (TCM treatment of liver diseases is derived from the regulation of liver function including storing blood and governing the free flow of qi, in which functional systems such as modern digestion, endocrine, and the gut-liver axis are involved, and is established on modern hepatic physiology, pathology, and etiology. To objectively reveal the characteristics and advantages of modern TCM treatment of liver diseases, we analyzed the clinical and research situation of TCM therapy for liver diseases in the last decade and collected major achievements that have been applied in clinical treatment of diseases, published in core journals, and confirmed by major scientific research programs. The results showed TCM combined with antiviral therapy can improve the clinical outcomes of chronic hepatitis B. TCM can help HBV carriers prevent disease progression. Integrated traditional Chinese and Western medicine therapy for acute-on-chronic liver failure can block the deterioration induced by endotoxin. TCM has been widely applied in protecting the liver through nonspecific anti-inflammation, alleviating hepatic fibrosis, and preventing non-alcoholic fatty liver. TCM plays an important role in treating some currently untreatable liver diseases. Therefore, it is our common responsibility to inherit and develop effective principle-method-recipe-medicines and create a better medical care system.

  19. Metabonomics Research Progress on Liver Diseases.

    Science.gov (United States)

    Yu, Mengqian; Zhu, Ying; Cong, Qingwei; Wu, Chunyan

    2017-01-01

    Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score. As a result, the clinical work becomes very complex. So it has broad prospects to explore the specific and sensitive biomarkers of liver diseases with metabolomics. In this paper, there are several summaries which are related to the current research progress and application of metabolomics on biomarkers of liver diseases.

  20. Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio

    Directory of Open Access Journals (Sweden)

    Dezarn William A

    2007-03-01

    Full Text Available Abstract Background Treatment records and follow-up data on 40 patients with primary and metastatic liver malignancies who underwent a single whole-liver treatment with Y-90 resin microspheres (SIR-Spheres® Sirtex Medical, Lake Forest, IL were retrospectively reviewed. The objective of the study was to evaluate the anatomic and physiologic determinants of radiation dose distribution, and the dose response of tumor and liver toxicity in patients with liver malignancies who underwent hepatic arterial Y-90 resin microsphere treatment. Methods Liver and tumor volume calculations were performed on pre-treatment CT scans. Fractional tumor and liver flow characteristics and lung shunt fractions were determined using hepatic arterial Tc-99m MAA imaging. Absorbed dose calculations were performed using the MIRD equations. Liver toxicity was assessed clinically and by liver function tests. Tumor response to therapy was assessed by CT and/or tumor markers. Results Of the 40 patients, 5 had hepatocellular cancer (HCC, and 35 had metastatic liver tumors (15 colorectal cancer, 10 neuroendocrine tumors, 4 breast cancer, 2 lung cancer, 1 ovarian cancer, 1 endometrial cancer, and 2 unknown primary adenocarcinoma. All patients were treated in a salvage setting with a 3 to 80 week follow-up (mean: 19 weeks. Tumor volumes ranged from 15.0 to 984.2 cc (mean: 294.9 cc and tumor to normal liver uptake ratios ranged from 2.8 to 15.4 (mean: 5.4. Average administered activity was 1.2 GBq (0.4 to 2.4 GBq. Liver absorbed doses ranged from 0.7 to 99.5 Gy (mean: 17.2 Gy. Tumor absorbed doses ranged from 40.1 to 494.8 Gy (mean: 121.5 Gy. None of the patients had clinical venoocclusive disease or therapy-induced liver failure. Seven patients (17.5 % had transient and 7 patients (17.5 % had persistent LFT abnormalities. There were 27 (67.5% responders (complete response, partial response, and stable disease. Tumor response correlated with higher tumor flow ratio as measured by

  1. Estimation of liver glucose metabolism after refeeding

    International Nuclear Information System (INIS)

    Rognstad, R.

    1987-01-01

    Refeeding or infusing glucose to rats fasted for 24 hr or more causes rapid liver glycogen synthesis, the carbon source now considered to be largely from gluconeogenesis. While substrate cycling between plasma glucose and liver glucose-6P is known to occur, this cycling has apparently been ignored when calculations are made of % contribution of direct and indirect pathways to liver glycogen synthesis, or when hepatic glucose output is calculated from glucose turnover minus the glucose infusion rate. They show that, isotopically, an estimate of the fluxes of liver glucokinase and glucose-6-phosphatase is required to quantitate sources of carbon for liver glycogen synthesis, and to measure hepatic glucose output (or uptake). They propose a method to estimate these fluxes, involving a short infusion of a 14 C labelled gluconeogenic precursor plus (6T)glucose, with determination of isotopic yields in liver glycogen and total glucose. Given also the rate of liver glycogen synthesis, this procedure permits the estimation of net gluconeogenesis and hepatic glucose output or uptake. Also, in vitro evidence against the notion of a drastic zonation of liver carbohydrate metabolism is presented, e.g. raising the glucose concentration from 10 to 25 mM increases the 14 C yield from H 14 CO 3 - in lactate, with the increased pyruvate kinase flux and decreased gluconeogenesis occurring in the same cell type, not opposing pathways in different hepatocyte types (as has been postulated by some to occur in vivo after refeeding

  2. Assessment of hepatocyte and kupffer cell function using Tc-99m DISIDA/Tc-99m tin colloid in thioacetamide-induced liver injury

    International Nuclear Information System (INIS)

    Ahn, B. C.; Chun, K. A.; Lee, J.; Lee, K. B.

    1997-01-01

    Toxic liver injury is not unusual in clinical field and liver biopsy is one of the most accurate method to define the severity of liver injury. But occasionally, it is impossible to obtain liver tissue in patients with acute toxic liver injury. The aim of this study is to evaluate the possibility of liver scintigraphy with Tc-99m DISIDA or Tc-99m tin colloid as a non-invasive tool in predicting functional status of hepatocyte and Kupffer cell and severity of liver injury. Intraperitoneal injection of thioacetamide was performed to make acute liver injury in mice and rats, and liver status was assessed by pathologic specimen and scintigraphic methods. Scintigraphic evaluation were performed by biodistribution of Tc-99m DISIDA or Tc-99m tin colloid in thioacetamide-treated mice. Liver time-activity curves were generated. Comparison between histologic data and scintigraphic data was done with SAS program. Thioacetamide-treated mice demonstrated hepatocyte necrosis in histologic examination and low liver/blood uptake ratios in biodistribution studies using both radiotracers. Biodistribution study using Tc-99m tin colloid revealed increased lung radioactivity in thioacetamide-treated mice. Twenty-four hours after thioacetamide administration, thioacetamide-treated rats demonstrated maximal hepatocyte necrosis and inflammation in histologic finding and delayed maximal uptake time (Tmax) and prolonged half time (T 1/2 ) of liver time-activity curve in liver scintigraphy. Histologic results and scintigraphic data were well correlated, and these two scintigraphic parameters (Tmax T 1/2 ) seemed to be good predictors of histologic change of liver. These data showed that liver injury could be assessed by non-invasive scintigraphic study in rat and mouse. This experimental study might be used as a animal model to evaluate the liver protecting drugs, and this scintigraphic study could be applied to acute toxic hepatitis for assessment of liver status in men

