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Sample records for quantitative liver function

  1. Assessment of liver function in chronic liver diseases and regional function of irradiated liver by means of 99mTc-galactosyl-human serum albumin liver scintigraphy and quantitative spectral analysis.

    PubMed

    Fukui, A; Murase, K; Tsuda, T; Fujii, T; Ikezoe, J

    2000-12-01

    Scintigraphy with 99mTc-diethylenetriamine pentaacetic acid galactosyl human serum albumin (99mTc-GSA) was performed on 102 patients, then the hepatic extraction fraction (HEF), the rate constant for liver uptake of the tracer from the blood (K1) and the hepatic blood flow index (HBFI) were determined by spectral analysis. The HEF, K1 and HBFI values correlated moderately or closely with various indices of hepatic function, and the HEF and K1 values decreased according to the stage of liver dysfunction. The HEF and K1 values linearly and nonlinearly correlated with HH15 and LHL15, respectively. The HEF, K1 and HBFI values for the irradiated portion of 20 patients before and alter irradiation were compared. The HEF value in patients with a cirrhotic liver significantly (p < 0.002) decreased compared with that in patients with a normal liver at a dose of less than 40 Gy, whereas the HBFI value in patients with a normal liver significantly (p < 0.05) decreased compared with that in patients with a cirrhotic liver at a dose of 40 Gy or greater. This method appears to be a simple, non-invasive and useful tool with which to quantitatively evaluate liver function and it also helps clarify changes in regional function of the irradiated liver.

  2. Three-Dimensional Quantitative Evaluation of the Segmental Functional Reserve in the Cirrhotic Liver Using Multi-Modality Imaging

    PubMed Central

    Xiang, Canhong; Chen, Yingmao; Shao, Mingzhe; Li, Can; Huang, Xin; Gong, Lei; Li, Ang; Duan, Weidong; Zhang, Aiqun; Dong, Jiahong

    2016-01-01

    Abstract To quantitatively evaluate the regional functional reserve in the cirrhotic liver and to seek related index that reflects diminished segmental liver function. A 3D system for quantitative evaluation of the liver was used to fuse technetium-99m galactosyl human serum albumin single-photon emission computed tomography and computed tomography images from 20 patients with cirrhotic liver and hepatocellular carcinoma. A set of parameters reflecting liver function including morphological liver volume, functional liver volume, functional liver density (FLD), and the drug absorption rate constant for hepatic cells (GSA-K) was calculated. Differences in FLD and GSA-K in intrahepatic segments were compared in patients with a tumor embolus (Group Y) and those without such an embolus (Group N) in the right portal vein. Differences in FLD and GSA-K in tumor-bearing (T+ group) and tumor-free (T− group) segments in patients with no tumor embolus (Group N) were also compared. Eleven living donor liver transplantation donor served as the control group. The FLD of the liver as a whole was significantly lower in patients with cirrhosis than in the control group (0.53 ± 0.13 vs 0.68 ± 0.10, P = 0.010). The FLD in segments of the right hemiliver was significantly lower than that in segments of the left hemiliver in Group Y (0.31 ± 0.21 vs 0.58 ± 0.12, P = 0.002) but not in Group N (0.60 ± 0.19 vs 0.55 ± 0.13, P = 0.294). FLD was 0.45 ± 0.17 in the T+ group and 0.60 ± 0.08 in the T− group (P = 0.008). Differences in GSA-K in intrahepatic segments were not significant. In the control group, differences in FLD and GSA-K in intrahepatic segments were not significant. The segmental liver functional reserve can be quantitatively calculated. FLD, but not GSA-K, is an index that reflects diminished regional liver function caused by portal flow obstruction or tumor compression. PMID:26945357

  3. Liver Function Tests

    MedlinePlus

    ... Your Liver > Liver Disease Information > Liver Function Tests Liver Function Tests Explore this section to learn more ... including a description and diagnosis. Why is the liver important? The liver is the second largest organ ...

  4. Quantitative functional MRI biomarkers improved early detection of colorectal liver metastases.

    PubMed

    Edrei, Yifat; Freiman, Moti; Sklair-Levy, Miri; Tsarfaty, Galia; Gross, Eitan; Joskowicz, Leo; Abramovitch, Rinat

    2014-05-01

    To implement and evaluate the performance of a computerized statistical tool designed for robust and quantitative analysis of hemodynamic response imaging (HRI) -derived maps for the early identification of colorectal liver metastases (CRLM). CRLM-bearing mice were scanned during the early stage of tumor growth and subsequently during the advanced-stage. Three experienced radiologists marked various suspected-foci on the early stage anatomical images and classified each as either highly certain or as suspected tumors. The statistical model construction was based on HRI maps (functional-MRI combined with hypercapnia and hyperoxia) using a supervised learning paradigm which was further trained either with the advanced-stage sets (late training; LT) or with the early stage sets (early training; ET). For each group of foci, the classifier results were compared with the ground-truth. The ET-based classification significantly improved the manual classification of the highly certain foci (P < 0.05) and was superior compared with the LT-based classification (P < 0.05). Additionally, the ET-based classification, offered high sensitivity (57-63%), accompanied with high positive predictive value (>94%) and high specificity (>98%) for suspected-foci. The ET-based classifier can strengthen the radiologist's classification of highly certain foci. Additionally, it can aid in classifying suspected-foci, thus enabling earlier intervention which can often be lifesaving. Copyright © 2013 Wiley Periodicals, Inc.

  5. Quantitative Assessment of Liver Function Using Gadoxetate-Enhanced Magnetic Resonance Imaging

    PubMed Central

    Georgiou, Leonidas; Penny, Jeffrey; Nicholls, Glynis; Woodhouse, Neil; Blé, François-Xavier; Hubbard Cristinacce, Penny L.; Naish, Josephine H.

    2017-01-01

    individual variability (repeatability; ki: ±0.06/min, kef: ±0.012/min). Data truncation demonstrated that the uptake rate estimates retained their precision as well as their group and individual reproducibility down to approximately 10 minutes of acquisition. Efflux rate estimates were underestimated (compared with the 50-minute acquisition) as the duration of the acquisition decreased, although these effects were more pronounced for acquisition times shorter than approximately 30 minutes. Conclusions This is the first study that reports estimates for the hepatic uptake and efflux transport process of gadoxetate in healthy volunteers in vivo. The results highlight that dynamic contrast-enhanced MRI with gadoxetate can provide novel quantitative insights into liver function and may therefore prove useful in studies that aim to monitor liver pathology, as well as being an alternative approach for studying hepatic drug-drug interactions. PMID:28002117

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

    PubMed

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

    2017-02-01

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

  7. Liver function tests

    MedlinePlus

    Liver function tests are common tests that are used to see how well the liver is working. Tests include: ... M, Bowne WB, Bluth MH. Evaluation of liver function. In: McPherson RA, Pincus MR, eds. Henry's Clinical ...

  8. Hepatic (Liver) Function Panel

    MedlinePlus

    ... related side effects. The hepatic function panel evaluates: Alanine aminotransferase (ALT). This enzyme, found in the liver, ... MORE ON THIS TOPIC Mononucleosis Hepatitis Blood Test: Alanine Aminotransferase (ALT, or SGPT) Blood Test: Aspartate Aminotransferase ( ...

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

    PubMed

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

    2014-01-01

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

  10. Portable device for the analysis of liver function: a boon to liver surgery and critical care.

    PubMed

    Mobley, Constance M; Zarrinpar, Ali

    2016-01-01

    Liver biology, liver disease and its management present a myriad of challenges to clinicians. Difficulties arise in determining liver functional capacity, which must be effectively measured in a quantitative reproducible manner. Measurement of indocyanine green (ICG) clearance, an exceptional tool that has been used for decades to assess liver function, has traditionally been cumbersome to perform. New technology now allows for rapid and noninvasive determination of ICG clearance making it clinically accessible. This adds ICG clearance measurement to the armamentarium of physiologic monitors that could be routinely used in the evaluation of patients undergoing liver surgery or in the intensive care setting.

  11. Oral contraceptives and liver function

    PubMed Central

    Hargreaves, Tom

    1969-01-01

    Oral contraceptives can cause liver damage and jaundice but this is very rare in women in the United Kingdom. The drugs are contraindicated where there is a history of recurrent intrahepatic cholestasis of pregnancy and acute or chronic disturbance of liver function which can be congenital or acquired. It is not yet known whether the oestrogenic or progestogenic components of oral contraceptives cause the hepatic abnormalities. The available data suggest that neither oestrogens nor progestogens in low doses impair hepatic excretory processes. The full implications of the continued administration of oestrogens and progestogens for many years on liver proteins are not yet known.

  12. Quantitative Trait Loci Affecting Liver Fat Content in Mice

    PubMed Central

    Minkina, Olga; Cheverud, James M.; Fawcett, Gloria; Semenkovich, Clay F.; Kenney-Hunt, Jane P.

    2012-01-01

    Nonalcoholic fatty liver disease, a condition in which excess fat accumulates in the liver, is strongly associated with the metabolic syndrome, including obesity and other related conditions. This disease has the potential to progress from steatosis to steatohepatitis, fibrosis, and cirrhosis. The recent increase in the prevalence of the metabolic syndrome is largely driven by changes in diet and activity levels. Individual variation in the response to this obesogenic environment, however, is attributable in part to genetic variation between individuals, but very few mammalian genetic loci have been identified with effects on fat accumulation in the liver. To study the genetic basis for variation in liver fat content in response to dietary fat, liver fat proportion was determined using quantitative magnetic resonance imaging in 478 mice from 16 LG/J X SM/J recombinant inbred strains fed either a high-fat (42% kcal from fat) or low-fat (15% kcal from fat) diet. An analysis of variance confirmed that there is a genetic basis for variation in liver fat content within the population with significant effects of sex and diet. Three quantitative trail loci that contribute to liver fat content also were mapped. PMID:22973538

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-01

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

  15. Assessment of liver volume variation to evaluate liver function.

    PubMed

    Tong, Cong; Xu, Xinsen; Liu, Chang; Zhang, Tianzheng; Qu, Kai

    2012-12-01

    In order to assess the value of liver volumetry in cirrhosis and acute liver failure (ALF) patients, we explored the correlation between hepatic volume and severity of the hepatic diseases. The clinical data of 48 cirrhosis patients with 60 normal controls and 39 ALF patients were collected. Computed tomography-derived liver volume (CTLV) and body surface area (BSA) of normal controls were calculated to get a regression formula for standard liver volume (SLV) and BSA. Then CTLV and SLV of all patients were calculated and grouped by Child-Turcotte-Pugh classification for cirrhosis patients and assigned according to prognosis of ALF patients for further comparison. It turned out that the mean liver volume of the control group was 1,058 ± 337 cm(3). SLV was correlated with BSA according to the regression formula. The hepatic volume of cirrhosis patients in Child A, B level was not reduced, but in Child C level it was significantly reduced with the lowest liver volume index (CTLV/SLV). Likewise, in the death group of ALF patients, the volume index was significantly lower than that of the survival group. Based on volumetric study, we proposed an ROC (receiver operating characteristic) analysis to predict the prognosis of ALF patients that CTLV/SLV < 83.9% indicates a poor prognosis. In conclusion, the CTLV/SLV ratio, which reflects liver volume variations, correlates well with the liver function and progression of cirrhosis and ALF. It is also a very useful marker for predicting the prognosis of ALF.

  16. Asialoglycoprotein receptor-targeted radiopharmaceuticals for measurement of liver function.

    PubMed

    Yang, W; Zhang, X; Liu, Y

    2014-01-01

    The number of Asialoglycoprotein (ASGP) receptors on the hepatocytes of patients with liver disease is reduced and is thus considered a good indicator for the evaluation of liver function. ASGP receptor-targeted radiopharmaceuticals permit a non-invasive way to evaluate total and regional hepatic function and hepatic functional reserve visually and quantitatively. Over the past three decades, a variety of ASGP receptor-targeted probes have been developed with different molecular backbones (albumin, polymer, small-molecular-weight ligand), different glycol-residues (galactose, lactose, N-acetyl-galactosamine) and different chelating systems suitable for radiolabeling with SPECT isotopes ((99m)Tc, (111)In, (67)Ga, (131/125)I, (153)Sm) and PET isotopes ((68)Ga, (18)F). In this review, we present an overview of ASGP receptor-targeted radiopharmaceuticals, discuss their chemistry, biodistribution, catabolism and challenge as well as application for measurement of liver function.

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

    SciTech Connect

    Zhuo, Shuangmu E-mail: hanry-yu@nuhs.edu.sg; Yan, Jie; Kang, Yuzhan; Peng, Qiwen; 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.

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

    PubMed

    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.

  19. Loss of brain function - liver disease

    MedlinePlus

    ... may be made by the body, such as ammonia. Or they may be substances that you take ... MRI EEG Liver function tests Prothrombin time Serum ammonia level Sodium level in the blood Potassium level ...

  20. Quantitative proteomic survey of endoplasmic reticulum in mouse liver.

    PubMed

    Song, Yanping; Jiang, Ying; Ying, Wantao; Gong, Yan; Yan, Yujuan; Yang, Dong; Ma, Jie; Xue, Xiaofang; Zhong, Fan; Wu, Songfeng; Hao, Yunwei; Sun, Aihua; Li, Tao; Sun, Wei; Wei, Handong; Zhu, Yunping; Qian, Xiaohong; He, Fuchu

    2010-03-05

    To gain a better understanding of the critical function of the endoplasmic reticulum (ER) in liver, we carried out a proteomic survey of mouse liver ER. The ER proteome was profiled with a new three-dimensional, gel-based strategy. From 6152 and 6935 MS spectra, 903 and 1042 proteins were identified with at least two peptides matches at 95% confidence in the rough (r) and smooth (s) ER, respectively. Comparison of the rER and sER proteomes showed that calcium-binding proteins are significantly enriched in the sER suggesting that the ion-binding function of the ER is compartmentalized. Comparison of the rat and mouse ER proteomes showed that 662 proteins were common to both, comprising 53.5% and 49.3% of those proteomes, respectively. We proposed that these proteins were stably expressed proteins that were essential for the maintenance of ER function. GO annotation with a hypergeometric model proved this hypothesis. Unexpectedly, 210 unknown proteins and some proteins previously reported to occur in the cytosol were highly enriched in the ER. This study provides a reference map for the ER proteome of liver. Identification of new ER proteins will enhance our current understanding of the ER and also suggest new functions for this organelle.

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

    PubMed Central

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

    2016-01-01

    AIM: To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve. METHODS: 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. RESULTS: 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 < 0.001). Specifically, the F4 group had a significantly higher elastic modulus than the F3, F2, and F0 groups (P = 0.002, P = 0.003, and P = 0.006, respectively), and the F3 group also had a significantly higher modulus than the control F0 group (P = 0.039). LSM was negatively associated with plasma MEGX concentrations at 30 min (r = -0.642; P = 0.013) and 60 min (r = -0.651; P = 0.012), time to ½ of the maximum concentration (r = -0.538; P = 0.047), and the area under the curve (r = -0.636; P = 0.014). Multiple comparisons showed identical differences in these three measures

  2. Multiphoton microscopy in defining liver function

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

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

    SciTech Connect

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

    1984-04-01

    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.

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

    PubMed

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

    1996-01-01

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

  5. Intermittent ischaemia maintains function after ischaemia reperfusion in steatotic livers

    PubMed Central

    Steenks, Mathilde; van Baal, Mark CPM; Nieuwenhuijs, Vincent B; de Bruijn, Menno T; Schiesser, Marc; Teo, Mike H; Callahan, Tom; Padbury, Rob TA; Barritt, Greg J

    2010-01-01

    Background: Ischaemic preconditioning (IPC) and intermittent ischaemia (INT) reduce liver injury after ischaemia reperfusion (IR). Steatotic livers are at a higher risk of IR injury, but the protection offered by IPC and INT is not well understood. The aim of the present study was to determine the effectiveness of IPC and INT in maintaining liver function in steatotic livers. Material and methods: A model of segmental hepatic ischaemia (45 min) and reperfusion (60 min) was employed using lean and obese Zucker rats. Bile flow recovery was measured to assess dynamic liver function, hepatocyte fat content quantified and blood electrolytes, metabolites and bile calcium measured to assess liver and whole body physiology. Liver marker enzymes and light and electron microscopy were employed to assess hepatocyte injury. Results: IPC was not effective in promoting bile flow recovery after IR in either lean or steatotic livers, whereas INT promoted good bile flow recovery in steatotic as well as lean livers. However, the bile flow recovery in steatotic livers was less than that in lean livers. In steatotic livers, ischaemia led to a rapid and substantial decrease in fat content. Steatotic livers were more susceptible to IR injury than lean livers, as indicated by increased blood ALT concentrations and major histological injury. Conclusion: INT is more effective than IPC in restoring liver function in the acute phase of IR in steatotic livers. In obese patients, INT may be useful in promoting better liver function after IR after liver resection. PMID:20590895

  6. [Value of spectral CT-based quantitative analysis in differential diagnosis of liver cancer and liver abscess].

    PubMed

    Gao, H Q; Hu, C H; Yu, Y X; Hu, S; Shi, C; Wang, X M; Guo, L

    2016-09-20

    Objective: To investigate the value of spectral CT-based quantitative analysis in the differential diagnosis of liver cancer and liver abscess. Methods: A total of 70 patients with space-occupying lesions in the liver(45 with liver cancer and 25 with liver abscess)underwent spectral CT scans to obtain spectral images in the arterial phase and portal venous phase. The solid constituents of lesions and the iodine and water concentrations in necrotic or cystic parts of lesions, normal hepatic tissue, and abdominal aorta in the arterial phase and portal venous phase were measured, and the normalized iodine concentration(NIC)and lesion-to-normal hepatic tissue ratio(LNR)of iodine concentration were calculated. The two samples t-test and the receiver operating characteristic(ROC)curve analysis were performed for the quantitative indices above. Results: The patients with liver cancer had higher NIC and LNR in solid constituents in the arterial phase than those with liver abscess(NIC: 0.15±0.06 mg/ml vs 0.14±0.02 mg/ml, P > 0.05; LNR: 2.78±0.65 vs 1.45±0.88, P < 0.001). The patients with liver abscess had significantly higher NIC and LNR in solid constituents in the portal venous phase than those with liver cancer(NIC: 0.65±0.08 mg/ml vs 0.52±0.08 mg/ml, P≤0.001; LNR: 1.22±0.23 vs 0.95±0.15, P≤0.001). There were no significant differences in NIC in the arterial phase or NIC and LNR in the portal venous phase in necrotic or cystic parts of lesions between the patients with liver cancer and liver abscess(P > 0.05). The optimal quantitative value for the differential diagnosis of liver cancer and liver abscess was LNR in arterial phase, and the cut-off value of 1.53 had a sensitivity of 100% and a specificity of 92%. Conclusion: Quantitative iodine concentration analysis in spectral CT imaging has a certain value in the differential diagnosis of liver cancer and liver abscess and can improve the accuracy of diagnosis.

  7. Cellular Organization of Normal Mouse Liver: A Histological, Quantitative Immunocytochemical, and Fine Structural Analysis

    PubMed Central

    Baratta, Janie L.; Ngo, Anthony; Lopez, Bryan; Kasabwalla, Natasha; Longmuir, Kenneth J.; Robertson, Richard T.

    2009-01-01

    The cellular organization of normal mouse liver was studied using light and electron microscopy and quantitative immunocytochemical techniques. The general histological organization of the mouse liver is similar to livers of other mammalian species, with a lobular organization based on the distributions of portal areas and central venules. The parenchymal hepatocytes were detected with immunocytochemical techniques to recognize albumin or biotin containing cells. The macrophage Kupffer cells were identified with F4-80 immunocytochemistry, Ito stellate cells were identified with GFAP immunocytochemistry, and endothelial cells were labeled with the CD-34 antibody. Kupffer cells were labeled with intravascularly administered fluorescently labeled latex microspheres of both large (0.5 μm) and small (0.03 μm) diameters, while endothelial cells were labeled only with small diameter microspheres. Neither hepatocytes nor Ito stellate cells were labeled by intravascularly administered latex microspheres. The principal fine structural features of hepatocytes and non-parenchymal cells of mouse liver are similar to those reported for rat. Counts of immunocytochemically labeled cells with stained nuclei indicated that hepatocytes constituted approximately 52% of all labeled cells, Kupffer cells about 18%, Ito cells about 8%, and endothelial cells about 22% of all labeled cells. Approximately 35% of the hepatocytes contained two nuclei; none of the Kupffer or Ito cells were double nucleated. The presence of canaliculi and a bile duct system appear similar to that reported for other mammalian species. The cellular organization of the mouse liver is quite similar to that of other mammalian species, confirming that the mouse presents a useful animal model for studies of liver structure and function. PMID:19255771

  8. Quantitative imaging of lymph function.

    PubMed

    Sharma, Ruchi; Wang, Wei; Rasmussen, John C; Joshi, Amit; Houston, Jessica P; Adams, Kristen E; Cameron, Arlin; Ke, Shi; Kwon, Sunkuk; Mawad, Michel E; Sevick-Muraca, Eva M

    2007-06-01

    Functional lymphatic imaging was demonstrated in the abdomen and anterior hindlimb of anesthetized, intact Yorkshire swine by using near-infrared (NIR) fluorescence imaging following intradermal administration of 100-200 microl of 32 microM indocyanine green (ICG) and 64 microM hyaluronan NIR imaging conjugate to target the lymph vascular endothelial receptor (LYVE)-1 on the lymph endothelium. NIR fluorescence imaging employed illumination of 780 nm excitation light ( approximately 2 mW/cm(2)) and collection of 830 nm fluorescence generated from the imaging agents. Our results show the ability to image the immediate trafficking of ICG from the plexus, through the vessels and lymphangions, and to the superficial mammary, subiliac, and middle iliac lymph nodes, which were located as deep as 3 cm beneath the tissue surface. "Packets" of ICG-transited lymph vessels of 2-16 cm length propelled at frequencies of 0.5-3.3 pulses/min and velocities of 0.23-0.75 cm/s. Lymph propulsion was independent of respiration rate. In the case of the hyaluronan imaging agent, lymph propulsion was absent as the dye progressed immediately through the plexus and stained the lymph vessels and nodes. Lymph imaging required 5.0 and 11.9 microg of ICG and hyaluronan conjugate, respectively. Our results suggest that microgram quantities of NIR optical imaging agents and their conjugates have a potential to image lymph function in patients suffering from lymph-related disorders.

  9. Liver gender dimorphism--insights from quantitative morphology.

    PubMed

    Marcos, Ricardo; Correia-Gomes, Carla; Miranda, Helena; Carneiro, Fatima

    2015-12-01

    It was shown recently that many genes are differentially expressed in the liver of males and females, thus strengthening the concept of liver gender dimorphism. This dimorphism exists in many pathological scenarios, from regeneration to fibrosis, which has led to the development of gender hepatology. Nevertheless, it is still unknown if gender dimorphism occurs in the structure of the normal liver. In recent years, it has been shown that, compared with male, the female rat liver bears less fibrotic tissue, more Kupffer cells (per volume unit) and has higher hepatocellularity, including binucleated hepatocytes (per volume unit). Our hypothesis is that the human liver also hides a gender dimorphic pattern. Baseline differences in fibrotic tissue would contribute to explain severe liver fibrosis in men. As to the disparity of Kupffer cells, this would clarify the stronger response to post-surgery infections in women, and it could be equated when appraising the higher susceptibility to alcohol. Regarding differences in hepatocytes, they not only justify existing differences in some liver parameters (e.g., transaminases and bilirubin), but they could also account for the higher regenerative potential of the female liver. The structural dimorphism in the human liver would sustain the concept of gender hepatology and, eventually, should be considered in the context of liver transplantation.

  10. Circadian Clock Control of Liver Metabolic Functions.

    PubMed

    Reinke, Hans; Asher, Gad

    2016-03-01

    The circadian clock is an endogenous biological timekeeping system that synchronizes physiology and behavior to day/night cycles. A wide variety of processes throughout the entire gastrointestinal tract and notably the liver appear to be under circadian control. These include various metabolic functions such as nutrient uptake, processing, and detoxification, which align organ function to cycle with nutrient supply and demand. Remarkably, genetic or environmental disruption of the circadian clock can cause metabolic diseases or exacerbate pathological states. In addition, modern lifestyles force more and more people worldwide into asynchrony between the external time and their circadian clock, resulting in a constant state of social jetlag. Recent evidence indicates that interactions between altered energy metabolism and disruptions in the circadian clock create a downward spiral that can lead to diabetes and other metabolic diseases. In this review, we provide an overview of rhythmic processes in the liver and highlight the functions of circadian clock genes under physiological and pathological conditions; we focus on their roles in regulation of hepatic glucose as well as lipid and bile acid metabolism and detoxification and their potential effects on the development of fatty liver and nonalcoholic steatohepatitis. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Moesin functionality in hypothermic liver preservation injury.

    PubMed

    Tian, Tao; Lindell, Susanne L; Kowalski, Chris; Mangino, Martin J

    2014-08-01

    The objective of this study was to determine how expression and functionality of the cytoskeletal linker protein moesin is involved in hepatic hypothermic preservation injury. Mouse livers were cold stored in University of Wisconsin (UW) solution and reperfused on an isolated perfused liver (IPL) device for one hour. Human hepatocytes (HepG2) and human or murine sinusoidal endothelial cells (SECs) were cold stored and rewarmed to induce hypothermic preservation injury. The cells were transfected with: wild type moesin, an siRNA duplex specific for moesin, and the moesin mutants T558D and T558A. Tissue and cell moesin expression and its binding to actin were determined by Western blot. Liver IPL functional outcomes deteriorated proportional to the length of cold storage, which correlated with moesin disassociation from the actin cytoskeleton. Cell viability (LDH and WST-8) in the cell models progressively declined with increasing preservation time, which also correlated with moesin disassociation. Transfection of a moesin containing plasmid or an siRNA duplex specific for moesin into HepG2 cells resulted in increased and decreased moesin expression, respectively. Overexpression of moesin protected while moesin knock-down potentiated preservation injury in the HepG2 cell model. Hepatocytes expressing the T558A (inactive) and T558D (active) moesin binding mutants demonstrated significantly more and less preservation injury, respectively. Cold storage time dependently caused hepatocyte detachment from the matrix and cell death, which was prevented by the T558D active moesin mutation. In conclusion, moesin is causally involved in hypothermic liver cell preservation injury through control of its active binding molecular functionality.

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

    PubMed

    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.

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

    PubMed

    Ploemen, Ivo H J; Prudêncio, Miguel; Douradinha, Bruno G; Ramesar, Jai; Fonager, Jannik; van Gemert, Geert-Jan; Luty, Adrian J F; Hermsen, Cornelus C; Sauerwein, Robert W; Baptista, Fernanda G; Mota, Maria M; Waters, Andrew P; Que, Ivo; Lowik, Clemens W G M; Khan, Shahid M; Janse, Chris J; Franke-Fayard, Blandine M D

    2009-11-18

    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 poorly studied compared to blood stages, for example in screening anti-malarial drugs. Here we report the use of a transgenic P. berghei parasite, PbGFP-Luc(con), expressing the bioluminescent reporter protein luciferase to visualize and quantify parasite development in liver cells both in culture and in live mice using real-time luminescence imaging. The reporter-parasite based quantification in cultured hepatocytes by real-time imaging or using a microplate reader correlates very well with established quantitative RT-PCR methods. For the first time the liver stage of Plasmodium is visualized in whole bodies of live mice and we were able to discriminate as few as 1-5 infected hepatocytes per liver in mice using 2D-imaging and to identify individual infected hepatocytes by 3D-imaging. The analysis of liver infections by whole body imaging shows a good correlation with quantitative RT-PCR analysis of extracted livers. The luminescence-based analysis of the effects of various drugs on in vitro hepatocyte infection shows that this method can effectively be used for in vitro screening of compounds targeting Plasmodium liver stages. Furthermore, by analysing the effect of primaquine and tafenoquine in vivo we demonstrate the applicability of real time imaging to assess parasite drug sensitivity in the liver. The simplicity and speed of quantitative analysis of liver-stage development by real-time imaging compared to the PCR methodologies, as well as the possibility to analyse liver development in live mice without surgery, opens up new possibilities for research on Plasmodium liver infections and for validating the effect of drugs and vaccines on the liver stage of

  14. Visualisation and Quantitative Analysis of the Rodent Malaria Liver Stage by Real Time Imaging

    PubMed Central

    Douradinha, Bruno G.; Ramesar, Jai; Fonager, Jannik; van Gemert, Geert-Jan; Luty, Adrian J. F.; Hermsen, Cornelus C.; Sauerwein, Robert W.; Baptista, Fernanda G.; Mota, Maria M.; Waters, Andrew P.; Que, Ivo; Lowik, Clemens W. G. M.; Khan, Shahid M.; Janse, Chris J.; Franke-Fayard, Blandine M. D.

    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 poorly studied compared to blood stages, for example in screening anti-malarial drugs. Here we report the use of a transgenic P. berghei parasite, PbGFP-Luccon, expressing the bioluminescent reporter protein luciferase to visualize and quantify parasite development in liver cells both in culture and in live mice using real-time luminescence imaging. The reporter-parasite based quantification in cultured hepatocytes by real-time imaging or using a microplate reader correlates very well with established quantitative RT-PCR methods. For the first time the liver stage of Plasmodium is visualized in whole bodies of live mice and we were able to discriminate as few as 1–5 infected hepatocytes per liver in mice using 2D-imaging and to identify individual infected hepatocytes by 3D-imaging. The analysis of liver infections by whole body imaging shows a good correlation with quantitative RT-PCR analysis of extracted livers. The luminescence-based analysis of the effects of various drugs on in vitro hepatocyte infection shows that this method can effectively be used for in vitro screening of compounds targeting Plasmodium liver stages. Furthermore, by analysing the effect of primaquine and tafenoquine in vivo we demonstrate the applicability of real time imaging to assess parasite drug sensitivity in the liver. The simplicity and speed of quantitative analysis of liver-stage development by real-time imaging compared to the PCR methodologies, as well as the possibility to analyse liver development in live mice without surgery, opens up new possibilities for research on Plasmodium liver infections and for validating the effect of drugs and vaccines on the liver stage of

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-12-01

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

  17. Impaired Physical Function Following Pediatric Liver Transplantation

    PubMed Central

    Feldman, Amy G.; Neighbors, Katie; Mukherjee, Shubra; Rak, Melanie; Varni, James W.; Alonso, Estella M.

    2016-01-01

    Objective Investigate the spectrum of physical function of pediatric liver transplant (LT) recipients 12–24 months post-LT. Study design Review data collected through the Functional Outcomes Group, an ancillary study of Studies of Pediatric Liver Transplantation registry. Patients were eligible if they had survived LT by 12–24 months. Children ≥ 8 years and parents completed the Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales, which includes 8 questions assessing physical function. Scores were compared to a matched healthy child population (n=1658), and between survivors with optimal versus non-optimal health. Results A total of 263 patients were included. Median age at transplant and survey was 4.8 years (IQR 1.3–11.4) and 5.9 years (IQR 2.6–13.1), respectively. The mean Physical Functioning Score on child and parent reports were 81.2± 17.3 and 77.1± 23.7, respectively. Compared to a matched healthy population, transplant survivors and their parents reported lower physical function scores (p<0.01). 32.9% of patients and 35.0% of parents reported a physical function score <75, which is >1 SD below the mean of a healthy population. Physical Function Scores were significantly higher in survivors with optimal health than those with non-optimal health (p<0.01). There was a significant relationship between Emotional Functioning and Physical Functioning Scores for LT recipients (r=0.69, p<0.001). In multivariate analysis, primary disease, height Z score<−1.64 at long term follow-up (LTF) visit, ≥4 days of hospitalization since LTF visit, and not listed as Status 1 were predictors of poor physical function. Conclusions Pediatric LT recipients 1–2 years post-LT and their parents report lower physical function than a healthy population. Findings suggest practitioners need to routinely assess physical function, and development of rehabilitation programs may be important. PMID:26850789

  18. Photoacoustic molecular imaging for in vivo liver iron quantitation

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

  1. Quantitative methods in assessment of neurologic function.

    PubMed

    Potvin, A R; Tourtellotte, W W; Syndulko, K; Potvin, J

    1981-01-01

    Traditionally, neurologists have emphasized qualitative techniques for assessing results of clinical trials. However, in recent years qualitative evaluations have been increasingly augmented by quantitative tests for measuring neurologic functions pertaining to mental state, strength, steadiness, reactions, speed, coordination, sensation, fatigue, gait, station, and simulated activities of daily living. Quantitative tests have long been used by psychologists for evaluating asymptomatic function, assessing human information processing, and predicting proficiency in skilled tasks; however, their methodology has never been directly assessed for validity in a clinical environment. In this report, relevant contributions from the literature on asymptomatic human performance and that on clinical quantitative neurologic function are reviewed and assessed. While emphasis is focused on tests appropriate for evaluating clinical neurologic trials, evaluations of tests for reproducibility, reliability, validity, and examiner training procedures, and for effects of motivation, learning, handedness, age, and sex are also reported and interpreted. Examples of statistical strategies for data analysis, scoring systems, data reduction methods, and data display concepts are presented. Although investigative work still remains to be done, it appears that carefully selected and evaluated tests of sensory and motor function should be an essential factor for evaluating clinical trials in an objective manner.

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

    PubMed

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

    2014-12-01

    Our objective is to explore the value of liver cancer contrast-enhanced ultrasound (CEUS) and MRI perfusion quantitative analysis in liver cancer and the correlation between these two analysis methods. Rabbit VX2 liver cancer model was established in this study. CEUS was applied. Sono Vue was applied in rabbits by ear vein to dynamically observe and record the blood perfusion and changes in the process of VX2 liver cancer and surrounding tissue. MRI perfusion quantitative analysis was used to analyze the mean enhancement time and change law of maximal slope increasing, which were further compared with the pathological examination results. Quantitative indicators of liver cancer CEUS and MRI perfusion quantitative analysis were compared, and the correlation between them was analyzed by correlation analysis. Rabbit VX2 liver cancer model was successfully established. CEUS showed that time-intensity curve of rabbit VX2 liver cancer showed "fast in, fast out" model while MRI perfusion quantitative analysis showed that quantitative parameter MTE of tumor tissue increased and MSI decreased: the difference was statistically significant (P < 0.01). The diagnostic results of CEUS and MRI perfusion quantitative analysis were not significantly different (P > 0.05). However, the quantitative parameter of them were significantly positively correlated (P < 0.05). CEUS and MRI perfusion quantitative analysis can both dynamically monitor the liver cancer lesion and surrounding liver parenchyma, and the quantitative parameters of them are correlated. The combined application of both is of importance in early diagnosis of liver cancer.

  3. Liver Function Tests Following Open Cardiac Surgery

    PubMed Central

    Sabzi, Feridoun; Faraji, Reza

    2015-01-01

    Introduction: The cardiopulmonary bypass may have multiple systemic effects on the body organs as liver. This prospective study was planned to explore further the incidence and significance of this change. Methods: Two hundred patients with coronary artery bypass grafting (CABG), were randomly selected for the study. Total and indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase were measured preoperatively and at 24, 48 and 72 hours, following coronary artery bypass grafting. Postoperative value of the liver function tests with respect to hypothermia or hypotension were compared by one way analysis of variance for repeated measure and compared with t test. Patient’s characteristics with bilirubin value (≤1.5 mg or >1.5 mg) were compared with t test. Results: A significant increase of total bilirubin, aspartate aminotransferase, and alkaline phosphatase were noted in the third postoperative day. Significant relation was seen between hypotension and alkaline phosphatase, and aspartate aminotransferase change but hypothermia had not affected alanine aminotransferase, total bilirubin and indirect bilirubin change. Pump time, alanine aminotransferase in third postoperative day and direct bilirubin in first and second day of postoperative period had significant relation with pre and post-operative bilirubin change. Conclusion: Transient but not permanent alterations of hepatic enzymes after coronary artery bypass grafting presumably attributed to the decreased hepatic flow, hypoxia, or pump-induced inflammation. PMID:26191391

  4. Hepatoprotective versus Oncogenic Functions of STAT3 in Liver Tumorigenesis

    PubMed Central

    Wang, Hua; Lafdil, Fouad; Wang, Lei; Park, Ogyi; Yin, Shi; Niu, Junyang; Miller, Andrew M.; Sun, Zhaoli; Gao, Bin

    2011-01-01

    Aberrantly hyperactivated STAT3 has been found in human liver cancers as an oncogene; however, STAT3 has also been shown to exert hepatoprotective effects during liver injury. The balancing act that STAT3 plays between hepatoprotection and liver tumorigenesis remains poorly defined. In this study, the diethylnitrosamine (DEN)-induced liver tumor model and the chronic carbon tetrachloride (CCl4)–induced liver fibrosis model were both used to investigate the role of STAT3 in liver tumorigenesis. Hepatocyte-specific STAT3 knockout mice were resistant to liver tumorigenesis induced by a single DEN injection, whose tumorigenesis was associated with minimal chronic liver inflammation, injury, and fibrosis. In contrast, long-term CCl4 treatment resulted in severe hepatic oxidative damage, inflammation, and fibrosis but rarely induced liver tumor formation in wild-type mice. Despite the oncogenic function of STAT3 in DEN-induced liver tumor, hepatocyte-specific STAT3 knockout mice were more susceptible to liver tumorigenesis after 16 weeks of CCl4 injection, which was associated with higher levels of liver injury, inflammation, fibrosis, and oxidative DNA damage compared with wild-type mice. These findings suggest that the hepatoprotective feature of STAT3 prevents hepatic damage and fibrosis under the condition of persistent inflammatory stress, consequently suppressing injury-driven liver tumor initiation. Once liver tumor cells have developed, STAT3 likely acts as an oncogenic factor to promote tumor growth. PMID:21684247

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

    PubMed

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

    2017-02-28

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

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

    PubMed

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

    2011-03-01

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

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

    PubMed

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

    2016-03-08

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

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

    PubMed Central

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

    2016-01-01

    Indocyanine green (ICG) kinetics (PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors (pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests. PMID:26981173

  9. Quantitative evaluation of noise reduction and vesselness filters for liver vessel segmentation on abdominal CTA images

    NASA Astrophysics Data System (ADS)

    Luu, Ha Manh; Klink, Camiel; Moelker, Adriaan; Niessen, Wiro; van Walsum, Theo

    2015-05-01

    Liver vessel segmentation in CTA images is a challenging task, especially in the case of noisy images. This paper investigates whether pre-filtering improves liver vessel segmentation in 3D CTA images. We introduce a quantitative evaluation of several well-known filters based on a proposed liver vessel segmentation method on CTA images. We compare the effect of different diffusion techniques i.e. Regularized Perona-Malik, Hybrid Diffusion with Continuous Switch and Vessel Enhancing Diffusion as well as the vesselness approaches proposed by Sato, Frangi and Erdt. Liver vessel segmentation of the pre-processed images is performed using a histogram-based region grown with local maxima as seed points. Quantitative measurements (sensitivity, specificity and accuracy) are determined based on manual landmarks inside and outside the vessels, followed by T-tests for statistic comparisons on 51 clinical CTA images. The evaluation demonstrates that all the filters make liver vessel segmentation have a significantly higher accuracy than without using a filter (p  <  0.05) Hybrid Diffusion with Continuous Switch achieves the best performance. Compared to the diffusion filters, vesselness filters have a greater sensitivity but less specificity. In addition, the proposed liver vessel segmentation method with pre-filtering is shown to perform robustly on a clinical dataset having a low contrast-to-noise of up to 3 (dB). The results indicate that the pre-filtering step significantly improves liver vessel segmentation on 3D CTA images.

  10. Quantitative evaluation of noise reduction and vesselness filters for liver vessel segmentation on abdominal CTA images.

    PubMed

    Luu, Ha Manh; Klink, Camiel; Moelker, Adriaan; Niessen, Wiro; van Walsum, Theo

    2015-05-21

    Liver vessel segmentation in CTA images is a challenging task, especially in the case of noisy images. This paper investigates whether pre-filtering improves liver vessel segmentation in 3D CTA images. We introduce a quantitative evaluation of several well-known filters based on a proposed liver vessel segmentation method on CTA images. We compare the effect of different diffusion techniques i.e. Regularized Perona-Malik, Hybrid Diffusion with Continuous Switch and Vessel Enhancing Diffusion as well as the vesselness approaches proposed by Sato, Frangi and Erdt. Liver vessel segmentation of the pre-processed images is performed using a histogram-based region grown with local maxima as seed points. Quantitative measurements (sensitivity, specificity and accuracy) are determined based on manual landmarks inside and outside the vessels, followed by T-tests for statistic comparisons on 51 clinical CTA images. The evaluation demonstrates that all the filters make liver vessel segmentation have a significantly higher accuracy than without using a filter (p  <  0.05); Hybrid Diffusion with Continuous Switch achieves the best performance. Compared to the diffusion filters, vesselness filters have a greater sensitivity but less specificity. In addition, the proposed liver vessel segmentation method with pre-filtering is shown to perform robustly on a clinical dataset having a low contrast-to-noise of up to 3 (dB). The results indicate that the pre-filtering step significantly improves liver vessel segmentation on 3D CTA images.

  11. Seasonal liver protein differences in a hibernator revealed by quantitative proteomics using whole animal isotopic labeling

    PubMed Central

    Rose, J. Cameron; Epperson, L. Elaine; Carey, Hannah V.; Martin, Sandra L.

    2011-01-01

    Hibernation is an energy-saving strategy used by diverse species of mammals to survive winter. It is characterized by cycles between multi-day periods of torpor with low body temperature (Tb), and short periods of rapid, spontaneous rewarming. The ability to retain cellular integrity and function throughout torpor and rewarming is a key attribute of hibernation. Livers from winter hibernators are resistant to cellular damage induced by cold storage followed by warm reperfusion. Identifying proteins that differ between the summer-sensitive and winter-protected phenotypic states is one useful approach that may elucidate the molecular mechanisms that underlie this protection. Here we employ a novel quantitative proteomics screening strategy whereby a newly-weaned 13-lined ground squirrel was metabolically labeled by ingesting heavy-isotope substituted (15N) Spirulina. The liver protein extract from this animal provided a common reference for quantitative evaluation of protein differences by its addition to extracts from pooled samples of summer active (SA) or winter entrance (Ent) phase hibernating ground squirrels. We identified 61 significantly different proteins between the two groups and compared them to proteins identified previously in the same samples using 2D gels. Of the 20 proteins common to the two datasets, the direction and magnitude of their differences were perfectly concordant for 18, providing confidence that both sets of altered proteins reflect bona fide differences between the two physiological states. Furthermore, the 41 novel proteins recovered in this study included many new enzymes in pathways identified previously: specifically, additional enzymes belonging to the urea cycle, amino acid and carbohydrate degradation, and lipid biosynthetic pathways were decreased, whereas enzymes involved in ketone body synthesis, fatty acid utilization, protein synthesis and gluconeogenesis were increased in the samples from entrance hibernators compared to

  12. The measurement of liver fat from single-energy quantitative computed tomography scans.

    PubMed

    Cheng, Xiaoguang; Blake, Glen M; Brown, J Keenan; Guo, Zhe; Zhou, Jun; Wang, Fengzhe; Yang, Liqiang; Wang, Xiaohong; Xu, Li

    2017-06-01

    Studies of soft tissue composition using computed tomography (CT) scans are often semi-quantitative and based on Hounsfield units (HU) measurements that have not been calibrated with a quantitative CT (QCT) phantom. We describe a study to establish the water (H2O) and dipotassium hydrogen phosphate (K2HPO4) basis set equivalent densities of fat and fat-free liver tissue. With this information liver fat can be accurately measured from any abdominal CT scan calibrated with a suitable phantom. Liver fat content was measured by comparing single-energy QCT (SEQCT) HU measurements of the liver with predicted HU values for fat and fat-free liver tissue calculated from their H2O and K2HPO4 equivalent densities and calibration data from a QCT phantom. The equivalent densities of fat were derived from a listing of its constituent fatty acids, and those of fat-free liver tissue from a dual-energy QCT (DEQCT) study performed in 14 healthy Chinese subjects. This information was used to calculate liver fat from abdominal SEQCT scans performed in a further 541 healthy Chinese subjects (mean age 62 years; range, 31-95 years) enrolled in the Prospective Urban Rural Epidemiology (PURE) Study. The equivalent densities of fat were 941.75 mg/cm(3) H2O and -43.72 mg/cm(3) K2HPO4, and for fat-free liver tissue 1,040.13 mg/cm(3) H2O and 21.34 mg/cm(3) K2HPO4. Liver fat in the 14 subjects in the DEQCT study varied from 0-17.9% [median: 4.5%; interquartile range (IQR): 3.0-7.9%]. Liver fat in the 541 PURE study subjects varied from -0.3-29.9% (median: 4.9%; IQR: 3.4-6.9%). We have established H2O and K2HPO4 equivalent densities for fat and fat-free liver tissue that allow a measurement of liver fat to be obtained from any abdominal CT scan acquired with a QCT phantom. Although radiation dose considerations preclude the routine use of QCT to measure liver fat, the method described here facilitates its measurement in patients having CT scans performed for other purposes. Further studies

  13. The measurement of liver fat from single-energy quantitative computed tomography scans

    PubMed Central

    Cheng, Xiaoguang; Brown, J. Keenan; Guo, Zhe; Zhou, Jun; Wang, Fengzhe; Yang, Liqiang; Wang, Xiaohong; Xu, Li

    2017-01-01

    Background Studies of soft tissue composition using computed tomography (CT) scans are often semi-quantitative and based on Hounsfield units (HU) measurements that have not been calibrated with a quantitative CT (QCT) phantom. We describe a study to establish the water (H2O) and dipotassium hydrogen phosphate (K2HPO4) basis set equivalent densities of fat and fat-free liver tissue. With this information liver fat can be accurately measured from any abdominal CT scan calibrated with a suitable phantom. Methods Liver fat content was measured by comparing single-energy QCT (SEQCT) HU measurements of the liver with predicted HU values for fat and fat-free liver tissue calculated from their H2O and K2HPO4 equivalent densities and calibration data from a QCT phantom. The equivalent densities of fat were derived from a listing of its constituent fatty acids, and those of fat-free liver tissue from a dual-energy QCT (DEQCT) study performed in 14 healthy Chinese subjects. This information was used to calculate liver fat from abdominal SEQCT scans performed in a further 541 healthy Chinese subjects (mean age 62 years; range, 31–95 years) enrolled in the Prospective Urban Rural Epidemiology (PURE) Study. Results The equivalent densities of fat were 941.75 mg/cm3 H2O and –43.72 mg/cm3 K2HPO4, and for fat-free liver tissue 1,040.13 mg/cm3 H2O and 21.34 mg/cm3 K2HPO4. Liver fat in the 14 subjects in the DEQCT study varied from 0–17.9% [median: 4.5%; interquartile range (IQR): 3.0–7.9%]. Liver fat in the 541 PURE study subjects varied from –0.3–29.9% (median: 4.9%; IQR: 3.4–6.9%). Conclusions We have established H2O and K2HPO4 equivalent densities for fat and fat-free liver tissue that allow a measurement of liver fat to be obtained from any abdominal CT scan acquired with a QCT phantom. Although radiation dose considerations preclude the routine use of QCT to measure liver fat, the method described here facilitates its measurement in patients having CT scans

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

    PubMed

    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.

  15. Renal Function and Transplantation in Liver Disease.

    PubMed

    Parajuli, Sandesh; Foley, David; Djamali, Arjang; Mandelbrot, Didier

    2015-09-01

    Kidney injury is associated with increased morbidity and mortality in liver transplant recipients. Since the introduction of the model for end-stage liver disease for the allocation of organs for liver transplantation in 2002, the heavy weighting of serum creatinine in the model for end-stage liver disease score has significantly increased the incidence of renal dysfunction seen among patients undergoing liver transplantation. As a result, the frequency of simultaneous liver-kidney (SLK) transplantation compared to liver transplantation alone (LTA) has also increased. The decision to perform SLK rather than LTA is an important one because the benefits to the liver transplant recipient receiving a kidney transplant must be balanced with the benefits of using that organ for a patient with end-stage renal disease. However, predicting whether or not a patient with liver failure has reversible kidney disease, and therefore does not also need a kidney transplant, is difficult. The severity and duration of pretransplant renal dysfunction, hepatitis c, diabetes, and other risk factors for kidney disease are associated with an increased risk of posttransplant end-stage renal disease. However, there are currently no clinical findings that accurately predict renal recovery post liver transplant. As a result, the rate of SLK versus LTA differs significantly between transplant centers. To increase consistency across centers, multiple guidelines have been proposed to guide the decision between SLK and LTA, but their poor predictive value has limited their uniform adoption. Nevertheless, adoption of uniform rules for the allocation of kidneys would reduce the variability between centers in rates of SLK transplant.