  3. Defining normal liver stiffness range in a normal healthy Chinese population without liver disease.

    Directory of Open Access Journals (Sweden)

    James Fung

    Full Text Available BACKGROUND: For patients with chronic liver disease, different optimal liver stiffness cut-off values correspond to different stages of fibrosis, which are specific for the underlying liver disease and population. AIMS: To establish the normal ranges of liver stiffness in the healthy Chinese population without underlying liver disease. METHODS: This is a prospective cross sectional study of 2,528 healthy volunteers recruited from the general population and the Red Cross Transfusion Center in Hong Kong. All participants underwent a comprehensive questionnaire survey, measurement of weight, height, and blood pressure. Fasting liver function tests, glucose and cholesterol was performed. Abdominal ultrasound and transient elastography were performed on all participants. RESULTS: Of the 2,528 subjects, 1,998 were excluded with either abnormal liver parenchyma on ultrasound, chronic medical condition, abnormal blood tests including liver enzymes, fasting glucose, fasting cholesterol, high body mass index, high blood pressure, or invalid liver stiffness scan. The reference range for the 530 subjects without known liver disease was 2.3 to 5.9 kPa (mean 4.1, SD 0.89. The median liver stiffness was higher in males compared with females (4.3 vs 4.0 kPa respectively, p55 years (p=0.001. CONCLUSIONS: The healthy reference range for liver stiffness in the Chinese population is 2.3 to 5.9 kPa. Female gender and older age group was associated with a lower median liver stiffness.

  4. Clearance of iron oxide particles in rat liver: effect of hydrated particle size and coating material on liver metabolism.

    Science.gov (United States)

    Briley-Saebo, Karen C; Johansson, Lars O; Hustvedt, Svein Olaf; Haldorsen, Anita G; Bjørnerud, Atle; Fayad, Zahi A; Ahlstrom, Haakan K

    2006-07-01

    We sought to evaluate the effect of the particle size and coating material of various iron oxide preparations on the rate of rat liver clearance. The following iron oxide formulations were used in this study: dextran-coated ferumoxide (size = 97 nm) and ferumoxtran-10 (size = 21 nm), carboxydextran-coated SHU555A (size = 69 nm) and fractionated SHU555A (size = 12 nm), and oxidized-starch coated materials either unformulated NC100150 (size = 15 nm) or formulated NC100150 injection (size = 12 nm). All formulations were administered to 165 rats at 2 dose levels. Quantitative liver R2* values were obtained during a 63-day time period. The concentration of iron oxide particles in the liver was determined by relaxometry, and these values were used to calculate the particle half-lives in the liver. After the administration of a high dose of iron oxide, the half-life of iron oxide particles in rat liver was 8 days for dextran-coated materials, 10 days for carboxydextran materials, 14 days for unformulated oxidized-starch, and 29 days for formulated oxidized-starch. The results of the study indicate that materials with similar coating but different sizes exhibited similar rates of liver clearance. It was, therefore, concluded that the coating material significantly influences the rate of iron oxide clearance in rat liver.

  5. A Polysaccharide from Ganoderma atrum Improves Liver Function in Type 2 Diabetic Rats via Antioxidant Action and Short-Chain Fatty Acids Excretion.

    Science.gov (United States)

    Zhu, Ke-Xue; Nie, Shao-Ping; Tan, Le-He; Li, Chuan; Gong, De-Ming; Xie, Ming-Yong

    2016-03-09

    The present study was to evaluate the beneficial effect of polysaccharide isolated from Ganoderma atrum (PSG-1) on liver function in type 2 diabetic rats. Results showed that PSG-1 decreased the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), while increasing hepatic glycogen levels. PSG-1 also exerted strong antioxidant activities, together with upregulated mRNA expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), glucose transporter-4 (GLUT4), phosphoinositide 3-kinase (PI3K), and phosphorylated-Akt (p-Akt) in the liver of diabetic rats. Moreover, the concentrations of short-chain fatty acids (SCFA) were significantly higher in the liver, serum, and faeces of diabetic rats after treating with PSG-1 for 4 weeks. These results suggest that the improvement of PSG-1 on liver function in type 2 diabetic rats may be due to its antioxidant effects, SCFA excretion in the colon from PSG-1, and regulation of hepatic glucose uptake by inducing GLUT4 translocation through PI3K/Akt signaling pathways.

  6. Acute Liver Failure Due to Regorafenib May Be Caused by Impaired Liver Blood Flow: A Case Report.

    Science.gov (United States)

    Akamine, Takaki; Ando, Koji; Oki, Eiji; Saeki, Hiroshi; Nakashima, Yuichiro; Imamura, Y U; Ohgaki, Kippei; Maehara, Yoshihiko

    2015-07-01

    Regorafenib has been approved for treatment of patients with unresectable or recurrent gastrointestinal stromal tumors resistant to imatinib or sunitinib. However, regorafenib has severe side-effects, including acute liver failure. We describe the case of a patient with multiple liver metastases of a small intestinal stromal tumor who experienced acute liver failure while being treated with regorafenib. A 50-year-old patient with an unresectable small intestinal stromal tumor resistant to prior treatment with imatinib and sunitinib was started on regorafenib, but experienced acute liver failure 10 days later. Plasma exchange and steroid pulse treatment improved her liver function. During liver failure, abdominal ultrasonography showed to-and-fro flow in the portal vein. Lactate dehydrogenase concentration was markedly elevated to 1633 U/l. These findings indicate that liver failure in this patient was due to impaired liver blood flow. Regorafenib may impair liver blood flow, inducing acute liver failure. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Postoperative Insulin-Like Growth Factor 1 Levels Reflect the Graft's Function and Predict Survival after Liver Transplantation.

    Directory of Open Access Journals (Sweden)

    Daniele Nicolini

    Full Text Available The reduction of insulin-like growth factor 1 (IGF-1 plasma levels is associated with the degree of liver dysfunction and mortality in cirrhotic patients. However, little research is available on the recovery of the IGF-1 level and its prognostic role after liver transplantation (LT.From April 2010 to May 2011, 31 patients were prospectively enrolled (25/6 M/F; mean age±SEM: 55.2±1.4 years, and IGF-1 serum levels were assessed preoperatively and at 15, 30, 90, 180 and 365 days after transplantation. The influence of the donor and recipient characteristics (age, use of extended criteria donor grafts, D-MELD and incidence of early allograft dysfunction on hormonal concentration was analyzed. The prognostic role of IGF-1 level on patient survival and its correlation with routine liver function tests were also investigated.All patients showed low preoperative IGF-1 levels (mean±SEM: 29.5±2.1, and on postoperative day 15, a significant increase in the IGF-1 plasma level was observed (102.7±11.7 ng/ml; p65 years or extended criteria donor grafts. An inverse correlation between IGF-1 and bilirubin serum levels at day 15 (r = -0.3924, p = 0.0320 and 30 (r = -0.3894, p = 0.0368 was found. After multivariate analysis, early (within 15 days IGF-1 normalization [Exp(b = 3.913; p = 0.0484] was the only prognostic factor associated with an increased 3-year survival rate.IGF-1 postoperative levels are correlated with the graft's quality and reflect liver function. Early IGF-1 recovery is associated with a higher 3-year survival rate after LT.

  8. Assessment of fibrotic liver disease with multimodal nonlinear optical microscopy

    Science.gov (United States)

    Lu, Fake; Zheng, Wei; Tai, Dean C. S.; Lin, Jian; Yu, Hanry; Huang, Zhiwei

    2010-02-01

    Liver fibrosis is the excessive accumulation of extracellular matrix proteins such as collagens, which may result in cirrhosis, liver failure, and portal hypertension. In this study, we apply a multimodal nonlinear optical microscopy platform developed to investigate the fibrotic liver diseases in rat models established by performing bile duct ligation (BDL) surgery. The three nonlinear microscopy imaging modalities are implemented on the same sectioned tissues of diseased model sequentially: i.e., second harmonic generation (SHG) imaging quantifies the contents of the collagens, the two-photon excitation fluorescence (TPEF) imaging reveals the morphology of hepatic cells, while coherent anti-Stokes Raman scattering (CARS) imaging maps the distributions of fats or lipids quantitatively across the tissue. Our imaging results show that during the development of liver fibrosis (collagens) in BDL model, fatty liver disease also occurs. The aggregated concentrations of collagen and fat constituents in liver fibrosis model show a certain correlationship between each other.

  9. 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,...

  10. Temporary Intraoperative Porto-Caval Shunts in Piggy-Back Liver Transplantation Reduce Intraoperative Blood Loss and Improve Postoperative Transaminases and Renal Function: A Meta-Analysis.

    Science.gov (United States)

    Pratschke, Sebastian; Rauch, Alexandra; Albertsmeier, Markus; Rentsch, Markus; Kirschneck, Michaela; Andrassy, Joachim; Thomas, Michael; Hartwig, Werner; Figueras, Joan; Del Rio Martin, Juan; De Ruvo, Nicola; Werner, Jens; Guba, Markus; Weniger, Maximilian; Angele, Martin K

    2016-12-01

    The value of temporary intraoperative porto-caval shunts (TPCS) in cava-sparing liver transplantation is discussed controversially. Aim of this meta-analysis was to analyze the impact of temporary intraoperative porto-caval shunts on liver injury, primary non-function, time of surgery, transfusion of blood products and length of hospital stay in cava-sparing liver transplantation. A systematic search of MEDLINE/PubMed, EMBASE and PsycINFO retrieved a total of 909 articles, of which six articles were included. The combined effect size and 95 % confidence interval were calculated for each outcome by applying the inverse variance weighting method. Tests for heterogeneity (I 2 ) were also utilized. Usage of a TPCS was associated with significantly decreased AST values, significantly fewer transfusions of packed red blood cells and improved postoperative renal function. There were no statistically significant differences in primary graft non-function, length of hospital stay or duration of surgery. This meta-analysis found that temporary intraoperative porto-caval shunts in cava-sparing liver transplantation reduce blood loss as well as hepatic injury and enhance postoperative renal function without prolonging operative time. Randomized controlled trials investigating the use of temporary intraoperative porto-caval shunts are needed to confirm these findings.

  11. Função sexual de homens submetidos a transplante hepático Sexual function of males subjected to liver transplantation

    Directory of Open Access Journals (Sweden)

    Júlio Cezar Uili Coelho

    2003-01-01

    Full Text Available OBJETIVO: Avaliar a qualidade de vida sexual masculina antes e depois do transplante hepático. MÉTODOS: Foi enviado questionário de avaliação para 56 doentes masculinos, que tinham idade superior a 18 anos e que sobreviveram mais de seis meses após o transplante hepático. O questionário continha 15 perguntas com cinco ou seis alternativas de resposta para mensurar a função sexual masculina segmentada por cinco componentes: função erétil, função orgástica, desejo sexual, satisfação com a relação sexual e satisfação com a vida sexual como um todo. As respostas geraram valores numéricos, os quais foram agrupados dentro de cada domínio e comparados antes e depois do transplante hepático. RESULTADOS: Vinte e cinco doentes responderam completamente o questionário. Todas os cinco componentes da função sexual melhoraram após o transplante hepático, sendo que o escore da função erétil aumentou de 21,12±8,07 para 26,52±5,22 (p=0,004, da função orgástica de 7,28±3,05 para 9,36±1,47 (p=0,008, da função desejo sexual de 6,64±2,58 para 8,68±1,35 (p=0,005, da satisfação com relação sexual de 9,16±3,83 para 12,52±2,65 (pBACKGROUND: Sexual dysfunction is very common in liver transplantation candidates. Our objective is to determine the sexual life quality of males before and after liver transplantation. METHODS: Questionnaire was sent to 56 males over 18 years of age with at least six-month survival after orthotopic liver transplantation. The self-administered questionnaire contained 15 questions with 5 or 6 alternatives to determine the male sexual function which may be divided into 5 domains: 1 erectile function; 2 orgasmic function; 3 sexual desire; 4 intercourse satisfaction; and 5 overall satisfaction with sexual life. Each answer received a score. Domains scores were computed by summing the scores for individual answers and they were compared before and after the liver transplantation. RESULTS: Twenty

  12. ENZYME MARKERS ACTIVITY AND BILE FORMATION FUNCTION OF LIVER IN CASES OF TUBERCULOSTATICS AND HEXAVALENT CHROMIUM COMPOUNDS AFFECTION IN RATS

    OpenAIRE

    N. I. Burmas; L. S. Fira; P. H. Lyhackyy

    2016-01-01

    Background. Currently, the growing incidence of toxic lesions of the liver is associated with industrial chemicalization and uncontrolled use of hepatotoxic drugs in everyday life. There are about one thousand drugs with high or low hepatotoxicity, such as anti-TB drugs. Objective. In this research we studied the intracellular enzymes activity and bile formation function of the liver in rats of different ages in cases of tuberculostatic (isoniazid and rifampicin) affection and chromium (p...