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

    PubMed Central

    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

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Function and volume recovery after partial hepatectomy: influence of preoperative liver function, residual liver volume, and obesity.

    PubMed

    Lock, Johan Friso; Malinowski, Maciej; Seehofer, Daniel; Hoppe, Steffi; Röhl, Rhea Isabel; Niehues, Stefan Markus; Neuhaus, Peter; Stockmann, Martin

    2012-12-01

    The regenerative capacity of the liver is an essential pre-condition for the successful application of partial hepatectomy. However, the actual kinetics of functional recovery remains unspecified and no adequate tool for its clinical monitoring has yet been available. Eighty-five patients receiving major hepatectomy were investigated from the preoperative evaluation until 12 weeks after surgery. Liver function was determined by the LiMAx test for the enzymatic capacity of cytochrome P450 1A2. Liver volume was determined by volumetric analysis of repeated computer tomography scans. Functional and volume recovery were compared during follow-up. Major hepatectomy decreased liver function capacity to 35.7 ± 13.8% of preoperative function. It was shown that functional recovery already reaches 77.2 ± 33.5% of preoperative values within 10 days. The actual kinetics were dependent from the type and extent of hepatectomy. Complete functional restoration was achieved within 12 weeks, while liver volume still remained at 73.2 ± 14.8% of preoperative. A constant but interindividually variable correlation between function and volume was observed at all points in time. Partial hepatectomy leads to fast and complete functional recovery, while volume recovery is delayed and remains often incomplete. The functional recovery is mainly influenced by the preoperative liver function, the residual liver volume, and by obesity.

  19. Signatures of Evolutionary Adaptation in Quantitative Trait Loci Influencing Trace Element Homeostasis in Liver

    PubMed Central

    Sabidó, Eduard; Bosch, Elena

    2016-01-01

    Essential trace elements possess vital functions at molecular, cellular, and physiological levels in health and disease, and they are tightly regulated in the human body. In order to assess variability and potential adaptive evolution of trace element homeostasis, we quantified 18 trace elements in 150 liver samples, together with the expression levels of 90 genes and abundances of 40 proteins involved in their homeostasis. Additionally, we genotyped 169 single nucleotide polymorphism (SNPs) in the same sample set. We detected significant associations for 8 protein quantitative trait loci (pQTL), 10 expression quantitative trait loci (eQTLs), and 15 micronutrient quantitative trait loci (nutriQTL). Six of these exceeded the false discovery rate cutoff and were related to essential trace elements: 1) one pQTL for GPX2 (rs10133290); 2) two previously described eQTLs for HFE (rs12346) and SELO (rs4838862) expression; and 3) three nutriQTLs: The pathogenic C282Y mutation at HFE affecting iron (rs1800562), and two SNPs within several clustered metallothionein genes determining selenium concentration (rs1811322 and rs904773). Within the complete set of significant QTLs (which involved 30 SNPs and 20 gene regions), we identified 12 SNPs with extreme patterns of population differentiation (FST values in the top 5% percentile in at least one HapMap population pair) and significant evidence for selective sweeps involving QTLs at GPX1, SELENBP1, GPX3, SLC30A9, and SLC39A8. Overall, this detailed study of various molecular phenotypes illustrates the role of regulatory variants in explaining differences in trace element homeostasis among populations and in the human adaptive response to environmental pressures related to micronutrients. PMID:26582562

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

    PubMed

    Gronemeyer, Thomas; Wiese, Sebastian; Ofman, Rob; Bunse, Christian; Pawlas, Magdalena; Hayen, Heiko; Eisenacher, Martin; Stephan, Christian; Meyer, Helmut E; Waterham, Hans R; Erdmann, Ralf; Wanders, Ronald J; Warscheid, Bettina

    2013-01-01

    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. The Proteome of Human Liver Peroxisomes: Identification of Five New Peroxisomal Constituents by a Label-Free Quantitative Proteomics Survey

    PubMed Central

    Ofman, Rob; Bunse, Christian; Pawlas, Magdalena; Hayen, Heiko; Eisenacher, Martin; Stephan, Christian; Meyer, Helmut E.; Waterham, Hans R.; Erdmann, Ralf; Wanders, Ronald J.; Warscheid, Bettina

    2013-01-01

    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. PMID:23460848

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

    PubMed

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

    2017-02-26

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

  3. Optimizing global liver function in radiation therapy treatment planning

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  4. Characterization of a functional C3A liver spheroid model.

    PubMed

    Gaskell, Harriet; Sharma, Parveen; Colley, Helen E; Murdoch, Craig; Williams, Dominic P; Webb, Steven D

    2016-06-01

    More predictive in vitro liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids have been shown to have an enhanced functional lifespan compared to 2D monocultures; however a detailed characterisation of spatiotemporal function and structure of spheroids still needs further attention before widespread use in industry. We have developed and characterized the structure and function of a 3D liver spheroid model formed from C3A hepatoma cells. Spheroids were viable and maintained a compact in vivo-like structure with zonation features for up to 32 days. MRP2 and Pgp transporters had polarised expression on the canalicular membrane of cells in the spheroids and were able to functionally transport CMFDA substrate into these canalicular structures. Spheroids expressed CYP2E1 and were able to synthesise and secrete albumin and urea to a higher degree than monolayer C3A cultures. Penetration of doxorubicin throughout the spheroid core was demonstrated. Spheroids showed increased susceptibility to hepatotoxins when compared to 2D cultures, with acetaminophen having an IC50 of 7.2 mM in spheroids compared to 33.8 mM in monolayer culture. To conclude, we developed an alternative method for creating C3A liver spheroids and demonstrated cellular polarisation and zonation, as well as superior liver-specific functionality and more sensitive toxicological response compared to standard 2D liver models, confirming a more in vivo-like liver model.

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

    PubMed

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

    2014-10-01

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

  6. Correlation analysis between four serum biomarkers of liver fibrosis and liver function in infants with cholestasis

    PubMed Central

    TANG, NING; ZHANG, YAPING; LIU, ZEYU; FU, TAO; LIANG, QINGHONG; AI, XUEMEI

    2016-01-01

    The aim of the present study was to investigate the correlation between four serum biomarkers of liver fibrosis and liver function in infants with cholestasis. A total of 30 infants with cholestasis and 20 healthy infants were included in the study. Biochemical assays based on the initial rate method and colorimetric assays were conducted to determine the levels of liver function markers in the serum [such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), γ-glutamyl transferase (γ-GT), cholinesterase (CHE) and total bile acids (TBA)] and four serum biomarkers of liver fibrosis were measured using radioimmunoassays [hyaluronic acid (HA), procollagen type III (PCIII), laminin (LN) and collagen type IV (cIV)]. The serum levels of ALT, AST, TBIL, DBIL, IBIL, γ-GT and TBA in the infants with cholestasis were significantly higher compared to the healthy infants (P<0.01); the serum levels of CHE in the infants with cholestasis were significantly lower compared to the healthy infants (P<0.01). The serum levels of HA, PCIII, and cIV in the infants with cholestasis were significantly higher compared to the healthy infants (P<0.01). Correlation analyses between liver function and the four biomarkers of liver fibrosis showed that HA was positively correlated with AST and γ-GT (P<0.05) and negatively correlated with ALT, CHE and TBA (P<0.05). cIV was positively correlated with γ-GT (P<0.05) and negatively correlated with CHE (P<0.05). In conclusion, statistically significant differences were identified for the liver function markers (ALT, AST, TBIL, DBIL, IBIL, γ-GT and TBA) and the biomarkers HA, PCIII and cIV of liver fibrosis between infants with cholestasis and healthy infants. Thus, the serum levels of HA, cIV, γ-GT and CHE are sensitive markers for cholestatic liver fibrosis in infants. PMID:27347413

  7. Function of GATA Factors in the Adult Mouse Liver

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2017-09-01

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

  9. Study on Assessment of Renal Function in Chronic Liver Disease

    PubMed Central

    Das, Nupur; Paria, Baishakhi; Sarkar, Sujoy

    2015-01-01

    Introduction: Renal dysfunction is common in chronic liver disease. The cause of this renal dysfunction is either multi-organ involvement in acute conditions or secondary to advanced liver disease. Objectives: The study was undertaken to assess the renal function in chronic liver diseases and find out the association of alteration of renal function with gradation of liver disease. (assessed by child-pugh criteria) and to find out the association of alteration of renal function among the cases of chronic liver disease of different aetiology. Materials and Methods: This cross-sectional, observational study was undertaken in Department of General Medicine, Calcutta National Medical College & Hospital, Kolkata during March 2012 to July 2013 with 50 admitted patients of chronic liver disease after considering the exclusion criteria. The patients were interviewed with a pre-designed and pre-tested schedule, examined clinically, followed by some laboratory investigations relevant to diagnose the aetiology of chronic liver disease, and to assess the severity of liver and renal dysfunction. Data was analysed by standard statistical method. Results: Eighty six percent of the patients were male and the mean age of study population was 43.58 y, 68% patients suffered from alcoholic liver disease, followed by 14% patients had chronic Hepatitis-B, 10% patients developed acute kidney injury, 20% had hepato renal syndrome and 14% had IgA deposition. The distribution of serum urea and creatinine across the categories of Child Pugh classification tested by Mann-Whitney test and the distribution was statistically significant. Conclusion: The present study has found significant association between severity of liver dysfunction and certain parameters of renal dysfunction. PMID:25954647

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

    PubMed

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

    2012-03-01

    Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P < 0.05). UC-MSC therapy also significantly improved liver function, as indicated by the increase of serum albumin levels, decrease in total serum bilirubin levels, and decrease in the sodium model for end-stage liver disease scores. UC-MSC transfusion is clinically safe and could improve liver function and reduce ascites in patients with decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC.

  11. Oral health and liver function in children and adolescents with cirrhosis of the liver

    PubMed Central

    Kowalczyk, Wojciech; Krasuska-Sławińska, Ewa; Dądalski, Maciej; Kostewicz, Krzysztof; Pawłowska, Joanna

    2014-01-01

    Introduction People with cirrhosis of the liver are predisposed to developing oral lesions. The occurrence and type of lesion depend on the degree of liver function impairment and its type, and on the severity and duration of systemic diseases. In children, the age at which the early symptoms of liver disease are experienced is also of great importance. Aim To assess the prevalence of oral pathological lesions in children and adolescents with cirrhosis of the liver, and their correlation with the degree of liver function impairment. Material and methods Clinical and laboratory results of liver function tests (Model of End-Stage Liver Disease/Score of Paediatric End-Stage Liver Disease, Child-Pugh score) were assessed in 35 patients with cirrhosis of the liver. The average age of the patients was 10.7 ±4.74 years. All patients also had their oral cavities examined (mucosa, gingiva – GI, hygiene – PLI, teeth – dmft/dmfs and DMFt/DMFs, DDE Index and Candida spp. presence) and this was then correlated to the degree of liver function impairment. Results According to the Child-Pugh scale, 16 patients were class A and 19 were class B/C. Jaundice during the first 3 years of life occurred in 9 patients. Mucosal lesions were found in 26 out of 35 patients (74%), including 10 out of 16 (63%) in Child-Pugh group A, and 16 out of 19 (84%) in group B/C (NS – non significant). Oral candidiasis occurred more often in class B/C than in class A (47.4% vs. 12.5%; p < 0.05). The GI index (Gingival Index) and PLI index (Dental Plaque Index) did not differ between the groups (A vs. B/C) but correlated in the whole group (R = 0.58) as well as in subgroups A (R = 0.65) and B/C (R = 0.59). Dmft/dmfs and DMFt/DMFs indexes did not differ between groups A and B/C, and neither did the DMFt/DMFs in patients with/without enamel defects. Conclusions Oral mucosal lesions are commonly found in children with cirrhosis of the liver. Advanced liver disease promotes oral candidiasis. Severity

  12. Liver function from Y to Z.

    PubMed

    Arias, Irwin M

    2012-08-01

    In the 1960s, my lab was interested in understanding how bilirubin and other organic anions are transferred from the plasma through the liver cell and into the bile. We performed gel filtration of liver supernatants and identified two protein fractions, designated Y and Z, which bound organic anions including bilirubin, and thus we proposed that they were involved in hepatic uptake of organic anions from plasma. Subsequently, the Y and Z proteins responsible for this binding activity were purified, cloned, and sequenced. Y was identified as a member of the glutathione S-transferase (GST) protein family and Z found to be a member of the fatty acid–binding protein (FABP) family. These proteins have since been shown to have additional surprising roles, but understanding of their full role in physiology and disease has not yet been achieved.

  13. Biomechanics and functionality of hepatocytes in liver cirrhosis.

    PubMed

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

    2014-06-27

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

  14. Quantitative Estimation of the Amount of Fibrosis in the Rat Liver Using Fractal Dimension of the Shape of Power Spectrum

    NASA Astrophysics Data System (ADS)

    Kikuchi, Tsuneo; Nakazawa, Toshihiro; Furukawa, Tetsuo; Higuchi, Toshiyuki; Maruyama, Yukio; Sato, Sojun

    1995-05-01

    This paper describes the quantitative measurement of the amount of fibrosis in the rat liver using the fractal dimension of the shape of power spectrum. The shape of the power spectrum of the scattered echo from biotissues is strongly affected by its internal structure. The fractal dimension, which is one of the important parameters of the fractal theory, is useful to express the complexity of shape of figures such as the power spectrum. From in vitro experiments using rat liver, it was found that this method can be used to quantitatively measure the amount of fibrosis in the liver, and has the possibility for use in the diagnosis of human liver cirrhosis.

  15. Application of quantitative stereology to the evaluation of enzyme-altered foci in rat liver.

    PubMed

    Campbell, H A; Pitot, H C; Potter, V R; Laishes, B A

    1982-02-01

    The mathematical science of quantitative stereology has established relationships for the quantitation of elements in three-dimensional space from observations on two-dimensional planes. This report describes the utilization and importance of such mathematical relationships for the quantitative analysis of focal hepatic lesions in terms relative to the volume of the liver. Three examples are utilized to demonstrate the utility of such calculations in the three-dimensional quantitation of hepatic focal lesions. The first is that of a computer-simulated experiment based on defined hypothetical situations. The simulations demonstrate the applicability of the computations described in this report to the evaluation of two-dimensional data from typical animal experiments. The other two examples are taken from actual experiments and involve the transplantation of hepatic cell populations into the liver suitably prepared hosts and the quantitation of altered foci produced by initiation with diethylnitrosamine-partial hepatectomy followed by promotion with phenobarbital. The quantitation of altered foci by means of a two-dimensional analysis (simple enumeration of focal intersections/area of tissue section) is proportional to the quantitation of foci per volume of liver provided that the mean diameter of the foci for each treatment is sufficiently uniform, as exemplified in the text by the transplantation experiment. When such mean diameters are unequal as in the diethylnitrosamine-phenobarbital experiment described herein, quantitation from three-dimensional analysis gives significantly different results as compared with enumeration of focal intersections on two-dimensional areas. These studies clearly demonstrate that the frequency and size of foci intersections viewed on two-dimensional tissue sections do not necessarily reflect the number of size of foci in the three-dimensional tissue. Only by quantitating the number and size of the foci in relation to the three

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

    PubMed

    Wang, Yan; Hou, Jin-Lin

    2016-05-01

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

  17. Distribution of Diseases Causing Liver Function Test Abnormality in Children and Natural Recovery Time of the Abnormal Liver Function

    PubMed Central

    2016-01-01

    Although liver function test abnormality is frequently noted in children, there is no report about the distribution of the etiology and natural recovery time of the abnormal liver function. From March 2005 to February 2014, clinical information was retrospectively collected from 559 children who had abnormal liver function and were hospitalized or visited the outpatient clinic at the Jeju National University Hospital. The etiology of abnormal liver function was classified into groups and the natural recovery time of abnormal liver function was analyzed. The etiological groups of 559 patients included ‘nonspecific hepatitis’ in 42 (7.5%), ‘infection’ in 323 (57.8%), ‘rheumatologic and autoimmune’ in 66 (11.8%), ‘nonalcoholic fatty liver disease’ in 57 (10.2%), ‘anatomic’ in 12 (2.1%), ‘toxic’ in 13 (2.1%), ‘metabolic’ in 8 (1.4%), ‘hematologic’ in 7 (1.3%), ‘hemodynamic’ in 4 (0.7%), and ‘others’ in 27 (4.8%). Among the ‘infection’ group (57.8%), the ‘viral infection in the respiratory tract’ subgroup, which had 111 patients (19.8%), was the most common. The natural recovery time of the abnormal liver function was 27 days (median) in ‘nonspecific hepatitis’, 13 days (median) in ‘viral respiratory tract disease’, 16 days (median) in ‘viral gastroenteritis’, 42 days (median) in ‘viral febrile illness”, and 7 days (median) in “Kawasaki disease”. The information on the natural recovery time of abnormal liver function may help the physician to perform good clinical consultation for patients and their parents. PMID:27709857

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

  19. Functions of autophagy in normal and diseased liver

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  1. Structure, Regulation and Function of Gap Junctions in Liver.

    PubMed

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

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

  2. A Local and Global Function Model of the Liver

    PubMed Central

    Wang, Hesheng; Feng, Mary; Jackson, Andrew; Ten Haken, Randall K.; Lawrence, Theodore S.; Cao, Yue

    2015-01-01

    Purposes To develop a local and global function model in the liver based upon 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 prior to, 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 min (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 based upon whether the patients had hepatocellular carcinoma (HCC) or not. Results The liver function model showed that 1) a perfusion value of 68.6 ml/(100g·min) yielded a local function probability of 0.5; 2) the probability reached 0.9 at a perfusion value of 98 ml/(100g·min), and 3) at a probability of 0.03 (corresponding perfusion of 38 ml/(100g·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 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. PMID:26700712

  3. Liver cirrhosis and thyroid function: Friend or foe?

    PubMed

    Vincken, Stefanie; Reynaert, Hendrik; Schiettecatte, Johan; Kaufman, Leon; Velkeniers, Brigitte

    2017-04-01

    The liver plays a central role in thyroid hormone metabolism, transport, and clearance. A normal function of both the thyroid gland and the liver is therefore necessary to maintain normal thyroid hormone levels and action. Data regarding thyroid function in patients with liver cirrhosis are scarce and variable. The most consistent finding is a decreased free triiodothyronine (fT3) level, which correlates with the severity of liver disease and has been proposed as a prognostic factor for liver-related complications. To evaluate thyroid hormone values in patients with stable liver cirrhosis and to compare them with healthy controls without liver disease. We also assessed the prevalence of thyroid autoimmunity and whether liver function tests correlated with thyroid function. We performed a prospective case-control study in an endocrinological setting. Twenty-nine patients with stable cirrhosis (20 males and 9 females, mean age 60.97 ± 7.17 years) were included in the case group and 50 healthy subjects (22 males and 28 females, mean age 61.70 ± 13.00 years) in the control group. We excluded patients with confounding factors known to influence thyroid function. Levels of serum thyroid-stimulating hormone (TSH), fT3, free thyroxine (fT4) and anti-TPO-antibodies (TPO-Ab) were measured. These thyroid hormone values were compared in both groups. Biochemical indices of liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [AP], gamma-glutamyl transpeptidase [GGT], INR, total bilirubin, and albumin levels) were correlated with thyroid function tests. fT3 en fT4 levels were significantly lower in patients with cirrhosis than in healthy subjects (p = 0.001 and 0.002, respectively). TSH levels were not statistically significantly different in the two groups. The level of TPO-Ab was not increased in patients with cirrhosis compared to healthy controls. fT3 correlated negatively with the Child-Pugh score. These results

  4. Musculoskeletal Health, Kidney and Liver Function in Retired Jockeys.

    PubMed

    Cullen, S; Donohoe, A; McGoldrick, A; McCaffrey, N; Davenport, C; Byrne, B; Donaghy, C; Tormey, W; Smith, D; Warrington, G

    2015-11-01

    The long-term implications of making-weight daily on musculoskeletal health and functioning of the kidney and liver remain unknown. This study aimed to investigate musculoskeletal health and kidney and liver function in a group of retired jockeys. 28 retired male jockeys (age 50-70 years) provided fasting blood samples for markers of bone metabolism and kidney and liver function. A dual-energy x-ray absorptiometry (DXA) scan was performed for the assessment of bone mineral density (BMD). Established reference ranges were used for interpretation of results. Comparisons were made between retired jockeys based on the professional racing licence held: Flat, National Hunt or Dual. Mean whole-body osteopenia was reported, with no differences between groups. Bone markers, micronutrients, electrolytes and associated hormones, and markers for kidney and liver function were within clinical normative ranges. No differences existed between groups. Results indicate the retired jockeys in this study do not demonstrate compromised bone health or kidney and liver function. However, the retired jockeys may not have undergone chronic weight cycling in the extreme manner evident in present-day jockeys, indicating the next generation of jockeys may face more of a problem. Jockeys should be tracked longitudinally throughout their racing career and beyond.

  5. Autophagy in the liver: functions in health and disease.

    PubMed

    Ueno, Takashi; Komatsu, Masaaki

    2017-03-01

    The concept of macroautophagy was established in 1963, soon after the discovery of lysosomes in rat liver. Over the 50 years since, studies of liver autophagy have produced many important findings. The liver is rich in lysosomes and possesses high levels of metabolic-stress-induced autophagy, which is precisely regulated by concentrations of hormones and amino acids. Liver autophagy provides starved cells with amino acids, glucose and free fatty acids for use in energy production and synthesis of new macromolecules, and also controls the quality and quantity of organelles such as mitochondria. Although the efforts of early investigators contributed markedly to our current knowledge of autophagy, the identification of autophagy-related genes represented a revolutionary breakthrough in our understanding of the physiological roles of autophagy in the liver. A growing body of evidence has shown that liver autophagy contributes to basic hepatic functions, including glycogenolysis, gluconeogenesis and β-oxidation, through selective turnover of specific cargos controlled by a series of transcription factors. In this Review, we outline the history of liver autophagy study, and then describe the roles of autophagy in hepatic metabolism under healthy and disease conditions, including the involvement of autophagy in α1-antitrypsin deficiency, NAFLD, hepatocellular carcinoma and viral hepatitis.

  6. Quantitative Functional Morphology by Imaging Flow Cytometry.

    PubMed

    Vorobjev, Ivan A; Barteneva, Natasha S

    2016-01-01

    This chapter describes advantages and limitations of imaging flow cytometry (IFC) based on Imagestream instrumentation using a hybrid approach of morphometric measurement and quantitation of multiparametric fluorescent intensities' distribution in cells and particles. Brief comparison is given of IFC with conventional flow cytometry and fluorescent microscopy. Some future directions of the IFC technology are described and discussed.

  7. Quantitative assessment of fibrosis and steatosis in liver biopsies from patients with chronic hepatitis C

    PubMed Central

    Zaitoun, A; Al, M; Awad, S; Ukabam, S; Makadisi, S; Record, C

    2001-01-01

    Backgrounds—Hepatic fibrosis is one of the main consequences of liver disease. Both fibrosis and steatosis may be seen in some patients with chronic hepatitis C and alcoholic liver disease (ALD). Aims—To quantitate fibrosis and steatosis by stereological and morphometric techniques in patients with chronic hepatitis C and compare the results with a control group of patients with ALD. In addition, to correlate the quantitative features of fibrosis with the Ishak modified histological score. Materials and methods—Needle liver biopsies from 86 patients with chronic hepatitis C and from 32 patients with alcoholic liver disease (disease controls) were analysed by stereological and morphometric analyses using the Prodit 5.2 system. Haematoxylin and eosin and Picro-Mallory stained sections were used. The area fractions (AA) of fibrosis, steatosis, parenchyma, and other structures (bile duct and central vein areas) were assessed by stereological method. The mean diameters of fat globules were determined by morphometric analysis. Results—Significant differences were found in the AA of fibrosis, including fibrosis within portal tract areas, between chronic hepatitis C patients and those with ALD (mean (SD): 19.14 (10.59) v 15.97 (12.51)). Portal and periportal (zone 1) fibrosis was significantly higher (p = 0.00004) in patients with chronic hepatitis C compared with the control group (mean (SD): 9.04 (6.37) v 3.59 (3.16)). Pericentral fibrosis (zone 3) occurred in both groups but was significantly more pronounced in patients with ALD. These results correlate well with the modified Ishak scoring system. However, in patients with cirrhosis (stage 6) with chronic hepatitis C the AA of fibrosis varied between 20% and 74%. The diameter of fat globules was significantly lower in patients with hepatitis C (p = 0.00002) than the ALD group (mean (SD): 14.44 (3.45) v 18.4 (3.32)). Microglobules were more frequent in patients with chronic hepatitis C than in patients with ALD

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

    PubMed Central

    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

    2014-01-01

    Background & Aims 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 operators. A new quantitative ultrasound (QUS) technique can identify steatosis in animal models. We assessed the accuracy of QUS in the diagnosis and quantification hepatic steatosis, comparing findings with those from MRI proton density fat fraction (MRI-PDFF) analysis as a reference. 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 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 randomly assigned to training (n=102; mean age, 51±17 years; mean body mass index, 31±7 kg/m2) and validation (n=102; mean age, 49±17 years; body mass index, 30±6 kg/m2) groups; 69% of patients in each group had NAFLD. Results BSC (range 0.00005–0.25 1/cm-sr) correlated with MRI-PDFF (Spearman’s ρ=0.80; P<.0001). In the training group, the BSC analysis identified patients with NAFLD with an area under the curve value of 0.98 (95% confidence interval, 0.95–1.00; P<.0001). The optimal BSC cutoff value identified patients with NAFLD in the training and validation groups with 93% and 87% sensitivity, 97% and 91% specificity, 86% and 76% negative predictive values, and 99% and 95% positive predictive values, respectively. Conclusions QUS measurements of BSC can accurately diagnose and quantify hepatic steatosis, based on a cross-sectional analysis that used MRI-PDFF as the

  9. Limitation of liver function tests in metastatic carcinoid tumors

    SciTech Connect

    Moinuddin, M.; Dean, P.; Vander Zwaag, R.; Dragutsky, M.

    1987-04-01

    To evaluate the utility of liver function tests (LFT) as indicators of metastatic carcinoid tumors, a retrospective study was performed. The LFT results of 17 patients with carcinoid tumors metastatic to the liver were compared with 17 patients with other malignant tumors. In the noncarcinoid group, 82.4% of the patients had elevated alkaline phosphatase (AP) or gamma glutamyl transpeptidase (GGTP), whereas only 28.6% of carcinoid patients had abnormal enzymes. The medians of all LFT values were significantly higher in noncarcinoid patients than in the carcinoid group, except for glutamic pyruvic transaminase (SGPT). Our data indicate that LFT are helpful in screening for liver metastases in patients with noncarcinoid tumors, but are unreliable in carcinoid tumors. Imaging tests should be used to rule out liver metastases in carcinoid tumors, irrespective of LFT results.

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Impaired liver function attenuates liver regeneration and hypertrophy after portal vein embolization

    PubMed Central

    Kageyama, Yumiko; Kokudo, Takashi; Amikura, Katsumi; Miyazaki, Yoshihiro; Takahashi, Amane; Sakamoto, Hirohiko

    2016-01-01

    AIM To clarify the clinical factors associated with liver regeneration after major hepatectomy and the hypertrophic rate after portal vein embolization (PVE). METHODS A total of 63 patients who underwent major hepatectomy and 13 patients who underwent PVE in a tertiary care hospital between January 2012 and August 2015 were included in the analysis. We calculated the remnant liver volume following hepatectomy using contrast-enhanced computed tomography (CT) performed before and approximately 3-6 mo after hepatectomy. Furthermore, we calculated the liver volume using CT performed 2-4 wk after PVE. Preoperative patient characteristics and laboratory data were analyzed to identify factors affecting postoperative liver regeneration or hypertrophy rate following PVE. RESULTS The remnant liver volume/total liver volume ratio negatively correlated with the liver regeneration rate after hepatectomy (ρ = -0.850, P < 0.001). The regeneration rate was significantly lower in patients with an indocyanine green retention rate at 15 min (ICG-R15) of ≥ 20% in the right hepatectomy group but not in the left hepatectomy group. The hypertrophic rate after PVE positively correlated with the regeneration rate after hepatectomy (ρ = 0.648, P = 0.017). In addition, the hypertrophic rate after PVE was significantly lower in patients with an ICG-R15 ≥ 20% and a serum total bilirubin ≥ 1.5 mg/dL. CONCLUSION The regeneration rate after major hepatectomy correlated with hypertrophic rate after PVE. Both of them were attenuated in the presence of impaired liver function. PMID:27729956

  12. In vivo quantitation of the rat liver's ability to eliminate endotoxin from portal vein blood

    SciTech Connect

    Yamaguchi, Y.; Yamaguchi, K.; Babb, J.L.; Gans, H.

    1982-12-01

    The in vivo uptake of endotoxin by the liver from portal vein blood was assessed during a single passage through the liver. /sup 51/Cr labeled and unlabeled endotoxin were infused in different amounts into the femoral vein of three groups of lead-sensitized rats: a nonoperated, a sham-operated, and a surgically created reversed Eck fistula (REF) group. Whereas in the former two the infused endotoxin encounters the lung as the first filter organ, the liver performs this function in the latter experimental model. The mortality rates observed in control and sham-operated, lead-sensitized rats were found to correlate closely and reproducibly to the degree of endotoxemia. This assay was then applied to determine the amount of endotoxin eliminated by the liver by establishing, in the REF rat, the amounts of endotoxin that escaped hepatic clearance. The capacity of the liver to eliminate endotoxin from portal vein blood during a single passage increases as the portal vein endotoxin level rises; it approaches a maximum, suggesting that endotoxin's interaction with the Kupffer cells conforms to classical saturation kinetics. A Lineweaver-Burk plot prepared from these data indicates that the maximal in vivo capacity of the liver to remove endotoxin from portal vein blood approximates 1.5 micrograms/gm liver/hr. Data obtained with the use of radiolabeled endotoxin corroborate the information obtained with the bioassay technique. Endotoxin eliminated by the Kupffer cells in these quantities is slowly disintegrated; 4 hr after termination of the endotoxin infusion, less than 4% of the radiolabel is found in the urine and none in the bile. These observations indicate that the Kupffer cell's functional capacity to sequester and detoxify endotoxin is extensive and far exceeds the requirements imposed by physiological and most pathological conditions.

  13. Multifeature analysis of an ultrasound quantitative diagnostic index for classifying nonalcoholic fatty liver disease

    PubMed Central

    Liao, Yin-Yin; Yang, Kuen-Cheh; Lee, Ming-Ju; Huang, Kuo-Chin; Chen, Jin-De; Yeh, Chih-Kuang

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome. This study applied an integrated analysis based on texture, backscattering, and attenuation features in ultrasound imaging with the aim of assessing the severity of NAFLD. Ultrasound radiofrequency data obtained from 394 clinical cases were analyzed to extract three texture features (autocorrelation, sum average, and sum variance), the signal-to-noise ratio (SNR), and the slope of the center-frequency downshift (CFDS slope). The texture, SNR, and CFDS slope were combined to produce a quantitative diagnostic index (QDI) that ranged from 0 to 6. We trained the QDI using training data and then applied it to test data to assess its utility. In training data, the areas (AUCs) under the receiver operating characteristic curves for NAFLD and severe NAFLD were 0.81 and 0.84, respectively. In test data, the AUCs were 0.73 and 0.81 for NAFLD and severe NAFLD, respectively. The QDI was able to distinguish severe NAFLD and a normal liver from mild NAFLD, and it was significantly correlated with metabolic factors. This study explored the potential of using the QDI to supply information on different physical characteristics of liver tissues for advancing the ability to grade NAFLD. PMID:27734972

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

    PubMed

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

    2013-06-01

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

  15. Association of serum zinc levels with liver function and survival in patients awaiting liver transplantation.

    PubMed

    Friedrich, Kilian; Baumann, Carina; Brune, Maik; Wannhoff, Andreas; Rupp, Christian; Scholl, Sabine G; Antoni, Christoph; Dollinger, Matthias; Neumann-Haefelin, Christoph; Weiss, Karl Heinz; Stremmel, Wolfgang; Schemmer, Peter; Gotthardt, Daniel Nils

    2015-10-01

    Zinc is an important trace element with catalytic and defensive functions. We assessed the impact of zinc deficiency in patients with end-stage liver disease awaiting liver transplantation. Serum zinc levels were measured at the time of evaluation for liver transplantation (n = 368). Patients were dichotomized in two groups based on low and normal zinc serum levels. Serum zinc levels are tightly associated with liver function as patients with low zinc levels (n = 226) had a higher Model for End-Stage Liver Disease (MELD) score (15.0 [5.0-40.0]) than patients with normal zinc (n = 142) levels (9.0 [6.0-34.0]; p < 0.00). Multivariate analysis demonstrated that serum zinc levels function as an independent predictor of hepatic decompensation (hydropic decompensation: odds ratio [OR] 0.82; 95% confidence interval [CI] 0.70-0.96; p = 0.015; hepatic encephalopathy: OR 0.80; 95% CI 0.71-0.90; p = 0.000; spontaneous bacterial peritonitis: OR 0.85; 95% CI 0.72-1.00; p = 0.047; hepatorenal syndrome: OR 0.83; 95% CI 0.72-0.95; p = 0.011). Actuarial survival free of liver transplantation was reduced for low-zinc patients (26.7 ± 4.0 months; 95% CI 18.8-34.6) compared to patients with normal zinc levels (30.9 ± 3.0 months; 95% CI 24.9-36.9; p = 0.008). Reduction of zinc levels for patients on the transplantation list resulted in a 28.3-fold increased risk of death/liver transplantation (95% CI 3.2-244.8, p < 0.001). Serum zinc levels are associated with reduced survival in end-stage liver disease patients. Whether or not zinc supplementation might be beneficial for patients on a liver transplantation list requires further study.

  16. Effects of environmental cadmium exposure on liver function in adults.

    PubMed

    Kang, Mo-Yeol; Cho, Soo-Hun; Lim, Youn-Hee; Seo, Jeong-Cheol; Hong, Yun-Chul

    2013-04-01

    There is inconsistency regarding the effects of cadmium exposure on liver function between the positive results found in animal studies and the negative results highlighted in epidemiological studies. We investigated whether environmental cadmium exposure is associated with an elevation in serum liver enzyme activity in Korean adults. This cross-sectional study evaluated adult participants without liver disease from the Korean National Health and Nutrition Examination Survey for 2008-2009. Multiple linear regression was conducted to investigate the association between blood cadmium concentration and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) adjusting for age, sex, body mass index and the amount of alcohol consumption. Subjects were stratified into quartiles by their cumulative cadmium exposure rank. We estimated the multivariate-adjusted ORs for liver enzyme elevation using logistic regression models with the first quartile as the reference group. Total number of the subjects in the analysis was 3914. The blood cadmium concentrations were significantly associated with liver enzyme levels (AST, β=2.677, p value <0.0001; ALT, β=3.696, p value <0.0001; ALP, β=11.730, p value <0.0001). As the cadmium levels approached higher quartiles, the ORs for an elevated AST, ALT and ALP was increased significantly. Environmental cadmium exposures are associated with an elevation in serum liver enzyme levels in Korean adults.

  17. Functional tissue engineering of the liver and islets.

    PubMed

    Ohashi, Kazuo; Okano, Teruo

    2014-01-01

    Cell-based therapies by using hepatocytes and islets have recently been evaluated as a new therapeutic modality for patients with many forms of liver diseases and insulin-deficient diabetes mellitus. In most of the recently conducted clinical trials, cells have been delivered into liver vasculatures by infusing them through the portal circulation. More recently, tissue engineering-based approaches have spurred significant interests, using hepatocytes and islets in which small but functional new tissues would be created in vivo. Under circumstances in which a higher level of cell engraftment could be obtained, these approaches could provide therapeutic effects. Considerable efforts have been given to sustaining engineered tissues and maintaining their therapeutic effects. This review highlights several strategies that can achieve a higher level of cell survival for creating new functional liver and islet tissues.

  18. Assessment of thyroid and gonadal function in liver diseases

    PubMed Central

    Kharb, Sandeep; Garg, M. K.; Puri, Pankaj; Brar, Karninder S.; Pandit, Aditi; Srivastava, Sharad

    2015-01-01

    Introduction: Liver is involved with the synthesis of carrier proteins and metabolism of various hormones and liver diseases may, therefore, be associated with various endocrine disturbances. This study was conducted to assess thyroid and gonadal function in subjects with acute hepatitis (AH), chronic liver disease (CLD), and those who had undergone liver transplantation (LT). Materials and Methods: Patients with AH, CLD with Child-Pugh stage A (CLD-1) and Child-Pugh stage B or C (CLD-2), and LT seen at our tertiary level hospital were assessed clinically, biochemically, and for thyroid and gonadal functions besides 25 healthy controls. Results: Thyroid dysfunction and hypogonadism were present in 14 (16%) and 24 (28%) patients with liver diseases respectively. Among thyroid dysfunction, the commonest was sick euthyroid syndrome six (7%), followed by subclinical hypothyroidism in three patients (3.5%), subclinical hyperthyroidism and thyrotoxicosis in two patients each (2.3%) and overt hypothyroidism in one patient. Among patients with LT and AH groups, the only abnormality was significantly lower total T3 compared with healthy controls. The CLD2 group had significantly lower levels of all thyroid hormones compared with controls and CLD1 group. Hypogonadism was commonest in patients with CLD-2 (14; 50%) followed by LT (3; 33%), CLD-1 (4; 20%), and AH (3; 14%). Hypogonadism was predicted by older age, lower levels of serum albumin, total cholesterol, and triglycerides and higher levels of plasma glucose, serum bilirubin, aspartate transaminases, and international normalized ratio. Gonadal functions showed recovery following LT. Conclusions: Thyroid dysfunction and hypogonadism form an important part of the spectrum of acute and CLD, and patients with LT. Deterioration of synthetic functions of liver disease predicts presence of hypogonadism. PMID:25593833

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

    PubMed

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

    2016-07-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  1. Evidence for regulatory genes on mouse chromosome 7 that affect the quantitative expression of proteins in the fetal and newborn liver.

    PubMed Central

    Giometti, C S; Gemmell, M A; Taylor, J; Tollaksen, S L; Angeletti, R; Gluecksohn-Waelsch, S

    1992-01-01

    A series of deletions around the albino locus on mouse chromosome 7 is believed to include one or more regulatory genes that control the activities of a cluster of liver enzymes. To further characterize the functions of this region of the mouse genome, we have used quantitative two-dimensional electrophoresis to analyze the effects of two of these deletions, c3H and c14CoS, on the expression of liver proteins. More than 400 distinct protein gene products were quantitated in livers from fetal and newborn wild-type homozygous (cch/cch), heterozygous (cch/c3H or cch/c14CoS), and deletion homozygous (c3H/c3H or c14CoS/c14CoS) mice. Livers of fetal and newborn c3H heterozygotes and homozygous wild-type littermates produced qualitatively identical protein patterns after two-dimensional electrophoresis. In livers of c3H homozygous fetuses, however, abnormal amounts (either increased or decreased relative to homozygous wild-type and heterozygous littermates) of 29 proteins were found. Twenty-eight of these 29 protein anomalies were also found in livers of newborn c3H homozygotes. Livers of fetal and newborn mice homozygous for the c14CoS deletion, which overlaps the c3H deletion and produces a similar phenotype, expressed normal amounts of these proteins. One of the 29 proteins (MSN807) has an amino-terminal sequence similar to a 23-kDa translationally controlled protein abundant in mouse erythroleukemia and sarcoma-180 cells. These results suggest that normal chromosome 7 contains genes, located within the region of the c3H but not the c14CoS deletion, that regulate the abundance of specific proteins in the liver. These proteins cannot be related to the phenotypic alterations shared by the c3H and c14CoS deletions. Images PMID:1549608

  2. Immunological quantitation and localization of ACAT-1 and ACAT-2 in human liver and small intestine.

    PubMed

    Chang, C C; Sakashita, N; Ornvold, K; Lee, O; Chang, E T; Dong, R; Lin, S; Lee, C Y; Strom, S C; Kashyap, R; Fung, J J; Farese, R V; Patoiseau, J F; Delhon, A; Chang, T Y

    2000-09-08

    By using specific anti-ACAT-1 antibodies in immunodepletion studies, we previously found that ACAT-1, a 50-kDa protein, plays a major catalytic role in the adult human liver, adrenal glands, macrophages, and kidneys but not in the intestine. Acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in the intestine may be largely derived from a different ACAT protein. To test this hypothesis, we produced specific polyclonal anti-ACAT-2 antibodies that quantitatively immunodepleted human ACAT-2, a 46-kDa protein expressed in Chinese hamster ovary cells. In hepatocyte-like HepG2 cells, ACAT-1 comprises 85-90% of the total ACAT activity, with the remainder attributed to ACAT-2. In adult intestines, most of the ACAT activity can be immunodepleted by anti-ACAT-2. ACAT-1 and ACAT-2 do not form hetero-oligomeric complexes. In differentiating intestinal enterocyte-like Caco-2 cells, ACAT-2 protein content increases by 5-10-fold in 6 days, whereas ACAT-1 protein content remains relatively constant. In the small intestine, ACAT-2 is concentrated at the apices of the villi, whereas ACAT-1 is uniformly distributed along the villus-crypt axis. In the human liver, ACAT-1 is present in both fetal and adult hepatocytes. In contrast, ACAT-2 is evident in fetal but not adult hepatocytes. Our results collectively suggest that in humans, ACAT-2 performs significant catalytic roles in the fetal liver and in intestinal enterocytes.

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

    SciTech Connect

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

    1987-12-01

    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-/sup 14/C)cholesterol, a polyprenol containing 15 isoprene units, and (1-/sup 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.

  4. Bioreactor Technologies to Support Liver Function In Vitro

    PubMed Central

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

    2014-01-01

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

  5. Quantitative assay and subcellular distribution of enzymes acting on dolichyl phosphate in rat liver

    PubMed Central

    Ravoet, A; Amar-Costesec, A; Godelaine, D; Beaufay, H

    1981-01-01

    To establish on a quantitative basis the subcellular distribution of the enzymes that glycosylate dolichyl phosphate in rat liver, preliminary kinetic studies on the transfer of mannose, glucose, and N-acetylglucosamine-1-phosphate from the respective (14)C- labeled nucleotide sugars to exogenous dolichyl phosphate were conducted in liver microsomes. Mannosyltransferase, glucosyltransferase, and, to a lesser extent, N- acetylglucosamine-phosphotransferase were found to be very unstable at 37 degrees C in the presence of Triton X-100, which was nevertheless required to disperse the membranes and the lipid acceptor in the aqueous reaction medium. The enzymes became fairly stable in the range of 10-17 degrees C and the reactions then proceeded at a constant velocity for at least 15 min. Conditions under which the reaction products are formed in amount proportional to that of microsomes added are described. For N- acetylglucosaminephosphotransferase it was necessary to supplement the incubation medium with microsomal lipids. Subsequently, liver homogenates were fractionated by differential centrifugation, and the microsome fraction, which contained the bulk of the enzymes glycosylating dolichyl phosphate, was analyzed by isopycnic centrifugation in a sucrose gradient without any previous treatment, or after addition of digitonin. The centrifugation behavior of these enzymes was compared to that of a number of reference enzymes for the endoplasmic reticulum, the golgi complex, the plasma membranes, and mitochondria. It was very simily to that of enzymes of the endoplasmic reticulum, especially glucose-6-phosphatase. Subcellular preparations enriched in golgi complex elements, plasma membranes, outer membranes of mitochondira, or mitoplasts showed for the transferases acting on dolichyl phosphate relative activities similar to that of glucose- 6-phosphatase. It is concluded that glycosylations of dolichyl phosphate into mannose, glucose, and N-acetylglucosamine-1

  6. Quantitation of rat liver xanthine oxidase by radioimmunoassay. A mechanism for sex-specific differences

    SciTech Connect

    Decker, D.E.; Levinson, D.J.

    1982-03-01

    To further delineate the mechanism responsible for the differences in xanthine oxidase activity in male and female Sprague-Dawley rats, a sensitive and specific radioimmunoassay (RIA) was developed for the measurement of hepatic xanthine oxidase. The RIA could detect as little as 5 mg of liver enzyme. Specificity of the RIA was confirmed by 1) Ouchterlony double immuno-diffusion in which a single precipitin band exhibited xanthine oxidase activity, when crude liver homogenate and an enzyme-specific stain were used; 2) parallelism between purified 125I-labeled xanthine oxidase and serial dilutions of crude liver homogenate; 3) a linear correlation between xanthine oxidase activity and the level of enzyme protein; and 4) a single protein band coincident with purified xanthine oxidase, when an immunoprecipitate prepared from antisera and crude liver homogenate was analyzed on sodium dodecyl sulfate (SDS) polyacrylamide gels. Whether xanthine oxidase activity was assayed in the absence of nicotinamide adenine dinucleotide (NAD+) (oxidase form) or in the presence of NAD+ (dehydrogenase), male values were consistently higher, and both forms of the enzyme correlated significantly with each other. When purified to homogeneity, neither form of the enzyme was appreciably affected by 17 beta-estradiol or testosterone propionate. When the RIA was employed, levels of hepatic xanthine oxidase were significantly greater in male than in female rats. We concluded from these data that increased xanthine oxidase activity in the male corresponds to a greater quantitative complement of xanthine oxidase protein. Furthermore, lower xanthine oxidase activity in the female cannot be explained by immunologically cross-reactive material without enzyme activity nor by a direct sex-steroid enzyme interaction.

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

    PubMed

    Leite, Luiz Arthur Calheiros; Pimenta Filho, Adenor Almeida; Ferreira, Rita de Cássia dos Santos; da Fonseca, Caíque Silveira Martins; dos Santos, Bianka Santana; Montenegro, Silvia Maria Lucena; Lopes, Edmundo Pessoa de Almeida; Domingues, Ana Lúcia Coutinho; Owen, James Stuart; Lima, Vera Lucia de Menezes

    2015-01-01

    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.

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

    PubMed Central

    Leite, Luiz Arthur Calheiros; Pimenta Filho, Adenor Almeida; Ferreira, Rita de Cássia dos Santos; da Fonseca, Caíque Silveira Martins; dos Santos, Bianka Santana; Montenegro, Silvia Maria Lucena; Lopes, Edmundo Pessoa de Almeida; Domingues, Ana Lúcia Coutinho; Owen, James Stuart; Lima, Vera Lucia de Menezes

    2015-01-01

    Background 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. Methodology/Principal Findings 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. Conclusion/Significance 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. PMID:26267788

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

    PubMed Central

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

    2009-01-01

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

  10. Quantitation of renal function using radioisotopic techniques.

    PubMed

    O'Malley, J P; Ziessman, H A

    1993-03-01

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

  11. Structural and functional hepatocyte polarity and liver disease

    PubMed Central

    Gissen, Paul; Arias, Irwin M.

    2015-01-01

    Summary Hepatocytes form a crucially important cell layer that separates sinusoidal blood from the canalicular bile. They have a uniquely organized polarity with a basal membrane facing liver sinusoidal endothelial cells, while one or more apical poles can contribute to several bile canaliculi jointly with the directly opposing hepatocytes. Establishment and maintenance of hepatocyte polarity is essential for many functions of hepatocytes and requires carefully orchestrated cooperation between cell adhesion molecules, cell junctions, cytoskeleton, extracellular matrix and intracellular trafficking machinery. The process of hepatocyte polarization requires energy and, if abnormal, may result in severe liver disease. A number of inherited disorders affecting tight junction and intracellular trafficking proteins have been described and demonstrate clinical and pathophysiological features overlapping those of the genetic cholestatic liver diseases caused by defects in canalicular ABC transporters. Thus both structural and functional components contribute to the final hepatocyte polarity phenotype. Many acquired liver diseases target factors that determine hepatocyte polarity, such as junctional proteins. Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus. However, the molecular mechanisms underlying these defects are not well understood. Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases. PMID:26116792

  12. Quantitative temporal analysis of /sup 99m/Technetium p-isopropyl-iminodiacetic acid (PIPIDA) as a measure of hepatic function in health and disease

    SciTech Connect

    Joshi, S.N.; George, E.A.; Perrillo, R.P.

    1981-01-01

    Excretory liver function was analyzed in 10 healthy volunteers and 28 subjects with acute or chronic liver injury following intravenous administration of /sup 99m/technetium p-isopropyl iminodiacetic acid. Hepatobiliary transit of this agent was quantitated at 5-min intervals for a total of 60 min. Indices of total liver activity, liver cell uptake, liver parenchymal clearance, and bile duct clearance of /sup 99m/technetium p-isopropyl iminodiacetic acid were calculated from time--activity curves over heart, liver, extrahepatic bile ducts, and gallbladder. Seven subjects with acute viral hepatitis, 15 with extrahepatic biliary obstruction, and 6 with intrahepatic cholestasis were evaluated. Compared with healthy volunteers, a significant (p less than 0.0001) reduction in total liver activity and liver parenchymal clearance was demonstrated in all patient groups. Major resolution in all liver-derived indices, particularly total liver activity, occurred during convalescence from hepatitis and after biliary drainage. Nonmeasurable bile duct clearance always indicated a diagnosis of extrahepatic obstruction in cholestatic subjects, and this index normalized in subjects following biliary drainage. Whereas visual assessment of /sup 99m/technetium p-isopropyl iminodiacetic acid scans provided limited, useful information about the functional status of the liver, quantitative temporal analysis proved to be a much more effective technique.

  13. Albumin Binding Function: The Potential Earliest Indicator for Liver Function Damage

    PubMed Central

    Ge, Penglei; Yang, Huayu; Lu, Jingfen; Liao, Wenjun; Du, Shunda; Xu, Yingli; Xu, Haifeng; Lu, Xin; Sang, Xinting; Zhong, Shouxian; Huang, Jiefu

    2016-01-01

    Background. Currently there is no indicator that can evaluate actual liver lesion for early stages of viral hepatitis, nonalcoholic fatty liver disease (NAFLD), and cirrhosis. Aim of this study was to investigate if albumin binding function could better reflect liver function in these liver diseases. Methods. An observational study was performed on 193 patients with early NAFLD, viral hepatitis, and cirrhosis. Cirrhosis patients were separated according to Child-Pugh score into A, B, and C subgroup. Albumin metal ion binding capacity (Ischemia-modified albumin transformed, IMAT) and fatty acid binding capacity (total binding sites, TBS) were detected. Results. Both IMAT and TBS were significantly decreased in patients with NAFLD and early hepatitis. In hepatitis group, they declined prior to changes of liver enzymes. IMAT was significantly higher in cirrhosis Child-Pugh class A group than hepatitis patients and decreased in Child-Pugh class B and class C patients. Both IMAT/albumin and TBS/albumin decreased significantly in hepatitis and NAFLD group patients. Conclusions. This is the first study to discover changes of albumin metal ion and fatty acid binding capacities prior to conventional biomarkers for liver damage in early stage of liver diseases. They may become potential earliest sensitive indicators for liver function evaluation. PMID:28101103

  14. Development of a bioartificial liver: properties and function of a hollow-fiber module inoculated with liver cells.

    PubMed

    Rozga, J; Williams, F; Ro, M S; Neuzil, D F; Giorgio, T D; Backfisch, G; Moscioni, A D; Hakim, R; Demetriou, A A

    1993-02-01

    We have developed a bioartificial liver support system utilizing hollow-fiber bioreactor, plasmapheresis and microcarrier cell culture technologies. Liver cells were obtained through portal vein perfusion with ethylenediaminetetraacetate or ethylenediaminetetraacetate/collagenase. A mathematical model of mass transport in a hollow-fiber module, at various plasma flow velocities and system configurations, was developed. The bioartificial liver's ability to carry out specific differentiated metabolic liver functions was tested in vitro and in vivo. A reproducible large-animal model of acute ischemic liver failure was developed. Most major first-generation cyclosporine and 19-norterstosterone metabolites were isolated after substrate addition to the bioartificial liver in vitro. After bioartificial liver treatment for 6 hr (with dog or pig liver cells), dogs with acute liver failure had significantly lower serum ammonia and lactate levels and significantly higher serum glucose levels than did control animals treated with a bioartificial liver system inoculated with microcarriers alone. In addition, bioartificial liver-treated animals had significantly higher mean systolic blood pressures than did controls. Liver cell viability at the end of the 6-hr in vivo experiment was greater than 90%.

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

    PubMed Central

    Shimamoto, Dai; Nishie, Akihiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Takayama, Yukihisa; Fujita, Nobuhiro; Shirabe, Ken; Hida, Tomoyuki; Kubo, Yuichiro; Honda, Hiroshi

    2015-01-01

    Purpose. To evaluate whether the diagnostic performance of Gd-EOB-DTPA-enhanced MRI in evaluating liver function and pathology is improved by considering liver volume (LV). Methods. This retrospective study included 104 patients who underwent Gd-EOB-DTPA-enhanced MRI before liver surgery. For each patient, using the precontrast and hepatobiliary phase images, we calculated the increase rate of the liver-to-spleen signal intensity ratio (LSR), that is, the “ΔLSR,” and the increase rate of the liver-to-muscle signal intensity ratio (LMR), that is, the “ΔLMR.” ΔLSR × LV and ΔLMR × LV were also calculated. The correlation of each MR parameter with liver function data or liver pathology was assessed. The correlation coefficients were compared between ΔLSR (ΔLMR) and ΔLSR (ΔLMR) × LV. Results. The correlation coefficient between ΔLSR (ΔLMR) × LV and cholinesterase was significantly higher than that between ΔLSR (ΔLMR) and cholinesterase. The correlation coefficient between ΔLSR (ΔLMR) × LV and the degree of fibrosis or necroinflammatory activity was significantly lower than that between ΔLSR (ΔLMR) and the degree of fibrosis or necroinflammatory activity. Conclusion. The inclusion of liver volume may improve Gd-EOB-DTPA-based predictions of liver function, but not in predictions of liver pathology. PMID:26609519

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

    PubMed

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

    2012-08-01

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

  17. Quantitative analysis of ultrasonic images of fibrotic liver using co-occurrence matrix based on multi-Rayleigh model

    NASA Astrophysics Data System (ADS)

    Isono, Hiroshi; Hirata, Shinnosuke; Hachiya, Hiroyuki

    2015-07-01

    In medical ultrasonic images of liver disease, a texture with a speckle pattern indicates a microscopic structure such as nodules surrounded by fibrous tissues in hepatitis or cirrhosis. We have been applying texture analysis based on a co-occurrence matrix to ultrasonic images of fibrotic liver for quantitative tissue characterization. A co-occurrence matrix consists of the probability distribution of brightness of pixel pairs specified with spatial parameters and gives new information on liver disease. Ultrasonic images of different types of fibrotic liver were simulated and the texture-feature contrast was calculated to quantify the co-occurrence matrices generated from the images. The results show that the contrast converges with a value that can be theoretically estimated using a multi-Rayleigh model of echo signal amplitude distribution. We also found that the contrast value increases as liver fibrosis progresses and fluctuates depending on the size of fibrotic structure.

  18. Microporous membrane-based liver tissue engineering for the reconstruction of three-dimensional functional liver tissues in vitro.

    PubMed

    Kasuya, Junichi; Tanishita, Kazuo

    2012-01-01

    To meet the increasing demand for liver tissue engineering, various three-dimensional (3D) liver cell culture techniques have been developed. Nevertheless, conventional liver cell culture techniques involving the suspending cells in extracellular matrix (ECM) components and the seeding of cells into 3D biodegradable scaffolds have an intrinsic shortcoming, low cell-scaffold ratios. We have developed a microporous membrane-based liver cell culture technique. Cell behaviors and tissue organization can be controlled by membrane geometry, and cell-dense thick tissues can be reconstructed by layering cells cultured on biodegradable microporous membranes. Applications extend from liver parenchymal cell monoculture to multi-cell type cultures for the reconstruction of 3D functional liver tissue. This review focuses on the expanding role for microporous membranes in liver tissue engineering, primarily from our research.

  19. A novel cause for abnormal liver function tests in pregnancy and the puerperium: non-alcoholic fatty liver disease.

    PubMed

    Page, L M; Girling, J C

    2011-11-01

    Non-alcoholic fatty liver disease (NAFLD) is the commonest liver disease in the western world, but has never been reported in pregnancy before. We suggest that NAFLD should also be considered as a cause for abnormal liver function tests during pregnancy. As NAFLD is driven by insulin resistance, it is biologically plausible that pregnancy may reveal previously subclinical disease. Obstetricians have a vital role in optimising maternal health during and after pregnancy and therefore we need to include NAFLD in the differential diagnosis for abnormal liver function tests and recommend lifestyle modifications that may prevent progression to cirrhosis and hepatocellular carcinoma.

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

    PubMed

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

    2004-01-01

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

  1. Atherosclerosis and Liver Function Tests in Coronary Angiography Patients

    PubMed Central

    Doganer, YC; Rohrer, JE; Aydogan, U; Agerter, DC; Cayci, T; Barcin, C

    2015-01-01

    ABSTRACT Objective: Elevated aminotransferase levels indicating liver function, even in the normal range, have attracted great concern as potential novel markers of cardiovascular risk assessment. We hypothesized the possibility that liver function test variations in the normal range might be meaningfully associated to coronary artery disease (CAD). Method: Eighty-eight patients were randomly selected from those who underwent coronary angiography from June 2010 to June 2011 after applying to the outpatient cardiology clinic in Gulhane Military Medical Academy. According to the results of angiographies, patients were classified into three groups as normal, non-critical (< 50% involvement in coronaries), and critical (≥ 50% involvement in coronaries). In addition to angiographic intervention, measurements of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, albumin and the other serum parameters were performed in all patients. Results: The patient groups of CAD were balanced (28 critical cases, 30 non-critical cases and 30 normal cases). Mean age was 51.93 ± 9.3 (range 32–65) years and 19.3 per cent (n = 17) were females. Multiple linear regression analysis of all three liver function tests explained a significant portion of the variance, but adjusted r-squares were small (AST = 0.174, ALT = 0.242, albumin = 0.124). Albumin was significantly higher for patients with critical CAD than for patients with no CAD (beta = 3.205, p = 0.002). Non-critical CAD was not significantly different from no CAD for any of the dependent variables. Mean AST was significantly higher for patients taking aspirin (beta = 0.218, p = 0.049), as was mean ALT (beta = 0.264, p = 0.015). Conclusion: Alanine aminotransferase and AST may not be associated with angiographically determined coronary atherosclerosis. Albumin may be more sensitive to demonstrate the burden of atherosclerosis. These results indicate that the association between the liver

  2. [Molecular Adsorbent Recirculating System in liver function replacement therapy].

    PubMed

    Marangoni, R

    2005-01-01

    The molecular adsorbent recirculating system (MARS) method removes from the blood catabolites either free in the plasma water such as uremic toxins and ammonia, taking advantage of dialysis or free albumin bound ones, like hepatic toxins, transferring them from the albumin in the blood to the albumin circulating in a closed loop where toxins are removed by adsorbtion on resins (charcoal and ion exchange resin). The efficacy of the method in removing the hepatic toxins either in the acute or in the acute on chronic liver failure is demonstrated in numerous studies. Based on these findings, 10 patients affected by acute on chronic liver failure were treated. The results demonstrated that the method, powerfully removing ammonia, bilirubin and bile acids (taken as method efficacy markers), reduced the blood concentrations of these molecules remarkably; allowing the elimination of the refractory pruritus (due to the lowering of plasma bile acid levels), an almost constant symptom in chronic liver diseases, especially with cholestasis, and improves other parameters (cholinesterase, alkaline phosphatase and prothrombin activity). These results agree with those reported in the literature concerning the efficacy of MARS in the replacement of the liver detoxifying function.

  3. Quantitative comparison of transient elastography (TE), shear wave elastography (SWE) and liver biopsy results of patients with chronic liver disease.

    PubMed

    Kim, Hyun-Jin; Lee, Hae-Kag; Cho, Jae-Hwan; Yang, Han-Jun

    2015-08-01

    [Purpose] The purpose of this study was to carry out a comparitive analysis of hepatic fibrosis results of the liver hardness of patients with chronic liver disease as measured by elastography (TE), shear wave elastography (SWE), and liver biopsy. [Subjects and Methods] This study was a retrospective analysis of 304 patients who underwent SWE and TE before and after liver biopsy, taken from among patients who had been checked for liver fibrosis by liver biopsy between August 2013 and August 2014. We used receiver operating characteristic (ROC) curve to prove the diagnostic significance of liver stiffness, and then analyzed the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of SWE and TE, as well as the kappa index through cross-analysis of SWE, TE, and liver biopsy. [Results] For liver hardness, the sensitivity of SWE was 84.39%, the specificity of SWE was 97.92%, the accuracy of SWE was 87.33%, the positive predictive value of SWE was 99.32%, and the negative predictive value of SWE was 63.51%. The sensitivity of TE was 94.80%, the specificity of TE was 77.08%, the accuracy of TE was 90.95%, the positive predictive value of TE was 93.97%, and the negative predictive value of TE was 80.43%. [Conclusion] It is our opinion that SWE and TE are non-invasive methods that are more effective than the invasive methods used for diagnosing liver hardness. Invasive methods cover only a section of liver tissue, and are more likely to cause side effects during biopsy.

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

    PubMed

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

    2016-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  6. Redox Control of Liver Function in Health and Disease

    PubMed Central

    Marí, Montserrat; Colell, Anna; Morales, Albert; von Montfort, Claudia; Garcia-Ruiz, Carmen

    2010-01-01

    Abstract Reactive oxygen species (ROS), a heterogeneous population of biologically active intermediates, are generated as by-products of the aerobic metabolism and exhibit a dual role in biology. When produced in controlled conditions and in limited quantities, ROS may function as signaling intermediates, contributing to critical cellular functions such as proliferation, differentiation, and cell survival. However, ROS overgeneration and, particularly, the formation of specific reactive species, inflicts cell death and tissue damage by targeting vital cellular components such as DNA, lipids, and proteins, thus arising as key players in disease pathogenesis. Given the predominant role of hepatocytes in biotransformation and metabolism of xenobiotics, ROS production constitutes an important burden in liver physiology and pathophysiology and hence in the progression of liver diseases. Despite the recognized role of ROS in disease pathogenesis, the efficacy of antioxidants as therapeutics has been limited. A better understanding of the mechanisms, nature, and location of ROS generation, as well as the optimization of cellular defense strategies, may pave the way for a brighter future for antioxidants and ROS scavengers in the therapy of liver diseases. Antioxid. Redox Signal. 12, 1295—1331. PMID:19803748

  7. Quantitation of human MAO A and B in liver, intestine and placenta: Reassessment of activity

    SciTech Connect

    Riley, L.A.

    1989-01-01

    Monoamine oxidases (MAO) oxidize a variety of exogenous and endogenous amines including neurotransmitters such as serotonin, dopamine and norepinephrine as well as the potent dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). The two forms of MAO (A and B) differ in molecular weight and inhibitor selectivity, and are differentially expressed in the nervous system and many other tissues. Although some substrates are preferentially oxidized by one form of MAO, substrates that can be oxidized by only one MAO form have not been reported. How well each MAO oxidizes various substrates has not been thoroughly characterized because of difficulties in separating and quantitating MAO A and B active sites. By immunoblotting SDS-polyacrylamide gels of mitochondrial extracts with monoclonal antibodies specific for each form of MAO, MAO B protein was detected in intestine and placenta, tissues that have been reported to contain MAO A activity. An improved procedure was developed for quantitating the ratio and amounts of MAO A and B active sites, using the ligand ({sup 3}H)-pargyline to label MAO and specific monoclonal antibodies to separate MAO A from B. Data from liver, placenta and platelets were used to re-evaluate the molecular activity of both MAO A and B for six commonly studied substrates.

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

    PubMed

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

    1979-01-01

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

  9. Warmer ambient temperatures depress liver function in a mammalian herbivore.

    PubMed

    Kurnath, Patrice; Dearing, M Denise

    2013-10-23

    Diet selection in mammalian herbivores is thought to be mainly influenced by intrinsic factors such as nutrients and plant secondary compounds, yet extrinsic factors like ambient temperature may also play a role. In particular, warmer ambient temperatures could enhance the toxicity of plant defence compounds through decreased liver metabolism of herbivores. Temperature-dependent toxicity has been documented in pharmacology and agriculture science but not in wild mammalian herbivores. Here, we investigated how ambient temperature affects liver metabolism in the desert woodrat, Neotoma lepida. Woodrats (n = 21) were acclimated for 30 days to two ambient temperatures (cool = 21°C, warm = 29°C). In a second experiment, the temperature exposure was reduced to 3.5 h. After temperature treatments, animals were given a hypnotic agent and clearance time of the agent was estimated from the duration of the hypnotic state. The average clearance time of the agent in the long acclimation experiment was 45% longer for animals acclimated to 29°C compared with 21°C. Similarly, after the short exposure experiment, woodrats at 29°C had clearance times 26% longer compared with 21°C. Our results are consistent with the hypothesis that liver function is reduced at warmer environmental temperatures and may provide a physiological mechanism through which climate change affects herbivorous mammals.

  10. Warmer ambient temperatures depress liver function in a mammalian herbivore

    PubMed Central

    Kurnath, Patrice; Dearing, M. Denise

    2013-01-01

    Diet selection in mammalian herbivores is thought to be mainly influenced by intrinsic factors such as nutrients and plant secondary compounds, yet extrinsic factors like ambient temperature may also play a role. In particular, warmer ambient temperatures could enhance the toxicity of plant defence compounds through decreased liver metabolism of herbivores. Temperature-dependent toxicity has been documented in pharmacology and agriculture science but not in wild mammalian herbivores. Here, we investigated how ambient temperature affects liver metabolism in the desert woodrat, Neotoma lepida. Woodrats (n = 21) were acclimated for 30 days to two ambient temperatures (cool = 21°C, warm = 29°C). In a second experiment, the temperature exposure was reduced to 3.5 h. After temperature treatments, animals were given a hypnotic agent and clearance time of the agent was estimated from the duration of the hypnotic state. The average clearance time of the agent in the long acclimation experiment was 45% longer for animals acclimated to 29°C compared with 21°C. Similarly, after the short exposure experiment, woodrats at 29°C had clearance times 26% longer compared with 21°C. Our results are consistent with the hypothesis that liver function is reduced at warmer environmental temperatures and may provide a physiological mechanism through which climate change affects herbivorous mammals. PMID:24046878

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

    PubMed

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

    1987-01-01

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

  12. Development of quantitative neuropsychological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria-multicenter collaborative study in Japanese.

    PubMed

    Kato, Akinobu; Kato, Motoichiro; Ishii, Hiromasa; Ichimiya, Yosuke; Suzuki, Kazuyuki; Kawasaki, Hironaka; Yamamoto, Shin-Ichiro; Kumashiro, Ryukichi; Yamamoto, Kyosuke; Kawamura, Naohiro; Hayashi, Naoaki; Matsuzaki, Shohei; Terano, Akira; Okita, Kiwamu; Watanabe, Akiharu

    2004-10-01

    At present, there are no generally accepted diagnostic criteria or methods for subclinical hepatic encephalopathy (SHE) associated with liver cirrhosis. We therefore developed an easily conducted computer-aided quantitative neuropsychiatric function test system for use in routine medical practice. We established normal values in healthy Japanese subjects and determined differences between healthy persons and liver cirrhosis patients without clinical encephalopathy in a multi-center clinical trial. The test system consists of eight tests: number connection tests A and B, a figure position test, a digit symbol test, a block design test, and reaction time tests A, B and C. The test results were affected by age, but not by gender or facility. No learning effect was noted. The results were therefore reported by 5-year quartile ranges and differences were evaluated between 542 healthy subjects and 292 cirrhotic patients. When the cut-off value was set at the 10th/90th percentile of the results in healthy subjects, the results of each of the 8 tests were abnormal in about 25% of cirrhotic patients, and at least 1 of the 8 tests gave values greater than the 10th/90th percentile cut-off value in 58.2% of the 292 liver cirrhosis patients. SHE patients were thought to be included in these 58.2% of patients. The developed test makes it possible to quantitatively assess neuropsychiatric function, and the results obtained can be used as a basis for the diagnosis of SHE.

  13. Structure and function of sinusoidal lining cells in the liver.

    PubMed

    Wisse, E; Braet, F; Luo, D; De Zanger, R; Jans, D; Crabbé, E; Vermoesen, A

    1996-01-01

    The hepatic sinusoid harbors 4 different cells: endothelial cells (100, 101), Kupffer cells (96, 102, 103), fat-storing cells (34, 51, 93), and pit cells (14, 107, 108). Each cell type has its own specific morphology and functions, and no transitional stages exist between the cells. These cells have the potential to proliferate locally, either in normal or in special conditions, that is, experiments or disease. Sinusoidal cells from a functional unit together with the parenchymal cells. Isolation protocols exist for all sinusoidal cells. Endothelial cells filter the fluids, exchanged between the sinusoid and the space of Disse through fenestrae (100), which measure 175 nm in diameter and are grouped in sieve plates. Fenestrae occupy 6-8% of the surface (106). No intact basal lamina is present under these cells (100). Various factors change the number and diameter of fenestrae [pressure, alcohol, serotonin, and nicotin; for a review, see Fraser et al (32)]. These changes mainly affect the passage of lipoproteins, which contain cholesterol and vitamin A among other components. Fat-storing cells are pericytes, located in the space of Disse, with long, contractile processes, which probably influence liver (sinusoidal) blood flow. Fat-storing cells possess characteristic fat droplets, which contain a large part of the body's depot of vitamin A (91, 93). These cells play a major role in the synthesis of extracellular matrix (ECM) (34, 39-41). Strongly reduced levels of vitamin A occur in alcoholic livers developing fibrosis (56). Vitamin A deficiency transforms fat-storing cells into myofibroblast-like cells with enhanced ECM production (38). Kupffer cells accumulate in periportal areas. They specifically endocytose endotoxin (70), which activates these macrophages. Lipopolysaccharide, together with interferon gamma, belongs to the most potent activators of Kupffer cells (28). As a result of activation, these cells secrete oxygen radicals, tumor necrosis factor

  14. Quantitative reactivity profiling predicts functional cysteines in proteomes

    PubMed Central

    Weerapana, Eranthie; Wang, Chu; Simon, Gabriel M.; Richter, Florian; Khare, Sagar; Dillon, Myles B.D.; Bachovchin, Daniel A.; Mowen, Kerri; Baker, David; Cravatt, Benjamin F.

    2010-01-01

    Cysteine is the most intrinsically nucleophilic amino acid in proteins, where its reactivity is tuned to perform diverse biochemical functions. The absence of a consensus sequence that defines functional cysteines in proteins has hindered their discovery and characterization. Here, we describe a proteomics method to quantitatively profile the intrinsic reactivity of cysteine residues en masse directly in native biological systems. Hyperreactivity was a rare feature among cysteines and found to specify a wide range of activities, including nucleophilic and reductive catalysis and sites of oxidative modification. Hyperreactive cysteines were identified in several proteins of uncharacterized function, including a residue conserved across eukaryotic phylogeny that we show is required for yeast viability and involved in iron-sulfur protein biogenesis. Finally, we demonstrate that quantitative reactivity profiling can also form the basis for screening and functional assignment of cysteines in computationally designed proteins, where it discriminated catalytically active from inactive cysteine hydrolase designs. PMID:21085121

  15. Liver reserve function assessment by acoustic radiation force impulse imaging

    PubMed Central

    Sun, Xiao-Lan; Liang, Li-Wei; Cao, Hui; Men, Qiong; Hou, Ke-Zhu; Chen, Zhen; Zhao, Ya-E

    2015-01-01

    AIM: To evaluate the utility of liver reserve function by acoustic radiation force impulse (ARFI) imaging in patients with liver tumors. METHODS: Seventy-six patients with liver tumors were enrolled in this study. Serum biochemical indexes, such as aminotransferase (ALT), aspartate aminotransferase (AST), serum albumin (ALB), total bilirubin (T-Bil), and other indicators were observed. Liver stiffness (LS) was measured by ARFI imaging, measurements were repeated 10 times, and the average value of the results was taken as the final LS value. Indocyanine green (ICG) retention was performed, and ICG-K and ICG-R15 were recorded. Child-Pugh (CP) scores were carried out based on patient’s preoperative biochemical tests and physical condition. Correlations among CP scores, ICG-R15, ICG-K and LS values were observed and analyzed using either the Pearson correlation coefficient or the Spearman rank correlation coefficient. Kruskal-Wallis test was used to compare LS values of CP scores, and the receiver-operator characteristic (ROC) curve was used to analyze liver reserve function assessment accuracy. RESULTS: LS in the ICG-R15 10%-20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant (2.19 ± 0.27 vs 1.59 ± 0.32, P < 0.01). LS in the ICG-R15 > 20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant (2.92 ± 0.29 vs 1.59 ± 0.32, P < 0.01). The LS value in patients with CP class A was lower than in patients with CP class B (1.57 ± 0.34 vs 1.86 ± 0.27, P < 0.05), while the LS value in patients with CP class B was lower than in patients with CP class C (1.86 ± 0.27 vs 2.47 ± 0.33, P < 0.01). LS was positively correlated with ICG-R15 (r = 0.617, P < 0.01) and CP score (r = 0.772, P < 0.01). Meanwhile, LS was negatively correlated with ICG-K (r = -0.673, P < 0.01). AST, ALT and T-Bil were positively correlated with LS, while ALB was negatively

  16. Controlled therapy by imaging of functional structures of intact liver

    NASA Astrophysics Data System (ADS)

    Wang, W.; Zhuang, Feng Y.; Ruan, G.; Kakihana, Yasuyuki; Krug, A.; Kessler, Manfred D.

    2000-04-01

    Ligustrazine, a Chinese herb medicine has been used to treat the diseases of cardiovascular and cerebral vascular diseases in China by Chinese traditional physicians or many years. Recently, results showed that ligustrazine is a powerful hepatic vasodilator. It can greatly change the blood supply of the tissues. Due to micro-optical tissue sensor developed recently it became possible to image functional structures of tissue on the level of intact blood capillaries. In our experiment we used the Oxyscan in order to study the effect of Ligustrazine on the oxygen supply of rat liver.

  17. [Effect of polydatin on miR-214 expression and liver function in ApoE-/- mice].

    PubMed

    Zhou, Feng-Hua; Wen, Zi-Yun; He, Ze-Huai; Li, Mei; Yin, Qiong-Li; Shi, Cheng-Gang; Cheng, Cai-Lian

    2016-06-01

    To study the effect of polydatin on the expression level of miR-214 and liver function in atherosclerotic mice. Forty male ApoE(-/-) mice were randomly allocated into 4 groups (n=10), namely the model group, low- and high-dose polydatin groups, and simvastin group, with 10 male C57BL/6J mice serving as the normal control group. Mouse models of atherosclerosis were established by feeding the ApoE(-/-) mice with a high-fat diet. After 12 weeks of treatment, blood levels of glucose, lipids, AST, and ALT and the contents of T-SOD and MDA in the liver tissue were detected. The pathologies of the liver were examined with HE staining, and miR-214 expression in the liver was detected using quantitative real-time PCR. Compared with the normal control mice, the mice in the model group showed significantly increased blood glucose, serum TC, TG, LDL-C, ALT, and AST levels, and MDA contents in the liver (P<0.01), with significantly decreased serum HDL-C level and SOD and miR-214 levels in liver (P<0.01). Polydatin treatment significantly ameliorated such changes in blood glucose, serum ALT, AST, TC, TG, LDL-C, and HDL-C levels, and MDA, SOD, and miR-214 contents in liver tissue (P<0.05). s Polydatin can reduce blood glucose and lipid levels and protect the liver function in atherosclerotic mice possibly by up-regulating the expression of miR-214 and T-SOD and down-regulating MDA in the liver.

  18. Delayed Liver Function Impairment Secondary to Interferon β-1a Use in Multiple Sclerosis

    PubMed Central

    Liao, Ming-Feng; Yen, Su-Chen; Chun-Yen, Lin; Rong-Kuo, Lyu

    2013-01-01

    Interferon β-1a is a widely used immunomodulation treatment for multiple sclerosis. Liver function impairment is a common side effect and usually develops in the first 6 months after interferon use. Here, we describe 2 multiple sclerosis patients who developed delayed liver function impairment 5 years after receiving interferon β-1a treatment. Their liver function recovered after discontinuing interferon use, and further detailed hepatological evaluations excluded other etiologies of liver function impairment. Our case reports illustrate that liver function impairment induced by interferon β-1a can be delayed for 5 years after starting treatment and, probably, this is an idiosyncratic reaction. Regular liver function monitoring in multiple sclerosis patients who receive interferon β is necessary even after the first 6 months of treatment, especially in those patients with concomitant use of other liver-toxic medications. PMID:23904853

  19. Liver Progenitors Isolated from Adult Healthy Mouse Liver Efficiently Differentiate to Functional Hepatocytes In Vitro and Repopulate Liver Tissue.

    PubMed

    Tanimizu, Naoki; Ichinohe, Norihisa; Ishii, Masayuki; Kino, Junichi; Mizuguchi, Toru; Hirata, Koichi; Mitaka, Toshihiro

    2016-12-01

    It has been proposed that tissue stem cells supply multiple epithelial cells in mature tissues and organs. However, it is unclear whether tissue stem cells generally contribute to cellular turnover in normal healthy organs. Here, we show that liver progenitors distinct from bipotent liver stem/progenitor cells (LPCs) persistently exist in mouse livers and potentially contribute to tissue maintenance. We found that, in addition to LPCs isolated as EpCAM(+) cells, liver progenitors were enriched in CD45(-) TER119(-) CD31(-) EpCAM(-) ICAM-1(+) fraction isolated from late-fetal and postnatal livers. ICAM-1(+) liver progenitors were abundant by 4 weeks (4W) after birth. Although their number decreased with age, ICAM-1(+) liver progenitors existed in livers beyond that stage. We established liver progenitor clones derived from ICAM-1(+) cells between 1 and 20W and found that those clones efficiently differentiated into mature hepatocytes (MHs), which secreted albumin, eliminated ammonium ion, stored glycogen, and showed cytochrome P450 activity. Even after long-term culture, those clones kept potential to differentiate to MHs. When ICAM-1(+) clones were transplanted into nude mice after retrorsine treatment and 70% partial hepatectomy, donor cells were incorporated into liver plates and expressed hepatocyte nuclear factor 4α, CCAAT/enhancer binding protein α, and carbamoylphosphate synthetase I. Moreover, after short-term treatment with oncostatin M, ICAM-1(+) clones could efficiently repopulate the recipient liver tissues. Our results indicate that liver progenitors that can efficiently differentiate to MHs exist in normal adult livers. Those liver progenitors could be an important source of new MHs for tissue maintenance and repair in vivo, and for regenerative medicine ex vivo. Stem Cells 2016;34:2889-2901.

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

    PubMed

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

    2011-01-01

    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. 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. 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.

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

    PubMed Central

    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

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

    SciTech Connect

    Choi, W; Wang, J; Lu, W; Kang, M

    2015-06-15

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

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

    PubMed

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

    2009-11-01

    The purpose of our study was to compare signal characteristics and image qualities of MR imaging at 3.0T and 1.5T in patients with diffuse parenchymal liver disease. 25 consecutive patients with diffuse parenchymal liver disease underwent abdominal MR imaging at both 3.0T and 1.5T within a 6-month interval. A retrospective study was conducted to obtain quantitative and qualitative data from both 3.0T and 1.5T MRI. Quantitative image analysis was performed by measuring the signal-to-noise ratios (SNRs) and the contrast-to-noise ratios (CNRs) by the Students t-test. Qualitative image analysis was assessed by grading each sequence on a 3- and 4-point scale, regarding the presence of artifacts and image quality, respectively. Statistical analysis consisted of the Wilcoxon signed-rank test. the mean SNRs and CNRs of the liver parenchyma and the portal vein were significantly higher at 3.0T than at 1.5T on portal and equilibrium phases of volumetric interpolated breath-hold examination (VIBE) images (P<0.05). The mean SNRs were significantly higher at 3.0T than at 1.5T on T1-weighted spoiled gradient echo (SGE) images (P<0.05). However, there were no significantly differences on T2-weighted short-inversion-time inversion recovery (STIR) images. Overall image qualities of the 1.5T non-contrast T1- and T2-weighted sequences were significantly better than 3.0T (P<0.01). In contrast, overall image quality of the 3.0T post-gadolinium VIBE sequence was significantly better than 1.5T (P<0.01). MR imaging of post-gadolinium VIBE sequence at 3.0T has quantitative and qualitative advantages of evaluating for diffuse parenchymal liver disease.

  4. The qualitative and quantitative image analysis of MR imaging in patients with acute-on-chronic liver failure.

    PubMed

    Kang, Tae Wook; Kim, Mimi; Kim, Young Kon; Kim, Seong Hyun; Sinn, Dong Hyun; Kim, Kyunga

    2017-08-10

    To evaluate the distinctive features of ACLF and chronic liver disease (CLD) on MR images using quantitative and qualitative analyses. Twelve patients with ACLF and 36 patients with CLD who had undergone MR images were included. MR imaging findings from both groups were assessed. Gallbladder edema, esophageal varix, and ascites were significantly more prevalent in the ACLF group (all P-values <0.05). The liver to muscle SI ratio on T2-WI was significantly higher in the ACLF group (P=0.002). MR imaging findings could be helpful in differentiating between patients with ACLF and those with CLD. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease

    PubMed Central

    Bell, Catherine C.; Hendriks, Delilah F. G.; Moro, Sabrina M. L.; Ellis, Ewa; Walsh, Joanne; Renblom, Anna; Fredriksson Puigvert, Lisa; Dankers, Anita C. A.; Jacobs, Frank; Snoeys, Jan; Sison-Young, Rowena L.; Jenkins, Rosalind E.; Nordling, Åsa; Mkrtchian, Souren; Park, B. Kevin; Kitteringham, Neil R.; Goldring, Christopher E. P.; Lauschke, Volker M.; Ingelman-Sundberg, Magnus

    2016-01-01

    Liver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability, and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI. PMID:27143246

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

    PubMed Central

    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

  7. Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function.

    PubMed

    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

    2008-06-01

    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. Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m(2)) 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-alpha (TNF-alpha), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting 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. CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD.

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

    PubMed

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

    2015-03-01

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

  9. Breath-hold black blood quantitative T1rho imaging of liver using single shot fast spin echo acquisition

    PubMed Central

    Chan, Queenie; Wáng, Yì-Xiáng J.

    2016-01-01

    Background Liver fibrosis is a key feature in most chronic liver diseases. T1rho magnetic resonance imaging is a potentially important technique for noninvasive diagnosis, severity grading, and therapy monitoring of liver fibrosis. However, it remains challenging to perform robust T1rho quantification of liver on human subjects. One major reason is that the presence of rich blood signal in liver can cause artificially high T1rho measurement and makes T1rho quantification susceptible to motion. Methods A pulse sequence based on single shot fast/turbo spin echo (SSFSE/SSTSE) acquisition, with theoretical analysis and simulation based on the extended phase graph (EPG) algorithm, was presented for breath-hold single slice quantitative T1rho imaging of liver with suppression of blood signal. The pulse sequence was evaluated in human subjects at 3.0 T with 500 Hz spinlock frequency and time-of-spinlock (TSL) 0, 10, 30 and 50 ms. Results Human scan demonstrated that the entire T1rho data sets with four spinlock time can be acquired within a single breath-hold of 10 seconds with black blood effect. T1rho quantification with suppression of blood signal results in significantly reduced T1rho value of liver compared to the results without blood suppression. Conclusions A signal-to-noise ratio (SNR) efficient pulse sequence was reported for T1rho quantification of liver. The black blood effect, together with a short breath-hold, mitigates the risk of quantification errors as would occur in the conventional methods. PMID:27190769

  10. Myocardial and liver iron status using a fast T*2 quantitative MRI (T*2qMRI) technique.

    PubMed

    Maris, Thomas G; Papakonstantinou, Olympia; Chatzimanoli, Vasiliki; Papadakis, Alekos; Pagonidis, Konstantinos; Papanikolaou, Nickolas; Karantanas, Apostolos; Gourtsoyiannis, Nicholas

    2007-04-01

    This work demonstrates the use of a fast and precise methodology for evaluating myocardial and liver iron status in multitransfused thalassemic patients by means of a fast T(2) (*) quantitative MRI (T(2) (*)qMRI) technique. Myocardial and liver T(2) (*) values were calculated in 48 thalassemic patients and 21 normal subjects on a 1.5T MRI system using a breath-hold 2D single-slice multiecho gradient-echo (MEGRE) sequence (16 echoes, TR/TE1/TE16/FA = 160/2.7/37.65 ms/25 degrees ). No ECG gating was used. Myocardial T(2) (*), liver T(2) (*), and myocardial to muscle (CR/MS) and liver to muscle (LV/MS) T(2) (*) ratios were correlated with serum ferritin concentration (SFC) levels for all patients. Significant differences in myocardial and liver mean T(2) (*), CR/MS, and LV/MS T(2) (*) values between patients and normal subjects were found (P < 0.0005). Differences in paraspinous muscle mean T(2) (*) values between patients and normal subjects were not significant. Myocardial T(2) (*) and CR/MS T(2) (*) values were not correlated with SFC levels. Liver T(2) (*) and LV/MS T(2) (*) values were significantly correlated with SFC (r = 0.540, P < 0.0005). Myocardial T(2) (*) and CR/MS T(2) (*) values were not correlated with either liver T(2) (*) or LV/MS T(2) (*) values, respectively. We conclude that myocardial and liver iron deposition can be evaluated using the fast non-ECG-gated T(2) (*)qMRI technique.

  11. Comparison of Liver Function, Emotional Status, and Quality of Life of Living Liver Donors in Taiwan.

    PubMed

    Shen, C-J; Huang, H-L; Chen, K-H; Weng, L-C; Wang, S-Y; Lee, W-C; Chou, H-F; Tsai, H-H

    2016-05-01

    Living donor liver transplantation may put the donor at risk of physical and psychological impacts. Recovery of physical and psychological function as well as quality of life (QOL) in living liver donors warrants investigation. This study aims to examine the recovery of liver function, emotional status, and QOL in living liver donors through a comparison with the general population and reference values. This descriptive, comparative study included 97 living liver donors who underwent surgery from 2008 to 2012 and were divided into 4 groups according to their postoperative period (1 year [n = 31], 2 years [n = 31], 3 years [n = 21], and 4 years above [n = 14]). Data were collected retrospectively in a medical center in northern Taiwan. The mean aspartate aminotransferase level was 20.2-32.1 U/L, the mean alanine aminotransferase level was 14.7-33.5 U/L, and the mean total bilirubin level was 10.8-15.5 μmol/L among the 4 groups. Among donors of the 4 groups, 23.8%-51.6% and 0%-29% were defined as having a mild level of anxiety and depression, respectively. Donors in the 1- and 2-year groups had poorer QOL in the physical function, role physical, vitality, and mental health domains than did the general population of Taiwan (P < .05). Liver function was at normal levels in all 4 groups. The emotional and psychological function of living liver donors should be monitored and health-related QOL should be promoted during the first and second year after liver donation. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed Central

    Zhang, Dong; Song, Xiao-jing; Li, Shun-yue; Wang, Shu-you; Chen, Bing-jun; Bai, Xiao-Dong; Tang, Li-mei

    2016-01-01

    Imaging methods to evaluate hepatic microcirculation (HM) and liver function (LF) by directly monitoring overall liver tissue remain lacking. This study establish imaging methods for LF that combines Laser speckle perfusion imaging (LSPI) and in vivo optical imaging (IVOI) technologies to investigate changes of hepatic microcirculation and reserve function in the animals gavaged with 50% ethanol (15 ml/kg·bw) for a model of acute alcoholic liver injury (ALI), and for evaluation of electroacupuncture (EA) effect. The liver blood perfusion and indocyanine green (ICG) distribution were observe by LSPI and IVOI separately. After EA, the livers were collected to measure the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), thromboxane A (TXA2), prostacyclin (PGI2) and endothelin (ET). The acquisitions of newly established LSPI of liver and ICG in vivo fluorescence imaging (ICG-IVFI), combining the results of other indexes showed: hepatic microcirculation perfusion (HMP) significantly reduced, ICG metabolism reduced, and ALT/AST increased in animal model with acute ALI. EA can reverse these changes. The use of LSPI of liver and ICG-IVFI, which was novel imaging methods for LF established in this study, could display the LF characteristics of ALI and the EA efficacy. PMID:27443832

  13. Liver Function Tests: MedlinePlus Health Topic

    MedlinePlus

    ... Liver Foundation) Liver Panel (American Association for Clinical Chemistry) Diagnosis and Tests Bilirubin Blood Test (National Library ... Spanish Specifics Albumin Test (American Association for Clinical Chemistry) ALP (Alkaline Phosphatase) Test (American Association for Clinical ...

  14. Preliminary study on liver function changes after trisectionectomy with versus without prior portal vein embolization.

    PubMed

    Malinowski, Maciej; Lock, Johan Friso; Seehofer, Daniel; Gebauer, Bernhard; Schulz, Antje; Demirel, Lina; Bednarsch, Jan; Stary, Victoria; Neuhaus, Peter; Stockmann, Martin

    2016-09-01

    Post-hepatectomy liver failure (PHLF) is the major risk factor for mortality after hepatectomy. Preoperative planning of the future liver remnant volume reduces PHLF rates; however, future liver remnant function (FLR-F) might have an even stronger predictive value. In this preliminary study, we used a new method to calculate FLR-F by the LiMAx test and computer tomography-assisted volumetric-analysis to visualize liver function changes after portal vein embolization (PVE) before extended hepatectomy. The subjects included patients undergoing extended right hepatectomy either directly (NO-PVE group) or after PVE (PVE group). Computed tomography (CT) scan and liver function tests (LiMAx) were done before PVE and preoperatively. FLR-F was calculated and correlated with the postoperative liver function. There were 12 patients in the NO-PVE group and 19 patients in the PVE group. FLR-F and postoperative liver function correlated significantly in both groups (p = 0.036, p = 0.011), although postoperative liver function was slightly overestimated, at 32 and 45 µg/kg/min, in the NO-PVE and PVE groups, respectively. LiMAx value did not change after PVE. Volume-function analysis using LiMAx and CT scan enables us to reliably predict early postoperative liver function. Global enzymatic liver function measured by the LiMAx test did not change after PVE, confirming that liver function distribution in the liver stays constant after PVE. An overestimation of FLR-F is needed to compensate for the intraoperative liver injury that occurs in patients undergoing extended hepatectomy.

  15. Validation of a simple liquid chromatographic method for determination and quantitation of residual ivermectin and doramectin in pig liver.

    PubMed

    Knold, Lone; Reitov, Marianne; Mortensen, Anna Birthe; Hansen-Møller, Jens

    2002-01-01

    A rapid and quantitative method for the extraction, derivatization, and liquid chromatography with fluorescence detection of ivermectin (IVM) and doramectin (DOM) residues in porcine liver was developed and validated. IVM and DOM were extracted from the liver samples with acetonitrile, the supernatant was evaporated to dryness at 37 degrees C under nitrogen, and the residue was reconstituted in 1-methylimidazole solution. After 2 min at room temperature, IVM and DOM were converted to a fluorescent derivative and then separated on a Hypersil ODS column. The derivatives of IVM and DOM were detected and quantitated with high specificity by fluorescence (excitation: 365 nm, emission: 475 nm). Abamectin was used as an internal standard. The mean extraction efficiencies from fortified samples (15 ng/g) were 75% for IVM and 70% for DOM. The limit of detection was 0.8 ng/g for both IVM and DOM.

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

    PubMed

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

    2009-04-01

    To compare the quantitative and qualitative image quality intra-individually, at 1.5 and 3.0 Tesla (T) in patients with chronic liver diseases. The study group included 24 consecutive patients (17 males, 7 females; mean age +/- standard deviation 56.5 +/- 11.5) who had chronic liver diseases and underwent abdominal MRI for the liver evaluation at both 1.5 and 3.0 T within a 4-month period. All MRI studies were retrospectively evaluated quantitatively and qualitatively. Quantitative analysis was performed by measuring signal to noise ratio (SNR) on various abdominal organs. Qualitative analysis was performed by two reviewers to assess image quality, artifacts, and imaging findings of chronic liver diseases. Quantitative and qualitative analyses findings were compared between 1.5 and 3.0 T using the paired Student t-test and Wilcoxon signed rank test, respectively. The statistically significant increase in SNRs in various abdominal tissues ranged from 1.3- to 3.5-fold at 3.0 T compared to 1.5 T. Three-dimensional gradient echo (3D-GE) sequences demonstrated significantly higher image quality at 3.0 T (P < 0.01), whereas precontrast spoiled gradient echo (SGE) sequences demonstrated significantly higher image quality at 1.5 T (P < 0.01). T2-weighted sequences did not show any significant difference in image quality between 1.5 and 3.0 T (P > 0.05). The SNRs of various abdominal tissues demonstrated significant increases at 3.0 T. The image quality of 3D-GE sequences was higher at 3.0 T, whereas the image quality of precontrast SGE sequences was higher at 1.5T.

  17. Learning Quantitative Sequence-Function Relationships from Massively Parallel Experiments

    NASA Astrophysics Data System (ADS)

    Atwal, Gurinder S.; Kinney, Justin B.

    2016-03-01

    A fundamental aspect of biological information processing is the ubiquity of sequence-function relationships—functions that map the sequence of DNA, RNA, or protein to a biochemically relevant activity. Most sequence-function relationships in biology are quantitative, but only recently have experimental techniques for effectively measuring these relationships been developed. The advent of such "massively parallel" experiments presents an exciting opportunity for the concepts and methods of statistical physics to inform the study of biological systems. After reviewing these recent experimental advances, we focus on the problem of how to infer parametric models of sequence-function relationships from the data produced by these experiments. Specifically, we retrace and extend recent theoretical work showing that inference based on mutual information, not the standard likelihood-based approach, is often necessary for accurately learning the parameters of these models. Closely connected with this result is the emergence of "diffeomorphic modes"—directions in parameter space that are far less constrained by data than likelihood-based inference would suggest. Analogous to Goldstone modes in physics, diffeomorphic modes arise from an arbitrarily broken symmetry of the inference problem. An analytically tractable model of a massively parallel experiment is then described, providing an explicit demonstration of these fundamental aspects of statistical inference. This paper concludes with an outlook on the theoretical and computational challenges currently facing studies of quantitative sequence-function relationships.

  18. Valproate-induced hyperammonemic encephalopathy with normal liver function.

    PubMed

    Rath, Amitav; Naryanan, T Jaishree; Chowdhary, G V S; Murthy, J M K

    2005-06-01

    Hyperammonemic encephalopathy with normal liver function is an uncommon serious adverse effect of valproate therapy. We retrospectively analyzed the case records of 5 patients of epilepsy on valproate with hyperammonemic encephalopathy. Of the 5 patients, 3 were on monotherapy. The mean valproate dose was 1250 mg/day and the duration of therapy ranged between 4 and 90 days. Alteration in the sensorium was the presenting clinical feature. The risk factors included high initial dose (2), long-term valproate therapy (1), and long-term valproate therapy with concomitant topiramate (1). There was good correlation between the fall in serum ammonia levels and clinical improvement. Hyperammonemic encephalopathy should be suspected in patients on valproate with altered sensorium. Response to treatment is rewarding.

  19. Quantitative Radiology: Automated CT Liver Volumetry Compared With Interactive Volumetry and Manual Volumetry

    PubMed Central

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

    2014-01-01

    OBJECTIVE 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. MATERIALS AND METHODS 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. RESULTS The average interactive liver volume was 1553 ± 343 cm3, and the average automated liver volume was 1520 ± 378 cm3. The average manual volume was 1486 ± 343 cm3. 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 < 0.05). CONCLUSION Both interactive and automated volumetry are accurate for measuring liver volume with CT, but automated volumetry is substantially more efficient. PMID:21940543

  20. Adrenal function in cats with cholestatic liver disease.

    PubMed

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

    2017-01-01

    Cats with cholestatic liver disease experience significant morbidity and mortality when they undergo invasive procedures under anesthesia. Although inadequate adrenal response might account for these outcomes, adrenal function in cats with cholestatic liver disease has not been documented, to our knowledge. The goal of our study was to describe adrenal function in these cats. Twenty-seven cats with a serum bilirubin >230 µmol/L (3 mg/dL) and serum alanine aminotransferase >2 times the upper limit of normal had pre- and 60-min post-adrenocorticotropic hormone (ACTH) cortisol analysis after administration of 5 µg/kg cosyntropin intravenously. The change in cortisol concentrations (delta cortisol) was calculated. Pre- and post-ACTH cortisol concentrations were compared to reference values. Pre-ACTH, post-ACTH, and delta cortisol values were compared between cats surviving to discharge or for 30 d postdischarge. Mean pre-ACTH cortisol levels (205 ± 113 nmol/L [7.4 ± 4.2 µg/dL]) and post-ACTH cortisol levels (440 ± 113 nmol/L [15.9 ± 4.1 g/dL]) in cholestatic cats were significantly greater than reference values in clinically normal cats. There was no association of pre- or post-ACTH cortisol with survival. Cats with a delta cortisol <179 nmol/L (6.5 µg/dL) were more likely to be non-survivors at 30 d post-discharge ( p = 0.037) than cats with delta cortisol >179 nmol/L (6.5 µg/dL). Results indicate that cats with cholestasis have high basal and ACTH-stimulated cortisol values. A delta cortisol <179 nmol/L (6.5 µg/dL) defines a population of cats that have decreased 30-d survival.