  13. 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

  14. FibroMeters: a family of blood tests for liver fibrosis.

    Science.gov (United States)

    Calès, P; Boursier, J; Oberti, F; Hubert, I; Gallois, Y; Rousselet, M-C; Dib, N; Moal, V; Macchi, L; Chevailler, A; Michalak, S; Hunault, G; Chaigneau, J; Sawadogo, A; Lunel, F

    2008-09-01

    FibroMeters are blood tests for liver fibrosis with several specificities: two main diagnostic targets (fibrosis stage and area of fibrosis); adaptation to specific causes; and results confirmed by an expert system. Thus, FibroMeters comprise six different tests: one for staging and one for quantitation of liver fibrosis in each of the three main causes of chronic liver disease-chronic viral hepatitis, alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). FibroMeters display a high overall diagnostic accuracy and are the only tests to correctly classify 100% of HCV patients without fibrosis or with cirrhosis. They have 90% predictive values in a higher proportion of patients than with other usual blood tests. A 90% correct classification is available in 100% of HCV patients with the following reliable diagnostic intervals: F0/1, F1/2, F2+/-1, F3+/-1. In real-life conditions, the reproducibility of FibroMeters is higher than that of liver biopsy or ultrasonographic elastometry. FibroMeters are robust tests with the most stable diagnostic performance across different centers. Optional tests are also available, such as a specific one for cirrhosis, which has a diagnostic accuracy of 93.0% (AUROC: 0.92) and a 100% positive predictive value for diagnosis of HCV cirrhosis. Determination by FibroMeters of the area of fibrosis - the only direct, non-invasive, quantitative measurement of liver fibrosis - are especially useful for following-up cirrhosis as it correlates well with clinical events. FibroMeters are also very accurate in HVB or HIV-HCV co-infected patients. The tests specific for ALD and NAFLD also have a high diagnostic accuracy (AUROCs: 0.96 and 0.94, respectively, for significant fibrosis).

  15. Improving lives through a bioartificial liver support system

    CSIR Research Space (South Africa)

    Naidoo, K

    2008-11-01

    Full Text Available This poster covers the development of a technology towards a novel bioartificial liver support system (BALSS) that is capable of providing liver functions, in patients with acute liver failure, while housed outside the body (extra corporeal...

  16. Splenectomy attenuates murine liver fibrosis with hypersplenism stimulating hepatic accumulation of Ly-6C(lo) macrophages.

    Science.gov (United States)

    Yada, Akito; Iimuro, Yuji; Uyama, Naoki; Uda, Yugo; Okada, Toshihiro; Fujimoto, Jiro

    2015-10-01

    Splenectomy in cirrhotic patients has been reported to improve liver function; however the underlying mechanism remains obscure. In the present study, we investigated the mechanism using a murine model, which represents well the compensated liver cirrhosis. C57BL/6 male mice were allowed to drink water including thioacetamide (TAA: 300 mg/L) ad libitum for 32 weeks. After splenectomy at 32 weeks, mice were sacrificed on days one, seven, and 28, respectively, while TAA-administration was continued. Perioperative changes in peripheral blood and liver tissues were analyzed. TAA treatment of mice for 32 weeks reproducibly achieved advanced liver fibrosis with splenomegaly, thrombocytopenia, and leukocytopenia. After splenectomy, liver fibrosis was attenuated, and macrophages/monocytes were significantly increased in peripheral blood, as well as in the liver. Progenitor-like cells expressing CK-19, EpCAM, or CD-133 appeared in the liver after TAA treatment, and gradually disappeared after splenectomy. Macrophages/monocytes accumulated in the liver, most of which were negative for Ly-6C, were adjacent to the hepatic progenitor-like cells, and quantitative RT-PCR indicated increased canonical Wnt and decreased Notch signals. As a result, a significant amount of β-catenin accumulated in the progenitor-like cells. Moreover, relatively small Ki67-positive hepatic cells were significantly increased. Protein expression of MMP-9, to which Ly-6G-positive neutrophils contributed, was also increased in the liver after splenectomy. The hepatic accumulation of macrophages/monocytes, most of which are Ly-6C(lo), the reduction of fibrosis, and the gradual disappearance of hepatic progenitor-like cells possibly play significant roles in the tissue remodeling process in cirrhotic livers after splenectomy. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  17. A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.

    Science.gov (United States)

    Cherkaoui-Rbati, Mohammed H; Paine, Stuart W; Littlewood, Peter; Rauch, Cyril

    2017-01-01

    All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ. Nevertheless, the lobule (liver unit), located at the end of each branch, is composed of many sinusoids where the blood flow can vary and therefore creates heterogeneity (e.g. drug concentration, enzyme level). A liver model was constructed by describing the geometry of a lobule, where the blood velocity increases toward the central vein, and by modeling the exchange mechanisms between the blood and hepatocytes. Moreover, the three major DDI mechanisms of metabolic enzymes; competitive inhibition, mechanism based inhibition and induction, were accounted for with an undefined number of drugs and/or enzymes. The liver model was incorporated into a physiological-based pharmacokinetic (PBPK) model and simulations produced, that in turn were compared to ten clinical results. The liver model generated a hierarchy of 5 sinusoidal levels and estimated a blood volume of 283 mL and a cell density of 193 × 106 cells/g in the liver. The overall PBPK model predicted the pharmacokinetics of midazolam and the magnitude of the clinical DDI with perpetrator drug(s) including spatial and temporal enzyme levels changes. The model presented herein may reduce costs and the use of laboratory animals and give the opportunity to explore different clinical scenarios, which reduce the risk of adverse events, prior to costly human clinical studies.

  18. A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.

    Directory of Open Access Journals (Sweden)

    Mohammed H Cherkaoui-Rbati

    Full Text Available All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs of new chemical entities (NCEs and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ. Nevertheless, the lobule (liver unit, located at the end of each branch, is composed of many sinusoids where the blood flow can vary and therefore creates heterogeneity (e.g. drug concentration, enzyme level. A liver model was constructed by describing the geometry of a lobule, where the blood velocity increases toward the central vein, and by modeling the exchange mechanisms between the blood and hepatocytes. Moreover, the three major DDI mechanisms of metabolic enzymes; competitive inhibition, mechanism based inhibition and induction, were accounted for with an undefined number of drugs and/or enzymes. The liver model was incorporated into a physiological-based pharmacokinetic (PBPK model and simulations produced, that in turn were compared to ten clinical results. The liver model generated a hierarchy of 5 sinusoidal levels and estimated a blood volume of 283 mL and a cell density of 193 × 106 cells/g in the liver. The overall PBPK model predicted the pharmacokinetics of midazolam and the magnitude of the clinical DDI with perpetrator drug(s including spatial and temporal enzyme levels changes. The model presented herein may reduce costs and the use of laboratory animals and give the opportunity to explore different clinical scenarios, which reduce the risk of adverse events, prior to costly human clinical studies.