  1. Quantitative studies on the in vitro metabolic activation of dimethylnitrosamine by rat liver postmitochondrial supernatant

    SciTech Connect

    Doolittle, D.J.; Goodman, J.I.

    1984-08-01

    The metabolic activation of dimethylnitrosamine (DMN) to mutagenic and/or cytotoxic intermediates in vitro has been characterized and the relationship between DMN demethylase and ethoxyresorufin-O-deethylase (EROD) or ethylmorphine-N-demethylase (EMND) has been evaluated. A mammalian assay system which uses the postmitochondrial supernatant (S-15 fraction) prepared from a rat liver homogenate as an enzyme source and V79 Chinese hamster cells as targets for chemically induced damage was used. The enzyme pattern of the S-15 fraction was altered by pretreatment of experimental animals in vivo and/or by the use of enzyme inhibitors in vitro. The results of these studies indicate that the concentration of S-15 fraction in the reaction mixture can markedly influence the degree of DMN-induced cytotoxicity when it is metabolized in vitro and that the degree of DMN-induced cytotoxicity and mutagenicity are linearly related. The degree of cytotoxicity and mutagenicity induced in V79 cells by DMN does not correlate with EROD activity (a measure of 3-methylcholanthrene-inducible mixed-function oxidases) nor with EMND activity (a measure of phenobarbital-inducible mixed function oxidases) in the S-15 fraction. 28 references, 4 figures.

  2. Quantitative functional MRI: concepts, issues and future challenges.

    PubMed

    Pike, G Bruce

    2012-08-15

    Since its inception 20 years ago, functional magnetic resonance imaging (fMRI) of the human brain based on the blood oxygenation level dependent (BOLD) contrast phenomenon has proliferated and matured. Today it is the predominant functional brain imaging modality with the majority of applications being in basic cognitive neuroscience where it has primarily been used as a tool to localize brain activity. While the magnitude of the BOLD response is often used in these studies as a surrogate for the level of neuronal activity, the link between the two is, in fact, quite indirect. The BOLD response is dependent upon hemodynamic (blood flow and volume) and metabolic (oxygen consumption) responses as well as acquisition details. Furthermore, the relationship between neuronal activity and the hemodynamic response, termed neurovascular coupling, is itself complex and incompletely understood. Quantitative fMRI techniques have therefore been developed to measure the hemodynamic and metabolic responses to modulations in brain activity. These methods have not only helped clarify the behaviour and origins of the BOLD signal under normal physiological conditions but they have also provided a potentially valuable set of tools for exploring pathophysiological conditions. Such quantitative methods will be critical to realize the potential of fMRI in a clinical context, where simple BOLD measurements cannot be uniquely interpreted, and to enhance the power of fMRI in basic neuroscience research. In this article, recent advances in human quantitative fMRI methods are reviewed, outstanding issues discussed and future challenges and opportunities highlighted.

  3. Cannabinoid receptor type 2 functional variant influences liver damage in children with non-alcoholic fatty liver disease.

    PubMed

    Rossi, Francesca; Bellini, Giulia; Alisi, Anna; Alterio, Arianna; Maione, Sabatino; Perrone, Laura; Locatelli, Franco; Miraglia del Giudice, Emanuele; Nobili, Valerio

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of disease ranging from simple steatosis to inflammatory steatohepatitis (NASH) with different degrees of fibrosis that can ultimately progress to cirrhosis. Accumulating evidence suggests the involvement of the endocannabinoid-system in liver disease and related complications. In particular, hepatoprotective properties for Cannabinoid Receptor type 2 (CB2) have been shown both through experimental murine models of liver injury and association study between a CB2 functional variant, Q63R, and liver enzymes in Italian obese children with steatosis.Here, in order to clarify the role of CB2 in severity of childhood NAFLD, we have investigated the association of the CB2 Q63R variant, with histological parameters of liver disease severity in 118 Italian children with histologically-proven NAFLD.CB2 Q63R genotype was assigned performing a TaqMan assay and a general linear model analysis was used to evaluate the association between the polymorphism and the histological parameters of liver damage.We have found that whereas CB2 Q63R variant is not associated with steatosis or fibrosis, it is associated with the severity of the inflammation (p = 0.002) and the presence of NASH (p = 0.02).Our findings suggest a critical role for CB2 Q63R variant in modulating hepatic inflammation state in obese children and in the consequent increased predisposition of these patients to liver damage.

  4. Cannabinoid Receptor Type 2 Functional Variant Influences Liver Damage in Children with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Rossi, Francesca; Bellini, Giulia; Alisi, Anna; Alterio, Arianna; Maione, Sabatino; Perrone, Laura; Locatelli, Franco

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of disease ranging from simple steatosis to inflammatory steatohepatitis (NASH) with different degrees of fibrosis that can ultimately progress to cirrhosis. Accumulating evidence suggests the involvement of the endocannabinoid-system in liver disease and related complications. In particular, hepatoprotective properties for Cannabinoid Receptor type 2 (CB2) have been shown both through experimental murine models of liver injury and association study between a CB2 functional variant, Q63R, and liver enzymes in Italian obese children with steatosis. Here, in order to clarify the role of CB2 in severity of childhood NAFLD, we have investigated the association of the CB2 Q63R variant, with histological parameters of liver disease severity in 118 Italian children with histologically-proven NAFLD. CB2 Q63R genotype was assigned performing a TaqMan assay and a general linear model analysis was used to evaluate the association between the polymorphism and the histological parameters of liver damage. We have found that whereas CB2 Q63R variant is not associated with steatosis or fibrosis, it is associated with the severity of the inflammation (p = 0.002) and the presence of NASH (p = 0.02). Our findings suggest a critical role for CB2 Q63R variant in modulating hepatic inflammation state in obese children and in the consequent increased predisposition of these patients to liver damage. PMID:22927922

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

    PubMed

    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.

  6. Functional Linear Models for Association Analysis of Quantitative Traits

    PubMed Central

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

    2014-01-01

    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. PMID:24130119

  7. Functional infrared imaging in medicine: a quantitative diagnostic approach.

    PubMed

    Merla, A; Romani, G L

    2006-01-01

    The role and the potentialities of high-resolution infrared thermography, combined to bio-heat modelling, have been largely described in the last years in a wide variety of biomedical applications. Quantitative assessment over time of the cutaneous temperature and/or of other biomedical parameters related to the temperature (e.g., cutaneous blood flow, thermal inertia, sympathetic skin response) allows for a better and more complete understanding and description of functional processes involved and/or altered in presence of ailment and interfering with the regular cutaneous thermoregulation. Such an approach to thermal medical imaging requires both new methodologies and tools, like diagnostic paradigms, appropriate software for data analysis and, even, a completely new way to look at data processing. In this paper, some of the studies recently made in our laboratory are presented and described, with the general intent of introducing the reader to these innovative methods to obtain quantitative diagnostic tools based on thermal imaging.

  8. Quantitative evaluation of bioorthogonal chemistries for surface functionalization of nanoparticles.

    PubMed

    Feldborg, Lise N; Jølck, Rasmus I; Andresen, Thomas L

    2012-12-19

    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 conjugation reactions in the field. Targeted liposomes that recognize overexpressed receptors or antigens on diseased cells have great potential in therapeutic and diagnostic applications. However, chemical modifications of nanoparticle surfaces by postfunctionalization approaches are less effective than in solution and often not high-yielding. In addition, the conjugation efficiency is often challenging to characterize and therefore not addressed in many reports. We present here an investigation of PEGylated liposomes functionalized with a neuroendocrine tumor targeting peptide (TATE), synthesized with a variety of functionalities that have been used for surface conjugation of nanoparticles. The reaction kinetics and overall yield were quantified by HPLC. Reactions were conducted in solution as well as by postfunctionalization of liposomes in order to study the effects of steric hindrance and possible affinity between the peptide and the liposome surface. These studies demonstrate the importance of choosing the correct chemistry in order to obtain a quantitative surface functionalization of liposomes.

  9. Exploring quantitative methods for evaluation of lip function.

    PubMed

    Sjögreen, L; Lohmander, A; Kiliaridis, S

    2011-06-01

    The objective was to explore quantitative methods for the measurement of lip mobility and lip force and to relate these to qualitative assessments of lip function. Fifty healthy adults (mean age 45 years) and 23 adults with diagnoses affecting the facial muscles (mean age 37 years) participated in the study. Diagnoses were Möbius syndrome (n=5), Facioscapulohumeral muscular dystrophy (n=6) and Myotonic dystrophy type 1 (n=12). A system for computerised 3D analysis of lip mobility and a lip force meter were tested, and the results were related to results from qualitative assessments of lip mobility, speech (articulation), eating ability and saliva control. Facial expressions studied were open mouth smile and lip pucker. Normative data and cut-off values for adults on lip mobility and lip force were proposed, and the diagnostic value of these thresholds was tested. The proposed cut-off values could identify all inviduals with moderate or severe impairment of lip mobility but not always the milder cases. There were significant correlations between the results from quantitative measurements and qualitative assessments. The examined instruments for measuring lip function were found to be reliable with an acceptable measuring error. The combination of quantitative and qualitative ways to evaluate lip function made it possible to show the strong relation between lip contraction, lip force, eating ability and saliva control. The same combination of assessments can be used in the future to study if oral motor exercises aimed at improving lip mobility and strength could have a positive effect on lip function. © 2010 Blackwell Publishing Ltd.

  10. Structural and functional changes in acute liver injury.

    PubMed Central

    Smuckler, E A

    1976-01-01

    Carbon tetrachloride produces liver cell injury in a variety of animal species. The first structurally recognizable changes occur in the endoplasmic reticulum, with alteration in ribosome-membrane interactions. Later there is an increase in intracellular fat, and the formation of tangled nets of the ergastoplasm. At no time are there changes in mitochondria or single membrane limited bodies in cells with intact plasmalemma, although a relative increase in cell sap may appear. In dead cells (those with plasmalemma discontinuties) crystalline deposits of calcium phosphatase may be noted. Functional changes are related to the endoplasmic reticulum and the plasma membrane. An early decrease in protein synthesis takes place; an accumulation of neutral lipid is related to this change. Later alterations in the ergastoplasmic functions (e.g., mixed function oxidation) occurs. Carbon tetrachloride is not the active agent; rather, a product of its metabolism, probably the CC1, free radical, is. The mechanisms of injury include macromolecular adduction and peroxide propagation. A third possibility includes a cascade effect with the production of secondary and tertiary products, also toxic in nature, with the ability to produce more widespread damage to intracellular structures. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 11. PMID:1001290

  11. Effects of exercise and ethanol on liver mitochondrial function

    SciTech Connect

    Ardies, C.M.; Morris, G.S.; Erickson, C.K.; Farrar, R.P.

    1987-03-16

    Rates of ADP stimulated respiration for various substrates were determined in mitochondria isolated from the livers of female Sprague-Dawley rats following 8 weeks of treatment with daily swimming, ethanol consumption, or both. All rats were fed an American Institute of Nutrition (AIN) type liquid diet with the ethanol treated rats receiving 35% of the calories as ethanol. Chronic exposure to ethanol depressed both state 3 respiration with glutamate as a substrate and cytochrome oxidase activity. Respiratory control ratios and P:O ratios, however, were unaffected by the ethanol exposure. Exercise alone had no effect on hepatic mitochondrial function. There were also no significant alterations in oxidative function of hepatic mitochondria from rats which were endurance-trained by swimming while receiving the ethanol diet. This lack of alteration in mitochondrial function was in spite of the fact that these rats consumed an identical amount of ethanol as those which incurred mitochondrial dysfunction. These results indicate that regular exercise has the potential to attenuate the ethanol induced decline in hepatic mitochondria. 32 references, 2 figures, 1 table.

  12. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.**

    EPA Science Inventory

    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...

  13. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.

    EPA Science Inventory

    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...

  14. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.

    EPA Science Inventory

    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...

  15. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.**

    EPA Science Inventory

    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...

  16. LIVER FUNCTION AFTER IRRADIATION BASED UPON CT PORTAL VEIN PERFUSION IMAGING

    PubMed Central

    Cao, Yue; Pan, Charlie; Balter, James M.; Platt, Joel F.; Francis, Isaac R.; Knol, James A.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.

    2009-01-01

    Purpose The role of radiation in the treatment of intrahepatic cancer is limited by the development of radiation-induced liver disease (RILD), which occurs weeks after the course of radiation is completed. We hypothesized that, as the pathophysiology of RILD is veno-occlusive disease, we could assess individual and regional liver sensitivity to radiation by measuring liver perfusion during a course of treatment using dynamic contrast enhanced CT (DCE-CT) scanning. Materials and Methods Patients with intrahepatic cancer undergoing conformal radiotherapy underwent DCE-CT (to measure perfusion distribution) and an indocyanine extraction study (to measure liver function) prior to, during, and one month after treatment. We wished to determine if the residual functioning liver (i.e. those regions showing portal vein perfusion) could be used to predict overall liver function after irradiation. Results Radiation doses from 45 to 84 Gy resulted in undectable regional portal vein perfusion one month after treatment. The volume of each liver with undectable portal vein perfusion ranged from 0% to 39% and depended both on the patient’s sensitivity and dose distribution. There was a significant correlation between indocyanine green clearance and the mean of the estimated portal vein perfusion in the functional liver parenchyma (P < .001). Conclusion This study reveals substantial individual variability in the sensitivity of the liver to irradiation. In addition, these findings suggest that hepatic perfusion imaging may be a marker for liver function, and has the potential to be a tool for individualizing therapy. PMID:17855011

  17. Caffeine clearance by enzyme multiplied immunoassay technique: a simple, inexpensive, and useful indicator of liver function.

    PubMed Central

    McDonagh, J E; Nathan, V V; Bonavia, I C; Moyle, G R; Tanner, A R

    1991-01-01

    The clinical value and sensitivity of serum caffeine clearance measurement has been evaluated as an indicator of hepatic disease. After a 17 hour caffeine exclusion period, 300 mg of caffeine citrate was administered orally to the study subjects. Serum samples were taken four and 16 hours later. Serum caffeine concentrations were measured using an enzyme multiplied immunoassay technique (EMIT) and a clearance value derived. Conventional liver function tests were measured at the same time. A total of 103 subjects attending the medical unit in a district general hospital were studied. Twenty one had alcoholic liver disease, 11 non-alcoholic cirrhosis, nine non-cirrhotic liver disease, 21 suspected liver disease, six hepatic tumours, and 35 were hospital and normal control subjects. Caffeine clearance values were lowest in subjects with alcoholic liver disease (median 0.19 ml/min/kg, range 0.04-0.61 ml/min/kg) and significantly reduced in all subjects with liver disease (median 0.32 ml/min/kg, range 0.04-2.68 ml/min/kg) compared with control subjects (median 1.27 ml/min/kg, p less than 0.001). In subjects with suspected liver disease subsequently shown to have another explanation for abnormal liver function test results, caffeine clearance values were normal (median 1.31 ml/min/kg, range 0.23-2.64 ml/min/kg) and significantly different, p less than 0.001, from those of subjects with liver disease. Serum albumen values were not different for these latter two groups. Using a cut off value of 0.86 ml/min/kg, caffeine clearance measurement was 100% sensitive for alcoholic liver disease and 89% sensitive for all liver disease. The respective sensitivities for conventional liver function test measurement were 76% and 83%. In the suspected liver disease group, caffeine clearance was abnormal in only 24%, conventional liver function tests were abnormal in 95%. The respective specificities for caffeine clearance and liver function test measurement in control subjects were 93

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

    NASA Astrophysics Data System (ADS)

    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.

  19. Quantitative ADME proteomics - CYP and UGT enzymes in the Beagle dog liver and intestine.

    PubMed

    Heikkinen, Aki T; Friedlein, Arno; Matondo, Mariette; Hatley, Oliver J D; Petsalo, Aleksanteri; Juvonen, Risto; Galetin, Aleksandra; Rostami-Hodjegan, Amin; Aebersold, Ruedi; Lamerz, Jens; Dunkley, Tom; Cutler, Paul; Parrott, Neil

    2015-01-01

    Beagle dogs are used to study oral pharmacokinetics and guide development of drug formulations for human use. Since mechanistic insight into species differences is needed to translate findings in this species to human, abundances of cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT) drug metabolizing enzymes have been quantified in dog liver and intestine. Abundances of enzymes were measured in Beagle dog intestine and liver using selected reaction monitoring mass spectrometry. Seven and two CYPs were present in the liver and intestine, respectively. CYP3A12 was the most abundant CYP in both tissues. Seven UGT enzymes were quantified in the liver and seven in the intestine although UGT1A11 and UGT1A9 were present only in the intestine and UGT1A7 and UGT2B31 were found only in the liver. UGT1A11 and UGT1A2 were the most abundant UGTs in the intestine and UGT2B31 was the most abundant UGT in the liver. Summed abundance of UGT enzymes was similar to the sum of CYP enzymes in the liver whereas intestinal UGTs were up to four times more abundant than CYPs. The estimated coefficients of variation of abundance estimates in the livers of 14 donors were separated into biological and technical components which ranged from 14 to 49% and 20 to 39%, respectively. Abundances of canine CYP enzymes in liver and intestine have been confirmed in a larger number of dogs and UGT abundances have been quantified for the first time. The biological variability in hepatic CYPs and UGTs has also been estimated.

  20. Liver Transplantation in Man—III, Studies of Liver Function, Histology, and Immunosuppressive Therapy

    PubMed Central

    Williams, Roger; Calne, R. Y.; Ansell, I. D.; Ashby, B. S.; Cullum, P. A.; Dawson, J. L.; Eddleston, A. L. W. F.; Evans, D. B.; Flute, P. T.; Herbertson, P. M.; Joysey, V.; McGregor, A. M. C.; Millard, P. R.; Murray-Lyon, I. M.; Pena, J. R.; Rake, M. O.; Sells, R. A.

    1969-01-01

    The experience gained from 13 hepatic transplant operations is described, with particular reference to the findings in nine patients who survived the immediate operative period. A major problem was found to be infection. Fulminant pneumonia caused death in two adults, at a time when liver function was virtually normal. Infection related to bile fistula and sepsis may be overcome by an improved method of biliary drainage by cholecyst-dochostomy, which was carried out in the last two patients. Jaundice in the second week due to rejection was observed in several patients. The striking histological change was centrilobular cholestasis. The jaundice, which was not prevented by administration of antilymphocyte globulin, was rapidly controlled by temporarily increasing die dose of prednisone. One patient who survived for four and a half months and who had a poor tissue match subsequently developed chronic rejection with progressive cholestatic jaundice. Five of the patients were able to go home and at time of publication two are alive and well 14 and 20 weeks after treatment. ImagesFig. 2Fig. 4Fig. 7Fig. 9 PMID:4306854

  1. Quantitative Comparison of PET and Bremsstrahlung SPECT for Imaging the In Vivo Yttrium-90 Microsphere Distribution after Liver Radioembolization

    PubMed Central

    Elschot, Mattijs; Vermolen, Bart J.; Lam, Marnix G. E. H.; de Keizer, Bart; van den Bosch, Maurice A. A. J.; de Jong, Hugo W. A. M.

    2013-01-01

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

  2. [Glycogen storage of the liver: a determining factor of initial function of the hepatic graft].

    PubMed

    Boudjema, K; Cinqualbre, J; Barguil, Y; Pattou, F; Kerr, J A; Wolf, P; Southard, J H; Jaeck, D

    1991-01-01

    In this study we have investigated the effects of hepatocytes glycogen storage on the quality of livers for transplantation. Rats were fed or fasted for 24 h and hepatocytes isolated and cold stored in UW solution for 24 and 48 hours. Viability of the cells was analyzed by LDH release after 2 hours incubation in L15 with O2. Also, rabbits were fed, fasted (48 h) or glucose fed (48 h) and livers cold stored for 6, 24 and 48 h in UW solution. Functions of the livers were analyzed by isolated perfusion for 2 hours. Hepatocytes from fasted rats released significantly more LDH than hepatocytes from fed rats after 24 and 48 h cold storage. In rabbit livers, fasting depleted glycogen by 85% but had no effect on ATP or glutathione concentration. Livers from fasted rabbits produced similar amount of bile, released similar concentrations of lactate dehydrogenase and aspartate transaminase into the perfusate, maintained similar concentrations of glutathione after 24 hours preservation when compared to fed animals. After 48 h preservation livers from fasted animals were less viable than livers from fed animals and the decrease of liver functions in livers from fasted animals preserved for 48 hours was prevented by feeding glucose. This study shows that liver glycogen storage in hepatocyte is an important metabolite for successful liver preservation. Glycogen may be a source for ATP and antioxydant synthesis during the early period of reperfusion.

  3. Functional Region Annotation of Liver CT Image Based on Vascular Tree

    PubMed Central

    Chen, Yufei; Wang, Gang

    2016-01-01

    Anatomical analysis of liver region is critical in diagnosis and treatment of liver diseases. The reports of liver region annotation are helpful for doctors to precisely evaluate liver system. One of the challenging issues is to annotate the functional regions of liver through analyzing Computed Tomography (CT) images. In this paper, we propose a vessel-tree-based liver annotation method for CT images. The first step of the proposed annotation method is to extract the liver region including vessels and tumors from the CT scans. And then a 3-dimensional thinning algorithm is applied to obtain the spatial skeleton and geometric structure of liver vessels. With the vessel skeleton, the topology of portal veins is further formulated by a directed acyclic graph with geometrical attributes. Finally, based on the topological graph, a hierarchical vascular tree is constructed to divide the liver into eight segments according to Couinaud classification theory and thereby annotate the functional regions. Abundant experimental results demonstrate that the proposed method is effective for precise liver annotation and helpful to support liver disease diagnosis. PMID:27891516

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

    PubMed

    Geller, L I; Griaznova, M V

    1987-01-01

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

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

    SciTech Connect

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

    2014-06-15

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

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

    NASA Astrophysics Data System (ADS)

    Payne, William Mark

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

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

    DTIC Science & Technology

    1981-01-01

    Frommer , 1975) and may also be sequestered in the liver in an attempt to protect the liver from harmful toxins (Snyder and Walker, 1976; Sobocinski et al...Res. 27, 589A. Frommer , D. (1975) Med. J. Aust. 2, 793- 796. Gabridge, M. G., Yip, D.-M. and Hedges, K. (1975) Infect. Immun. 12, 233-239. Garg, S. P

  8. Age-dependent hepatocyte transplantation for functional liver tissue reconstitution.

    PubMed

    Stock, Peggy

    2014-01-01

    The transplantation of hepatocytes could be an alternative therapeutic option to the whole organ transplantation for the treatment of end-stage liver diseases. However, this cell-based therapy needs the understanding of the molecular mechanisms to improve efficacy. This chapter includes a detailed method of a rat model for liver regeneration studies after age-dependent hepatocyte transplantation.

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

    PubMed

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

    2015-07-01

    Growth-related traits are economically important traits to the pig industry. Identification of causative gene and mutation responsible for growth-related QTL will facilitate the improvement of pig growth through marker-assisted selection. In this study, we applied whole genome gene expression and quantitative trait transcript (QTT) analyses in 497 liver and 586 longissimus dorsi muscle samples to identify candidate genes and dissect the genetic basis of pig growth in a white Duroc × Erhualian F2 resource population. A total of 20,108 transcripts in liver and 23,728 transcripts in muscle with expression values were used for association analysis between gene expression level and phenotypic value. At the significance threshold of P < 0.0005, we identified a total of 169 and 168 QTTs for nine growth-related traits in liver and muscle, respectively. We also found that some QTTs were correlated to more than one trait. The QTTs identified here showed high tissue specificity. We did not identify any QTTs that were associated with one trait in both liver and muscle. Through an integrative genomic approach, we identified SDR16C5 as the important candidate gene in pig growth trait. These findings contribute to further identification of the causative genes for porcine growth traits and facilitate improvement of pig breeding.

  10. Quantitation of renal function with technetium-99m MAG3

    SciTech Connect

    Russell, C.D.; Thorstad, B.L.; Yester, M.V.; Stutzman, M.; Dubovsky, E.V.

    1988-12-01

    The technetium-labeled hippuran analog (/sup 99m/Tc)MAG3 was compared with ( T I)hippuran in 50 patients using a quantitative renal function protocol that includes: (a) estimation of effective renal plasma flow by a single-injection, single-sample plasma clearance method, (b) determination of relative function of right and left kidney from the initial count rate over each kidney, and (c) comparison of recovered urine activity with plasma disappearance. This protocol is suitable for routine clinical use, and, in fact, has been used heavily at our clinic for a number of years. By slight modification of the formulas, the results obtained with (/sup 99m/Tc)MAG3 agreed well with those using ( T I)hippuran. We conclude that (/sup 99m/Tc)MAG3 can be substituted for ( T I)hippuran in the quantitative protocol, with the better image quality and lower radiation dose (in abnormals) of a technetium-labeled agent.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2017-06-21

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

  13. Biodegradable and synthetic membranes for the expansion and functional differentiation of rat embryonic liver cells.

    PubMed

    Piscioneri, Antonella; Campana, Carla; Salerno, Simona; Morelli, Sabrina; Bader, Augustinus; Giordano, Francesca; Drioli, Enrico; Bartolo, Loredana De

    2011-01-01

    The insufficient availability of donor organs for orthotopic liver transplantation worldwide has urgently increased the requirement for new therapies for acute and chronic liver disease. The creation of an unlimited source of donor cells for hepatocyte transplantation therapy and pharmaceutical applications may be the isolation and expansion of liver progenitor cells or stem cells. Here we report the expansion and functional differentiation of rat embryonic liver cells on biodegradable and synthetic polymeric membranes in comparison with traditional substrates, such as collagen and polystyrene culture dishes. Membranes prepared from chitosan and modified polyetheretherketone were used for the culture of liver progenitor cells derived from rat embryonic liver. Cells proliferated, with a significant increase in their number within 8-11 days. The cells displayed functional differentiation showing urea synthesis, albumin production and diazepam biotransformation on all substrates investigated. In particular, on a chitosan membrane liver-specific functions were expressed at significantly higher levels for prolonged times compared with other synthetic membranes, utilizing traditional substrates (collagen and PSCD) as references. These results demonstrate that chitosan membranes offer cells favourable conditions to promote the expansion and functional differentiation of embryonic liver cells that could be effectively used in liver tissue engineering and in pharmaceutical applications. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Functional Regression Models for Epistasis Analysis of Multiple Quantitative Traits.

    PubMed

    Zhang, Futao; Xie, Dan; Liang, Meimei; Xiong, Momiao

    2016-04-01

    To date, most genetic analyses of phenotypes have focused on analyzing single traits or analyzing each phenotype independently. However, joint epistasis analysis of multiple complementary traits will increase statistical power and improve our understanding of the complicated genetic structure of the complex diseases. Despite their importance in uncovering the genetic structure of complex traits, the statistical methods for identifying epistasis in multiple phenotypes remains fundamentally unexplored. To fill this gap, we formulate a test for interaction between two genes in multiple quantitative trait analysis as a multiple functional regression (MFRG) in which the genotype functions (genetic variant profiles) are defined as a function of the genomic position of the genetic variants. We use large-scale simulations to calculate Type I error rates for testing interaction between two genes with multiple phenotypes and to compare the power with multivariate pairwise interaction analysis and single trait interaction analysis by a single variate functional regression model. To further evaluate performance, the MFRG for epistasis analysis is applied to five phenotypes of exome sequence data from the NHLBI's Exome Sequencing Project (ESP) to detect pleiotropic epistasis. A total of 267 pairs of genes that formed a genetic interaction network showed significant evidence of epistasis influencing five traits. The results demonstrate that the joint interaction analysis of multiple phenotypes has a much higher power to detect interaction than the interaction analysis of a single trait and may open a new direction to fully uncovering the genetic structure of multiple phenotypes.

  15. Fate of Entamoeba histolytica during Establishment of Amoebic Liver Abscess Analyzed by Quantitative Radioimaging and Histology

    PubMed Central

    Rigothier, Marie-Christine; Khun, Hout; Tavares, Paulo; Cardona, Ana; Huerre, Michel; Guillén, Nancy

    2002-01-01

    The protozoan parasite Entamoeba histolytica is the causative agent of amoebiasis, a human disease characterized by dysentery and liver abscess. The physiopathology of hepatic lesions can be satisfactorily reproduced in the hamster animal model by the administration of trophozoites through the portal vein route. Hamsters were infected with radioactively labeled amoebas for analysis of liver abscess establishment and progression. The radioimaging of material from parasite origin and quantification of the number inflammation foci, with or without amoebas, described here provides the first detailed assessment of trophozoite survival and death during liver infection by E. histolytica. The massive death of trophozoites observed in the first hours postinfection correlates with the presence of a majority of inflammatory foci without parasites. A critical point for success of infection is reached after 12 h when the lowest number of trophozoites is observed. The process then enters a commitment phase during which parasites multiply and the size of the infection foci increases fast. The liver shows extensive areas of dead hepatocytes that are surrounded by a peripheral layer of parasites facing inflammatory cells leading to acute inflammation. Our results show that the host response promotes massive parasite death but also suggest also that this is a major contributor to the establishment of inflammation during development of liver abscess. PMID:12011016

  16. Quantitative elemental analysis on aluminum accumulation by HVTEM-EDX in liver tissues of mice orally administered with aluminum chloride.

    PubMed

    Kametani, Kiyokazu; Nagata, Tetsuji

    2006-06-01

    Quantitative elemental analysis on Al was carried out by high-accelerating voltage transmission electron microscopy (HVTEM) equipped with energy-dispersive X-ray microanalysis (EDX) using an accelerating voltage at 300 kV with high permeability in 1-mum-thick samples obtained from mice administered with aluminum chloride solution for 3, 9, and 17 weeks. By light microscopic observation, no morphological changes were observed in the hepatocytes and macrophages in the liver tissues of mice that were administered with excess Al as compared with the normal control mice. In contrast, by electron microscopic observation, ultrastructural changes were observed in the lysosomes in the hepatocytes as well as the pinocytotic vesicles in the macrophages in the experimental animals. Therefore, the concentrations of Al detected in lysosomes in hepatocytes and pinocytotic vesicles in macrophages of livers of mice administered with Al were measured in relationship to those administration periods. Moreover, transitional changes of hepatocyte lysosome ratios by image analysis and the macrophage counts in the unit area increased in liver tissues of mice administered with Al as compared with normal control mice. From the results, it was demonstrated that hepatocyte lysosome ratio and macrophage count increased in liver tissues of treated mice during those short-term excessive Al administration periods. It was also clarified that the concentrations of Al in both hepatocytes and macrophages increased as observed by HVTEM-EDX. In conclusion, Al accumulated in hepatocytes and macrophages at 3 and 9 weeks administration, while the ultrastructural changes remained in the hepatocytes and macrophages. In contrast, Al concentration did not increase in the liver at 17 weeks administration.

  17. Perioperative Liver Function after Hepatectomy in a Tertiary University Hospital in Damascus

    PubMed

    Ahmad, Basel; Turkmani, Khaled; Marwa, Mohamad Essam; Ahmad, Tareq; Baghdadi, Ramez; Aboudamaah, Shaimaa; Alkhatib, Khetam; Ahmad, Mohamad

    2017-08-27

    Background: Liver resection is the only viable therapeutic treatment option for several neoplastic entities of the liver. Although, the number of resectable patients is increasing in Syria, liver failure is still a major complication affecting mortality and morbidity rates. Methods: Between 2009 and 2016, 104 patients undergoing liver resection in Damascus University Faculty of Medicine were retrospectively analyzed. Liver function tests were conducted before surgery (ps) and in the perioperative period (po) and comparisons were performed with division into anatomic VS non-anatomic or malignant VS non-malignant groups. Results: Liver synthetic, excretory and detoxifying functions deteriorated after liver resection (INR ps ‘presurgery’=1.129 po ‘perioperative’=1.426 P<0.001, TP ps=7.426 po=5.581 P<0.001, ALB ps=4.204 po=3.242 P<0.001, T-Bill ps=0.061 po=0.136 P<0.001) and liver cell necrosis increased after resection (ALT ps=27.597 po=200.221 P<0.001, AST ps=33.395 po=190.553 P<0.001). There was no significant difference in liver functions when we compared anatomic VS non-anatomic groups or malignant VS non-malignant groups, but liver cell necrosis was higher with malignancies (ALT malignant group=236.475 non-malignant group=89.5 P=0.002, AST malignant group=222.644 non-malignant group=101.125 P=0.001). Conclusion: Although liver resection affects liver function significantly, no differences in outcomes were found between anatomic VS non anatomic or malignant VS non-malignant groups. Creative Commons Attribution License

  18. Quantitative Imaging of Lymphatic Function with Liposomal Indocyanine Green

    PubMed Central

    Proulx, Steven T.; Luciani, Paola; Derzsi, Stefanie; Rinderknecht, Matthias; Mumprecht, Viviane; Leroux, Jean-Christophe; Detmar, Michael

    2010-01-01

    Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift towards longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near infrared imaging of intradermally-injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C expressing tumors without metastases while a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method likely will facilitate quantitative studies of lymphatic function in preclinical studies and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer. PMID:20823159

  19. The effects of melatonin on liver functions in arsenic-induced liver damage

    PubMed Central

    Bali, İlhan; Bilir, Bülent; Emir, Seyfi; Turan, Filiz; Yılmaz, Ahsen; Gökkuş, Tuba; Aydın, Murat

    2016-01-01

    Objective Arsenic exposure is increasing in communities due to environmental pollution and industrial development. Arsenic is toxic to organ systems because it causes oxidative stress, enzymatic inhibition, and damage to protein structures. The liver, for example, is an organ that may be damaged by arsenic, and this damage may cause various clinical conditions like hepatic failure or cancer. Melatonin is a hormone that acts like an antioxidant, an anti-inflammatory agent, and a cytoprotective agent. In this study, we aimed to evaluate melatonin’s protective effects on livers damaged by arsenic toxicity. Materials and Methods Twenty-four Sprague-Dawley male rats were classified into three groups: a control group, an arsenic applied group, and an arsenic plus 10 mg/kg melatonin applied group. At the end of the fifteen-day experiment, the rats were sacrificed. Albumin, interleukin-6 (IL-6), total protein, alanine transaminase, aspartate transaminase, macrophage migration inhibitory factor, and monocyte chemotactic protein-1 measurements were obtained. Results In rats with liver damage due to arsenic exposure, melatonin administration significantly decreased the levels of IL-6, macrophage migration inhibitory factor, and monocyte chemotactic protein-1 (p<0.001, p=0.02 and p=0.04, respectively). Conclusion After evaluating liver enzymes and inflammatory markers, this study determined that melatonin exposure improves liver tissue damage caused by arsenic exposure, with the degree of improvement varying based on the levels of arsenic exposure. PMID:28149117

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

    PubMed

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

    2012-04-01

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

  1. [Functional state of the liver at modeling hemodynamic effects of the weightlessness in human organism].

    PubMed

    Afonin, B V; Ermolenko, A E; Inozemtsev, S L

    2012-01-01

    The radioisotope researches (RR) ofcholeresis function of a liver, the ultrasonic researches (USR) of a liver, the contractile gallbladder function (GF) and the gastroduodenoscopy (GDS) were carried out at 8 men after 24 hour duration of stay in antiorthostatic position--12 degrees (AOP), simulating arising in weightlessness of hemodynamics changes in abdominal cavity. The dynamic difficulty of venous blood outflow from a liver at simulated in antiorthostatic position changes of activation choleresis on an empty stomach was produced, by increase of a zone central perfusion of a liver parenchyma, biliary ductules dilation and of a gallbladder reduction, and were accompanied by choleresis in duodenum. The activation choleresis in a liver was accompanied by of reduction of the area of radioactive marker distribution in a liver, the decrease of hepatocytes metabolic activity and concentration function ofbiliary excretion system. Specificity of a functional condition of a liver within AOP reflects reaction caused by plethoric changes induced by body position, which is negative to vector of gravity. The mechanism of the revealed changes includes occurrence dynamic venous plethora in a liver, centralization hepatic blood flow with activation choleresis activity against the background tissual blood flow depletion in peripheral zones, reduction of hepatocytes metabolic activity and concentration function biliary excretion system.

  2. Quantitative Trait Loci Identify Functional Noncoding Variation in Cancer.

    PubMed

    Heyn, Holger

    2016-03-01

    The interpretation of noncoding alterations in cancer genomes presents an unresolved problem in cancer studies. While the impact of somatic variations in protein-coding regions is widely accepted, noncoding aberrations are mostly considered as passenger events. However, with the advance of genome-wide profiling strategies, alterations outside the coding context entered the focus, and multiple examples highlight the role of gene deregulation as cancer-driving events. This review describes the implication of noncoding alterations in oncogenesis and provides a theoretical framework for the identification of causal somatic variants using quantitative trait loci (QTL) analysis. Assuming that functional noncoding alterations affect quantifiable regulatory processes, somatic QTL studies constitute a valuable strategy to pinpoint cancer gene deregulation. Eventually, the comprehensive identification and interpretation of coding and noncoding alterations will guide our future understanding of cancer biology.

  3. Quantitative evaluation of activation state in functional brain imaging.

    PubMed

    Hu, Zhenghui; Ni, Pengyu; Liu, Cong; Zhao, Xiaohu; Liu, Huafeng; Shi, Pengcheng

    2012-10-01

    Neuronal activity can evoke the hemodynamic change that gives rise to the observed functional magnetic resonance imaging (fMRI) signal. These increases are also regulated by the resting blood volume fraction (V (0)) associated with regional vasculature. The activation locus detected by means of the change in the blood-oxygen-level-dependent (BOLD) signal intensity thereby may deviate from the actual active site due to varied vascular density in the cortex. Furthermore, conventional detection techniques evaluate the statistical significance of the hemodynamic observations. In this sense, the significance level relies not only upon the intensity of the BOLD signal change, but also upon the spatially inhomogeneous fMRI noise distribution that complicates the expression of the results. In this paper, we propose a quantitative strategy for the calibration of activation states to address these challenging problems. The quantitative assessment is based on the estimated neuronal efficacy parameter [Formula: see text] of the hemodynamic model in a voxel-by-voxel way. It is partly immune to the inhomogeneous fMRI noise by virtue of the strength of the optimization strategy. Moreover, it is easy to incorporate regional vascular information into the activation detection procedure. By combining MR angiography images, this approach can remove large vessel contamination in fMRI signals, and provide more accurate functional localization than classical statistical techniques for clinical applications. It is also helpful to investigate the nonlinear nature of the coupling between synaptic activity and the evoked BOLD response. The proposed method might be considered as a potentially useful complement to existing statistical approaches.

  4. Quantitative assessment of rabbit alveolar macrophage function by chemiluminescence

    SciTech Connect

    Brennan, P.C.; Kirchner, F.R.

    1985-08-01

    Rabbit alveolar macrophages (RAM) were cultured for 24 hr with concentrations ranging from 3 to 12 ..mu..g/ml of vanadium oxide (V/sub 2/O/sub 5/), a known cytotoxic agent, or with high-molecular-weight organic by-products from coal gasification processes. After culture the cells were harvested and tested for functional capacity using three types of indicators: (1) luminol-amplified chemiluminescence (CL), which quantitatively detects photon emission due to respiratory burst activity measured in a newly designed instrument with standardized reagents; (2) the reduction of nitro blue tetrazolium-saturated polyacrylamide beads, a semiquantitative measure of respiratory burst activity; and (3) phagocytic efficiency, defined as percentage of cells incorporating immunoglobulin-coated polyacrylamide beads. Chemiluminescence declined linearly with increasing concentrations of V/sub 2/O/sub 5/ over the dose range tested. Dye reduction and phagocytic efficiency similarly decreased with increasing V/sub 2/O/sub 5/ concentration, but were less sensitive indicators of functional impairment than CL as measured by the amount required to reduce the response to 50% of untreated cells. The effect of coal gasification condensates on RAM function varied, but in general these test also indicated that the CL response was the most sensitive indicator.

  5. Quantitative Proteomic Profiles of Androgen Receptor Signaling in the Liver of Fathead Minnows Pimephalus promelas

    EPA Science Inventory

    Androgenic chemicals are present in the environment at concentrations that impair reproductive processes in fish. The objective of this experiment was to identify proteins altered by an androgen receptor agonist (17â-trenbolone) and antagonist (flutamide) in the liver. Female fa...

  6. Qualitative and quantitative histochemical changes in the caecum and liver of turkeys infected with Histomonas meleagridis.

    PubMed

    Wilkins, D; Lee, D L

    1976-02-01

    Changes in the amount and distribution of acid and alkaline phosphatase, non-specific esterase, glycogen, lipid and acid mucopolysaccharide in the caecal wall and liver of turkey poults infected with Histomonas meleagridis have been studied histochemically. A microdensitometer was used to measure changes in activity and distribution of acid phosphatase and non-specific esterase in the caecal mucosa. During the course of the infection there is a marked reduction in activity and distribution of acid phosphatase and non-specific esterase but little change in the amounts and distribution of alkaline phosphatase, glycogen, lipid and acid mucopolysaccharide in the wall of the main part of the caecum. Similar, but smaller, changes occurred in the wall of the neck region of the caecum. In the liver most changes occurred in the immediate vicinity of the parasites. Initially, there was a reduction in the amount of glycogen in the parasitic lesions but later in the infection there was a marked loss of glycogen in all regions of the liver. Changes in the caecum are apparently brought about by the parasite prior to and after invasion of the caecal tissues; changes in the liver occur after it has been invaded.

  7. Quantitative Proteomic Profiles of Androgen Receptor Signaling in the Liver of Fathead Minnows Pimephalus promelas

    EPA Science Inventory

    Androgenic chemicals are present in the environment at concentrations that impair reproductive processes in fish. The objective of this experiment was to identify proteins altered by an androgen receptor agonist (17â-trenbolone) and antagonist (flutamide) in the liver. Female fa...

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

    PubMed

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

    1998-07-01

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

  9. Enzymatic liver function capacity correlates with disease severity of patients with liver cirrhosis: a study with the LiMAx test.

    PubMed

    Malinowski, Maciej; Jara, Maximilian; Lüttgert, Katja; Orr, James; Lock, Johan Friso; Schott, Eckart; Stockmann, Martin

    2014-12-01

    Assessment and quantification of actual liver function is crucial in patients with chronic liver disease to monitor disease progression and predict individual prognosis. Mathematical models, such as model for end-stage liver disease, are used for risk stratification of patients with chronic liver disease but do not include parameters that reflect the actual functional state of the liver. We aimed to evaluate the potential of a (13)C-based liver function test as a stratification tool by comparison with other liver function tests and clinical parameters in a large sample of healthy controls and cirrhotic patients. We applied maximum liver function capacity (LiMAx) to evaluate actual liver function in 347 patients with cirrhosis and in 86 controls. LiMAx showed strong negative correlation with Child-Pugh Score (r = -0.707; p < 0.001), MELD (r = -0.686; p < 0.001) and liver function tests. LiMAx was lower in patients with liver cirrhosis compared to healthy controls [99 (57-160) µg/kg/h vs. 412 (365-479) µg/kg/h, p < 0.001] and differed among Child-Pugh classes [a: 181 (144-227) µg/kg/h, b: 96 (62-132) µg/kg/h and c: 52 (37-81) µg/kg/h; p < 0.001]. When stratified patients according to disease severity, LiMAx results were not different between cirrhotic patients and cirrhotic patients with transjugular intrahepatic portosystemic shunt. LiMAx appears to provide reliable information on remnant enzymatic liver function in chronic liver disease and allows graduation of disease severity.

  10. The multiple functions of heme oxygenase-1 in the liver.

    PubMed

    Sass, G; Barikbin, R; Tiegs, G

    2012-01-01

    Heme oxygenases (HO) are essential enzymes which degrade heme into carbon monoxide (CO), biliverdin and free iron. Due to its anti-inflammatory, anti-apoptotic and, as recently described, anti-viral properties the inducible HO isoform HO-1 is an important molecule which could find its way into therapy of gastrointestinal diseases. Acute and chronic liver injuries including acute liver failure, alcoholic or viral hepatitis, chronic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma are life threatening diseases and as a consequence might result in the necessity of liver transplantation. HO-1 as well as its reaction products of heme degradation has been linked to cytoprotection. HO-1 induction in rodent models of acute and chronic hepatic inflammation resulted in improvement of liver damage and down-regulation of pro-inflammatory cytokine levels. Furthermore HO-1 induction interfered with fibrosis progression in mice and partially resolved existing fibrosis. Likewise, HO-1 induction interfered with replication of hepatitis viruses B and C, which frequently are the reason for chronic hepatitis and subsequent tumor growth. Liver transplantation is limited by ischemia/reperfusion (I/R) injury, which is characterized by hypoxia and nutrient deficiency resulting in oxidative stress, apoptosis and immune activation. Induction of HO-1 and application predominantly of CO have been shown to interfere with I/R liver injury and to improve recipient and graft survival. On the other hand HO-1 has been shown to be over-expressed in various tumors, including hepatocellular carcinoma (HCC). Due to its anti-apoptotic properties this bears the risk to promote tumor growth. Anti-apoptotic effects are predominantly mediated by CO. This review aims to summarize beneficial as well as detrimental effects of HO-1 and its products within the liver.

  11. Molecular Adsorbent Recirculating System Effectively Replaces Hepatic Function in Severe Acute Liver Failure.

    PubMed

    Hanish, Steven I; Stein, Deborah M; Scalea, Joseph R; Essien, Eno-Obong; Thurman, Paul; Hutson, William R; Bartlett, Stephen T; Barth, Rolf N; Scalea, Thomas M

    2017-10-01

    Patients with severe acute liver failure (ALF) have extreme physiologic dysfunction and often die if transplantation is not immediately available. Patients may be supported with MARS (Baxter International Inc., Deerfield, IL) until transplantation or spontaneous recovery occurs. We present the largest series in the United States of MARS therapy as temporary hepatic replacement for ALF. MARS was used to support patients with severe liver trauma (SLT), in ALF patients as a bridge to transplantation (BTT), and as definitive therapy for toxic ingestion or idiopathic liver failure (DT) in a level 1 trauma center and large transplant center. Patient demographics, etiology of ALF, and laboratory values were recorded. Endpoints were patient survival ± liver transplant and/or recovery of liver function. Twenty-seven patients with severe ALF received MARS therapy. Five patients with SLT had a 60% survival with recovery of liver and renal function. Thirteen patients received MARS as a BTT, of which 9 were transplanted with a 1-year survival of 78% (program overall survival 85% at 1 year). All 4 who were not transplanted expired. Nine patients with ALF from toxic ingestion received MARS as DT with liver recovery and survival in 67%. MARS therapy resulted in significant improvement in liver function, coagulation, incidence of encephalopathy, and creatinine. MARS therapy successfully replaced hepatic function in ALF allowing time for spontaneous recovery or transplantation. Spontaneous recovery was remarkably common if support can be sustained.

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

    PubMed Central

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

    2016-01-01

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

  13. Quantitative proteomics of rat livers shows that unrestricted feeding is stressful for proteostasis with implications on life span

    PubMed Central

    Pinto, Galit; Quadroni, Manfredo; Shtaif, Biana; Goloubinoff, Pierre

    2016-01-01

    Studies in young mammals on the molecular effects of food restriction leading to prolong adult life are scares. Here, we used high-throughput quantitative proteomic analysis of whole rat livers to address the molecular basis for growth arrest and the apparent life-prolonging phenotype of the food restriction regimen. Over 1800 common proteins were significantly quantified in livers of ad libitum, restriction- and re-fed rats, which summed up into 92% of the total protein mass of the cells. Compared to restriction, ad libitum cells contained significantly less mitochondrial catabolic enzymes and more cytosolic and ER HSP90 and HSP70 chaperones, which are hallmarks of heat- and chemically-stressed tissues. Following re-feeding, levels of HSPs nearly reached ad libitum levels. The quantitative and qualitative protein values indicated that the restriction regimen was a least stressful condition that used minimal amounts of HSP-chaperones to maintain optimal protein homeostasis and sustain optimal life span. In contrast, the elevated levels of HSP-chaperones in ad libitum tissues were characteristic of a chronic stress, which in the long term could lead to early aging and shorter life span. PMID:27508340

  14. Quantitative Assessment of Neuromotor Function in Adolescents with High Functioning Autism and Asperger Syndrome

    ERIC Educational Resources Information Center

    Freitag, Christine M.; Kleser, Christina; Schneider, Marc; von Gontard, Alexander

    2007-01-01

    Background: Motor impairment in children with Asperger Syndrome (AS) or High functioning autism (HFA) has been reported previously. This study presents results of a quantitative assessment of neuromotor skills in 14-22 year old HFA/AS. Methods: 16 HFA/AS and 16 IQ-matched controls were assessed by the Zurich Neuromotor Assessment (ZNA). Results:…

  15. Molecular acidity: A quantitative conceptual density functional theory description.

    PubMed

    Liu, Shubin; Schauer, Cynthia K; Pedersen, Lee G

    2009-10-28

    Accurate predictions of molecular acidity using ab initio and density functional approaches are still a daunting task. Using electronic and reactivity properties, one can quantitatively estimate pKa values of acids. In a recent paper [S. B. Liu and L. G. Pedersen, J. Phys. Chem. A 113, 3648 (2009)], we employed the molecular electrostatic potential (MEP) on the nucleus and the sum of valence natural atomic orbital (NAO) energies for the purpose. In this work, we reformulate these relationships on the basis of conceptual density functional theory and compare the results with those from the thermodynamic cycle method. We show that MEP and NAO properties of the dissociating proton of an acid should satisfy the same relationships with experimental pKa data. We employ 27 main groups and first to third row transition metal-water complexes as illustrative examples to numerically verify the validity of these strong linear correlations. Results also show that the accuracy of our approach and that of the conventional method through the thermodynamic cycle are statistically similar.