  19. Novel Action of Carotenoids on Non-Alcoholic Fatty Liver Disease: Macrophage Polarization and Liver Homeostasis.

    Science.gov (United States)

    Ni, Yinhua; Zhuge, Fen; Nagashimada, Mayumi; Ota, Tsuguhito

    2016-06-24

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis.

  20. CT of liver steatosis after subtotal pancreatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Lundstedt, C.; Andren-Sandberg, A. (Lund Univ. (Sweden). Dept. of Diagnostic Radiology Lund Univ. (Sweden). Dept. of Surgery)

    1991-01-01

    The liver attenuation of 50 patients operated with a subtotal pancreatectomy for pancreatic and duodenal tumors was evaluated with CT. Of 18 patients surviving more than 18 months after surgery, 7 developed a markedly reduced liver attenuation indicating liver steatosis. No patient became diabetic or showed evidence of malnutrition after surgery. No correlation between the liver attenuation values and the patients' liver function test was noted. The steatosis was reversible in 4 of the 7 patients. The pathophysiological cause of the steatosis remains unknown. Partial pancreatectomy should be included among the reasons listed for liver steatosis. (orig.).

  1. CT of liver steatosis after subtotal pancreatectomy

    International Nuclear Information System (INIS)

    Lundstedt, C.; Andren-Sandberg, A.; Lund Univ.

    1991-01-01

    The liver attenuation of 50 patients operated with a subtotal pancreatectomy for pancreatic and duodenal tumors was evaluated with CT. Of 18 patients surviving more than 18 months after surgery, 7 developed a markedly reduced liver attenuation indicating liver steatosis. No patient became diabetic or showed evidence of malnutrition after surgery. No correlation between the liver attenuation values and the patients' liver function test was noted. The steatosis was reversible in 4 of the 7 patients. The pathophysiological cause of the steatosis remains unknown. Partial pancreatectomy should be included among the reasons listed for liver steatosis. (orig.)

  2. CT of liver steatosis after subtotal pancreatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Lundstedt, C; Andren-Sandberg, A [Lund Univ. (Sweden). Dept. of Diagnostic Radiology Lund Univ. (Sweden). Dept. of Surgery

    1991-01-01

    The liver attenuation of 50 patients operated with a subtotal pancreatectomy for pancreatic and duodenal tumors was evaluated with CT. Of 18 patients surviving more than 18 months after surgery, 7 developed a markedly reduced liver attenuation indicating liver steatosis. No patient became diabetic or showed evidence of malnutrition after surgery. No correlation between the liver attenuation values and the patients' liver function test was noted. The steatosis was reversible in 4 of the 7 patients. The pathophysiological cause of the steatosis remains unknown. Partial pancreatectomy should be included among the reasons listed for liver steatosis. (orig.).

  3. Campylobacter in chicken livers and their destruction by pan frying.

    Science.gov (United States)

    Whyte, R; Hudson, J A; Graham, C

    2006-12-01

    To enumerate Campylobacter spp. on the external surface and internal portions of chicken livers, and to assess the cooking required to inactivate naturally present cells. Of 30 livers tested all yielded Campylobacter spp. on their surfaces and 90% were found to contain the organism in internal tissue. Four (13%) livers contained >10(4) MPN campylobacters, and an additional seven (23%) contained >10(3) MPN campylobacters per liver. The internal temperature of pan-fried livers under the conditions used reached a maximum of 70-80 degrees C, and maintaining this temperature for 2-3 min was necessary to inactivate naturally occurring Campylobacter spp. All isolates identified were either C. jejuni or C. coli. Chicken livers represent a potential source of human campylobacteriosis as they contained >10(4) MPN per liver in 13% of the samples tested. Pan-frying can produce an acceptable product that is safe to eat. SIGNIFICANCE AND IMPACT OF THIS STUDY: The data provided can be used in exposure assessments of Campylobacter in poultry products in terms of both quantitative data and assessing pan-frying and its ability to destroy campylobacters.

  4. Biochemical markers of the functional disorders of the liver in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    L.F. Bogmat

    2017-05-01

    Full Text Available Background. Systemic lupus erythematosus (SLE in the basis of the pathogenesis has generalized autoimmune inflammation, which leads to the development of a wide range of immune-inflammatory organ disorders. Among them, the liver deserves special attention, since its functional state can reflect not only the severity of the pathological process, but also the response on aggressive treatment. The purpose of the work was studying the biochemical markers of the functional state of the liver in children with initial stages of SLE. Materials and methods. Features of the lipid, carbohydrate spectrum of the blood, indicators of pigment exchange, markers of cytolysis, cholestasis, fibrosis and protein-synthetic function of the liver were studied in children and adolescents with SLE. Twenty six patients aged 7–18 years were examined. Two groups were formed: 10 patients (38.4 % with the duration of the disease of 1–3 years and 16 people (61.5 % with duration of more than 3 years. Results. The average blood lipids levels did not exceed the reference values and did not have statistical differences among the patients of the selected groups. The levels of total cholesterol and triglycerides in both groups of patients significantly exceeded the control values (p < 0.05. Indicators of low density lipoprotein cholesterol increased already in the early stages of the disease (p < 0.05 and reached the maximum values in individuals with a course of SLE over 3 years (p < 0.05. Concentration of high density lipoprotein cholesterol in patients of the second group decreased somewhat (p < 0.1. There was an increase in the average values of atherogenic index by 1.7 times among patients in the first group (p < 0.05 and 2.25 times in persons from the second group (p < 0.05. Studies of other metabolic links showed that the average values of glycaemia and immunoreactive insulin (IRI were consistent with the physiological norm. However, half of patients with SLE had

  5. A simple and sensitive method for the determination of fibric acids in the liver by liquid chromatography.

    Science.gov (United States)

    Karahashi, Minako; Fukuhara, Hiroto; Hoshina, Miki; Sakamoto, Takeshi; Yamazaki, Tohru; Mitsumoto, Atsushi; Kawashima, Yoichi; Kudo, Naomi

    2014-01-01

    Fibrates are used in biochemical and pharmacological studies as bioactive tools. Nevertheless, most studies have lacked information concerning the concentrations of fibric acids working inside tissues because a simple and sensitive method is not available for their quantitation. This study aimed to develop a simple and sensitive bioanalytical method for the quantitation of clofibric, bezafibric and fenofibric acids in samples of very small portions of tissues. Fibric acids were extracted into n-hexane-ethyl acetate from tissue homogenates (10 mg of liver, kidney or muscle) or serum (100 µL) and were derivatized with 4-bromomethyl-6,7-dimethoxycoumarin, followed by HPLC with fluorescence detection. These compounds were separated isocratically on a reversed phase with acetonitrile-water. Standard analytical curves were linear over the concentration range of 0.2-20 nmol/10 mg of liver. Precision and accuracy were within acceptable limits. Recovery from liver homogenates ranged from 93.03 to 112.29%. This method enabled the quantitation of fibric acids in 10 mg of liver from rats treated with clofibric acid, bezafibric acid or fenofibrate. From these analytical data, it became clear that there was no large difference in ratio of acyl-CoA oxidase 1 (Acox1) mRNA level to fibric acid content in the liver among the three fibric acids, suggesting that these three fibric acids have similar potency to increase expression of the Acox1 gene, which is a target of peroxisome proliferator-activated receptor α. Thus, the proposed method is a simple, sensitive and reliable tool for the quantitation of fibric acids working in vivo inside livers.

  6. Structural changes in the liver in metabolic syndrome

    Directory of Open Access Journals (Sweden)

    D. V. Vasendin

    2015-01-01

    Full Text Available Scientifically proven close relationship of nonalcoholic fatty liver disease with development of metabolic syndrome and its individual components involves the conclusion that the target organ in metabolic symptom, even regardless of the severity of obesity, the liver occupies a dominant position, as the body undergoes the first characteristic of non-alcoholic fatty liver disease changes, involving violation of metabolism in the body. Dislipoproteinemia plays an important role in the formation of metabolic syndrome in obesity and other obesity-associated diseases. Altered liver function are the root cause of violations of processes of lipid metabolism and, consequently, abnormal functioning of the liver may be a separate, additional and independent risk factor for development of dyslipidemia and obesity as the main component of the metabolic syndrome.

  7. Calcium signaling in liver.

    Science.gov (United States)

    Gaspers, Lawrence D; Thomas, Andrew P

    2005-01-01

    In hepatocytes, hormones linked to the formation of the second messenger inositol 1,4,5-trisphosphate (InsP3) evoke transient increases or spikes in cytosolic free calcium ([Ca2+]i), that increase in frequency with the agonist concentration. These oscillatory Ca2+ signals are thought to transmit the information encoded in the extracellular stimulus to down-stream Ca2+-sensitive metabolic processes. We have utilized both confocal and wide field fluorescence microscopy techniques to study the InsP3-dependent signaling pathway at the cellular and subcellular levels in the intact perfused liver. Typically InsP3-dependent [Ca2+]i spikes manifest as Ca2+ waves that propagate throughout the entire cytoplasm and nucleus, and in the intact liver these [Ca2+]i increases are conveyed through gap junctions to encompass entire lobular units. The translobular movement of Ca2+ provides a means to coordinate the function of metabolic zones of the lobule and thus, liver function. In this article, we describe the characteristics of agonist-evoked [Ca2+]i signals in the liver and discuss possible mechanisms to explain the propagation of intercellular Ca2+ waves in the intact organ.

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

    Directory of Open Access Journals (Sweden)

    Ricky H Bhogal

    2011-03-01

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

  9. Controlled cell morphology and liver-specific function of engineered primary hepatocytes by fibroblast layer cell densities.

    Science.gov (United States)

    Sakai, Yusuke; Koike, Makiko; Kawahara, Daisuke; Hasegawa, Hideko; Murai, Tomomi; Yamanouchi, Kosho; Soyama, Akihiko; Hidaka, Masaaki; Takatsuki, Mitsuhisa; Fujita, Fumihiko; Kuroki, Tamotsu; Eguchi, Susumu

    2018-03-05

    Engineered primary hepatocytes, including co-cultured hepatocyte sheets, are an attractive to basic scientific and clinical researchers because they maintain liver-specific functions, have reconstructed cell polarity, and have high transplantation efficiency. However, co-culture conditions regarding engineered primary hepatocytes were suboptimal in promoting these advantages. Here we report that the hepatocyte morphology and liver-specific function levels are controlled by the normal human diploid fibroblast (TIG-118 cell) layer cell density. Primary rat hepatocytes were plated onto TIG-118 cells, previously plated 3 days before at 1.04, 5.21, and 26.1×10 3  cells/cm 2 . Hepatocytes plated onto lower TIG-118 cell densities expanded better during the early culture period. The hepatocytes gathered as colonies and only exhibited small adhesion areas because of the pushing force from proliferating TIG-118 cells. The smaller areas of each hepatocyte result in the development of bile canaliculi. The highest density of TIG-118 cells downregulated albumin synthesis activity of hepatocytes. The hepatocytes may have undergone apoptosis associated with high TGF-β1 concentration and necrosis due to a lack of oxygen. These occurrences were supported by apoptotic chromatin condensation and high expression of both proteins HIF-1a and HIF-1b. Three types of engineered hepatocyte/fibroblast sheets comprising different TIG-118 cell densities were harvested after 4 days of hepatocyte culture and showed a complete cell sheet format without any holes. Hepatocyte morphology and liver-specific function levels are controlled by TIG-118 cell density, which helps to design better engineered hepatocytes for future applications such as in vitro cell-based assays and transplantable hepatocyte tissues. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  10. 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.

  11. Transcriptional ontogeny of the developing liver

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    Lee Janice S

    2012-01-01

    Full Text Available Abstract Background During embryogenesis the liver is derived from endodermal cells lining the digestive tract. These endodermal progenitor cells contribute to forming the parenchyma of a number of organs including the liver and pancreas. Early in organogenesis the fetal liver is populated by hematopoietic stem cells, the source for a number of blood cells including nucleated erythrocytes. A comprehensive analysis of the transcriptional changes that occur during the early stages of development to adulthood in the liver was carried out. Results We characterized gene expression changes in the developing mouse liver at gestational days (GD 11.5, 12.5, 13.5, 14.5, 16.5, and 19 and in the neonate (postnatal day (PND 7 and 32 compared to that in the adult liver (PND67 using full-genome microarrays. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were under expressed. Comparison of the dataset to a number of previously published microarray datasets revealed 1 a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2 a nucleated erythrocyte signature in the fetus and 3 under expression of most xenobiotic metabolism genes throughout development, with the exception of a number of transporters associated with either hematopoietic cells or cell proliferation in hepatocytes. Conclusions Overall, these findings reveal the complexity of gene expression changes during liver development and maturation, and provide a foundation to predict responses to chemical and drug exposure as a function of early life-stages.