  16. MR cholangiography in potential liver donors: quantitative and qualitative improvement with administration of an oral effervescent agent.

    PubMed

    Kwon, Heon-Ju; Kim, Kyoung Won; Choi, Sang Hyun; Jung, Jin-Hee; Kim, So Yeon; Kim, Se-Young; Lee, Jeongjin; Jung, Dong-Hwan; Ha, Tae-Yong; Song, Gi-Won; Lee, Sung-Gyu

    2017-03-23

    To determine whether an oral effervescent agent improves magnetic resonance cholangiography (MRC) images, both qualitatively and quantitatively, in potential live liver donors. This retrospective study was approved by the Institutional Review Board, and informed consent was waived. Seventy potential liver donors underwent 2D MRC before and after administration of an oral effervescent agent. One radiologist measured relative contrast ratio (rC) and relative signal intensity (rS) for right and left intrahepatic ducts (RHD and LHD), and common hepatic duct (CHD). After assessment of overall image quality, two other radiologists independently scored visualization of five ductal segments (RHD, LHD, CHD, cystic, and common bile duct) and assessed the preferred image set. In consensus, they assessed the biliary anatomy. The data were analyzed using a paired t-test, Wilcoxon's signed-rank test, and chi-square test. Both rC and rS of RHD and CHD were significantly higher on MRC images after administration of an oral effervescent agent than before (P < 0.03). The overall image quality grades and biliary visualization scores for all five duct segments were significantly higher on MRC images after administration of an oral effervescent agent than before (P < 0.0001). Between these images, both readers more often preferred MRC images with an effervescent agent rather than those without this agent (reader 1: 56/70, 80.0%; reader 2: 55/70, 78.6%; P = 0.0003). The readers correctly assessed second-order biliary tract anatomy in two more subjects on MRC after administration of an effervescent agent than before. Oral administration of an effervescent agent improves MRC images, both qualitatively and quantitatively, in live liver donors. 3 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.

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

    PubMed

    Hu, Y; Chen, B; Qian, J; Jin, L; Jin, T; Lu, D

    2010-03-01

    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) > or =25 kg/m(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.

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

    PubMed

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

    1989-01-01

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

  19. Determining liver stage parasite burden by real time quantitative PCR as a method for evaluating pre-erythrocytic malaria vaccine efficacy.

    PubMed

    Witney, A A; Doolan, D L; Anthony, R M; Weiss, W R; Hoffman, S L; Carucci, D J

    2001-12-01

    The detection and quantitation of blood stage parasitaemia is typically used as a surrogate endpoint for estimating the efficacy of vaccines targeted against the hepatic stage, as well as the erythrocytic stage, of the parasite. However, this does not provide an adequate means of evaluating the efficacy of vaccines, which may be only partially effective at the liver-stage. This is a particular concern for effective evaluation of immune enhancement strategies for candidate pre-erythrocytic stage vaccines. Here, we have developed and validated a method for detecting and quantitating liver stage parasites, using the TaqMan fluorescent real-time quantitative PCR system (PE Applied Biosystems). This method uses TaqMan primers designed to the Plasmodium yoelii 18S rRNA gene and rodent GAPDH to amplify products from infected mouse liver cDNA. The technique is highly reproducible as demonstrated with plasmid controls and capable of efficiently quantitating liver-stage parasite burden following a range of sporozoite challenge doses in strains of mice, which differ in their susceptibility to sporozoite infection. We have further demonstrated the capacity of this technique to evaluate the efficacy of a range of pre-erythrocytic stage vaccines. Our data establish this quantitative real-time PCR assay to be a fast and reproducible way of accurately assessing liver stage parasite burden and vaccine efficacy in rodent malaria models.

  20. Ectopic fat depots and left ventricular function in nondiabetic men with nonalcoholic fatty liver disease.

    PubMed

    Granér, Marit; Nyman, Kristofer; Siren, Reijo; Pentikäinen, Markku O; Lundbom, Jesper; Hakkarainen, Antti; Lauerma, Kirsi; Lundbom, Nina; Nieminen, Markku S; Taskinen, Marja-Riitta

    2015-01-01

    Nonalcoholic fatty liver disease has emerged as a novel cardiovascular risk factor. The aim of the study was to assess the effect of different ectopic fat depots on left ventricular (LV) function in subjects with nonalcoholic fatty liver disease. Myocardial and hepatic triglyceride contents were measured with 1.5 T magnetic resonance spectroscopy and LV function, visceral adipose tissue (VAT) and subcutaneous adipose tissue, epicardial and pericardial fat by MRI in 75 nondiabetic men. Subjects were stratified by hepatic triglyceride content into low, moderate, and high liver fat groups. Myocardial triglyceride, epicardial and pericardial fat, VAT, and subcutaneous adipose tissue increased stepwise from low to high liver fat group. Parameters of LV diastolic function showed a stepwise decrease over tertiles of liver fat and VAT, and they were inversely correlated with hepatic triglyceride, VAT, and VAT/subcutaneous adipose tissue ratio. In multivariable analyses, hepatic triglyceride and VAT were independent predictors of LV diastolic function, whereas myocardial triglyceride was not associated with measures of diastolic function. Myocardial triglyceride, epicardial and pericardial fat increased with increasing amount of liver fat and VAT. Hepatic steatosis and VAT associated with significant changes in LV structure and function. The association of LV diastolic function with hepatic triglyceride and VAT may be because of toxic systemic effects. The effects of myocardial triglyceride on LV structure and function seem to be more complex than previously thought and merit further study. © 2014 American Heart Association, Inc.

  1. An accurate method of extracting fat droplets in liver images for quantitative evaluation

    NASA Astrophysics Data System (ADS)

    Ishikawa, Masahiro; Kobayashi, Naoki; Komagata, Hideki; Shinoda, Kazuma; Yamaguchi, Masahiro; Abe, Tokiya; Hashiguchi, Akinori; Sakamoto, Michiie

    2015-03-01

    The steatosis in liver pathological tissue images is a promising indicator of nonalcoholic fatty liver disease (NAFLD) and the possible risk of hepatocellular carcinoma (HCC). The resulting values are also important for ensuring the automatic and accurate classification of HCC images, because the existence of many fat droplets is likely to create errors in quantifying the morphological features used in the process. In this study we propose a method that can automatically detect, and exclude regions with many fat droplets by using the feature values of colors, shapes and the arrangement of cell nuclei. We implement the method and confirm that it can accurately detect fat droplets and quantify the fat droplet ratio of actual images. This investigation also clarifies the effective characteristics that contribute to accurate detection.

  2. Simplified [18F]FDG Image-Derived Input Function Using the Left Ventricle, Liver, and One Venous Blood Sample

    PubMed Central

    Tantawy, Mohammed Noor; Peterson, Todd E.

    2014-01-01

    A relatively simple, almost entirely noninvasive imaging-based method is presented for deriving arterial blood input functions for quantitative [18F]2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomographic (PET) studies in rodents. It requires only one venous blood sample at the end of the scan. MicroPET images and arterial blood time-activity curves (TACs) were downloaded from the Mouse Quantitation Program database at the University of California, Los Angeles. Three-dimensional regions of interest were drawn around the blood-pool region of the left ventricle and within the liver to derive their respective TACs. To construct the “hybrid” image-derived input function (IDIF), the initial part of the left ventricle TAC, containing the peak concentration of [18F]FDG in the arterial blood, was corrected for spillout (ie, partial-volume effect yielding a recovery coefficient < 1) and then joined to the liver TAC (normalized to the 60-minute arterial blood sample) immediately after it peaks. To validate our method, the [18F]FDG influx constant (Ki) was estimated using a two-tissue compartment model and compared to estimates of Ki obtained using measured arterial blood TACs. No significant difference in the Ki estimates was obtained with the arterial blood input function and our hybrid IDIF. We conclude that the normalized hybrid IDIF can be used in practice to obtain reliable Ki estimates. PMID:20236605

  3. Differential proteomics analysis of liver failure in peripheral blood mononuclear cells using isobaric tags for relative and absolute quantitation

    PubMed Central

    Lin, Hua; Tan, Qiu-Pei; Sui, Wei-Guo; Chen, Wen-Biao; Peng, Wu-Jian; Liu, Xing-Chao; Dai, Yong

    2017-01-01

    The aim of the present study was to examine differentially expressed proteome profiles for candidate biomarkers in peripheral blood mononuclear cells (PBMCs) of liver failure (LF) patients. Ten patients were diagnosed as LF and 10 age- and gender-matched subjects were recruited as healthy controls. Isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic technology is efficiently applicable for identification and relative quantitation of the proteomes of PBMCs. Eight-plex iTRAQ coupled with strong cation exchange chromatography, and liquid chromatography coupled with tandem mass spectrometry were used to analyze total proteins in LF patients and healthy control subjects. Molecular variations were detected using the iTRAQ method, and western blotting was used to verify the results. LF is a complex type of medical emergency that evolves following a catastrophic insult to the liver, and its outcome remains the most ominous of all gastroenterologic diseases. Serious complications tend to occur during the course of the disease and further exacerbate the problems. Using the iTRAQ method, differentially expressed proteome profiles of LF patients were determined. In the present study, 627 proteins with different expression levels were identified in LF patients compared with the control subjects; with 409 proteins upregulated and 218 proteins downregulated. Among them, four proteins were significantly differentially expressed; acylaminoacyl-peptide hydrolase and WW domain binding protein 2 were upregulated, and resistin and tubulin β 2A class IIa were downregulated. These proteins demonstrated differences in their expression levels compared with other proteins with normal expression levels and the significant positive correlation with LF. The western blot results were consistent with the results from iTRAQ. Thus, investigation of the molecular mechanism of the proteins involved in LF may facilitate an improved understanding of the

  4. Oral glucose tolerance test for preoperative assessment of liver function in liver resection

    PubMed Central

    Rachapoodivenkata, Raghavendra Rao

    2017-01-01

    Backgrounds/Aims We intended to determine the role of the Oral glucose tolerance test (OGTT), in addition to volumetry, in preoperative assessment of patients undergoing liver resection. Methods This was a prospective study conducted at a tertiary care hospital, between February 2009 and February 2011. OGTT curve (parabolic/linear), linearity index (LI) and Parenchymal Hepatic Resection Rate (PHRR) were correlated with postoperative outcomes in terms of postoperative liver failure (PLF), by 50-50 criteria, morbidity, mortality and hospital stay. Results Of the 33 patients included in the study, 23 (69.7%) patients underwent major liver resections. Hepatocellular carcinoma (30.3%) was the leading indication. The overall postoperative morbidity rate was 72.7%, but major complications occurred in 3 (9.1%) patients only. There was no 90-day mortality. The 50-50 criteria were met by 3 patients undergoing major resection. Significant correlation was noted between the linear OGTT curve and the overall hospital stay (12.1 days vs. 9.6 days in parabolic; p=0.04). Patients with linear OGTT met the 50-50 criteria more often (18%) than those having a parabolic curve (4.5%; p=0.25). Although the OGTT was more often linear with occurrence of morbidity (41.7% vs 11.1%), major morbidity (66.7% vs 30%) and PLF by 50-50 criteria (66.7% vs 30%), it was not statistically significant. The linearity index was marginally lower (0.9 vs 1.2) in the presence of major morbidity and PLF by 50-50 criteria. Conclusions Linear OGTT affects the PLF and major morbidity, therein impacting the hospital stay. OGTT LI and PHRR can help predict postoperative outcome for a given extent of liver resection. PMID:28317039

  5. Quantitative MR Imaging of Hepatic Steatosis: Validation in Ex Vivo Human Livers

    PubMed Central

    Bannas, Peter; Kramer, Harald; Hernando, Diego; Agni, Rashmi; Cunningham, Ashley M.; Mandal, Rakesh; Motosugi, Utaroh; Sharma, Samir D.; del Rio, Alejandro Munoz; Fernandez, Luis; Reeder, Scott B.

    2015-01-01

    Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have demonstrated tremendous promise for accurate quantification of hepatic triglyceride concentration. These methods quantify the “proton density fat-fraction” (PDFF), which reflects the concentration of triglycerides in tissue. Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with the underlying hepatic triglyceride content remained unknown. The aim of this ex vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction and histology as three independent reference standards. A secondary aim was to compare the precision of MRI-PDFF relative to biopsy for the quantification of hepatic steatosis. MRI-PDFF was prospectively performed at 1.5T in 13 explanted human livers. We performed co-localized paired evaluation of liver fat content in all nine Couinaud segments using single-voxel MRS-PDFF (n=117), tissue wedges for biochemical triglyceride extraction (n=117), and five core biopsies performed in each segment for histologic grading (n=585). Accuracy of MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride extraction and histology. Intra-observer agreement, inter-observer agreement and repeatability of MRI-PDFF and histologic grading were assessed through Bland-Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r=0.984; CI: 0.978–0.989) and strong correlation with histology (r=0.850; CI: 0.791–0.894) and triglyceride extraction (r=0.871; CI: 0.818–0.909). Intra-observer agreement, inter-observer agreement and repeatability showed a significantly smaller variance for MRI-PDFF than for histologic steatosis grading (all p<0.001). Conclusion MRI-PDFF is an accurate

  6. Importance of Endocytic Pathways in Liver Function and Disease

    PubMed Central

    Schroeder, Barbara; McNiven, Mark A.

    2015-01-01

    Hepatocellular endocytosis is a highly dynamic process responsible for the internalization of a variety of different receptor ligand complexes, trophic factors, lipids, and, unfortunately, many different pathogens. The uptake of these external agents has profound effects on seminal cellular processes including signaling cascades, migration, growth, and proliferation. The hepatocyte, like other well-polarized epithelial cells, posses a host of different endocytic mechanisms and entry routes to ensure the selective internalization of cargo molecules. These pathways include receptor-mediated endocytosis, lipid raft associated endocytosis, caveolae, or fluid-phase uptake although there are likely many others. Understanding and defining the regulatory mechanisms underlying these distinct entry routes, sorting and vesicle formation, as well as the postendocytic trafficking pathways is of high importance especially in the liver, as their mis-regulation can contribute to aberrant liver pathology and liver diseases. Further, these processes can be “hijacked” by a variety of different infectious agents and viruses. This review provides an overview of common components of the endocytic and postendocytic trafficking pathways utilized by hepatocytes. It will also discuss in more detail how these general themes apply to liver-specific processes including iron homeostasis, HBV infection, and even hepatic steatosis. PMID:25428849

  7. Cognitive and Adaptive Functioning after Liver Transplantation for Maple Syrup Urine Disease: A Case Series

    PubMed Central

    Shellmer, D. A.; Dabbs, A. DeVito; Dew, M. A.; Noll, R. B.; Feldman, H.; Strauss, K.; Morton, D. H.; Vockley, G.; Mazariegos, G. V.

    2011-01-01

    MSUD is a complex metabolic disorder that has been associated with central nervous system damage, developmental delays, and neurocognitive deficits. Although liver transplantation provides a metabolic cure for MSUD, changes in cognitive and adaptive functioning following transplantation have not been investigated. In this report we present data from 14 patients who completed cognitive and adaptive functioning testing pre- and one year and/or three years post-liver transplantation. Findings show either no significant change or improvement in IQ scores pre- to post-liver transplantation. Greater variability was observed in adaptive functioning scores, but the majority of patients evidenced either no significant change or improvement in adaptive scores. In general, findings may indicate that liver transplantation curtails additional central nervous system damage and neurocognitive decline providing an opportunity for stabilization or improvement in functioning. PMID:20946191

  8. β-Glucuronidase is a suitable internal control gene for mRNA quantitation in pathophysiological and non-pathological livers.

    PubMed

    Yamaguchi, Hiromi; Matsumoto, Sawako; Ishibashi, Mariko; Hasegawa, Kiyoshi; Sugitani, Masahiko; Takayama, Tadatoshi; Esumi, Mariko

    2013-10-01

    The level of expression of housekeeping genes is in general considered stable, and a representative gene such as glyceraldehyde-3-phosphate dehydrogenase is commonly used as an internal control for quantitating mRNA. However, expression of housekeeping genes is not always constant under pathological conditions. To determine which genes would be most suitable as internal controls for quantitative gene expression studies in human liver diseases, we quantified 12 representative housekeeping genes in 27 non-cancerous liver tissues (normal, chronic hepatitis C with and without liver cirrhosis). We identified β-glucuronidase as the most suitable gene for studies on liver by rigorous statistical analysis of inter- and intra-group comparisons. We conclude that it is important to determine the most appropriate control gene for the particular condition to be analyzed. © 2013 Elsevier Inc. All rights reserved.

  9. Distinct development and functions of resident and recruited liver Kupffer cells/macrophages.

    PubMed

    Ikarashi, Masami; Nakashima, Hiroyuki; Kinoshita, Manabu; Sato, Atsushi; Nakashima, Masahiro; Miyazaki, Hiromi; Nishiyama, Kiyoshi; Yamamoto, Junji; Seki, Shuhji

    2013-12-01

    Although mouse liver F4/80(+) Kupffer cells consist of cytokine-producing CD11b(+) cells and phagocytic CD68(+) cells, an undefined CD11b(-) CD68(-) subset (30%) also exists. We herein demonstrate a more fundamental classification by adding CD32 (FcγRII), which covers most liver F4/80(+) cells and the distinct functions of them. Among the F4/80(+) cells, 50%, 40%, and 30% of cells were CD32(+), CD68(+), and CD11b(+), respectively, and one-half of the CD68(+) cells coexpressed CD32. CD68(+) and CD32(+) cells, but not CD11b(+) cells, expressed a phagocytosis-related CRIg. Gy (6) irradiation depleted liver CD11b(+) cells and those in the spleen, bone marrow, and peripheral blood but not liver CD32/CD68(+) cells. Transfer of bone marrow cells into the irradiated mice reconstituted liver CD11b(+) cells. Conversely, clodronate pretreatment depleted only liver CD32/CD68(+) cells but not liver CD11b(+) cells and peripheral blood or spleen CD11b(+) monocytes/macrophages. Moreover, the CD32(+) cells might be precursors of CD68(+) cells, as a large proportion of CD32(+) cells expressed the c-kit (CD117), and CD34 and CD32(+) cells acquired CD68 immediately after bacteria administration. CD32/CD68(+) cells, but not CD11b(+) cells, expressed resident macrophage-specific MerTK and CD64 (FcγRI). Challenge with Staphylococcus aureus or liver metastatic EL-4 tumor cells indicated that the CD68(+) subset is engaged in systemic bactericidal activity, whereas the CD11b(+) subset is pivotal for liver antitumor immunity. Human liver CD14(+) Kupffer cells could also be classified into three similar subsets. These results suggest that liver CD68(+) Kupffer cells and CD11b(+) Kupffer cells/macrophages are developmentally and functionally distinct subsets.

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

    PubMed

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

    2012-01-01

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

  11. Quantitative ionization energies and work functions of aqueous solutions.

    PubMed

    Olivieri, Giorgia; Goel, Alok; Kleibert, Armin; Cvetko, Dean; Brown, Matthew A

    2016-10-26

    Despite the ubiquitous nature of aqueous solutions across the chemical, biological and environmental sciences our experimental understanding of their electronic structure is rudimentary-qualitative at best. One of the most basic and seemingly straightforward properties of aqueous solutions-ionization energies-are (qualitatively) tabulated at the water-air interface for a mere handful of solutes, and the manner in which these results are obtained assume the aqueous solutions behave like a gas in the photoelectron experiment (where the vacuum levels of the aqueous solution and of the photoelectron analyzer are equilibrated). Here we report the experimental measure of a sizeable offset (ca. 0.6 eV) between the vacuum levels of an aqueous solution (0.05 M NaCl) and that of our photoelectron analyzer, indicating a breakdown of the gas-like vacuum level alignment assumption for the aqueous solution. By quantifying the vacuum level offset as a function of solution chemical composition our measurements enable, for the first time, quantitative determination of ionization energies in liquid solutions. These results reveal that the ionization energy of liquid water is not independent of the chemical composition of the solution as is usually inferred in the literature, a finding that has important ramifications as measured ionization energies are frequently used to validate theoretical models that posses the ability to provide microscopic insight not directly available by experiment. Finally, we derive the work function, or the electrochemical potential of the aqueous solution and show that it too varies with the chemical composition of the solution.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  14. Deep gray matter iron measurement in patients with liver cirrhosis using quantitative susceptibility mapping: Relationship with pallidal T1 hyperintensity.

    PubMed

    Lee, Song; Nam, Yoonho; Jang, Jinhee; Na, Gun Hyung; Kim, Dong Goo; Shin, Na-Young; Choi, Hyun Seok; Jung, So-Lyung; Ahn, Kook-Jin; Kim, Bum-Soo

    2017-08-17

    The liver is a central organ for the metabolism of iron and manganese and the places where those metals are commonly deposited overlap in the brain. To elucidate the relationship between pallidal T1 hyperintensity and iron deposition in the deep gray matter of liver cirrhosis patients using quantitative susceptibility mapping (QSM). Retrospective case-control study SUBJECTS: In all, 38 consecutive liver cirrhosis patients who received brain magnetic resonance imaging (MRI) as pretransplant evaluation. QSM was reconstructed from 3D multi- or single-echo phase images at 3T. T1 -weighted images were used for the assessment of pallidal hyperintensity and pallidal index (PI). Patients were divided into two groups according to the presence of pallidal hyperintensity by consensus of two radiologists. Susceptibility values were acquired for five deep gray matter structures. QSM measures were compared between two groups using the t-test. We also calculated Pearson correlations between QSM measures and PI. In all, 26 patients showed pallidal hyperintensity (T1 h group) and 12 did not (T1 n group). The susceptibility of the globus pallidus (GP) in the T1 h group (120.6 ± 38.1 ppb) was significantly lower than that in the T1 n group (150.0 ± 35.2, P = 0.030). The susceptibility of the dentate nucleus (DN) in the T1 h group (88.1 ± 31.0) was significantly lower than that in the T1 n group (125.6 ± 30.6, P = 0.001). Negative correlation between the susceptibility of GP (r = -0.37, P = 0.022) and the PI, and between DN (r = -0.43, P < 0.001) and the PI was found. Liver cirrhosis patients with pallidal T1 hyperintensity had lower susceptibility values in the GP and DN than those without it. This suggests a possible interaction between iron and manganese in the brains of liver cirrhosis patients. 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.

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

    PubMed

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

    2016-09-01

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

  16. Effect of Non-speckle Echo Signals on Tissue Characteristics for Liver Fibrosis using Probability Density Function of Ultrasonic B-mode image

    NASA Astrophysics Data System (ADS)

    Mori, Shohei; Hirata, Shinnosuke; Yamaguchi, Tadashi; Hachiya, Hiroyuki

    To develop a quantitative diagnostic method for liver fibrosis using an ultrasound B-mode image, a probability imaging method of tissue characteristics based on a multi-Rayleigh model, which expresses a probability density function of echo signals from liver fibrosis, has been proposed. In this paper, an effect of non-speckle echo signals on tissue characteristics estimated from the multi-Rayleigh model was evaluated. Non-speckle signals were determined and removed using the modeling error of the multi-Rayleigh model. The correct tissue characteristics of fibrotic tissue could be estimated with the removal of non-speckle signals.

  17. The Differential Expression and Possible Function of Long Noncoding RNAs in Liver Cells Infected by Dengue Virus.

    PubMed

    Wang, Xiao-Jun; Jiang, Shi-Chen; Wei, Hai-Xia; Deng, Sheng-Qun; He, Cheng; Peng, Hong-Juan

    2017-10-02

    The function of long noncoding RNAs (lncRNAs) in liver injury resulted by dengue virus (DENV) infection have not yet been explored. The differential expression profiles of lncRNAs coupled with mRNAs in L-02 liver cells in the DENV1 infected, DENV2 infected, and untreated control group were analyzed after high throughput RNA sequencing, the significantly upregulated and downregulated lncRNAs or mRNAs comparing with the control group were identified with a cutoff value at log2 (ratio) ≥ 1.5 and log2 (ratio) ≤ -1.5, respectively. Several differentially expressed lncRNAs were verified with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Target gene analysis, pre-miRNA prediction, and the lncRNA-mRNA co-expression network construction were performed to predict the function of the differentially expressed lncRNAs. The differentially expressed lncRNAs were associated with biosynthesis, DNA/RNA related processes, inhibition of estrogen signaling pathway, sterol biosynthetic process, protein dimerization activity, vesicular fraction in DENV1 infection group; and with protein secretion, methyltransferase process, host cell cytoskeleton reorganization and the small GTPase Ras superfamily, inhibition of cell proliferation, induction of apoptosis in DENV2 infection. LncRNAs might be novel diagnostic markers and targets for further researches on dengue infection and liver injury resulted by dengue virus.

  18. Assessment of liver function among nickel-plating workers in Egypt.

    PubMed

    El-Shafei, H M

    2011-06-01

    Currently no reports are available from Egypt regarding occupational exposure to nickel and its effects on the liver. The aim of this study was to assess the liver function of workers occupationally exposed to nickel. Standard liver function tests were applied to blood samples from 25 nickel-plating workers in Damietta, Egypt and 30 administrative workers as a reference group. Levels of urine nickel, measured by inductively coupling plasma-emission spectroscopy, were significantly higher in nickel-exposed workers compared with the reference group. The levels of alanine aminotransferase and aspartate aminotransferase were significantly higher in nickel-exposed workers. The level of serum albumin was significantly negatively correlated and the levels of serum aminotransferases, and serum gamma-glutamyl-transpeptidase were significantly positively correlated with urine nickel levels. Liver function is compromised in nickel-plating workers compared with non-exposed administrative workers.

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

    PubMed

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

    2014-01-01

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

  20. Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

    PubMed Central

    Reichen, J; Egger, B; Ohara, N; Zeltner, T B; Zysset, T; Zimmermann, A

    1988-01-01

    We investigated the determinants of hepatic clearance functions in a rat model of liver cirrhosis induced by phenobarbital/CCl4. Aminopyrine N-demethylation (ABT), galactose elimination (GBT), and serum bile acids (SBA) were determined in vivo. The livers were then characterized hemodynamically: intrahepatic shunting (IHS) was determined by microspheres and sinusoidal capillarization by measuring the extravascular albumin space (EVA) by a multiple indicator dilution technique. The intrinsic clearance was determined by assaying the activity of the rate-limiting enzymes in vitro. Hepatocellular volume (HCV) was measured by morphometry. ABT and SBA, but not GBT, differentiated cirrhotic from normal liver. IHS ranged from normal to 10%; all cirrhotic livers showed evidence of sinusoidal capillarization (reduced EVA). The cirrhotic livers showed a bimodal distribution of HCV, HCV being decreased in 50% of the cirrhotic livers. Multivariate analysis showed EVA and portal flow to be the main determinants of microsomal (ABT) and cytosolic (GBT) clearance function; SBA, by contrast, were determined solely by IHS. We conclude that sinusoidal capillarization is the main determinant of hepatic clearance, while serum bile acids reflect intrahepatic shunting. These findings emphasize the importance of alterations of hepatic nutritional flow to explain reduced clearance function in cirrhosis of the liver. PMID:3198765

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

    PubMed

    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.

  2. Engineering functional two- and three-dimensional liver systems in vivo using hepatic tissue sheets.

    PubMed

    Ohashi, Kazuo; Yokoyama, Takashi; Yamato, Masayuki; Kuge, Hiroyuki; Kanehiro, Hiromichi; Tsutsumi, Masahiro; Amanuma, Toshihiro; Iwata, Hiroo; Yang, Joseph; Okano, Teruo; Nakajima, Yoshiyuki

    2007-07-01

    Hepatic tissue engineering using primary hepatocytes has been considered a valuable new therapeutic modality for several classes of liver diseases. Recent progress in the development of clinically feasible liver tissue engineering approaches, however, has been hampered mainly by insufficient cell-to-cell contact of the engrafted hepatocytes. We developed a method to engineer a uniformly continuous sheet of hepatic tissue using isolated primary hepatocytes cultured on temperature-responsive surfaces. Sheets of hepatic tissue transplanted into the subcutaneous space resulted in efficient engraftment to the surrounding cells, with the formation of two-dimensional hepatic tissues that stably persisted for longer than 200 d. The engineered hepatic tissues also showed several characteristics of liver-specific functionality. Additionally, when the hepatic tissue sheets were layered in vivo, three-dimensional miniature liver systems having persistent survivability could be also engineered. This technology for liver tissue engineering is simple, minimally invasive and free of potentially immunogenic biodegradable scaffolds.

  3. Liver function in workers exposed of the cosmetics industry.

    PubMed

    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 <0.05. The analysis of the results shows that 35.4% of workers in the cosmetics industry had liver test values above the range. We noted a statistically significant higher prevalence of GPT (p <0.05) and total bilirubin (p <0.05) in the workers of the 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. Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?

    PubMed Central

    Ehler, Johannes; Wagner, Nana-Maria

    2017-01-01

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

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

    PubMed

    Sauer, Martin; Doß, Sandra; Ehler, Johannes; Mencke, Thomas; Wagner, Nana-Maria

    2017-01-01

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

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

    SciTech Connect

    Cao Yue; Wang Hesheng; Johnson, Timothy D.; Pan, Charlie; Hussain, Hero; Balter, James M.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    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

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

    PubMed Central

    Cao, Yue; Wang, Hesheng; Johnson, Timothy D.; Pan, Charlie; Hussain, Hero; Balter, James M.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

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

    PubMed

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

    2011-10-01

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

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

    PubMed

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

    2016-02-01

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

  11. Mechanical Model Analysis for Quantitative Evaluation of Liver Fibrosis Based on Ultrasound Tissue Elasticity Imaging

    NASA Astrophysics Data System (ADS)

    Shiina, Tsuyoshi; Maki, Tomonori; Yamakawa, Makoto; Mitake, Tsuyoshi; Kudo, Masatoshi; Fujimoto, Kenji

    2012-07-01

    Precise evaluation of the stage of chronic hepatitis C with respect to fibrosis has become an important issue to prevent the occurrence of cirrhosis and to initiate appropriate therapeutic intervention such as viral eradication using interferon. Ultrasound tissue elasticity imaging, i.e., elastography can visualize tissue hardness/softness, and its clinical usefulness has been studied to detect and evaluate tumors. We have recently reported that the texture of elasticity image changes as fibrosis progresses. To evaluate fibrosis progression quantitatively on the basis of ultrasound tissue elasticity imaging, we introduced a mechanical model of fibrosis progression and simulated the process by which hepatic fibrosis affects elasticity images and compared the results with those clinical data analysis. As a result, it was confirmed that even in diffuse diseases like chronic hepatitis, the patterns of elasticity images are related to fibrous structural changes caused by hepatic disease and can be used to derive features for quantitative evaluation of fibrosis stage.

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

    PubMed

    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.

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

    PubMed

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

    2016-08-01

    , Bartell SM, 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.

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

    PubMed Central

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

    2016-01-01

    diagnosed liver disease. Citation: Darrow LA, Groth AC, Winquist A, Shin HM, Bartell SM, 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 PMID:26978841

  15. Toxicity effect of nigella sativa on the liver function of rats.

    PubMed

    Dollah, Mohammad Aziz; Parhizkar, Saadat; Latiff, Latiffah Abdul; Bin Hassan, Mohammad Hafanizam

    2013-01-01

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

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

    PubMed Central

    Dollah, Mohammad Aziz; Parhizkar, Saadat; Latiff, Latiffah Abdul; Bin Hassan, Mohammad Hafanizam

    2013-01-01

    Purpose: The aim of this study was to determine the toxic effect of Nigella sativa powder on the liver function which was evaluated by measuring liver enzymes and through histopathological examination of liver tissue. Methods: Twenty four male Sprague Dawley rats were allotted randomly to four groups including: control (taking normal diet); low dose (supplemented with 0.01 g/kg/day Nigella sativa); normal dose (supplemented with 0.1 g/kg/day Nigella sativa) and high dose (supplemented with 1 g/kg/day Nigella sativa). All of supplements administered in powder form mixed with rats’ pellet for 28 days. To assess liver toxicity, liver enzymes measurement and histological study were done at the end of supplementation. Results: The finding revealed that there was no significant change in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between treatment groups. Histopathological study showed very minimal and mild changes in fatty degeneration in normal and high doses of Nigella sativa treated group. Inflammation and necrosis were absent. Conclusion: The study showed that supplementation of Nigella sativa up to the dose of 1 g/kg supplemented for a period of 28 days resulted no changes in liver enzymes level and did not cause any toxicity effect on the liver function. PMID:24312819

  17. Evaluation of liver function tests in scleroderma patients.

    PubMed

    Salem, Gehan Ibrahim Abdelrazek; Abdulrahman, Awni Ali

    2012-08-01

    Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs, and the walls of blood vessels. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. This study was done to evaluate the frequency of liver disease in patients with scleroderma and, secondarily, to study the frequency of infection of hepatitis B and C virus in these patients and determine frequency of serum auto-antibodies in this disease. We studied patients with scleroderma, localized or systemic, in the outpatient clinic of rheumatology and dermatology departments, at King Khalid University Hospital. As for a comparison, healthy persons coming to the clinic with the same mean age were considered as control group. Forty patients with the diagnosis of scleroderma included in this work, 35% had elevated gamma-glutamyl-transferase (γ-GT), 30% had elevated alkaline phosphatase (AP) and in 17.5%, the alanine-amino-transferase (ALT) was above the reference values. The ALT had changed to be more in scleroderma patients than in controls. Twenty percent (20%) of the patients tested positive for anti-smooth muscle antibodies (anti-SMA) and only one patient had anti-mitochondrial antibodies (AMA). There was no statistical difference between the two groups regarding antibody testing. Anti-HCV antibodies were observed in one patient, and HBsAg was detected in another scleroderma patient. There was no patient with clinically significant hepatic disease. In this study, although changes in liver enzymes in patients with scleroderma were not uncommon, there was no scleroderma patient with clinical manifestations of liver disease.

  18. Effects of Bariatric Surgery on Liver Function Tests in Patients with Nonalcoholic Fatty Liver Disease.

    PubMed

    Ooi, Geraldine J; Burton, Paul R; Doyle, Lisa; Wentworth, John M; Bhathal, Prithi S; Sikaris, Ken; Cowley, Michael A; Roberts, Stuart K; Kemp, William; Earnest, Arul; O'Brien, Paul E; Brown, Wendy A

    2017-06-01

    Nonalcoholic fatty liver disease (NAFLD) affects over 80% of obese patients and is fueled by the metabolic syndrome. Weight loss is strongly advocated as a central treatment for NAFLD and has been shown to induce histological improvement. We aimed to define the patterns of improvement in NAFLD with weight loss and determine target weight goals for NAFLD resolution. A prospective study of 84 morbidly obese patients with NAFLD undergoing bariatric surgery was conducted. Intraoperative liver biopsies were taken. Monthly follow-up, including blood tests and measurements, was performed. We monitored improvements in NAFLD by monthly alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) levels over 1 year. There was rapid improvement in ALT, particularly in the first 6 months following surgery, with statistically significant reduction in ALT at 2 months (35 vs 27 IU/L, p < 0.001). In multivariate analysis, there were significantly increased odds of ALT normalization after a %TBWL of 10-15% (odds ratio 2.49, p = 0.005). The odds of resolution increased with increasing weight loss. Triglyceride levels (odds ratio 0.59, p = 0.021) and baseline NAFLD activity score (odds ratio 0.28, p < 0.001) were also significantly related to ALT normalization. Improvements in ALT occurred prior to metabolic improvement and well before traditional ideal weight goals were reached. Improvements in NAFLD occurred rapidly after bariatric surgery and were closely related to weight loss and metabolic factors. A 10-15% reduction in body weight is an appropriate target to achieve substantial improvement in ALT levels. Australian Clinical Trials Registry (ACTRN12610000049077).

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

    PubMed

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

    1983-10-01

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

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

    PubMed

    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 < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, gamma GT and ALP remained within the normal range. The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the 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

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

    PubMed Central

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

    2008-01-01

    Aim To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Methods 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 (γGT), 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. Results Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, γGT and ALP remained within the normal range. Conclusion The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the 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. What is already known about this subject 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. What this study adds Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Giampieri, Francesca; Alvarez-Suarez, Josè M; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Y; Afrin, Sadia; Rubini, Corrado; Zizzi, Antonio; Quiles, Josè L; Mezzetti, Bruno; Battino, Maurizio

    2017-08-01

    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. Validation of an efficient LC-microdialysis method for gemifloxacin quantitation in lung, kidney and liver of rats.

    PubMed

    de Araújo, Bibiana Verlindo; Laureano, João Victor; Grünspan, Lauren Dockhorn; Dalla Costa, Teresa; Tasso, Leandro

    2013-03-01

    A liquid chromatography method has been established for the reliable determination of unbound gemifloxacin concentrations in kidney, lung and liver microdialysates of rats. Microdialysis probes were inserted into tissues of rats, and then dialysates were collected at regular time intervals after intravenous administration of gemifloxacin (40 mg kg(-1)). A pilot study was performed to assess gemifloxacin penetration in lung, kidney and liver of rats. Gemifloxacin was separated on a C(18) column eluted using triethylamine solution (0.5%, v/v), adjusted to pH 3.0±0.1 with 85% phosphoric acid, methanol and acetonitrile (71:15:14, v/v/v) as mobile phase at a flow rate of 1.1 mL min(-1). The fluorescence detector was set at excitation and emission wavelengths of 344 nm and 399 nm, respectively. The limit of quantitation was found to be 50 ng mL(-1). Linearity was found to be over a concentration range of 50-2000 ng mL(-1). The intra-assay and inter-assay precision and accuracy values were determined from the analysis of six quality control samples. The results obtained at three concentration levels showed R.S.D. values lower than 6.06% and 4.10% for repeatability and intermediate precision, respectively. The accuracy (R.E.%) ranged from 90.0 to 106.5%. The chromatographic run time of each sample was performed in 9 min. Drug stability in microdialysates was shown at room temperature for 8h, after three freeze-thaw cycles, in freezer at -80 °C for 14 days, and in the autosampler after processing for 8h. The relative recoveries determined by extraction efficiency (EE) and retrodialysis (RD) in vitro employing a flow rate of 1.5 μL min(-1) were 29.24±3.67% and 23.67±3.31%, respectively. In vivo recoveries determined by RD in Wistar rats' kidney, lung and liver were 27.69±2.09%, 23.12±3.79% and 17.38±0.68%, respectively. The method was successfully applied to investigate tissue penetration of unbound gemifloxacin into the kidney, lung and liver of rats. Copyright

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

    SciTech Connect

    Andre, M; Heba, E; Lin, S; Wolfson, T; Ang, B; Gamst, A; Sirlin, C; Loomba, R; Han, A; Erdman, J; O’Brien, W

    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

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  8. Liver function in alpha-1-antitrypsin deficient individuals at 37 to 40 years of age

    PubMed Central

    Mostafavi, Behrouz; Diaz, Sandra; Tanash, Hanan A.; Piitulainen, Eeva

    2017-01-01

    Abstract Severe alpha-1-antitrypsin (AAT) deficiency (PiZZ) is a risk factor for liver disease, but the prevalence of liver cirrhosis and hepatocellular cancer in PiZZ adults is unknown. The risk of liver disease in adults with moderate AAT deficiency (PiSZ) is also unknown. A cohort of 127 PiZZ, 2 PiZnull, 54 PiSZ, and 1 PiSnull individuals were identified by the Swedish national neonatal AAT screening program between 1972 and 1974, when all 200,000 newborn infants in Sweden were screened for AAT deficiency. The cohort has been followed up since birth. Our aim was to study liver function and signs of liver disease in this cohort at 37 to 40 years of age in comparison with a matched, random sample of control subjects identified from the population registry. Eighty seven PiZZ, 32 PiSZ, and 92 control subjects (PiMM) answered a questionnaire on medication and alcohol consumption and provided blood samples. Liver stiffness was assessed by Acoustic Radiation Force Impulse (ARFI) elastography in 32 PiZZ, 15 PiSZ, and 51 PiMM subjects. The median of liver function tests and procollagen-III-peptide were within the normal range in all Pi subgroups. However, the PiZZ men had significantly higher plasma bilirubin than the PiMM men (P = 0.018). Plasma ɣ-glutamyl transferase (GGT) was significantly higher in the PiZZ men (P = 0.009) and the PiSZ men (P = 0.021) compared with the PiMM men. The median of liver stiffness was significantly higher in the PiZZ men (P = 0.037) and the PiSZ men (P = 0.032) compared with the PiMM men. The PiZZ women taking medication influencing liver enzymes had significantly higher GGT than the PiMM women on the corresponding treatment (P = 0.023). These AAT-deficient individuals identified by neonatal screening have normal plasma levels of liver function tests, and no clinical signs indicating liver disease at the age of 37 to 40 years. However, bilirubin, GGT, and liver stiffness are significantly higher in PiZZ men than Pi

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

    PubMed Central

    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

    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. PMID:26488607

  10. UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration

    PubMed Central

    Waage, Johannes; Jakobsen, Janus S.; Damgaard, Inge; Bergström, Frida C.; Blom, Anna M.; Borup, Rehannah; Bisgaard, Hanne Cathrine; Porse, Bo T.

    2010-01-01

    Background Nonsense-mediated mRNA decay (NMD) is a post-transcriptional RNA surveillance process that facilitates the recognition and destruction of mRNAs bearing premature terminations codons (PTCs). Such PTC-containing (PTC+) mRNAs may arise from different processes, including erroneous processing and expression of pseudogenes, but also from more regulated events such as alternative splicing coupled NMD (AS-NMD). Thus, the NMD pathway serves both as a silencer of genomic noise and a regulator of gene expression. Given the early embryonic lethality in NMD deficient mice, uncovering the full 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 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. 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. PMID:20657840

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

    PubMed

    Thoren, Lina A; Nørgaard, Gitte A; Weischenfeldt, Joachim; Waage, Johannes; Jakobsen, Janus S; Damgaard, Inge; Bergström, Frida C; Blom, Anna M; Borup, Rehannah; Bisgaard, Hanne Cathrine; Porse, Bo T

    2010-07-19

    Nonsense-mediated mRNA decay (NMD) is a post-transcriptional RNA surveillance process that facilitates the recognition and destruction of mRNAs bearing premature terminations codons (PTCs). Such PTC-containing (PTC+) mRNAs may arise from different processes, including erroneous processing and expression of pseudogenes, but also from more regulated events such as alternative splicing coupled NMD (AS-NMD). Thus, the NMD pathway serves both as a silencer of genomic noise and a regulator of gene expression. Given the early embryonic lethality in NMD deficient mice, uncovering the full regulatory potential of the NMD pathway in mammals will require the functional assessment of NMD in different tissues. 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 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. 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.

  12. Liver condition of Holstein cows affects mitochondrial function and fertilization ability of oocytes.

    PubMed

    Tanaka, Hiroshi; Takeo, Shun; Abe, Takahito; Kin, Airi; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

    2016-06-17

    The aim of the present study was to examine the fertilization ability and mitochondrial function of oocytes derived from cows with or without liver damage. Oocytes were collected from the ovaries of cows with damaged livers (DL) and those of cows with healthy livers (HL), subjected to in vitro maturation, and fertilized in vitro. A significantly high abnormal fertilization rate was observed for oocytes from DL cows compared to oocytes from HL cows. The time to dissolve the zona pellucida by protease before fertilization was similar between the two liver conditions, whereas after fertilization treatment this time was shorter for DL cows than for HL cows. The percentage of oocytes with equivalent cortical granule distributions underneath the membrane was greater for in vitro matured oocytes from HL cows, whereas an immature distribution pattern was observed for oocytes from DL cows. In addition, a greater percentage of oocytes derived from HL cows released cortical granules following fertilization compared with oocytes from DL cows. Mitochondrial function determined by ATP content and membrane potential were similar at the germinal vesicle stage, but post-in vitro maturation, the oocytes derived from HL cows showed higher values than DL cows. The mitochondrial DNA copy number in oocytes was similar between the two liver conditions for both the germinal vesicle and post-in vitro maturation oocytes. In conclusion, liver damage induces low fertilization, likely because of incomplete cortical granule distribution and release, and the maturation of oocytes from DL cows contain low-functioning mitochondria compared to their HL counterparts.

  13. Quantitative alterations in the liver and adrenal gland in pregnant rats induced by Pyralene 3000

    SciTech Connect

    Vreci, M.; Sek, S.; Lorger, J.; Bavdek, S.; Pogacnik, A.

    1995-06-01

    Polychlorinated biphenyls (PCBs) are among the most widespread environmental pollutants known in the world. The half-life of PCBs is very long and, therefore, once released into the environment, they accumulate in food chains and tissues of various mammals, including man. Their presence can cause numerous toxic effects, e.g., hepatotoxicity, immunotoxicity, dermatotoxicity, neurotoxicity, and disorders of the reproductive system, among others. These effects depend on the distribution route in the organism, the rate of metabolism and excretion. Their characteristics are closely associated with the number and position of the chlorine atoms in the molecule. Previous studies of trichlorobiphenyl distributions in various tissues demonstrated that low chlorinated trichlorobiphenyls do no accumulate in endocrine organs, whereas higher chlorinated biphenyls, such as hexa- and octachlorobiphenyl, are deposited and retained in the adrenal gland. A selective distribution of radioabelled tetrachlorobiphenyl to the zona fasciculata, accompanied by morphometric evidence of the hypertrophy of the zona fasciculata, was also noted. The purpose of this study was to examine changes in the tissue structure of the pregnant rat liver and adrenal gland induced experimentally by Pyralene 3000 administration. We chose this commercial low chlorinated PCB because it was in use in Slovenia and, discharged from the electroindustrial plants, caused a serious incidence of environmental pollution in the region of Bela Krajina. Our further aim was to research the transplacental influences of Pyralene 3000 in rats. 17 refs., 1 fig., 3 tabs.

  14. Quantitative analysis of aberrant protein glycosylation in liver cancer plasma by AAL-enrichment and MRM mass spectrometry.

    PubMed

    Ahn, Yeong Hee; Shin, Park Min; Kim, Yong-Sam; Oh, Na Ree; Ji, Eun Sun; Kim, Kwang Hoe; Lee, Yeon Jung; Kim, Sung Ho; Yoo, Jong Shin

    2013-11-07

    A lectin-coupled mass spectrometry (MS) approach was employed to quantitatively monitor aberrant protein glycosylation in liver cancer plasma. To do this, we compared the difference in the total protein abundance of a target glycoprotein between hepatocellular carcinoma (HCC) plasmas and hepatitis B virus (HBV) plasmas, as well as the difference in lectin-specific protein glycoform abundance of the target glycoprotein. Capturing the lectin-specific protein glycoforms from a plasma sample was accomplished by using a fucose-specific aleuria aurantia lectin (AAL) immobilized onto magnetic beads via a biotin-streptavidin conjugate. Following tryptic digestion of both the total plasma and its AAL-captured fraction of each HCC and HBV sample, targeted proteomic mass spectrometry was conducted quantitatively by a multiple reaction monitoring (MRM) technique. From the MRM-based analysis of the total plasmas and AAL-captured fractions, differences between HCC and HBV plasma groups in fucosylated glycoform levels of target glycoproteins were confirmed to arise from both the change in the total protein abundance of the target proteins and the change incurred by aberrant fucosylation on target glycoproteins in HCC plasma, even when no significant change occurs in the total protein abundance level. Combining the MRM-based analysis method with the lectin-capturing technique proved to be a successful means of quantitatively investigating aberrant protein glycosylation in cancer plasma samples. Additionally, it was elucidated that the differences between HCC and control groups in fucosylated biomarker candidates A1AT and FETUA mainly originated from an increase in fucosylation levels on these target glycoproteins, rather than an increase in the total protein abundance of the target glycoproteins.