  12. Vitamin D status, liver enzymes, and incident liver disease and mortality

    DEFF Research Database (Denmark)

    Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Borglykke, Anders

    2014-01-01

    , alcohol consumption, smoking, physical activity, dietary habits, education, body mass index, and ALT). The risk of having a high level of ALT, AST, or GGT tended to be higher for lower vitamin D levels, although not statistically significant. In this general population study, vitamin D status...... was inversely associated with incident liver disease. Further studies are needed to determine whether patients in risk of developing impaired liver function should be screened for vitamin D deficiency for preventive purposes....

  13. Observation of Liver Color Scan

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Y K; Ahn, S B [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1969-09-15

    In the past few years, scintigraphy has become increasingly important in clinical practice, and the use of a color-printing technique has permitted a more accurate interpretation of the scan image. Our liver color scintigrams consist of 51 hepatomas, 35 liver cirrhosis, 22 liver abscesses, 10 hepatitis and other 13 cases of the liver diseases which were clinically and pathologically diagnosed at Severance Hospital, Yonsei Univ. since Feb. 1969 through Sept. 1969. These scintigrams have been analyzed in terms of various pathologic morphology, such as size, shape, margin of the liver, distribution of radioactivity, and shape of the space occupying lesions. The results are as follows: 1) Enlargement of the liver was the most common finding in the diseased livers. The Rt. lobe enlargement was particularly prominent in the liver abscess. 2) Irregular distribution of radioactivity in the liver (so called mottling) was present in 78% of hepatoma, while it was seen only in 31% of liver abscesses. 3) Liver cirrhosis tends to show perihilar accumulation of the isotope (57%). 4) The deformity of the lower most angle of the Rt. lobe, and the Lt. lateral margin of the Lt. lobe was also impressive throughout the cases (74-95% of all diseased livers). 5) The frequency of visualization of the spleen was influenced by the size of space occupying lesions and the amount of functioning liver. 6) Differentiation between the liver abscess and hepatoma seems to be possible on scintigram, when shape an margin of defect and patterns of distribution of radioactivity in the remaining liver are clearly demonstrated.

  14. Observation of Liver Color Scan

    International Nuclear Information System (INIS)

    Choe, Y. K.; Ahn, S. B.

    1969-01-01

    In the past few years, scintigraphy has become increasingly important in clinical practice, and the use of a color-printing technique has permitted a more accurate interpretation of the scan image. Our liver color scintigrams consist of 51 hepatomas, 35 liver cirrhosis, 22 liver abscesses, 10 hepatitis and other 13 cases of the liver diseases which were clinically and pathologically diagnosed at Severance Hospital, Yonsei Univ. since Feb. 1969 through Sept. 1969. These scintigrams have been analyzed in terms of various pathologic morphology, such as size, shape, margin of the liver, distribution of radioactivity, and shape of the space occupying lesions. The results are as follows: 1) Enlargement of the liver was the most common finding in the diseased livers. The Rt. lobe enlargement was particularly prominent in the liver abscess. 2) Irregular distribution of radioactivity in the liver (so called mottling) was present in 78% of hepatoma, while it was seen only in 31% of liver abscesses. 3) Liver cirrhosis tends to show perihilar accumulation of the isotope (57%). 4) The deformity of the lower most angle of the Rt. lobe, and the Lt. lateral margin of the Lt. lobe was also impressive throughout the cases (74-95% of all diseased livers). 5) The frequency of visualization of the spleen was influenced by the size of space occupying lesions and the amount of functioning liver. 6) Differentiation between the liver abscess and hepatoma seems to be possible on scintigram, when shape an margin of defect and patterns of distribution of radioactivity in the remaining liver are clearly demonstrated.

  15. ENZYME MARKERS ACTIVITY AND BILE FORMATION FUNCTION OF LIVER IN CASES OF TUBERCULOSTATICS AND HEXAVALENT CHROMIUM COMPOUNDS AFFECTION IN RATS

    Directory of Open Access Journals (Sweden)

    N. I. Burmas

    2016-05-01

    Full Text Available Background. Currently, the growing incidence of toxic lesions of the liver is associated with industrial chemicalization and uncontrolled use of hepatotoxic drugs in everyday life. There are about one thousand drugs with high or low hepatotoxicity, such as anti-TB drugs. Objective. In this research we studied the intracellular enzymes activity and bile formation function of the liver in rats of different ages in cases of tuberculostatic (isoniazid and rifampicin affection and chromium (potassium dichromate intoxication. Methods. The experimental affection of rats of different ages was performed by combined injection of hexavalent chromium compounds (a solution of potassium dichromate, 3 mg/kg, isoniazid (0.05 g/kg and rifampicin (0.25 g/kg. On the 7th and 14th days the rats were injected with enterosorbent Sorbex (150 mg/kg. Enzyme markers activity of the liver was evaluated due to alanine and aspartate aminotransferases (ALT and AST and alkaline phosphatase (ALP rates. Bile formation function of the liver was evaluated by total bilirubin and bile acids content in blood. Results. The disorders in hepatocytes plasma membranes permeability were defined by the increased rates of ALT, AST and alkaline phosphatase in blood serum which were decreased in the liver. It was determined that total bilirubin and bile acids content in blood serum of the affected animals increased. It influenced hepatocytes excretion in bile capillaries and caused cholestasis and revenues decrease in bile. Conclusions. The most significant metabolic disorders in cases of chrome-isoniazid-rifampicin affection were defined in immature and senior animals in comparison with mature animals.

  16. Identification and characterization of a liver stage-specific promoter region of the malaria parasite Plasmodium.

    Directory of Open Access Journals (Sweden)

    Susanne Helm

    Full Text Available During the blood meal of a Plasmodium-infected mosquito, 10 to 100 parasites are inoculated into the skin and a proportion of these migrate via the bloodstream to the liver where they infect hepatocytes. The Plasmodium liver stage, despite its clinical silence, represents a highly promising target for antimalarial drug and vaccine approaches. Successfully invaded parasites undergo a massive proliferation in hepatocytes, producing thousands of merozoites that are transported into a blood vessel to infect red blood cells. To successfully develop from the liver stage into infective merozoites, a tight regulation of gene expression is needed. Although this is a very interesting aspect in the biology of Plasmodium, little is known about gene regulation in Plasmodium parasites in general and in the liver stage in particular. We have functionally analyzed a novel promoter region of the rodent parasite Plasmodium berghei that is exclusively active during the liver stage of the parasite. To prove stage-specific activity of the promoter, GFP and luciferase reporter assays have been successfully established, allowing both qualitative and accurate quantitative analysis. To further characterize the promoter region, the transcription start site was mapped by rapid amplification of cDNA ends (5'-RACE. Using promoter truncation experiments and site-directed mutagenesis within potential transcription factor binding sites, we suggest that the minimal promoter contains more than one binding site for the recently identified parasite-specific ApiAP2 transcription factors. The identification of a liver stage-specific promoter in P. berghei confirms that the parasite is able to tightly regulate gene expression during its life cycle. The identified promoter region might now be used to study the biology of the Plasmodium liver stage, which has thus far proven problematic on a molecular level. Stage-specific expression of dominant-negative mutant proteins and

  17. The relationship between lung function impairment and quantitative computed tomography in chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Mets, O.M.; Murphy, K.; Zanen, P.; Lammers, J.W.; Gietema, H.A.; Jong, P.A. de; Ginneken, B. van; Prokop, M.

    2012-01-01

    To determine the relationship between lung function impairment and quantitative computed tomography (CT) measurements of air trapping and emphysema in a population of current and former heavy smokers with and without airflow limitation. In 248 subjects (50 normal smokers; 50 mild obstruction; 50 moderate obstruction; 50 severe obstruction; 48 very severe obstruction) CT emphysema and CT air trapping were quantified on paired inspiratory and end-expiratory CT examinations using several available quantification methods. CT measurements were related to lung function (FEV 1 , FEV 1 /FVC, RV/TLC, Kco) by univariate and multivariate linear regression analysis. Quantitative CT measurements of emphysema and air trapping were strongly correlated to airflow limitation (univariate r-squared up to 0.72, p < 0.001). In multivariate analysis, the combination of CT emphysema and CT air trapping explained 68-83% of the variability in airflow limitation in subjects covering the total range of airflow limitation (p < 0.001). The combination of quantitative CT air trapping and emphysema measurements is strongly associated with lung function impairment in current and former heavy smokers with a wide range of airflow limitation. (orig.)

  18. Assessment of response to therapy with hydroxyurea in patients with functional asplenia

    International Nuclear Information System (INIS)

    Santos A, O.; Demange, M.N.; Severiche, F.A.; Bomediano, V.H.; Silva, V.R.; Anjos, A.C.; Brandalise, S.R.; Etchebehere, E.C.S.C.; Cunha, M.L.; Camargo, E.E.

    1997-01-01

    Full text: Functional asplenia is a chronic complication of sickle cell (SC) disease. As the concentration of fetal hemoglobin (hemoglobin F) increases in the re blood cells (RBCs), the polymerization of hemoglobin S declines. This makes it possible for a therapeutic approach with drugs that induce hemoglobin F synthesis, leading to improvement of the acute and chronic consequences of SC disease. Hydroxyurea is a chemotherapeutic agent capable of increasing the levels of hemoglobin F in RBCs. Its long term use as an anti-sicklemic agent has been proposed recently. The purpose of this investigation was to evaluate the long term effects of hydroxyurea on the recovery of splenic function in pts with SC disease. Six pts with the disease (5 males, 1 female; 4 to 22 yrs; 5 with SS hemoglobinopathy, , 1 with Sβ o hemoglobinopathy; 4 black, 2 white) were studied. All pts received an intravenous injection of 74-185 MBq of [Tc-99m] sulfur colloid and liver-spleen imaging was performed 10 minutes later in the anterior and posterior views, with and without hepatic shielding. Pts were studied before and immediately after 6 months of treatment with hydroxyurea. All studied were submitted to visual and semi-quantitative analysis. Liver/spleen ratios were obtained before and after 6 months of treatment. Baseline images showed functional asplenia both visually and semi-quantitatively in all 5 SS pts and severely impaired splenic function in the Sβ o pt. Follow-up images performed after 6 months of treatment demonstrated significant splenic function improvement in 4 pts while 2 pts did not show any improvement. It was to demonstrate, using liver/spleen scintigraphy, that hydroxyurea is capable of reversing functional asplenia in pts with SC disease. The best results were observed in the youngest pts and in the Sβ o pt, probably because the amount of splenic fibrosis was less significant

  19. Impaired TFEB-mediated Lysosome Biogenesis and Autophagy Promote Chronic Ethanol-induced Liver Injury and Steatosis in Mice.

    Science.gov (United States)

    Chao, Xiaojuan; Wang, Shaogui; Zhao, Katrina; Li, Yuan; Williams, Jessica A; Li, Tiangang; Chavan, Hemantkumar; Krishnamurthy, Partha; He, Xi C; Li, Linheng; Ballabio, Andrea; Ni, Hong-Min; Ding, Wen-Xing

    2018-05-18

    Defects in lysosome function and autophagy contribute to pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes, evaluating the functions transcription factor EB (TFEB), which regulates lysosomal biogenesis. We performed studies with GFP-LC3 mice, mice with liver-specific deletion of transcription factor EB (TFEB), mice with disruption of the transcription factor E3 gene (TFE3-knockout mice), mice with disruption of the Tefb and Tfe3 genes (TFEB, TFE3 double-knockout mice), and Tfeb flox/flox albumin cre-negative mice (controls). TFEB was overexpressed from adenoviral vectors or knocked down with small interfering RNAs in mouse livers. Mice were placed on diets of chronic ethanol feeding plus an acute binge to induce liver damage (ethanol diet); some mice were also given injections of torin1, an inhibitor of the kinase activity of the mechanistic target of rapamycin (mTOR). Liver tissues were collected and analyzed by immunohistochemistry, immunoblots, and quantitative real-time PCR to monitor lysosome biogenesis. We analyzed levels of TFEB in liver tissues from patients with alcoholic hepatitis and from healthy donors (controls) by immunohistochemistry. Liver tissues from mice on the ethanol diet had lower levels of total and nuclear TFEB, compared with control mice, and hepatocytes had reduced lysosome biogenesis and autophagy. Hepatocytes from mice on the ethanol diet had increased translocation of mTOR into lysosomes, resulting increased mTOR activation. Administration of torin1 increased liver levels of TFEB and reduced steatosis and liver injury induced by ethanol. Mice that overexpressed TFEB in liver developed less-severe ethanol-induced liver injury and had increased lysosomal biogenesis and mitochondrial bioenergetics compared to mice carrying a control vector. Mice with knockdown of TFEB, as well as TFEB, TFE3 double-knockout mice, developed more severe liver injury in response to the

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

    Science.gov (United States)

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

    2013-09-21

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