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  16. Quantitative Histological Assessment of Xenobiotic-Induced Liver Enzyme Induction and Pituitary-Thyroid Axis Stimulation in Rats Using Whole-Slide Automated Image Analysis

    PubMed Central

    Zabka, Tanja S.; Tao, Jianhua; Fielden, Mark; Fretland, Adrian; Albassam, Mudher

    2013-01-01

    Preclinical evaluation of a new compound, RO2910, identified a hypertrophic response in liver, thyroid gland, and pituitary gland (pars distalis). We aimed to develop and validate automated image analysis methods to quantify and refine the interpretation of semi-quantitative histology. Wistar-Han rats were administered RO2910 for 14 days. Liver, thyroid, and pituitary gland tissues were processed for routine histology and immunolabeled with anti–thyroid stimulating hormone (TSH) antibody (pituitary) and anti–topoisomerase II antibody (thyroid). Glass slides were scanned, image analysis methods were developed and applied to whole-slide images, and numerical results were compared with histopathology, circulating hormone levels, and liver enzyme mRNA expression for validation. Quantitative analysis of slides had strong individual correlation with semi-quantitative histological evaluation of all tissues studied. Hepatocellular hypertrophy quantification also correlated strongly with liver enzyme mRNA expression. In the pars distalis, measurement of TSH weak-staining areas correlated with both hypertrophy scores and circulating TSH levels. Whole-slide image analysis enabled automated quantification of semi-quantitative histopathology findings and a more refined interpretation of these data. The analysis also enabled a direct correlation with non-histological parameters using straightforward statistical analysis to provide a more refined dose- and sex-response relationship and integration among affected parameters. These findings demonstrate the utility of our image analysis to support preclinical safety evaluations. PMID:23456825

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

    PubMed

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

    2014-09-01

    Despite its invasiveness, liver biopsy is still considered the gold standard for the assessment of hepatic fibrosis. Non-invasive ultrasound-based techniques are increasingly employed to assess parenchymal stiffness and the progression of chronic diffuse liver diseases. Real-time elastography is a rapidly evolving technique that can reveal the elastic properties of tissues. This review examines qualitative and semi-quantitative methods developed for analysis of real-time liver elastograms, to estimate parenchymal stiffness and, indirectly, the stage of fibrosis. Qualitative analysis is the most immediate approach for elastogram analysis, but this method increases intra- and inter-observer variability, which is seen as a major limitation of real-time elastography. Semi-quantitative methods include analysis of the histogram derived from color-coded maps, as well as calculation of the elastic ratio and fibrosis index. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  18. Association between liver function and metabolic syndrome in Chinese men and women

    PubMed Central

    Wang, Sen; Zhang, Jie; Zhu, Li; Song, Linlin; Meng, Zhaowei; Jia, Qiang; Li, Xue; Liu, Na; Hu, Tianpeng; Zhou, Pingping; Zhang, Qing; Liu, Li; Song, Kun; Jia, Qiyu

    2017-01-01

    Metabolic syndrome (MS) could be associated with liver function. Our study aimed to investigate the association between liver function and MS in a large cohort of Chinese men and women. We enrolled 32,768 ostensibly healthy participants. The associations between liver function and MS of both genders were analyzed separately after dividing total bilirubin (TBIL), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) into quartiles. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher MS prevalence. We used TBIL, GGT and ALT quartiles as categorical variables in binary logistic regression models. Significantly decreased MS risks were demonstrated in TBIL quartiles 2 to 4 for males, and quartiles 3 to 4 for females. As to GGT and ALT, significantly increased MS risks were shown in high quartiles for both genders. Aging also resulted in significantly higher MS risks in both genders except for young females. This study displayed close associations between liver function and MS, which were influenced by gender and age. A high TBIL level had protective effect against MS, while high GGT and ALT levels were risk factors for MS. It is meaningful that liver function is used as clinical risk predictors for MS. PMID:28317840

  19. Association between liver function and metabolic syndrome in Chinese men and women.

    PubMed

    Wang, Sen; Zhang, Jie; Zhu, Li; Song, Linlin; Meng, Zhaowei; Jia, Qiang; Li, Xue; Liu, Na; Hu, Tianpeng; Zhou, Pingping; Zhang, Qing; Liu, Li; Song, Kun; Jia, Qiyu

    2017-03-20

    Metabolic syndrome (MS) could be associated with liver function. Our study aimed to investigate the association between liver function and MS in a large cohort of Chinese men and women. We enrolled 32,768 ostensibly healthy participants. The associations between liver function and MS of both genders were analyzed separately after dividing total bilirubin (TBIL), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) into quartiles. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher MS prevalence. We used TBIL, GGT and ALT quartiles as categorical variables in binary logistic regression models. Significantly decreased MS risks were demonstrated in TBIL quartiles 2 to 4 for males, and quartiles 3 to 4 for females. As to GGT and ALT, significantly increased MS risks were shown in high quartiles for both genders. Aging also resulted in significantly higher MS risks in both genders except for young females. This study displayed close associations between liver function and MS, which were influenced by gender and age. A high TBIL level had protective effect against MS, while high GGT and ALT levels were risk factors for MS. It is meaningful that liver function is used as clinical risk predictors for MS.

  20. Transarterial chemo-embolisation of hepatocellular carcinoma: impact of liver function and vascular invasion

    PubMed Central

    Waked, Imam; Berhane, Sarah; Toyoda, Hidenori; Chan, Stephen L; Stern, Nicholas; Palmer, Daniel; Tada, Toshifumi; Yeo, Winnie; Mo, Frankie; Bettinger, Dominik; Kirstein, Martha M; Iñarrairaegui, Mercedes; Gomaa, Asmaa; Vogel, Arndt; Meyer, Tim; Sangro, Bruno; Lai, Paul; Kumada, Takashi; Johnson, Philip J

    2017-01-01

    Background: Transarterial chemo-embolisation (TACE) is recommended for patients with BCLC intermediate stage hepatocellular carcinoma (stage B), particularly in patients with good underlying liver function and minimal symptoms. The hepatoma arterial embolisation prognostic (HAP) score combines measures of liver function and tumour-related factors to offer a simple prognostic scoring system. The Albumin-Bilirubin (ALBI) grade permits assessment of the impact of liver function on survival. We aimed to investigate these two models and vascular invasion (VI). Methods: In an international cohort of 3030 patients undergoing TACE, we examined the impact of liver function as assessed by the ALBI score, the HAP score and VI on survival. Results: Classification according to ALBI grade resulted in non-overlapping survival curves in the overall data set and all regional cohorts. The HAP score was also validated. Tumour number, aetiology and VI were identified as additional independent prognostic risk factors not currently included in the HAP score. Survival was particularly poor for patients with VI. Conclusions: The ALBI grade categorised patients receiving TACE into three clear prognostic groups, thereby emphasising the importance of underlying liver function in the outcome of TACE. The HAP score has been validated internationally and the serious adverse impact of VI is clearly shown. PMID:28125820

  1. Irisin levels in relation to metabolic and liver functions in Egyptian patients with metabolic syndrome.

    PubMed

    Rizk, Fatma H; Elshweikh, Samah A; Abd El-Naby, Amira Y

    2016-04-01

    Irisin is a new myokine that is suspected to influence metabolic syndrome (MetS). However, there is a great controversy with respect to its level in cases of MetS and its correlation with different metabolic parameters. The present study assesses irisin levels in MetS patients and studies its relationship to metabolic and liver functions to evaluate the possible role of the liver in regulation of this level. Sixty subjects were included in this experiment, who were divided into 3 groups: group I (normal control), group II (MetS patients with normal liver enzymes), and group III (MetS with elevated liver enzymes and fatty liver disease). Serum irisin levels showed significant increases in groups II and III compared with group I, and significant increases in group III compared with group II. Also, irisin levels were positively correlated with body mass index, serum triglycerides, homeostatic model assessment of insulin resistance index (HOMA-IR), and liver enzymes. We concluded that serum irisin levels increased in patients with MetS, especially those with elevated liver enzymes, and had a positive correlation with parameters of lipid metabolism and glucose homeostasis with the possibility of hepatic clearance to irisin.

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

    ERIC Educational Resources Information Center

    Moore, Kevin C.

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Moore, Kevin C.

    2014-01-01

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

  4. Molecular regulation of urea cycle function by the liver glucocorticoid receptor.

    PubMed

    Okun, Jürgen G; Conway, Sean; Schmidt, Kathrin V; Schumacher, Jonas; Wang, Xiaoyue; de Guia, Roldan; Zota, Annika; Klement, Johanna; Seibert, Oksana; Peters, Achim; Maida, Adriano; Herzig, Stephan; Rose, Adam J

    2015-10-01

    One of the major side effects of glucocorticoid (GC) treatment is lean tissue wasting, indicating a prominent role in systemic amino acid metabolism. In order to uncover a novel aspect of GCs and their intracellular-receptor, the glucocorticoid receptor (GR), on metabolic control, we conducted amino acid and acylcarnitine profiling in human and mouse models of GC/GR gain- and loss-of-function. Blood serum and tissue metabolite levels were determined in Human Addison's disease (AD) patients as well as in mouse models of systemic and liver-specific GR loss-of-function (AAV-miR-GR) with or without dexamethasone (DEX) treatments. Body composition and neuromuscular and metabolic function tests were conducted in vivo and ex vivo, the latter using precision cut liver slices. A serum metabolite signature of impaired urea cycle function (i.e. higher [ARG]:[ORN + CIT]) was observed in human (CTRL: 0.45 ± 0.03, AD: 1.29 ± 0.04; p < 0.001) and mouse (AAV-miR-NC: 0.97 ± 0.13, AAV-miR-GR: 2.20 ± 0.19; p < 0.001) GC/GR loss-of-function, with similar patterns also observed in liver. Serum urea levels were consistently affected by GC/GR gain- (∼+32%) and loss (∼-30%) -of-function. Combined liver-specific GR loss-of-function with DEX treatment revealed a tissue-autonomous role for the GR to coordinate an upregulation of liver urea production rate in vivo and ex vivo, and prevent hyperammonaemia and associated neuromuscular dysfunction in vivo. Liver mRNA expression profiling and GR-cistrome mining identified Arginase I (ARG1) a urea cycle gene targeted by the liver GR. The liver GR controls systemic and liver urea cycle function by transcriptional regulation of ARG1 expression.

  5. Novel strategy to decrease reperfusion injuries and improve function of cold-preserved livers using normothermic ex vivo liver perfusion machine.

    PubMed

    Banan, Babak; Xiao, Zhenyu; Watson, Rao; Xu, Min; Jia, Jianluo; Upadhya, Gundumi A; Mohanakumar, Thalachallour; Lin, Yiing; Chapman, William

    2016-03-01

    Normothermic extracorporeal liver perfusion (NELP) can decrease ischemia/reperfusion injury to the greatest degree when cold ischemia time is minimized. Warm perfusion of cold-stored livers results in hepatocellular damage, sinusoidal endothelial cell (SEC) dysfunction, and Kupffer cell activation. However, the logistics of organ procurement mandates a period of cold preservation before NELP. The aim of this study was to determine the beneficial effects of gradual rewarming of cold-stored livers by placement on NELP. Three female porcine livers were used for each group. In the immediate NELP group, procured livers were immediately placed on NELP for 8 hours. In the cold NELP group, livers were cold-stored for 4 hours followed by NELP for 4 hours. In rewarming groups, livers were cold-stored for 4 hours, then gradually rewarmed in different durations to 38°C and kept on NELP for an additional 4 hours. For comparison purposes, the last 4 hours of NELP runs were considered to be the evaluation phase. Immediate NELP livers had significantly lower concentrations of liver transaminases, hyaluronic acid, and β-galactosidase and had higher bile production compared to the other groups. Rewarming livers had significantly lower concentrations of hyaluronic acid and β-galactosidase compared to the cold NELP livers. In addition, there was a significant decline in international normalized ratio values, improved bile production, reduced biliary epithelial cell damage, and improved cholangiocyte function. Thus, if a NELP machine is not available at the procurement site and livers will need to undergo a period of cold preservation, a gradual rewarming protocol before NELP may greatly reduce damages that are associated with reperfusion. In conclusion, gradual rewarming of cold-preserved livers upon NELP can minimize the hepatocellular damage, Kupffer cell activation, and SEC dysfunction.

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

    PubMed

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

    2017-03-01

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

  7. Functional Liver Recovery After Bariatric Surgery--a Prospective Cohort Study with the LiMAx Test.

    PubMed

    Alizai, Patrick H; Wendl, Janica; Roeth, Anjali A; Klink, Christian D; Luedde, Tom; Steinhoff, Inga; Neumann, Ulf P; Schmeding, Maximilian; Ulmer, Florian

    2015-11-01

    Bariatric surgery provides long-term weight loss and improvement of obesity-associated diseases such as nonalcoholic steatohepatitis (NASH). Histologic improvement of NASH has been reported in some studies after bariatric surgery. This study was designed to assess the liver function in obese patients as well as its recovery after bariatric surgery with a noninvasive test method. In a prospective cohort study from October 2011 to May 2014, morbidly obese individuals receiving bariatric surgery were investigated for functional liver recovery (n = 34). Liver function was determined by the LiMAx test (enzymatic capacity of cytochrome P450 1A2) preoperatively, 6 and 12 months postoperatively. Liver biopsy specimens were obtained from 18 participants and classified according to the nonalcoholic fatty liver disease (NAFLD) activity score (NAS). The mean age of participants was 44 years, and the mean body mass index (BMI) was 52 kg/m(2). The mean percent excess BMI loss (%EBMIL) was 53 % after 6 months and 68 % after 1 year. Mean liver function capacity increased significantly from 255 μg/kg/h preoperative to 324 μg/kg/h after 6 months and 342 μg/kg/h after 12 months. A negative correlation was observed between %EBMIL and alteration of liver function capacity in the first 6 months. Finally, the median NAS showed a negative correlation with liver function capacity. Bariatric surgery leads to a significant functional recovery of the liver. An initial marked weight loss may negatively influence functional liver recovery.

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

    Vesin, P.; Traverso, H.

    1975-01-01

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

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

    PubMed

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

    2016-12-01

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

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

    PubMed Central

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

    2004-01-01

    AIM: To investigate whether the non-invasive real-time Indocynine green (ICG) clearance is a sensitive index of liver viability in patients before, during, and after liver transplantation. METHODS: Thirteen patients were studied, two before, three during, and eight following liver transplantation, with two patients suffering acute rejection. The conventional invasive ICG clearance test and ICG pulse spectrophotometry non-invasive real-time ICG clearance test were performed simultaneously. Using linear regression analysis we tested the correlation between these two methods. The transplantation condition of these patients and serum total bilirubin (T. Bil), alanine aminotransferase (ALT), and platelet count were also evaluated. RESULTS: The correlation between these two methods was excellent (r2 = 0.977). CONCLUSION: ICG pulse spectrophotometry clearance is a quick, non-invasive, and reliable liver function test in transplantation patients. PMID:15285026

  12. Expression of Functional Cell-Cell Channels from Cloned Rat Liver Gap Junction Complementary DNA

    NASA Astrophysics Data System (ADS)

    Dahl, G.; Miller, T.; Paul, D.; Voellmy, R.; Werner, R.

    1987-06-01

    An oocyte expression system was used to test the relation between a complementary DNA (cDNA) clone encoding the liver gap junction protein and cell-cell channels. Total liver polyadenylated messenger RNA injected into oocytes induced cell-cell channels between paired oocytes. This induction was blocked by simultaneous injection of antisense RNA transcribed from the gap junction cDNA. Messenger RNA selected by hybridization to the cDNA clone and translated in oocyte pairs yielded a higher junctional conductance than unselected liver messenger RNA. Cell-cell channels between oocytes were also formed when the cloned cDNA was expressed under the control of a heat-shock promoter. A concentration-dependent induction of channels was observed in response to injection with in vitro transcribed gap junction messenger RNA. Thus, the liver gap junction cDNA encodes a protein that is essential for the formation of functional cell-cell channels.

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

    PubMed

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

    2006-01-01

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

  14. Purinergic effects of a hydroalcoholic Agaricus brasiliensis (A. blazei) extract on liver functions.

    PubMed

    de Oliveira, Andrea L; Eler, G Jacklin; Bracht, Adelar; Peralta, Rosane M

    2010-06-23

    The effects of a hydroalcoholic extract of Agaricus brasiliensis (A. blazei) on functional parameters in the perfused rat liver were examined with emphasis on its content of nucleotides and nucleosides. Several nucleosides and nucleotides were identified in the A. brasiliensis extract, which was active on several liver functions. A significant part of the effects is the result of the purinergic action of nucleosides and nucleotides: pressure increment, glycogenolysis stimulation, transient inhibition of oxygen consumption, and redox state changes. Other phenomena such as the stimulation of gluconeogenesis, ureogenesis, and oxygen consumption are more likely consequences of the metabolic transformation of substrates contained within the extract, especially amino acids. It seems apparent that consumption of A. brasiliensis represents not only the ingestion of metabolic precursors but also the ingestion of substances that, even at low concentrations, can exert important signaling functions in the liver as well as in the organism as a whole.

  15. Role of Gut Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Dai, Xin; Wang, Bangmao

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease, and its incidence is increasing year by year. Many efforts have been made to investigate the pathogenesis of this disease. Since 1998 when Marshall proposed the conception of “gut-liver axis,” more and more researchers have paid close attention to the role of gut barrier function in the pathogenesis of NAFLD. The four aspects of gut barrier function, including physical, chemical, biological, and immunological barriers, are interrelated closely and related to NAFLD. In this paper, we present a summary of research findings on the relationship between gut barrier dysfunction and the development of NAFLD, aiming at illustrating the role of gut barrier function in the pathogenesis of this disease. PMID:25945084

  16. Different induction of LPA receptors by chemical liver carcinogens regulates cellular functions of liver epithelial WB-F344 cells.

    PubMed

    Hirane, Miku; Ishii, Shuhei; Tomimatsu, Ayaka; Fukushima, Kaori; Takahashi, Kaede; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

    2016-11-01

    Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA1 to LPA6 ) mediates a variety of cellular functions, including cell motility. In the present study, we investigated the effects of LPA receptors on cell motile activity during multi-stage hepatocarcinogenesis in rat liver epithelial WB-F344 cells treated with chemical liver carcinogens. Cells were treated with a initiator (N-nitrosodiethylamine (DEN)) and three promoters (phenobarbital (PB), okadaic acid (OA) and clofibrate) every 24 h for 2 days. Cell motile activity was elevated by DEN, correlating with Lpar3 expression. PB, OA, and clofibrate elevated Lpar1 expression and inhibited cell motile activity. To evaluate the effects of long-term treatment on cell motility, cells were treated with DEN and/or PB for at least 6 months. Lpar3 expression and cell motile activity were significantly elevated by the long-term DEN treatment with or without further PB treatment. In contrast, long-term PB treatment with or without further DEN elevated Lpar1 expression and inhibited cell motility. When the synthesis of extracellular LPA was blocked by a potent ATX inhibitor S32826 before cell motility assay, the cell motility induced by DEN and PB was markedly suppressed. These results suggest that activation of the different LPA receptors may regulate the biological functions of cells treated with chemical carcinogens. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  17. Dual function microscope for quantitative DIC and birefringence imaging

    NASA Astrophysics Data System (ADS)

    Li, Chengshuai; Zhu, Yizheng

    2016-03-01

    A spectral multiplexing interferometry (SXI) method is presented for integrated birefringence and phase gradient measurement on label-free biological specimens. With SXI, the retardation and orientation of sample birefringence are simultaneously encoded onto two separate spectral carrier waves, generated by a crystal retarder oriented at a specific angle. Thus sufficient information for birefringence determination can be obtained from a single interference spectrum, eliminating the need for multiple acquisitions with mechanical rotation or electrical modulation. In addition, with the insertion of a Nomarski prism, the setup can then acquire quantitative differential interference contrast images. Red blood cells infected by malaria parasites are imaged for birefringence retardation as well as phase gradient. The results demonstrate that the SXI approach can achieve both quantitative phase imaging and birefringence imaging with a single, high-sensitivity system.

  18. Quantitative analysis of liver fibrosis in rats with shearwave dispersion ultrasound vibrometry: comparison with dynamic mechanical analysis.

    PubMed

    Zhu, Ying; Zhang, Xinyu; Zheng, Yi; Chen, Xin; Shen, Yuanyuan; Lin, Haoming; Guo, Yanrong; Wang, Tianfu; Chen, Siping

    2014-11-01

    Ultrasonic elastography, a non-invasive technique for assessing the elasticity properties of tissues, has shown promising results for disease diagnosis. However, biological soft tissues are viscoelastic in nature. Shearwave dispersion ultrasound vibrometry (SDUV) can simultaneously measure the elasticity and viscosity of tissue using shear wave propagation speeds at different frequencies. In this paper, the viscoelasticity of rat livers was measured quantitatively by SDUV for normal (stage F0) and fibrotic livers (stage F2). Meanwhile, an independent validation study was presented in which SDUV results were compared with those derived from dynamic mechanical analysis (DMA), which is the only mechanical test that simultaneously assesses the viscoelastic properties of tissue. Shear wave speeds were measured at frequencies of 100, 200, 300 and 400 Hz with SDUV and the storage moduli and loss moduli were measured at the frequency range of 1-40 Hz with DMA. The Voigt viscoelastic model was used in the two methods. The mean elasticity and viscosity obtained by SDUV ranged from 0.84±0.13 kPa (F0) to 1.85±0.30 kPa (F2) and from 1.12±0.11 Pa s (F0) to 1.70±0.31 Pa s (F2), respectively. The mean elasticity and viscosity derived from DMA ranged from 0.62±0.09 kPa (F0) to 1.70±0.84 kPa (F2) and from 3.38±0.32 Pa s (F0) to 4.63±1.30 Pa s (F2), respectively. Both SDUV and DMA demonstrated that the elasticity of rat livers increased from stage F0 to F2, a finding which was consistent with previous literature. However, the elasticity measurements obtained by SDUV had smaller differences than those obtained by DMA, whereas the viscosities obtained by the two methods were obviously different. We suggest that the difference could be related to factors such as tissue microstructure, the frequency range, sample size and the rheological model employed. For future work we propose some improvements in the comparative tests between SDUV and DMA, such as enlarging the harmonic

  19. Functional liver tissue engineering by an adult mouse liver-derived neuro-glia antigen 2-expressing stem/progenitor population.

    PubMed

    Zhang, Hongyu; Siegel, Christopher T; Li, Jing; Lai, Jiejuan; Shuai, Ling; Lai, Xiangdong; Zhang, Yujun; Jiang, Yan; Bie, Ping; Bai, Lianhua

    2016-09-17

    Deaths due to end-stage liver diseases (ESLD) are increasingly registered annually in the world. Liver transplantation is the ultimate treatment for ESLD to date, which has been hampered by a critical shortage of organs. The potential of decellularized liver scaffolds (DLS) derived from solid organs as a three dimensional (3D) platform has been evolved as a promising approach in liver tissue engineering for translating functional liver organ replacements, but questions still exist regarding the optimal cell population for seeding in DLS and the preparation of the DLS themselves. The aim of our study was to utilize a sodium dodecyl sulfate (SDS) decellularization procedure in combination with a low concentration of trypsin (0.005%)-EDTA (0.002%) process to manufacture DLS from whole mouse livers and recellularized with hepatic stem/progenitors for use in liver tissue engineering and injured liver treatment. Results showed that the DLS generated with all the necessary microstructure and the extracellular components to support seeded hepatic stem/progenitor cell attachment, functional hepatic cell differentiation. Hepatic differentiation from stem/progenitor cells loaded by DLS was more efficient than that of the stem/progenitor cells in the 2D cell culture model. In summary, the method of DLS loaded by hepatic stem/progenitor cells provided by this study was effective in maintaining DLS extracellular matrix (ECM) to introduce seeded stem/progenitor cell differentiation, hepatic-like tissue formation and functional hepatic protein production in vitro that promoted functional recovery and survival in a mouse model of dimethylnitrosamine (DEN)-induced liver cirrhosis after auxiliary heterotopic liver transplantation.

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

    PubMed

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

    1999-06-01

    We used color kinesis, a recent echocardiographic technique that provides regional information on the magnitude and timing of endocardial wall motion, to quantitatively assess regional right ventricular (RV) systolic and diastolic properties in 76 subjects who were divided into five groups, as follows: normal (n = 20), heart failure (n = 15), pressure/volume overload (n = 14), pressure overload (n = 12), and RV hypertrophy (n = 15). Quantitative segmental analysis of color kinesis images was used to obtain regional fractional area change (RFAC), which was displayed in the form of stacked histograms to determine patterns of endocardial wall motion. Time curves of integrated RFAC were used to objectively identify asynchrony of diastolic endocardial motion. When compared with normal subjects, patients with pressure overload or heart failure exhibited significantly decreased endocardial motion along the RV free wall. In the presence of mixed pressure/volume overload, the markedly increased ventricular septal motion compensated for decreased RV free wall motion. Diastolic endocardial wall motion was delayed in 17 of 72 segments (24%) in patients with RV pressure overload, and in 31 of 90 segments (34%) in patients with RV hypertrophy. Asynchrony of diastolic endocardial wall motion was greater in the latter group than in normal subjects (16% versus 10%: p < 0.01). Segmental analysis of color kinesis images allows quantitative assessment of regional RV systolic and diastolic properties.

  1. The function of a colloid in liver cold-storage preservation.

    PubMed

    Ar'Rajab, A; Ahrén, B; Sundberg, R; Bengmark, S

    1991-07-01

    the development of interstitial edema, and, hence, improve the liver function.

  2. Quantitative trait loci influencing blood and liver cholesterol concentration in rats.

    PubMed

    Bonné, Anita C M; den Bieman, Maria G; Gillissen, Gert F; Lankhorst, Aegidius; Kenyon, Christopher J; van Zutphen, Bert F M; van Lith, Hein A

    2002-12-01

    The LEW/OlaHsd and BC/CpbU rat inbred strains differ markedly in blood and hepatic cholesterol levels before and after a cholesterol-rich diet. To define loci controlling these traits and related phenotypes, an F2 population derived from these strains was genetically analyzed. For each of the 192 F2 animals, phenotypes were determined, and genomic DNA was screened for polymorphic microsatellite markers. Significant quantitative trait loci (QTLs) were detected for basal serum cholesterol level on chromosome 1 (D1Rat335-D1Rat27: total population, lod score 9.6; females, lod score 10.3) and chromosome 7 (D7Rat69: males, lod score 4.1), for postdietary serum cholesterol level on chromosome 2 (D2Rat69: total population, lod score 4.4) and chromosome 16 (D16Rat6-D16Rat44: total population, lod score 3.3), for postdietary serum phospholipid level on chromosome 11 (D11Rat10: total population, lod score 4.1; females, lod score 3.6), and for postdietary serum aldosterone level on chromosome 1 (D1Rat14: females, lod score 3.7) and chromosome 18 (D18Rat55-D18Rat8: females, lod score 2.9). In addition, QTLs with borderline significance were found on chromosomes 3, 5 to 11, 15, and 18. QTLs involved in blood and/or hepatic cholesterol concentrations (or related phenotypes) in the rat were identified. This contributes to the value of the rat as an animal model in studies researching the role of cholesterol in the pathogenesis of atherosclerosis and other cholesterol-related diseases.

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

    PubMed

    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 < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

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

    PubMed Central

    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

    2016-01-01

    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 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. PMID:27649152

  5. Maintenance of human hepatocyte function in vitro by liver-derived extracellular matrix gels.

    PubMed

    Sellaro, Tiffany L; Ranade, Aarati; Faulk, Denver M; McCabe, George P; Dorko, Kenneth; Badylak, Stephen F; Strom, Stephen C

    2010-03-01

    Tissue engineering and regenerative medicine (TE&RM) approaches to treating liver disease have the potential to provide temporary support with biohybrid-liver-assist devices or long-term therapy by replacing the diseased liver with functional constructs. A rate-limiting step for TE&RM strategies has been the loss of hepatocyte-specific functions after hepatocytes are isolated from their highly specialized in vivo microenvironment and placed in in vitro culture systems. The identification of a biologic substrate that can maintain a functional hepatocyte differentiation profile during in vitro culture would advance potential TE&RM therapeutic strategies. The present study compared two different biologic substrates for their ability to support human hepatocyte function in vitro: porcine-liver-derived extracellular matrix (PLECM) or Matrigel. Because Matrigel has been shown to be the most useful matrix for static, traditional hepatocyte culture, we directly compared PLECM with Matrigel in each experiment. Albumin secretion, hepatic transport activity, and ammonia metabolism were used to determine hepatocyte function. Hepatocytes cultured between two layers of PLECM or Matrigel showed equally high levels of albumin expression and secretion, ammonia metabolism, and hepatic transporter expression and function. We conclude that like Matrigel, PLECM represents a favorable substrate for in vitro culture of human hepatocytes.

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

    PubMed

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

    2017-02-01

    Dietary restriction (DR) can delay senescence, prolong lifespan of mammals and improve their learning-memory activity. The purpose of the study was to explore the effects of DR on hypolipidemic action and liver function of mice with hyperlipidemia. To investigate these effects, hyperlipidemia mouse models were established with high-fat diet (HFD) (34% of energy), then randomly divided into HFD group, DR30% group and DR50% group. Mice in DR30% and DR50% group were respectively supplied with HFD as much as about 70% and 50% of the consumption of HFD in the mice of HFD group. Rats in control group were fed routinely. After DR for 5 weeks, the average body weight, liver weight, liver index, serum lipids and glucose levels in both DR groups decreased significantly as compared with the HFD group (P<0.05 or P<0.01), so did alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) levels and the ratio of LDL-C/HDL-C in the DR50% group (P<0.05 or P<0.01). Histopathology examination of liver tissues further proved ameliorative effect of DR on liver function. Western blotting showed that DR significantly increased the expression of silent mating type information regulation 2 homolog 1 (SIRT1) in liver and adipose, while notably decreased the expression of peroxisome proliferators-activated receptors-gamma (PPARγ) in adipose (P<0.05 or P<0.01). The increase of SIRT1 and decrease of PPARγ may be a mechanism by which DR reduces blood lipids and ameliorates liver function.

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

    PubMed

    Liu, Wenyang; Sung, Kyunghyun; Ruan, Dan

    2014-12-01

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

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

    PubMed Central

    Liu, Wenyang; Sung, Kyunghyun; Ruan, Dan

    2014-01-01

    from 30.3 and 38.2 to 8.3 and 11.7 within two manually selected regions of interest, respectively. Conclusions: The developed motion compensation method has demonstrated its ability to facilitate quantitative MRU functional analysis, with improved accuracy of pharmacokinetic modeling and quantitative parameter estimations. Future work will consider performing more intensive clinical verifications with sophisticated pharmacokinetic models and generalizing the proposed method to other quantitative DCE analysis, such as on liver or prostate function. PMID:25471978

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

    PubMed

    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 < 0.05 to all). Significant decrease in hepatic artery perfusion was also observed in pericancerous liver tissue, but other parameters kept constant. CT perfusion imaging is able to detect decrease in blood perfusion of liver cancer post-argon-helium knife therapy. Therefore, CTP imaging would play an important role for liver cancer management followed argon-helium knife therapy.

  10. Functional Role of Monocytes and Macrophages for the Inflammatory Response in Acute Liver Injury

    PubMed Central

    Zimmermann, Henning W.; Trautwein, Christian; Tacke, Frank

    2012-01-01

    Different etiologies such as drug toxicity, acute viral hepatitis B, or acetaminophen poisoning can cause acute liver injury 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-1beta, or monocyte-chemoattractant protein-1 (MCP-1, CCL2) as well as activating other non-parenchymal liver cells, e.g., endothelial or hepatic stellate cells. 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-κB). 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. PMID:23091461

  11. Effects of ursodeoxycholic acid treatment on nutrition and liver function in patients with cystic fibrosis and longstanding cholestasis.

    PubMed Central

    Cotting, J; Lentze, M J; Reichen, J

    1990-01-01

    The prevalence of biliary and hepatic diseases is increasing in patients with cystic fibrosis as more of them reach adult life. There is no effective treatment or method of preventing cholestasis in cystic fibrosis, although beneficial effects have been ascribed to the tertiary bile acid, ursodeoxycholate, in other forms of chronic cholestasis. We evaluated prospectively the effects of a six month course of ursodeoxycholate (15-20 mg/kg per day) in eight, mostly adult, patients with cystic fibrosis and chronic cholestasis. Bile acid treatment improved inflammatory activity (average decrease in alanine aminotransferase, 60%, p less than 0.005) and cholestasis (alkaline phosphatase, 47%; p less than 0.01) in all patients. Quantitative liver function, measured by 45 minute sulphobromophthalein retention and by the 14C-aminopyrine breath test, improved in all patients while galactose elimination capacity showed a slight decrease. Patients' nutritional state improved as evidenced by a 1.8 kg weight gain and an increase in muscle mass suggested by a 26% increase in 24 hour urinary creatinine excretion. Steatorrhea was not affected by bile acid treatment. Ursodeoxycholic acid may be beneficial in the treatment of chronic cholestasis in cystic fibrosis by improving liver function and also the patient's nutritional state. PMID:2387518

  12. Effects of ursodeoxycholic acid treatment on nutrition and liver function in patients with cystic fibrosis and longstanding cholestasis.

    PubMed

    Cotting, J; Lentze, M J; Reichen, J

    1990-08-01

    The prevalence of biliary and hepatic diseases is increasing in patients with cystic fibrosis as more of them reach adult life. There is no effective treatment or method of preventing cholestasis in cystic fibrosis, although beneficial effects have been ascribed to the tertiary bile acid, ursodeoxycholate, in other forms of chronic cholestasis. We evaluated prospectively the effects of a six month course of ursodeoxycholate (15-20 mg/kg per day) in eight, mostly adult, patients with cystic fibrosis and chronic cholestasis. Bile acid treatment improved inflammatory activity (average decrease in alanine aminotransferase, 60%, p less than 0.005) and cholestasis (alkaline phosphatase, 47%; p less than 0.01) in all patients. Quantitative liver function, measured by 45 minute sulphobromophthalein retention and by the 14C-aminopyrine breath test, improved in all patients while galactose elimination capacity showed a slight decrease. Patients' nutritional state improved as evidenced by a 1.8 kg weight gain and an increase in muscle mass suggested by a 26% increase in 24 hour urinary creatinine excretion. Steatorrhea was not affected by bile acid treatment. Ursodeoxycholic acid may be beneficial in the treatment of chronic cholestasis in cystic fibrosis by improving liver function and also the patient's nutritional state.

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

    PubMed Central

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

    2008-01-01

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

  14. Acoustic radiation force impulse elastography for chronic liver disease: comparison with ultrasound-based scores of experienced radiologists, Child-Pugh scores and liver function tests.

    PubMed

    Kim, Ji Eun; Lee, Jae Young; Kim, Yoon Jun; Yoon, Jung Hwan; Kim, Se Hyung; Lee, Jeong Min; Han, Joon Koo; Choi, Byung Ihn

    2010-10-01

    The purpose of our study was to investigate whether acoustic radiation force impulse (ARFI) elastography provides better diagnostic performance for diagnosis of chronic liver disease and correlates better with Child-Pugh scores and liver function tests, compared with an ultrasound (US) scoring system based on visual assessment of conventional B-mode US images by experienced radiologists. Five hundred and twenty-one patients with clinically proven chronic liver disease (n = 293), fatty liver (n = 95) or normal liver (n = 133) were included in this study. B-mode liver US and ARFI elastography were performed in all patients. ARFI elastography was performed at least five times, with each measurement obtained at a different area of the right hepatic lobe; mean shear wave velocity (SWV) was calculated for each patient. The mean SWV was compared with US-based scores from two radiologists (based on liver surface nodularity, parenchyma echotexture and hepatic vein contour), Child-Pugh scores and liver function tests. The mean SWV of the normal liver group was 1.08 m/s ± 0.15; of the fatty liver group, 1.02 m/s ± 0.16; and of the chronic liver disease group, 1.66 m/s ± 0.60 (p < 0.001). The area under the receiver operating characteristics curve of the mean SWV in ARFI elastography was significantly higher than that of the conventional B-mode US-based scores by two radiologists (0.89 vs. 0.74 and 0.77, p < 0.05), with a sensitivity of 75.4% and a specificity of 89.5% at the cut-off value of 1.22 m/s. The sensitivity of the mean SWV was significantly higher than the US-based scores (p < 0.001), although the specificity was not (p > 0.05). The mean SWV was better correlated with Child-Pugh scores and all liver function tests (except total protein) than the US-based scores from two radiologists. In conclusion, ARFI elastography showed better diagnostic performance than visual assessment of experienced radiologists for diagnosis of chronic liver disease, as well as for

  15. Functional abnormalities of sinusoidal endothelial cells in rats with acute liver rejection.

    PubMed

    Yokoi, Y; Nakamura, S; Muro, H; Baba, S

    1994-01-01

    The purpose of this study was to determine the changes of hepatic sinusoidal endothelial cell (SEC) function in acute liver rejection with respect to receptor-mediated endocytosis. Orthotopic rat liver transplantation was performed in Lewis rats grafted with DA livers and in Lewis rats grafted with Lewis livers as rejectors and controls, respectively. Animals were killed at 1, 3, 5, 7, and 10 days after the operation. Fc receptors (FcRs) were histochemically stained on frozen liver sections by applying peroxidase-antiperoxidase IgG complex as a ligand, and the FcR activity, i.e., capacity of binding the ligands represented by the FcR staining intensity, was semiquantitatively analyzed as an indicator of SEC function. The serum level of hyaluronic acid, which is specifically cleared from the circulation by receptor-mediated SEC endocytosis, was also assayed, along with the total serum bilirubin. Three days after the operation, the SECs of rejectors showed a significantly weaker FcR staining intensity of about half the value of that seen in the controls (P < 0.05), and staining disappeared after 5 days (P < 0.01). The decrease of FcR staining intensity, i.e., FcR activity, showed a correlation with elevation of the serum hyaluronic acid level (r = -0.77; P < 0.001). Histological evidence of endothelialitis and a significant elevation of total serum bilirubin (P < 0.01) were also present at 3 and 5 days, respectively. These results suggest that impairment of the endocytic function of SECs occurs at an earlier phase of acute liver rejection when compared with development of abnormalities of traditional indicators. Determination of receptor-mediated SEC endocytic functions may thus provide useful information for the early diagnosis of acute rejection.

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

    PubMed Central

    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 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 (Cyp)3a 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. PMID:26967735

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

    PubMed

    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 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 (Cyp)3a 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.

  18. Free radical scavengers improve liver function but not morphological changes induced by reperfusion injury.

    PubMed

    Arab, Hossein-Ali; Walker, Neal I; Cheung, Kee; Hickman, Peter E; Potter, Jolia M; Kadkhodaee, Mehri; Roberts, Michael S

    2015-04-01

    Reperfusion injury (RI) is associated with high generation of reactive oxygen species (ROS), but the extent of involvement of these agents in the injury remains controversial. The present study aimed to examine the effectiveness of ROS scavengers against hepatic reperfusion injury in the rat. The RI was induced in the liver using an isolated slow-flow, reflow perfused rat liver in both anterograde and retrograde perfusion. The effects of gentisic acid, N-acetyl cysteine, and trolox C on the superoxide production, liver function, and morphological changes were examined using different biochemical and histological assays. The hepatic RI caused a significant (p < 0.05) increase in superoxide production and enzyme releases and a decrease in bile flow in both directions. Histological changes induced by RI include apoptosis, necrosis, pale cytoplasm, cell vacuolation, and attenuation of cell cords. Although the production of superoxide in retrograde direction was significantly less than the anterograde, the extent of the injury in the retrograde was greater than the anterograde direction. Pretreatment of the livers with each of the test compounds significantly reduced the release of lactate dehydrogenase and aspartate aminotransferase and improved bile flow in the liver exposed to hypoxia/reperfusion. However, they failed to protect the liver against the structural alterations induced by RI. ROS scavengers can reduce superoxide-induced damage and improve the liver function, but they are not able to prevent the structural changes. It shows that ROS are not the sole causative mechanism of hepatic RI and other mechanisms and mediators may be involved.

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

    SciTech Connect

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

    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

  20. Gd-EOB-DTPA-enhanced MRI for evaluation of liver function: Comparison between signal-intensity-based indices and T1 relaxometry

    PubMed Central

    Haimerl, Michael; Verloh, Niklas; Zeman, Florian; Fellner, Claudia; Nickel, Dominik; Lang, Sven A.; Teufel, Andreas; Stroszczynski, Christian; Wiggermann, Philipp

    2017-01-01

    Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a paramagnetic hepatobiliary magnetic resonance (MR) contrast agent. Due to its OATP1B1/B3-dependent hepatocyte-specific uptake and paramagnetic properties increasing evidence has emerged to suggest that Gd-EOB-DTPA-enhanced MRI can be potentially used for evaluation of liver function. In this paper we compare the diagnostic performance of Gd-EOB-DTPA-enhanced relaxometry-based and commonly used signal-intensity (SI)-based indices, including the hepatocellular uptake index (HUI) and SI-based indices corrected by spleen or muscle, for evaluation of liver function, determined using the Indocyanin green clearance (ICG) test. Simple linear regression model showed a significant correlation of the plasma disappearance rate of ICG (ICG-PDR) with all Gd-EOB-DTPA-enhanced MRI-based liver function indices with a significantly better correlation of relaxometry-based indices on ICG-PDR compared to SI-based indices. Among SI-based indices, HUI achieved best correlation on ICG-PDR and no significant difference of respective correlations on ICG-PDR could be shown. Assessment of liver volume and consecutive evaluation of multiple linear regression model revealed a stronger correlation of ICG-PDR with both (SI)-based and T1 relaxometry-based indices. Thus, liver function can be estimated quantitatively from Gd-EOB-DTPA–enhanced MRI-based indices. Here, indices derived from T1 relaxometry are superior to SI-based indices, and all indices benefit from taking into account respective liver volumes. PMID:28266528

  1. CT/99mTc-GSA SPECT fusion images demonstrate functional differences between the liver lobes

    PubMed Central

    Sumiyoshi, Tatsuaki; Shima, Yasuo; Tokorodani, Ryoutarou; Okabayashi, Takehiro; Kozuki, Akihito; Hata, Yasuhiro; Noda, Yoshihiro; Murata, Yoriko; Nakamura, Toshio; Uka, Kiminori

    2013-01-01

    AIM: To evaluate the functional differences between the 2 liver lobes in non-cirrhotic patients by using computed tomography/99mTc-galactosyl human serum albumin (CT/99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODS: Between December 2008 and March 2012, 264 non-cirrhotic patients underwent preoperative liver function assessment using CT/99mTc-GSA SPECT fusion images. Of these, 30 patients, in whom the influence of a tumor on the liver parenchyma was estimated to be negligible, were selected. Specifically, the selected patients were required to meet either of the following criteria: (1) the presence of an extrahepatic tumor; or (2) presence of a single small intrahepatic tumor. These 30 patients were retrospectively analyzed to calculate the percentage volume (%Volume) and the percentage function (%Function) of each lobe. The ratio between the %Function and %Volume (function-to-volume ratio) of each lobe was also calculated, and the ratios were compared between the 2 lobes. Furthermore, the correlations between the function-to-volume ratio and each of 2 liver parameters [lobe volume and diameter ratio of the left portal vein to the right portal vein (LPV-to-RPV diameter ratio)] were investigated. RESULTS: The median values of %Volume and %Function were 62.6% and 67.1% in the right lobe, with %Function being significantly higher than %Volume (P < 0.01). The median values of %Volume and %Function were 31.0% and 28.7% in the left lobe, with %Function being significantly lower than %Volume (P < 0.01). The function-to-volume ratios of the right lobe (1.04-1.14) were significantly higher than those of the left lobe (0.74-0.99) (P < 0.01). The function-to-volume ratio showed no significant correlation between the lobe volume in either lobe. In contrast, the function-to-volume ratio showed significant correlations with the LPV-to-RPV diameter ratio in both lobes (right lobe: negative correlation, rs = -0.37, P = 0.048; left lobe: positive

  2. Quantitative Assessment of Population Variability in Hepatic Drug Metabolism Using a Perfused Three-Dimensional Human Liver Microphysiological System

    PubMed Central

    Tsamandouras, N.; Kostrzewski, T.; Stokes, C. L.; Griffith, L. G.; Hughes, D. J.

    2017-01-01

    In this work, we first describe the population variability in hepatic drug metabolism using cryopreserved hepatocytes from five different donors cultured in a perfused three-dimensional human liver microphysiological system, and then show how the resulting data can be integrated with a modeling and simulation framework to accomplish in vitro–in vivo translation. For each donor, metabolic depletion profiles of six compounds (phenacetin, diclofenac, lidocaine, ibuprofen, propranolol, and prednisolone) were measured, along with metabolite formation, mRNA levels of 90 metabolism-related genes, and markers of functional viability [lactate dehydrogenase (LDH) release, albumin, and urea production]. Drug depletion data were analyzed with mixed-effects modeling. Substantial interdonor variability was observed with respect to gene expression levels, drug metabolism, and other measured hepatocyte functions. Specifically, interdonor variability in intrinsic metabolic clearance ranged from 24.1% for phenacetin to 66.8% for propranolol (expressed as coefficient of variation). Albumin, urea, LDH, and cytochrome P450 mRNA levels were identified as significant predictors of in vitro metabolic clearance. Predicted clearance values from the liver microphysiological system were correlated with the observed in vivo values. A population physiologically based pharmacokinetic model was developed for lidocaine to illustrate the translation of the in vitro output to the observed pharmacokinetic variability in vivo. Stochastic simulations with this model successfully predicted the observed clinical concentration-time profiles and the associated population variability. This is the first study of population variability in drug metabolism in the context of a microphysiological system and has important implications for the use of these systems during the drug development process. PMID:27760784

  3. Quantitative Assessment of Population Variability in Hepatic Drug Metabolism Using a Perfused Three-Dimensional Human Liver Microphysiological System.

    PubMed

    Tsamandouras, N; Kostrzewski, T; Stokes, C L; Griffith, L G; Hughes, D J; Cirit, M

    2017-01-01

    In this work, we first describe the population variability in hepatic drug metabolism using cryopreserved hepatocytes from five different donors cultured in a perfused three-dimensional human liver microphysiological system, and then show how the resulting data can be integrated with a modeling and simulation framework to accomplish in vitro-in vivo translation. For each donor, metabolic depletion profiles of six compounds (phenacetin, diclofenac, lidocaine, ibuprofen, propranolol, and prednisolone) were measured, along with metabolite formation, mRNA levels of 90 metabolism-related genes, and markers of functional viability [lactate dehydrogenase (LDH) release, albumin, and urea production]. Drug depletion data were analyzed with mixed-effects modeling. Substantial interdonor variability was observed with respect to gene expression levels, drug metabolism, and other measured hepatocyte functions. Specifically, interdonor variability in intrinsic metabolic clearance ranged from 24.1% for phenacetin to 66.8% for propranolol (expressed as coefficient of variation). Albumin, urea, LDH, and cytochrome P450 mRNA levels were identified as significant predictors of in vitro metabolic clearance. Predicted clearance values from the liver microphysiological system were correlated with the observed in vivo values. A population physiologically based pharmacokinetic model was developed for lidocaine to illustrate the translation of the in vitro output to the observed pharmacokinetic variability in vivo. Stochastic simulations with this model successfully predicted the observed clinical concentration-time profiles and the associated population variability. This is the first study of population variability in drug metabolism in the context of a microphysiological system and has important implications for the use of these systems during the drug development process. Copyright © 2016 by The Author(s).

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

    PubMed

    Olinga, P; Groen, K; Hof, I H; De Kanter, R; Koster, H J; Leeman, W R; Rutten, A A; Van Twillert, K; Groothuis, G M

    1997-10-01

    Precision-cut liver slices are presently used for various research objects, e.g. to study metabolism, transport, and toxicity of xenobiotics. Various incubation systems are presently employed, but a systematic comparison between these incubation systems with respect to preservation of slice function has not been performed yet. Therefore, we started a comparative study to evaluate five of these systems: the shaken flask (an Erlenmeyer in a shaking water bath), the stirred-well (24-well culture plate equipped with grids and magnetic stirrers), rocker platform (6-well culture plate with Netwell insert rocked on a platform), the roller system (dynamic organ culture rolled on an insert in a glass vial), and the 6-well shaker (6-well culture plate in a shaking water bath). The liver slices were incubated in these incubation systems for 0.5, 1.5, and 24.5 h and subsequently subjected to viability and metabolic function tests. The viability of the incubated liver slices was evaluated by: potassium content, MTT assay, energy charge, histomorphology, and LDH leakage. Their metabolic functions were studied by determination of the metabolism of lidocaine, testosterone, and antipyrine. Up to 1.5 h of incubation all five incubation systems gave similar results with respect to viability and metabolic function of the liver slices. However, after 24 h, the shaken flask, the rocker platform, and the 6-well shaker incubation systems appeared to be superior to the stirred well and the roller incubation systems.

  5. Effect of sweetener and flavoring agent on oxidative indices, liver and kidney function levels in rats.

    PubMed

    Amin, Kamal A; Al-muzafar, Hessa M; Abd Elsttar, Adel H

    2016-01-01

    Food additives while attract consumers, improve quality, control weight and replace sugar, may affect seriously children and adults health. Here, we investigated the adverse effects of saccharin and methylsalicyltaes as sweetener and flavoring agent on lipid profile, blood glucose, renal, hepatic function and oxidative stress/antioxidants (lipid peroxidation, catalase and reduced glutathione in liver tissues). Saccharin and methylsalicylate were administered orally in young male albino rats at low and high dose for 30 days. Rats were divided into 5 groups, 1st control group, 2nd and 3rd (low and high saccharin-treated groups) and 4th and 5th (low and high methylsalicylate-treated group). Serum total cholesterol, triglyceride, glucose levels and body weight gain were found decreased in saccharin high dose group compared to control. Rats consumed high dose of saccharin showed a significant decrease in serum triglycerides, cholesterol and LDL levels. Low and high doses of saccharin exhibited a significant increase in liver function marker of ALT, AST, ALP activity, total proteins and albumin levels and renal function test (urea and creatinine levels) in comparison with control group. Further, saccharin at high dose induced significant decrease in liver GSH levels, catalase and SOD activity and increase in hepatic MDA level. Overall saccharin harmfully altered biochemical markers in liver and kidney at higher as well as lower doses. Whereas, methyl salicylates did not pose a risk for renal function and hepatic oxidative markers.

  6. Liver condition of Holstein cows affects mitochondrial function and fertilization ability of oocytes

    PubMed Central

    TANAKA, Hiroshi; TAKEO, Shun; ABE, Takahito; KIN, Airi; SHIRASUNA, Koumei; KUWAYAMA, Takehito; IWATA, Hisataka

    2016-01-01

    The aim of the present study was to examine the fertilization ability and mitochondrial function of oocytes derived from cows with or without liver damage. Oocytes were collected from the ovaries of cows with damaged livers (DL) and those of cows with healthy livers (HL), subjected to in vitro maturation, and fertilized in vitro. A significantly high abnormal fertilization rate was observed for oocytes from DL cows compared to oocytes from HL cows. The time to dissolve the zona pellucida by protease before fertilization was similar between the two liver conditions, whereas after fertilization treatment this time was shorter for DL cows than for HL cows. The percentage of oocytes with equivalent cortical granule distributions underneath the membrane was greater for in vitro matured oocytes from HL cows, whereas an immature distribution pattern was observed for oocytes from DL cows. In addition, a greater percentage of oocytes derived from HL cows released cortical granules following fertilization compared with oocytes from DL cows. Mitochondrial function determined by ATP content and membrane potential were similar at the germinal vesicle stage, but post-in vitro maturation, the oocytes derived from HL cows showed higher values than DL cows. The mitochondrial DNA copy number in oocytes was similar between the two liver conditions for both the germinal vesicle and post-in vitro maturation oocytes. In conclusion, liver damage induces low fertilization, likely because of incomplete cortical granule distribution and release, and the maturation of oocytes from DL cows contain low-functioning mitochondria compared to their HL counterparts. PMID:26832309

  7. All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver.

    PubMed

    Tripathy, Sasmita; Chapman, John D; Han, Chang Y; Hogarth, Cathryn A; Arnold, Samuel L M; Onken, Jennifer; Kent, Travis; Goodlett, David R; Isoherranen, Nina

    2016-05-01

    All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. The liver is the main storage organ of vitamin A, but activation of the retinoic acid receptors (RARs) in mouse liver and in human liver cell lines has also been shown. AlthoughatRA treatment improves mitochondrial function in skeletal muscle in rodents, its role in modulating mitochondrial function in the liver is controversial, and little data are available regarding the human liver. The aim of this study was to determine whetheratRA regulates hepatic mitochondrial activity.atRA treatment increased the mRNA and protein expression of multiple components of mitochondrialβ-oxidation, tricarboxylic acid (TCA) cycle, and respiratory chain. Additionally,atRA increased mitochondrial biogenesis in human hepatocytes and in HepG2 cells with and without lipid loading based on peroxisome proliferator activated receptor gamma coactivator 1αand 1βand nuclear respiratory factor 1 mRNA and mitochondrial DNA quantification.atRA also increasedβ-oxidation and ATP production in HepG2 cells and in human hepatocytes. Knockdown studies of RARα, RARβ, and PPARδrevealed that the enhancement of mitochondrial biogenesis andβ-oxidation byatRA requires peroxisome proliferator activated receptor delta. In vivo in mice,atRA treatment increased mitochondrial biogenesis markers after an overnight fast. Inhibition ofatRA metabolism by talarozole, a cytochrome P450 (CYP) 26 specific inhibitor, increased the effects ofatRA on mitochondrial biogenesis markers in HepG2 cells and in vivo in mice. These studies show thatatRA regulates mitochondrial function and lipid metabolism and that increasingatRA concentrations in human liver via CYP26 inhibition may increase mitochondrial biogenesis and fatty acidβ-oxidation and provide therapeutic benefit in diseases associated with mitochondrial dysfunction. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Quantitative assessment of protein function prediction from metagenomics shotgun sequences.

    PubMed

    Harrington, E D; Singh, A H; Doerks, T; Letunic, I; von Mering, C; Jensen, L J; Raes, J; Bork, P

    2007-08-28

    To assess the potential of protein function prediction in environmental genomics data, we analyzed shotgun sequences from four diverse and complex habitats. Using homology searches as well as customized gene neighborhood methods that incorporate intergenic and evolutionary distances, we inferred specific functions for 76% of the 1.4 million predicted ORFs in these samples (83% when nonspecific functions are considered). Surprisingly, these fractions are only slightly smaller than the corresponding ones in completely sequenced genomes (83% and 86%, respectively, by using the same methodology) and considerably higher than previously thought. For as many as 75,448 ORFs (5% of the total), only neighborhood methods can assign functions, illustrated here by a previously undescribed gene associated with the well characterized heme biosynthesis operon and a potential transcription factor that might regulate a coupling between fatty acid biosynthesis and degradation. Our results further suggest that, although functions can be inferred for most proteins on earth, many functions remain to be discovered in numerous small, rare protein families.

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

    PubMed

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

    2017-07-01

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

  10. Reformation of functional liver polyribosomes from ribosome monomers in the absence of RNA synthesis.

    PubMed

    Stewart, G A; Farber, E

    1967-07-07

    The administration to rats of the ethyl analog of methionine, ethionine, results in the rapid decrease in the hepatic concentration of adenosine triphosphate followed by an extensive disaggregation of polysomes to ribosome monomers and a concomitant inhibition of protein synthesis. These effects are readily reversed by the injection of methionine or precursors of adenine nucleotides such as adenine. The reformation of liver polyribosomes in such animals following the administration of adenine plus methionine was found to occur under conditions in which new RNA synthesis was markedly inhibited. Free messenger RNA without attached ribosomes must be capable of remaining functionally active in the liver cytoplasm for many hours.

  11. Comparison of quantitative Y-90 SPECT and non-time-of-flight PET imaging in post-therapy radioembolization of liver cancer.

    PubMed

    Yue, Jianting; Mauxion, Thibault; Reyes, Diane K; Lodge, Martin A; Hobbs, Robert F; Rong, Xing; Dong, Yinfeng; Herman, Joseph M; Wahl, Richard L; Geschwind, Jean-François H; Frey, Eric C

    2016-10-01

    Radioembolization with yttrium-90 microspheres may be optimized with patient-specific pretherapy treatment planning. Dose verification and validation of treatment planning methods require quantitative imaging of the post-therapy distribution of yttrium-90 (Y-90). Methods for quantitative imaging of Y-90 using both bremsstrahlung SPECT and PET have previously been described. The purpose of this study was to compare the two modalities quantitatively in humans. Calibration correction factors for both quantitative Y-90 bremsstrahlung SPECT and a non-time-of-flight PET system without compensation for prompt coincidences were developed by imaging three phantoms. The consistency of these calibration correction factors for the different phantoms was evaluated. Post-therapy images from both modalities were obtained from 15 patients with hepatocellular carcinoma who underwent hepatic radioembolization using Y-90 glass microspheres. Quantitative SPECT and PET images were rigidly registered and the total liver activities and activity distributions estimated for each modality were compared. The activity distributions were compared using profiles, voxel-by-voxel correlation and Bland-Altman analyses, and activity-volume histograms. The mean ± standard deviation of difference in the total activity in the liver between the two modalities was 0% ± 9% (range -21%-18%). Voxel-by-voxel comparisons showed a good agreement in regions corresponding roughly to treated tumor and treated normal liver; the agreement was poorer in regions with low or no expected activity, where PET appeared to overestimate the activity. The correlation coefficients between intrahepatic voxel pairs for the two modalities ranged from 0.86 to 0.94. Cumulative activity volume histograms were in good agreement. These data indicate that, with appropriate reconstruction methods and measured calibration correction factors, either Y-90 SPECT/CT or Y-90 PET/CT can be used for quantitative post-therapy monitoring of Y

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

    PubMed

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

    2016-02-01

    To report changes in liver function tests observed with canagliflozin, a sodium glucose co-transporter 2 inhibitor, across phase 3 studies in patients with type 2 diabetes, and to examine the relationship between changes in liver function tests and the weight loss and glycaemic improvements observed with canagliflozin. Data were pooled from four 26-week, placebo-controlled studies of canagliflozin 100 and 300mg (n=2313) and two 52-week, active-controlled studies of canagliflozin 300mg versus sitagliptin 100mg (n=1488). Analysis of covariance was performed to determine the contribution of changes in body weight and HbA1c to the changes in liver function tests. Reductions in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transferase, and increases in bilirubin were seen with canagliflozin 100 and 300mg versus placebo (nominal P<0.001 for alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase [both doses]; P<0.001 for alkaline phosphatase and P=0.015 for bilirubin [canagliflozin 300mg only]) at week 26 and with canagliflozin 300mg versus sitagliptin 100mg (nominal P<0.001 for alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase and bilirubin, and P<0.01 for alkaline phosphatase) at week 52. Few patients met predefined limits of change criteria for liver function tests, and none met Hy's law criteria. In both populations, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase reductions were fully explained by HbA1c and body weight reductions. Canagliflozin provided improvements in liver function tests versus either placebo or sitagliptin treatments that were fully explained by the combined effects of HbA1c and body weight reductions with canagliflozin. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Quantitative Evaluation of the Reticuloendothelial System Function with Dynamic MRI

    PubMed Central

    Liu, Ting; Choi, Hoon; Zhou, Rong; Chen, I-Wei

    2014-01-01

    Purpose To evaluate the reticuloendothelial system (RES) function by real-time imaging blood clearance as well as hepatic uptake of superparamagnetic iron oxide nanoparticle (SPIO) using dynamic magnetic resonance imaging (MRI) with two-compartment pharmacokinetic modeling. Materials and Methods Kinetics of blood clearance and hepatic accumulation were recorded in young adult male 01b74 athymic nude mice by dynamic T2* weighted MRI after the injection of different doses of SPIO nanoparticles (0.5, 3 or 10 mg Fe/kg). Association parameter, Kin, dissociation parameter, Kout, and elimination constant, Ke, derived from dynamic data with two-compartment model, were used to describe active binding to Kupffer cells and extrahepatic clearance. The clodrosome and liposome were utilized to deplete macrophages and block the RES function to evaluate the capability of the kinetic parameters for investigation of macrophage function and density. Results The two-compartment model provided a good description for all data and showed a low sum squared residual for all mice (0.27±0.03). A lower Kin, a lower Kout and a lower Ke were found after clodrosome treatment, whereas a lower Kin, a higher Kout and a lower Ke were observed after liposome treatment in comparison to saline treatment (P<0.005). Conclusion Dynamic SPIO-enhanced MR imaging with two-compartment modeling can provide information on RES function on both a cell number and receptor function level. PMID:25090653

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

    PubMed

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

    2007-05-01

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

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

    NASA Astrophysics Data System (ADS)

    Yazdani, Farshad; Fattahi, Bahare; Azizi, Najmodin

    2016-05-01

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

  16. Cholesterol esterification in plasma as a biomarker for liver function and prediction of mortality.

    PubMed

    Kaiser, Thorsten; Kinny-Köster, Benedict; Bartels, Michael; Berg, Thomas; Scholz, Markus; Engelmann, Cornelius; Seehofer, Daniel; Becker, Susen; Ceglarek, Uta; Thiery, Joachim

    2017-04-20

    Advanced stages of liver cirrhosis lead to a dramatically increased mortality. For valid identification of these patients suitable biomarkers are essential. The most important biomarkers for liver function are bilirubin and prothrombin time expressed as International Normalized Ratio (INR). However, the influence of several anticoagulants on the prothrombin time limits its diagnostic value. Aim of this study was the evaluation of cholesterol esterification (CE) fraction (esterified cholesterol vs. total cholesterol) as an alternative biomarker for liver synthesis and mortality prediction. Under physiological conditions the CE fraction in blood is closely regulated by lecithin-cholesterol acyltransferase (LCAT) which is produced in the liver. One hundred forty-two patients with liver disease clinically considered for orthotopic liver transplant for different indications were enrolled in the study. One patient was excluded because of the intake of a direct oral factor Xa inhibitor which has a strong impact on prothrombin time. Results of CE fraction were in good agreement with INR (R(2) = 0.73; p < 0.001). In patients who died or survived within three months mean CE fraction was 56% vs. 74% (p < 0.001) and mean INR was 2.0 vs. 1.3 (p < 0.001), respectively. The predictive value of CE fraction for three-month mortality risk was higher compared to INR (p = 0.04). Results for one-year mortality were comparable. The cholesterol esterification fraction is a valid biomarker for liver synthesis and allows reliable prediction of mortality. In contrast to INR, it is independent of anticoagulation and other analytical limitations of coagulation tests.

  17. Comparison of 10- and 20-min hepatobiliary phase images on Gd-EOB-DTPA-enhanced MRI T1 mapping for liver function assessment in clinic.

    PubMed

    Zhou, Zhi-Peng; Long, Li-Ling; Qiu, Wei-Jia; Cheng, Ge; Huang, Li-Juan; Yang, Teng-Fei; Huang, Zhong-Kui

    2017-04-10

    To compare hepatobiliary phase (HBP) images obtained 10 and 20 min after Gd-EOB-DTPA-enhanced MRI for liver function assessment in clinic on 3.0 T MR imaging. 103 patients were separated into four groups: 38 patients for the normal liver function (NLF) group, 33 patients for the liver cirrhosis with Child-Pugh A (LCA) group, 21 patients for the liver cirrhosis with Child-Pugh B group, and 11 patients for a liver cirrhosis with Child-Pugh C group. T1 relaxation times (T1rt) were measured on T1 mapping and reduction rates of T1rt (rrT1rt) were calculated. HBP images were obtained at the 10- and 20-min mark after Gd-EOB-DTPA enhancement. T1rt on pre-enhancement imaging showed no significant difference (p > 0.05) among all four groups. T1rt for both the 10-min HBP and the 20-min HBP showed a significant difference (p < 0.05) among all groups, but showed no significant difference (p > 0.05) between the NLF group and the LCA group. T1rt and rrT1rt showed no significant difference (p > 0.05) between 10-min HBP and 20-min HBP among all groups. The ROC analysis on 10-min HBP and 20-min HBP showed a lower diagnostic performance between NLF group and LCA group (AUC from 0.532 to 0.582), but high diagnostic performance (AUC from 0.788 to 1.000) among others group. In comparing 10-min HBP and 20-min HBP T1 mapping after Gd-EOB-DTPA enhancement, our results suggest that 10-min HBP T1 mapping is a feasible option for quantitatively assessing liver function.

  18. Diagnostic value of semi-quantitative and quantitative analysis of functional parameters in multiparametric MRI of the prostate.

    PubMed

    Hauth, Elke; Halbritter, Daniela; Jaeger, Horst; Hohmuth, Horst; Beer, Meinrad

    2017-10-01

    To determine the diagnostic value of semi-quantitative and quantitative parameters of three functional techniques in multiparametric (mp)-MRI of the prostate. Mp-MRI was performed in 110 patients with suspicion of prostate cancer (PCA) before transrectal ultrasound (TRUS)-guided core biopsy. Peak-enhancement, initial and post-initial enhancement, initial area under gadolinium curve, Ktrans (forward rate constant), Kep (efflux rate constant), Ve (extracellular volume), ADC (apparent diffusion coefficient) and MR spectroscopy ratio were obtained for malignant and benign lesions. For iAUGC, Ktrans, Kep and Ve we evaluated median, mean and the difference (Diff) between mean and median. For ADC we evaluated mean, median, Diff between mean and median, and min. In addition, we evaluated these parameters in dependence of Gleason score in PCA. Receiver operating characteristic analysis and area under curve (AUC) were determined. ADC min and Kep Diff were the best predictors of malignancy in all lesions (AUC: 0.765). ADC min was the best predictor of malignancy for lesions in peripheral zone (PZ) (AUC: 0.7506) and Kep Diff was the best predictor of malignancy for lesions in transitional zone (AUC: 0.7514). Peak enhancement was the best parameter in differentiation of low-grade PCA with Gleason score 6 from high-grade PCA with Gleason score ≥ 7 (AUC: 0.7692). ADC min can differentiate PCA from benign prostate lesions in PZ. Kep Diff could possibly improve prostate cancer detection in. Peak enhancement might be able to differentiate low grade from high-grade PCA. Semi-quantitative and quantitative parameters may be useful for the functional techniques in mp-MRI. Advances in knowledge: ADC min can differentiate PCA from benign prostate lesions in PZ. Peak enhancement might be able to differentiate low grade from high-grade PCA.

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

    ERIC Educational Resources Information Center

    Lobato, Joanne; Bowers, Janet

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

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

    PubMed

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

    2013-11-01

    To qualitatively and quantitatively compare T2-weighted MR imaging of the liver using volumetric spin-echo with sampling perfection with application-optimized contrast using different flip angle evolutions (SPACE) with conventional turbo spin-echo (TSE) sequence for fat-suppressed T2-weighted MR imaging of the liver. Thirty-three patients with suspected focal liver lesions had SPACE MR imaging and conventional fat-suppressed TSE MR imaging. Images were analyzed quantitatively by measuring the lesion-to-liver contrast-to-noise ratio (CNR), and the signal-to-noise ratio (SNR) of main focal hepatic lesions, hepatic and splenic parenchyma and qualitatively by evaluating the presence of vascular, respiratory motion and cardiac artifacts. Wilcoxon signed rank test was used to search for differences between the two sequences. SPACE MR imaging showed significantly greater CNR for focal liver lesions (median=22.82) than TSE MR imaging (median=14.15) (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. 162.1s; P<.001). 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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2004-12-30

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

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

    PubMed

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

    2010-09-01

    Alcohol dehydrogenase (ADH) catalyzes oxidation of ingested ethanol to acetaldehyde, the first step in hepatic metabolism. The purpose of this study was to establish an ex vivo rat liver perfusion system under defined and verified steady states with respect to the metabolites and the metabolic rates, and to quantitatively correlate the observed rates with simulations based on the kinetic mechanism-based rate equations of rat liver ADH. Class I ADH1 was isolated from male Sprague-Dawley rats and characterized by steady-state kinetics in the Krebs-Ringer perfusion buffer with supplements. Nonrecirculating liver perfusion with constant input of ethanol at near physiological hepatic blood flow rate was performed in situ. Ethanol and the related metabolites acetaldehyde, acetate, lactate, and pyruvate in perfusates were determined. Results of the initial velocity, product, and dead-end inhibition studies showed that rat ADH1 conformed to the Theorell-Chance Ordered Bi Bi mechanism. Steady-state metabolism of ethanol in the perfused liver maintained up to 3h as evidenced by the steady-state levels of ethanol and metabolites in the effluent, and the steady-state ethanol disappearance rates and acetate production rates. The changes of the metabolic rates were qualitatively and in general quantitatively correlated to the results from simulations with the kinetic rate equations of ADH1 under a wide range of ethanol, in the presence of competitive inhibitor 4-methylpyrazole and of uncompetitive inhibitor isobutyramide. Preliminary flux control analysis estimated that apparent C(ADH)(J) in the perfused liver may approximate 0.7 at constant infusion with 1-2 mM ethanol, suggesting that ADH plays a major but not the exclusive role in governing hepatic ethanol metabolism. The reported steady-state rat liver perfusion system may potentially be applicable to other drug or drug-ethanol interaction studies. Copyright © 2010 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2017-09-09

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

  4. Inflammatory bowel disease, liver diseases and endothelial function: is there a linkage?

    PubMed

    Ciccone, Marco Matteo; Principi, Mariabeatrice; Ierardi, Enzo; Di Leo, Alfredo; Ricci, Gabriella; Carbonara, Santa; Gesualdo, Michele; Devito, Fiorella; Zito, Annapaola; Cortese, Francesca; Scicchitano, Pietro

    2015-01-01

    Atherosclerosis is a systemic inflammatory disease able to deeply worsen the outcome of patients because of its serious clinical consequences. The complex inflammatory background underlining such a disease makes atherosclerosis linked to several systemic inflammatory conditions able to impair endothelial function and morphology. Inflammatory bowel diseases are a group of gastrointestinal diseases including Crohn's disease and ulcerative colitis, that is, syndromes characterized by changes in mucosal immunity and gastrointestinal physiology, which could negatively influence the vascular endothelial function and structure. Hepatitis (i.e. inflammatory diseases of the liver mainly due to viral infections) and nonalcoholic fatty liver disease could be aligned to inflammatory bowel disease in such an induction of atherosclerosis disease.Many studies tried to point out the relationship between bowel and liver inflammatory diseases and early vascular changes, considered the first step for atherosclerosis development.The aim of such a narrative review is to explain the relationship between inflammatory bowel disease, hepatitis and nonalcoholic fatty liver disease and their role in increasing cardiovascular risk profile due to early impairment in vascular function and morphology.

  5. Quantitative analysis of cytochrome P450 isoforms in human liver microsomes by the combination of proteomics and chemical probe-based assay.

    PubMed

    Liu, Xidong; Hu, Lianghai; Ge, Guangbo; Yang, Bo; Ning, Jing; Sun, Shixin; Yang, Ling; Pors, Klaus; Gu, Jingkai

    2014-08-01

    Cytochrome P450 (CYP) is one of the most important drug-metabolizing enzyme families, which participates in the biotransformation of many endogenous and exogenous compounds. Quantitative analysis of CYP expression levels is important when studying the efficacy of new drug molecules and assessing drug-drug interactions in drug development. At present, chemical probe-based assay is the most widely used approach for the evaluation of CYP activity although there are cross-reactions between the isoforms with high sequence homologies. Therefore, quantification of each isozyme is highly desired in regard to meeting the ever-increasing requirements for carrying out pharmacokinetics and personalized medicine in the academic, pharmaceutical, and clinical setting. Herein, an absolute quantification method was employed for the analysis of the seven isoforms CYP1A2, 2B6, 3A4, 3A5, 2C9, 2C19, and 2E1 using a proteome-derived approach in combination with stable isotope dilution assay. The average absolute amount measured from twelve human liver microsomes samples were 39.3, 4.3, 54.0, 4.6, 10.3, 3.0, and 9.3 (pmol/mg protein) for 1A2, 2B6, 3A4, 3A5, 2C9, 2C19, and 2E1, respectively. Importantly, the expression level of CYP3A4 showed high correlation (r = 0.943, p < 0.0001) with the functional activity, which was measured using bufalin-a highly selective chemical probe we have developed. The combination of MRM identification and analysis of the functional activity, as in the case of CYP3A4, provides a protocol which can be extended to other functional enzyme studies with wide application in pharmaceutical research.

  6. A quantitative overview of biophysical forces impinging on neural function

    NASA Astrophysics Data System (ADS)

    Mueller, Jerel K.; Tyler, William J.

    2014-10-01

    The fundamentals of neuronal membrane excitability are globally described using the Hodgkin-Huxley (HH) model. The HH model, however, does not account for a number of biophysical phenomena associated with action potentials or propagating nerve impulses. Physical mechanisms underlying these processes, such as reversible heat transfer and axonal swelling, have been compartmentalized and separately investigated to reveal neuronal activity is not solely influenced by electrical or biochemical factors. Instead, mechanical forces and thermodynamics also govern neuronal excitability and signaling. To advance our understanding of neuronal function and dysfunction, compartmentalized analyses of electrical, chemical, and mechanical processes need to be revaluated and integrated into more comprehensive theories. The present perspective is intended to provide a broad overview of biophysical forces that can influence neural function, but which have been traditionally underappreciated in neuroscience. Further, several examples where mechanical forces have been shown to exert their actions on nervous system development, signaling, and plasticity are highlighted to underscore their importance in sculpting neural function. By considering the collective actions of biophysical forces influencing neuronal activity, our working models can be expanded and new paradigms can be applied to the investigation and characterization of brain function and dysfunction.

  7. A quantitative overview of biophysical forces impinging on neural function.

    PubMed

    Mueller, Jerel K; Tyler, William J

    2014-08-26

    The fundamentals of neuronal membrane excitability are globally described using the Hodgkin-Huxley (HH) model. The HH model, however, does not account for a number of biophysical phenomena associated with action potentials or propagating nerve impulses. Physical mechanisms underlying these processes, such as reversible heat transfer and axonal swelling, have been compartmentalized and separately investigated to reveal neuronal activity is not solely influenced by electrical or biochemical factors. Instead, mechanical forces and thermodynamics also govern neuronal excitability and signaling. To advance our understanding of neuronal function and dysfunction, compartmentalized analyses of electrical, chemical, and mechanical processes need to be revaluated and integrated into more comprehensive theories. The present perspective is intended to provide a broad overview of biophysical forces that can influence neural function, but which have been traditionally underappreciated in neuroscience. Further, several examples where mechanical forces have been shown to exert their actions on nervous system development, signaling, and plasticity are highlighted to underscore their importance in sculpting neural function. By considering the collective actions of biophysical forces influencing neuronal activity, our working models can be expanded and new paradigms can be applied to the investigation and characterization of brain function and dysfunction.

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

    PubMed Central

    Calvopina, Diego A.; Coleman, Miranda A.; Lewindon, Peter J.; Ramm, Grant A.

    2016-01-01

    MicroRNAs (miRNAs) are short non-coding RNAs involved in biological and pathological processes of every cell type, including liver cells. Transcribed from specific genes, miRNA precursors are processed in the cytoplasm into mature miRNAs and as part of the RNA-induced silencing complex (RISC) complex binds to messenger RNA (mRNA) by imperfect complementarity. This leads to the regulation of gene expression at a post-transcriptional level. The function of a number of different miRNAs in fibrogenesis associated with the progression of chronic liver disease has recently been elucidated. Furthermore, miRNAs have been shown to be both disease-and tissue-specific and are stable in the circulation, which has led to increasing investigation on their utility as biomarkers for the diagnosis of chronic liver diseases, including those in children. Here, we review the current knowledge on the biogenesis of microRNA, the mechanisms of translational repression and the use of miRNA as circulatory biomarkers in chronic paediatric liver diseases including cystic fibrosis associated liver disease, biliary atresia and viral hepatitis B. PMID:27801781

  9. Differential phenotypic and functional properties of liver-resident NK cells and mucosal ILC1s.

    PubMed

    Tang, Ling; Peng, Hui; Zhou, Jing; Chen, Yongyan; Wei, Haiming; Sun, Rui; Yokoyama, Wayne M; Tian, Zhigang

    2016-02-01

    Group 1 innate lymphoid cells (ILCs) consist of conventional natural killer (cNK) cells, tissue-resident NK cells and mucosal ILC1s. Recently identified liver-resident NK cells, which can mount contact hypersensitivity responses, and mucosal ILC1s that are involved in pathogenesis of colitis are distinct from cNK cells in several aspects, but the issue of how they are related to each other has not been clearly clarified. Here, we show that liver-resident NK cells and mucosal ILC1s have different phenotypes, as evidenced by distinct expression patterns of homing-associated molecules. Moreover, mucosal ILC1s exhibit tissue residency akin to liver-resident NK cells. Importantly, liver-resident NK cells express relative high levels of cytotoxic effector molecules, which are poorly expressed by mucosal ILC1s, and exhibit stronger cytotoxic activity compared with mucosal ILC1s. These results demonstrate differential phenotypic and functional characteristics of liver-resident NK cells and mucosal ILC1s, shedding new light on the diversity of ILC family.

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

    PubMed

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

    2013-12-01

    Hepatic impairment, portal hypertension, and multi-systemic damage could occur during liver cirrhosis's late stage. Bleeding is a complication of hepatic cirrhosis along with several changes including blood platelet count (BPC), mean platelet volume (MPV), platelet crit (PCT) and expression of platelet CD62P. Blood platelet count (BPC), mean platelet volume (MPV), platelet distribution width, and other indices are indirect reflections of CD62P parameters. To investigate the changes in platelet functional parameters and CD62 P expression in liver cirrhosis as a possible guide in clinical treatments and prognoses of liver cirrhosis. CD62P was tested by flow cytometry in liver cirrhosis. BPC, MPV, and PCT in peripheral blood were tested using an auto blood cell analyzer. Data were analyzed using SPSS11.0. The values of CD62P and MPV in patients was significantly higher than those of healthy donors (P<0.01), while the values of BPC and PCT were significantly lower than those of the control group (P<0.01). CD62P, BPC, MPV, and platelet crit (PCT) show several changes in liver cirrhosis. It is useful to understand the relationship between hepatic cirrhosis severity and CD62P, BPC, MPV, PCT, timely monitoring of CD62P for treatment of hepatic cirrhosis in clinical treatment and prognosis.

  11. Quantitative Study of Elasticity of Rabbit VX2 Liver Tumor with Alternated Cooling and Heating Treatment based on ARFI Ultrasound Imaging Technique

    PubMed Central

    Sun, Di; Wei, Cong; Shen, E.; Ying, Tao; Hu, Bing

    2016-01-01

    Acoustic radiation force impulse (ARFI) ultrasound imaging technique is used to quantitatively evaluate the elasticity of rabbit VX2 liver tumor with alternated cooling and heating treatment (ACHT). ACHT was performed on fifteen VX2 liver tumor models established in fifteen male New Zealand white rabbits with open tumor plant. ARFI was performed on day 0, 1, 7 and 14 after ACHT and shear wave velocity (SWV) in ARFI was recorded to evaluate the elasticity of the treated area. The SWV value of the lesion on day 0, 1, 7 and 14 was 2.33 ± 0.19 m/s, 3.09 ± 0.40 m/s, 2.64 ± 0.37 m/s and 2.26 ± 0.24 m/s, respectively, indicating the treated areas get stiffer on day 1 and then get softer gradually by day. All the difference between adjacent time points was statistically significant. The SWV value of different parts on day 7 approved that the hardness of the treated area is heterogenous: the treated area in the center >the peripheral strip-shaped area >normal liver tissues, consistent with pathological changes. Meanwhile, ARFI combined with conventional US imaging can qualitatively and quantitatively exam the healing process of rabbit VX2 liver tumor after ACHT, and corresponds well to the pathological results. PMID:27381362

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

    PubMed

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

    2017-01-01

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

  13. Improvement of graft function and animal survival by fat emulsion in liver transplant rats.

    PubMed

    Ma, Zheng-Wei; Liu, Li-Dong; Li, Kun; Zhang, Yu-Jun; Dong, Jia-Hong

    2007-01-15

    Nutritional supports are required for liver transplant patients. However, no systematical assessment has been made of the optimal composition of energy yielding substrates in these patients. This study is to evaluate whether mixed energy system consisting of carbohydrate and lipid emulsions is more advantageous over single energy source of glucose for nutritional support in liver transplant recipients and whether structured lipid emulsion (STG) is superior to medium-chain triglyceride/long-chain triglycerides (MCT/LCT) and long-chain triglycerides (LCT) using a total parenteral nutrition model. Liver transplant rats were randomly divided to four groups according to the energy source, i.e. glucose (GLU), MCT/LCT, STG and LCT groups. Sham operated rats served as control. Hepatic function and lipid profile were determined to investigate the roles of lipid emulsion in hepatic function and lipid metabolism. Morphological changes of liver were observed, and nitrogen balance was determined. The results showed that infusion of lipid emulsion was well tolerated. The 1-week survival rate in the lipid emulsion groups was significantly higher than in the GLU group (100% versus 50%, P<0.05); compared with the GLU group, hepatic function recovered quickly and returned to normal level, and morphological alterations were less severer in the lipid emulsion groups, especially in the STG group; the lipid emulsions groups had normal serum TG and TC levels, especially STG and MCT/LCT groups; the lipid emulsions groups achieved a positive nitrogen balance on day 7 compared with the GLU group, and the STG group had the highest nitrogen balance. In conclusion, lipid emulsion is beneficial in improving hepatic function and the recipients' survival and does not influence the lipid metabolism. Mixed energy system consisting of carbohydrate and lipid is more advantageous over single energy source of glucose after liver transplantation, and STG is superior to MCT/LCT and LCT.

  14. Quantitative Measurements of Enhancement on Preprocedure Triphasic CT Can Predict Response of Colorectal Liver Metastases to Radioembolization

    PubMed Central

    Boas, F. Edward; Brody, Lynn A.; Erinjeri, Joseph P.; Yarmohammadi, Hooman; Shady, Waleed; Kishore, Sirish; Sofocleous, Constantinos T.

    2016-01-01

    Objective Colorectal liver metastases (CLM) have a variable response to radioembolization. This may be due at least partly to differences in tumor arterial perfusion. The present study examines whether quantitative measurements of enhancement on preprocedure triphasic CT can be used to predict the response of CLM to radioembolization. Materials and Methods We retrospectively reviewed patients with CLM treated with radioembolization who underwent pretreatment PET/CT and triphasic CT examinations and posttreatment PET/CT examinations. A total of 31 consecutive patients with 60 target tumors were included in the present study. For each tumor, we calculated the hepatic artery coefficient (HAC), portal vein coefficient (PVC), and arterial enhancement fraction (AEF) based on enhancement measurements on pretreatment triphasic CT. HAC and PVC are estimates of the hepatic artery and portal vein blood supply. AEF, which is the arterial phase enhancement divided by the portal phase enhancement, provides an estimate of the hepatic artery blood supply as a fraction of the total blood supply. For each tumor, the metabolic response to radioembolization was based on findings from the initial follow-up PET/CT scan obtained at 4–8 weeks after treatment. Results A total of 55% of CLM had a complete or partial metabolic response. Arterial phase enhancement, the HAC, and the PVC did not predict which tumors responded to radioembolization. However, the AEF was statistically significantly greater in tumors with a complete or partial metabolic response than in tumors with no metabolic response (i.e., those with stable disease or disease progression) (p = 0.038). An AEF of less than 0.4 was associated with a 40% response rate, whereas an AEF greater than 0.75 was associated with a 78% response rate. Conclusion Response to radioembolization can be predicted using the AEF calculated from the preprocedure triphasic CT. PMID:27248430

  15. Integrating Drug's Mode of Action into Quantitative Structure-Activity Relationships for Improved Prediction of Drug-Induced Liver Injury.

    PubMed

    Wu, Leihong; Liu, Zhichao; Auerbach, Scott; Huang, Ruili; Chen, Minjun; McEuen, Kristin; Xu, Joshua; Fang, Hong; Tong, Weida

    2017-04-24

    Drug-induced liver injury (DILI) is complex in mechanism. Different drugs could undergo different mechanisms but result in the same DILI type, while the same drug could lead to different DILI types via different mechanisms. Therefore, predicting a drug's potential for DILI should take its underlying mechanisms into consideration. To achieve that, we constructed a novel approach by incorporating the drug's Mode of Action (MOA) into Quantitative Structure-Activity Relationship (QSAR) modeling. This MOA-DILI approach was examined using a data set of 333 drugs. The drugs were first grouped according to their MOA profiles (positive or negative in each MOA) based on the Tox21 qHTS assays. QSAR models for individual MOA assays were developed and subsequently combined to obtain the MOA-DILI model. A hold-out testing strategy (222 drugs for training and 111 drugs as a test set) was employed, which yielded a predictive accuracy of 0.711. The MOA-DILI model was directly compared with the standard QSAR approach using the same hold-out strategy, and the QSAR model yielded an accuracy of 0.662. To minimize the random chance in splitting training/test sets, the hold-out testing process was repeated 1000 times, and the observed difference in prediction accuracy between MOA-DILI and QSARs was statistically significant (P value <0.0001). Out of 17 MOAs used, four assays (i.e., antioxidant response elements, PPAR-gamma, estrogen receptor, and thyroid receptor assays) contributed most to the improved prediction of the MOA-DILI model over QSARs. In conclusion, the MOA-DILI approach has the potential to significantly improve predictive outcomes and to reveal complex relationships between MOAs and DILI, all of which would be helpful in developing DILI predictive models in drug screening and for risk assessment of industrial chemicals.

  16. Quantitative Amyloid Imaging Using Image-Derived Arterial Input Function

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  18. Boron determination in liver tissue by combining quantitative neutron capture radiography (QNCR) and histological analysis for BNCT treatment planning at the TRIGA Mainz.

    PubMed

    Schütz, C; Brochhausen, C; Altieri, S; Bartholomew, K; Bortolussi, S; Enzmann, F; Gabel, D; Hampel, G; Kirkpatrick, C J; Kratz, J V; Minouchehr, S; Schmidberger, H; Otto, G

    2011-09-01

    The typical primary malignancies of the liver are hepatocellular carcinoma and cholangiocarcinoma, whereas colorectal liver metastases are the most frequently occurring secondary tumors. In many cases, only palliative treatment is possible. Boron neutron capture therapy (BNCT) represents a technique that potentially destroys tumor tissue selectively by use of externally induced, locally confined secondary particle irradiation. In 2001 and 2003, BNCT was applied to two patients with colorectal liver metastases in Pavia, Italy. To scrutinize the rationale of BNCT, a clinical pilot study on patients with colorectal liver metastases was carried out at the University of Mainz. The distribution of the (10)B carrier (p-borono-phenylalanine) in the liver and its uptake in cancerous and tumor-free tissue were determined, focusing on a potential correlation between the uptake of p-borono-phenylalanine and the biological characteristics of cancerous tissue. Samples were analyzed using quantitative neutron capture radiography of cryosections combined with histological analysis. Methodological aspects of the combination of these techniques and results from four patients enrolled in the study are presented that indicate that the uptake of p-borono-phenylalanine strongly depends on the metabolic activity of cells.

  19. Linezolid in liver failure: exploring the value of the maximal liver function capacity (LiMAx) test in a pharmacokinetic pilot study.

    PubMed

    Wicha, Sebastian G; Frey, Otto R; Roehr, Anka C; Pratschke, Johann; Stockmann, Martin; Alraish, Rawan; Wuensch, Tilo; Kaffarnik, Magnus

    2017-10-01

    Patients in the intensive care unit frequently require antibiotic treatment. Liver impairment poses substantial challenges for dose selection in these patients. The aim of the present pilot study was to assess the novel maximal liver function capacity (LiMAx test) in comparison with conventional liver function markers as covariates of drug clearance in liver failure using linezolid as a model drug. A total of 28 patients with different degrees of liver failure were recruited. LiMAx test as well as plasma, dialysate and urine sampling were performed under linezolid steady-state therapy (600 mg twice daily). NONMEM(®) was used for a pharmacometric analysis in which the different clearance routes of linezolid were elucidated. Linezolid pharmacokinetics was highly variable in patients with liver failure. The LiMAx score displayed the strongest association with non-renal clearance (CLnon-renal) [ = 4.46∙(body weight/57.9) (0.75)∙(LiMAx/221.5)(0.388) L/h], which reduced interindividual variability in CLnon-renal from 46.6% to 33.6%, thereby being superior to other common markers of liver function (international normalised ratio, gamma-glutaryl transferase, bilirubin, thrombocytes, alanine aminotransferase, aspartate aminotransferase). For LiMAx < 100 µg/kg/h, 64% of linezolid trough concentrations were above the recommended trough concentration of 8 mg/L, indicating the necessity of therapeutic drug monitoring in these patients. This is the first pilot application of the LiMAx test in a pharmacokinetic (PK) study demonstrating its potential to explain PK variability in linezolid clearance. Further studies with a larger patient collective and further drugs are highly warranted to guide dosing in patients with severe liver impairment. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

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

    PubMed

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

    2012-01-01

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

  1. Functional life-long maintenance of engineered liver tissue in mice following transplantation under the kidney capsule.

    PubMed

    Ohashi, Kazuo; Koyama, Fumikazu; Tatsumi, Kohei; Shima, Midori; Park, Frank; Nakajima, Yoshiyuki; Okano, Teruo

    2010-02-01

    The ability to engineer biologically active cells and tissue matrices with long-term functional maintenance has been a principal focus for investigators in the field of hepatocyte transplantation and liver tissue engineering. The present study was designed to determine the efficacy and temporal persistence of functional engineered liver tissue following transplantation under the kidney capsule of a normal mouse. Hepatocytes were isolated from human alpha-1 antitrypsin (hA1AT) transgenic mouse livers. Hepatocytes were subsequently transplanted under the kidney capsule space in combination with extracellular matrix components (Matrigel) for engineering liver tissues. The primary outcome of interest was to assess the level of engineering liver tissue function over the experimental period, which was 450 days. Long-term survival by the engineered liver tissue was confirmed by measuring the serum level of hA1AT in the recipient mice throughout the experimental period. In addition, administration of chemical compounds at day 450 resulted in the ability of the engineered liver tissue to metabolize exogenously circulating compounds and induce drug-metabolizing enzyme production. Moreover, we were able to document that the engineered tissues could retain their native regenerative potential similar to that of naïve livers. Overall, these results demonstrated that liver tissues could be engineered at a heterologous site while stably maintaining its functionality for nearly the life span of a normal mouse.

  2. The physiological position of the liver in the circulation is not a major determinant of its functional capacity.

    PubMed

    Wagenaar, G T; Chamuleau, R A; Maas, M A; de Bruin, K; Korfage, H A; Lamers, W H

    1994-12-01

    The zonal patterns of gene expression in the liver of the rat are not affected by alteration of the afferent hepatic blood source. We investigated whether afferent hepatic blood source or flow rate affects the metabolic capacity of the liver. Using microsurgical techniques, we changed the afferent hepatic blood source to solely arterial blood, solely portal blood or solely caval blood. The transhepatic flow rate was four times higher in arterialized than in cavalized livers. Liver function was tested 2 wk after surgery. Three liver functions were tested (elimination of hepatic iminodiacetic acid from the liver and elimination of galactose and ammoniumbicarbonate from the circulation). Our results show that the afferent hepatic blood flow rate rather than the source of the afferent hepatic blood affects the elimination of the substrates tested. We found that at the physiological flow rate of approximately 15 ml/min and beyond, metabolic function does not depend on the flow of the afferent hepatic blood but that at lower flow rates the flow becomes a major determinant of the metabolic function of the liver. We conclude that the position of the liver within the circulation (i.e. between the gastrointestinal tract and the systemic circulation) is apparently not a prerequisite for adequate metabolic activity, at least for the substrates tested, provided that the liver is sufficiently perfused with blood.

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

    PubMed

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

    2016-12-01

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

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

    PubMed

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

    2006-08-01

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

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

    PubMed

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

    1996-08-01

    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. 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 involved in metabolic liver functions, i.e. ureagenesis, gluconeogenesis, and drug metabolism, for acute phase proteins, "house-keeping" proteins, and for proteins related to liver regeneration. Results were expressed as per cent of the level in similarly fasted, untreated rats of the same stock After the smaller dose of acetaminophen, most of the examined mRNA levels were increasing during the experimental period, being two- to four-fold elevated in relation to control after 6 to 12 h. Rats receiving the lethal dose either showed no or a later and smaller increase, and in several cases a fall towards the end of the experiment. The greatest differences were seen for mRNA of arginase, beta-fibrinogen, alpha 1-acid glycoprotein, alpha-tubulin, histone 3, TGF beta, and cyclin d, i.e. proteins associated with acute phase response and liver cell replication and maintenance. It is concluded that reversible intoxication with acetaminophen induces an adaptive modulation of mRNA expression of liver functions and regeneration which is lacking after severe intoxication. This adaptation, with emphasis on acute phase response and regeneration, may be crucial for recovery after acetaminophen intoxication. If this also applies to the intoxication in man, estimates of the corresponding variables may be clues to the prognosis of acetaminophen-induced fulminant hepatic failure.

  6. HepatoProteomics: Applying Proteomic Technologies to the Study of Liver Function and Disease

    SciTech Connect

    Diamond, Deborah L.; Proll, Sean; Jacobs, Jon M.; Chan, Eric Y.; Camp, David G.; Smith, Richard D.; Katze, Michael G.

    2006-08-01

    The wealth of human genome sequence information now available, coupled with technological advances in robotics, nanotechnology, mass spectrometry, and information systems, has given rise to a method of scientific inquiry known as functional genomics. By using these technologies to survey gene expression and protein production on a near global scale, the goal of functional genomics is to assign biological function to genes with currently unknown roles in physiology. This approach carries particular appeal in disease research, where it can uncover the function of previously unknown genes and molecular pathways that are directly involved in disease progression. With this knowledge may come improved diagnostic techniques, prognostic capabilities, and novel therapeutic approaches. In this regard, the continuing evolution of proteomic technologies has resulted in an increasingly greater impact of proteome studies in many areas of research and hepatology is no exception. Our laboratory has been extremely active in this area, applying both genomic and proteomic technologies to the analysis of virus-host interactions in several systems, including the study of hepatitis C virus (HCV) infection and HCV-associated liver disease. Since proteomic technologies are foreign to many hepatologists (and to almost everyone else), this article will provide an overview of proteomic methods and technologies and describe how they're being used to study liver function and disease. We use our studies of HCV infection and HCV-associated liver disease to present an operational framework for performing high throughput proteome analysis and extracting biologically meaningful information.

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

    PubMed Central

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

    2015-01-01

    AIM: To investigate the value of magnetic resonance elastography (MRE) with regard to assessing liver functional reserve. METHODS: Data from inpatients diagnosed with a liver tumor at an interventional radiology department from July 2013 to June 2014 were analyzed. A 3.0 Tesla magnetic resonance unit was used to scan 32 patients with confirmed diagnoses of hepatocellular carcinoma (HCC); an MRE sequence was added to the protocol, and the data were reconstructed and analyzed by two attending radiologists. Regions of interest were identified in different slices of the non-tumor liver parenchyma to measure average stiffness. In addition, the indocyanine green (ICG) test was performed no more than 1 wk before or after the magnetic resonance examination for all 32 patients; the ICG retention rate at 15 min (ICGR-15) and the ICG plasma clearance rate (ICG-K) were recorded. Correlational analyses were performed between the liver stiffness values and the ICGR-15 as well as between the liver stiffness values and the ICG-K. RESULTS: Magnetic resonance imaging, including an MRE sequence and the ICG test, was performed successfully in all 32 enrolled patients. None of the patients developed complications. The mean ± SD of the elasticity values measured by the two attending radiologists were 4.7 ± 2.2 kPa and 4.7 ± 2.1 kPa, respectively. The average liver stiffness value of the non-tumor parenchyma measured using MRE in HCC patients was 4.7 ± 2.2 kPa. The average ICGR-15 was 0.089 ± 0.077, and the average ICG-K was 0.19 ± 0.07. We found that the liver stiffness value of the non-tumor parenchyma was significantly and positively related to the ICGR-15 (r = 0.746, P < 0.01) as well as significantly and negatively related to the ICG-K (r = -0.599, P < 0.01). The ICGR-15 was significantly and negatively related to the ICG-K (r = -0.852, P < 0.01). CONCLUSION: MRE is accurate and non-invasive; furthermore, it can be used to effectively assess the liver functional reserve of HCC

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

    PubMed

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

    2015-06-28

    To investigate the value of magnetic resonance elastography (MRE) with regard to assessing liver functional reserve. Data from inpatients diagnosed with a liver tumor at an interventional radiology department from July 2013 to June 2014 were analyzed. A 3.0 Tesla magnetic resonance unit was used to scan 32 patients with confirmed diagnoses of hepatocellular carcinoma (HCC); an MRE sequence was added to the protocol, and the data were reconstructed and analyzed by two attending radiologists. Regions of interest were identified in different slices of the non-tumor liver parenchyma to measure average stiffness. In addition, the indocyanine green (ICG) test was performed no more than 1 wk before or after the magnetic resonance examination for all 32 patients; the ICG retention rate at 15 min (ICGR-15) and the ICG plasma clearance rate (ICG-K) were recorded. Correlational analyses were performed between the liver stiffness values and the ICGR-15 as well as between the liver stiffness values and the ICG-K. Magnetic resonance imaging, including an MRE sequence and the ICG test, was performed successfully in all 32 enrolled patients. None of the patients developed complications. The mean ± SD of the elasticity values measured by the two attending radiologists were 4.7 ± 2.2 kPa and 4.7 ± 2.1 kPa, respectively. The average liver stiffness value of the non-tumor parenchyma measured using MRE in HCC patients was 4.7 ± 2.2 kPa. The average ICGR-15 was 0.089 ± 0.077, and the average ICG-K was 0.19 ± 0.07. We found that the liver stiffness value of the non-tumor parenchyma was significantly and positively related to the ICGR-15 (r = 0.746, P < 0.01) as well as significantly and negatively related to the ICG-K (r = -0.599, P < 0.01). The ICGR-15 was significantly and negatively related to the ICG-K (r = -0.852, P < 0.01). MRE is accurate and non-invasive; furthermore, it can be used to effectively assess the liver functional reserve of HCC patients.

  9. Peripheral blood monocytes from patients with HBV related decompensated liver cirrhosis can differentiate into functional hepatocytes.

    PubMed

    Yan, Li; Han, Ying; Wang, Jingbo; Liu, Jingmei; Hong, Liu; Fan, Daiming

    2007-11-01

    Peripheral blood monocytes (PBMCs) have the potential to differentiate into various progenitor cells. Here we have investigated the differentiation potential of PBMCs derived from patients with HBV related decompensated liver cirrhosis into hepatocyte-like cells. In our clinical trial, the PBMCs from 2 patients were mobilized by the recombinant human granulocyte colony stimulating factor, followed by leukapheresis and transplantation of PBMCs. PBMCs, induced by recombinant human hepatocyte growth factors, were identified by the expression of hepatocyte markers and specific biological functions with biochemical assays in vitro. Patients showed a lasting clinical amelioration for more than one year after transplantation, and hepatocyte-like cells were identified by expressing liver specific genes, synthesizing albumin, urea, aspirate transaminase, and glycogen, which were all similar to the human normal hepatic cell line QZG. Our results clearly demonstrated that mobilized PBMCs from patients with HBV related decompensated liver cirrhosis could differentiate into functional hepatocyte-like cells, indicating the possibility of autologous cell transplantation for treating patients with HBV related decompensated liver cirrhosis.

  10. Combined effects of fluoride and cadmium on liver and kidney function in male rats.

    PubMed

    Zhang, Junmin; Song, Jingjuan; Zhang, Jun; Chen, Xiao; Zhou, Meixia; Cheng, Guang; Xie, Xinyou

    2013-12-01

    It has been shown that cadmium and fluoride may both have adverse effects on liver and kidney functions, but most studies focus on a single agent. In this study, we observed the effects of cadmium and fluoride on liver and kidney functions using a rat model. Total of 24 Sprague-Dawley male rats were divided into four groups, one control group and three exposure groups that were given cadmium (50 mg/L) and fluoride (100 mg/L) alone or in combination via drinking water. At the 12th week, urine, blood, and kidney tissues were collected. Aspartate transaminase, alanine transaminase (ALT), urinary β2-microglobulin, and albumin were determined. Contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in liver and kidney homogenates were measured to evaluate oxidative stress. There was a significant increase in serum ALT and urinary β2-microglobulin of rats in exposure groups compared with control. Serum ALT and urinary β2-microglobulin of rats exposed to cadmium and fluoride in combination was significantly higher than those treated with cadmium alone and fluoride alone. SOD declined significantly and MDA increased in combination group compared with control and those treated with cadmium and fluoride alone. Cadmium and fluoride co-exposure increase the liver and kidney damage compared with that exposed to cadmium or fluoride alone.

  11. Evaluation of Liver Function After Proton Beam Therapy for Hepatocellular Carcinoma

    SciTech Connect

    Mizumoto, Masashi; Okumura, Toshiyuki; Hashimoto, Takayuki; Fukuda, Kuniaki; Oshiro, Yoshiko; Fukumitsu, Nobuyoshi; Abei, Masato; Kawaguchi, Atsushi; Hayashi, Yasutaka; Ohkawa, Ayako; Hashii, Haruko; Kanemoto, Ayae; Moritake, Takashi; Tohno, Eriko; Tsuboi, Koji; Sakae, Takeji; Sakurai, Hideyuki

    2012-03-01

    Purpose: Our previous results for treatment of hepatocellular carcinoma with proton beam therapy (PBT) revealed excellent local control. In this study, we focused on the impact of PBT on normal liver function. Methods and Materials: The subjects were 259 patients treated with PBT at University of Tsukuba between January 2001 and December 2007. We evaluated the Child-Pugh score pretreatment, on the final day of PBT, and 6, 12, and 24 months after treatment with PBT. Patients who had disease progression or who died with tumor progression at each evaluation point were excluded from the analysis to rule out an effect of tumor progression. An increase in the Child-Pugh score of 1 or more was defined as an adverse event. Results: Of the 259 patients, 241 had no disease progression on the final day of PBT, and 91 had no progression within 12 months after PBT. In univariate analysis, the percentage volumes of normal liver receiving at least 0, 10, 20, and 30 GyE in PBT (V0, 10, 20, and 30) were significantly associated with an increase of Child-Pugh score at 12 months after PBT. Of the 91 patients evaluated at 12 months, 66 had no increase of Child-Pugh score, 15 had a 1-point increase, and 10 had an increase of {>=}2 points. For the Youden index, the optimal cut-offs for V0, V10, V20, and V30 were 30%, 20%, 26%, and 18%, respectively. Conclusion: Our findings indicate that liver function after PBT is significantly related to the percentage volume of normal liver that is not irradiated. This suggests that further study of the relationship between liver function and PBT is required.

  12. Chenodeoxycholic Acid Derivative HS-1200 Inhibits Hepatocarcinogenesis and Improves Liver Function in Diethylnitrosamine-Exposed Rats by Downregulating MTH1

    PubMed Central

    Zhao, Qi; Liu, Hui; Qi, Jianni

    2017-01-01

    Aim. To investigate the effects of HS-1200 on liver tumorigenesis and liver function in a diethylnitrosamine- (DEN-) induced hepatocellular carcinoma (HCC) rat model. Methods. Rats were randomly assigned into five groups: control, HS-1200, HCC, HCC + low dose HS-1200, and HCC + high dose HS-1200 groups. Rat HCC model was established by intraperitoneal injection of DEN. And rats were given HS-1200 by daily oral gavage. After 20 weeks, we examined animal body weight, liver weight, liver pathological changes, serum levels of AST, ALT, and AFP, and mutT homologue gene 1 (MTH1) in liver tissue. Results. Oral gavage of HS-1200 significantly increased animal body weight and decreased liver weight as well as liver coefficient in HCC rats (P < 0.05 versus HCC group). Moreover, oral administration of HS-1200 suppressed tumorigenesis, attenuated pathological changes in liver tissues, and decreased serum levels of AST, ALT, and AFP in HCC rats (P < 0.05 versus HCC group). In addition, the mRNA level of MTH1 was upregulated in the liver tissues of HCC rats (P < 0.05 versus control group), which was reversed by HS-1200 treatment in a dose-dependent manner (P < 0.05 versus HCC group). Conclusions. HS-1200 inhibits hepatocarcinogenesis and improves liver function maybe by inducing downregulation of MTH1. PMID:28261604

  13. Chronic kidney disease-epidemiology formula and model for end-stage liver disease score in the assessment of renal function in candidates for liver transplantation.

    PubMed

    Tinti, F; Lai, S; Umbro, I; Mordenti, M; Barile, M; Ginanni Corradini, S; Rossi, M; Poli, L; Nofroni, I; Berloco, P B; Mitterhofer, A P

    2010-05-01

    Assessment of renal function in patients with end-stage liver disease (ESLD) awaiting liver transplantation (OLT) is critical. Various conditions may cause renal damage in ESLD. Renal and liver functions are intertwined due to splanchnic hemodynamic relationships; renal failure rarely occurs in patients without advanced decompensated cirrhosis. The recent literature suggests that evaluation of renal function should include an assessment of liver function. The aim of this study was to evaluate different methods to estimate glomerular filtration rate (GFR) in patient among ESLD candidates for OLT over 1 year. We also correlated renal and hepatic functions. Fifty-two cirrhotic patients Model for End-Stage Liver Disease [MELD] > 10) were enrolled in the study. All patients were evaluated at baseline and every 4 months (T1-T4) thereafter for 1 year. The GFR was calculated by creatinine clearance, and estimated by Cockroft and Gault, Modified Diet Renal Disease (MDRD) 4 and 6 variable and Chronic Kidney Disease-Epidemiology (CKD-EPI) formulae. Hepatic functions were evaluated by MELD score, albumin, bilirubin, and International Normalized Ratio (INR). We observed not statistically significant increase mean value of MELD score, bilirubin, serum creatinine, and blood urea nitrogen and a reduced serum sodium. There were no significant differences among various methods to evaluate GFR at each time over 1 year. We did not observe any association between renal and hepatic function, except at T4 for MELD and GFR estimated with MDRD 4 (P = .009) and 6 (P = .008) parameters or CKD-EPI (P = .036), and MELD and sodium (P = .001). Our results showed that evaluation of renal function in cirrhosis should include an evaluation of hepatic function. In our case, MDRD and CKD-EPI seemed to be the more accurate formulae to evaluate renal function in relation to hepatic function. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  14. Quantitative simulation of intracellular signaling cascades in a Virtual Liver: estimating dose dependent changes in hepatocellular proliferation and apoptosis

    EPA Science Inventory

    The US EPA Virtual Liver (v-Liver™) is developing an approach to predict dose-dependent hepatotoxicity as an in vivo tissue level response using in vitro data. The v-Liver accomplishes this using an in silico agent-based systems model that dynamically integrates environmental exp...

  15. Quantitative simulation of intracellular signaling cascades in a Virtual Liver: estimating dose dependent changes in hepatocellular proliferation and apoptosis

    EPA Science Inventory

    The US EPA Virtual Liver (v-Liver™) is developing an approach to predict dose-dependent hepatotoxicity as an in vivo tissue level response using in vitro data. The v-Liver accomplishes this using an in silico agent-based systems model that dynamically integrates environmental exp...

  16. The Groningen hypothermic liver perfusion pump: functional evaluation of a new machine perfusion system.

    PubMed

    van der Plaats, A; Maathuis, M H J; 'T Hart, N A; 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

    2006-12-01

    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, sufficient oxygenation, a maintained 0-4 degrees C temperature and sterile conditions. Porcine livers were perfused with pump pressures that were set at 4 mmHg (continuous, portal vein) and 30/20 mmHg, at 60 BPM (pulsatile, hepatic artery). Control livers were preserved using the clinical golden standard: static cold storage. In the HMP group, pressure, flow and temperature were continuously monitored for 24 h. At time-points t = 0, 2, 4, 8, 12, and 24 h samples of University of Wisconsin machine preservation solution were taken for measurement of partial oxygen pressure (pO(2)) and lacto-dehydrogenase. Biopsies in every lobe were taken for histology and electron microscopy; samples of ice, preservation solution, liver surface, and bile were taken and cultured to determine sterility. Results showed that temperature was maintained at 0-4 degrees C; perfusion pressure was maintained at 4 mmHg and 30/20 mmHg for portal vein and hepatic artery, respectively. Flow was approximately 350 and 80 ml/min, respectively, but decreased in the portal vein, probably due to edema formation. Arterial pO(2) was kept at 100 kPa. Histology showed complete perfusion of the liver with no major damage to hepatocytes, bile ducts, and non-parenchymal cells compared to control livers. The machine perfusion system complied to the design criteria and will have to demonstrate the superiority of machine perfusion over cold storage in transplant experiments.

  17. [The clinical practice of improvement the "Volume and Quality" of functional liver in autologous liver transplantation for the patients with alveolar echinococcosis].

    PubMed

    Tuerganaili, Aji; Shao, Y M; Zhao, J M; Li, T; Ran, B; Jiang, T M; Zhang, R Q; Tuerhongjiang, Tuxun; Wu, L; Guo, M; Wen, H

    2017-01-24

    Objective: To investigate the clinical significance of accurate assessment of "volume and quality" of functional liver in Autologous liver transplantation (ALT) in the treatment of the advanced hepatic alveolar echinococcosis (HAE). Methods: The clinical data of 12 patients with advanced HAE who underwent ALT at the First Affiliated Hospital of Xinjiang Medical University from May 2015 to July 2016 were retrospectively analyzed. Results: The preoperative hepatic functions of 12 patients were 8 Child-Pugh Grade A, 1 Grade B, and 3 Grade C. Three of the patients had moderate or severe jaundice. Three of the patients calculated functional liver graft volume (GV) and standard liver volume (SLV) ratio (GV/SLV) were <30%. After the protection of liver function, anti-infection, percutaneous transhepatic cholangiography drainage (PTCD), selective portal vein embolization (PVE), and staging liver resection, liver function Child-Pugh grade of 11 patients was raised to A grade, and the other patient was B grade, meanwhile the bilirubin was reduced to 2 times the normal value. The GV/SLV ratios of 3 patients with low GV/SLV ratio had reached 44.4%, 47.2% and 56.2% respectively. In this study, the GV/SLV ratios of the 12 patients were between 73.2% and 40.8% with an average of 55.6%. Operation time was 11.5-20.5 h, with an average of 12.3 h. Anhepatic phase time was 193-375 min with median 253.5 min. The red blood cell suspension was 0-6 U during the operation. The average hospitalization was 10-42 d, with the average 22.7 d. Total hospital costs were 121 600-434 800 Yuan, with the median cost of 174 400 Yuan. One patient died of septic shock a week after surgery. Conclusion: (1)ALT may provide feasibility for the advanced HAE. (2)Accurate assessment of functional liver "volume and quality" appeared as the key points to the ALT. (3)Precise surgery and individualized treatment could improve and protect the functional liver "volume and quality" .

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

    PubMed

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

    2017-09-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. Estimating Functional Liver Reserve Following Hepatic Irradiation: Adaptive Normal Tissue Response Models

    PubMed Central

    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 2005–2011, 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-R15pre-RT/ICG-R15post-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. PMID:24813090

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

    PubMed

    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.

  2. Liver injury in hypervitaminosis A: Evidence for activation of Kupffer cell function

    SciTech Connect

    Sim, W.L.W.

    1988-01-01

    The most important and novel finding of this work was enhanced liver Kupffer cell phagocytic and metabolic function by hypervitaminosis A. An animal model of hypervitaminosis A was developed in male Sprague-Dawley rats gavaged with 250,000 I.U. retinol/kg body weight/day for 3 weeks. Presence of hypervitaminosis A was indicated by characteristic changes in the fur coat, presence of brittle bones and spontaneous fractures and a significant increase in plasma and liver concentrations of retinyl palmitate while retinol levels remained the same as in controls. Hypervitaminosis A did not cause severe liver abnormalities as reflected by normal plasma glutamate pyruvate transaminase activity and bilirubin. The main change was a marked increase in size of the fat or Vitamin A storing cells. Measurement of clearance from blood of indocyanine green and {sup 99m}Tc-disofenin indicated this hepatocyte function was normal. Kupffer cell phagocytic function was enhanced in hypervitaminosis A as determined by clearance from blood of {sup 99m}Tc-sulfur colloid. In vitro, there was also evidence that treatment with high doses of Vitamin A activated or enhanced Kupffer cell function. Kupffer cells from control and Vitamin A treated rats were isolated by enzymatic dispersion, purified by centrifugal elutriation, and placed in culture. Activation was indicated by (1) increased phagocytosis of {sup 51}Cr-labeled opsonized sheep red blood cells (2) enhanced release of superoxide anion and (3) enhanced production of tumor cytolytic factor by Kupffer cells from Vitamin A treated rats.

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

    PubMed Central

    Yi, Yongwoo

    2016-01-01

    Perceptual thresholds are commonly assayed in the laboratory and clinic. When precision and accuracy are required, thresholds are quantified by fitting a psychometric function to forced-choice data. The primary shortcoming of this approach is that it typically requires 100 trials or more to yield accurate (i.e., small bias) and precise (i.e., small variance) psychometric parameter estimates. We show that confidence probability judgments combined with a model of confidence can yield psychometric parameter estimates that are markedly more precise and/or markedly more efficient than conventional methods. Specifically, both human data and simulations show that including confidence probability judgments for just 20 trials can yield psychometric parameter estimates that match the precision of those obtained from 100 trials using conventional analyses. Such an efficiency advantage would be especially beneficial for tasks (e.g., taste, smell, and vestibular assays) that require more than a few seconds for each trial, but this potential benefit could accrue for many other tasks. PMID:26763777

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

    PubMed

    Yi, Yongwoo; Merfeld, Daniel M

    2016-04-01

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

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

    PubMed

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

    2015-08-01

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

  6. Quantitative analysis of functional changes caused by pinhole glasses.

    PubMed

    Kim, Won Soo; Park, In Ki; Chun, Yeoun Sook

    2014-08-12

    To quantify the visual functional changes caused by pinhole glasses. Healthy subjects underwent ophthalmic examinations including uncorrected distance visual acuity (UDVA) and corrected near visual acuity (CNVA), pupil size, depth of focus (DOF), accommodative amplitude, visual field (VF) test, contrast sensitivity (CS), and stereopsis. Subjects underwent the same examinations while wearing pinhole glasses 1 week later. Forty-eight eyes of 48 subjects (24 male and 24 female) with a mean age of 35.5±6.7 years and a mean spherical equivalent of -2.4±3.3 diopters (D) were enrolled. The pinhole glasses significantly improved UDVA and CNVA (logMAR) from 0.44±0.46 and 0.26±0.40 to 0.19±0.25 and 0.14±0.22, respectively. The pinhole glasses markedly enlarged pupils from 3.6±0.5 mm photopic size to 6.0±0.5 mm, very close to the mesopic size of 6.2±0.6 mm. Mean DOF and accommodative amplitude also significantly increased by approximately 50%, while VF featured a general reduction of sensitivity. Mean deviation (MD) significantly decreased from -0.48±1.57 to -4.22±1.66 dB, and visual field index (VFI) decreased from 99.4±0.7% to 98.4±1.3%. The CS decreased significantly at all four spatial frequencies, and stereopsis deteriorated with pinhole glasses. The pinhole glasses improved visual acuity, DOF, and accommodative amplitude; however, they resulted in decreased visual quality including general reduction of VF sensitivity, CS, and stereopsis. Therefore, particular attention is needed when wearing pinhole glasses while driving, playing sports, or working with instruments. (ClinicalTrials.gov number, NCT02111356.). Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

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

    SciTech Connect

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

    2002-03-15

    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.

  8. Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

    PubMed Central

    Manon-Jensen, Tina; Genovese, Federica; Kristensen, Jacob H.; Nielsen, Mette J.; Sand, Jannie Marie B.; Hansen, Niels-Ulrik B.; Bay-Jensen, Anne-Christine; Bager, Cecilie L.; Krag, Aleksander; Blanchard, Andy; Krarup, Henrik; Leeming, Diana J.; Schuppan, Detlef

    2015-01-01

    Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential information needed for maintenance of a sophisticated structure anchoring the cells and sustaining normal function of tissues. Therefore, the matrix itself may be considered as a paracrine/endocrine entity, with more complex functions than previously appreciated. The aims of this review are to 1) 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 and their posttranslational modifications often harbor multiple domains with different signaling potential, in particular when modified during inflammation or wound healing. This signaling by the ECM should be considered a paracrine/endocrine function, as it affects cell phenotype, function, fate, and finally tissue homeostasis. These properties should be exploited to establish novel biochemical markers and antifibrotic treatment strategies for liver fibrosis as well as other fibrotic diseases. PMID:25767261

  9. Abnormal liver function test in Graves' disease: a prospective study of comparison between the hyperthyroid state and the euthyroid state.

    PubMed

    Sarinnapakorn, Veerasak; Noppavetchwich, Pornchanok; Sunthorntepwarakul, Thongkum; Deerochanawong, Chaicharn; Ngongamrut, Supannee

    2011-03-01

    Abnormal liver function test is sometimes seen in hyperthyroidism but no study had been carried out to compare liver function test in the hyperthyroid state and the euthyroid state. This study aimed to find the prevalence of abnormal liver function test in Graves' disease and compare liver function test result in the hyperthyroid state with the euthyroid state. This is a prospective study of 112 patients who had Graves' disease. These patients were new cases or recurrent cases of Graves' disease whose medication had been discontinue for more than 3 months. We followed-up 86 patients received treatment with antithyroid drugs up to the euthyroid state and compared liver function test at diagnosis and in the euthyroid state. An abnormal level of serum globulin was the most abnormal liver function test results in Graves' disease at 30.4%, followed by an abnormal level of serum alkaline phosphatase of 25.0% and gamma-glutamyl transpeptidase (GGT) of 23.3%. The trend of GGT levels returned to normal but there was an increased in serum alkaline phosphatase after treatment until the euthyroid state in the follow-up group. Abnormal liver function tests in Graves' disease are common, after treatment until the euthyroid state, experienced an improvement in GGT level but also an increase in serum alkaline phosphatase level.

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

    PubMed

    Reinehr, Roland; Sommerfeld, Annika; Häussinger, Dieter

    2013-04-01

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

  11. Vicarious liver visualization in solitary functioning kidney with technetium-99m ethylenedicysteine renal scintigraphy

    PubMed Central

    Jain, Tarun Kumar; Phulsunga, Rohit Kumar; Gupta, Nitin; Sood, Ashwani; Bhattacharya, Anish; Mittal, Bhagwant Rai

    2015-01-01

    We present a case of 3-year-old boy who was incidentally diagnosed to have single left kidney on ultrasonography. Dynamic technetium-99m ethylenedicysteine renal scintigraphy was acquired for assessing the existing kidney function showed the tracer localization in bilateral renal fossae during the entire study. The single-photon emission computerized tomography/computerized tomography study revealed activity in the right renal fossa to be in the enlarged right lobe of the liver, which was mimicking as impaired functioning right kidney in planar images. The hybrid imaging helped in accurate delineation of tracer uptake by confirming it to be the false appearance of the right kidney in planar imaging. This case report also highlights the possible mechanism of renal tracer uptake in the liver parenchyma. PMID:26170576

  12. Proteomic analysis of physiological function response to hot summer in liver from lactating dairy cows.

    PubMed

    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.

  13. Long Term Liver Engraftment of Functional Hepatocytes Obtained from Germline Cell-Derived Pluripotent Stem Cells

    PubMed Central

    Fagoonee, Sharmila; Famulari, Elvira Smeralda; Silengo, Lorenzo; Tolosano, Emanuela; Altruda, Fiorella

    2015-01-01

    One of the major hurdles in liver gene and cell therapy is availability of ex vivo-expanded hepatocytes. Pluripotent stem cells are an attractive alternative. Here, we show that hepatocyte precursors can be isolated from male germline cell-derived pluripotent stem cells (GPSCs) using the hepatoblast marker, Liv2, and induced to differentiate into hepatocytes in vitro. These cells expressed hepatic-specific genes and were functional as demonstrated by their ability to secrete albumin and produce urea. When transplanted in the liver parenchyma of partially hepatectomised mice, Liv2-sorted cells showed regional and heterogeneous engraftment in the injected lobe. Moreover, approximately 50% of Y chromosome-positive, GPSC-derived cells were found in the female livers, in the region of engraftment, even one month after cell injection. This is the first study showing that Liv2-sorted GPSCs-derived hepatocytes can undergo long lasting engraftment in the mouse liver. Thus, GPSCs might offer promise for regenerative medicine. PMID:26323094

  14. Quantitative descriptions of generalized arousal, an elementary function of the vertebrate brain

    PubMed Central

    Quinkert, Amy Wells; Vimal, Vivek; Weil, Zachary M.; Reeke, George N.; Schiff, Nicholas D.; Banavar, Jayanth R.; Pfaff, Donald W.

    2011-01-01

    We review a concept of the most primitive, fundamental function of the vertebrate CNS, generalized arousal (GA). Three independent lines of evidence indicate the existence of GA: statistical, genetic, and mechanistic. Here we ask, is this concept amenable to quantitative analysis? Answering in the affirmative, four quantitative approaches have proven useful: (i) factor analysis, (ii) information theory, (iii) deterministic chaos, and (iv) application of a Gaussian equation. It strikes us that, to date, not just one but at least four different quantitative approaches seem necessary for describing different aspects of scientific work on GA. PMID:21555568

  15. LIVER FUNCTION TESTS IN PREDICTING CBD STONES IN ACUTE BILIARY PANCREATITIS.

    PubMed

    Thomson, J T; Smith, M D; Omoshoro-Jones, J A O; Devar, J D; Gaylard, P D; Khan, Z K; Jugmohan, B J

    2017-06-01

    Acute biliary pancreatitis is a significant cause of pancreatitis. The role and timing of endoscopic retrograde cholangiopancreatography in the setting of acute biliary pancreatitis is still controversial. Persistent choledocholithiasis in acute biliary pancreatitis occurs and establishing which patients require an endoscopic retrograde cholangiopancreatography based on liver function tests only can be challenging. Retrospective analysis of the Chris Hani Baragwanath Academic Hospital's ERCP database was performed. All ERCPs performed in patients with acute biliary pancreatitis were identified and analysed. A total of 2830 ERCPs were performed during the study period. In total 99 (3%) were performed for suspected choledocholithiasis in acute biliary pancreatitis with abnormal liver function tests. Thirty (30%) of the ERCPs confirmed choledocholithiasis while the remaining 69 (70%) yielded no choledocholithiasis. A significantly higher proportion of patients with choledocholithiasis required a needle knife sphincterotomy for deep biliary cannulation. The incidence of immediate complications, such as bleeding, false tract formation and perforation were comparable between the two groups. Two models were developed to determine specific cut-off values for conjugated bilirubin, ALP, GGT, AST and ALT. The calculated cut-off values yielded poor correlation between sensitivity and specificity. Determining persistent choledocholithiasis in acute biliary pancreatitis based on liver function test alone is not ideal. Using conjugated bilirubin, ALP, GGT, AST and ALT to guide one to perform an ERCP in acute biliary pancreatitis can be misleading.

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

    PubMed

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

    2012-11-01

    Bioartificial liver (BAL) system is promising as an alternative treatment for liver failure. We have developed a bioreactor with stacked sandwich culture plates for the application of BAL. This bioreactor design addresses some of the persistent problems in flat-bed bioreactors through increasing cell packing capacity, eliminating dead flow, regulating shear stress, and facilitating the scalability of the bioreactor unit. The bioreactor contained a stack of twelve double-sandwich-culture plates, allowing 100 million hepatocytes to be housed in a single cylindrical bioreactor unit (7 cm of height and 5.5 cm of inner diameter). The serial flow perfusion through the bioreactor increased cell-fluid contact area for effective mass exchange. With the optimal perfusion flow rate, shear stress was minimized to achieve high and uniform cell viabilities across different plates in the bioreactor. Our results demonstrated that hepatocytes cultured in the bioreactor could re-establish cell polarity and maintain liver-specific functions (e.g. albumin and urea synthesis, phase I&II metabolism functions) for seven days. The single bioreactor unit can be readily scaled up to house adequate number of functional hepatocytes for BAL development. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Intrasurgical dignity assessment of hepatic tumors using semi-quantitative strain elastography and contrast-enhanced ultrasound for optimisation of liver tumor surgery.

    PubMed

    Platz Batista da Silva, N; Schauer, M; Hornung, M; Lang, S; Beyer, L P; Wiesinger, I; Stroszczynski, C; Jung, E M

    2016-01-01

    To evaluate the efficacy of strain elastography (SE) using semi-quantitative measurement methods compared to constrast enhanced ultrasound during liver tumor surgery (Io-CEUS) for dignity assessment of focal liver lesions(FLL). Prospective data acquisition and retrospective analysis of US data of 100 patients (116 lesions) who underwent liver tumor surgery between 10/2010 and 03/2016. Retrospective reading of SE color patterns was performed establishing groups depending on dominant color (>50% blue = stiff, inhomogenous, >50% yellow/red/green = soft tissue). Semi-quantitative analysis was performed by Q-analysis based on a scale from 0 (soft) to 6 (stiff). 2 ROIs were placed centrally, 5 ROIs in the lesion's surrounding tissue. Io-CEUS was performed by bolus injection of 5-10 ml sulphurhexaflourid microbubbles evaluating wash-in- and -out- kinetics in arterial, portal venous and late phase. Histopathology after surgical resection served as goldstandard. 100 patients (m: 65, f: 35, mean age 60.5 years) with 116 liver lesions were included. Lesion's size ranged from 0.5 to 8.4 cm (mean 2.42 cm SD±1.44 cm). Postoperative histology showed 105 malignant and 11 benign lesions. Semi-quantitative analysis showed central indurations of >2.5 in 76/105 cases suggesting malignancy. 7 benign lesions displayed no central indurations correctly characterized benign by SE. ROC-analysis and Youden index showed a sensitivity of 72.4% and specificity of 63.6% assuming a cut-off of 2.5. Io-CEUS correctly characterized 103/105 as malignant. Sensitivity was 98%, specificity 72.7%. Strain elastography is a valuable tool for non-invasive characterization of FLLs. Semi-quantitative intratumoral stiffness values of >2.5 suggested malignancy. However, sensitivity of Io-CEUS in detecting malignant lesions was higher compared to SE. In conclusion SE should be considered for routine use during intraoperative US in addition to Io-CEUS for optimization of curative liver surgery.

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

    PubMed

    Zhu, Hong; Marco, Catena; Gianfranco, Ferla

    2009-04-01

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

  19. RIFLE criteria and hepatic function in the assessment of acute renal failure in liver transplantation.

    PubMed

    Tinti, F; Umbro, I; Meçule, A; Rossi, M; Merli, M; Nofroni, I; Corradini, S Ginanni; Poli, L; Pugliese, F; Ruberto, F; Berloco, P B; Mitterhofer, A P

    2010-05-01

    Renal dysfunction in cirrhotic patients is primary related to disturbances of circulatory function, triggered by portal hypertension with chronic intrarenal vasoconstriction and hypoperfusion. Pretransplant renal function is an important factor implicated in the development of acute renal failure (ARF) after liver transplantation (OLT), but other factors mostly related to liver function seem to influence the development of ARF. The Acute Dialysis Quality Initiative workgroup developed the RIFLE classification to define ARF. We sought to evaluate the incidence of ARF among patients undergoing OLT, to evaluate the association of ARF with pre-OLT renal and hepatic functions, and to evaluate the influence of ARF on chronic kidney disease (CKD) at 1 month post-OLT. Clinical, renal, hepatic function, and donor risk index data of 24 patients who underwent deceased donor OLT were collected before transplantation, in the perioperative period and in the first month post-OLT. ARF occurred in 37.5% of patients with 56% developing the R grade and 44% the I grade; no patient showed the F grade. An association was observed between ARF and a higher Model for End-Stage Liver Disease (MELD) score and between ARF and a reduced pre-OLT serum albumin. No association was noted between ARF and other pre-OLT parameters. In cirrhotic patients serum creatinine is a bias for renal function assessment and the Modification of Diet in Renal Disease formula overestimates GFR. Post-OLT CKD was present in 6.7% of patients without ARF and in 44.4% of patients with ARF. The R grade developed more frequently among patients with viral cirrhosis. The association of ARF with MELD and hypoalbuminemia may be the result of a close relationship between renal and hepatic functions among cirrhotic patients. Post-OLT CKD may be the result of unrecognized, preexisting CKD and/or the effects of not fully resolved acute damage to an injured kidney. Copyright (c) 2010 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-03-01

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

  1. [(68)Ga]NOTA-Galactosyl Human Serum Albumin: a Tracer for Liver Function Imaging with Improved Stability.

    PubMed

    Haubner, Roland; Schmid, Andreas M; Maurer, Andreas; Rangger, Christine; Roig, Llanos Geraldo; Pichler, Bernd J; Virgolini, Irene J

    2017-02-13

    Non-invasive techniques allowing quantitative determination of the functional liver mass are of great interest for patient management in a variety of clinical settings. Recently, we presented [(68)Ga]DTPA-GSA to target the hepatic asialoglycoprotein receptor for this purpose. Here, we introduce [(68)Ga]NOTA-GSA to improve metabolic stability of the radiopharmaceutical and compare the imaging properties with [(68)Ga]DTPA-GSA. Labeling of the compounds was carried out at room temperature using 1.9 M sodium acetate as buffer. For quality control, thin-layer, high-performance liquid, and size exclusion chromatographies were used. Metabolic stability was studied in rat and human serums. For in vivo evaluation, Fischer rats were scanned by positron emission tomography and magnetic resonance imaging and subsequently sacrificed for biodistribution studies. Time activity curves (TACs) for heart and liver were generated and corresponding parameters (T50, T90, LHL15, HH15) were calculated. [(68)Ga]NOTA-GSA can be produced in high radiochemical yield and purity (>95 %) within 15 min. Stability studies revealed almost no metabolite formation over the 2-h observation period. Analysis of the TACs showed comparable results for most of the investigated parameters. The only significant difference was found in the T90 value, where [(68)Ga]NOTA-GSA showed slower uptake in comparison with (68)Ga-DTPA-GSA (123 ± 10 vs. 89 ± 3 s, p < 0.01). [(68)Ga]NOTA-GSA showed a significant increase of the metabolic stability and in most organs lower background activity. However, comparison of LHL15 and HH15 indicates that the increased stability did not further improve the diagnostic value. Thus, [(68)Ga]NOTA-GSA and [(68)Ga]DTPA-GSA can be used equivalent for imaging hepatic function with positron emission tomography.

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

    PubMed

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

    2005-01-01

    The aim of this study was to evaluate a new method of image analysis used to quantify the iron load in routinely processed liver biopsies. Sixty-four liver biopsies from the same number of patients were studied. Both biochemical determination of iron concentration and histopathological semiquantification and quantification were performed. The latter was performed on Perls-stained liver sections by a semiautomatic system of image analysis that yields the percentage of stained liver tissue. In 43 samples with an hepatic iron content higher than 2000microg/mg of dry tissue, this morphometric index was compared to the liver iron load measured biochemically, showing a significant correlation (Spearman's test) between both variables (rho = 0.686, p<0.001). Moreover, there is a better correlation when the semiquantitative Deugnier's histological index is compared with the biochemical method (rho = 0.425, p<0.004). Thus, we conclude that image analysis may be a valid method to assess hepatic iron storage in patients with liver diseases and that it may be more accurate than semiquantitative grading systems, such as the one described by Deugnier, since the morphometric method shows a closer correlation with the hepatic iron concentration determined biochemically.

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

    PubMed Central

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

    2017-01-01

    Aim 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. Methods 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. Results 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). Conclusions 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. PMID:28542386

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

    PubMed

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

    2017-01-01

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

  5. Quantitative theory of a relaxation function in a glass-forming system.

    PubMed

    Lerner, Edan; Procaccia, Itamar

    2008-08-01

    We present a quantitative theory for a relaxation function in a simple glass-forming model (binary mixture of particles with different interaction parameters). It is shown that the slowing down is caused by the competition between locally favored regions (clusters) that are long-lived but each of which relaxes as a simple function of time. Without the clusters, the relaxation of the background is simply determined by one typical length, which we deduce from an elementary statistical mechanical argument. The total relaxation function (which depends on time in a nontrivial manner) is quantitatively determined as a weighted sum over the clusters and the background. The "fragility" in this system can be understood quantitatively since it is determined by the temperature dependence of the number fractions of the locally favored regions.

  6. Role of exercise in optimizing the functional status of patients with nonalcoholic fatty liver disease.

    PubMed

    Gerber, Lynn H; Weinstein, Ali; Pawloski, Lisa

    2014-02-01

    Nonalcoholic fatty liver disease (NAFLD) is frequently concomitant with obesity. This article discusses factors that influence health and functional outcomes of people who develop NAFLD, including increased burden of illness, whole body function, performance, and perception of self-efficacy. Changes in macronutrients, amount of calories consumed, and decreased physical activity all negatively influence patient outcome. The benefits of exercise in this population are also discussed. To be effective, exercise must be performed, regularly and in conjunction with dietary and other behavioral change. Therefore, a lifelong commitment to exercise, activity, and diet are needed if NAFLD is to be successfully treated.

  7. Impact of splenic artery ligation after major hepatectomy on liver function, regeneration and viability.

    PubMed

    Carrapita, Jorge; Abrantes, Ana Margarida; Campelos, Sofia; Gonçalves, Ana Cristina; Cardoso, Dulce; Sarmento-Ribeiro, Ana Bela; Rocha, Clara; Santos, Jorge Nunes; Botelho, Maria Filomena; Tralhão, José Guilherme; Farges, Olivier; Barbosa, Jorge Maciel

    2016-10-11

    It was reported that prevention of acute portal overpressure in small-for-size livers by inflow modulation results in a better postoperative outcome. The aim is to investigate the impact of portal blood flow reduction by splenic artery ligation after major hepatectomy in a murine model. Forty-eight rats were subjected to an 85% hepatectomy or 85% hepatectomy and splenic artery ligation. Both groups were evaluated at 24, 48, 72 and 120 post-operative hours: liver function, regeneration and viability. All methods and experiments were carried out in accordance with Coimbra University guidelines. Splenic artery ligation produces viability increase after 24 h, induces a relative decrease in oxidative stress during the first 48 hours, allows antioxidant capacity increment after 24 h, which is reflected in a decrease of half-time normalized liver curve at 48 h and at 72 h and in an increase of mitotic index between 48 h and 72 h. Splenic artery ligation combined with 85% hepatectomy in a murine model, allows portal inflow modulation, promoting an increase in hepatocellular viability and regeneration, without impairing the function, probably by inducing a less marked elevation of oxidative stress at first 48 hours.

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

    PubMed Central

    2010-01-01

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

  9. Impact of splenic artery ligation after major hepatectomy on liver function, regeneration and viability

    PubMed Central

    Carrapita, Jorge; Abrantes, Ana Margarida; Campelos, Sofia; Gonçalves, Ana Cristina; Cardoso, Dulce; Sarmento-Ribeiro, Ana Bela; Rocha, Clara; Santos, Jorge Nunes; Botelho, Maria Filomena; Tralhão, José Guilherme; Farges, Olivier; Barbosa, Jorge Maciel

    2016-01-01

    It was reported that prevention of acute portal overpressure in small-for-size livers by inflow modulation results in a better postoperative outcome. The aim is to investigate the impact of portal blood flow reduction by splenic artery ligation after major hepatectomy in a murine model. Forty-eight rats were subjected to an 85% hepatectomy or 85% hepatectomy and splenic artery ligation. Both groups were evaluated at 24, 48, 72 and 120 post-operative hours: liver function, regeneration and viability. All methods and experiments were carried out in accordance with Coimbra University guidelines. Splenic artery ligation produces viability increase after 24 h, induces a relative decrease in oxidative stress during the first 48 hours, allows antioxidant capacity increment after 24 h, which is reflected in a decrease of half-time normalized liver curve at 48 h and at 72 h and in an increase of mitotic index between 48 h and 72 h. Splenic artery ligation combined with 85% hepatectomy in a murine model, allows portal inflow modulation, promoting an increase in hepatocellular viability and regeneration, without impairing the function, probably by inducing a less marked elevation of oxidative stress at first 48 hours. PMID:27725728

  10. Function of the liver and bile ducts in humans exposed to lead.

    PubMed

    Kasperczyk, A; Dziwisz, M; Ostałowska, A; Swietochowska, E; Birkner, E

    2013-08-01

    Lead is very common in the environment, and it is therefore important to characterize its possible adverse health effects. The aim of this study was to evaluate the impact of lead exposure on selected functions of the liver and bile ducts in people who are chronically exposed to the metal because of their occupations. To provide this information, the activity of specific enzymes and the bilirubin concentration were determined in blood serum, and morphological parameters of the liver and bile ducts were evaluated using the ultrasonic imaging method. Healthy male employees of a lead-zinc processing facility (n = 145) who were occupationally exposed to lead were divided into two subgroups as a function of the lead concentrations in blood (PbB): low lead exposure (PbB = 20-35 μg/dl; n = 57) and high lead exposure (PbB = 35-60 μg/dl; n = 88). Human exposure to lead compounds was found to cause liver enlargement and to activate inflammatory reactions with the characteristics of moderate cholestasis within the bile ducts, while no characteristics of necrotic damage of hepatic cells were noted. It seems that lipid peroxidation can be one of the toxic mechanisms of lead which induce moderate cholestasis. The effects depend on the extent of the lead exposure and were greater in subjects with higher exposure levels, particularly subjects with PbB values greater than 35 μg/dl.

  11. Green light for liver function monitoring using indocyanine green? An overview of current clinical applications.

    PubMed

    Vos, J J; Wietasch, J K G; Absalom, A R; Hendriks, H G D; Scheeren, T W L

    2014-12-01

    The dye indocyanine green is familiar to anaesthetists, and has been studied for more than half a century for cardiovascular and hepatic function monitoring. It is still, however, not yet in routine clinical use in anaesthesia and critical care, at least in Europe. This review is intended to provide a critical analysis of the available evidence concerning the indications for clinical measurement of indocyanine green elimination as a diagnostic and prognostic tool in two areas: its role in peri-operative liver function monitoring during major hepatic resection and liver transplantation; and its role in critically ill patients on the intensive care unit, where it is used for prediction of mortality, and for assessment of the severity of acute liver failure or that of intra-abdominal hypertension. Although numerous studies have demonstrated that indocyanine green elimination measurements in these patient populations can provide diagnostic or prognostic information to the clinician, 'hard' evidence - i.e. high-quality prospective randomised controlled trials - is lacking, and therefore it is not yet time to give a green light for use of indocyanine green in routine clinical practice.

  12. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions.

    PubMed

    Bian, Xiaoming; Tu, Pengcheng; Chi, Liang; Gao, Bei; Ru, Hongyu; Lu, Kun

    2017-09-01

    Maintaining the balance of the gut microbiota and its metabolic functions is vital for human health, however, this balance can be disrupted by various external factors including food additives. A range of food and beverages are sweetened by saccharin, which is generally considered to be safe despite controversial debates. However, recent studies indicated that saccharin perturbed the gut microbiota. Inflammation is frequently associated with disruptions of the gut microbiota. The aim of this study is to investigate the relationship between host inflammation and perturbed gut microbiome by saccharin. C57BL/6J male mice were treated with saccharin in drinking water for six months. Q-PCR was used to detect inflammatory markers in mouse liver, while 16S rRNA gene sequencing and metabolomics were used to reveal changes of the gut microbiota and its metabolomic profiles. Elevated expression of pro-inflammatory iNOS and TNF-α in liver indicated that saccharin induced inflammation in mice. The altered gut bacterial genera, enriched orthologs of pathogen-associated molecular patterns, such as LPS and bacterial toxins, in concert with increased pro-inflammatory metabolites suggested that the saccharin-induced liver inflammation could be associated with the perturbation of the gut microbiota and its metabolic functions. Copyright © 2017. Published by Elsevier Ltd.

  13. A Comparison of Muscle Function, Mass, and Quality in Liver Transplant Candidates: Results From the Functional Assessment in Liver Transplantation Study.

    PubMed

    Wang, Connie W; Feng, Sandy; Covinsky, Kenneth E; Hayssen, Hilary; Zhou, Li-Qin; Yeh, Benjamin M; Lai, Jennifer C

    2016-08-01

    Sarcopenia and functional impairment are common and lethal extrahepatic manifestations of cirrhosis. We aimed to determine the association between computed tomography (CT)-based measures of muscle mass and quality (sarcopenia) and performance-based measures of muscle function. Adults listed for liver transplant underwent testing of muscle function (grip strength, Short Physical Performance Battery [SPPB]) within 3 months of abdominal CT. Muscle mass (cm/m) = total cross-sectional area of psoas, paraspinal, and abdominal wall muscles at L3 on CT, normalized for height. Muscle quality = mean Hounsfield units for total skeletal muscle area at L3. Among 292 candidates, median grip strength was 31 kg, SPPB score was 11, muscle mass was 49 cm/m, and muscle quality was 35 Hounsfield units. Grip strength weakly correlated with muscle mass (ρ = 0.26, P < 0.001) and quality (ρ = 0.27, P < 0.001) in men, and muscle quality (ρ = 0.23, P = 0.02), but not muscle mass, in women. Short Physical Performance Battery correlated weakly with muscle quality in men (ρ = 0.38, P < 0.001) and women (ρ = 0.25, P = 0.02), however, did not correlate with muscle mass in men or women. After adjustment for sex, model for end-stage liver disease (MELD)-Na, hepatocellular carcinoma, and body mass index, grip strength (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.59-0.92; P = 0.008), SPPB (HR, 0.89; 95% CI, 0.82-0.97; P = 0.01), and muscle quality (HR, 0.77; 95% CI, 0.63-0.95; P = 0.02) were associated with waitlist mortality, but muscle mass was not (HR, 0.91; 95% CI, 0.75-1.11; P = 0.35). Performance-based tests of muscle function are only modestly associated with CT-based muscle measures. Given that they predict waitlist mortality and can be conducted quickly and economically, tests of muscle function may have greater clinical utility than CT-based measures of sarcopenia.

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

    PubMed

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

    2012-09-01

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

  15. A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.

    PubMed

    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.

  16. Lipid Profiling and Transcriptomic Analysis Reveals a Functional Interplay between Estradiol and Growth Hormone in Liver

    PubMed Central

    Fernández-Pérez, Leandro; Santana-Farré, Ruymán; de Mirecki-Garrido, Mercedes; García, Irma; Guerra, Borja; Mateo-Díaz, Carlos; Iglesias-Gato, Diego; Díaz-Chico, Juan Carlos; Flores-Morales, Amilcar; Díaz, Mario

    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, 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 marked influence on

  17. Anatrophic nephrolithotomy: preservation of renal function demonstrated by differential quantitative radionuclide renal scans

    SciTech Connect

    Belis, J.A.; Morabito, R.A.; Kandzari, S.J.; Lai, J.C.; Gabriele, O.F.

    1981-06-01

    Differential quantitative radionuclide renal scans have been used to confirm that early removal of staghorn calculi by anatrophic nephrolithotomy preserves renal parenchyma without significant renal damage by the surgical procedure. The /sup 99m/technetium diethylenetriaminepentaacetic acid scan was useful in predicting recovery of function in the involved kidney, while the /sup 131/iodine orthoiodohippurate scan provided a quantitative evaluation of the effect of the surgical procedure on individual kidney function. All of 13 consecutive patients evaluated by /sup 131/iodine orthoiodohippurate renal scans had stable or improved effective renal plasma flow to the involved kidney and an unchanged or improved total excretory index 6 months after nephrolithotomy.

  18. Anatrophic nephrolithotomy: preservation of renal function demonstrated by differential quantitative radionuclide renal scans.

    PubMed

    Belis, J A; Morabito, R A; Kandzari, S J; Lai, J C; Gabriele, O F

    1981-06-01

    Differential quantitative radionuclide renal scans have been used to confirm that early removal of staghorn calculi by anatrophic nephrolithotomy preserves renal parenchyma without significant renal damage by the surgical procedure. The 99mtechnetium diethylenetriaminepentaacetic acid scan was useful in predicting recovery of function in the involved kidney, while the 131iodine orthoiodohippurate scan provided a quantitative evaluation of the effect of the surgical procedure on individual kidney function. All of 13 consecutive patients evaluated by 131iodine orthoiodohippurate renal scans had stable or improved effective renal plasma flow to the involved kidney and an unchanged or improved total excretory index 6 months after nephrolithotomy.

  19. Nonalcoholic fatty liver disease associated with impairment of kidney function in nondiabetes population

    PubMed Central

    Li, Guolin; Shi, Wang; Hu, Hui; Chen, Yaqin; Liu, Li; Yin, Dazhong

    2012-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is associated with the increased burden of kidney. However, there is still no large population study to explore the potential relationship between NAFLD and mild kidney function damage (MKFD) after adjusted for confounding factors. This study is to test the hypothesis that NAFLD is associated with MKFD under controlling the effects of confounding factors. Materials and methods: Levels of serum fasting glucose, creatinine, cholesterol, triglyceride, alanine aminotransferase and aspartate aminotransferase were analyzed from 1412 Chinese Han adults. Questionnaire and physical examination were performed to explore the potential association of NAFLD with kidney function. Results: NAFLD was associated with impairment of kidney function. Multivariate-adjusted odds ratio illustrated that, compared to subjects with normal liver, NAFLD subjects had a significantly higher risk of MKFD with or without adjusted for blood glucose and other covariates (P = 0.041). Further results from multi-interaction analysis demonstrated that the underlying mechanisms linked NAFLD with impaired kidney function may be that they share common risk factors and similar pathological processes. Conclusions: The most striking finding of this study is that NAFLD is negatively associated with kidney function, in nondiabetic population. NAFLD and MKFD may share similar risk factors and/or pathological processes. PMID:22384523

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

    PubMed

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

    2016-11-01

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